tbuckley/cabot-search huggingface dataset:
Stress and Cardiovascular Disease: The Role of Affective Traits and Mental Disorders
Authors: Richard J. Contrada
Journal: Annual Review of Clinical Psychology (2025)

Personality traits involving negative affect, as well as mental disorders including depression, anxiety, and posttraumatic stress disorder, are cardiovascular risk factors. However, which of these confer risk independently is uncertain, and the implications of their overlap, combinations, and interactions are poorly understood. Potential explanatory mechanisms are being characterized with increasing detail and sophistication. Of particular interest are psychobiological processes initiated by stress. Other mechanisms involve stress-related health behaviors and illness behaviors that delay or reduce the effectiveness of medical treatment. With some promising exceptions, findings of intervention trials are uncertain regarding the effectiveness of psychological treatments for modifying affective traits and mental disorders to reduce their impact on cardiovascular disease. Recent developments include novel conceptualizations of mental disorders; examination of the interplay between cognitive factors and emotion; and theoretical frameworks that integrate psychological stress processes with neuroscience, health behavior, and social cognition. Also promising is increased attention to gender identity and minority group membership.
Oral obeldesivir provides postexposure protection against Marburg virus in nonhuman primates
Authors: Robert W Cross, Courtney Woolsey, Abhishek N Prasad, Viktoriya Borisevich, Krystle N Agans, Daniel J Deer, Mack B Harrison, Natalie S Dobias, Karla A Fenton, Tomas Cihlar, Anh-Quan Nguyen, Darius Babusis, Roy Bannister, Meghan S Vermillion, Victor C Chu, Thomas W Geisbert
Journal: Nature Medicine (2025)
Highlighted Research Articles
Journal: Cancer Discovery (2025)

In This Issue| January 13 2025 Highlighted Research Articles Author & Article Information Online ISSN: 2159-8290 Print ISSN: 2159-8274 ©2024 American Association for Cancer Research2024American Association for Cancer Research Cancer Discov (2025) 15 (1): 5–7. https://doi.org/10.1158/2159-8290.CD-15-1-ITI Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Article Versions Icon Versions Version of Record January 13 2025 Citation Highlighted Research Articles. Cancer Discov 1 January 2025; 15 (1): 5–7. https://doi.org/10.1158/2159-8290.CD-15-1-ITI Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest Search Advanced Search Extrachromosomal DNA (ecDNA) frequently drives cancers, yet ecDNA formation remains poorly understood. Using a CRISPR-based method, Rose and colleagues generated and extensively characterized newly formed ecDNA, revealing that circularization of megabase-scale DNA segments was efficient, irrespective of 3D genome context. Non-homologous end joining and microhomology-mediated end joining both contributed to ecDNA formation, while inhibition of DNA-PK and ATM exhibited opposing effects. EcDNA and the corresponding chromosomal deletion formed at different rates and responded differently to DNA-PK and ATM inhibition. These results support a model in which double strand break ends dissociate and misjoin to form the ecDNA and chromosomal deletion. See article, p. 69. The vast majority of small cell lung carcinomas (SCLC) arise in smokers and harbor RB1 and TP53 genomic alterations. In this study, Rekhtman and colleagues identified a rare subset of SCLC that arises in the absence of smoking-mediated mutagenesis or RB1 and TP53 mutations. This... You do not currently have access to this content.
Two-Photon Photosensitizer for Specific Targeting and Induction of Tumor Pyroptosis to Elicit Systemic Immunity-Boosting Anti-Tumor Therapy
Authors: Yubo Tan, Guosheng Hu, Man Li, Yibo An, Ziying Wang, Renyuan Liu, Dazhuang Xu, Xinyu Tan, Yun Zeng, Yaohui He, Zhixiang Lu, Gang Liu
Journal: Biomaterials (2025)
Prognostic significance of immune reconstitution following CD19 CAR T‐cell therapy for relapsed/refractory B‐cell lymphoma
Authors: Sophia Stock, Veit L. Bücklein, Viktoria Blumenberg, Giulia Magno, Alica‐Joana Emhardt, Alessandra M. E. Holzem, David M. Cordas dos Santos, Christian Schmidt, Stefanie Grießhammer, Lisa Frölich, Sebastian Kobold, Michael von Bergwelt‐Baildon, Kai Rejeski, Marion Subklewe
Journal: HemaSphere (2025)

