tbuckley/cabot-search huggingface dataset:
Mental Illness and Substance Use Disorder Stigma: Mapping Pathways Between Structures and Individuals to Accelerate Research and Intervention
Authors: Valerie A. Earnshaw, Mohammad Mousavi, Xueli Qiu, Annie B. Fox
Journal: Annual Review of Clinical Psychology (2025)

Researchers, interventionists, and clinicians are increasingly recognizing the importance of structural stigma in elevating the risk of mental illnesses (MIs) and substance use disorders (SUDs) and in undermining MI/SUD treatment and recovery. Yet, the pathways through which structural stigma influences MI/SUD-related outcomes remain unclear. In this review, we aim to address this gap by summarizing scholarship on structural MI/SUD stigma and identifying pathways whereby structural stigma affects MI/SUD-related outcomes. We introduce a conceptual framework that describes how structural-level stigma mechanisms influence the MI/SUD treatment cascade via ( a ) interpersonal- and individual-level stigma mechanisms and ( b ) mediating processes among people with MI/SUD (i.e., access to resources, psychological responses, behavioral responses, social isolation). We consider intersections between MI/SUD stigma and stigma based on race/ethnicity, gender identity, and sexual orientation. Finally, we discuss the implications of this review for future research, interventions, and clinical practice.
The roles of KRAS in cancer metabolism, tumor microenvironment and clinical therapy
Authors: Qinglong Ma, Wenyang Zhang, Kongming Wu, Lei Shi
Journal: Molecular Cancer (2025)

Abstract KRAS is one of the most mutated genes, driving alternations in metabolic pathways that include enhanced nutrient uptaking, increased glycolysis, elevated glutaminolysis, and heightened synthesis of fatty acids and nucleotides. However, the beyond mechanisms of KRAS-modulated cancer metabolisms remain incompletely understood. In this review, we aim to summarize current knowledge on KRAS-related metabolic alterations in cancer cells and explore the prevalence and significance of KRAS mutation in shaping the tumor microenvironment and influencing epigenetic modification via various molecular activities. Given that cancer cells rely on these metabolic changes to sustain cell growth and survival, targeting these processes may represent a promising therapeutic strategy for KRAS-driven cancers.
ACC/AHA/ASE/HFSA/HRS/SCAI/SCCT/SCMR 2025 Appropriate Use Criteria for Implantable Cardioverter-Defibrillators, Cardiac Resynchronization Therapy, and Pacing
Authors: Andrea M. Russo, Milind Y. Desai, Monika M. Do, Javed Butler, Mina K. Chung, Andrew E. Epstein, Maya E. Guglin, Wayne C. Levy, Jonathan P. Piccini, Nicole M. Bhave, Andrea M. Russo, Milind Y. Desai, Monika M. Do, Amrut V. Ambardekar, Nancy C. Berg, Kenneth C. Bilchick, G. William Dec, Rakesh Gopinathannair, Janet K. Han, Liviu Klein, Rachel J. Lampert, Gurusher S. Panjrath, Ryan R. Reeves, Danita Marie Yoerger Sanborn, Lynne W. Stevenson, Quynh A. Truong, Paul D. Varosy, Todd C. Villines, Annabelle S. Volgman, Karolina M. Zareba
Journal: Journal of the American College of Cardiology (2025)
Myeloid Cells Induce Infiltration and Activation of B Cells and CD4+ T Follicular Helper Cells to Sensitize Brain Metastases to Combination Immunotherapy
Authors: Toshifumi Ninomiya, Naoya Kemmotsu, Fumiaki Mukohara, Masaki Magari, Ai Miyamoto, Youki Ueda, Takamasa Ishino, Joji Nagasaki, Tomohiro Fujiwara, Hidetaka Yamamoto, Hidetoshi Hayashi, Kota Tachibana, Joji Ishida, Yoshihiro Otani, Shota Tanaka, Shinichi Toyooka, Isamu Okamoto, Yosuke Togashi
Journal: Cancer Research (2025)

