tbuckley/cabot-search huggingface dataset:
Long-term sequelae post-hospitalization for respiratory syncytial virus versus Omicron SARS-CoV-2 or influenza in adults and children: a retrospective cohort study
Authors: Liang En Wee, Reen Wan Li Ho, Jue Tao Lim, Calvin J Chiew, Barnaby Young, Chee-Fu Yung, Chia Yin Chong, David Chien Boon Lye, Kelvin Bryan Tan
Journal: Clinical Microbiology and Infection (2025)
Indoleamine-2,3-dioxygenase: An important controller in maintaining mesenchymal stem cell-mediated immunomodulatory homeostasis
Authors: Yufei Hui, Xue Jiao, Li Yang, Dejin Lu, Yanbo Han, Wen Yang, Yanli Cao, Yuxi Miao, Shiqiang Gong, Minjie Wei
Journal: Acta Pharmaceutica Sinica B (2025)
Active Treatment and Survival Trends for Periviable Births by Race and Ethnicity
Authors: Nansi S. Boghossian, Lucy T. Greenberg, Erika M. Edwards, Jeffrey D. Horbar
Journal: JAMA (2025)

This retrospective cohort study analyzes infants born prematurely between 2014 and 2023 to determine changes in the rate of active treatment and in-hospital survival over time and assess differences based on gestational age, race, and ethnicity.
Exploring the diagnostic potential: magnetic particle imaging for brain diseases
Authors: Li-Shuang Guo, Yu An, Ze-Yu Zhang, Chen-Bin Ma, Jia-Qian Li, Zhen Dong, Jie Tian, Zhen-Yu Liu, Jian-Gang Liu
Journal: Military Medical Research (2025)

Abstract Brain diseases are characterized by high incidence, disability, and mortality rates. Their elusive nature poses a significant challenge for early diagnosis. Magnetic particle imaging (MPI) is a novel imaging technique with high sensitivity, high temporal resolution, and no ionizing radiation. It relies on the nonlinear magnetization response of superparamagnetic iron oxide nanoparticles (SPIONs), allowing visualization of the spatial concentration distribution of SPIONs in biological tissues. MPI is expected to become a mainstream technology for the early diagnosis of brain diseases, such as cancerous, cerebrovascular, neurodegenerative, and inflammatory diseases. This review provides an overview of the principles of MPI, explores its potential applications in brain diseases, and discusses the prospects for the diagnosis and management of these diseases.
Clinical Outcomes, Genomic Heterogeneity, and Therapeutic Considerations Across Histologic Subtypes of Urothelial Carcinoma
Authors: Carissa E Chu, Ziyu Chen, Karissa Whiting, Irina Ostrovnaya, Andrew T Lenis, Timothy N Clinton, Rayan Rammal, Gamze Gokturk Ozcan, Dilara Akbulut, Merve Basar, Jie-Fu Chen, Ying-Bei Chen, Anuradha Gopalan, Samson W Fine, Satish K Tickoo, Maria Arcila, A Rose Brannon, Michael F Berger, Eugene K Cha, Alvin C Goh, Timothy F Donahue, Dean F Bajorin, Min Yuen Teo, Jonathan E Rosenberg, Gopa Iyer, Eugene J Pietzak, Bernard H Bochner, Victor E Reuter, Judy Sarungbam, David B Solit, Hikmat Al-Ahmadie
Journal: European Urology (2025)
Biofabrication of Spatially Organized Temporo‐mandibular Fibrocartilage Assembloids
Authors: Alexandre Dufour, Lucie Essayan, Beomjoon Kim, Vincent Salles, Christophe Marquette
Journal: Advanced Healthcare Materials (2025)

