tbuckley/cabot-search huggingface dataset:
STMiner: Gene-centric spatial transcriptomics for deciphering tumor tissues
Authors: Peisen Sun, Stephen J. Bush, Songbo Wang, Peng Jia, Mingxuan Li, Tun Xu, Pengyu Zhang, Xiaofei Yang, Chengyao Wang, Linfeng Xu, Tingjie Wang, Kai Ye
Journal: Cell Genomics (2025)

Highlights•Spot-based methods struggle to handle the complexity of tumor samples•STMiner avoids background bias by optimal transport theory•STMiner retains both high- and low-expression genes based on spatial distribution•STMiner identifies overlapping regions from a gene-based perspectiveSummaryAnalyzing spatial transcriptomics data from tumor tissues poses several challenges beyond those of healthy samples, including unclear boundaries between different regions, uneven cell densities, and relatively higher cellular heterogeneity. Collectively, these bias the background against which spatially variable genes are identified, which can result in misidentification of spatial structures and hinder potential insight into complex pathologies. To overcome this problem, STMiner leverages 2D Gaussian mixture models and optimal transport theory to directly characterize the spatial distribution of genes rather than the capture locations of the cells expressing them (spots). By effectively mitigating the impacts of both background bias and data sparsity, STMiner reveals key gene sets and spatial structures overlooked by spot-based analytic tools, facilitating novel biological discoveries. The core concept of directly analyzing overall gene expression patterns also allows for a broader application beyond spatial transcriptomics, positioning STMiner for continuous expansion as spatial omics technologies evolve.Graphical abstract
A meta-analysis of the gut microbiome in inflammatory bowel disease patients identifies disease-associated small molecules
Authors: Moamen M Elmassry, Kohei Sugihara, Pranatchareeya Chankhamjon, Yeji Kim, Francine R Camacho, Shuo Wang, Yuki Sugimoto, Seema Chatterjee, Lea Ann Chen, Nobuhiko Kamada, Mohamed S Donia
Journal: Cell Host & Microbe (2025)
Secure and federated quantitative trait loci mapping with privateQTL
Authors: Yoolim Annie Choi, Yebin Kim, Peihan Miao, Tuuli Lappalainen, Gamze Gürsoy
Journal: Cell Genomics (2025)

Highlights•privateQTL is a novel tool for multi-center eQTL mapping studies that protects privacy•Cryptographic techniques are used for data pre-processing and eQTL mapping•privateQTL is more accurate than meta-analysis in a real-world study with batch effects•privateQTL is a scalable and practical solution for real-world applicationsSummaryUnderstanding the relationship between genotypes and phenotypes is crucial for advancing personalized medicine. Expression quantitative trait loci (eQTL) mapping plays a significant role by correlating genetic variants to gene expression levels. Despite the progress made by large-scale projects, eQTL mapping still faces challenges in statistical power and privacy concerns. Multi-site studies can increase sample sizes but are hindered by privacy issues. We present privateQTL, a novel framework leveraging secure multi-party computation for secure and federated eQTL mapping. When tested in a real-world scenario with data from different studies, privateQTL outperformed meta-analysis by accurately correcting for covariates and batch effect and retaining higher accuracy and precision for both eGene-eVariant mapping and effect size estimation. In addition, privateQTL is modular and scalable, making it adaptable for other molecular phenotypes and large-scale studies. Our results indicate that privateQTL is a practical solution for privacy-preserving collaborative eQTL mapping.Graphical abstract
Activation of the imprinted Prader-Willi syndrome locus by CRISPR-based epigenome editing
Authors: Dahlia Rohm, Joshua B Black, Sean R McCutcheon, Alejandro Barrera, Shanté S Berry, Daniel J Morone, Xander Nuttle, Celine E de Esch, Derek J C Tai, Michael E Talkowski, Nahid Iglesias, Charles A Gersbach
Journal: Cell Genomics (2025)
Overcoming collaboration barriers in quantitative trait loci analysis
Authors: Wen Zhang, Xiaohong Wu, Jing Gong
Journal: Cell Genomics (2025)