Brain metastasis (BM) is a poor prognostic factor in cancer patients. Despite showing efficacy in many extracranial tumors, immunotherapy with anti-PD-1 monoclonal antibody (mAb) or anti-CTLA-4 mAb appears to be less effective against intracranial tumors. Promisingly, recent clinical studies have reported that combination therapy with anti-PD-1 and anti-CTLA-4 mAbs has a potent antitumor effect on BM, highlighting the need to elucidate the detailed mechanisms controlling the intracranial tumor microenvironment (TME) to develop effective immunotherapeutic strategies. Here, we analyzed the tumor-infiltrating lymphocytes in murine models of BM that responded to anti-CTLA-4 mAb to anti-PD-1 mAb. Activated CD4+ T follicular helper (TFH) cells with high CTLA-4 expression characteristically infiltrated the intracranial TME, which were activated by the combination anti-CTLA-4 and anti-PD-1 treatment. Loss of TFH cells suppressed the additive effect of CTLA-4 blockade on anti-PD-1 mAb. B cell-activating factor belonging to the TNF family (BAFF) and a proliferation-inducing ligand (APRIL) produced by abundant myeloid cells, particularly CD80hiCD206lo pro-inflammatory M1-like macrophages, in the intracranial TME, induced B cell and TFH cell infiltration and activation. Furthermore, the intracranial TME of patients with non-small cell lung cancer featured TFH and B cell infiltration as tertiary lymphoid structures. Together, these findings provide insights into the immune cell crosstalk in the intracranial TME that facilitates an additive anti-tumor effect of CTLA-4 blockade with anti-PD-1 treatment, supporting the potential of a combination immunotherapeutic strategy for BM.
Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition
Authors: Antonino Glaviano, Hannah Si-Hui Lau, Lukas M. Carter, E. Hui Clarissa Lee, Hiu Yan Lam, Elena Okina, Donavan Jia Jie Tan, Wency Tan, Hui Li Ang, Daniela Carbone, Michelle Yi-Hui Yee, Muthu K. Shanmugam, Xiao Zi Huang, Gautam Sethi, Tuan Zea Tan, Lina H. K. Lim, Ruby Yun-Ju Huang, Hendrik Ungefroren, Elisa Giovannetti, Dean G. Tang, Tullia C. Bruno, Peng Luo, Mads Hald Andersen, Bin-Zhi Qian, Jun Ishihara, Derek C. Radisky, Salem Elias, Saurabh Yadav, Minah Kim, Caroline Robert, Patrizia Diana, Kurt A. Schalper, Tao Shi, Taha Merghoub, Simone Krebs, Anjali P. Kusumbe, Matthew S. Davids, Jennifer R. Brown, Alan Prem Kumar
Journal: Journal of Hematology & Oncology (2025)

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, and signaling molecules that interact to promote tumor growth and therapeutic resistance. Elucidating the intricate interactions between cancer cells and the TME is crucial in understanding cancer progression and therapeutic challenges. A critical process induced by TME signaling is the epithelial-mesenchymal transition (EMT), wherein epithelial cells acquire mesenchymal traits, which enhance their motility and invasiveness and promote metastasis and cancer progression. By targeting various components of the TME, novel investigational strategies aim to disrupt the TME's contribution to the EMT, thereby improving treatment efficacy, addressing therapeutic resistance, and offering a nuanced approach to cancer therapy. This review scrutinizes the key players in the TME and the TME's contribution to the EMT, emphasizing avenues to therapeutically disrupt the interactions between the various TME components. Moreover, the article discusses the TME's implications for resistance mechanisms and highlights the current therapeutic strategies toward TME modulation along with potential caveats.
Increased clonal hematopoiesis in long-term survivors of pediatric hematopoietic cell transplantation
Authors: Konradin F. Müskens, Nienke Wieringa, Maaike G.J.M. van Bergen, Joëll E. Bense, Brigit M. te Pas, Anne P.J. de Pagter, Arjan C. Lankester, Marc B. Bierings, Donna S. Neuberg, Saskia Haitjema, Leontien C.M. Kremer, Gerwin A. Huls, Stefan Nierkens, Joop H. Jansen, Caroline A. Lindemans, Aniek O. de Graaf, Mirjam E. Belderbos
Journal: Blood Cancer Discovery (2025)

