tbuckley/cabot-search huggingface dataset:
An Immune Subtype Classification System Enables the Development of Strategies to Predict and Enhance Immunotherapy Responses in Colorectal Cancer
Authors: Dingchang Li, Xianqiang Liu, Wenxing Gao, Wen Zhao, Shuaifei Ji, Sizhe Wang, Jinran Yang, Dingling Li, Zhengyao Chang, Yi Chen, Xu Sun, Jingcheng Zhou, Yanan Jiao, Xiaohui Du, Guanglong Dong
Journal: Cancer Research (2025)

Colorectal cancer (CRC) is the second leading cause of cancer-related mortality globally. While immunotherapeutic approaches are effective in a subset of CRC patients, the majority of CRC cases receive limited benefits from immunotherapy. This study developed an immune subtype classification system based on diverse immune cells and pathways. A model constructed through machine learning based on immune subtypes could accurately predict the sensitivity of CRC patients to immunotherapy. Validation of this model across public datasets and clinical samples confirmed its high precision and reliability. Furthermore, drug screening based on the immune subtypes identified the IGF1R inhibitor I-OMe-AG-538 (AG-538) as a potent enhancer of antitumor immunity. Mechanistic investigations revealed that AG-538 induced reactive oxygen species (ROS)-dependent DNA damage and downregulated the expression of multiple repair genes, triggering cGAS/STING-mediated type I IFN signaling within tumor cells. This signaling cascade increased tumor immunogenicity and refined the tumor immune microenvironment, thereby enhancing efficacy of immune checkpoint blockade treatment. In summary, these findings present a predictive model for immune response and highlight the potential of AG-538 combined with anti-PD1 antibodies as a chemoimmunotherapeutic strategy.
CAR-T entering a new “phase”: Improving CAR-T function by harnessing phase separation
Authors: Xiaolei Su
Journal: Cancer Research (2025)

Biomolecular condensation has emerged as a general principle in organizing biological processes, including immune response. Xu and colleagues recently reported that the cytoplasmic tail of the CD3ɛ subunit of TCR complex, when fused to CAR, can promote CAR condensation by liquid-liquid phase separation. Through sequence engineering, the authors identified modified CD3ɛ sequences that enhance the maturation of the immunological synapse and co-receptor signaling, leading to an improvement of cytotoxicity in vitro and anti-tumor effects in mouse xenograft models. These results demonstrated that biomolecular condensation could be exploited to improve the function of CAR-T cells, highlighting an exciting strategy for developing next-generation cell therapies.
Breaking the Rhythm: Harnessing the Menstrual Cycle for Better Chemotherapy.
Authors: Pranay Dey, Cathrin Brisken
Journal: Cancer Research (2025)

A recent publication by Bornes and colleagues explored the impact of the estrous cycle on mammary tumor response to neoadjuvant chemotherapy (NAC). Using genetically engineered mouse models, Bornes and colleagues revealed that chemotherapy is less effective when initiated during the diestrus stage compared to during the estrus stage. A number of changes during diestrous were identified that may reduce chemosensitivity of mammary tumors: an increased mesenchymal state of breast cancer cells during diestrous, decreased blood vessel diameters, and higher numbers of macrophages in the tumor microenvironment. Macrophage depletion was sufficient to mitigate this resistance. To translate these findings to humans, retrospective analyses of premenopausal breast cancer patients were conducted. Serum progesterone levels served to determine the menstrual cycle phases, which revealed that treatment efficacy is reduced in women receiving NAC during the luteal (progesterone-high) phase compared to those treated during the follicular (progesterone-low) phase. The findings show that physiological hormone fluctuations may influence chemosensitivity through tumor cell-extrinsic mechanisms with the important implication that aligning treatment initiation with the menstrual cycle improves therapeutic outcomes and that consideration of systemic factors may improve therapy outcome.
Imiquimod Cream Preceded by Superficial Curettage vs Surgical Excision for Nodular Basal Cell Carcinoma
Authors: Babette J. A. Verkouteren, Patty J. Nelemans, Kelly A. E. Sinx, Nicole W. J. Kelleners-Smeets, Véronique J. L. Winnepenninckx, Aimée H. M. M. Arits, Klara Mosterd
Journal: JAMA Dermatology (2025)