Abstract Immune deficits after CD19 chimeric antigen receptor (CAR) T‐cell therapy can be long‐lasting, predisposing patients to infections and non‐relapse mortality. In B‐cell non‐Hodgkin lymphoma (B‐NHL), the prognostic impact of immune reconstitution (IR) remains ill‐defined, and detailed cross‐product comparisons have not been performed to date. In this retrospective observational study, we longitudinally characterized lymphocyte subsets and immunoglobulin levels in 105 B‐NHL patients to assess patterns of immune recovery arising after CD19 CAR‐T. Three key IR criteria were defined as CD4 + T helper (T H ) cells &gt; 200/µL, any detectable B cells, and serum immunoglobulin G (IgG) levels &gt;4 g/L. After a median follow‐up of 24.6 months, 38% of patients displayed T H cells, 11% showed any B cells, and 41% had IgG recovery. Notable product‐specific differences emerged, including deeper T H cell aplasia with CD28z‐ versus longer B‐cell aplasia with 41BBz‐based products. Patients with any IR recovery experienced extended progression‐free survival (PFS) (median 20.8 vs. 1.7 months, p &lt; 0.0001) and overall survival (OS) (34.9 vs. 4.0 months, p &lt; 0.0001). While landmark analysis at 90 days confirmed improved PFS in patients with any recovery (34.9 vs. 8.6 months, p = 0.005), no significant OS difference was noted. Notably, 72% of patients with refractory disease never displayed recovery of any IR criteria. Early progressors showed diminished IR at the time of progression/relapse compared to patients with late progression/recurrence (after Day 90). Our results highlight the profound immune deficits observed after CD19 CAR‐T and shed light on the intersection of IR and efficacy in B‐NHL. Importantly, IR was impaired considerably postprogression, carrying significant implications for subsequent T‐cell‐engaging therapies and treatment sequencing.
Estimating the Exposure–Response Relationship between Fine Mineral Dust Concentration and Coccidioidomycosis Incidence Using Speciated Particulate Matter Data: A Longitudinal Surveillance Study
Authors: Amanda K. Weaver, Nicole Keeney, Jennifer R. Head, Alexandra K. Heaney, Simon K. Camponuri, Philip Collender, Abinash Bhattachan, Gregory S. Okin, Ellen A. Eisen, Gail Sondermeyer-Cooksey, Alexander Yu, Duc J. Vugia, Seema Jain, John Balmes, John Taylor, Justin V. Remais, Matthew J. Strickland
Journal: Environmental Health Perspectives (2025)