In pediatric hematopoietic cell transplantation (HCT) recipients, transplanted donor cells may need to function far beyond normal human lifespan. Here, we investigated the risk of clonal hematopoiesis (CH) in 144 pediatric long-term HCT survivors and 258 non-transplanted controls. CH was detected in 16% of HCT recipients and 8% of controls, at variant allele frequencies (VAFs) of 0.01-0.31. Mutations were predominantly in DNMT3A (80%) and TET2 (20%). Older hematopoietic age (odds ratio: 1.07, p<0.001) and the HCT procedure (odds ratio: 2.53, p=0.02) independently increased the risk of CH, indicating both aging- and transplantation-induced effects. Large clones (VAF >0.10) were found exclusively in HCT recipients. Notably, CH was also detected within 15 years after a cord blood HCT. Inflammatory processes around graft infusion were associated with CH presence. Future studies are required to track the evolution of post-transplant CH and its impact on future cardiovascular disease, second malignancies and overall survival.
Psychedelic Medicine Exceptionalism
Authors: I. Glenn Cohen, Mason Marks
Journal: The American Journal of Bioethics (2025)

Research on psychedelic medicines is experiencing a revival. Some clinicians, scientists, and ethicists believe that psychedelics are so different from other treatments that they warrant special consideration in how they are researched, regulated, commercialized, and administered. Others argue that psychedelic medicines show clinical potential, but they should be treated like other medical interventions. In other words, identical standards should apply. This article analyzes whether psychedelic medicines warrant special consideration from a regulatory and ethical perspective.
Clonally expanded, targetable, natural killer-like NKG7 T cells seed the aged spinal cord to disrupt myeloid-dependent wound healing
Authors: Guiping Kong, Yayue Song, Yuyang Yan, Samantha M Calderazzo, Madhu Sudhana Saddala, Fabian De Labastida Rivera, Jonathan D Cherry, Noah Eckman, Eric A Appel, Adam Velenosi, Vivek Swarup, Riki Kawaguchi, Susanna S Ng, Brian K Kwon, David Gate, Christian R Engwerda, Luming Zhou, Simone Di Giovanni
Journal: Neuron (2025)

Spinal cord injury (SCI) increasingly affects aged individuals, where functional impairment and mortality are highest. However, the aging-dependent mechanisms underpinning tissue damage remain elusive. Here, we find that natural killer-like T (NKLT) cells seed the intact aged human and murine spinal cord and multiply further after injury. NKLT cells accumulate in the spinal cord via C-X-C motif chemokine receptor 6 and ligand 16 signaling to clonally expand by engaging with major histocompatibility complex (MHC)-I-expressing myeloid cells. NKLT cells expressing natural killer cell granule protein 7 (Nkg7) disrupt myeloid-cell-dependent wound healing in the aged injured cord. Nkg7 deletion in mice curbs NKLT cell degranulation to normalize the myeloid cell phenotype, thus promoting tissue repair and axonal integrity. Monoclonal antibodies neutralizing CD8+ T cells after SCI enhance neurological recovery by promoting wound healing. Our results unveil a reversible role for NKG7+CD8+ NKLT cells in exacerbating tissue damage, suggesting a clinically relevant treatment for SCI.
Wolves Among Sheep: Sexual Violations in Psychedelic-Assisted Therapy
Authors: Tahlia R. Harrison, Sonya C. Faber, Manzar Zare, Matthieu Fontaine, Monnica T. Williams
Journal: The American Journal of Bioethics (2025)

The integration of psychedelic substances into modern Western therapeutic practice has sparked a critical examination of many topics including: efficacy of psychedelics to treat mental health diagnoses without psychotherapeutic intervention, what models of therapy to use, and ethical implications related to altered states of consciousness. Of utmost concern are issues of power dynamics leading to incidents of sexual abuse. These issues underscore the importance of understanding therapeutic dynamics within the context of psychedelic-assisted therapy. This paper aims to explore these intersections, addressing sexual abuse issues in Western psychedelic-assisted therapy while elucidating pathways towards ethical practice and regulatory frameworks.
Supportive Touch in Psychedelic Assisted Therapy
Authors: Logan Neitzke-Spruill, Caroline Beit, Lynnette A. Averill, Amy L. McGuire
Journal: The American Journal of Bioethics (2025)