Interest in noninvasive treatment of basal cell carcinoma (BCC) has been increasing. For superficial BCC, it has been demonstrated that imiquimod cream, 5%, has high long-term efficacy, but for nodular BCC (nBCC), long-term evidence is sparse. To evaluate whether superficial curettage (SC) followed by imiquimod cream, 5%, is noninferior to surgical excision (SE) in nBCC after 5 years of treatment. In this secondary analysis of the noninferiority Surgery Versus Combined Treatment With Curettage and Imiquimod for Nodular Basal Cell Carcinoma (SCIN) randomized clinical trial, patients with a primary nBCC of 4 to 20 mm were assigned to either SC plus imiquimod, 5%, or SE between January 1, 2016, to November 30, 2017, at 2 outpatient dermatology departments in the Netherlands. The primary outcome of the SCIN trial was the 1-year probability of remaining free from treatment failure; the prespecified secondary trial outcomes were the probability after 5 years of follow-up, completed September 7, 2022. Both an intention-to-treat analysis and per-protocol analysis were planned. SC plus imiquimod vs SE. The 5-year probability of remaining free from treatment failure (ie, freedom from recurrence; with 95% CI) was estimated with Kaplan-Meier analysis using data on treatment response from 3 planned follow-up visits at 3 months and 1 and 5 years after the end-of-treatment date. Additional analyses accounting for death as competing risk were also performed. A total of 145 patients (77 [53.1%] male; median age, 68 [IQR, 31-89] years) with a primary, histologically proven nBCC were randomized to treatment with SC plus imiquimod (n = 73) or SE (n = 72). In total, 15 treatment failures occurred in the SC plus imiquimod group (5 treatment failures occurred between 1 and 5 years after treatment) and 1 in the SE group. The 5-year probability of remaining free from treatment failure was 77.8% (95% CI, 65.7%-86.0%) after SC plus imiquimod and 98.2% (95% CI, 88.0%-99.8%) after SE. The relative risk of treatment failure was 15.93 (95% CI, 2.10-120.64). The 95% CI does not exclude the noninferiority margin of 5.22. Death due to causes unrelated to BCC occurred in 20 patients, and the subhazard ratio from competing risk regression was 16.16 (95% CI, 2.18-119.72). This secondary analysis of a randomized clinical trial found that although it cannot be concluded that SC plus imiquimod is noninferior to SE, SC plus imiquimod was substantially less effective at 5 years after treatment. Most treatment failures occurred in the first year after treatment, and the probability of tumor-free survival 5 years after treatment with SC plus imiquimod was still 77.8%. The information in this trial can be used to counsel patients on the relative benefits and trade-offs of the different treatment options for nBCC. ClinicialTrials.gov Identifier: NCT02242929.
Serum Immunoglobulin G Levels and Nicastrin Variation in Hidradenitis Suppurativa
Authors: Dillon Mintoff, Nikolai P. Pace
Journal: JAMA Dermatology (2025)