Coccidioidomycosis, caused by inhalation of Coccidioides spp. spores, is an emerging infectious disease that is increasing in incidence throughout the southwestern US. The pathogen is soil-dwelling, and spore dispersal and human exposure are thought to co-occur with airborne mineral dust exposures, yet fundamental exposure-response relationships have not been conclusively estimated. We estimated associations between fine mineral dust concentration and coccidioidomycosis incidence in California from 2000 to 2017 at the census tract level, spatiotemporal heterogeneity in exposure-response, and effect modification by antecedent climate conditions. We acquired monthly census tract-level coccidioidomycosis incidence data and modeled fine mineral dust concentrations from 2000 to 2017. We fitted zero-inflated distributed-lag nonlinear models to estimate overall exposure-lag-response relationships and identified factors contributing to heterogeneity in exposure-responses. Using a random-effects meta-analysis approach, we estimated county-specific and pooled exposure-responses for cumulative exposures. We found a positive exposure-response relationship between cumulative fine mineral dust exposure in the 1-3 months before estimated disease onset and coccidioidomycosis incidence across the study region [incidence rate ratio (IRR) for an increase from 0.1 to 1.1 μg/m3=1.60; 95% CI: 1.46, 1.74]. Positive, supralinear associations were observed between incidence and modeled fine mineral dust exposures 1 [IRR=1.13 (95% CI: 1.10, 1.17)], 2 [IRR=1.15 (95% CI: 1.09, 1.20)] and 3 [IRR=1.08 (95% CI: 1.04, 1.12)] months before estimated disease onset, with the highest exposures being particularly associated. The cumulative exposure-response relationship varied significantly by county [lowest IRR, western Tulare: 1.05 (95% CI: 0.54, 2.07); highest IRR, San Luis Obispo: 3.01 (95% CI: 2.05, 4.42)]. Season of exposure and prior wet winter were modest effect modifiers. Lagged exposures to fine mineral dust were strongly associated with coccidioidomycosis incidence in the endemic regions of California from 2000 to 2017. https://doi.org/10.1289/EHP13875.
MTHFD2 Enhances cMYC O-GlcNAcylation to Promote Sunitinib Resistance in Renal Cell Carcinoma
Authors: Jinwen Liu, Gaowei Huang, Hao Lin, Rui Yang, Wenhao Zhan, Cheng Luo, Yukun Wu, Lingwu Chen, Xiaopeng Mao, Junxing Chen, Bin Huang
Journal: Cancer Research (2025)

Sunitinib is a first-line targeted therapy for patients with renal cell carcinoma (RCC), but resistance represents a significant obstacle to the treatment of advanced and metastatic RCC. Metabolic reprogramming is a characteristic of RCC, and changes in metabolic processes might contribute to resistance to sunitinib. Here, we identified MTHFD2, a mitochondrial enzyme involved in one-carbon metabolism, as a critical mediator of sunitinib resistance in RCC. MTHFD2 was elevated in sunitinib resistant RCC cells, and loss of MTHDF2 conferred sensitivity to sunitinib. In patients, MTHFD2 was highly expressed in RCC and was associated with poor outcomes. Mechanistically, MTHFD2 stimulated UDP-GlcNAc biosynthesis and promoted cMYC O-GlcNAcylation by driving the folate cycle. O-GlcNAcylation enhanced cMYC stability and promoted MTHFD2 and CCND1 transcription. Targeting MTHFD2 or cyclin D1 sensitized tumor cells to sunitinib in vitro and in vivo. Consistently, development of a peptide drug capable of efficiently degrading MTHFD2 enabled reversal of sunitinib resistance in RCC. These findings identify a noncanonical metabolic function of MTHFD2 in cell signaling and response to therapy and reveal the interplay between one-carbon metabolism and sunitinib resistance in RCC. Targeting MTHFD2 could be an effective approach to overcome sunitinib resistance.
PIN1 prolyl isomerase promotes initiation and progression of bladder cancer through the SREBP2-mediated cholesterol biosynthesis pathway
Authors: Xue Wang, Derrick Lee, Haibo Xu, Yuan Sui, Jill Meisenhelder, Tony Hunter
Journal: Cancer Discovery (2025)