In August 2024, The U.S. Food and Drug Administration rejected Lykos Therapeutics, Inc.'s new drug application for midomafetamine with psychological intervention (MDMA-AT) to treat post-traumatic stress disorder (PTSD). Among the many issues raised during review was concern about a highly publicized case of alleged sexual misconduct by an unlicensed therapist during a Phase 2 study of MDMA and the potential risk of future abuse. This incident of misconduct, along with several other publicized cases of misconduct by guides, facilitators, and shaman offering psychedelic retreats, has raised the question of whether physical contact is ever appropriate during psychedelic-assisted therapy (PAT). Drawing on research about supportive touch in other clinical contexts and taking into consideration features of psychedelics that exacerbate the potential for harm associated with supportive touch, we advocate for a precautionary approach to harm-reduction while arguing that supportive touch ought not be thrown out whole-cloth.
Enabling tumor-specific drug delivery by targeting the Warburg effect of cancer
Authors: Jian Zhang, Tony Pan, Jimmy Lee, Sanja Goldberg, Sarah Ann King, Erting Tang, Yifei Hu, Lifeng Chen, Alex Hoover, Linyong Zhu, Oliver S Eng, Benjamin Dekel, Jun Huang, Xiaoyang Wu
Journal: Cell Reports Medicine (2025)

Metabolic reprogramming of tumor cells is an emerging hallmark of cancer. Among all the changes in cancer metabolism, increased glucose uptake and the accumulation of lactate under normoxic conditions (the "Warburg effect") is a common feature of cancer cells. In this study, we develop a lactate-responsive drug delivery platform by targeting the Warburg effect. We design and test a gold/mesoporous silica Janus nanoparticle system as a gated drug carrier, in which the gold particles are functionalized with lactate oxidase and the silica particles are capped with α-cyclodextrin through surface arylboronate modification. In the presence of lactate, the lactate oxidase generates hydrogen peroxide, which induces the self-immolation reaction of arylboronate, leading to uncapping and drug release. Our results demonstrate greatly improved drug delivery specificity and therapeutic efficacy with this platform for the treatment of different cancers. Our findings present an effective approach for drug delivery by metabolic targeting of tumors.
High cellular plasticity state of medulloblastoma local recurrence and distant dissemination
Authors: Hailong Liu, Jing Zhang, Ziwei Wang, Wei Wang, Dongming Han, Xuan Chen, Yu Su, Jiao Zhang, Craig Daniels, Olivier Saulnier, Zeyuan John Wang, Chunyu Gu, Fei Liu, Kaiwen Deng, Dongyang Wang, Zhaoyang Feng, Yahui Zhao, Yifei Jiang, Yu Gao, Zijia Liu, Mingxu Ma, Yanong Li, Zitong Zhao, Hongyu Yuan, Youliang Sun, Yanfeng Shi, Tao Yang, Wenxing Li, Xueling Qi, Zejun Duan, Junping Zhang, Mingshan Zhang, Chunjiang Yu, Wei Jin, Xinguang Yu, Yu Tian, Shuaicheng Li, Chunde Li, Michael D Taylor, Jiankang Li, Yong-Qiang Liu, Xiaoguang Qiu, Tao Jiang
Journal: Cell Reports Medicine (2025)

