tbuckley/cabot-search huggingface dataset:
The Glycosyltransferase XYLT1 Activates NF-κB Signaling to Promote Metastasis of Early-Stage Lung Adenocarcinoma
Authors: Jian Han, Jianan Du, Xiangmeng Li, Qingbo Zhou, Jiayu Zeng, Jun-Tao Lin, Wenle Zhou, Jiayi Cai, Yaokai Ye, Bosui Yang, Junsheng Wang, Xiang Zhou, Rong Lian, Yi Yang, Xun Zhu, Hongyu Guan, Liping Liu, Junchao Cai, Jueheng Wu, Yun Li, Mengfeng Li, Han Tian
Journal: Cancer Research (2025)

Abstract Early-stage lung adenocarcinoma (LUAD) generally has a favorable prognosis. However, more than 30% of early-stage LUAD cases relapse within 5 years of initial treatment, even following complete removal of the primary tumor. Identification of the factors contributing to early-stage LUAD metastasis is needed to develop effective prevention and treatment strategies. Here, we found upregulation of xylosyltransferase 1 (XYLT1), a glycosyltransferase that initiates biosynthesis of sulfated glycosaminoglycan (sGAG) chains, in metastatic recurrent lesions of early-stage LUAD, which correlated with poor prognosis. In vitro and in vivo experiments showed that XYLT1 promoted LUAD cell survival and metastasis by activating the NF-κB pathway. Mechanistically, XYLT1 interacted with IκBα and facilitated biosynthesis of sGAG-conjugated IκBα, which enhanced the interaction between IκBα and IKKs to promote proteasomal degradation of IκBα. These results illustrate that proteoglycan modification-mediated activation of NF-κB signaling is a driver of early-stage LUAD metastasis, providing a possibility for detection and intervention of early LUAD metastasis.
Tumorigenesis Driven by BRAFV600E Requires Secondary Mutations that Overcome it’s Feedback Inhibition of RAC1 and Migration
Authors: Sunyana Gadal, Jacob A. Boyer, Simon F. Roy, Noah A. Outmezguine, Malvika Sharma, Hongyan Li, Ning Fan, Eric Chan, Yevgeniy Romin, Afsar Barlas, Qing Chang, Priya Pancholi, Neilawattie Merna. Timaul, Michael Overholtzer, Rona Yaeger, Katia Manova-Todorova, Elisa de Stanchina, Marcus W. Bosenberg, Neal Rosen
Journal: Cancer Research (2025)

Abstract BRAFV600E mutations occur in 46% of melanomas and drive high levels of ERK activity and ERK-dependent proliferation. However, BRAFV600E is insufficient to drive melanoma in genetically engineered mouse models, and 82% of human benign nevi harbor BRAFV600E mutations. We found that BRAFV600E inhibited mesenchymal migration by causing feedback inhibition of RAC1 activity. ERK pathway inhibition induced RAC1 activation and restored migration and invasion. In cells with BRAFV600E, mutant RAC1 or PTEN inactivation restored RAC1 activity and cell motility. Together, these lesions occurred in 26% of melanomas with BRAFV600E mutations. Thus, although BRAFV600E activation of ERK deregulates cell proliferation, it prevents full malignant transformation by causing feedback inhibition of RAC1. Secondary mutations are, therefore, required for tumorigenesis. One mechanism underlying tumor evolution may be the selection of lesions that rescue the deleterious effects of oncogenic drivers.
Platelet-derived extracellular vesicle drug delivery system loaded with kaempferol for treating corneal neovascularization
Authors: Guei-Sheung Liu, Huai-An Chen, Che-Yi Chang, Yin-Ju Chen, Yu-Yi Wu, Ariel Widhibrata, Ya-Han Yang, Erh-Hsuan Hsieh, Liling Delila, I-Chan Lin, Thierry Burnouf, Ching-Li Tseng
Journal: Biomaterials (2025)
Clinical Epidemiological Characteristics of Hospitalized Pediatric Viral Community-Acquired Pneumonia in Mainland China
Authors: Qianyu Feng, Jinjin Wang, Xinyu Wang, Jiao Tian, Linlin Zhang, Dilara Dilmurat, Mengjia Liu, Junhong Ai, Guoshuang Feng, Yueping Zeng, Ran Wang, Zhengde Xie
Journal: Journal of Infection (2025)