Identities of functional pSer/Thr.Pro protein substrates of the PIN1 prolyl isomerase and its effects on downstream signaling in bladder carcinogenesis remain largely unknown. Phenotypically, we found that PIN1 positively regulated bladder cancer cell proliferation, cell motility and urothelium clearance capacity in vitro and controlled tumor growth and potential metastasis in vivo. Mechanistically, we observed a negative enrichment of SREBP2-driven cholesterol metabolism pathways and a decrease in free/total cholesterol levels in PIN1-knockout bladder cancer cells. Moreover, we showed that PIN1 interacted with SREBP2 following its phosphorylation by the JNK MAP kinase at Ser455, which lies near the Site-2 cleavage site that generates the active, nuclear-form of SREBP2. Therapeutically, a combination of the sulfopin PIN1 covalent inhibitor and the simvastatin HMGCoA reductase inhibitor suppressed cell proliferation in vitro and tumor growth in vivo synergistically. Together, these findings emphasize that PIN1 can act as a driver and potential therapeutic target in bladder cancer.
The (re)emergence of aerosol delivery: Treatment of pulmonary diseases and its clinical challenges
Authors: Rosy Ghanem, Raphaëlle Youf, Tanguy Haute, Xavier Buin, Martijn Riool, Jérémie Pourchez, Tristan Montier
Journal: Journal of Controlled Release (2025)

Aerosol delivery represents a rapid and non-invasive way to directly reach the lungs while escaping the hepatic first-pass effect. The development of pulmonary drugs for respiratory diseases such as cystic fibrosis, lung infections, pulmonary fibrosis or lung cancer requires an enhanced understanding of the relationships between the natural physiology of the respiratory system and the pathophysiology of these conditions. This knowledge is crucial to better predict and thereby control drug deposition. Moreover, aerosol administration faces several challenges, including the pulmonary tract, immune system, mucociliary clearance, the presence of fluid on the airway surfaces, and, in some cases, bacterial colonisation. Each of them directly influences on the bioavailability of the active molecule. In addition to these challenges, particle size and the device used to administer the treatment are critical factors that can significantly impact the biodistribution of the drugs. Nanoparticles are very promising in the development of new formulations for aerosol drug delivery, as they can be fine-tuned to reach the entire pulmonary tract and overcome the difficulties encountered along the way. However, to properly assess drug delivery, preclinical studies need to be more thorough to efficiently enhance drug delivery.
Unveiling the drug delivery mechanism of graphene oxide dots at the atomic scale
Authors: Giulia Frigerio, Stefano Motta, Paulo Siani, Edoardo Donadoni, Cristiana Di Valentin
Journal: Journal of Controlled Release (2025)

Graphene oxide (GO) is an amphiphilic and versatile graphene-based nanomaterial that is extremely promising for targeted drug delivery, which aims to administer drugs in a spatially and temporally controlled manner. A typical GO nanocarrier features a polyethylene glycol coating and conjugation to an active targeting ligand. However, it is challenging to accurately model GO dots, because of their intrinsically complex and not unique structure. Here, realistic atomistic GO models are designed as homogeneously/inhomogeneously oxidized flakes and then coated with stealth polymeric chains conjugated to an active targeting ligand (PEG-cRGD). Doxorubicin (DOX) adsorption is investigated by metadynamics simulations for accelerated loading/release events. The presence of PEG and cRGD are found not to affect the DOX adsorption, whereas the homogeneity of oxidation plays a crucial role. We also proved that a change in pH towards acidic conditions causes a reduction in the GO/DOX affinity in line with a pH-triggered release mechanism. Based on this study, the ideal graphene-based DOX carrier is identified as a homogeneously highly oxidized GO where graphitic regions with strong DOX π-π stacking are limited. Such interactions excessively stabilize DOX and are not weakened by a pH-change. On the contrary, DOX interactions with surface oxidized groups are H-bonding and electrostatic, which can effectively be modified by a pH reduction. Our findings are useful to the experimental community to further develop successful drug delivery systems.
Hair Straightener Use in Relation to Prevalent and Incident Fibroids in the Sister Study with a Focus on Black Women
Authors: Kemi Ogunsina, Katie M. O’Brien, Alexandra J. White, Che-Jung Chang, Symielle A. Gaston, Chandra L. Jackson, Dale P. Sandler
Journal: Environmental Health Perspectives (2025)

