tbuckley/cabot-search huggingface dataset:
Deep Learning Model of Primary Tumor and Metastatic Cervical Lymph Nodes From CT for Outcome Predictions in Oropharyngeal Cancer
Authors: Bolin Song, Amaury Leroy, Kailin Yang, Sirvan Khalighi, Krunal Pandav, Tanmoy Dam, Jonathan Lee, Sarah Stock, Xiao T. Li, Jay Sonuga, Pingfu Fu, Shlomo Koyfman, Nabil F. Saba, Mihir R. Patel, Anant Madabhushi
Journal: JAMA Network Open (2025)

Primary tumor (PT) and metastatic cervical lymph node (LN) characteristics are highly associated with oropharyngeal squamous cell carcinoma (OPSCC) prognosis. Currently, there is a lack of studies to combine imaging characteristics of both regions for predictions of p16+ OPSCC outcomes. To develop and validate a computed tomography (CT)-based deep learning classifier that integrates PT and LN features to predict outcomes in p16+ OPSCC and to identify patients with stage I disease who may derive added benefit associated with chemotherapy. In this retrospective prognostic study, radiographic CT scans were analyzed of 811 patients with p16+ OPSCC treated with definitive radiotherapy or chemoradiotherapy from 3 independent cohorts. One cohort from the Cancer Imaging Archive (1998-2013) was used for model development and validation and the 2 remaining cohorts (2002-2015) were used to externally test the model performance. The Swin Transformer architecture was applied to fuse the features from both PT and LN into a multiregion imaging risk score (SwinScore) to predict survival outcomes across and within subpopulations at various stages. Data analysis was performed between February and July 2024. Definitive radiotherapy or chemoradiotherapy treatment for patients with p16+ OPSCC. Hazard ratios (HRs), log-rank tests, concordance index (C index), and net benefit were used to evaluate the associations between multiregion imaging risk score and disease-free survival (DFS), overall survival (OS), and locoregional failure (LRF). Interaction tests were conducted to assess whether the association of chemotherapy with outcome significantly differs across dichotomized multiregion imaging risk score subgroups. The total patient cohort comprised 811 patients with p16+ OPSCC (median age, 59.0 years [IQR, 47.4-70.6 years]; 683 men [84.2%]). In the external test set, the multiregion imaging risk score was found to be prognostic of DFS (HR, 3.76 [95% CI, 1.99-7.10]; P < .001), OS (HR, 4.80 [95% CI, 2.22-10.40]; P < .001), and LRF (HR, 4.47 [95% CI, 1.43-14.00]; P = .01) among all patients with p16+ OPSCC. The multiregion imaging risk score, integrating both PT and LN information, demonstrated a higher C index (0.63) compared with models focusing solely on PT (0.61) or LN (0.58). Chemotherapy was associated with improved DFS only among patients with high scores (HR, 0.09 [95% CI, 0.02-0.47]; P = .004) but not those with low scores (HR, 0.83 [95% CI, 0.32-2.10]; P = .69). This prognostic study of p16+ OPSCC describes the development of a CT-based imaging risk score integrating PT and metastatic cervical LN features to predict recurrence risk and identify suitable candidates for treatment tailoring. This tool could optimize treatment modulations of p16+ OPSCC at a highly granular level.
Management of Adult Acute Lymphoblastic Leukemia
Authors: Hagop Kantarjian, Ibrahim Aldoss, Elias Jabbour
Journal: JAMA Oncology (2025)