In this issue of Cell Genomics, Choi et al.1 report a novel approach, privateQTL, which leverages secure multiparty computation (MPC) to enable federated expression quantitative trait loci (eQTL) mapping across institutions without compromising data privacy. Zhang et al. preview their approach and discuss its application in future genetic analyses.
Stabilization of RUNX1 Induced by O-GlcNAcylation Promotes PDGF-BB-Mediated Resistance to CDK4/6 Inhibitors in Breast Cancer
Authors: Shuyan Zhou, Yi Zhang, Julie Belmar, Chunyan Hou, Yaqin Zhang, Changmin Peng, Yunxiao Meng, Zhuqing Li, Muhammad Jameel. Mughal, Yanjun Gao, Edward Seto, Min Shen, Matthew D. Hall, Junfeng Ma, Cynthia X. Ma, Shunqiang Li, Wenge Zhu
Journal: Cancer Research (2025)

Abstract Cyclin-dependent kinases 4 and 6 (CDK4/6) are crucial in regulating cell cycle progression and cancer development. Targeting CDK4/6 has shown considerable promise in treating various cancers, including breast cancer. Despite significant therapeutic efficacy, resistance to CDK4/6 inhibitors (CDK4/6i), such as palbociclib, remains a substantial hurdle in clinical practice. Using a co-culture system, cytokine array, and quantitative high-throughput combinatorial screening (qHTCS), we discovered a mechanism by which the RUNX1-PDGF-BB axis regulates palbociclib resistance in breast cancer cells. Specifically, RUNX1 functioned as a transcription factor to drive expression of PDGF-BB, leading to resistance to palbociclib by enhancing the Akt pathway and suppressing senescence. Furthermore, in resistant cells, RUNX1 was O-GlcNAcylated at serine 252 (S252) by OGT, resulting in the stabilization of RUNX1 by preventing ubiquitin-mediated degradation. Inhibition of the RUNX1-PDGF-BB axis by specific inhibitors overcame palbociclib resistance both in vitro and in vivo. Notably, the RUNX1-PDGF-BB axis was upregulated in resistant patient-derived xenograft (PDX) lines and in breast cancer patients following treatment with CDK4/6i. These findings not only unveil O-GlcNAcylation-mediated activation of a RUNX1-PDGF-BB pathway as a driver of palbociclib resistance but also provide clinical evidence supporting the repurposing of FDA-approved PDGFR inhibitors as a therapeutic strategy to treat CDK4/6i-resistant breast cancer patients.
The dynamic axon initial segment: From neuronal polarity to network homeostasis
Authors: Amélie Fréal, Casper C. Hoogenraad
Journal: Neuron (2025)

The axon initial segment (AIS) is a highly specialized compartment in neurons that resides in between axonal and somatodendritic domains. The localization of the AIS in the proximal part of the axon is essential for its two major functions: generating and modulating action potentials and maintaining neuron polarity. Recent findings revealed that the incredibly stable AIS is generated from highly dynamic components and can undergo extensive structural and functional changes in response to alterations in activity levels. These activity-dependent alterations of AIS structure and function have profound consequences for neuronal functioning, and AIS plasticity has emerged as a key regulator of network homeostasis. This review highlights the functions of the AIS, its architecture, and how its organization and remodeling are influenced by developmental plasticity and both acute and chronic adaptations. It also discusses the mechanisms underlying these processes and explores how dysregulated AIS plasticity may contribute to brain disorders.
The effect of amubarvimab-romlusevimab on clinical outcomes in patients with COVID-19: a meta-analysis
Authors: Guangyu Ao, Toni Li, Yushu Wang, Nathan Balzer, Jie Luo, Min Chen
Journal: Journal of Infection (2025)

Highlights•First meta-analysis evaluating the clinical efficacy of amubarvimab-romlusevimab in COVID-19 patients•Meta-analysis included five studies with a total of 1,665 patients from diverse clinical settings•Amubarvimab-romlusevimab treatment did not show a significant reduction in mortality or morbidity.
Meet the author: Hector L. Franco
Authors: Hector L. Franco
Journal: Cell Genomics (2025)

Hector Franco is a group leader at the University of Puerto Rico Comprehensive Cancer Center (UPRCCC), having re-located from the University of North Carolina in 2023. His laboratory focuses on gene regulation, non-coding RNA, and the tumor microenvironment. In this issue of <i>Cell Genomics</i>, his team presents the resource "Defining the regulatory logic of breast cancer using single-cell epigenetic and transcriptome profiling," which highlights non-coding mechanisms of gene regulation in breast cancer.
Symbionts of predatory protists are widespread in the oceans and related to animal pathogens
Authors: Fabian Wittmers, Camille Poirier, Charles Bachy, Charlotte Eckmann, Olga Matantseva, Craig A. Carlson, Stephen J. Giovannoni, Ursula Goodenough, Alexandra Z. Worden
Journal: Cell Host & Microbe (2025)
Learning from tobacco control to tackle gambling industry harms
Authors: May C I van Schalkwyk, Benjamin Hawkins, Rebecca Cassidy, Jeff Collin, Anna B Gilmore, Mark Petticrew
Journal: BMJ (2025)

