tbuckley/cabot-search huggingface dataset:
Disparities in HPV Vaccination Among Adolescents by Health Care Facility Type
Authors: Mrudula Nair, Joël Fokom Domgue, Christine L. M. Joseph, Elizabeth R. Alleman, Amy M. Williams, Dina K. Abouelella, Oluwole A. Babatunde, Nosayaba Osazuwa-Peters, Eric Adjei Boakye
Journal: JAMA Pediatrics (2024)

Importance Approximately 31 000 cases of human papillomavirus (HPV)–associated cancers are diagnosed annually in the US. The HPV vaccine can prevent more than 90% of these cancers, yet national uptake remains lower than the Healthy People 2030 target of 80% completion. To devise targeted interventions to increase the uptake of HPV vaccines, it is crucial to understand the vaccination rates across various health care settings. Objective To examine the association between health care facility type and adolescent HPV vaccine uptake and clinician recommendation for the vaccine in the US. Design, Setting, and Participants This cross-sectional study uses a complex sampling design of data from the 2020 National Immunization Survey–Teen. The study included adolescents aged 13 to 17 years. The data analysis was completed between March 1 and May 31, 2022. Exposure Health care facility type classified as public, hospital-based, private, mixed (more than 1 type), and other facilities (eg, military health care facility; Women, Infants, and Children clinic; school-based health center; pharmacy). Main Outcomes and Measures Initiation of HPV vaccination was defined as the receipt of at least 1 dose of the HPV vaccine and completion as receipt of at least 2 or 3 doses, depending on age of initiation. Parent or guardian self-reported clinician recommendation was categorized as yes or no. Weighted, multivariable logistic regression models were used to estimate the odds of initiating and completing the HPV vaccine series and receiving clinician recommendation by health care facility type adjusted for adolescent and maternal characteristics. Results A total of 20 162 adolescents (mean [SD] age, 14.9 [1.4] years; 51.0% male) were included. Clinician recommendation for the HPV vaccine was received by 81.4% of adolescents, and 75.1% initiated and 58.6% completed the HPV vaccine series. In the adjusted analyses, adolescents who received recommended vaccinations at public facilities had lower odds of initiating (adjusted odds ratio [AOR], 0.71; 95% CI, 0.58-0.88) and completing (AOR, 0.62; 95% CI, 0.51-0.76) HPV vaccination compared with those who received recommended vaccinations at private facilities. Similarly, adolescents who received recommended vaccinations at public facilities (AOR, 0.62; 95% CI, 0.51-0.77) had lower odds of receiving a clinician recommendation for the HPV vaccine compared with those who received recommended vaccinations at private facilities. Conclusions and Relevance These findings reveal health disparities in HPV vaccination among adolescent populations served by public health care facilities, suggesting that a greater focus is needed on vaccine recommendations and uptake in public facilities.
Opioid Use Disorder Medications After Hospitalization—Rethinking Engagement in Care
Authors: Honora Englander
Journal: JAMA Internal Medicine (2024)

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Impact of second autologous stem‐cell transplantation at relapsed multiple myeloma: A French multicentric real‐life study
Authors: Axel André, Lydia Montes, Damien Roos‐Weil, Laurent Frenzel, Marguerite Vignon, Thomas Chalopin, Pierre‐Edouard Debureaux, Alexis Talbot, Agathe Farge, Fabrice Jardin, Karim Belhadj, Bruno Royer, Jean‐Pierre Marolleau, Bertrand Arnulf, Pierre Morel, Stéphanie Harel
Journal: HemaSphere (2024)

