tbuckley/cabot-search huggingface dataset:
Changes in time-to-treatment initiation for breast, nonsmall cell lung, Colon, or rectal cancers throughout the COVID-19 pandemic in the United States
Authors: Qinjin Fan, Weichuan Dong, Elizabeth J Schafer, Nikita Sandeep Wagle, Jingxuan Zhao, Kewei Sylvia Shi, Xuesong Han, K Robin Yabroff, Leticia M Nogueira
Journal: JNCI Journal of the National Cancer Institute (2025)

Abstract The COVID-19 pandemic disrupted healthcare and reduced cancer diagnoses in the U.S., raising concerns about its impact on time-to-treatment initiation (TTI), a critical factor for survival. This study examined the changes in TTI for 1,213,481 individuals newly diagnosed with female breast, non-small cell lung, colon, or rectal cancer between 2019 and 2022, using the National Cancer Database. We compared TTI in 2020-2022 with 2019 by cancer site, diagnosis time of year, stage, and treatment modality. In 2020, TTI significantly decreased for all cancers compared to 2019, especially in the second quarter (2.97 to 4.29 days). However, TTI increased across sites in 2021 (0.31 to 2.15 days) and in 2022 (1.43 to 5.07 days). Reduced diagnoses and efforts to prioritize cancer care during the pandemic may partly explain observed TTI decreases, whereas workforce constraints likely contributed to the later increases. Ongoing evaluation of TTI and associations with patient outcomes is warranted.
Mitochondria-targeting of oxidative phosphorylation inhibitors to alleviate hypoxia and enhance anticancer treatment efficacy
Authors: Anne P.M. Beerkens, Sandra Heskamp, Flavia V. Reinema, Gosse J. Adema, Paul N. Span, Johan Bussink
Journal: Clinical Cancer Research (2025)

Abstract Hypoxia is a common feature of solid tumors and is associated with a poor response to anticancer therapies. Hypoxia also induces metabolic changes, such as a switch to glycolysis. This glycolytic switch causes acidification of the tumor microenvironment (TME), thereby attenuating the anticancer immune response. A promising therapeutic strategy to reduce hypoxia and thereby sensitize tumors to irradiation and/or antitumor immune responses is pharmacological inhibition of oxidative phosphorylation (OXPHOS). Several OXPHOS inhibitors (OXPHOSi) have been tested in clinical trials. However, moderate responses and/or substantial toxicity has hampered clinical implementation. OXPHOSi tested in clinical trials inhibit the oxidative metabolism in tumor cells as well as healthy cells. Therefore, new strategies are needed to improve the efficacy of OXPHOSi while minimizing side effects. To enhance the therapeutic window, available OXPHOSi have, for instance, been conjugated to triphenylphosphonium (TPP+) to preferentially target the mitochondria of cancer cells, resulting in increased tumor uptake compared to healthy cells, as cancer cells have a higher mitochondrial membrane potential. However, OXPHOS inhibition also induces reactive oxygen species (ROS), and subsequent antioxidant responses, which may influence the efficacy of therapies, such as platinum-based chemotherapy and radiotherapy. Here, we review the limitations of the clinically tested OXPHOSi metformin, atovaquone, tamoxifen, BAY 87-2243 and IACS-010759 and the potential of mito-targeted OXPHOSi and their influence on ROS production. Furthermore, the effect of the mitochondria-targeting moiety TPP+ on mitochondria is discussed as this affects mitochondrial bioenergetics.
End-of-life care quality for American Indians with cancer
Authors: Marc A Emerson, Lisa P Spees, Bradford E Jackson, Soroush Fariman, Joel Begay, Hayley N Morris, Ana I Salas, Christopher D Baggett, Tomi Akinyemiju, Ronny A Bell, Stephanie B Wheeler
Journal: JNCI Journal of the National Cancer Institute (2025)