The use of tobacco industry tactics by the gambling and other health harming industries means governments must act to prevent large scale avoidable harm, argue <b>May van Schalkwyk and colleagues</b>
Rates of Fertility Discussions and Counseling Before, During, and After Anticancer Treatments
Authors: Verity Chadwick, Georgia Mills, Catherine Tang, Antoinette Anazodo, Rachel Dear, Rachael Rogers, Orly Lavee, Samuel Milliken, Georgia McCaughan, Nada Hamad
Journal: Journal of the National Comprehensive Cancer Network (2025)

Background: Cancer treatment can significantly reduce reproductive potential in female patients. This study sought to explore the incidence of fertility counseling in women of childbearing potential before, during, and after anticancer therapies. Methods: We conducted a retrospective medical record review at a major Australian cancer center of premenopausal females aged 18 to 49 years diagnosed with cancer between 2017 and 2020. Results: A total of 143 patients met inclusion criteria. Of these patients, only 12.6% had a reproductive health history documented at the first consult and just more than half (58%) had a fertility preservation discussion documented with their primary hematologist or oncologist. A quarter (25.9%) saw a specialist gynecologist to discuss fertility preservation options, and 11.2% were offered a referral but declined. Conclusions: In an Australian major cancer center, only half of women with a new malignancy diagnosis had documented reproductive counseling. Promoting and facilitating reproductive counseling needs to be addressed through strengthening working relationships between fertility preservation specialists and oncologists/hematologists, implementing technology systems to ensure fertility preservation documentation, and improving staff education.
Burdens of Gastroenteropancreatic Neuroendocrine Neoplasm by Diverse Race and Ethnicities— A Rigorous Structural Equation Modeling
Authors: Alan Paciorek, Claire Mulvey, Meg McKinley, Li Zhang, Iona Cheng, Farhana Moon, Bryan Khuong Le, Brandon E. Shih, Julia Whitman, Emily Bergsland
Journal: Journal of the National Comprehensive Cancer Network (2025)

Background: It is unclear whether patients of all races and ethnicities with gastroenteropancreatic (GEP) neuroendocrine neoplasm (NEN) have equivalent incidence and cancer-specific survival. Patients and Methods: Using the California Cancer Registry, all patients with GEP-NEN in California’s large and diverse population from 1992 to 2019 were identified. Age-adjusted incidence rates (AIRs) and cancer-specific mortality (CSM) risks were compared across racial and ethnic subgroups using structural equation modeling. Results: The non-Hispanic (NH) Black population had the highest rate of diagnosis every year (AIR 2019 , 7.4 per 100,000; 95% CI, 6.4–8.5). The AIRs across races and ethnicities and primary sites vary, and in 2019 statistically significantly increased for stomach, small intestine, pancreatic, and rectal NEN and for only the NH White population. Risk of mortality was neutral across many races and ethnicities for many primary sites. The only statistically significant disparity was a higher CSM rate for Hispanic patients compared with NH Black patients with small intestine NEN (subdistribution hazard ratio, 1.45; 95% CI, 1.10–1.91; P =.008). Findings suggest a higher CSM among NH Black and NH White patients with rectal NEN. Disparities in who presents with GEP-NEN were revealed across racial and ethnic populations and primary sites. The NH Black population incurred the highest rate overall consistently every year. This is the first study to evaluate cancer-specific survival disparities in all GEP-NEN primary sites across the Asian American/Native Hawaiian/Pacific Islander, Hispanic, NH Black, and NH White racial and ethnic populations. Many clinical and sociodemographic measures associated with risk of mortality differed across race and ethnicities. After careful control of those imbalances, there were few racial and ethnic disparities in risk of CSM. Conclusions: There is room to improve equity in the health care system and close the gap in diagnoses for the NH Black population with all GEP-NEN and in mortality for the Hispanic population with small intestine NEN.
Predicting c-KIT Inhibitor Efficacy in Patient-Derived Models of Sinonasal Mucosal Melanomas through Integrated Histogram Analysis of Whole-Tumor DKI, IVIM, and DCE-MRI
Authors: Cong Wang, Xuewei Niu, Tianyi Xia, Peng Wang, Yuzhe Wang, Zhongshuai Zhang, Jianyuan Zhang, Shenghong Ju, Zebin Xiao
Journal: Clinical Cancer Research (2025)

