tbuckley/cabot-search huggingface dataset:
Associations of concomitant medications with immune-related adverse events and survival in advanced cancers treated with immune checkpoint inhibitors: a comprehensive pan-cancer analysis
Authors: Katsuhiko Nara, Satoru Taguchi, Sebastiano Buti, Taketo Kawai, Yukari Uemura, Takehito Yamamoto, Haruki Kume, Tappei Takada
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background While concomitant medications can affect the efficacy of immune checkpoint inhibitors (ICIs), few studies have assessed associations of concomitant medications with the occurrence and profile of immune-related adverse events (irAEs). Methods This study assessed associations of concomitant medication (antibiotics/proton pump inhibitors (PPIs)/corticosteroids)-based risk model termed the “drug score” with survival and the occurrence and profile of irAEs in 851 patients with advanced cancer treated with ICIs (with or without other agents). The study also assessed the survival impact of the occurrence of irAEs, using a landmark analysis to minimize immortal time bias. Multivariable Cox proportional hazard analyses were conducted for progression-free survival (PFS) and overall survival (OS). Results The drug score classified patients into three risk groups, with significantly different PFS and OS. Notably, the score’s predictive capability was better in patients treated with ICIs only than in those treated with ICIs plus other agents. The landmark analysis showed that patients who developed irAEs had significantly longer PFS and OS than those without irAEs. Generally, concomitant medications were negatively associated with the occurrence of irAEs, especially endocrine irAEs, whereas PPI use was positively associated with gastrointestinal irAEs, as an exception. Conclusions Using a large pan-cancer cohort, the prognostic ability of the drug score was validated, as well as that of the occurrence of irAEs. The negative association between concomitant medications and irAE occurrence could be an indirect measure of the detrimental effect on the immune system induced by one or more concomitant drugs.
Joint analysis of mutational and transcriptional landscapes in human cancer reveals key perturbations during cancer evolution
Authors: Jae-Won Cho, Jingyi Cao, Martin Hemberg
Journal: Genome biology (2024)

Abstract Background Tumors are able to acquire new capabilities, including traits such as drug resistance and metastasis that are associated with unfavorable clinical outcomes. Single-cell technologies have made it possible to study both mutational and transcriptomic profiles, but as most studies have been conducted on model systems, little is known about cancer evolution in human patients. Hence, a better understanding of cancer evolution could have important implications for treatment strategies. Results Here, we analyze cancer evolution and clonal selection by jointly considering mutational and transcriptomic profiles of single cells acquired from tumor biopsies from 49 lung cancer samples and 51 samples with chronic myeloid leukemia. Comparing the two profiles, we find that each clone is associated with a preferred transcriptional state. For metastasis and drug resistance, we find that the number of mutations affecting related genes increases as the clone evolves, while changes in gene expression profiles are limited. Surprisingly, we find that mutations affecting ligand-receptor interactions with the tumor microenvironment frequently emerge as clones acquire drug resistance. Conclusions Our results show that lung cancer and chronic myeloid leukemia maintain a high clonal and transcriptional diversity, and we find little evidence in favor of clonal sweeps. This suggests that for these cancers selection based solely on growth rate is unlikely to be the dominating driving force during cancer evolution.
Mortality in recipients of allogeneic haematopoietic cell transplantation in the era of cytomegalovirus primary prophylaxis: a single-centre retrospective experience
Authors: Anthony Febres-Aldana, Fareed Khawaja, Oscar Morado-Aramburo, Terri Lynn Shigle, Gabriela Rondon, Joseph Sassine, Amy Spallone, Krithika Srinivasan, Jeremy Ramdial, Amin Alousi, Richard Champlin, George Chen, May Daher, Katayoun Rezvani, Ella J. Ariza-Heredia, Elizabeth J. Shpall, Roy F. Chemaly
Journal: Clinical Microbiology and Infection (2024)
CNP Ameliorates Macrophage Inflammatory Response and Atherosclerosis
Authors: Qiankun Bao, Bangying Zhang, Lu Zhou, Qian Yang, Xiaofeng Mu, Xing Liu, Shiying Zhang, Meng Yuan, Yue Zhang, Jingjin Che, Wen Wei, Tong Liu, Guangping Li, Jinlong He
Journal: Circulation Research (2024)