Abstract The combination of mesenchymal stem cell (MSC) spheroids and polymeric scaffolds has been actively explored for engineering organized hyaline cartilage; however, its application to other types of cartilage remains under‐explored. The temporo‐mandibular joint (TMJ) fibrocartilage is a stratified tissue whose recapitulation remains challenging. In this study, the shape and growth orientation of assembloids are controlled by seeding early mature human adipose‐derived MSC spheroids into scaffolds with a dual architecture of micron‐scale fibers. This results in flattened asymmetric tissues with a single‐sided articular surface. The engineered fibrocartilage mimics the histotypical organization of native human condylar fibrocartilage, featuring a thick fibrous zone with flattened cells. A native‐like distribution of glycosaminoglycans, type I and II collagens, aggrecan core protein, and fibronectin is observed. Collagen organization is also found to be similar to that of native human tissue, up to the fibril level. Zonal‐dependent micromechanical properties are identified in both the engineered and native tissues, although lower mechanical properties are observed in the fibrous zone of the engineered tissue. This work provides further evidence that the combination of MSC spheroids and micron‐sized fiber scaffolds is a versatile approach for engineering stratified cartilage and a promising strategy for engineering biomimetic fibrocartilage grafts for TMJ reconstruction.
Mandible-derived extracellular vesicles regulate early tooth development in miniature swine via targeting KDM2B
Authors: Ye Li, Meng Sun, Yi Ding, Ang Li
Journal: International Journal of Oral Science (2025)

Abstract Tissue interactions play a crucial role in tooth development. Notably, extracellular vesicle-mediated interactions between the mandible and tooth germ are considered essential. Here, we revealed that mandible extracellular vesicles could modulate the proliferation and differentiation of dental mesenchymal cells by regulating the histone demethylase KDM2B. Further investigation showed that mandible derived extracellular vesicles could deliver miR-206 to KDM2B, thereby regulating tooth development. An animal study demonstrated that the miR-206/KDM2B pathway affected tooth morphogenesis and mineralization after eight weeks of subcutaneous transplantation in nude mice. In conclusion, this study suggested that the mandible played a critical role in tooth morphogenesis and mineralization, which could be a potential therapeutic target for abnormal tooth development and an alternative model for tooth regeneration.
Correction: The cGAS‒STING pathway in cancer immunity: mechanisms, challenges, and therapeutic implications
Authors: Mengzhou Shen, Xianjie Jiang, Qiu Peng, Linda Oyang, Zongyao Ren, Jiewen Wang, Mingjing Peng, Yujuan Zhou, Xiyun Deng, Qianjin Liao
Journal: Journal of Hematology & Oncology (2025)
A multicenter, open-label, single-arm, phase Ib clinical trial of HH2853 treatment in patients with relapsed and/or refractory peripheral T-cell lymphoma
Authors: Huangming Hong, Zegeng Chen, Mingzhi Zhang, Zhigang Peng, Jianzhen Shen, Yuerong Shuang, Hui Zhou, Hongqiang Guo, He Huang, Fei Li, Zhengzi Qian, Lihong Liu, Liang Wang, Wei Yang, Liling Zhang, Pengcheng He, Shen Qian, Fugen Li, Meng Li, Tongyu Lin
Journal: Journal of Hematology & Oncology (2025)

Peripheral T-cell lymphoma (PTCL) is an aggressive malignancy with limited treatment options and poor prognosis, particularly for relapsed or refractory (r/r) patients. HH2853, a novel dual inhibitor of EZH1/2, has previously demonstrated clinical benefits in solid tumors. Here, we report safety and efficacy data from a phase Ib trial of HH2853 in r/r PTCL. A phase Ib clinical trial in PTCL was conducted from July 2022-August 2023 at 15 sites in China. The study employed a dose-escalation phase (300 mg, 400 mg, and 600 mg BID) to determine the recommended phase II dosage (RP2D), followed by a dose expansion phase (300 mg and 400 mg BID). The primary endpoints were safety and the overall response rate (ORR). Thirty-four patients with various r/r PTCL histology types, a median age of 58 years, and a median of 2 prior systemic therapies were enrolled. Treatment-related adverse events (TRAEs) were observed in 92.1% of the patients, with 20.6% experiencing grade 3 TRAEs. The most common TRAEs included anemia (67.6%), thrombocytopenia (52.9%), leukopenia (44.1%), and diarrhea (38.2%). One patient (2.9%) receiving 600 mg BID experienced dose-limiting toxicity due to grade 4 thrombocytopenia. The dose of 400 mg BID was selected as the RP2D. The ORR was 67.6%, comprising 29.4% complete remission and 38.2% partial remission. As of the data cutoff in September 2024, the median follow-up period was 15.7 months, with a median duration of response of 14.8 months; overall survival had not yet been reached. The selective EZH1/2 dual inhibitor HH2853 demonstrated acceptable and manageable safety profiles and promising efficacy in r/r PTCL patients, indicating its therapeutic potential for this difficult-to-treat patient population. NCT04390737.
The Future of Personalized Cancer Vaccines
Authors: Dylan J. Martini, Catherine J. Wu
Journal: Cancer Discovery (2025)