Community acquired pneumonia (CAP) is a major global public health concern among children, with viral pathogens playing a significant role. Despite this, national multicenter studies on viral community acquired pneumonia (VCAP) in hospitalized children remain scarce. The study employed a multicenter approach to investigate the clinical epidemiology and burden of VCAP in hospitalized children across China. Data were extracted from the face sheets of discharge medical records (FSMRs) within the FuTang Update Medical Records (FUTURE) database, spanning 2016 to 2022. VCAP cases from 33 tertiary children's hospitals were identified and analyzed. Epidemiological characteristics, length of stay (LOS), and hospitalization costs were compared using appropriate statistical methods. Between January 2016 to December 2022, 72,905 hospitalized cases of CAP with confirmed diagnoses of viral pathogens were documented, accounting 4.07% of all CAP cases (72,905/1,791,343). Respiratory syncytial virus (RSV) was the leading cause, responsible for 57.21% of cases, followed by adenovirus, parainfluenza virus, human rhinovirus and influenza virus. The male-to-female ratio was 1.69:1, and infants under 1 year of age represented 59.84% of hospitalizations. Temporal trends showed an increase in VCAP hospitalizations from 2016 to 2019, a decline in 2020, followed by a resurgence in 2021 and 2022. Seasonally, the majority of cases occurred during winter (December to February, 41.67%), while summer (June to August) had the lowest proportion (16.80%). A total of 40 deaths were reported, representing a mortality rate of 0.05%. The median LOS was 7 days, with a median hospitalization cost of 907.38 USD. Although the proportion of CAP cases in children with confirmed viral pathogen in China is relatively low, VCAP remains a significant health burden for children. RSV is the most prevalent viral cause of VCAP, particularly affecting infants under 1 year of age, while adenovirus is associated with the highest mortality, longest LOS, and highest hospitalization costs. VCAP cases peak during the winter months. While the prognosis is generally favorable, the disease continues to pose a considerable public health challenge.
Comparative Bleeding Risk in Older Patients With HIV and Atrial Fibrillation Receiving Oral Anticoagulants
Authors: Claire M. Quinlan, Jerry Avorn, Aaron S. Kesselheim, Daniel E. Singer, Yichi Zhang, Alex Cervone, Kueiyu Joshua Lin
Journal: JAMA Internal Medicine (2025)