Abstract Purpose: To evaluate whole-tumor histogram analysis of diffusion kurtosis imaging (DKI), intravoxel incoherent motion (IVIM), and dynamic contrast-enhanced MRI (DCE-MRI), in predicting the efficacy of imatinib, a c-KIT inhibitor, for treating patient derived models derived from sinonasal mucosal melanomas (MMs). Experimental Design: This study included 38 patients with histologically confirmed sinonasal MM, who underwent DKI, IVIM, and DCE-MRI. Patient-derived tumor xenograft (PDX) models and precision-cut tumor slices (PCTS) were established to evaluate tumor response to imatinib. Whole-tumor histogram analysis was conducted on imaging parameters, and logistic regression models were applied to determine the predictive value of these metrics in differentiating responders from non-responders. Results: Among the 38 sinonasal MM patients, 12 were classified as responders and 26 as non-responders based on PDX and PCTS model responses to imatinib. The DKI model revealed significant differences in mean, median, P10, and P90 values of Dk and K between responders and non-responders (P &amp;lt; 0.05). The IVIM model indicated significant differences in P10 and mean values of D, with kurtosis f being a strong predictor. The DCE-MRI model, using the P90 Ktrans metric, demonstrated robust predictive performance, achieving an AUC of 0.89, with 80.77% specificity and 91.67% sensitivity. The combined logistic model integrating DKI, IVIM, and DCE-MRI metrics produced the highest predictive accuracy, with an AUC of 0.90. Conclusions: Whole-tumor histogram analysis of DKI, IVIM, and DCE-MRI offers a non-invasive method for predicting the efficacy of c-KIT inhibitors in sinonasal MMs, presenting valuable implications for guiding targeted treatment in this rare cancer type.
Unlocking the Potential: Antihistamine Use and Breast Cancer Risk in Women With Type 2 Diabetes Mellitus
Authors: Kang-Chuang Chai, Ta-Chun Chou, Wan-Ming Chen, Ben-Chang Shia, Ruey-Shyang Soong, Szu-Yuan Wu
Journal: Journal of the National Comprehensive Cancer Network (2025)

Background: The association between the use of antihistamines targeting histamine receptor H1 (AH1) and breast cancer risk in individuals with type 2 diabetes mellitus (T2DM) remains understudied, warranting further investigation. Methods: Using the Taiwan National Health Insurance Research Database from 2008 to 2018, we conducted a cohort study on women aged ≥18 years with T2DM, employing propensity score matching (PSM) to compare breast cancer risk between AH1 users (defined as at least 28 cumulative defined daily doses annually) and nonusers. Cox regression models were used to estimate adjusted hazard ratios (aHRs). Results: The baseline characteristics of the study population were assessed, with 142,642 women enrolled between 2008 and 2018. After PSM, the AH1 use and nonuse groups showed comparable variables. The aHR for breast cancer was significantly lower in the AH1 use group compared with the nonuse group (aHR, 0.54; 95% CI, 0.44–0.66; P &lt;.0001). Dose-dependent analysis revealed a significant trend ( P trend =.0002), indicating a lower breast cancer risk with increasing AH1 use. The incidence rate of breast cancer was lower in AH1 users compared with nonusers, with an incidence rate ratio of 0.78 (95% CI, 0.65–0.93). Conclusions: AH1 use shows promise in reducing breast cancer risk in individuals with T2DM, particularly with higher dosages, warranting further research and consideration by health care practitioners.
Integrated Nicotine Replacement and Behavioral Support to Reduce Smoking in Opioid Agonist Therapy
Authors: Karl Trygve Druckrey-Fiskaaen, Tesfaye Madebo, Jan Tore Daltveit, Jørn Henrik Vold, Einar Furulund, Fatemeh Chalabianloo, Torgeir Gilje Lid, Lars Thore Fadnes
Journal: JAMA Psychiatry (2025)