Abstract In early clinical studies, genomics-guided personalized cancer vaccines (PCVs) have demonstrated the capabilities of inducing long-term, tumor-specific immune responses across various malignancies, clinical settings, and treatment regimens. Now that PCVs have advanced to large-scale, randomized clinical trials, we are at a pivotal time. The future success of PCVs will likely be dictated by our collective ability to apply and iterate upon the foundational lessons from early and ongoing in-depth studies so that we can rationally exploit the cytolytic capabilities of PCVs to eradicate advanced cancer, cure patients in the adjuvant setting, and prevent the development of malignancy in high-risk patients.
A Guide to Extrachromosomal DNA: Cancer’s Dynamic Circular Genome
Authors: Natasha E. Weiser, Thomas B.K. Watkins, Howard Y. Chang, Paul S. Mischel
Journal: Cancer Discovery (2025)

Abstract Focal amplifications of oncogenes are important cancer drivers. They can occur on chromosomes or in the context of circular extrachromosomal DNA (ecDNA). Many key features of ecDNAs were described in the 1960s to 1980s, including their “unstable” nature and their ability to confer drug resistance. With the benefit of new technologies, our understanding of ecDNAs has advanced dramatically in the last decade, both in breadth and in depth, including the remarkable discovery that ecDNAs are present in 17% of all cancers and are associated with worse patient outcomes. In this study, we present a guide to ecDNA tools and biology. Significance: Focal amplifications on ecDNAs are commonly found in cancer and are associated with poor patient outcomes and distinct biology. In this review, we provide a guide to ecDNA biology and available tools as well as our perspective on this rapidly evolving field.
COnventional vs. Optimized PERiprocedural Analgosedation vs. Total IntraVEnous Anesthesia for Pulsed-Field Ablation: a Three-Arm Randomized Controlled Trial (COOPERATIVE-PFA)
Authors: Veronika Sochorová, Veronika Kunštátová, Pavel OsmanČík, František Duška, Dalibor Heřman, Petr Waldauf, Lukáš Povišer, Jakub Karch, Lucie Znojilová, Věra Filipcová, Jana Hozmanová, Jana Veselá, Marek Hozman
Journal: Circulation (2025)