Importance People living with HIV and atrial fibrillation (AF) often receive anticoagulation that may interact with their antiretroviral therapy (ART). No studies exist comparing the safety of oral anticoagulants in this population. Objective To compare the bleeding risks among warfarin, rivaroxaban, and apixaban users in a national US cohort with AF and HIV. Design, Setting, and Participants A new-user, active-comparator, propensity score overlap-weighted cohort study using the target trial emulation framework including Medicare claims database data (January 1, 2013, to December 31, 2020) was carried out. The analysis was conducted from July 2023 to April 2024. Exposure New initiators of warfarin vs apixaban, rivaroxaban vs apixaban, and rivaroxaban vs warfarin aged 50 years or older with nonvalvular AF and HIV. Main Outcomes and Measures The primary outcome was hospitalization for major bleeding. Secondary outcomes included hospitalization for gastrointestinal bleeding, ischemic stroke, and all-cause mortality. Results Overall, 2683 individuals (mean [SD] age, 66.22 [8.97] years; 580 female individuals [21.6%]) in the warfarin vs apixaban cohort, 2176 (mean [SD] age, 66.61 [8.87] years; 455 female individuals [20.9%]) in the rivaroxaban vs apixaban cohort, and 1787 (mean age, 65.47 years; 377 female individuals [21.1%]) in the rivaroxaban vs warfarin cohort. After propensity score overlap weighting, warfarin initiation was associated with a higher rate of major bleeding than initiation of apixaban (hazard ratio [HR], 2.60; 95% CI, 1.51-4.49), including major gastrointestinal bleeding (HR, 2.99; 95% CI, 1.52-5.90). This association was intensified in the 71% of patients taking concurrent ART (major bleeding, HR, 6.68; 95% CI, 2.78-16.02; gastrointestinal bleeding, HR, 5.28; 95% CI, 2.08-13.42). Rivaroxaban vs apixaban was also associated with a higher rate of major bleeding (HR, 2.15; 95% CI, 1.18-3.94) and gastrointestinal bleeding (HR, 3.38; 95% CI, 1.57-7.25), with a stronger association in those using ART (major bleeding, HR, 4.83; 95% CI, 2.11-11.08; gastrointestinal bleeding, HR, 4.76; 95% CI, 1.78-12.70). Estimates were similar when comparing rivaroxaban with warfarin. No significant difference was observed in the rate of ischemic stroke or mortality among the 3 oral anticoagulants. Conclusions and Relevance This study found that in patients with HIV and AF, especially those treated with ART, warfarin and rivaroxaban were associated with higher rates of major bleeding compared with apixaban, suggesting a superior safety profile for apixaban in this high-risk population.
Antimicrobial Prophylaxis Use and Outcomes for Children Undergoing Cholecystectomy
Authors: Kerri A. McKie, Anoosha Moturu, Dionne A. Graham, Melvin Coleman, Reiping Huang, Catherine Grant, Jacqueline M. Saito, Bruce L. Hall, Robert A. Cina, Jason G. Newland, Clifford Ko, Shawn J. Rangel
Journal: JAMA Pediatrics (2025)