Importance Approximately 85% of individuals receiving opioid agonist therapy for opioid dependence smoke tobacco. Despite the significant health risks associated with smoking-related diseases, there has been limited evaluation of smoking interventions tailored to this population. Objective To determine the effectiveness of an intervention combining nicotine replacement with brief behavioral support in reducing cigarette use. Design, Setting, and Participants This multicenter randomized clinical trial was conducted from April 2022 to October 2023 in 7 specialized opioid agonist therapy clinics in Bergen and Stavanger, Norway. The analyst was blinded to patient groupings. Assessors (study nurses) were not fully blinded to participant allocation. Individuals diagnosed with opioid dependency receiving opioid agonist therapy at participating clinics and smoking at least 1 cigarette per day were eligible for participation. Data analysis was performed from December 2023 through October 2024. Intervention In addition to standard opioid agonist therapy, participants in the intervention group received a 16-week integrated treatment combining nicotine replacement with brief behavioral support. Participants in the control group received only standard opioid agonist therapy. Main Outcomes and Measures The primary outcome was at least a 50% reduction in the number of cigarettes smoked, self-reported as cigarette use in the past 7 days at week 16. The analysis followed intention-to-treat principles. Cigarette use was self-reported as per the timeline-follow-back method. Results Among the 259 participants (mean [SD] age, 48.5 [10.4] years; 80 [30.9%] female), 135 were allocated to the intervention group and 124 to the control group. The odds ratio of at least halving the number of cigarettes smoked was 2.07 (95% CI, 1.14-3.75) in the intervention group compared with the control group. Conclusions and Relevance Providing integrated nicotine replacement and behavioral support at opioid agonist treatment clinics effectively helped opioid-dependent participants reduce the number of cigarettes smoked. Trial Registration ClinicalTrials.gov Identifier: NCT05290025
A Digital Intervention to Address Sexual Health in Hematopoietic Stem Cell Transplant Survivors
Authors: Areej El-Jawahri, Jennifer B. Reese, Lara Traeger, Don Dizon, Corey Cutler, Sharon Bober, Joseph A. Greer, Julie Vanderklish, Dustin J. Rabideau, Katherine Cronin, Mathew Reynolds, Nneka Ufere, Julia Rice, Madison Clay, Richard Newcomb, Zachariah DeFilipp, Vincent Ho, Robert J. Soiffer, Nicole Pensak, Yi-Bin Chen, Jennifer S. Temel
Journal: Journal of the National Comprehensive Cancer Network (2025)

Background: Interventions to address sexual health in hematopoietic stem cell transplant (HSCT) survivors are limited. Methods: We conducted a pilot randomized trial of a digital app, SHIFT (Sexual Health and Intimacy Following Transplant), to address sexual dysfunction in HSCT survivors who were ≥3 months post autologous or allogeneic HSCT. Patients were randomly assigned to SHIFT or enhanced usual care. All participants first underwent a brief physical examination by a trained HSCT clinician. Participants assigned to the intervention received access to SHIFT for 8 weeks. SHIFT consists of 5 modules addressing the biological, interpersonal, social, and psychological causes of sexual dysfunction. The primary endpoint was feasibility, defined a priori as ≥60% enrollment of eligible patients, and 60% of those assigned to SHIFT completing ≥70% of the modules. We assessed patient satisfaction with sex, interest in sex, orgasm pleasure (using the Patient-Reported Outcomes Measurement Information System [PROMIS]), quality of life (QoL; using the Functional Assessment of Cancer Therapy – Bone Marrow Transplant [FACT-BMT]), and anxiety and depression symptoms (using the Hospital Anxiety and Depression Scale [HADS]) at baseline, 8 weeks, and 12 weeks. The preliminary effects of SHIFT on study outcomes were explored using analysis of covariance (ANCOVA) and estimates of effect size at 8 weeks (Cohen’s d). Results: We enrolled 64.2% (61/95) of eligible patients. Of those assigned to the intervention, 70.0% completed 4 of the 5 SHIFT modules and 66.7% completed all SHIFT modules. At 8 weeks, SHIFT participants reported improved satisfaction with sex (14.6 vs 12.3; d=0.46), interest in sex (6.7 vs 5.7; d=0.59), orgasm pleasure (9.7 vs 8.3; d=0.37), QoL (115.6 vs 108.3; d=0.45), and symptoms of anxiety (4.5 vs 6.4; d=0.47) and depression (3.6 vs 5.4; d=0.62) compared with the control group. Conclusions: The SHIFT digital app to address sexual dysfunction demonstrated feasibility and promising preliminary efficacy in improving sexual health outcomes, QoL, and psychological distress for HSCT survivors.