Research in acute lymphoblastic leukemia (ALL) is translating into rapid changes in therapy and outcomes. Historically, adult ALL was treated with intensive chemotherapy extending over 2.5 to 3 years. This established tradition, accepted because of the high cure rates in childhood ALL, has been challenged by the development of highly active targeted therapies. Treatment modalities, combined with less and shorter chemotherapy durations, have produced better results than chemotherapy. The novel therapies include using the more potent BCR::ABL1 tyrosine kinase inhibitors (eg, ponatinib, dasatinib) with the bispecific CD3-CD19 T-cell engager antibody blinatumomab in Philadelphia chromosome-positive ALL and combining blinatumomab and/or inotuzumab (CD22 antibody drug conjugate) with standard chemotherapy in B-cell ALL. These have been associated with improved 4-year survival rates of 85% to 90% in Philadelphia chromosome-positive ALL and 80% to 85% in B-cell ALL. The management of ALL is changing rapidly. Investigators have evaluated frontline and later-line regimens with combinations of tyrosine kinase inhibitors and immunotherapies with less or no chemotherapy. Future research will evaluate CD19, CD20, and CD22 multitargeting antibodies and chimeric antigen receptor T-cell therapies, new antibody formulations, and less intensive/shorter regimens.
Racial and Ethnic Disparities in Receipt of ERBB2-Targeted Therapy for Breast Cancer, 2010-2020
Authors: Sudarshan Krishnamurthy, Shelley A. Jazowski, Mya L. Roberson, Katherine Reeder-Hayes, Jasmyn J. Tang, Stacie B. Dusetzina, Utibe R. Essien
Journal: JAMA Network Open (2025)

Among older women (aged ≥50 years) with ERBB2 (formerly HER2 or HER2/neu)-positive breast cancer, research has shown racial and ethnic disparities in access to ERBB2-targeted therapies, with Black women receiving treatment at lower rates than their White counterparts. To examine racial and ethnic disparities in receipt of ERBB2-targeted therapies and changes in receipt over time. This retrospective cohort study used Surveillance, Epidemiology, and End Results-Medicare linked data from January 1, 2010, to December 31, 2020. Beneficiaries who were diagnosed with ERBB2-positive breast cancer between 2010 and 2019, were aged 66 years or older at diagnosis, were continuously enrolled in Medicare Parts A and B in the 12 months before and after diagnosis, and had localized or regional stage disease at diagnosis were included. Data were analyzed from February through September 2024. Race and ethnicity defined as non-Hispanic Black or African American, Hispanic, or non-Hispanic White. The primary outcome was receipt of ERBB2-targeted therapies in the 12 months after diagnosis of ERBB2-positive breast cancer. Modified Poisson regression was used to evaluate the probability of receiving ERBB2-targeted therapy by race and ethnicity. Among 12 765 beneficiaries with ERBB2-positive breast cancer (median [IQR] age, 74 [69-80] years; 99.2% female), 8.1% were of Black, 6.9% Hispanic, and 85.0% White race and ethnicity, and 54.2% received ERBB2-targeted therapy. The overall proportion who received ERBB2-targeted therapies increased from 41.3% in 2010-2011 to 64.3% in 2018-2019. Compared with White patients, Black patients had a lower likelihood of receiving ERBB2-targeted therapies in 2010-2011 (adjusted risk ratio [ARR], 0.81; 95% confidence limit [CL], 0.68-0.97), as did Hispanic patients (ARR, 0.75; 95% CL, 0.62-0.92). Racial and ethnic disparities in receipt of ERBB2-targeted therapies narrowed over time, with no significant differences observed across racial and ethnic groups in 2018-2019 for Black patients (ARR, 0.97; 95% CL, 0.87-1.08) and Hispanic patients (ARR, 1.05; 95% CL, 0.95-1.16). These findings suggest a narrowing of racial and ethnic disparities in receipt of ERBB2-targeted therapies over time among older Medicare beneficiaries with ERBB2-positive breast cancer. Future research is needed to understand the practices that contributed to the narrowing of racial and ethnic disparities and to develop implementation strategies to effectively improve the quality and equity of breast cancer care.
High-dimensional temporal mapping of CAR T cells reveals phenotypic and functional remodeling during manufacturing
Authors: Amaia Cadinanos-Garai, Christian L Flugel, Anson Cheung, Enzi Jiang, Alix Vaissié, Mohamed Abou-El-Enein
Journal: Molecular Therapy (2025)

