tbuckley/cabot-search huggingface dataset:
Spatial Profiling Identifies Regionally Distinct Microenvironments and Targetable Immunosuppressive Mechanisms in Pediatric Osteosarcoma Pulmonary Metastases
Authors: Jason Eigenbrood, Nathan Wong, Paul Mallory, Janice S. Pereira, Demond Williams, Douglass W. Morris-II, Jessica A. Beck, James C. Cronk, Carly M. Sayers, Monica Mendez, Linus Kaiser, Julie Galindo, Jatinder Singh, Ashley Cardamone, Milind Pore, Michael Kelly, Amy K. LeBlanc, Jennifer Cotter, Rosandra N. Kaplan, Troy A. McEachron
Journal: Cancer Research (2025)

Osteosarcoma is the most common malignant bone tumor in young patients and remains a significant clinical challenge, particularly at the metastatic stage. Studies detailing the immunosuppressive mechanisms within the metastatic osteosarcoma microenvironment are needed to elucidate the cellular communities in the metastatic microenvironment that support metastatic growth and to identify therapeutic approaches to target the crosstalk between cancer cells and the microenvironment. Here, we performed spatial transcriptional profiling on a cohort of osteosarcoma pulmonary metastases from pediatric patients. The data revealed a conserved spatial gene expression pattern resembling a foreign body granuloma, characterized by peripheral inflammatory signaling, fibrocollagenous encapsulation, lymphocyte exclusion, and peritumoral macrophage accumulation. The intratumoral microenvironment of these lesions, however, lacked inflammatory signaling. Exploration of spatially distinct drug-gene interactions identified the CXCR4 signaling axis, which displayed spatial heterogeneity and complexity, as a potential therapeutic target that bridges both the intratumoral and extratumoral microenvironments. Collectively, this study reveals that metastatic osteosarcoma is comprised of multiple regionally distinct immunosuppressive microenvironments.
Engineering Protocell Networks for Prototissue Development
Authors: Zhetong Liu, Lei Liu, Rong Huang, Fu‐Jian Xu, Nana Zhao, Yiyang Lin
Journal: Advanced Healthcare Materials (2025)

The assembly of protocells into prototissues represents a significant step forward in mimicking the hierarchical structure and complex functions of biological tissues. This review explores the construction of various protocell models, including lipid vesicles, polymer vesicles, proteinosomes, membraneless coacervates, and emulsion droplets. It examines the range of chemical and physical methods employed to spatially organize these protocells into structured, functional prototissues. Furthermore, the review highlights the distinctive properties of prototissues, such as their ability to facilitate intra- and inter-protocell communication, exhibit collective behaviors like oscillations and deformation, and their promising applications in biomedicine. By bridging the gap between synthetic cells and functional tissue-like systems, this review provides insights into the design, fabrication, and potential applications of prototissues in synthetic biology and regenerative medicine.
Expert consensus on orthodontic treatment of patients with periodontal disease
Authors: Wenjie Zhong, Chenchen Zhou, Yuanyuan Yin, Ge Feng, Zhihe Zhao, Yaping Pan, Yuxing Bai, Zuolin Jin, Yan Xu, Bing Fang, Yi Liu, Hong He, Faming Chen, Weiran Li, Shaohua Ge, Ang Li, Yi Ding, Lili Chen, Fuhua Yan, Jinlin Song
Journal: International Journal of Oral Science (2025)

Patients with periodontal disease often require combined periodontal-orthodontic interventions to restore periodontal health, function, and aesthetics, ensuring both patient satisfaction and long-term stability. Managing these patients involving orthodontic tooth movement can be particularly challenging due to compromised periodontal soft and hard tissues, especially in severe cases. Therefore, close collaboration between orthodontists and periodontists for comprehensive diagnosis and sequential treatment, along with diligent patient compliance throughout the entire process, is crucial for achieving favorable treatment outcomes. Moreover, long-term orthodontic retention and periodontal follow-up are essential to sustain treatment success. This expert consensus, informed by the latest clinical research and practical experience, addresses clinical considerations for orthodontic treatment of periodontal patients, delineating indications, objectives, procedures, and principles with the aim of providing clear and practical guidance for clinical practitioners.
H1‐0 is a specific mediator of the repressive ETV6::RUNX1 transcriptional landscape in preleukemia and B cell acute lymphoblastic leukemia
Authors: Vera H. Jepsen, Andrea Hanel, Daniel Picard, Rigveda Bhave, Rebecca Hasselmann, Juha Mehtonen, Julian Schliehe‐Diecks, Carla‐Johanna Kath, Vithusan Suppiyar, Yash Prasad, Katerina Schaal, Jia‐Wey Tu, Nadine Rüchel, Ersen Kameri, Nan Qin, Herui Wang, Zhengping Zhuang, Rabea Wagener, Lena Blümel, Tobias Lautwein, Daniel Hein, David Koppstein, Gesine Kögler, Marc Remke, Sanil Bhatia, Merja Heinäniemi, Arndt Borkhardt, Ute Fischer
Journal: HemaSphere (2025)