BACKGROUND: CNP (C-type natriuretic peptide), an endogenous short peptide in the natriuretic peptide family, has emerged as an important regulator to govern vascular homeostasis. However, its role in the development of atherosclerosis remains unclear. This study aimed to investigate the impact of CNP on the progression of atherosclerotic plaques and elucidate its underlying mechanisms. METHODS: Plasma CNP levels were measured in patients with acute coronary syndrome. The potential atheroprotective role of CNP was evaluated in apolipoprotein E-deficient (ApoE −/− ) mice through CNP supplementation via osmotic pumps, genetic overexpression, or LCZ696 administration. Various functional experiments involving CNP treatment were performed on primary macrophages derived from wild-type and CD36 (cluster of differentiation 36) knockout mice. Proteomics and multiple biochemical analyses were conducted to unravel the underlying mechanism. RESULTS: We observed a negative correlation between plasma CNP concentration and the burden of coronary atherosclerosis in patients. In early atherosclerotic plaques, CNP predominantly accumulated in macrophages but significantly decreased in advanced plaques. Supplementing CNP via osmotic pumps or genetic overexpression ameliorated atherosclerotic plaque formation and enhanced plaque stability in ApoE −/− mice. CNP promoted an anti-inflammatory macrophage phenotype and efferocytosis and reduced foam cell formation and necroptosis. Mechanistically, we found that CNP could accelerate HIF-1α (hypoxia-inducible factor 1-alpha) degradation in macrophages by enhancing the interaction between PHD (prolyl hydroxylase domain–containing protein) 2 and HIF-1α. Furthermore, we observed that CD36 bound to CNP and mediated its endocytosis in macrophages. Moreover, we demonstrated that the administration of LCZ696, an orally bioavailable drug recently approved for treating chronic heart failure with reduced ejection fraction, could amplify the bioactivity of CNP and ameliorate atherosclerotic plaque formation. CONCLUSIONS: Our study reveals that CNP enhanced plaque stability and alleviated macrophage inflammatory responses by promoting HIF-1α degradation, suggesting a novel atheroprotective role of CNP. Enhancing CNP bioactivity may offer a novel pharmacological strategy for treating related diseases.
Exosome circATP8A1 induces macrophage M2 polarization by regulating the miR-1-3p/STAT6 axis to promote gastric cancer progression
Authors: Cuncan Deng, Mingyu Huo, Hongwu Chu, Xiaomei Zhuang, Guofei Deng, Wenchao Li, Hongfa Wei, Leli Zeng, Yulong He, Huashan Liu, Jia Li, Changhua Zhang, Hengxing Chen
Journal: Molecular Cancer (2024)

Abstract Circular RNAs (circRNAs) play important roles in gastric cancer progression but the regulatory role of circRNAs in controlling macrophage function remains elusive. Exosomes serve as cargo for circRNAs and play a crucial role as mediators in facilitating communication between cancer cells and the tumor microenvironment. In this study, we found that circATP8A1, a previously unreported circular RNA, is highly expressed in both gastric cancer tissues and exosomes derived from plasma. Increased circATP8A1 was associated with advanced TNM stage and worse prognosis in patients with gastric cancer. We showed that the circATP8A1 knockdown significantly inhibited gastric cancer proliferation and invasion in vitro and in vivo. Functionally, exosome circATP8A1 induced the M2 polarization of macrophages through the STAT6 pathway instead of the STAT3 pathway. Mechanistically, circATP8A1 was shown to activate the STAT6 pathway through competitive binding to miR-1-3p, as confirmed by Fluorescence In Situ Hybridization (FISH), RNA immunoprecipitation, RNA pulldown, and Luciferase reporter assays. The reversal of circATP8A1-induced STAT6 pathway activation and macrophage polarization was observed upon blocking miR-1-3p. Macrophages treated with exosomes from gastric cancer cells overexpressing circATP8A1 were able to promote gastric cancer migration, while knockdown of circATP8A1 reversed these effects in vivo. In summary, exosome-derived circATP8A1 from gastric cancer cells induce macrophages M2 polarization via the circATP8A1/miR-1-3p/STAT6 axis, and tumor progression. Our results highlight circATP8A1 as a potential prognostic biomarker and therapeutic target in gastric cancer.
Dialysis-Dependent Acute Kidney Injury—A Risk Factor for Adverse Outcomes
Authors: Marlies Ostermann, Nuttha Lumlertgul, Matthew T. James
Journal: JAMA Network Open (2024)