Abstract Background American Indians (AI) experience disparities in cancer outcomes. Little is known about the quality of end-of-life (EOL) care in AI patients with cancer. Methods We retrospectively analyzed EOL care for North Carolina patients who died (decedents) diagnosed with any cancer (2003-2018) using the Cancer Information and Population Health Resource. Measures of EOL care quality were informed by existing literature and included in-hospital death, hospice use and other healthcare utilization within the last 30 days of life. Associations between race/ethnicity and EOL outcomes were evaluated to estimate adjusted risk ratios (aRRs). Because within group heterogeneity can influence health outcomes and intervention effectiveness, we also evaluated associations among AI individuals only. Results We identified 163,285 (1,769 AI and 161,516 White) decedents. The majority (60%) of AIs lived in a geographic area characterized by non-federally recognized tribes. AI decedents had greater proportions of rural residence than White decedents (54.5% AI vs 30.4% White) and dual Medicaid/Medicare enrollment (37.4% AI vs 17.7% White). Compared with White decedents, AI decedents had increased hospital admission (aRR, 1.10, 95% confidence interval [CI], 1.06-1.15), ICU admission (aRR, 1.21; 95% CI, 1.11-1.32), and &amp;gt;1 ED visit (aRR, 1.31; 95% CI, 1.20-1.44) in the last 30 days of life. We observed significant within-group variation in EOL care quality among AI patients. Conclusions Structural barriers to care and rurality may contribute to lower quality EOL care among AI decendents, when compared with White patients. High-quality, culturally appropriate EOL care will require a better understanding of care decision-making and access.
Factors associated with longitudinal progression of the cumulative burden of morbidity and overall mortality after cisplatin-based chemotherapy for testicular cancer
Authors: Sarah L Kerns, Paul C Dinh, Patrick O Monahan, Timothy Stump, Chunkit Fung, Howard D Sesso, Darren R Feldman, Robert J Hamilton, David J Vaughn, Robert Huddart, Christian Kollmannsberger, Neil E Martin, Kathryn Nevel, John Kincaid, Lawrence H Einhorn, Lois B Travis
Journal: JNCI Journal of the National Cancer Institute (2025)

Abstract Background To comprehensively evaluate the longitudinal progression of cumulative burden of morbidity (CBM) in testicular cancer survivors (TCS) following standard-dose cisplatin-chemotherapy and the impact of modifiable risk factors on morbidity and early-mortality. Methods Participants completed first-line chemotherapy ≥6 months before baseline assessments with comprehensive questionnaires and physical-examinations. Based on follow-up assessments (median: 7 years later), longitudinal progression of adverse health outcomes (AHOs) and CBM score (encompassing AHO number and severity) was examined. Baseline health behaviors and AHOs were evaluated for associations with mortality using mixed-effects parametric proportional-hazards regression to identify modifiable risk factors. Results Among 616 TCS longitudinally assessed, 23% experienced worsening CBM post-chemotherapy (median: 11 years [IQR = 7-15]). Declines were driven by worsening treatment-related AHOs: tinnitus (29.7%), hearing loss (24.4%), Raynaud’s (22.6%), neuropathy (18.5%), and neuropathic-pain (10.7%). Baseline factors associated with worsening neuropathy included lack of aerobic physical-activity (OR = 1.98, 95%CI = 1.06-3.72) and obesity (OR = 1.85, 95%CI = 1.17-2.92). These were also related to worsening neuropathic-pain (OR = 2.82, p = .009; and OR = 2.29; p = .023). Twenty-nine deaths occurred among 1,830 five-year TCS (4.2% cumulative hazard) (median age: 48-years [range = 22-74]). Participants reporting neuropathic-pain (HR = 3.64, 95%CI = 1.45-9.10), no aerobic (HR = 6.56, 95%CI = 2.73-15.8), or no low-impact physical-activity (HR = 3.96, 95%CI = 1.40-11.2) had significantly higher mortality, as did TCS indicating fair (HR = 9.23, 95%CI = 3.08-27.8) or poor (HR = 18.5, 95%CI = 3.30-103) health. Relationships between pain and mortality were mediated through lowered physical-activity (p = .036). Conclusions Clinically-actionable factors associated with early mortality identify high-risk TCS in need of closer monitoring and targeted interventions. The significant relationship between neuropathic-pain and mortality, mediated by low physical-activity, is the first to our knowledge in TCS.
Correction: The landscape of BRAF transcript and protein variants in human cancer
Authors: Andrea Marranci, Zhijie Jiang, Marianna Vitiello, Elena Guzzolino, Laura Comelli, Samanta Sarti, Simone Lubrano, Cinzia Franchin, Ileabett Echevarría-Vargas, Andrea Tuccoli, Alberto Mercatanti, Monica Evangelista, Paolo Sportoletti, Giorgio Cozza, Ettore Luzi, Enrico Capobianco, Jessie Villanueva, Giorgio Arrigoni, Giovanni Signore, Silvia Rocchiccioli, Letizia Pitto, Nicholas Tsinoremas, Laura Poliseno
Journal: Molecular Cancer (2025)
Addressing Health Disparities in Hematologic Malignancies: from Genes to Outreach
Authors: Christopher R. Flowers, Rachel W. Anantha, Veronica Leautaud, Pinkal Desai, Chancellor E. Donald, Michelle A.T. Hildebrandt, Jean L. Koff, Rulla M. Tamimi, Wendy Cozen, Chijioke Nze, Ari M. Melnick
Journal: Blood Cancer Discovery (2025)