Abstract A second autologous stem‐cell transplantation (ASCT2) is considered for relapsed multiple myeloma (RMM) patients showing prolonged response after a first ASCT. However, given breakthrough treatments like anti‐CD38 and immunotherapy, its role remains debated. We conducted a real‐life study in 10 French centers (1996–2017) involving 267 RMM patients receiving ASCT2. The median age was 61 years, with 49% females. Most patients received melphalan 200 mg/m² before ASCT2, with low early mortality (1%). Very good partial response or better (VGPR+) rate post ASCT2 was 78%. Post ASCT2, 48% received consolidation therapy and 40% maintenance therapy. Median event‐free survival (EFS) after ASCT2 was 2.6 years (95% confidence interval [CI]: 2.3–2.8), and 2‐year EFS estimate was 63% (95% CI: 57–70). Median overall survival (OS) was 8.1 years (95% CI: 5.9–NA), and 2‐year OS estimate was 92% (95% CI: 88–95). Multivariate analysis revealed that VGPR+ status and maintenance therapy post ASCT2 were associated with better EFS (hazard ratio [HR]: 0.6; 95% CI: 0.3–0.9, p = 0.012 and HR: 0.4; 95% CI: 0.3–0.6, p &lt; 0.001, respectively) and OS (HR: 0.4; 95% CI: 0.2–0.9, p = 0.017 and HR: 0.2; 95% CI: 0.1–0.4, p &lt; 0.001, respectively), while male sex correlated with poorer outcomes for EFS (HR: 2.5; 95% CI: 1.7–3.7, p &lt; 0.001) and OS (HR: 2.7; 95% CI: 1.4–4.9, p = 0.002). Overall, ASCT2 appeared efficient with low toxicity in RMM. Maintenance therapy was associated with extended EFS and OS, particularly in patients with VGPR+ status post ASCT2. These findings underscore ASCT2's potential in RMM when coupled with maintenance therapy in selected patients.
Multi-Dimensional Fragmentomics Enables Early and Accurate Detection of Colorectal Cancer
Authors: Yuepeng Cao, Nannan Wang, Xuxiaochen Wu, Wanxiangfu Tang, Hua Bao, Chengshuai Si, Peng Shao, Dongzheng Li, Xin Zhou, Dongqin Zhu, Shanshan Yang, Fufeng Wang, Guoqing Su, Ke Wang, Qifan Wang, Yao Zhang, Qiangcheng Wang, Dongsheng Yu, Qian Jiang, Jun Bao, Liu Yang
Journal: Cancer Research (2024)

Abstract Colorectal cancer is frequently diagnosed in advanced stages, highlighting the need for developing approaches for early detection. Liquid biopsy using cell-free DNA (cfDNA) fragmentomics is a promising approach, but the clinical application is hindered by complexity and cost. This study aimed to develop an integrated model using cfDNA fragmentomics for accurate, cost-effective early-stage colorectal cancer detection. Plasma cfDNA was extracted and sequenced from a training cohort of 360 participants, including 176 patients with colorectal cancer and 184 healthy controls. An ensemble stacked model comprising five machine learning models was employed to distinguish patients with colorectal cancer from healthy controls using five cfDNA fragmentomic features. The model was validated in an independent cohort of 236 participants (117 patients with colorectal cancer and 119 controls) and a prospective cohort of 242 participants (129 patients with colorectal cancer and 113 controls). The ensemble stacked model showed remarkable discriminatory power between patients with colorectal cancer and controls, outperforming all base models and achieving a high area under the receiver operating characteristic curve of 0.986 in the validation cohort. It reached 94.88% sensitivity and 98% specificity for detecting colorectal cancer in the validation cohort, with sensitivity increasing as the cancer progressed. The model also demonstrated consistently high accuracy in within-run and between-run tests and across various conditions in healthy individuals. In the prospective cohort, it achieved 91.47% sensitivity and 95.58% specificity. This integrated model capitalizes on the multiplex nature of cfDNA fragmentomics to achieve high sensitivity and robustness, offering significant promise for early colorectal cancer detection and broad patient benefit. Significance: The development of a minimally invasive, efficient approach for early colorectal cancer detection using advanced machine learning to analyze cfDNA fragment patterns could expedite diagnosis and improve treatment outcomes for patients. See related commentary by Rolfo and Russo, p. 3128
Rapid iPSC inclusionopathy models shed light on formation, consequence, and molecular subtype of α-synuclein inclusions
Authors: Isabel Lam, Alain Ndayisaba, Amanda J. Lewis, YuHong Fu, Giselle T. Sagredo, Anastasia Kuzkina, Ludovica Zaccagnini, Meral Celikag, Jackson Sandoe, Ricardo L. Sanz, Aazam Vahdatshoar, Timothy D. Martin, Nader Morshed, Toru Ichihashi, Arati Tripathi, Nagendran Ramalingam, Charlotte Oettgen-Suazo, Theresa Bartels, Manel Boussouf, Max Schäbinger, Erinc Hallacli, Xin Jiang, Amrita Verma, Challana Tea, Zichen Wang, Hiroyuki Hakozaki, Xiao Yu, Kelly Hyles, Chansaem Park, Xinyuan Wang, Thorold W. Theunissen, Haoyi Wang, Rudolf Jaenisch, Susan Lindquist, Beth Stevens, Nadia Stefanova, Gregor Wenning, Wilma D.J. van de Berg, Kelvin C. Luk, Rosario Sanchez-Pernaute, Juan Carlos Gómez-Esteban, Daniel Felsky, Yasujiro Kiyota, Nidhi Sahni, S. Stephen Yi, Chee Yeun Chung, Henning Stahlberg, Isidro Ferrer, Johannes Schöneberg, Stephen J. Elledge, Ulf Dettmer, Glenda M. Halliday, Tim Bartels, Vikram Khurana
Journal: Neuron (2024)