Uterine fibroids disproportionately affect Black women, and exposure to chemicals from hair relaxers or straighteners ("straighteners") may contribute to fibroid development. We examined the association between straightener use and prevalent young-onset uterine fibroids (diagnosed before age 36 y), as well as incident fibroids (diagnosed age 36-60 y), with a focus on Black women. We also examined differences in associations across birth cohorts as proxies for formulation changes. Data from 4,162 Black women in the Sister Study, a prospective cohort of women 35-74 y of age (enrolled 2003-2009), were analyzed. We used logistic regression to estimate odds ratios (ORs) for the association of straightener use at 10-13 y of age and self-reported young-onset fibroids. We used Cox regression to assess hazard ratios (HRs) for straightener use (age 10-13 y and in 12 months before enrollment) and incident fibroids among 779 premenopausal Black women. Similar analyses were conducted in 40,782 non-Hispanic White women. Over 70% of Black women used straighteners. In comparison with no use, any [OR=1.15; 95% confidence interval (CI): 0.96, 1.36] and frequent use (OR=1.18; 95% CI: 0.99, 1.42) of straighteners at 10-13 y of age were associated with young-onset fibroids. This association was most apparent among those born between 1928 and 1945 (OR=1.78; 95% CI: 1.15, 2.74) and 1965-1974 (OR=1.64; 95% CI: 0.82, 3.29). Fibroid incidence from 36 to 60 y of age was modestly associated with use of straighteners at 10-13 y of age [hazard ratio (HR)=1.14; 95% CI: 0.81, 1.63] and in the 12 months prior to enrollment (HR=1.32; 95% CI: 0.88, 2.00). Among non-Hispanic White women, straightener use at 10-13 y of age was similarly associated with young-onset fibroids (OR=1.23; 95% CI: 1.03, 1.47) despite lower use (≤5%) of straighteners. Sensitivity analyses indicated a potential for bias due to fibroid misclassification, with an overestimation of the effect likely if nulliparous women or women from households with lower education reported their fibroid status less accurately. Hair straightener use may be positively associated with fibroid risk. https://doi.org/10.1289/EHP14493.
Comparative Single-Cell Transcriptomics of Human Neuroblastoma and Preclinical Models Reveals Conservation of an Adrenergic Cell State
Authors: Bethel Tesfai Embaie, Hirak Sarkar, Adele Mirna. Alchahin, Jörg Otte, Thale Kristin. Olsen, Conny Tümmler, Polina Kameneva, Artem V. Artemov, Natalia Akkuratova, Igor Adameyko, Jan-Bernd Stukenborg, Malin Wickström, Per Kogner, John Inge Johnsen, Shenglin Mei, Peter V. Kharchenko, Ninib Baryawno
Journal: Cancer Research (2025)

Abstract Transgenic mice and organoid models, such as three-dimensional tumoroid cultures, have emerged as powerful tools for investigating cancer development and targeted therapies. Yet, the extent to which these preclinical models recapitulate the cellular identity of heterogeneous malignancies, like neuroblastoma (NB), remains to be validated. Here, we characterized the transcriptional landscape of TH-MYCN tumors by single-cell RNA sequencing (scRNA-seq) and developed ex vivo tumoroids. Integrated analysis with murine fetal adrenal samples confirmed that both TH-MYCN tumors and tumoroids closely mirror the cellular profiles of normal embryonic sympathoblasts and chromaffin cells. Comprehensive comparison between tumors from NB patients and TH-MYCN mice demonstrated similarities in adrenergic tumor cell composition. Ex vivo tumoroid cultures displayed histological resemblance and shared transcriptional profiles with the originating TH-MYCN tumors and human NB. Importantly, subpopulations within tumoroids exhibited gene expression associated with poor NB patient survival. Notably, recurrent observations of a low-proliferative chromaffin phenotype connected to the highly proliferative sympathetic phenotype suggested that pushing sympathoblasts into a chromaffin-like state may offer an interesting therapeutic strategy for NB. Together, this study not only deepens our understanding of a widely used transgenic mouse NB model but also introduces an ex vivo model that maintains critical adrenergic cell state identity, thereby enhancing its translational potential for NB research.
Evolutionary Pressures Shape Undifferentiated Pleomorphic Sarcoma Development and Radiotherapy Response
Authors: Erik Blomain, Shaghayegh Soudi, Ziwei Wang, Anish Somani, Ajay Subramanian, Serey C.L. Nouth, Eniola Oladipo, Chistin New, Deborah E. Kenney, Neda Nemat-Gorgani, Thomas Kindler, Raffi S. Avedian, Robert J. Steffner, David G. Mohler, Susan M. Hiniker, Alexander L. Chin, Anusha Kalbasi, Michael S. Binkley, Marius Fried, Matthias M. Gaida, Matt van de Rijn, Everett J. Moding
Journal: Cancer Research (2025)