Abstract Hematologic malignancies exhibit disparities in risk and outcomes across populations. A systematic review to identify prospective studies addressing disparities among patients with hematologic malignancies with an intervention or analysis at any level in the “Cells-to-Society” model identified few studies and demonstrated literature gaps, which experts have supplemented with relevant citations. This review presents current research on diagnosis, treatment, and survival disparities and explores the roles of biology, cancer centers, community outreach, patient advocacy, and policies. Emphasis is placed on multilevel collaborative approaches to promote equity in healthcare delivery and improve survival. Significance: This review underscores our shared responsibility to champion multidimensional strategies rooted in basic and translational science, community involvement, and societal responsiveness for a meaningful impact. Unifying themes include the need to enhance collaborative infrastructure to engage laboratory researchers, epidemiologists, data scientists, clinicians, patients, community leaders, and policymakers; patient-level support services; outreach, education, and navigation for patients at the community level; recruitment and retention of underrepresented groups in the healthcare and research workforce; and funding for these efforts.
SELP+ TEC:CD8+ T cell crosstalk associates with improved radiotherapy efficacy in cervical cancer
Authors: Qingyu Huang, Wenhui Yang, Fuhao Wang, Rui Huang, Qian Wang, Xiaohui Li, Tianyu Lei, Shengqin Yue, Wenxue Zou, Qi An, Jinbo Yue, Qinyong Hu, Chao Liu
Journal: Molecular Cancer (2025)