Background: Deep analgosedation (DAS) or general anesthesia (GA) is mandatory for pulsed-field ablation (PFA) of atrial fibrillation (AF). In contrast to DAS, GA (conventional or total intravenous anesthesia [TIVA]) requires airway management. To find the optimal sedation regimen, this study compared ketamine-remimazolam DAS and propofol-opioid TIVA to propofol-opioid DAS, focusing on sedation-related adverse events. Methods: Patients indicated for AF catheter ablation were randomly assigned in a 1:1:1 ratio to (1) DAS using intermittent propofol-opioid boluses (arm P), (2) continuous remimazolam-ketamine DAS (arm R), or (3) continuous propofol-opioid TIVA with secured airways (arm TIVA). Catheter ablation was performed using the FARAPULSE system (Boston Scientific, MA, USA). The major exclusion criterion was obstructive sleep apnea syndrome. The primary endpoint was defined as a composite of hypoxemia, hypotensive, or hypertensive events requiring intervention or leading to procedure discontinuation. Secondary endpoints included hemodynamic instability events, procedure time, serious adverse events, and patient satisfaction. Results: One-hundred and twenty-seven patients (mean age 62.9 ± 10.3 years, 35.1% female, 47.2% with paroxysmal AF) were enrolled and randomized to the P (N = 42), R (N = 43) or TIVA (N = 42) arms. The primary endpoint occurred in 85.7% of P pts., 27.9% of R pts., and 66.7% of TIVA pts. (P &lt; 0.001), driven by hypoxemia in the P arm (100% of pts. with the primary endpoint) and by hypotension in the TIVA arm (100%). The R arm showed a similar distribution of hypoxemia (50%) and hypotensive (66.7%) events. No differences were observed in mean procedural times, rates of serious adverse events, and assessment of patient satisfaction. Conclusions: In PFA procedures for AF, remimazolam-ketamine DAS was superior to propofol-opioid regimens (either boluses or continuous) and had the lowest risk of hypoxemia and hypotensive events. More than 80% of patients undergoing conventional propofol-opioid analgosedation experienced hypoxemia.
Nonoperative Management of Mismatch Repair–Deficient Tumors
Authors: Andrea Cercek, Michael B. Foote, Benoit Rousseau, J. Joshua Smith, Jinru Shia, Jenna Sinopoli, Jill Weiss, Melissa Lumish, Lindsay Temple, Miteshkumar Patel, Callahan Wilde, Leonard B. Saltz, Guillem Argiles, Zsofia Stadler, Oliver Artz, Steven Maron, Geoffrey Ku, Ping Gu, Yelena Y. Janjigian, Daniela Molena, Gopa Iyer, Jonathan Coleman, Wassim Abida, Seth Cohen, Kevin Soares, Mark Schattner, Vivian E. Strong, Rona Yaeger, Philip Paty, Marina Shcherba, Ryan Sugarman, Paul B. Romesser, Alice Zervoudakis, Avni Desai, Neil H. Segal, Imane El Dika, Maria Widmar, Iris Wei, Emmanouil Pappou, Gerard Fumo, Santiago Aparo, Mithat Gonen, Marc Gollub, Vetri S. Jayaprakasham, Tae-Hyung Kim, Julio Garcia Aguilar, Martin Weiser, Luis A. Diaz
Journal: New England Journal of Medicine (2025)

Among patients with mismatch repair-deficient (dMMR), locally advanced rectal cancer, neoadjuvant checkpoint blockade eliminated the need for surgery in a high proportion of patients. Whether this approach can be extended to all early-stage dMMR solid tumors, regardless of tumor site, is unknown. We conducted a phase 2 study in which patients with stage I, II, or III dMMR solid tumors that were amenable to curative-intent surgery were treated with neoadjuvant dostarlimab, a programmed cell death 1 (PD-1) blocking agent, for 6 months. The response to treatment was assessed in two cohorts: patients in cohort 1 had dMMR, locally advanced rectal cancer, and patients in cohort 2 had dMMR nonrectal solid tumors. Patients with a clinical complete response could elect to proceed with nonoperative management; those with residual disease were to undergo resection. In this analysis, the primary end point, assessed in cohort 1, was a sustained clinical complete response at 12 months. Recurrence-free survival and safety were evaluated. A total of 117 patients were included in the analysis. In cohort 1, all 49 patients who completed treatment had a clinical complete response and elected to proceed with nonoperative management. A total of 37 patients had a sustained clinical complete response at 12 months, a finding that met the criterion for efficacy. In cohort 2, a total of 35 of 54 patients who completed treatment had a clinical complete response, and 33 elected to proceed with nonoperative management. Among the 103 patients who completed treatment across both cohorts, 84 had a clinical complete response, and 82 did not undergo surgery. Among the 117 total patients, recurrence-free survival at 2 years was 92% (95% confidence interval, 86 to 99); the median follow-up for recurrence was 20.0 months (range, 0 to 60.8). The majority of patients (95%) had reversible, grade 1 or 2 adverse events (60%) or had no adverse events (35%). The option for curative resection was not compromised during or after treatment in any of the patients. Among patients with early-stage dMMR solid tumors that were amenable to curative-intent surgery, neoadjuvant PD-1 blockade led to organ preservation in a high proportion of patients. (Funded by Swim Across America and others; ClinicalTrials.gov number, NCT04165772.).
HPV16-Expressing Tumors Release Multiple IL-1 Ligands to Orchestrate Systemic Immunosuppression Whose Disruption Enables Efficacy of a Therapeutic Vaccine
Authors: Morgane Lecointre, Jérémy Guillot, Rachel Marcone, Dilara Ozdoganlar, Marjorie Cayatte, Elin Jaensson Gyllenbäck, David Liberg, Nadine Fournier, Krisztian Homicsko, Douglas Hanahan
Journal: Cancer Discovery (2025)