Importance Variation in nicastrin ( NCSTN ) is associated with a monogenic subtype of hidradenitis suppurativa. Dysregulation of humoral immunity has been suggested as a potential mechanistic link between NCSTN variation and hidradenitis suppurativa. There is a paucity of biomarkers that can predict disease-associated variation. Objective To investigate whether serum immunoglobulin levels, as a surrogate marker of humoral immunity, can identify individuals with hidradenitis suppurativa who have a specific disease-associated NCSTN variant. Design, Setting, and Participants Maltese individuals with hidradenitis suppurativa genotyped for a disease-associated NCSTN in-frame deletion prevalent in the local patient cohort were invited to participate in this cross-sectional study from January to July 2023. Participation was restricted to adult individuals with hidradenitis suppurativa without known or suspected pathologies that would be associated with serum immunoglobulin levels. Data were analyzed between October 2023 and December 2023. Exposure Serum immunoglobulin G levels and other hematological paraments were analyzed. Main Outcome and Measure Main outcomes were the associations between serum immunoglobulin levels and an underlying NCSTN variation in individuals with hidradenitis suppurativa. Results A total of 125 individuals (64 female individuals [51.2%]) with hidradenitis suppurativa of Maltese ethnicity were recruited in the study, of whom 17 (13.6%) who were from 7 genealogically unrelated families were heterozygous for the disease-associated NCSTN variant. Deletion carriers had a higher serum immunoglobulin G level (1370 mg/dL vs 1140 mg/dL [to convert to g/L, multiply by 0.01]; P &amp;amp;lt; .001). The association between NCSTN variation and elevated immunoglobulin G levels retained significance despite adjusting for multiple confounders, including markers of disease severity, age of recruitment, age of disease onset, treatment with adalimumab, and liver transaminase levels. Serum immunoglobulin G demonstrated a strong discriminatory capacity in identifying patients who were heterozygous for the NCSTN variant. Conclusion and Relevance The results of this cross-sectional study suggest an altered humoral immune state in patients harboring a specific NCSTN variant and support the role of serum immunoglobulin G levels as a potential predictive biomarker of monogenic hidradenitis suppurativa. This may aid in identifying and prioritizing individuals with monogenic hidradenitis suppurativa.
Hidradenitis Suppurativa Surgery Complication Rates Among Patients With Obesity or Diabetes or Who Smoke
Authors: Rayad B. Shams, Christopher J. Sayed
Journal: JAMA Dermatology (2025)

Importance Surgery is frequently required for hidradenitis suppurativa (HS) treatment, but the impact of common comorbidities such as obesity, diabetes, and smoking on outcomes has been sparsely studied. Observations A total of 12 studies met final inclusion criteria for investigating complication rates associated with at least 1 comorbidity. Complication rates were associated with obesity in 3 of 10 studies. Obesity was modestly associated with dehiscence and readmission for flap reconstruction, debridement, and skin-grafting techniques in one study, dehiscence in a second, and delayed wound healing in another. One of 5 studies that reported complication rates in patients with diabetes found increased hospital readmissions for debridement (deroofing or excision without flap/graft) and flap reconstruction. No studies evaluating smoking found increased associated risks. Conclusions and Relevance This review highlights a greater need for consistent analysis and reporting of the surgical outcomes among patients with HS and certain comorbidities. Further rigorous clinical trials are needed to validate these findings and improve access to surgery in this patient population.
LINE-1 Retrotransposons as Cell-free DNA Biomarkers for Multi-Cancer Early Detection
Authors: Jeffrey J. Szymanski, Pradeep S. Chauhan, Aadel A. Chaudhuri
Journal: Clinical Cancer Research (2025)

LINE-1 retrotransposons, comprising 17% of the genome, drive cancer instability through hypomethylation. The DIAMOND assay, targeting LINE-1 hypomethylation with bisulfite sequencing of cell free DNA, achieved AUCs of 88% to 100% across six cancer types, surpassing mutation-based diagnostics and suggesting utility in early cancer detection and management.
Genomic Analysis Reveals Racial and Age-Related Differences in the Somatic Landscape of Breast Cancer and the Association with Socioeconomic Factors
Authors: Sarah C. Van Alsten, Michael I. Love, Benjamin C. Calhoun, Eboneé N. Butler, Charles M. Perou, Katherine A. Hoadley, Melissa A. Troester
Journal: Cancer Research (2025)

