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Correction to: A machine learning approach to leveraging electronic health records for enhanced omics analysis (Nature Machine Intelligence, (2025), 7, 2, (293-306), 10.1038/s42256-024-00974-9)

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Nature Machine Intelligence 2025年

作者： Mataraso, Samson J. Espinosa, Camilo A. Seong, David Reincke, S. Momsen Berson, Eloise Reiss, Jonathan D. Kim, Yeasul Ghanem, Marc Shu, Chi-Hung James, Tomin Tan, Yuqi Shome, Sayane Stelzer, Ina A. Feyaerts, Dorien Wong, Ronald J. Shaw, Gary M. Angst, Martin S. Gaudilliere, Brice Stevenson, David K. Aghaeepour, Nima Department of Anesthesiology Perioperative and Pain Medicine Stanford University School of Medicine StanfordCA United States Department of Pediatrics Stanford University School of Medicine StanfordCA United States Department of Biomedical Data Science Stanford University School of Medicine StanfordCA United States Immunology Program Stanford University School of Medicine StanfordCA United States Medical Scientist Training Program Stanford University School of Medicine StanfordCA United States Department of Pathology Stanford University School of Medicine StanfordCA United States Department of Microbiology and Immunology Stanford University School of Medicine StanfordCA United States Department of Pathology University of California San Diego La Jolla CA United States

Correction to: Nature Machine Intelligencehttps://***/10.1038/s42256-024-00974-9, published online 16 January 2025. In the version of the article initially published, in the "COMET deep learning architecture" section of the Methods, the equations for MSE and BSE were switched and have now been corrected as shown: (Formula presented.) and (Formula presented.) Additionally, the grey background circles in Fig. 4d were incorrectly offset from the clusters and have now been corrected. These corrections have been made to the HTML and PDF versions of the article. © The Author(s) 2025.

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Correction to: Droplet Hi-C enables scalable, single-cell profiling of chromatin architecture in heterogeneous tissues (Nature Biotechnology, (2024), 10.1038/s41587-024-02447-1)

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Nature Biotechnology 2025年

作者： Chang, Lei Xie, Yang Taylor, Brett Wang, Zhaoning Sun, Jiachen Armand, Ethan J. Mishra, Shreya Xu, Jie Tastemel, Melodi Lie, Audrey Gibbs, Zane A. Indralingam, Hannah S. Tan, Tuyet M. Bejar, Rafael Chen, Clark C. Furnari, Frank B. Hu, Ming Ren, Bing Department of Cellular and Molecular Medicine University of California San Diego La JollaCA United States Biomedical Sciences Graduate Program University of California San Diego La JollaCA United States Medical Scientist Training Program University of California San Diego La JollaCA United States Department of Quantitative Health Sciences Lerner Research Institute Cleveland Clinic Foundation ClevelandOH United States Systems Biology and Bioinformatics PhD Program Case Western Reserve University School of Medicine ClevelandOH United States Bioinformatics and Systems Biology Program University of California San Diego La JollaCA United States Moores Cancer Center UC San Diego La JollaCA United States Department of Neurosurgery University of Minnesota MinneapolisMN United States Department of Medicine University of California San Diego School of Medicine La JollaCA United States Center for Epigenomics Institute for Genomic Medicine School of Medicine University of California San Diego La JollaCA United States

Correction to: Nature Biotechnologyhttps://***/10.1038/s41587-024-02447-1, published online 18 October 2024. In the version of the article initially published, in the Methods section, both mentions of "MboII" should have read "MboI (NEB, R0147M)" and have now been corrected in the HTML and PDF versions of the article. © The Author(s) 2025.