Radiotherapy is an integral component in the treatment of many types of cancer, with approximately half of cancer patients receiving radiotherapy. Systemic therapy applies pressure that can select for resistant tumor subpopulations, underscoring the importance of understanding how radiation impacts tumor evolution to improve treatment outcomes. We integrated temporal genomic profiling of 120 spatially distinct tumor regions from 20 patients with undifferentiated pleomorphic sarcomas (UPS), longitudinal circulating tumor DNA (ctDNA) analysis, and evolutionary biology computational pipelines to study UPS evolution during tumorigenesis and in response to radiotherapy. Most unirradiated UPS displayed initial linear evolution followed by subsequent branching evolution with distinct mutational processes during early and late development. Metrics of genetic divergence between regions provided evidence of strong selection pressures during UPS development that further increased during radiotherapy. Subclone abundance changed following radiotherapy with subclone contraction tied to alterations in calcium signaling, and inhibiting calcium transporters radiosensitized sarcoma cells. Finally, ctDNA analysis accurately measured subclone abundance and enabled non-invasive monitoring of subclonal changes. These results demonstrate that radiation exerts selective pressures on UPS and suggest that targeting radioresistant subclonal populations could improve outcomes after radiotherapy.
Supported Mindfulness-Based Self-Help Intervention as an Adjunctive Treatment for Rapid Symptom Change in Emotional Disorders: A Practice-Oriented Multicenter Randomized Controlled Trial
Authors: Yanjuan Li, Yi Zhang, Chun Wang, Jia Luo, Yang Yu, Shixing Feng, Chunxue Wang, Qianwen Xu, Pengchong Wang, Junxuan Chen, Ning Zhang, Qianmei Yu, Yuqing Liu, Danyun Chen, Stefan G. Hofmann, Xinghua Liu
Journal: Psychotherapy and Psychosomatics (2025)

Introduction: Rapid symptom relief is crucial for individuals with emotional disorders. The current study aimed to determine whether facilitator-supported mindfulness-based self-help (MBSH) intervention as an adjunctive treatment could provide rapid improvement for individuals with emotional disorders. Methods: A practice-oriented randomized controlled trial was conducted on a sample of 302 patients with emotional disorders from four centers. Participants were randomly assigned to either MBSH+TAU (treatment as usual; n = 152) or TAU-only group (n = 150). Assessments were conducted at baseline, week 3, week 5, immediately after intervention and at a 3-month follow-up. Primary outcomes included self-reported and clinician-reported anxiety and depression symptoms. Secondary outcomes included mindfulness, physical symptoms, perceived stress, sleep quality, and inner peace. Results: The MBSH+TAU group achieved significantly greater improvements in all primary and secondary outcome measures as compared with TAU-only immediately after intervention (Cohen’s d = 0.19–0.51). In addition, relatively greater improvements were observed in self-reported depression, mindfulness, physical symptoms, perceived stress, and inner peace as early as week 3 or 5, which were sustained at the 3-month follow-up (Cohen’s d = 0.20–0.34). Conclusions: Facilitator-supported MBSH offers a scalable and effective adjunctive treatment option for patients with emotional disorders in clinical practice, facilitating rapid improvements.