P-selectin (SELP) expression in tumor cells has been implicated in promoting tumor progression and treatment resistance across various cancers. However, our prior study identified SELP expression in a specific subpopulation of endothelial cells within cervical cancer (CC) and potentially linked to anti-cancer immune response. The precise mechanisms by which SELP influences anti-cancer immunity and its involvement in radiotherapy response in CC, however, remain elusive. To address these gaps, this study analyzed tumor tissue samples from 205 CC patients undergoing radiotherapy, scRNA-seq data from 42,159 cells of eight patients, and bulk RNA-sequencing data from 187 radiotherapy-treated patients. The results revealed that elevated SELP expression in tumor endothelial cells (TECs) was significantly correlated with improved survival outcomes in patients treated with radiotherapy. The SELPhigh group exhibited a prominent enrichment of immune-related pathways, coupled with a diminished enrichment in epithelial cell proliferation and angiogenesis pathways. Notably, this group demonstrated increased infiltration of CD8+ T cells and enhanced expression of chemokine receptors, including ACKR1. Furthermore, our data suggest that SELP+ TECs engage in crosstalk with CD8+ T cells via the ACKR1-CCL5 axis, which is associated with improved radiotherapy efficacy. In conclusion, these findings underscore the pivotal role of SELP+ TEC:CD8+ T cell interactions through the ACKR1-CCL5 pathway in enhancing radiotherapy response in CC. Targeting this crosstalk may offer novel therapeutic strategies to mitigate treatment resistance and improve patient survival.
Are contemporary antifungal doses sufficient for critically ill patients? Outcomes from an international, multicenter pharmacokinetics study for Screening Antifungal Exposure in Intensive Care Units—the SAFE-ICU study
Authors: Jason A. Roberts, Fekade B. Sime, Jeffrey Lipman, María Patricia Hernández-Mitre, João Pedro Baptista, Roger J. Brüggemann, Jai Darvall, Jan J. De Waele, George Dimopoulos, Jean-Yves Lefrant, Mohd Basri Mat Nor, Jordi Rello, Leonardo Seoane, Monica A. Slavin, Miia Valkonen, Mario Venditti, Giancarlo Ceccarelli, Wai Tat Wong, Markus Zeitlinger, Claire Roger
Journal: Intensive Care Medicine (2025)

Appropriate antifungal therapy is a major determinant of survival in critically ill patients with invasive fungal disease. We sought to describe whether contemporary dosing of antifungals achieves therapeutic exposures in critically ill patients. In a prospective, open-label, multicenter pharmacokinetic study, intensive care unit (ICU) patients prescribed azoles, echinocandins, or polyene antifungals for treatment or prophylaxis of invasive fungal disease were enrolled. Blood samples were collected on two occasions, with three samples taken during a single dosing interval on each occasion. Total concentrations were centrally measured using validated chromatographic methods. Pharmacokinetic parameters were estimated using noncompartmental methods. Antifungal dosing adequacy was assessed using predefined PK/PD targets. We included 339 patients from 30 ICUs across 12 countries. Median age 62 (interquartile range [IQR], 51-70) years, median APACHE II score 22 (IQR, 17-28), and 61% males. Antifungal therapy was primarily prescribed for treatment (80.8%). Fluconazole was the most frequently prescribed antifungal (40.7%). The most common indication for treatment was intra-abdominal infection (30.7%). Fungi were identified in 45% of patients, of which only 26% had a minimum inhibitory concentration available. Target attainment was higher for patients receiving prophylaxis (> 80% for most drugs). For patients receiving treatment, low target attainment was noted for voriconazole (57.1%), posaconazole (63.2%), micafungin (64.1%) and amphotericin B (41.7%). This study highlights the varying degrees of target attainment across antifungal agents in critically ill patients. While a significant proportion of patients achieved the predefined PK/PD targets, wide variability and subtherapeutic exposures persist. ClinicalTrials.gov Identifier: NCT03136926, 2017-04-21.
Multi-INTACT: integrative analysis of the genome, transcriptome, and proteome identifies causal mechanisms of complex traits
Authors: Jeffrey Okamoto, Xianyong Yin, Brady Ryan, Joshua Chiou, Francesca Luca, Roger Pique-Regi, Hae Kyung Im, Jean Morrison, Charles Burant, Eric B. Fauman, Markku Laakso, Michael Boehnke, Xiaoquan Wen
Journal: Genome biology (2025)

Abstract We present multi-integration of transcriptome-wide association studies and colocalization (Multi-INTACT), an algorithm that models multiple “gene products” (e.g., encoded RNA transcript and protein levels) to implicate causal genes and relevant gene products. In simulations, Multi-INTACT achieves higher power than existing methods, maintains calibrated false discovery rates, and detects the true causal gene product(s). We apply Multi-INTACT to GWAS on 1408 metabolites, integrating the GTEx expression and UK Biobank protein QTL datasets. Multi-INTACT infers 52 to 109% more metabolite causal genes than protein-alone or expression-alone analyses and indicates both gene products are relevant for most gene nominations.
Molecular subtypes of adamantinomatous craniopharyngiomas
Authors: Wenhao An, Shouwei Li, Yihua An, Zhixiong Lin
Journal: Neuro-Oncology (2025)