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Dynamics of Daily Glioblastoma Evolution During Chemoradiation Therapy on the 0.35T Magnetic Resonance Imaging-Linear Accelerator

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International Journal of Radiation Oncology Biology Physics 2024年

作者： Cullison, Kaylie Samimi, Kayla Bell, Jonathan B. Maziero, Danilo Valderrama, Alessandro Breto, Adrian L. Jones, Kolton De La Fuente, Macarena I. Kubicek, Gregory Meshman, Jessica Azzam, Gregory A. Ford, John C. Stoyanova, Radka Mellon, Eric A. Department of Radiation Oncology Sylvester Comprehensive Cancer Center University of Miami Miller School of Medicine MiamiFL United States Department of Biomedical Engineering University of Miami Coral GablesFL United States Medical Scientist Training Program University of Miami Miller School of Medicine MiamiFL United States Department of Radiation Oncology David Geffen School of Medicine University of California Los AngelesCA United States West Physics AtlantaGA United States Department of Neurology Sylvester Comprehensive Cancer Center University of Miami Miller School of Medicine MiamiFL United States

Purpose: Glioblastoma changes during chemoradiation therapy are inferred from magnetic resonance imaging (MRI) before and after treatment but are rarely investigated due to logistics of frequent MRI. Using a combination MRI-linear accelerator (MRI-linac), we evaluated changes during daily chemoradiation therapy. Methods and Materials: Patients with glioblastoma were prospectively imaged daily during chemoradiation therapy on 0.35T MRI-linac and at 3 timepoints with and without contrast on standalone high-field MRI. Tumor or edema (lesion) and resection cavity dynamics throughout treatment were analyzed and compared with standalone T1 postcontrast (T1+C) and T2 volumes. Results: Of 36 patients included in this analysis, 8 had cavity only, 12 had lesion only, and 16 had both cavity and lesion. Of these, 64% had lesion growth and 46% had cavity shrinkage during treatment on MRI-linac scans. The average MRI-linac migration distance was 1.3 cm (range, 0-4.1 cm) for lesion and 0.6 cm (range, 0.1-2.1 cm) for cavity. Standalone versus MRI-linac volumes correlated strongly with R2 values: 0.991 (T2 vs MRI-linac cavity), 0.972 (T1+C vs MRI-linac cavity), and 0.973 (T2 vs MRI-linac lesion). There was a moderate correlation between T1+C and MRI-linac lesion (R2 = 0.609), despite noncontrast MRI-linac inability to separate contrast enhancement from surrounding nonenhancing tumor and edema. From pretreatment to posttreatment in patients with all available scans (n = 35), T1+C and MRI-linac lesions changed together—shrank (n = 6), grew (n = 12), or unchanged (n = 8)—in 26 (74%) patients. Another 9 patients (26%) had growth on MRI-linac, although the T1+C component shrank. In no patient did T1+C lesion grow while MRI-linac lesion shrank. Conclusions: Anatomic changes are seen in patients with glioblastoma imaged daily on MRI-linac throughout the chemoradiation therapy course. As surgical resection cavities shrink, margins may be reduced to save normal brain. Patients with unresecte

关键词： Chemoradiotherapy

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Effects of perinatal iron deficiency on spinal dorsal horn circuits

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The journal of pain 2025年 32卷 105434页

作者： Judy J Yoo Elizabeth K Serafin Mark L Baccei Medical Scientist Training Program and Neuroscience Graduate Program University of Cincinnati College of Medicine 231 Albert Sabin Way Cincinnati OH 45267 USA Pain Research Center Department of Anesthesiology University of Cincinnati Medical Center 231 Albert Sabin Way Cincinnati OH 45267 USA. Pain Research Center Department of Anesthesiology University of Cincinnati Medical Center 231 Albert Sabin Way Cincinnati OH 45267 USA. Electronic address: mark.baccei@uc.edu.

