tbuckley/cabot-search huggingface dataset:
Sequential carbonyl derivatives and hydrazone adduct formation on myeloperoxidase contribute to development of ANCA-vasculitis
Authors: Gang Xi, Elizabeth A. Mclnnis, Olivier Lardinois, Peiqi Hu, John S. Poulton, Meghan E. Free, Dhruti P. Chen, Evan M. Zeitler, Eveline Y. Wu, Nicole M. Orzechowski, Vimal K. Derebail, J. Charles Jennette, Ronald J. Falk
Journal: Journal of Clinical Investigation (2025)

Drug-induced autoimmune diseases are increasingly recognized although mechanistic insight into disease causation is lacking. Hydralazine exposure has been linked to autoimmune diseases, including anti-neutrophil cytoplasmic autoantibody (ANCA) vasculitis. Our hypothesis posits that hydralazine covalently binds to myeloperoxidase (MPO), triggering the autoimmune response in ANCA vasculitis. We in vitro observed formation of carbonyl derivatives on amine groups in the presence of acrolein. This facilitated the subsequent binding of hydralazine to heme-containing proteins, including MPO, via a Michael addition. Our studies demonstrated that carbonyl derivatives and hydrazone adducts induce conformational changes in the MPO heavy chain, potentially changing its immunogenicity. We identified hydrazone adducts on circulating MPO in patients with hydralazine-associated ANCA vasculitis. These patients exhibited elevated anti-MPO IgM levels, while anti-MPO IgG levels were comparable between hydralazine-associated and non-hydralazine-associated vasculitis patients. IgM isolated from hydralazine-associated MPO ANCA patients demonstrated a heightened affinity to hydralazine-modified MPO and activated neutrophil-like HL-60 cells. Hydralazine-modified MPO was pathogenic, as demonstrated by splenocyte transfer in a mouse model of ANCA vasculitis. Our findings unveil a mechanism of drug-induced autoimmunity wherein stepwise chemical modifications of MPO lead to conformational changes and hydrazone adduct formation producing a neoantigen to which pathogenic autoantibodies are generated.
Polygenic risk scores for pan-cancer risk prediction in the Chinese population: A population-based cohort study based on the China Kadoorie Biobank
Authors: Meng Zhu, Xia Zhu, Yuting Han, Zhimin Ma, Chen Ji, Tianpei Wang, Caiwang Yan, Ci Song, Canqing Yu, Dianjianyi Sun, Yue Jiang, Jiaping Chen, Ling Yang, Yiping Chen, Huaidong Du, Robin Walters, Iona Y Millwood, Juncheng Dai, Hongxia Ma, Zhengdong Zhang, Zhengming Chen, Zhibin Hu, Jun Lv, Guangfu Jin, Liming Li, Hongbing Shen
Journal: PLoS Medicine (2025)

Background Polygenic risk scores (PRSs) have been extensively developed for cancer risk prediction in European populations, but their effectiveness in the Chinese population remains uncertain. Methods and findings We constructed 80 PRSs for the 13 most common cancers using seven schemes and evaluated these PRSs in 100,219 participants from the China Kadoorie Biobank (CKB). The optimal PRSs with the highest discriminatory ability were used to define genetic risk, and their site-specific and cross-cancer associations were assessed. We modeled 10-year absolute risk trajectories for each cancer across risk strata defined by PRSs and modifiable risk scores and quantified the explained relative risk (ERR) of PRSs with modifiable risk factors for different cancers. More than 60% (50/80) of the PRSs demonstrated significant associations with the corresponding cancer outcomes. Optimal PRSs for nine common cancers were identified, with each standard deviation increase significantly associated with corresponding cancer risk (hazard ratios (HRs) ranging from 1.20 to 1.76). Compared with participants at low genetic risk and reduced modifiable risk scores, those with high genetic risk and elevated modifiable risk scores had the highest risk of incident cancer, with HRs ranging from 1.97 (95% confidence interval (CI): 1.11–3.48 for cervical cancer, P = 0.020) to 8.26 (95% CI: 1.92–35.46 for prostate cancer, P = 0.005). We observed nine significant cross-cancer associations for PRSs and found the integration of PRSs significantly increased the prediction accuracy for most cancers. The PRSs contributed 2.6%–20.3%, while modifiable risk factors explained 2.3%–16.7% of the ERR in the Chinese population. Conclusions The integration of existing evidence has facilitated the development of PRSs associated with nine common cancer risks in the Chinese population, potentially improving clinical risk assessment.
Personalized tumor-specific amplified DNA junctions in peripheral blood of patients with glioblastoma
Authors: Mohamed F. Ali, Cecile Riviere-Cazaux, Sarah H. Johnson, Rebecca Salvatori, Alan R. Penheiter, James B. Smadbeck, Stephen J. Murphy, Faye R. Harris, Lex F. McCune, Lucas P. Carlstrom, Michael T. Barrett, Farhad Kosari, Leila A. Jones, Cristiane Ida, Mitesh J. Borad, Bernard R. Bendok, Alfredo Quiñones-Hinojosa, Alyx B. Porter, Maciej M. Mrugala, Kurt A. Jaeckle, Panos Z. Anastasiadis, Sani H. Kizilbash, John C. Cheville, David M. Routman, Terry C. Burns, George Vasmatzis
Journal: Clinical Cancer Research (2025)