ETV6::RUNX1, the most common oncogenic fusion in pediatric B cell precursor acute lymphoblastic leukemia (BCP-ALL), induces a clinically silent preleukemic state that can persist in carriers for over a decade and may progress to overt leukemia upon acquisition of secondary lesions. The mechanisms contributing to quiescence of ETV6::RUNX1+ preleukemic cells still remain elusive. In this study, we identify linker histone H1-0 as a critical mediator of the ETV6::RUNX1+ preleukemic state by employing human -induced pluripotent stem cell (hiPSC) models engineered by using CRISPR/Cas9 gene editing. Global gene expression analysis revealed upregulation of H1-0 in ETV6::RUNX1+ hiPSCs that was preserved upon hematopoietic differentiation. Moreover, whole transcriptome data of 1,727 leukemia patient samples showed significantly elevated H1-0 levels in ETV6::RUNX1+ BCP-ALL compared to other leukemia entities. Using dual-luciferase promoter assays, we show that ETV6::RUNX1 induces H1-0 promoter activity. We further demonstrate that depletion of H1-0 specifically inhibits ETV6::RUNX1 signature genes, including RAG1 and EPOR. Single-cell sequencing showed that H1-0 is highly expressed in quiescent hematopoietic cells. Importantly, H1-0 protein levels correspond to susceptibility of BCP-ALL cells towards histone deacetylase inhibitors (HDACis) and combinatorial treatment using the H1-0-inducing HDACi Quisinostat showed promising synergism with established chemotherapeutic drugs. Taken together, our data identify H1-0 as a key regulator of the ETV6::RUNX1+ transcriptome and indicate that the addition of Quisinostat may be beneficial to target non-responsive or relapsing ETV6::RUNX1+ BCP-ALL.
Nonlinear recurrent inhibition through facilitating serotonin release in the raphe
Authors: Michael B Lynn, Sean D Geddes, Mohamad Chahrour, Sébastien Maillé, Léa Caya-Bissonnette, Emerson Harkin, Érik Harvey-Girard, Samir Haj-Dahmane, Richard Naud, Jean-Claude Béïque
Journal: Nature Neuroscience (2025)
Immune checkpoints regulate acute myeloid leukemia stem cells
Authors: Chantal Reinhardt, Adrian F Ochsenbein
Journal: Leukemia (2025)