Heng-Chih Pan, MD; Hsing-Yu Chen, PhD; Nai-Chi Teng, MS; Fang-Yu Yeh, MS; Tao-Min Huang, MD; Chun Yin See, MD; Chiao-Yin Sun, PhD; Yung-Chang Chen, MD; Likwang Chen, PhD; Vin-Cent Wu, PhD
Mucosal T-cell responses to chronic viral infections: Implications for vaccine design
Authors: Mohammed Al-Talib, Sandra Dimonte, Ian R Humphreys
Journal: Cellular and Molecular Immunology (2024)

Mucosal surfaces that line the respiratory, gastrointestinal and genitourinary tracts are the major interfaces between the immune system and the environment. Their unique immunological landscape is characterized by the necessity of balancing tolerance to commensal microorganisms and other innocuous exposures against protection from pathogenic threats such as viruses. Numerous pathogenic viruses, including herpesviruses and retroviruses, exploit this environment to establish chronic infection. Effector and regulatory T-cell populations, including effector and resident memory T cells, play instrumental roles in mediating the transition from acute to chronic infection, where a degree of viral replication is tolerated to minimize immunopathology. Persistent antigen exposure during chronic viral infection leads to the evolution and divergence of these responses. In this review, we discuss advances in the understanding of mucosal T-cell immunity during chronic viral infections and how features of T-cell responses develop in different chronic viral infections of the mucosa. We consider how insights into T-cell immunity at mucosal surfaces could inform vaccine strategies: not only to protect hosts from chronic viral infections but also to exploit viruses that can persist within mucosal surfaces as vaccine vectors.
Patient Care Technician Staffing and Outcomes Among US Patients Receiving In-Center Hemodialysis
Authors: Laura C. Plantinga, Alexis A. Bender, Megan Urbanski, Clarica Douglas-Ajayi, Jennifer Craft Morgan, Karen Woo, Bernard G. Jaar
Journal: JAMA Network Open (2024)

Importance Dialysis patient care technicians (PCTs) play a critical role in US in-center hemodialysis (HD) care, but little is known about the association of PCT staffing with patient outcomes at US HD facilities. Objective To estimate the associations of in-center HD patient outcomes with facility-level PCT staffing. Design, Setting, and Participants This was a retrospective cohort study, with data analysis performed from March 2023 to January 2024. Data on US patients with end-stage kidney disease and their treatment facilities were obtained from the US Renal Data System. Participants included patients (aged 18-100 years) initiating in-center HD between January 1, 2016, and December 31, 2018, who continued receiving in-center HD for 90 days or more and had data on PCT staffing at their initial treating HD facility. Exposure Facility-level patient-to-PCT ratios (number of HD patients divided by the number of PCTs reported by the treating facility in the prior year), categorized into quartiles (highest quartile denotes the highest PCT burden). Main Outcomes and Measures Patient-level outcomes included 1-year patient mortality, hospitalization, and transplantation. Associations of outcomes with quartile of patient-to-PCT ratio were estimated using incidence rate ratios (IRRs) from mixed-effects Poisson regression, with adjustment for patient demographics and clinical and facility factors. Results A total of 236 126 patients (mean [SD] age, 63.1 [14.4] years; 135 952 [57.6%] male; 65 945 [27.9%] Black; 37 777 [16.0%] Hispanic; 153 637 [65.1%] White; 16 544 [7.0%] other race; 146 107 [61.9%] with diabetes) were included. After full adjustment, the highest vs lowest quartile of facility-level patient-to-PCT ratio was associated with a 7% higher rate of patient mortality (IRR, 1.07; 95% CI, 1.02-1.12), a 5% higher rate of hospitalization (IRR, 1.05; 95% CI, 1.02-1.08), an 8% lower rate of waitlisting (IRR, 0.92; 95% CI, 0.85-0.98), and a 20% lower rate of transplant (IRR, 0.80; 95% CI, 0.71-0.91). The highest vs lowest quartile of patient-to-PCT ratio was also associated with an 8% higher rate of sepsis-related hospitalization (IRR, 1.08; 95% CI, 1.03-1.14) and a 15% higher rate of vascular access–related hospitalization (IRR, 1.15; 95% CI, 1.03-1.28). Conclusions and Relevance These findings suggest that initiation of treatment in facilities with the highest patient-to-PCT ratios may be associated with worse early mortality, hospitalization, and transplantation outcomes. These results support further investigation of the impact of US PCT staffing on patient safety and quality of US in-center HD care.
Implementation of pooled saliva tests for universal screening of cCMV infection
Authors: Lior Merav, Noa Ofek Shlomai, Esther Oiknine-Djian, Orit Caplan, Ayala Livneh, Tal Sido, Amir Peri, Aviad Shtoyer, Eden Amir, Kerem Ben Meir, Yutti Daitch, Mila Rivkin, Esther Kripper, Irit Fogel, Hadar Horowitz, Sraya Greenberger, Mevaseret Cohen, Miriam Geal-Dor, Oren Gordon, Diana Averbuch, Zivanit Ergaz-Shaltiel, Smadar Eventov Friedman, Dana G Wolf, Moran Yassour
Journal: Nature Medicine (2024)