Abstract Adamantinomatous craniopharyngioma (ACP) is the most common benign tumor in the sellar region of children and originates from embryonic remnants. Owing to its unique location and frequent tight adhesion to and invasion of surrounding structures, the ACP poses significant challenges for neurosurgical treatment. Traditionally, the core treatment for ACPs has been surgical resection supplemented with radiotherapy in cases of residual or recurrent tumors. As a result, ACP classification has been based primarily on the tumor's relationship with surrounding anatomical and histological structures, guiding the selection of surgical approaches and the prevention of complications. Moreover, efforts to explore pharmacological treatments for ACP have yielded varying results across different cases, creating confusion among researchers. This variability also suggests the possibility of different molecular subtypes within ACPs, despite being driven by a single gene mutation. With advancements in molecular biological studies, such as ACP RNA sequencing, whole-exome sequencing, and methylation analysis, along with the discovery of interactions between different molecular pathways within ACP, researchers have been continuously exploring the molecular subtyping of ACP and predicting the efficacy of targeted therapies on the basis of these subtypes. This review focuses on summarizing and synthesizing the molecular mechanisms and potential subtypes of ACP, aiming to provide theoretical support for future research on the molecular subtyping of ACP.
A fully phased octoploid strawberry genome reveals the evolutionary dynamism of centromeric satellites
Authors: Xin Jin, Haiyuan Du, Maoxian Chen, Xu Zheng, Yiying He, Andan Zhu
Journal: Genome biology (2025)

We systematically examine the application of different phasing strategies to decrypt strawberry genome organization and produce a fully phased and accurate reference genome for Fragaria x ananassa cv. "EA78" (2n = 8x = 56). We identify 147 bp canonical centromeric repeats across 50 strawberry chromosomes and uncover the formation of six neocentromeres through centromere turnover. Our findings indicate strawberry genomes have diverged centromeric satellite arrays among chromosomes, particularly across homoeologs, while maintaining high sequence similarity between homologs. We trace the evolutionary dynamics of centromeric repeats and find substantial centromere size expansion in wild and cultivated octoploids compared to the diploid ancestor, F. vesca.
Engineering a bacterial toxin deaminase from the DYW-family into a novel cytosine base editor for plants and mammalian cells
Authors: Dingbo Zhang, Fiona Parth, Laura Matos da Silva, Teng-Cheong Ha, Axel Schambach, Jens Boch
Journal: Genome biology (2025)

Abstract Base editors are precise editing tools that employ deaminases to modify target DNA bases. The DYW-family of cytosine deaminases is structurally and phylogenetically distinct and might be harnessed for genome editing tools. We report a novel CRISPR/Cas9-cytosine base editor using SsdA, a DYW-like deaminase and bacterial toxin. A G103S mutation in SsdA enhances C-to-T editing efficiency while reducing its toxicity. Truncations result in an extraordinarily small enzyme. The SsdA-base editor efficiently converts C-to-T in rice and barley protoplasts and induces mutations in rice plants and mammalian cells. The engineered SsdA is a highly efficient genome editing tool.
A barley pan-transcriptome reveals layers of genotype-dependent transcriptional complexity
Authors: Wenbin Guo, Miriam Schreiber, Vanda B. Marosi, Paolo Bagnaresi, Morten Egevang Jørgensen, Katarzyna B. Braune, Ken Chalmers, Brett Chapman, Viet Dang, Christoph Dockter, Anne Fiebig, Geoffrey B. Fincher, Agostino Fricano, John Fuller, Allison Haaning, Georg Haberer, Axel Himmelbach, Murukarthick Jayakodi, Yong Jia, Nadia Kamal, Peter Langridge, Chengdao Li, Qiongxian Lu, Thomas Lux, Martin Mascher, Klaus F. X. Mayer, Nicola McCallum, Linda Milne, Gary J. Muehlbauer, Martin T. S. Nielsen, Sudharsan Padmarasu, Pai Rosager Pedas, Klaus Pillen, Curtis Pozniak, Magnus W. Rasmussen, Kazuhiro Sato, Thomas Schmutzer, Uwe Scholz, Danuta Schüler, Hana Šimková, Birgitte Skadhauge, Nils Stein, Nina W. Thomsen, Cynthia Voss, Penghao Wang, Ronja Wonneberger, Xiao-Qi Zhang, Guoping Zhang, Luigi Cattivelli, Manuel Spannagl, Micha Bayer, Craig Simpson, Runxuan Zhang, Robbie Waugh
Journal: Nature Genetics (2025)