Cancer genomics consortia have identified somatic drivers of breast cancer subtypes. However, these studies have predominantly included older, non-Black women, and the related socioeconomic status (SES) data is limited. Increased representation and depth of social data are crucial for understanding how health inequity is intertwined with somatic landscapes. Here, we conducted targeted sequencing on primary tumors from the Carolina Breast Cancer Study (N = 357; 52% Black, 47% <50) and compared the results to The Cancer Genome Atlas (N = 948; 18% Black, 27% <50). Race (Black vs. non-Black), age, and SES were evaluated in association with mutations, copy number alterations, and aneuploidy using generalized linear models. Pathway dysfunction was also assessed by aggregating mutation and copy number alterations. Adjusting for age, Black participants (N =350) were significantly more likely to have TP53 and FAT1 mutations and less likely to have PIK3CA, CDH1, DDR2, and GATA3 mutations than non-Black participants. Younger participants had more GATA3 alterations and fewer KMT2C, PTEN, MAP3K1 and CDH1 alterations. Black participants had significant enrichment for MYC (8q) and PIK3CA (3q26) amplifications and higher total aneuploidy, but age was not associated with copy number variation. SES was associated with different patterns of alteration in Black versus non-Black women. Overall, Black participants showed modest differences in TP53, PIK3CA, and other alterations that further varied by SES. Race is a social construct, and varying distributions of etiologic factors across social strata may predispose Black, young, and low SES women to cancer subtypes characterized by these alterations.
Functional impairment in COPD can be predicted using genomic-derived data
Authors: Rui Marçalo, Guilherme Rodrigues, Miguel Pinheiro, Sonya Neto, Sofia L Marques, Paula Simão, Vitória Martins, Lília Andrade, Maria Aurora Mendes, Manuel Santos, Vera Afreixo, Alda Marques, Gabriela Moura
Journal: Thorax (2025)

Objective Reduced functional capacity and muscle weakness are two major contributors to functional impairment in chronic obstructive pulmonary disease (COPD). The underlying causes of functional impairment are poorly understood and, therefore, we sought to investigate the contribution of genetic factors. Methods We conducted a cross-sectional analysis of sociodemographic, clinical and genetic information of people with COPD. Hierarchical clustering based on functional capacity (6-minute walk test and 1-minute sit-to-stand test) and muscle strength (quadriceps isometric muscle strength and handgrip muscle strength) was performed. A genome-wide association study (GWAS) was performed using cluster assignment as phenotype. Polygenic risk scores (PRSs) were calculated for each variable. Genomic-derived data was used to construct a model to predict functional impairment. Results Two clusters were identified among 245 individuals. Cluster 1 (n=104) was composed of younger, less symptomatic patients, with preserved functional capacity and muscle strength, whereas cluster 2 (n=141) included those older, more symptomatic, with reduced functional capacity and muscle weakness. GWAS identified two polymorphisms suggestively associated with functional impairment, mapped to xanthine dehydrogenase . Cluster 2 was enriched in individuals with risk alleles for rs1991541 and rs10524730, and lower PRSs for functional capacity and muscle strength. A prediction model using genomic-derived data was constructed (n=159) and tested (n=37), yielding an area under the curve of 0.87 (0.76–0.99). Conclusion Genetic factors are significantly associated with functional impairment in COPD. The incorporation of genetic information, particularly PRSs, into a predictive model offers a promising avenue for timely identifying individuals at greater risk of functional decline, potentially facilitating personalised and preventive interventions. Further studies on independent external cohorts are needed to validate our model.
Technique for Laparoscopic Fluorescence–Guided Retroperitoneal Lymph Node Dissection
Authors: Luigi Boni, Elisa Cassinotti, Ludovica Baldari
Journal: JAMA Surgery (2025)

This Surgical Innovation describes a technique to identify the retroperitoneal lymph using ICG fluorescence, enabling a clear visualization of lymphatics, and nodes that need to be dissected from the surrounding structures.
Verrucous Tungiasis
Authors: Sara Becerril-Andrés, Gloria Masenga, Doriane Sabushimike
Journal: JAMA Dermatology (2025)

This case report describes a man in his 30s presenting with foul-smelling verrucous plaques and whitish papules with central black dots observed on the feet, legs, knees, buttocks, elbows, and hands, with nail dystrophy.
When Medicine Seems Thankless: Poetry and Gratitude
Authors: Rafael Campo
Journal: JAMA (2025)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors JAMA+ AI Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2025 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
A 58-Year-Old Woman With Urticaria, Fever, and Joint Pain
Authors: Hanna Bonnekoh, Melba Munoz, Pavel Kolkhir
Journal: JAMA (2025)

A 58-year-old woman with no allergies or rheumatic disease had a 2-year history of spontaneous wheals that occurred daily, accompanied by pruritus, arthralgia, and intermittent fevers; the wheals resolved after several hours without residual hyperpigmentation or bruising. C-reactive protein level was elevated, and skin biopsy showed dermal neutrophilic infiltration. What is the diagnosis and what would you do next?
N7-methylguanosine modification in cancers: from mechanisms to therapeutic potential
Authors: Qihui Wu, Xiaodan Fu, Guoqian Liu, Xiaoyun He, Yimin Li, Chunlin Ou
Journal: Journal of Hematology & Oncology (2025)