Acute myeloid leukemia stem cells (LSCs) express major histocompatibility complex (MHC) class I and II and many different immune checkpoint ligands and receptors, in which respect they resemble professional antigen-presenting cells. In addition, LSCs reside in the bone marrow (BM), a primary and secondary lymphoid organ, surrounded by immune cells. The function of these immune checkpoints (ICs) in the regulation of an anti-tumor immune response is well studied and IC inhibitors (ICIs) became a standard of care in many solid tumors. However, ICIs have very limited efficacy in AML. Nevertheless, the expression especially of immune activating ligands and receptors on LSCs is somewhat unexpected, since these cells have to evade protective immunity. Many ICs have been shown to mediate direct signaling in AML blasts and LSCs and thereby regulate self-renewal, differentiation and expansion of leukemic cells. Thus, the expression of ICs on the cell surface or their soluble forms often correlate with worse survival. In this review we summarize recent data on selected ICs of the immunoglobulin superfamily (IgSF) and the tumor necrosis factor receptor superfamily (TNFRSF) that have a documented role in the regulation of LSCs, independent of their immune regulatory role, and might become novel therapeutic targets.
High‐dose therapy followed by autologous stem cell transplantation emerges as the preferred salvage therapy in patients with limited‐stage Hodgkin lymphoma progressing/relapsing after initial therapy: A subset analysis of the EORTC/LYSA/FIL H10 trial
Authors: Gotti Manuel, Yana Stepanishyna, Tetiana Skrypets, Luigi Marcheselli, Caterina Cristinelli, Barbara Botto, Sanne Tonino, Doriane Cavalieri, Alessandro Pulsoni, Martin Hutchings, Mohammad Hammoud, Catherine Fortpied, Luigi Rigacci, Wouter Plattel, Marc André, Massimo Federico
Journal: HemaSphere (2025)
Clinicopathologic characteristics and outcomes of patients with clonal hematopoiesis who progress to myeloid neoplasms
Authors: Kelly S Chien, Julie S Braish, Ziyi Li, Sanam Loghavi, Alex Bataller, Guillermo Montalban-Bravo, Koji Sasaki, Rashmi Kanagal-Shamanna, Koichi Takahashi, Courtney D DiNardo, Mahesh Swaminathan, Hagop M Kantarjian, Guillermo Garcia-Manero
Journal: Leukemia (2025)
Effects of Evolocumab on Coronary Plaque Composition and Microcalcification Activity by Coronary PET and CT Angiography
Authors: Donghee Han, Evangelos Tzolos, Rebekah Park, Heidi Gransar, Mark Hyun, John D Friedman, Sean W Hayes, Louise E J Thomson, Alan C Kwan, Matthew Budoff, Prediman K Shah, Jacek Kwieciński, Sarah Wetzel, Chloe Findling, Piotr J Slomka, Damini Dey, Balaji K Tamarappoo, Daniel S Berman
Journal: JACC. Cardiovascular imaging (2025)
Maternal consumption of urbanized diet compromises early-life health in association with gut microbiota
Authors: Rong Huang, Guicheng Zhou, Jie Cai, Cha Cao, Zhenjun Zhu, Qingping Wu, Fen Zhang, Yu Ding
Journal: Gut Microbes (2025)

Urbanization has significantly transformed dietary habits worldwide, contributing to a globally increased burden of non-communicable diseases and altered gut microbiota landscape. However, it is often overlooked that the adverse effects of these dietary changes can be transmitted from the mother to offspring during early developmental stages, subsequently influencing the predisposition to various diseases later in life. This review aims to delineate the detrimental effects of maternal urban-lifestyle diet (urbanized diet) on early-life health and gut microbiota assembly, provide mechanistic insights on how urbanized diet mediates mother-to-offspring transfer of bioactive substances in both intrauterine and extrauterine and thus affects fetal and neonatal development. Moreover, we also further propose a framework for developing microbiome-targeted precision nutrition and diet strategies specifically for pregnant and lactating women. The establishment of such knowledge can help develop proactive preventive measures from the beginning of life, ultimately reducing the long-term risk of disease and improving public health outcomes.
Prognostic and Predictive Insights From Genomic Assays for Breast Cancer in Diverse Populations
Authors: Yara Abdou, Olga Kantor, Jennifer Racz, Lisa Newman, Lori J. Pierce, Eric P. Winer
Journal: JAMA Oncology (2025)

Despite recent declines in breast cancer mortality rates, substantial disparities persist among race and ethnicity groups. Genomic assays are crucial for understanding the biological characteristics of tumors, providing valuable insights into prognosis and treatment response. Their integration into personalized clinical decision-making has notably enhanced outcomes, making these assays particularly valuable for underrepresented populations, which often face disproportionately poorer prognoses. Expanding research to evaluate the performance and predictive value of these assays across diverse groups is essential to ensure equitable benefits for all patients. This review evaluated the distribution of risk estimates from multigene assays, primarily focusing on 21-, 70-, and 50-gene signature assays, their predictive capabilities and impact on breast cancer recurrence and survival outcomes across race and ethnicity groups. Findings indicate that racial and ethnic disparities in breast cancer outcomes were influenced by a complex interplay of biological, social, and systemic factors. Black women were more likely to have aggressive tumor phenotypes, such as luminal B and basal-like subtypes, which contributed to poorer outcomes. These disparities persist even after adjusting for genomic assay results and molecular subtypes, suggesting that genomic factors alone cannot fully explain differences in clinical outcomes. Although subgroup analyses from 2 randomized clinical trials showed no apparent differences in the 21-gene signature's predictive value across racial groups, further research is needed to ensure that genomic assays are equitably calibrated for diverse populations. This review supports genomic assays as valuable tools for informing prognosis and treatment decisions in breast cancer; however, they do not fully capture factors associated with racial and ethnic disparities in outcomes. A comprehensive approach that integrates genomic data with a deeper understanding of social determinants and systemic inequities is essential to ensure all patients benefit equitably from advancements in personalized medicine.
Comparison of Serum Creatinine- and Cystatin C–Based eGFR at Baseline and Their Prediction of Incident Moderate Albuminuria in Individuals With Type 1 Diabetes
Authors: Valma Harjutsalo, Lena M. Thorn, Per-Henrik Groop
Journal: Diabetes Care (2025)