Abstract A pan-transcriptome describes the transcriptional and post-transcriptional consequences of genome diversity from multiple individuals within a species. We developed a barley pan-transcriptome using 20 inbred genotypes representing domesticated barley diversity by generating and analyzing short- and long-read RNA-sequencing datasets from multiple tissues. To overcome single reference bias in transcript quantification, we constructed genotype-specific reference transcript datasets (RTDs) and integrated these into a linear pan-genome framework to create a pan-RTD, allowing transcript categorization as core, shell or cloud. Focusing on the core (expressed in all genotypes), we observed significant transcript abundance variation among tissues and between genotypes driven partly by RNA processing, gene copy number, structural rearrangements and conservation of promotor motifs. Network analyses revealed conserved co-expression module::tissue correlations and frequent functional diversification. To complement the pan-transcriptome, we constructed a comprehensive cultivar (cv.) Morex gene-expression atlas and illustrate how these combined datasets can be used to guide biological inquiry.
Spatial transcriptomics identifies molecular niche dysregulation associated with distal lung remodeling in pulmonary fibrosis
Authors: Annika Vannan, Ruqian Lyu, Arianna L. Williams, Nicholas M. Negretti, Evan D. Mee, Joseph Hirsh, Samuel Hirsh, Niran Hadad, David S. Nichols, Carla L. Calvi, Chase J. Taylor, Vasiliy. V. Polosukhin, Ana P. M. Serezani, A. Scott McCall, Jason J. Gokey, Heejung Shim, Lorraine B. Ware, Matthew J. Bacchetta, Ciara M. Shaver, Timothy S. Blackwell, Rajat Walia, Jennifer M. S. Sucre, Jonathan A. Kropski, Davis J. McCarthy, Nicholas E. Banovich
Journal: Nature Genetics (2025)

Abstract Large-scale changes in the structure and cellular makeup of the distal lung are a hallmark of pulmonary fibrosis (PF), but the spatial contexts that contribute to disease pathogenesis have remained uncertain. Using image-based spatial transcriptomics, we analyzed the gene expression of 1.6 million cells from 35 unique lungs. Through complementary cell-based and innovative cell-agnostic analyses, we characterized the localization of PF-emergent cell types, established the cellular and molecular basis of classical PF histopathologic features and identified a diversity of distinct molecularly defined spatial niches in control and PF lungs. Using machine learning and trajectory analysis to segment and rank airspaces on a gradient of remodeling severity, we identified compositional and molecular changes associated with progressive distal lung pathology, beginning with alveolar epithelial dysregulation and culminating with changes in macrophage polarization. Together, these results provide a unique, spatially resolved view of PF and establish methods that could be applied to other spatial transcriptomic studies.
Genomics of rare diseases in the Greater Middle East
Authors: Ikram Chekroun, Shruti Shenbagam, Mohamed A Almarri, Younes Mokrab, Mohammed Uddin, Omer S Alkhnbashi, Maha S Zaki, Hossein Najmabadi, Kimia Kahrizi, Khalid A Fakhro, Naif A M Almontashiri, Fahad R Ali, Uğur Özbek, Bruno Reversade, Fowzan S Alkuraya, Alawi Alsheikh-Ali, Ahmad N Abou Tayoun
Journal: Nature Genetics (2025)