Abstract It is well-established that symptomatic cancers evade immune destruction by coalescing tumor microenvironments to suppress adaptive immunity. Additionally, mouse models of cervical and other cancers have revealed a capability of tumors to systemically induce the expansion of neutrophils that cripple T-cell development in spleen and lymph nodes, further impairing immune responses. Now we show that human papillomavirus type 16 (HPV16)–driven squamous cell tumors in the cervix and skin release into the circulatory system four immunoregulatory ligands – IL-1α, IL-1β, IL-33, and IL-36β – that bias the bone marrow toward granulocytic myelopoiesis, producing immunosuppressive neutrophils populating spleens and tumors. An IL-1 family coreceptor antagonist, anti-IL1RAP, abrogates this neutrophil expansion and complements an otherwise inefficacious HPV16 E7 peptide vaccine to elicit an effective antitumor immune response that is further sustained by anti–CTLA-4. Evidence for similarly IL-1–driven systemic immunosuppression in human cervical tumors encourages evaluation of this combinatorial therapeutic strategy for treating a largely immunoevasive cancer type. Significance: Cervical cancer is the fourth leading cause of cancer deaths in women worldwide. Although the disease is driven by two antigenic viral oncoproteins, therapeutic vaccines have proved ineffective, inferentially due to systemic immunosuppression. This study elucidated an actionable mechanism, whose disruption renders an oncoprotein vaccine efficacious, with translational potential.
Blocking Nitrosylation Induces Immunogenic Cell Death by Sensitizing NRAS-Mutant Melanoma to MEK Inhibitors
Authors: Jyoti Srivastava, Vipin K. Yadav, Rachel V. Jimenez, Pravin R. Phadatare, Ninad A. Inamdar, Montana M. Young, Antonella Bacchiocchi, Ruth Halaban, Bin Fang, Alvaro de Mingo. Pulido, Kenneth Y. Tsai, Keiran S.M. Smalley, John M. Koomen, Paulo C. Rodriguez, Sanjay Premi
Journal: Cancer Research (2025)

Abstract Activating NRAS mutations occur in 15-25% of all melanomas. However, this subtype remains refractory to existing therapeutics, including immunotherapy and RAS inhibitors; therefore, identifying innovative treatment strategies is of utmost importance. We investigated the role of nitrosylation, a nitric oxide-induced post-translational modification, in melanoma progression and therapeutic resistance. Inhibiting nitrosylation sensitized NRAS-mutant melanomas to targeted MEK inhibitors (MEKi), leading to sustained downregulation of the ERK-MAPK pathway, along with concomitant de-nitrosylation of NRAS, MEK, ERK, RSK1, and DUSPs. Global nitrosylome profiling using mass-spectrometry revealed nitrosylation of multiple ERK regulators. Gain- and loss-of-function studies confirmed a positive association between nitrosylation and ERK activation. ERK and MEK proteins harbored potential nitrosylation sites, mutation of which abrogated their phosphorylation and inhibited cell growth. The nitrosylome also contained death-associated molecular patterns (DAMPs), factors known to induce immunogenic cell death (ICD). Notably, nitrosylation inhibition combined with MEKi markedly inhibited Nras-mutant melanoma growth in an immunocompetent mouse model. This was accompanied by downregulated MEK-ERK signaling and extracellular release of DAMPs like calreticulin, phospho-eIF2α, and HMGB1, confirming ICD induction. Furthermore, the combination significantly increased the repertoire of CD8+ T cells, dendritic cells (DCs), and macrophages in the tumor microenvironment, which was validated in co-cultures of DCs and T-lymphocytes. In conclusion, the current study demonstrates that nitrosylation inhibition sensitizes NRAS-mutant melanomas to targeted MEKi-induced cell death and causes the release of non-nitrosylated (active) DAMPs that induce a potent anti-melanoma immune response via ICD. These findings highlight potential therapeutic vulnerabilities in the currently untreatable NRAS-mutant melanoma subtype.
Overcoming B-ALL Resistance to Targeted and Immune Therapies by Rational Combination Strategies
Authors: Miguel Quijada-Álamo, Grace Freed, Elvin Wagenblast
Journal: Blood Cancer Discovery (2025)