Clinical association studies have identified early life iron deficiency (ID) as a risk factor for the development of chronic pain. ID during the perinatal period has long-term consequences for the developing nervous system. Mounting evidence from both clinical and preclinical studies suggests that ID alters pain perception. However, nothing is yet known about how perinatal ID impacts nociceptive circuitry. The present study sought to characterize the effects of ID on the spinal superficial dorsal horn (SDH). Using ex vivo patch clamp electrophysiology in a mouse model of perinatal ID, the excitability of inhibitory and putative excitatory interneurons in the SDH was measured. It was found that early life ID did not significantly change the intrinsic excitability of either interneuron cell type in adolescence or adulthood. The investigation of synaptic inputs onto these two populations revealed that ID modulates spontaneous glutamatergic transmission within the SDH, but did not affect the excitatory drive or balance of synaptic excitation and inhibition. Interestingly, while ID altered the pattern of primary afferent inputs onto presumed glutamatergic interneurons in the mature SDH, the overall efficacy of these synapses was not affected by ID. Collectively, these results suggest that spinal nociceptive circuits are resilient to change following perinatal ID. PERSPECTIVE: This study demonstrates that perinatal iron deficiency (ID) elicits few changes to the intrinsic membrane excitability of superficial dorsal horn neurons or the efficacy of their synaptic inputs. These findings represent a critical first step towards elucidating the effects of ID on nociceptive processing in the central nervous system.

关键词： development electrophysiology nociception spinal cord synaptic transmission

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Cost-effectiveness of hypothetical miRNA biomarker testing for post-treatment surveillance of HPV-negative OPSCC

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Oral Oncology Reports 2023年 8卷 100122-100122页

作者： Shah, Rema Tyagi, Sidharth Vageli, Dimitra Judson, Benjamin Yale University School of Medicine New Haven CT United States Division of Otolaryngology-Head and Neck Surgery Department of Surgery Yale University School of Medicine New Haven CT United States Medical Scientist Training Program Yale University School of Medicine New Haven CT United States Department of Neurology Yale University School of Medicine New Haven CT United States

Objective: To determine the theoretical cost-effectiveness of a miRNA-biomarker test for HPV– oropharyngeal squamous cell carcinoma surveillance compared to current National Comprehensive Cancer Network (NCCN) guidelines. Study design: Cost-effectiveness modeling using a hypothetical patient cohort. Setting: The participants in the model were disease-free patients aged 18+ in the United States who are in remission after completing treatment for HPV- OPSCC. Methods: A Markov model simulated the different post-treatment surveillance options available and probabilities for recurrence at various time-points. A sensitivity analysis adjusted for variations in cost and biomarker test characteristics. Results: The NCCN pathway was $4028.38 more costly and 0.05 QALY more effective than the miRNA pathway. The Extra Imaging pathway was $16,619.83 more costly and 0.18 QALY more effective than the miRNA pathway. The ICER between the miRNA and NCCN strategy was $81,074/QALY and $100,815/QALY between the NCCN and Extra Imaging pathways. The biomarker serum surveillance pathway is more cost-effective than the NCCN approach until the willingness to pay (WTP) threshold exceeds ∼$82,000. At the standard WTP threshold of $50,000/QALY, the serum test pathway is more cost-effective. We also determined the theoretical characteristics of a cost-effective miRNA test. Probabilistic analysis revealed a cost-effective miRNA test should cost less than $451.80, have a sensitivity of greater than 57 %, and a specificity greater than 50 %. Conclusion: The miRNA biomarker strategy is a cost-effective surveillance option for HPV- oropharyngeal cancer. By reducing the reliance on repeated imaging, radiation and in-person follow-up, this strategy can provide more equitable and accessible healthcare. © 2023 The Authors

关键词： Biomarker Cost-effectiveness miRNA Oropharyngeal squamous cell carcinoma Surveillance

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Neurocognitive and Resting-State Functional Magnetic Resonance Imaging Changes in Patients With Diffuse Gliomas After Chemoradiation Therapy

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International Journal of Radiation Oncology Biology Physics 2025年

作者： Liu, Zhihua Mitchell, Timothy J. Luo, Chongliang Park, Ki Yun Shimony, Joshua S. Fucetola, Robert Leuthardt, Eric C. Perkins, Stephanie M. Snyder, Abraham Z. Zhu, Tong Huang, Jiayi Department of Radiation Oncology Washington University School of Medicine St LouisMissouri United States Division of Public Health Sciences Washington University School of Medicine St LouisMissouri United States Medical Scientist Training Program Washington University School of Medicine St. LouisMissouri United States Department of Radiology Division of Medical Oncology Washington University School of Medicine St LouisMissouri United States Department of Neurology Washington University School of Medicine St LouisMissouri United States Department of Neurological Surgery and Division of Neurotechnology Washington University School of Medicine St LouisMissouri United States Brain Tumor Center Siteman Cancer Center Washington University School of Medicine St. LouisMissouri United States