To assess the concordance between serum creatinine (SCr)- and serum cystatin C (SCysC)-based estimated glomerular filtration rate (eGFR) in individuals with type 1 diabetes (T1D) at different stages of albuminuria; identify the factors associated with the discordance; and study the association of SCysC, eGFR of creatinine (eGFRcr), and eGFR of cystatin C (eGFRcys) with incident moderate albuminuria. We included 3,769 FinnDiane Study participants (51.8% men) with T1D but not kidney failure and with available data on SCr and SCysC. Median age was 36.6 (interquartile range [IQR] = 27.7-46.4) years, and median duration of diabetes was 19.5 (IQR = 10.9-29.2) years. eGFRcys and eGFRcr were calculated using the Chronic Kidney Disease Epidemiology Collaboration equations. We assessed the rate of concordance and discordance in the following three groups: -15 ≤ eGFRdiff < 15, eGFRdiff < -15, and eGFRdiff ≥ 15 mL/min/1.73 m2 (where eGFRdiff = eGFRcys minus eGFRcr), as well as the variables that contributed to the discordance. In addition, the association of CysC, eGFRcr, and eGFRcys with the incidence of moderate albuminuria was evaluated. The mean (±SD) absolute eGFRdiff was 14.0 ± 12.2 mL/min/1.73 m2. The overall concordance rate was 62.9%, the negative discordance rate was 20.4%, and the positive discordance rate was 16.7%. Sex, albuminuria status, smoking, retinal laser photocoagulation, HbA1c, HDL cholesterol, high-sensitivity C-reactive protein, and insulin dose per kilogram contributed to the discordance. Both SCysC and eGFRcys were associated with the incidence of moderate albuminuria, whereas eGFRcr was not. Discordant eGFRcys and eGFRcr values were common in individuals with T1D. These findings suggest SCysC may facilitate early identification of individuals at risk for albuminuria.
Dissection of single-cell landscapes for the development of chimeric antigen receptor T cells in Hodgkin lymphoma
Authors: Adrian Gottschlich, Ruth Grünmeier, Gordon Victor Hoffmann, Sayantan Nandi, Vladyslav Kavaka, Philipp Jie Müller, Jakob Jobst, Arman Oner, Rainer Kaiser, Jan Gärtig, Ignazio Piseddu, Stephanie Frenz-Wiessner, Savannah D. Fairley, Heiko Schulz, Veronika Igl, Thomas Alexander Janert, Lea Di Fina, Maité Mulkers, Moritz Thomas, Daria Briukhovetska, Donjetë Simnica, Emanuele Carlini, Christina Angeliki Tsiverioti, Marcel P. Trefny, Theo Lorenzini, Florian Märkl, Pedro Mesquita, Ruben Brabenec, Thaddäus Strzalkowski, Sophia Stock, Stefanos Michaelides, Johannes Hellmuth, Martin Thelen, Sarah Reinke, Wolfram Klapper, Pascal Francois Gelebart, Leo Nicolai, Carsten Marr, Eduardo Beltrán, Remco T. A. Megens, Christoph Klein, Fanny Baran-Marszak, Andreas Rosenwald, Michael von Bergwelt-Baildon, Paul J. Bröckelmann, Stefan Endres, Sebastian Kobold
Journal: Blood (2025)
CircTADA2A stabilizes p53 via interacting with TRIM28 and suppresses the maintenance of FLT3-ITD acute myeloid leukemia
Authors: Ran Li, Xiaolu Wu, Kai Xue, Shishuang Wu, Ge Jiang, Mengke He, Yi Xia, Hailing Liu, Miao Zhong, Jianyong Li, Lei Fan, Junmin Li
Journal: Leukemia (2025)
Resident Physician Intentions Regarding Unionization
Authors: Laura K. Barger, Matthew D. Weaver, Christopher P. Landrigan, Jason P. Sullivan, Rebecca Robbins, Ariel S. Winn, Charles A. Czeisler
Journal: JAMA Network Open (2025)