Medulloblastoma (MB), a heterogeneous pediatric brain tumor, poses challenges in the treatment of tumor recurrence and dissemination. To characterize cellular diversity and genetic features, we comprehensively analyzed single-cell/nucleus RNA sequencing (sc/snRNA-seq), single-nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq), and spatial transcriptomics profiles and identified distinct cellular populations in SHH (sonic hedgehog) and Group_3 subgroups, with varying proportions in local recurrence or dissemination. Local recurrence showed higher cycling tumor cell enrichment, whereas disseminated lesions had a relatively notable presence of differentiated subsets. Chromosomal alteration evaluation revealed distinct genetic subclones during MB progression, such as chr7q gain and chr11 loss in Group_3 disseminations. A subpopulation termed "high cellular plasticity (HCP)" emerged during MB progression and was associated with increased dividing potential and chromatin accessibility, contributing to recurrence. Inhibiting HCP-associated markers, like protein tyrosine phosphatase receptor type Z1 (PTPRZ1), efficiently suppressed MB progression in preclinical models. These findings address critical gaps in understanding the cellular diversity, chromosomal alterations, and biological dynamics of recurrent MB, offering potential therapeutic insights.
Single-molecule systems for the detection and monitoring of plasma-circulating nucleosomes and oncoproteins in diffuse midline glioma
Authors: Nir Erez, Noa Furth, Vadim Fedyuk, Jack Wadden, Rayan Aittaleb, Tiffany Adam, Kallen Schwark, Michael Niculcea, Madeline Miclea, Rajen Mody, Andrea Franson, Hemant A Parmar, Mohannad Ibrahim, Benison Lau, Augustine Eze, Niku Nourmohammadi, Iris Fried, Javad Nazarian, Guy Ron, Sriram Venneti, Carl Koschmann, Efrat Shema
Journal: Cell Reports Medicine (2025)

The analysis of cell-free tumor DNA (ctDNA) and proteins in the blood of patients with cancer potentiates a new generation of non-invasive diagnostic approaches. However, confident detection of tumor-originating markers is challenging, especially in the context of brain tumors, where these analytes in plasma are extremely scarce. Here, we apply a sensitive single-molecule technology to profile multiple histone modifications on individual nucleosomes from the plasma of patients with diffuse midline glioma (DMG). The system reveals epigenetic patterns unique to DMG, significantly differentiating this group of patients from healthy subjects or individuals diagnosed with other cancer types. We further develop a method to directly quantify the tumor-originating oncoproteins, lysine 27 to methionine substitution in histone H3 (H3-K27M) and mutant p53, from <1 mL of plasma, allowing for the accurate molecular classification of patients with DMG. We show that our strategy correlates with MRI and droplet-digital PCR (ddPCR) measurements of ctDNA, highlighting the clinical potential of single-molecule-based, multi-parametric assays for DMG diagnosis and treatment monitoring.
Dual ferroptosis induction in N2-TANs and TNBC cells via FTH1 targeting: A therapeutic strategy for triple-negative breast cancer
Authors: Yichen Liu, Qingyan Sun, Jingwen Guo, Li Yan, Yue Yan, Yiting Gong, Jiayi Lin, Hu Yuan, Jinmei Jin, Bei Wang, Hongzhuan Chen, Lijun Zhang, Weidong Zhang, Xin Luan
Journal: Cell Reports Medicine (2025)

Tumor-associated neutrophils (TANs) play a critical role in the progression and prognosis of triple-negative breast cancer (TNBC), with N2-type TANs known for their pro-tumor characteristics. This study introduces CT-1, a derivative of cryptotanshinone that effectively suppresses TNBC growth while selectively reducing the proportion of N2-type TANs within tumor tissue. Notably, CT-1 induces simultaneous ferroptosis in both N2-type TANs and TNBC cells, a dual mechanism that enhances its therapeutic efficacy. The study identifies ferritin heavy chain 1 (FTH1), a key protein in iron metabolism, as the direct target of CT-1. By targeting FTH1, CT-1 facilitates the interaction between NCOA4 and ferritin, triggering ferritinophagy-mediated ferroptosis. These findings position CT-1 as a promising therapeutic agent, offering a strategy to combat TNBC by inducing ferroptosis in both N2-type TANs and cancer cells. This approach underscores the potential of FTH1 as a therapeutic target for treating TNBC.
Initial Decline in Glomerular Filtration Rate With Finerenone in HFmrEF/HFpEF
Authors: Shingo Matsumoto, Pardeep S. Jhund, Alasdair D. Henderson, Johann Bauersachs, Brian L. Claggett, Akshay S. Desai, Meike Brinker, Patrick Schloemer, Prabhakar Viswanathan, Jon W. Mares, Andrea Scalise, Carolyn S.P. Lam, Gerard C.M. Linssen, Jose Francisco Kerr Saraiva, Michele Senni, Richard Troughton, Jacob A. Udell, Adriaan A. Voors, Faiez Zannad, Bertram Pitt, Muthiah Vaduganathan, Scott D. Solomon, John J.V. McMurray
Journal: Journal of the American College of Cardiology (2025)