Despite the notable success of chimeric antigen receptor (CAR) T cell therapies in hematological malignancies, clinical outcomes remain variable, making it critical to understand how manufacturing influences product composition and function. We developed a 36-marker spectral flow cytometry panel enabling integrated profiling of phenotypic, metabolic, and functional attributes across CAR T cell production. Mid-expansion products (day 5) retained stem-like, metabolically active CD4+ Th1 subsets with high proliferative capacity, whereas prolonged culture (day 10) enriched terminally differentiated CD8+ Tc1 cells and NK-like T cell populations. CAR+ and CAR- T cells showed similar differentiation trajectories, suggesting that culture conditions may have a larger impact on phenotypic remodeling than CAR integration. Upon antigen encounter and restimulation, day 5 and day 10 products showed comparable cytotoxicity, while differing in their activation and checkpoint profiles. Cryopreservation modestly affected stem cell memory, activation, and metabolic markers but preserved overall phenotype and cytotoxic function. These findings establish a high-dimensional framework for mapping CAR T cell dynamics to support manufacturing optimization and next-generation cell therapy design.
Diagnostic validation of novel Borrelia antigens discovered by whole-proteome microarray: Advancing early detection and test of cure for Lyme disease
Authors: Abhijeet Nayak, M E Baarsma, Jacqueline A van Eck, Arlo Z Randall, Jeanine Ursinus, Andy A Teng, Jozelyn V Pablo, Chris Hung, Doris U M Wopereis, Freek van de Schoor, Calin D Popa, Cees C van den Wijngaard, Bart-Jan Kullberg, Leo A B Joosten, Herman Kuiper, Joseph J Campo, Xiaouw Liang, Joppe W Hovius
Journal: Cell Reports Medicine (2025)

Lyme disease serodiagnosis has limited early sensitivity and cannot distinguish active from past infections. To address this, we screen a Borrelia afzelii whole-proteome microarray (1,296 proteins) using human (n = 149) and murine (n = 32) sera. We evaluate three early-stage antigens-BafPKo_A0001, BafPKo_D0016, and BafPKo_A0029. ELISA cutoffs are established using discovery cohort sera (n = 99) and validated with the validation (n = 242) and the prospective (n = 223) cohorts. A0001 demonstrates 87.8% sensitivity, outperforming C6 (69.4%) and STTT (22.5%) in the discovery cohort. In the validation cohort, A0001 reaches 90.5% sensitivity, surpassing C6 by 11.6% and STTT by 50%. In hyper-acute erythema migrans sera (from the prospective cohort), A0001 achieves 55.1% sensitivity, exceeding C6 and STTT by 14.6% and 33.3%, respectively. COMBO-3 and COMBO-2 yield the highest sensitivity of 92.9% and 66.1% in the validation and prospective cohort, respectively. A0001 and D0016 show enhanced and robust seroreversion after antibiotic treatment suggesting their potential as test of cure biomarkers in early Lyme disease.
Low T cell diversity associates with poor outcome in bladder cancer: A comprehensive longitudinal analysis of the T cell receptor repertoire
Authors: Asbjørn Kjær, Nanna Kristjánsdóttir, Randi Istrup Juul, Iver Nordentoft, Karin Birkenkamp-Demtröder, Johanne Ahrenfeldt, Trine Strandgaard, Deema Radif, Darren Hodgson, Christopher Abbosh, Hugo J W L Aerts, Mads Agerbæk, Jørgen Bjerggaard Jensen, Nicolai J Birkbak, Lars Dyrskjøt
Journal: Cell Reports Medicine (2025)

T cells are crucial effector cells in the endogenous defense against cancer, yet the clinical impact of their quantity, diversity, and dynamics remains underexplored. Here, we investigate the clinical relevance of the T cell receptor (TCR) repertoire in patients with bladder cancer. In advanced-stage disease, low pre-treatment peripheral TCR diversity is associated with worse overall survival (p = 0.024), particularly when coupled with low circulating T cell fractions (p = 0.00049). These low-diversity repertoires are dominated by hyper-expanded clones that persist throughout treatment. Further longitudinal analysis reveals reductions in TCR diversity after treatment, indicating adverse effects on the immune system. In early-stage disease, immunotherapy increases TCR diversity in patients with good outcomes. Furthermore, single-cell sequencing identifies most hyper-expanded clones as cytotoxic T cells, while non-expanded clones are predominantly naive T cells. Overall, this highlights TCR diversity as a promising biomarker, offering opportunities for tailored oncological treatments to enhance clinical outcomes.
Super RNA Pol II domains enhance minor ZGA through 3D interaction to ensure the integrity of major transcriptional waves in late-ZGA mammals
Authors: Jingcheng Zhang, Hengkuan Li, Linmi Li, Jie Wu, Linjie Song, Xin Liu, Zhangyuan Pan, Chuan Zhou, Wenying Li, Zixiao Liu, Mei Jiao, Mingyang Hu, Zhenyu Dong, Hexu Zhang, Binqiang Shi, Yong Wang, Debao Wang, Benjamin Carter, Shuhong Zhao, Gang Ren, Yunxia Zhao, Yong Zhang
Journal: Cell Genomics (2025)