Abstract Congenital cytomegalovirus (cCMV) is the most common intrauterine infection, leading to neurodevelopmental disabilities. Universal newborn infant screening of cCMV has been increasingly advocated. In the absence of a high-throughput screening test, which can identify all infected newborn infants, the development of an accurate and efficient testing strategy has remained an ongoing challenge. Here we assessed the implementation of pooled saliva polymerase chain reaction (PCR) tests for universal screening of cCMV, in two hospitals of Jerusalem from April 2022 through April 2023. During the 13-month study period, 15,805 infants (93.6% of all live newborn infants) were screened for cCMV using the pooled approach that has since become our routine screening method. The empirical efficiency of the pooling was six (number of tested newborn infants per test), thereby sparing 83% of the saliva tests. Only a minor 3.05 PCR cycle loss of sensitivity was observed for the pooled testing, in accordance with the theoretical prediction for an eight-sample pool. cCMV was identified in 54 newborn infants, with a birth prevalence of 3.4 per 1,000; 55.6% of infants identified with cCMV were asymptomatic at birth and would not have been otherwise targeted for screening. The study demonstrates the wide feasibility and benefits of pooled saliva testing as an efficient, cost-sparing and sensitive approach for universal screening of cCMV.
Incidence of Nonkeratinocyte Skin Cancer After Breast Cancer Radiation Therapy
Authors: Shawheen J. Rezaei, Edward Eid, Jean Y. Tang, Allison W. Kurian, Bernice Y. Kwong, Eleni Linos
Journal: JAMA Network Open (2024)

Importance Previous studies have suggested that radiation therapy may contribute to an increased risk of subsequent nonkeratinocyte (ie, not squamous and basal cell) skin cancers. Objective To test the hypothesis that radiation therapy for breast cancer increases the risk of subsequent nonkeratinocyte skin cancers, particularly when these cancers are localized to the skin of the breast or trunk. Design, Setting, and Participants This population-based cohort study used longitudinal data from the Surveillance, Epidemiology, and End Results (SEER) Program for January 1, 2000, to December 31, 2019. The SEER database includes population-based cohort data from 17 registries. Patients with newly diagnosed breast cancer were identified and were evaluated for subsequent nonkeratinocyte skin cancer development. Data analysis was performed from January to August 2023. Exposures Radiation therapy, chemotherapy, or surgery for breast cancer. Main Outcomes and Measures The primary outcomes were standardized incidence ratios (SIRs) for subsequent nonkeratinocyte skin cancer development from 2000 to 2019 based on treatment type (radiation therapy, chemotherapy, or surgery), skin cancer site on the body, and skin cancer subtype. Results Among the 875 880 patients with newly diagnosed breast cancer included in this study, 99.3% were women, 51.6% were aged older than 60 years, and 50.3% received radiation therapy. A total of 11.2% patients identified as Hispanic, 10.1% identified as non-Hispanic Black, and 69.5% identified as non-Hispanic White. From 2000 to 2019, there were 3839 patients with nonkeratinocyte skin cancer, including melanoma (3419 [89.1%]), Merkel cell carcinoma (121 [3.2%]), hemangiosarcoma (104 [2.7%]), and 32 other nonkeratinocyte skin cancers (195 [5.1%]), documented to occur after breast cancer treatment. The risk of nonkeratinocyte skin cancer diagnosis after breast cancer treatment with radiation was 57% higher (SIR, 1.57 [95% CI, 1.45-1.7]) than that of the general population when considering the most relevant site: the skin of the breast or trunk. When risk at this site was stratified by skin cancer subtype, the SIRs for melanoma and hemangiosarcoma were both statistically significant at 1.37 (95% CI, 1.25-1.49) and 27.11 (95% CI, 21.6-33.61), respectively. Receipt of radiation therapy was associated with a greater risk of nonkeratinocyte skin cancer compared with chemotherapy and surgical interventions. Conclusions and Relevance In this study of patients with breast cancer, an increased risk of melanoma and hemangiosarcoma after breast cancer treatment with radiation therapy was observed. Although occurrences of nonkeratinocyte skin cancers are rare, physicians should be aware of this elevated risk to help inform follow-up care.
Visualization of the Internal Thoracic Arteries in Giant Cell Arteritis on 18F-FDG Semiconductor PET/CT
Authors: Takashi Maki, Yohji Matsusaka, Ryota Egi, Akira Seto, Ichiei Kuji
Journal: Clinical Nuclear Medicine (2024)