An initial decline in estimated glomerular filtration rate (eGFR) often leads to reluctance to continue life-saving therapies in patients with heart failure (HF). The goal of this study was to describe the association between initial decline in eGFR and subsequent clinical outcomes in patients randomized to placebo or finerenone. In this prespecified analysis of FINEARTS-HF (Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients with Heart Failure), we examined the association between initial decline in eGFR (≥15%) from randomization to 1 month and subsequent outcomes in patients assigned to finerenone or placebo. The primary outcome was the composite of total HF events and cardiovascular death. Among 5,587 patients with an eGFR measurement at both baseline and 1 month, 1,018 (18.2%) experienced a ≥15% decline in eGFR. The proportion of patients experiencing a ≥15% decline in eGFR was 23.0% with finerenone and 13.4% with placebo (OR: 1.95; 95% CI: 1.69-2.24; P < 0.001). After adjustment, an eGFR decline was associated with a higher risk of the primary outcome in patients assigned to placebo (adjusted rate ratio: 1.50; 95% CI: 1.20-1.89) but not in those assigned to finerenone (adjusted rate ratio: 1.07; 95% CI: 0.84-1.35; Pinteraction = 0.04). By contrast, the efficacy of finerenone was consistent across the range of change in eGFR from baseline to 1 month (Pinteraction = 0.50 for percent change in eGFR), and safety, including hyperkalemia, was similar regardless of an early eGFR decline. Although an initial decline in eGFR was associated with worse outcomes in patients assigned to placebo, this relationship was not as strong in those treated with finerenone. An early decline in eGFR can be anticipated with finerenone and should not automatically lead to the discontinuation of this disease-modifying therapy (FINEARTS-HF Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients with Heart Failure [NCT04435626]; A Multicenter, Randomized, Double-Bline, Parallel-Group, Placebo-Controlled Study to Evaluate the efficacy and safety of finerenone on morbidity and mortality in participants With Heart Failure [NYHA II-IV] and left ventricular ejection fraction ≥40% [EudraCT 2020-000306-29]).
Gut microbial GABA imbalance emerges as a metabolic signature in mild autism spectrum disorder linked to overrepresented Escherichia
Authors: Dilong Wang, Youheng Jiang, Jian Jiang, Yihang Pan, Yanming Yang, Xiaoyi Fang, Liyang Liang, Hai Li, Zepeng Dong, Shilu Fan, Daqing Ma, Xue-Song Zhang, Huiliang Li, Yulong He, Ningning Li
Journal: Cell Reports Medicine (2025)

Gut microbiota (GM) alterations have been implicated in autism spectrum disorder (ASD), yet the specific functional architecture remains elusive. Here, employing multi-omics approaches, we investigate stool samples from two distinct cohorts comprising 203 children with mild ASD or typical development. In our screening cohort, regression-based analysis for metabolomic profiling identifies an elevated γ-aminobutyric acid (GABA) to glutamate (Glu) ratio as a metabolic signature of ASD, independent of age and gender. In the validating cohort, we affirm the GABA/Glu ratio as an ASD diagnostic indicator after adjusting for geography, age, gender, and specific food-consuming frequency. Integrated analysis of metabolomics, 16S rRNA sequencing, and metagenomics reveals a correlation between overrepresented Escherichia and disrupted GABA metabolism. Furthermore, we observe social behavioral impairments in weaning mice transplanted with E. coli, suggesting a potential link to ASD symptomatology. Collectively, these findings provide insights into potential diagnostic and therapeutic strategies aimed at evaluating and restoring gut microbial neurotransmitter homeostasis.