Abstract PURPOSE: Monitoring disease progression in patients with high-grade gliomas (HGGs) is challenging due to treatment-related changes on imaging and the requirement for neurosurgical intervention to obtain diagnostic tissue. DNA junctions in HGGs often amplify oncogenes, making these DNA fragments potentially more abundant in blood than monoallelic mutations. Herein, we piloted a cell-free DNA approach for disease detection in plasma of patients with HGGs by leveraging patient-specific DNA junctions associated with oncogene amplifications. EXPERIMENTAL DESIGN: Whole genome sequencing of grade 3 or 4 IDH-mutant or wild-type astrocytomas was utilized to identify amplified junctions. Individualized qPCR assays were developed using patient-specific primers designed for the amplified junction. ctDNA levels containing these junctions were measured in patient plasma samples. RESULTS: Unique amplified junctions were evaluated by individualized semi-quantitative PCR assays in presurgical plasma of 18 patients, 15 with tumor-associated focal amplifications and three without. High-copy number junctions were robustly detected in plasma of 14/15 patients (93.3%) with amplified junctions and none of the controls. Changes in junction abundance correlated with disease trajectory in serial plasma samples from five patients, including increased abundance of amplified junctions preceding radiographic disease progression. CONCLUSION: In patients with grade 3 or 4 astrocytomas who had tumor-associated amplifications, patient-specific amplified junctions were successfully detected in assayed plasma from most patients. Longitudinal analysis of plasma samples correlated with disease trajectory, including cytoreduction and progression.
Integrating Botanicals into Oncology Care: Consideration of FDA Regulation of Botanical Products and Botanical Clinical Trials
Authors: Tara A. Berman, Eran Ben-Arye, Gunver S. Kienle, Viraj Master, Alissa Huston, Channing J. Paller
Journal: Clinical Cancer Research (2025)

Abstract Modern cancer pharmacotherapy consists of contributions from natural products, their structural analogues, and chemotherapies. Interest in natural products is being revitalized in oncology. Natural products may be classified as food, dietary supplements, drugs, or cosmetics depending on their intended use. A natural product intended to prevent, diagnose, cure, mitigate, or treat disease would be regulated as a drug. Most natural products are regulated as dietary supplements, intended to affect the structure or function of the body. In 2023, Americans spent around $58 billion on dietary supplements, with a majority intended to prevent or treat cancer. Almost 50% of newly diagnosed patients with cancer report taking dietary supplements after diagnosis. Botanicals, natural products made from plants, plant parts, or plant extracts, are one of the most highly-used supplements. The natural product market is zealous to promote their supplements and often claim their products will help in combatting disease. Unlike with FDA-approved drugs, botanical dietary supplements may be marketed without proving they work as claimed and do not require clinical trials. To date, only four botanical drug products have been approved for marketing as prescription drugs in the U.S. Here, we evaluate the current paradigm for dietary supplement marketing and FDA approval and its impact on the treatment of patients with cancer. We underscore the need for rigorous clinical trials for clinicians to access sufficient evidence-based data to advise on the safety and efficacy of these products, alone or in conjunction with active treatment for cancer.
Systematic review of clinical effectiveness of interventions for treatment resistant late-life depression
Authors: Beatriz Pozuelo Moyano, Denise Gomez Bautista, Karla Jocelyn Porras Ibarra, Christoph Mueller, Armin von Gunten, Pierre Vandel, Setareh Ranjbar, Robert Howard, Allan H Young, Robert Stewart, Suzanne Reeves, Vasiliki Orgeta
Journal: Ageing Research Reviews (2025)