Abstract A 72-year-old woman presented with the fever and the pain of skull and face for 2 weeks. 18 F-FDG PET/CT equipped with semiconductor detectors revealed strong uptake not only in the temporal, cervical, subclavian arteries, and aorta, but also in the bilateral internal thoracic arteries. The diagnosis of giant cell arteritis was made. Semiconductor PET can visualize small arteries such as the internal thoracic artery. The patients with giant cell arteritis are at a high risk of ischemic heart disease, and inflammatory involvement of the internal thoracic arteries may affect the outcome of coronary artery bypass grafting.
MRD at the end of induction and EFS in T-cell lymphoblastic lymphoma: Children’s Oncology Group trial AALL1231
Authors: Robert J. Hayashi, Michelle L. Hermiston, Brent L. Wood, David T. Teachey, Meenakshi Devidas, Zhiguo Chen, Robert D. Annett, Barbara L. Asselin, Keith August, Steve Cho, Kimberly P. Dunsmore, Jason Lawrence Freedman, Paul J. Galardy, Paul Harker-Murray, Terzah M. Horton, Alok Jaju, Allison Lam, Yoav H. Messinger, Rodney R. Miles, Maki Okada, Samir Patel, Eric S. Schafer, Tal Schechter, Kristin A. Shimano, Neelam Singh, Amii Steele, Maria L. Sulis, Sarah L. Vargas, Stuart S. Winter, Charlotte Wood, Patrick A. Zweidler-McKay, Mignon L. Loh, Stephen P. Hunger, Elizabeth A. Raetz, Catherine M. Bollard, Carl E. Allen
Journal: Blood (2024)
Bridging the literacy gap for surgical consents: an AI-human expert collaborative approach
Authors: Rohaid Ali, Ian D. Connolly, Oliver Y. Tang, Fatima N. Mirza, Benjamin Johnston, Hael F. Abdulrazeq, Rachel K. Lim, Paul F. Galamaga, Tiffany J. Libby, Neel R. Sodha, Michael W. Groff, Ziya L. Gokaslan, Albert E. Telfeian, John H. Shin, Wael F. Asaad, James Zou, Curtis E. Doberstein
Journal: npj Digital Medicine (2024)

Despite the importance of informed consent in healthcare, the readability and specificity of consent forms often impede patients' comprehension. This study investigates the use of GPT-4 to simplify surgical consent forms and introduces an AI-human expert collaborative approach to validate content appropriateness. Consent forms from multiple institutions were assessed for readability and simplified using GPT-4, with pre- and post-simplification readability metrics compared using nonparametric tests. Independent reviews by medical authors and a malpractice defense attorney were conducted. Finally, GPT-4's potential for generating de novo procedure-specific consent forms was assessed, with forms evaluated using a validated 8-item rubric and expert subspecialty surgeon review. Analysis of 15 academic medical centers' consent forms revealed significant reductions in average reading time, word rarity, and passive sentence frequency (all P < 0.05) following GPT-4-faciliated simplification. Readability improved from an average college freshman to an 8th-grade level (P = 0.004), matching the average American's reading level. Medical and legal sufficiency consistency was confirmed. GPT-4 generated procedure-specific consent forms for five varied surgical procedures at an average 6th-grade reading level. These forms received perfect scores on a standardized consent form rubric and withstood scrutiny upon expert subspeciality surgeon review. This study demonstrates the first AI-human expert collaboration to enhance surgical consent forms, significantly improving readability without sacrificing clinical detail. Our framework could be extended to other patient communication materials, emphasizing clear communication and mitigating disparities related to health literacy barriers.
Putative novel CSF biomarkers of Alzheimer’s disease based on the novel concept of generic protein misfolding and proteotoxicity: the PRAMA cohort
Authors: Alessandra Bigi, Giulia Fani, Valentina Bessi, Liliana Napolitano, Silvia Bagnoli, Assunta Ingannato, Lorenzo Neri, Roberta Cascella, Paolo Matteini, Sandro Sorbi, Benedetta Nacmias, Cristina Cecchi, Fabrizio Chiti
Journal: Translational Neurodegeneration (2024)