The heterogeneity of protein-rich inclusions and its significance in neurodegeneration is poorly understood. Standard patient-derived iPSC models develop inclusions neither reproducibly nor in a reasonable time frame. Here, we developed screenable iPSC "inclusionopathy" models utilizing piggyBac or targeted transgenes to rapidly induce CNS cells that express aggregation-prone proteins at brain-like levels. Inclusions and their effects on cell survival were trackable at single-inclusion resolution. Exemplar cortical neuron α-synuclein inclusionopathy models were engineered through transgenic expression of α-synuclein mutant forms or exogenous seeding with fibrils. We identified multiple inclusion classes, including neuroprotective p62-positive inclusions versus dynamic and neurotoxic lipid-rich inclusions, both identified in patient brains. Fusion events between these inclusion subtypes altered neuronal survival. Proteome-scale α-synuclein genetic- and physical-interaction screens pinpointed candidate RNA-processing and actin-cytoskeleton-modulator proteins like RhoA whose sequestration into inclusions could enhance toxicity. These tractable CNS models should prove useful in functional genomic analysis and drug development for proteinopathies.
Optimized ultrasound neuromodulation for non-invasive control of behavior and physiology
Authors: Keith R Murphy, Jordan S Farrell, Jonas Bendig, Anish Mitra, Charlotte Luff, Ina A Stelzer, Hiroshi Yamaguchi, Christopher C Angelakos, Mihyun Choi, Wenjie Bian, Tommaso DiIanni, Esther Martinez Pujol, Noa Matosevich, Raag Airan, Brice Gaudillière, Elisa E Konofagou, Kim Butts-Pauly, Ivan Soltesz, Luis de Lecea
Journal: Neuron (2024)
A practical approach on the classifications of myeloid neoplasms and acute leukemia: WHO and ICC
Authors: Wenbin Xiao, Valentina Nardi, Eytan Stein, Robert P. Hasserjian
Journal: Journal of Hematology & Oncology (2024)