Zygotic genome activation (ZGA) occurs at distinct stages across mammals, with mice initiating ZGA at the 2-cell stage and bovines and humans activating the process in the 4- to 8-cell stages. RNA polymerase II (RNA Pol II) gradually initiates ZGA in mice, but regulation in late-ZGA species remains unclear. Here, RNA Pol II profiling in bovine embryos identified strong intergenic clusters that boost minor ZGA gene expression via chromatin interactions and are named super RNA Pol II domains (SPDs). CRISPRi perturbation of SPDs in bovine embryos decreases the expression of minor ZGA genes, whereas the knockdown of these genes disrupts major ZGA and embryogenesis. Rapid enhancement of minor ZGA genes also occurs in human embryos. Alternatively, mouse and porcine oocytes precociously express these minor ZGA genes without SPDs. Thus, SPDs appear to be an adaptation in bovine embryos, promoting minor ZGA gene expression to comparable levels as early-ZGA species, illuminating species-specific regulation of ZGA timing.
Liquid and tissue biopsies for identifying MET exon 14 skipping NSCLC: Analyses from the Phase II VISION study of tepotinib
Authors: Christian Rolfo, Aurora O’Brate, Christoph Menzel, Rolf Bruns, Dilafruz Juraeva, Christopher Stroh, Andreas Johne, Paul K. Paik
Journal: Clinical Cancer Research (2025)

The VISION trial of tepotinib, a selective MET inhibitor, enrolled patients with NSCLC and prospectively detected MET exon 14 skipping (METex14) in liquid biopsies (LBx) and/or tissue biopsies (TBx). We evaluated patient characteristics and outcomes according to METex14 positivity in LBx (LBx-positive) or TBx (TBx-positive). METex14 was centrally assessed by next-generation sequencing of ctDNA from LBx (Guardant360®/Archer®MET) and/or RNA from TBx (Oncomine Focus/Archer®MET) or, in Japan only, local TBx polymerase chain reaction. Parallel LBx/TBx testing was recommended but not mandatory. Eligibility required LBx-positive or TBx-positive status. ctDNA burden was analyzed in patients with baseline Guardant360® data. METex14 was detected in 469/7,937 prescreened/screened patients, of whom 313 were enrolled (TBx-positive, n=208; LBx-positive, n=178). LBx-positive patients had higher radiographic tumor burden than TBx-positive patients, including higher median sum of target lesion diameters per RECIST v1.1 (67.1 vs 55.2 mm), and more patients with ≥3 target lesions (27.5% vs 18.8%). In 180 TBx-positive patients with matching LBx results, objective response rates were slightly higher in TBx-positive/LBx-positive patients, but TBx-positive/LBx-negative patients had longer duration of response, progression-free survival (PFS), and overall survival (OS). In ctDNA analysis (n=165), detectable baseline ctDNA burden was associated with shorter PFS and OS. Tepotinib had robust, durable activity in TBx-positive/LBx-negative and TBx-positive/LBx-positive patients. While LBx is a complementary method to TBx for detecting METex14, it may preferentially select patients with higher tumor burden and poorer prognosis. Undetectable METex14 in baseline ctDNA (due to low ctDNA shedding) may define more favorable treatment outcomes.
Nerve Types and Classification of Neurons Innervating Oral Cancer
Authors: Cindy G. Perez-Pacheco, Laura A. Gonzalez-Maldonado, Allison Furgal, Ligia B. Schmitd, Brian S.C. Constantinescu, Yihan Li, Noam Gannot, Sienna K. Perry, Laura Rozek, Greg Wolf, Joshua J. Emrick, Peng Li, Nisha J. D'Silva
Journal: Clinical Cancer Research (2025)