Resident physicians provide frontline care to approximately 70% of hospitalized patients. After decades of relative stability with a small minority of resident physicians unionized, unionization movements have succeeded in recent years at multiple major academic medical centers. To evaluate resident physicians' unionization intention and the factors informing their unionization consideration at their institution. This nationwide survey study was conducted in May 2023 among a cohort of resident physicians, which was established over the course of 3 academic years (2020-2023). Resident physicians were invited to participate in an end-of-study survey on contemporary topics, which included questions on unionization. Consideration of unionization by resident physicians. The main outcomes were the presence of a union at the institution for physicians in training, the presence of a movement to unionize, whether the resident physician would vote to unionize, and the factors most important in considering unionization. All measures were self-reported. A total of 1235 participants (mean [SD] age, 28.8 [3.6] years; 737 of 1224 females [60%]; 791 of 1086 (73%) in their first postgraduate year) responded to survey questions regarding unionization. Twenty percent of participants (n = 249) reported that physicians in training belonged to a union at their institution. Among the 986 nonunionized resident physicians, 63% (625) reported they would vote to unionize, whereas less than 10% (96) would not vote to unionize. Pay and work hours were the most commonly cited factors in considering unionization (88% [1081 of 1235 participants] and 76% [941 of 1235 participants], respectively). In this survey study, most resident physicians (>70%) reported either being in a union or supporting unionization at their institution, citing pay and financial security as critical factors in their consideration of unionization. Future research should investigate other factors and whether unionization achieves its goals of increased pay and benefits, work hours, and well-being.
Chromosome 1p Loss and 1q Gain for Grading of Meningioma
Authors: Alexander P. Landry, Justin Z. Wang, Vikas Patil, Jeff Liu, Chloe Gui, Yosef Ellenbogen, Andrew Ajisebutu, Leeor Yefet, Qingxia Wei, Olivia Singh, Julio Sosa, Sheila Mansouri, Aaron A. Cohen-Gadol, Ghazaleh Tabatabai, Marcos Tatagiba, Felix Behling, Jill S. Barnholtz-Sloan, Andrew E. Sloan, Silky Chotai, Lola B. Chambless, Alireza Mansouri, Serge Makarenko, Stephen Yip, Felix Ehret, David Capper, Derek S. Tsang, Jennifer Moliterno, Murat Gunel, Pieter Wesseling, Felix Sahm, Kenneth Aldape, Andrew Gao, Gelareh Zadeh, Farshad Nassiri
Journal: JAMA Oncology (2025)

The World Health Organization (WHO) classification of central nervous system tumors (CNS) grading for meningioma was updated in 2021 to include rare molecular features, namely homozygous deletions of CDKN2A or CDKN2B and TERT promotor alterations. Previous work, including the cIMPACT-NOW statement, has discussed the potential value of including chromosomal copy number alterations to help refine the current grading system. To identify chromosomal copy number alterations that could be used to improve the current CNS WHO grading of meningioma. In this cohort study, patients with surgically treated meningioma were followed-up until recurrence or progression of disease or death. Chromosomal copy number alterations were then correlated with progression-free survival (PFS) to identify new outcome biomarkers. This study included patients with a histopathological diagnosis of meningioma from multiple institutions in Canada, the US, and Germany, with molecular data collection starting in 2016. Data were analyzed from January to September 2024. All patients underwent surgery for meningioma and a subset underwent radiation therapy. The main outcome was PFS. Cox regression analysis was used to identify copy number alterations associated with outcomes in the context of WHO grading. Among 1964 patients with meningioma (1256 female; median [IQR] age, 58 [48-69] years) assessed, loss of chromosome 1p in WHO grade 1 meningiomas was associated with significantly worse outcomes compared with tumors without loss of 1p (median PFS, 5.83 [95% CI, 4.36-∞] years vs 34.54 [95% CI, 16.01-∞] years; log-rank P < .001). Outcomes of patients with WHO grade 1 tumors with loss of chromosome 1p were comparable to those of patients with WHO grade 2 tumors (median PFS, 4.48 [95% CI, 4.09-5.18] years). Combined loss of chromosome 1p and gain of chromosome 1q were associated with outcomes that were highly concordant with WHO grade 3 tumors, regardless of initial grade (median PFS: grade 1, 2.23 [95% CI, 1.28-∞] years; grade 2, 1.90 [95% CI, 1.23-2.25] years; grade 3, 2.27 [95% CI, 1.68-3.05] years). These findings highlight a role for cytogenetic profiling in the next iteration of CNS WHO grading, with a specific focus on chromosome 1p loss and 1q gain, suggesting that chromosome 1p loss, in addition to 22q loss, should be added as a criterion for a CNS WHO grade of 2 and addition of 1q gain as a criterion for a CNS WHO grade of 3.