Summary: Despite the remarkable efficacy of targeted therapies and immunotherapies in B-cell acute lymphoblastic leukemia (B-ALL), relapsed and refractory cases remain a major challenge. In this review, we discuss how integrating targeted agents with immunotherapy could help overcome resistance and improve long-term patient outcomes in B-ALL.
Mutant p53 Gain of Function: Why Many See It, Why Some Do not
Authors: Guillermina Lozano, Carol Prives, Kanaga Sabapathy
Journal: Cancer Discovery (2025)

Summary: Mutations in the TP53 tumor-suppressor gene in human cancer are unique in that 60% to 70% are of the missense variety, resulting in a full-length protein that is often highly expressed in patients’ tumors. These missense mutant proteins often exhibit pro-oncogenic activities (referred to as gain of function) in mouse models and human cell lines and correlate with poor cancer prognosis in some cases.
Outcomes after DCD Cardiac Transplantation: An international, multicenter retrospective study
Authors: John O Louca, Marco Öchsner, Sai Bhagra, Ashish Shah, Kelly Schlendorf, Brian Lima, Chen Chia Wang, Hasan Siddiqi, Ali Irshad, Jacob Schroder, Sarah Casalinova, Carmelo Milano, Kiran Khush, Anette Skoda, Helen Luikart, Euan Ashley, Nader Moazami, Les James, Owais Dar, Mailen Konicoff, Marian Urban, John Um, Anthony Castleberry, Jordan R H Hoffman, Sarah Y Park, Michael T Cain, Katharina Fetten, Dan Meyer, Addison Xu, Francisco Gonzalez-Vilchez, Beatriz Domínguez-Gil, Mario Royo-Villanova, Iris Garrido, Janne Brouckaert, Filip Rega, Vincent Tchana-Sato, Marius Berman, James Bae, Sanjay Sinha, Stephen Pettit, Simon Messer, Stephen Large
Journal: JACC Heart Failure (2025)

As donation after circulatory determination of death (DCD) heart transplantation (HT) becomes more widely adopted, there is a need to establish the most clinically effective method of organ procurement. This international, multicenter study compares outcomes of DCD-HT across Europe and the United States (US) between recipients whose donor hearts were retrieved using thoraco-abdominal normothermic regional perfusion (taNRP) to those whose hearts were recovered using direct procurement and perfusion (DPP). This was a retrospective observational study across 20 heart transplant centers in Belgium, Spain, the United Kingdom (UK) and the US. This study included all patients undergoing DCD-HT at participating centers, from the start of each center's DCD program through 01/01/2023. DCD-HT with recovery using either taNRP or DPP were compared to one-another. Post-transplant outcomes included (i)survival at 1-year, (ii)incidence of severe primary graft dysfunction (PGD), (iii)episodes of treated, biopsy-proven acute-cellular rejection (ACR) in the first year following transplantation. 504 DCD-HT took place in the study period. Survival at one year was similar for taNRP and DPP recipients (91% vs 88%, p=0.1). taNRP recipients had a lower rate of severe PGD (7.6% vs 19.2%, p<0.001) and fewer episodes of biopsy-proven, ACR requiring treatment in the first-year post-transplantation (13% vs 25%,p<0.001). In an international study of DCD-HT, recipients of hearts retrieved by taNRP technique had lower rates of severe PGD and fewer episodes of biopsy-proven ACR in the first year when compared with those retrieved utilizing DPP. These results should be further investigated with randomized control trials.