Importance Consensus guidelines from the Infectious Disease Society of America recommend against antimicrobial prophylaxis in the operative management of uncomplicated cholelithiasis; however, these guidelines were derived entirely from the adult surgical population. Objective To compare surgical site infection (SSI) outcomes between children undergoing cholecystectomy who received prophylaxis and those who did not. Design, Setting, and Participants This was a cohort study using data from 141 hospitals participating in the National Surgical Quality Improvement Program–Pediatric. Patients younger than 18 years who underwent cholecystectomy for uncomplicated cholelithiasis from January 2021 to December 2022 were identified. Exclusion criteria included diagnoses of acute cholecystitis, pancreatitis, choledocholithiasis, hematologic disorders, and emergent procedures. Exposure Administration of prophylactic antibiotics before incision. Main Outcomes and Measures The main outcomes were 30-day postoperative SSI and readmission. Propensity score weighting on the likelihood of receiving prophylaxis was used to balance groups on case acuity, duration of surgery, hospital discharge diagnosis, and patient characteristics. The association between outcomes and the use of prophylaxis was estimated using logistic regression models, weighted by the inverse probability of treatment with a random effect by hospital to control for hospital-level clustering. A secondary analysis was performed exploring the association between broad-spectrum prophylaxis and outcomes. Results Of 2234 children who met criteria for inclusion (median age, 15.3 years; 19.7% male [399 of 2025]), 2025 (90.6%) received prophylaxis (utilization rates ranged from 0% to 100% among hospitals). Cefazolin was the most commonly used antibiotic (69.2% [1401 of 2025]), and 559 of 2025 patients (27.6%) received extended-spectrum prophylaxis (compared with cefazolin). In the propensity-weighted cohort, SSI rates were lower for children who received prophylaxis compared with those who did not (18.0 of 2016 [0.9%] vs 7.8 of 212 [3.7%]; adjusted odds ratio [AOR], 0.28; 95% CI, 0.11-0.70), and rates were similar between children receiving cefazolin and those receiving more extended-spectrum antibiotics in a secondary propensity-weighted analysis (13.9 of 1399 [1.0%] vs 2.9 of 558 [0.5%]; AOR, 0.54; 95% CI, 0.15-1.95). Conclusions and Relevance The results of this study support prophylaxis use for children undergoing nonemergent cholecystectomy; however, use of extended-spectrum antibiotics was not associated with superior outcomes compared with cefazolin alone. Opportunities to optimize infection prevention or antimicrobial stewardship were identified in more than one-third of all children undergoing cholecystectomy.
Postvaccination Immunogenicity Among Pediatric Solid Organ Transplant Recipients
Authors: Amy G. Feldman, Brenda L. Beaty, Jose A. Ferrolino, Gabriela Maron, Saira A. Ali, Leandra Bitterfeld, Adam Blatt, Mary Alice Boulware, Kathleen M. Campbell, Emily Carr, Benhur Cetin, Shelley Chapman, Yeh-Chung Chang, Ryan Cunningham, Ronald H. Dallas, Keerti L. Dantuluri, Bryanna N. Domenick, Noelle H. Ebel, Scott Elisofon, Rima Fawaz, Marc Foca, Hayley A. Gans, Vani V. Gopalareddy, Nitika A. Gupta, Katherine Harmann, Jessica Hollenbeck, Anna R. Huppler, Catalina Jaramillo, Nagraj Kasi, Nanda Kerkar, Stacee Lerret, Steven J. Lobritto, M. James Lopez, Alisha Mavis, Sonia Mehra, Sindhu Mohandas, Flor M. Munoz, Krupa R. Mysore, Nadia Ovchinsky, Kerrigan Perkins, Stacy Postma, Lauren Pratscher, Elizabeth B. Rand, Regina K. Rowe, Daniel Ruderfer, Danielle Schultz, Katherine Sear, Megan L. Sell, Tanvi S. Sharma, Janis Stoll, Jerry Turner, Kristen G. Valencia Deray, Dominique Villarin, Carly Weaver, Phoebe Wood, Olivia Woodford-Berry, George Yanni, Lara A. Danziger-Isakov
Journal: JAMA Pediatrics (2025)

This cohort study assesses the protection provided by live attenuated viral vaccines among a pediatric population of solid organ transplant recipients 1 year after vaccination.
Knowledge of and Preferences for Medical Aid in Dying
Authors: Elissa Kozlov, Elizabeth A. Luth, Sam Nemeth, Todd D. Becker, Paul R. Duberstein
Journal: JAMA Network Open (2025)

Importance Medical aid in dying (MAID) is legal in jurisdictions covering more than one-fifth of the US population and has been used by a largely White, educated population. The extent to which knowledge of MAID and preferences for personal use align with patterns of use is unknown. Objective To evaluate knowledge among US adults of the legal status of MAID as well as interest in using MAID. Design, Setting, and Participants This cross-sectional, self-report online survey study used a national Prime Panels–based sample of US adults recruited between July 16 and August 10, 2024. A total of 3227 respondents aged 18 years or older from all US states and Washington, DC, were included. Individuals from states with legal MAID, aged 60 years or older, and members of racial and ethnic minority groups were oversampled. Main Outcomes and Measures Knowledge of the legality of MAID in the US and in respondents’ state of residence as well as potential interest in future use of MAID. Descriptive statistics and χ 2 tests were used to examine associations by demographic characteristics and place of residence. Results Of 3227 respondents (mean [SD] age, 55.7 [17.4] years; 1839 women [57.0%]), 1654 (51.3%) did not know if MAID was legal the US, and 1638 (50.8%) did not know if MAID was legal in their state. Respondents in states where MAID is legal were more likely to know that MAID is legal in the US compared with those in states where MAID is not legal (728 of 2164 [33.6%] vs 216 of 1063 [20.3%]; P &amp;amp;lt; .001). Across all respondents, 1420 (44.0%), including 96 of 222 Asian respondents (43.2%), 206 of 605 Black respondents (34.0%), and 129 of 308 Hispanic respondents (41.9%), reported they would definitely or probably consider MAID if they received a diagnosis of a terminal illness. Conclusions and Relevance In this online survey study of US adults, substantial interest in using MAID as well as significant knowledge gaps regarding the legality of MAID were reported. These findings highlight the need for public education, policy initiatives, and patient-clinician discussions to ensure equitable access to patient-centered end-of-life options and informed decision-making.
Availability of Mobile Crisis Services in Mental Health Facilities
Authors: Andrew Anderson, Stas Spivak, Alene Kennedy Hendricks
Journal: JAMA Network Open (2025)