Treatment-resistant late-life depression (TRLLD) affects nearly half of older adults with major depression. This systematic review evaluates published evidence of effectiveness of both pharmacological and non-pharmacological treatments for TRLLD. A search of MEDLINE, EMBASE, CINAHL, PsycINFO, the Cochrane Library, and online trial registries up to March 2024 was conducted to identify randomized controlled trials (RCTs) evaluating pharmacological and non-pharmacological interventions for TRLLD. Seven studies assessed the effectiveness of pharmacological interventions (antidepressants, antipsychotics, mood stabilizers, or ketamine) and another seven examined non-pharmacological approaches (psychotherapy, electroconvulsive therapy, repetitive transcranial magnetic stimulation (rTMS), and computerized cognitive remediation). Aripiprazole (2 studies), venlafaxine (1 study), ketamine (1 study), and lithium (1 study) were associated with a reduction in depressive symptoms post-treatment compared to the comparator treatment group. rTMS (2 studies), sequential bilateral theta burst stimulation (1 study) and cognitive remediation (1 study) also showed significant improvements in depressive symptoms post-treatment compared to a comparator treatment group. Quality of evidence varied from very low to medium among the included studies. Most studies reported data on small sample sizes. We identified a small number of RCTs evaluating treatments for TRLLD. Aripiprazole augmentation appears to be an effective treatment based on two studies, with an acceptable side effect profile. Other treatments may be effective, but the evidence is based on very low-quality evidence. Future large-scale RCTs are urgently needed to draw firm conclusions.
Indoor Air Pollution, CT Airway-to-Lung Ratio and Lung Function Decline: Analyses from SPIROMICS AIR
Authors: Sarath Raju, Han Woo, Coralynn Sack, Eric A. Hoffman, Joel D. Kaufman, Igor Barjaktarevic, R. Graham Barr, Alejandro Comellas, Christopher B. Cooper, Robert Paine, Benjamin M Smith, Nadia N Hansel
Journal: American Journal of Respiratory and Critical Care Medicine (2025)
Teledermatology’s Impact on Concordance in Bagamoyo, Tanzania: A Retrospective Study
Authors: Michael Esson, Omar Juma, Gasper Mmbaga, Jane Mcharo, Sara Bertan, Miquela Teske, Helen Lozier, Nina Punyamurthy, Stephen Humphrey, Karolyn A Wanat
Journal: Journal of the American Academy of Dermatology (2025)
Acidity-Unlocked Glucose Oxidase as Drug Vector to Boost Intratumor Copper Homeostatic Imbalance-Enhanced Cuproptosis for Metastasis Inhibition and Anti-Tumor Immunity
Authors: Junrong Wang, Yulin Xie, Guoqing Zhu, Yanrong Qian, Qianqian Sun, Haoze Li, Chunxia Li
Journal: Biomaterials (2025)
Restoring somatotopic sensory feedback in lower limb amputees through non-invasive nerve stimulation
Authors: Andrea Demofonti, Marco Germanotta, Andrea Zingaro, Gaia Bailo, Sabina Insalaco, Francesca Cordella, Irene Giovanna Aprile, Loredana Zollo
Journal: Cyborg and Bionic Systems (2025)

Patients with lower limb amputation experience ambulation disorders since they rely exclusively on visual information in addition to the tactile information they receive from stump–socket interface. The lack of sensory feedback in commercial lower limb prostheses is essential in their abandonment by patients with transtibial amputation (TTA) or transfemoral amputation (TFA). Recent studies have obtained promising results using invasive interfaces with peripheral nervous system presenting drawbacks related to surgery. This paper aims to (a) investigate the potential of transcutaneous electrical nerve stimulation (TENS) as noninvasive means for restoring somatotopic sensory feedback in lower limb amputees and (b) evaluate the effect of the system over a 4-week experimental protocol. The first phase of the study involved 13 participants (6 with TTA and 7 with TFA), and the second one evaluated the long-term effect of TENS on ambulation performance of 2 participants (S1 with TTA and S7 with TFA). The proposed system enhanced participant’s ambulation significantly increasing the body weight distribution between legs (S1: from 134% to 143%, P &lt; 0.0055; S7: from 66% to 72%, P &lt; 0.0055) and gait symmetry (S1: step length symmetry index from 11% to 5%, P &lt; 0.0055; S7: stance phase symmetry index from −4% to −2%, P &lt; 0.0055). It led to a postamputation neuropathic pain reduction in S1 (neuropathic pain symptom inventory score diminished from 6 to 0). This demonstrates how TENS enhanced prosthesis embodiment, enabling greater load bearing and more physiological gait patterns. This study highlights TENS as noninvasive solution for restoring somatotopic sensory feedback, addressing the current limitations and paving the way for further research.
Participation in Clinic-Based Referral and Navigation Services Among Families With Social Needs
Authors: Abigail Seide, Omolara Thomas Uwemedimo, Rehana Rasul, Caren Steinway, Michelle Katzow, Sophia Jan, Eun Ji Kim
Journal: JAMA Network Open (2025)