Abstract In 2022, two new classifications of myeloid neoplasms and acute leukemias were published: the 5th edition WHO Classification (WHO-HAEM5) and the International Consensus Classification (ICC). As with prior classifications, the WHO-HAEM5 and ICC made updates to the prior classification (revised 4th edition WHO Classification, WHO-HAEM4R) based on a consensus of groups of experts, who examined new evidence. Both WHO-HAEM5 and ICC introduced several new disease entities that are based predominantly on genetic features, superseding prior morphologic definitions. While it is encouraging that two groups independently came to similar conclusions in updating the classification of myeloid neoplasms and acute leukemias, there are several divergences in how WHO-HAEM5 and ICC define specific entities as well as differences in nomenclature of certain diseases. In this review, we highlight the similarities and differences between the WHO-HAEM5 and ICC handling of myeloid neoplasms and acute leukemias and present a practical approach to diagnosing and classifying these diseases in this current era of two divergent classification guidelines.
NQO1 Triggers Neutrophil Recruitment and NET formation to Drive Lung Metastasis of Invasive Breast Cancer
Authors: Xinzhi Wang, Yi Qu, Qianqian Xu, Zeyu Jiang, Hang Wang, Binyan Lin, Zehong Cao, Yuqi Pan, Sheng Li, Yili Hu, Hui Yang, Li He, Hang Chang, Bo Hang, Hongmei Wen, Hao Wu, Jian-Hua Mao
Journal: Cancer Research (2024)

Abstract Metastasis to the lungs is a leading cause of death for patients with breast cancer. Therefore, effective therapies are urgently needed to prevent and treat lung metastasis. In this study, we uncovered a mechanism by which NAD(P)H:quinone oxidoreductase 1 (NQO1) orchestrates lung metastasis. NQO1 stabilized and upregulated peptidyl-prolyl cis-trans isomerase A (PPIA), a chaperone that regulates protein conformation and activity, by preventing its oxidation at a critical cysteine residue C161. PPIA subsequently activated CD147, a membrane protein that facilitates cell invasion. Moreover, NQO1-induced secretion of PPIA modulated the immune landscape of both primary and lung metastatic sites. Secreted PPIA engaged CD147 on neutrophils and triggered the release of neutrophil extracellular traps (NET) and neutrophil elastase, which enhanced tumor progression, invasiveness, and lung colonization. Pharmacological targeting of PPIA effectively inhibited NQO1-mediated breast cancer lung metastasis. These findings reveal a previously unrecognized NQO1-PPIA-CD147-NET axis that drives breast cancer lung metastasis. Inhibiting this axis is a potential therapeutic strategy to limit lung metastasis in patients with breast cancer. Significance: NQO1 stabilizes and promotes the secretion of PPIA to activate CD147 in neutrophils and stimulate NET formation, promoting breast cancer lung metastasis and providing therapeutic targets for this fatal condition.
Harnessing extracellular vesicles using liquid biopsy for cancer diagnosis and monitoring: highlights from AACR Annual Meeting 2024
Authors: Xinming Su, Zeping Shan, Shiwei Duan
Journal: Journal of Hematology & Oncology (2024)

Abstract Liquid biopsy, an advanced technology for analyzing body fluid samples, is gaining traction in cancer diagnostics and monitoring. Blood-based liquid biopsy, particularly focusing on cell-free DNAs (cf-DNAs), circulating tumor cells (CTCs), and extracellular vesicles (EVs), has garnered significant attention. EVs stand out for their potential in tumor diagnosis, prognosis prediction, and treatment response assessment, owing to their stable molecular cargo and clear extraction process. At the recent American Association for Cancer Research (AACR) Annual Meeting 2024, groundbreaking EVs-based liquid biopsy studies showcased promising strides in early detection and diagnosis of various cancers, including breast cancer (BC), high-grade serous ovarian cancer (HGSOC), pancreatic ductal adenocarcinoma (PDAC), colorectal cancer (CRC), colon adenocarcinoma (COAD), head and neck cancer (HNC), neuroblastoma, and retinoblastoma (RB). Despite these advancements, challenges persist in translating EVs biomarkers into clinical practice. Overcoming these challenges promises to propel EVs-based liquid biopsy into a new era of personalized precision medicine, revolutionizing cancer detection, monitoring, and treatment.
Brain ischemia causes systemic Notch1 activity in endothelial cells to drive atherosclerosis
Authors: Mingming Liu, Danni Wang, Caiyun Qi, Ming Zou, Jiawei Song, Lili Li, Hengchang Xie, Honglei Ren, Hongying Hao, Guili Yang, Zixiao Li, Qiang Zhang, Jie Zhou, Ding Ai, Qiang Liu
Journal: Immunity (2024)
Decreasing unnecessary use of continuous cardiac monitoring (telemetry) in hospitalised patients
Authors: William K Silverstein, Irene Y Chang, Shiva Sreenivasan, Sanket S Dhruva
Journal: BMJ (2024)