Purpose: This prospective observational study employed resting-state functional magnetic resonance imaging (rs-fMRI) to investigate network-level disturbances associated with neurocognitive function (NCF) changes in patients with gliomas following partial-brain radiation therapy (RT). Methods and Materials: Adult postoperative patients with either isocitrate dehydrogenase (IDH)–wild-type or IDH-mutant gliomas underwent computerized NCF testing and rs-fMRI at baseline and 6 months post-RT. rs-fMRI data were assessed using seed-based functional connectivity (FC). NCF changes were quantified by the percent change in age-normalized composite scores from baseline (ΔNCFcomp). Connectivity regression analysis assessed the association between network FC changes and NCF changes, using a split-sample approach with a 26-patient training set and a 6-patient validation set, iterated 200 times. Permutation tests evaluated the significance of network selection. Results: Between September 2020 and December 2023, 43 patients were enrolled, with 32 completing both baseline and follow-up evaluations. The mean ΔNCFcomp was 2.9% (SD, 13.7%), with 38% experiencing a decline. Patients with IDH-mutant glioma had similar NCF changes compared with those with IDH–wild-type glioma. Intrahemispheric FC was similar between ipsilateral and contralateral hemispheres for 91% of patients at baseline, and 69% had similar intrahemispheric FC change posttreatment. FC changes accounted for a moderate fraction of variance in NCF changes (mean R2, 0.301;SD, 0.249), with intranetwork FC of the parietal memory network (PMN-PMN, P = .001) and internetwork FC between the PMN and the visual network (PMN-VN, P = .002) as the most significant factors. Similar findings were obtained by sensitivity analyses using only the FC data from the hemisphere contralateral to the tumor. Conclusions: Post-RT rs-fMRI changes significantly reflected NCF decline, highlighting rs-fMRI as a promising imaging biomarker for neuroco

关键词： Regression analysis

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A Clinical Dataset for the Evaluation of Motion Planners in medical Applications

arXiv

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arXiv 2022年

作者： Fried, Inbar Akulian, Jason A. Alterovitz, Ron The Department of Computer Science University of North Carolina at Chapel Hill Chapel HillNC27599 United States The Medical Scientist Training Program University of North Carolina School of Medicine Chapel HillNC27599 United States The Division of Pulmonary Diseases and Critical Care Medicine The University of North Carolina Chapel HillNC27599 United States

The prospect of using autonomous robots to enhance the capabilities of physicians and enable novel procedures has led to considerable efforts in developing medical robots and incorporating autonomous capabilities. Motion planning is a core component for any such system working in an environment that demands near perfect levels of safety, reliability, and precision. Despite the extensive and promising work that has gone into developing motion planners for medical robots, a standardized and clinically-meaningful way to compare existing algorithms and evaluate novel planners and robots is not well established. We present the medical Motion Planning Dataset (Med-MPD), a publicly-available dataset of real clinical scenarios in various organs for the purpose of evaluating motion planners for minimally-invasive medical robots. Our goal is that this dataset serve as a first step towards creating a larger robust medical motion planning benchmark framework, advance research into medical motion planners, and lift some of the burden of generating medical evaluation data. © 2022, CC BY-SA.

关键词： Motion planning

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Single-Cell RNA Sequencing Identifies Expression Patterns Associated with Clinical Responses to Dual-Targeted CAR-T Cell Therapy

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BLOOD 2020年 136卷 33-34页

作者： Kearl, Tyce Mei, Ao Brown, Ryan Johnson, Bryon Schneider, Dina Dropulic, Boro Hari, Parameswaran Shah, Nirav N. Malarkannan, Subramaniam Division of Hematology Oncology and Bone Marrow Transplantation Department of Pediatrics Medical College of Wisconsin Milwaukee WI Blood Research Institute Versiti Milwaukee WI Department of Microbiology and Immunology Medical College of Wisconsin Milwaukee WI Medical Scientist Training Program Medical College of Wisconsin Milwaukee WI Division of Hematology and Oncology Department of Medicine Medical College of Wisconsin Milwaukee WI Lentigen Technology Inc. a Miltenyi Biotec Company Gaithersburg MD