Importance Social determinants of health (SDOH) are associated with health outcomes. Thus, providing referrals for unmet social needs within clinical settings may improve the health of children. Objective To examine the prevalence and demographic characteristics of pediatric families with unmet social needs and their association with families accepting help from a pediatric clinical practice. Design, Setting, and Participants This cross-sectional study examined data from a comprehensive SDOH screening and referral program at a large academic pediatric practice in the US. Participants were caregivers of patients younger than 17 years and indicated at least 1 social need. Data were collected from April 16, 2018, through September 29, 2019, and analyzed from November 18, 2019, through December 17, 2019. The data review was finalized December 20, 2023. Exposure Screening for SDOH in primary care. Main Outcome and Measures The main outcome was interest in assistance among patient families with at least 1 social need. Factor analyses categorized social needs as basic needs, stress, challenges to economic mobility, and marginalization. χ 2 Tests and multivariable Poisson regression were used to examine the associations between patient characteristics and caregiver interest in assistance. Results There were 758 caregivers (median [IQR] age, 34 [29-40] years; 614 mothers [81.0%]) reporting at least 1 unmet social need, such as food or utility insecurity or unemployment. The median age of children was 23 months (IQR, 4-70 months), and 163 (21.5%)were of Asian, Pacific Islander, or Native Hawaiian ; 213 (28.1%) of Black; 156 (20.6%) of Latino or Hispanic; 37 (4.9%) of White ; and 122 (16.1%) of other race and ethnicity. A total of 315 caregivers (41.6%) were not interested in assistance. Families with basic needs (adjusted prevalence ratio [PR], 5.56; 95% CI, 3.33-10.00), stress (adjusted PR, 1.75; 95% CI, 1.43-2.17), challenges to economic mobility (adjusted PR, 2.17; 95% CI, 1.67-2.86), or marginalization (adjusted PR, 1.41; 95% CI, 1.15-1.72) were more likely to be interested in assistance. Additionally, Black race (adjusted PR, 1.23; 95% CI, 1.01-1.49), other race and ethnicity (adjusted PR, 1.22; 95% CI, 1.01-1.47), and inadequate social support (adjusted PR, 1.85; 95% CI, 1.32-2.63) were associated with acceptance of referral services. Conclusions and Relevance These findings suggest that the implementation of referral programs may help to achieve health equity, especially among marginalized populations, and improve the referral process for families who have social needs but are not interested in assistance.
Physical Health Decline After Chemotherapy or Endocrine Therapy in Breast Cancer Survivors
Authors: Clara Bodelon, Matthew Masters, Den E Bloodworth, Peter J. Briggs, Erika Rees-Punia, Lauren E. McCullough, Alpa V. Patel, Lauren R. Teras
Journal: JAMA Network Open (2025)

Importance Women with a history of breast cancer (BC) experience greater physical health decline compared with age-matched women without cancer. However, whether this decline differs in patients who received chemotherapy and endocrine therapy is not well understood. Objective To investigate physical health decline in BC survivors who received chemotherapy or endocrine therapy compared with age-matched women without cancer. Design, Setting, and Participants This prospective cohort study was conducted as part of the Cancer Prevention Study-3, a prospective US cohort study that enrolled participants in 35 states, the District of Columbia, and Puerto Rico between 2006 and 2013. Follow-up for this analysis was through April 1, 2020. Statistical analyses were conducted between May 2023 and December 2024. Female participants diagnosed with nonmetastatic BC who returned a survey at least 90 days after their diagnosis were matched on age and year of survey return with up to 5 women without cancer. Exposure Cancer status and treatment information. Main Outcomes and Measures Outcomes of interest were measures of physical health, assessed using the Patient-Reported Outcomes Measurement Information System Global Health Scale instrument. Linear regression was used to estimate associations (β) and 95% CIs of treatment with physical health. Results This analysis included 2566 individuals diagnosed with BC and 12 826 age-matched women without cancer. Median (IQR) age at diagnosis was 56.3 (49.9-61.9) years. Of women with BC, 1223 (47.7%) received endocrine therapy, 276 (10.8%) received chemotherapy, and 634 (24.7%) received both. Compared with women without cancer, there was a greater physical health decline within 2 years of diagnosis for BC survivors receiving endocrine therapy (β = −1.12; 95% CI, −1.64 to −0.60), chemotherapy (β = −3.13; 95% CI, −4.19 to −2.07), or both (β = −3.26; 95% CI, −3.97 to −2.55). The decline among endocrine therapy users was restricted to women receiving aromatase inhibitors. More than 2 years after diagnosis, the decline was only observed in women who received chemotherapy. Conclusions and Relevance In this cohort study of 15 392 BC survivors and age-matched women without cancer, BC survivors who received chemotherapy had a long-lasting physical health decline, unlike survivors who received endocrine therapy without chemotherapy. Further studies are needed to confirm these results and to better understand the health consequences of these treatments.
Graph-based Prototype Inverse-Projection for Identifying Cortical Sulcal Pattern Abnormalities in Congenital Heart Disease
Authors: Hyeokjin Kwon, Seungyeon Son, Sarah U Morton, David Wypij, John Cleveland, Caitlin K Rollins, Hao Huang, Elizabeth Goldmuntz, Ashok Panigrahy, Nina H Thomas, Wendy K Chung, Evdokia Anagnostou, Ami Norris-Brilliant, Bruce D Gelb, Patrick McQuillen, George A Porter, Martin Tristani-Firouzi, Mark W Russell, Amy E Roberts, Jane W Newburger, P Ellen Grant, Jong-Min Lee, Kiho Im
Journal: Medical Image Analysis (2025)
Researcher Proposes New Framework for Language Equity in Health Technology
Authors: Yulin Hswen, Nora Collins
Journal: JAMA (2025)