Although the association between neural invasion and poor survival in oral cavity squamous cell carcinoma (OSCC) is known, innervating nerve types have not been definitively established; this has confounded mechanistic and translational studies. Therefore, we investigated innervation in human OSCC and further explored these findings in mice. Sensory, sympathetic, and parasympathetic nerves were identified by immunohistochemistry and linked to neural phenotypes in 71 patients. Additionally, we investigated sensory innervation of OSCC using neuronal tracing with transcriptomic profiling, and transgenic mice. In OSCC, most nerves are exclusively sensory or sensory mixed with other types. The presence of exclusively sensory nerves and mixed sensory and sympathetic nerves was significantly increased within the tumor bulk compared to the margin, whereas mixed sympathetic and parasympathetic nerves were decreased. The proportion of exclusively sensory, and mixed sensory and sympathetic PNI+ (perineural invasion) nerves was significantly higher, whereas the proportion of mixed sympathetic and parasympathetic nerves was significantly lower than PNI(-) nerves. Classification of tumor-innervating trigeminal sensory neurons in mice revealed an increase in Calca+ peptidergic nociceptors and reduction in low-threshold mechanoreceptors. Using transgenic reporter mice to verify innervation, we identified that mouse tongue SCC is innervated by Pirt+ and Calca+ nociceptors. This study is the first comprehensive characterization of nerve types in OSCC with classification of innervating trigeminal sensory neurons. Our findings emphasize the importance of sensory innervation in OSCC and are highly relevant for mechanistic and translational studies on treatment strategies.
Presurgical ablative radiation is associated with local control and immune response in pancreatic cancer
Authors: Peter Q. Leung, Eslam A. Elghonaimy, Ahmed M. Elamir, Megan Wachsmann, Song Zhang, Neha Barrows, Hollis Notgrass, Ethan Johnson, Cheryl M. Lewis, Rachel von Ebers, Cassandra Hamilton, Samy Castillo-Flores, Ricardo E. Nunez-Rocha, Grace Josephson, Zhikai Chi, Salwan Al Mutar, Patricio M. Polanco, Nina N. Sanford, Syed M. Ali Kazmi, Matthew R. Porembka, David Hsiehchen, Adam C. Yopp, John C. Mansour, Muhammad S. Beg, Herbert J. Zeh, Todd A. Aguilera
Journal: Clinical Cancer Research (2025)

To compare outcomes and molecular characteristics of patients who had surgery after neoadjuvant chemotherapy, with and without ablative radiotherapy (SAbR) for pancreas cancer. Insight could clarify the benefits of SAbR and provide molecular guidance for future therapeutic regimens. This single-institution, tertiary care academic center cohort study included all patients diagnosed with pancreatic cancer between 2012-2023 treated with neoadjuvant chemotherapy, with or without SAbR. We compared therapeutic responses, performed patient matching, and conducted Cox modeling to identify differences between groups. We assessed molecular response using RNA sequencing to identify SAbR-induced biologic differences. Among 133 patients receiving chemotherapy and 48 receiving chemotherapy + SAbR, RNA sequencing was available for 29 and 14 patients, respectively. Despite more advanced baseline disease, the SAbR group showed better post-treatment pathology and similar overall survival (HR = 0.97, 95% CI = 0.58-1.60, P = .9). Patient matching indicated that SAbR improved locoregional recurrence-free survival (HR = 0.24, 95% CI = 0.07-0.88, P = .009). Arterial involvement raised local failure risk with chemotherapy alone (HR = 3.37, 95% CI = 1.74-6.54, P < .001), which was significantly reduced with SAbR (HR = 0.28; 95% CI = 0.12-0.68; P = .005). Gene set enrichment analysis showed immune activation, with CD8 and NK/NKT cell signatures associated with local control and Treg signatures associated with worse control. Neoadjuvant SAbR is associated with improved pathological outcomes, enhanced local control, and maintained survival while inducing a distinct immune response. Well-powered studies are needed to clarify its clinical benefits.
Intraspecies dynamics underlie the apparent stability of two important skin microbiome species
Authors: Jacob S Baker, Evan Qu, Christopher P Mancuso, A Delphine Tripp, Arolyn Conwill, Tami D Lieberman
Journal: Cell Host & Microbe (2025)