N7-methylguanosine (m7G) is an important RNA modification involved in epigenetic regulation that is commonly observed in both prokaryotic and eukaryotic organisms. Their influence on the synthesis and processing of messenger RNA, ribosomal RNA, and transfer RNA allows m7G modifications to affect diverse cellular, physiological, and pathological processes. m7G modifications are pivotal in human diseases, particularly cancer progression. On one hand, m7G modification-associated modulate tumour progression and affect malignant biological characteristics, including sustained proliferation signalling, resistance to cell death, activation of invasion and metastasis, reprogramming of energy metabolism, genome instability, and immune evasion. This suggests that they may be novel therapeutic targets for cancer treatment. On the other hand, the aberrant expression of m7G modification-associated molecules is linked to clinicopathological characteristics, including tumour staging, lymph node metastasis, and unfavourable prognoses in patients with cancer, indicating their potential as tumour biomarkers. This review consolidates the discovery, identification, detection methodologies, and functional roles of m7G modification, analysing the mechanisms by which m7G modification-associated molecules contribute to tumour development, and exploring their potential clinical applications in cancer diagnostics and therapy, thereby providing innovative strategies for tumour identification and targeted treatment.
Competitive behaviors in Serratia marcescens are coordinately regulated by a lifestyle switch frequently inactivated in the clinical environment
Authors: David J Williams, Alexandra Hawkins, Ruth E Hernandez, Giuseppina Mariano, Katharine Mathers, Grant Buchanan, Barnaby J Stonier, Teresa Inkster, Alistair Leanord, James D Chalmers, Nicholas R Thomson, Matthew T G Holden, Sarah J Coulthurst
Journal: Cell Host & Microbe (2025)
Amygdalo-cortical dialogue underlies memory enhancement by emotional association
Authors: Yoshihito Saito, Yuma Osako, Maya Odagawa, Yasuhiro Oisi, Chie Matsubara, Shigeki Kato, Kazuto Kobayashi, Mitsuhiro Morita, Joshua P Johansen, Masanori Murayama
Journal: Neuron (2025)
Author Correction: Establishing responsible use of AI guidelines: a comprehensive case study for healthcare institutions
Authors: Agustina D. Saenz, Thomas McCoy, Allison Bryant Mantha, Robert Martin, Robert Damiano, Deborah Adair, David Heaney, Rachel Sisodia, Lee Park, Robert Forsberg, Gerry Tuffy, Shawn Murphy, Keith Dreyer, Martha Jones, Heather Jean Cosier, Merranda Logan, Yogendra Bundela, Amanda Centi, David Ting, Jacqueline G. You, Adam Landman, Rebecca G. Mishuris
Journal: npj Digital Medicine (2025)
Impact of technical, patient and measurement variables on Serial HU-based quantitative coronary plaque analysis in CT: Time for a New Chapter
Authors: Francesca Calicchio, Elizabeth Epstein, Melinda Boussoussou, Borbála Vattay, Alexander van Rosendael, Shawn Newlander, Márton Kolossváry, Bálint Szilveszter, Pál Maurovich-Horvat, Hugo Marques, Elliot McVeigh, George Wesbey
Journal:  (2025)

Abstract This review article explores the challenges and controversies involved in accurately identifying and reliably quantifying coronary plaque over time through coronary computed tomography angiography (CCTA), particularly focusing on lipid-rich, low-attenuation plaques. It highlights significant variability in lipid-rich plaque measurements across studies, questioning their reliability for tracking biological plaque transformation in clinical practice. To address this issue, the review article proposes suggestions for serial CCTA plaque measurements, aiming for realistic goals for reproducible and meaningful serial plaque coronary CT angiography imaging. It also emphasizes the necessity of standardized, validated methods for quantitative plaque analysis and underscores the potential of phantom-based calibration to improve the reliability and consistency of serial plaque measurements in clinical practice.