This Medical News article is an interview with Pilar Ortega, MD, MGM, about the need for interventions to improve health care quality and access for patients with non-English language preference, and why equitable design is essential for new AI-driven health technologies and digital advancements.
DTX2 attenuates Lenvatinib-induced ferroptosis by suppressing docosahexaenoic acid biosynthesis through HSD17B4-dependent peroxisomal β-oxidation in hepatocellular carcinoma
Authors: Zhongyan Zhang, Qi Zhou, Zhenchong Li, Fuxin Huang, Ke Mo, Cheng Shen, Xing Niu, Baohua Hou, Chuanzhao Zhang, Shanzhou Huang
Journal: Drug Resistance Updates (2025)
The combination of flaxseed lignans and PD-1/ PD-L1 inhibitor inhibits breast cancer growth via modulating gut microbiome and host immunity
Authors: Hao Wu, Jiena Liu, Xing-Hua Zhang, Shengye Jin, Ping Li, Huidi Liu, Liuying Zhao, Jianyu Wang, Shilu Zhao, Hong-Da Tian, Jin-Ru Lai, Yi Hao, Gui-Rong Liu, Kaijian Hou, Meisi Yan, Shu-Lin Liu, Da Pang
Journal: Drug Resistance Updates (2025)

Patients with breast cancer (BC) who benefit from the PD-1/PD-L1 inhibitor (PDi) is limited, necessitating novel strategies to improve immunotherapy efficacy of BC. Here we aimed to investigate the inhibitory effects of flaxseed lignans (FL) on the biological behaviors of BC and evaluate the roles of FL in enhancing the anticancer effects of PDi. HPLC was used to detect the content of enterolactone (ENL), the bacterial transformation product of FL. Transcript sequencing was performed and identified CD38 as a downstream target gene of ENL. CD38-overexpressing cells were constructed and cell proliferation, colony formation, wound healing and transwell assays were used to assess the function of ENL/CD38 axis on BC cells in vitro. Multiplexed immunohistochemistry (mIHC) and CyTOF were used to detect the changes of the tumor immune microenvironment (TIM). 16S rDNA sequencing was used to explore the changes of gut microbiota in mice. A series of in vivo experiments were conducted to investigate the anticancer effects and mechanisms of FL and PDi. FL was converted to ENL by gut microbiota and FL administration inhibited the progression of BC. ENL inhibited the malignant behaviors of BC by downregulating CD38, a key gene associated with immunosuppression and PD-1/PD-L1 blockade resistance. The mIHC assay revealed that FL administration enhanced CD3+, CD4+ and CD8+ cells and reduced F4/80+ cells in TIM. CyTOF confirmed the regulatory effects of FL and FL in combination with PDi (FLcPDi) on TIM. In addition, 16S rDNA analysis demonstrated that FLcPDi treatment significantly elevated the abundance of Akkermansia and, importantly, Akkermansia administration enhanced the response to PDi in mice treated with antibiotics. The FL/ENL/CD38 axis inhibited BC progression. FL enhanced the anticancer effects of PDi by modulating gut microbiota and host immunity.