Importance Rates of suicide ideation, severe depression, and acute psychosis have surged, paralleling an increase in emergency department visits for psychiatric emergencies. Mobile crisis services can play an important role in delivering timely, community-based interventions. Objective To assess the national availability of mobile crisis services in mental health treatment facilities and to identify key facility, geographic, and state-level factors associated with the availability of these services. Design, Setting, and Participants This cross-sectional study analyzed data from the 2022 National Substance Use and Mental Health Services Survey, which included 9036 mental health treatment facilities in the US. Facility zip codes were linked to the Agency for Healthcare Research and Quality’s Social Determinants of Health database to assess area-level factors. The study population included facilities that reported whether they offered mobile crisis services. Data were analyzed from August to September 2024. Main Outcomes and Measures The primary outcome was the availability of mobile crisis services at mental health treatment facilities, as reported by facility directors. Key independent variables included facility characteristics, local area factors, and state Medicaid policies. Logistic regression models were used to examine the associations between these factors and the availability of mobile crisis services. Results Of 9036 facilities, 1882 (20.8%) reported offering mobile crisis services. Facilities providing integrated dual diagnosis services (marginal effect, 3.44 [95% CI, 1.41-5.53] percentage points), suicide prevention services (marginal effect, 6.74 [95% CI, 4.29-9.20] percentage points), and assertive community treatment (marginal effect, 11.26 [95% CI, 9.02-13.51] percentage points) were significantly more likely to offer mobile health crisis services. Facilities in areas with lower percentages of residents with only a high school education were also more likely to offer mobile crisis services (marginal effect, 1.33 [95% CI, 0.15-2.51] percentage points). Conclusions and Relevance In this cross-sectional study of US mental health facilities, facilities with integrated services and located in areas with certain geographic characteristics were more likely to offer mobile crisis services. Addressing gaps in service availability is essential to improving access to crisis care.
Arginine Deprivation Induces Quiescence and Confers Vulnerability to Ferroptosis in Colorectal Cancer
Authors: Yanyun Lin, Yanhong Zhang, Tianze Huang, Junguo Chen, Guanman Li, Bin Zhang, Liang Xu, Kai Wang, Hui He, Hao Chen, Danling Liu, Shuang Guo, Xiaosheng He, Ping Lan
Journal: Cancer Research (2025)

Metabolic reprogramming is a hallmark of cancer. Rewiring of amino acid metabolic processes provides the basis for amino acid deprivation therapies. In this study, we found that arginine biosynthesis is limited in colorectal cancer (CRC) due to the deficiency of ornithine transcarbamylase (OTC). Accordingly, CRC cells met the demand for arginine by increasing external uptake. The addiction to environmental arginine resulted in the susceptibility of CRC to arginine deprivation, which dramatically decreased proliferation in CRC cells and promoted these cells to enter a reversible quiescence state. Arginine deprivation induced quiescence by activating the AMPK-p53-p21 pathway. RNA sequencing data indicated that CRC cells may be vulnerable to ferroptosis during arginine deprivation, and the combination of ferroptosis inducers and arginine deprivation strongly impeded tumor growth in vivo. These findings suggest that dietary modification combined with ferroptosis induction could be a potential therapeutic strategy for CRC.
Palmitic Acid Accumulation Activates Fibroblasts and Promotes Matrix Stiffness in Colorectal Cancer
Authors: Shenghe Deng, Jun Wang, Falong Zou, Denglong Cheng, Mian Chen, Junnan Gu, Jianguo Shi, Jia Yang, Yifan Xue, Zhengxin Jiang, Le Qin, Fuwei Mao, Xiaona Chang, Xiu Nie, Li Liu, Yinghao Cao, Kailin Cai
Journal: Cancer Research (2025)