INTRODUCTION Chimeric Antigen Receptor (CAR)-T cell therapy is emerging as a powerful treatment for relapsed or refractory B cell lymphomas. However, a variety of escape mechanisms prevent CAR-T cell therapy from being more uniformly effective. To better understand mechanisms of CAR-T failure among patients treated with dual-targeted CAR-T cells, we performed single-cell RNA sequencing of samples from a Phase 1 trial (NCT03019055). The clinical trial used anti-CD20, anti-CD19 CAR-T cells for the treatment of relapsed/refractory B-cell non-Hodgkin Lymphoma. Clinical responses from this study are reported independently (Shah et al. in press in Nat Med ). While robust clinical responses occurred, not all patients had similar outcomes. In single-antigen specific CAR-T cells, mechanisms of resistance include antigen down-regulation, phenotype switch, or PD-1 inhibition (Song et al. Int J Mol Sci 2019). However, very little is understood about the mechanisms of failure that are specific to dual-targeted CAR-T cells. Interestingly, loss of CD19 antigen was not observed in treatment failures in the study. METHODS De-identified patient samples were obtained as peripheral blood mononuclear cells on the day of harvest (“pre” samples), at the peak of in vivo CAR-T cell expansion which varied from day 10 to day 21 after infusion (“peak” samples), and on day 28 post-infusion (“d28” samples). The CAR-T cell infusion product was obtained on day 14 of on-site manufacturing (“product” samples). All samples were cryopreserved and single cell preparation was performed with batched samples using 10X Genomics kits. Subsequent analysis was performed in R studio using the Seurat package (Butler et al. Nat Biotech 2018) with SingleR being used to identify cell types in an unbiased manner (Aran et al. Nat Immunol 2019). RESULTS We found that distinct T cell clusters were similarly represented in the responder and non-responder samples. The patients' clinical responses did not depend on the l

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Chronic femoral diaphyseal osteomyelitis with radiographs initially concerning for Paget disease of the bone

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Radiology Case Reports 2020年第4期15卷 344-348页

作者： Reasoner, Seth A. Colazo, Juan M. Tucci, Jonathan Cates, Justin Dahir, Kathryn M. Medical Scientist Training Program Vanderbilt University School of Medicine Nashville TN United States Department of Pathology Microbiology and Immunology Vanderbilt University Medical Center Nashville TN United States Endocrinology and Diabetes Vanderbilt University Medical Center 8210 Medical Center East 1215 21st Avenue South Nashville 37232-8148 TN United States

Chronic osteomyelitis can be difficult to diagnose given its similar radiographic appearance to other lesions. This case report describes a 48-year-old woman, who presented with left thigh pain and on radiography a large disorganized sclerotic lesion involving nearly the entire femoral diaphysis, concerning for Paget disease or malignancy. Biopsy suggested chronic osteomyelitis but did not identify a causative organism. Treatment with antibiotics led to resolution of pain and improvement of biochemical markers. This case exemplifies the role of radiographic imaging in the diagnosis of chronic osteomyelitis and the possible utility of antibiotics for culture-negative chronic osteomyelitis. We review imaging modalities for the diagnosis of chronic osteomyelitis and Paget disease. © 2020

关键词： Bone infection Chronic osteomyelitis Metabolic bone disease Paget disease of bone

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STIMULUS-INDEPENDENT ACTIVITY IN THE DEVELOPING BRAIN: A PERSPECTIVE FROM THE FLY

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IBRO neuroscience Reports 2023年 15卷 S45-S45页

作者： Sassan Suarez Jun Reichl Harpreet Randhawa Orkun Akin University California Los Angeles Neuroscience Interdepartmental Program Los Angeles United States of America David Geffen School of Medicine University California Los Angele Medical Scientist Training Program Los Angeles United States of America David Geffen School of Medicine University California Los Angeles Department Of Neurobiology Los Angeles United States of America

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