### What you need to know Since its development in 1949, in-hospital continuous electrocardiographic monitoring (hereinafter "telemetry") has become increasingly important for clinical care of hospitalised patients.1 Telemetry is used for a variety of applications, including diagnosis and monitoring of arrhythmias, detection of myocardial ischaemia, and monitoring of ST segments and QT intervals. Specialist societies around the world have published practice standards to inform clinicians when telemetry should be used.234 Appropriate clinical indications are listed in box 1 and include patients with suspected or confirmed acute coronary syndromes, acute decompensated heart failure, high grade arrhythmias, post-cardiac arrest, severe electrolyte derangements, use of certain medications, and ingestion of pro-arrhythmic agents.234 Box 1 ### Indications for appropriate continuous electrocardiographic monitoring recommended by international specialist societies #### Agency for Clinical Innovation's Clinical Practice Guide (Australia)2RETURN TO TEXT
A microbial metabolite inhibits the HIF-2α-ceramide pathway to mediate the beneficial effects of time-restricted feeding on MASH
Authors: Yi Zhang, Xuemei Wang, Jun Lin, Jia Liu, Kai Wang, Qixing Nie, Chuan Ye, Lulu Sun, Yanpeng Ma, Ruize Qu, Yuejian Mao, Xuguang Zhang, Hua Lu, Pengyan Xia, Dongyu Zhao, Guang Wang, Zhipeng Zhang, Wei Fu, Changtao Jiang, Yanli Pang
Journal: Cell Metabolism (2024)
Novel natural killer cell-based therapies for hematologic and solid malignancies: latest updates from ASCO 2024
Authors: Xubo Gong, Lianjun Zhang, Xin He, Jing Yang, Xiang Li, Weiwei Liu, Bin Zhang, Zhihua Tao, Wenbin Qian
Journal: Journal of Hematology & Oncology (2024)

Natural killer (NK) cell-based therapies have made great progress in treating both hematological and solid tumors. Their unique mechanism of action does not rely on antigen presentation to recognize and eliminate tumor cells, making them a promising approach for cancer immunotherapy. In this review, we present a comprehensive summary of the latest clinical data of the novel NK cell-based therapies from the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, highlighting the potential of these advancements to revolutionize the treatment of hematologic malignancies and solid tumors.
Joint AI-driven event prediction and longitudinal modeling in newly diagnosed and relapsed multiple myeloma
Authors: Zeshan Hussain, Edward De Brouwer, Rebecca Boiarsky, Sama Setty, Neeraj Gupta, Guohui Liu, Cong Li, Jaydeep Srimani, Jacob Zhang, Rich Labotka, David Sontag
Journal: npj Digital Medicine (2024)