Adult human facial skin microbiomes are remarkably similar at the species level, dominated by Cutibacterium acnes and Staphylococcus epidermidis, yet each person harbors a unique community of strains. Understanding how person-specific communities assemble is critical for designing microbiome-based therapies. Here, using 4,055 isolate genomes and 356 metagenomes, we reconstruct on-person evolutionary history to reveal on- and between-person strain dynamics. We find that multiple cells are typically involved in transmission, indicating ample opportunity for migration. Despite this accessibility, family members share only some of their strains. S. epidermidis communities are dynamic, with each strain persisting for an average of only 2 years. C. acnes strains are more stable and have a higher colonization rate during the transition to an adult facial skin microbiome, suggesting this window could facilitate engraftment of therapeutic strains. These previously undetectable dynamics may influence the design of microbiome therapeutics and motivate the study of their effects on hosts.
Nicotinic acid riboside maintains NAD+ homeostasis and ameliorates aging-associated NAD+ decline
Authors: Won-Suk Song, Xiyu Shen, Kang Du, Cuauhtemoc B Ramirez, Sang Hee Park, Yang Cao, Johnny Le, Hosung Bae, Joohwan Kim, Yujin Chun, Nikki Joyce Khong, Marie Kim, Sunhee Jung, Wonsuk Choi, Miranda L Lopez, Zaid Said, Zehan Song, Sang-Guk Lee, Dequina Nicholas, Yo Sasaki, Jeffrey Milbrandt, David K Imagawa, Dorota Skowronska-Krawczyk, Danica Chen, Gina Lee, Cholsoon Jang, Qin Yang
Journal: Cell Metabolism (2025)
Interleukin-34-dependent perivascular macrophages promote vascular function in the brain
Authors: Hannah Van Hove, Chaim Glück, Wiebke Mildenberger, Ekaterina Petrova, Upasana Maheshwari, Philipp Häne, Victor Kreiner, Mitchell Bijnen, Caroline Mussak, Sebastian G Utz, Jeanne Droux, Florian Ingelfinger, Christian Ashworth, Sebastian A Stifter, Elsa Roussel, Iva Lelios, Marijne Vermeer, Sheng-Fu Huang, Quanyu Zhou, Zhenyue Chen, Charlotte Calvet, Soline Bourgeois, Johanna Schaffenrath, Daniel Razansky, Jean X Juang, Kenichi Asano, Pawel Pelczar, Sarah Mundt, Bruno Weber, Susanne Wegener, Sonia Tugues, Christian Stockmann, Burkhard Becher, Annika Keller, Mohamad El Amki, Melanie Greter
Journal: Immunity (2025)

The development of most macrophages depends on the colony-stimulating factor 1 (CSF-1) receptor, which has two ligands: CSF-1 and interleukin-34 (IL-34). While IL-34 is required for the homeostasis of microglia, the parenchymal macrophages in the central nervous system (CNS), it is unclear whether brain border-associated macrophages (BAMs) also depend on this cytokine. Here, we demonstrated that the embryonic development of murine BAMs in the choroid plexus, leptomeninges, and perivascular spaces required CSF-1, while IL-34 was critical for their maintenance in adulthood. In the brain, Il34 was expressed by mural cells and perivascular fibroblasts, and its transgenic deletion in these cells interrupted BAM maintenance. Il34 deficiency coincided with transcriptional changes in vascular cells, leading to increased flow velocity and vasomotion in pial and penetrating arterioles. Similarly, Mrc1CreCsf1rfl/fl mice lacking CD206+ perivascular BAMs exhibited increased hemodynamics in arterial networks. These findings reveal a crosstalk between vascular cells and CNS macrophages regulating cerebrovascular function.