Abstract Obstructions can occur during any stage of colorectal cancer (CRC) and correspond with poor prognosis. Obstructive colorectal cancer (OCRC) is harder and exhibits increased tumor budding and proliferation of myofibroblasts compared to non-obstructive CRC, suggesting that the occurrence of obstruction may be related to extracellular matrix (ECM) remodeling. Here, we found that CRC and OCRC samples differed substantially in ECM composition, specifically in collagen (newly formed and mature) and proteoglycans (including glycosaminoglycan, hyaluronic acid, and chondroitin sulfate). OCRC also exhibited considerable changes in ECM biomechanics and collagen arrangement. Interestingly, OCRC samples presented a notable increase in matrix cancer-associated fibroblasts (mCAFs). The abundance of mCAFs correlated with the accumulation of palmitic acid (PA), and high concentrations of PA increased the secretion of ECM-related proteins by mCAFs. Additionally, PA did not directly affect normal fibroblasts (NFs) but rather activated the NF-κB pathway in tumor cells to stimulate secretion of CSF-1, TGF-β1 and CXCL8, which promoted the activation of NFs into mCAFs and exacerbated ECM stiffening. Drug screening with a natural compound library identified vanillylacetone as a potential inhibitor of PA-induced cytokine secretion and ECM stiffening. These findings highlight intratumoral PA accumulation as a key mechanism driving ECM alterations and OCRC progression and suggest that targeting this axis may be useful for treating CRC patients with risk of obstruction.
Intratumoral Fusobacterium nucleatum Recruits Tumor-Associated Neutrophils to Promote Gastric Cancer Progression and Immune Evasion
Authors: Tianhao Zhang, Ying Li, Ertao Zhai, Risheng Zhao, Yan Qian, Zhixin Huang, Yinan Liu, Zeyu Zhao, Xiang Xu, Jianqiu Liu, Zikang Li, Zhi Liang, Ran Wei, Linying Ye, Jinping Ma, Qingping Wu, Jianhui Chen, Shirong Cai
Journal: Cancer Research (2025)

Intratumoral microbiota can impact the development and progression of many types of cancer, including gastric cancer (GC). A better understanding of the precise mechanisms by which microbiota support GC could lead to improved therapeutic approaches. Here, we investigated the effect of intratumoral microbiota on the tumor immune microenvironment (TIME) during GC malignant progression. Analysis of human GC tissues with 16S rRNA amplicon sequencing revealed that Fusobacterium nucleatum (F. nucleatum) was significantly enriched in GC tissues with lymph node metastasis and correlated with a poor prognosis. F. nucleatum infection spontaneously induced chronic gastritis and promoted gastric mucosa dysplasia in mice. Furthermore, GC cells infected with F. nucleatum showed accelerated growth in immunocompetent mice compared to immunodeficient mice. Single-cell RNA sequencing uncovered that F. nucleatum recruited tumor-associated neutrophils (TANs) to reshape the tumor immune microenvironment. Mechanistically, F. nucleatum invaded GC cells and activated IL-17/NF-κB/RelB signaling, inducing TAN recruitment. F. nucleatum also stimulated TAN differentiation into the pro-tumoral subtype and subsequent promotion of PD-L1 expression, further facilitating GC immune evasion while also enhancing the efficacy of anti-PD-L1 antibody therapy. Together, this data uncovers mechanisms by which F. nucleatum affects GC immune evasion and immunotherapy efficacy, providing insights for developing effective treatment strategies.