Abstract Multiple myeloma management requires a balance between maximizing survival, minimizing adverse events to therapy, and monitoring disease progression. While previous work has proposed data-driven models for individual tasks, these approaches fail to provide a holistic view of a patient’s disease state, limiting their utility to assist physician decision-making. To address this limitation, we developed a transformer-based machine learning model that jointly (1) predicts progression-free survival (PFS), overall survival (OS), and adverse events (AE), (2) forecasts key disease biomarkers, and (3) assesses the effect of different treatment strategies, e.g., ixazomib, lenalidomide, dexamethasone (IRd) vs lenalidomide, dexamethasone (Rd). Using TOURMALINE trial data, we trained and internally validated our model on newly diagnosed myeloma patients ( N = 703) and externally validated it on relapsed and refractory myeloma patients ( N = 720). Our model achieved superior performance to a risk model based on the multiple myeloma international staging system (ISS) ( p &lt; 0.001, Bonferroni corrected ) and comparable performance to survival models trained separately on each task, but unable to forecast biomarkers. Our approach outperformed state-of-the-art deep learning models, tailored towards forecasting, on predicting key disease biomarkers ( p &lt; 0.001, Bonferroni corrected ). Finally, leveraging our model’s capacity to estimate individual-level treatment effects, we found that patients with IgA kappa myeloma appear to benefit the most from IRd. Our study suggests that a holistic assessment of a patient’s myeloma course is possible, potentially serving as the foundation for a personalized decision support system.
Correction: Targeting CERS6-AS1/FGFR1 axis as synthetic vulnerability to constrain stromal cells supported proliferation in Mantle cell lymphoma
Authors: Udita Jindal, Mukesh Mamgain, Uttam Kumar Nath, Isha Sharma, Bhaskar Pant, Ankita Sharma, Archita Gupta, Khaliqur Rahman, Sunil Yadav, Manish Pratap Singh, Shaktiprasad Mishra, Chandra Praksah Chaturvedi, Jose Courty, Navin Singh, Seema Gupta, Sanjeev Kumar, Shailendra Prasad Verma, Saumyaranjan Mallick, Ajay Gogia, Sunil Raghav, Jayanta Sarkar, Kinshuk Raj Srivastava, Dipak Datta, Neeraj Jain
Journal: Leukemia (2024)
Iron Chelation Therapy Elicits Innate Immune Control of Metastatic Ovarian Cancer
Authors: Tito A. Sandoval, Camilla Salvagno, Chang-Suk Chae, Deepika Awasthi, Paolo Giovanelli, Matias Marin Falco, Sung-Min Hwang, Eli Teran-Cabanillas, Lasse Suominen, Takahiro Yamazaki, Hui-Hsuan Kuo, Jenna E. Moyer, M. Laura Martin, Jyothi Manohar, Kihwan Kim, Maria A. Sierra, Yusibeska Ramos, Chen Tan, Alexander Emmanuelli, Minkyung Song, Diana K. Morales, Dmitriy Zamarin, Melissa K. Frey, Evelyn Cantillo, Eloise Chapman-Davis, Kevin Holcomb, Christopher E. Mason, Lorenzo Galluzzi, Zhen Ni Zhou, Anna Vähärautio, Suzanne M. Cloonan, Juan R. Cubillos-Ruiz
Journal: Cancer Discovery (2024)

Abstract Iron accumulation in tumors contributes to disease progression and chemoresistance. Although targeting this process can influence various hallmarks of cancer, the immunomodulatory effects of iron chelation in the tumor microenvironment are unknown. Here, we report that treatment with deferiprone, an FDA-approved iron chelator, unleashes innate immune responses that restrain ovarian cancer. Deferiprone reprogrammed ovarian cancer cells toward an immunostimulatory state characterized by the production of type-I IFN and overexpression of molecules that activate NK cells. Mechanistically, these effects were driven by innate sensing of mitochondrial DNA in the cytosol and concomitant activation of nuclear DNA damage responses triggered upon iron chelation. Deferiprone synergized with chemotherapy and prolonged the survival of mice with ovarian cancer by bolstering type-I IFN responses that drove NK cell-dependent control of metastatic disease. Hence, iron chelation may represent an alternative immunotherapeutic strategy for malignancies that are refractory to current T-cell–centric modalities. Significance: This study uncovers that targeting dysregulated iron accumulation in ovarian tumors represents a major therapeutic opportunity. Iron chelation therapy using an FDA-approved agent causes immunogenic stress responses in ovarian cancer cells that delay metastatic disease progression and enhance the effects of first-line chemotherapy. See related commentary by Bell and Zou, p. 1771