tbuckley/cabot-search huggingface dataset:
Generative Artificial Intelligence to Transform Inpatient Discharge Summaries to Patient-Friendly Language and Format
Authors: Jonah Zaretsky, Jeong Min Kim, Samuel Baskharoun, Yunan Zhao, Jonathan Austrian, Yindalon Aphinyanaphongs, Ravi Gupta, Saul B. Blecker, Jonah Feldman
Journal: JAMA Network Open (2024)

Importance By law, patients have immediate access to discharge notes in their medical records. Technical language and abbreviations make notes difficult to read and understand for a typical patient. Large language models (LLMs [eg, GPT-4]) have the potential to transform these notes into patient-friendly language and format. Objective To determine whether an LLM can transform discharge summaries into a format that is more readable and understandable. Design, Setting, and Participants This cross-sectional study evaluated a sample of the discharge summaries of adult patients discharged from the General Internal Medicine service at NYU (New York University) Langone Health from June 1 to 30, 2023. Patients discharged as deceased were excluded. All discharge summaries were processed by the LLM between July 26 and August 5, 2023. Interventions A secure Health Insurance Portability and Accountability Act–compliant platform, Microsoft Azure OpenAI, was used to transform these discharge summaries into a patient-friendly format between July 26 and August 5, 2023. Main Outcomes and Measures Outcomes included readability as measured by Flesch-Kincaid Grade Level and understandability using Patient Education Materials Assessment Tool (PEMAT) scores. Readability and understandability of the original discharge summaries were compared with the transformed, patient-friendly discharge summaries created through the LLM. As balancing metrics, accuracy and completeness of the patient-friendly version were measured. Results Discharge summaries of 50 patients (31 female [62.0%] and 19 male [38.0%]) were included. The median patient age was 65.5 (IQR, 59.0-77.5) years. Mean (SD) Flesch-Kincaid Grade Level was significantly lower in the patient-friendly discharge summaries (6.2 [0.5] vs 11.0 [1.5]; P &amp;amp;lt; .001). PEMAT understandability scores were significantly higher for patient-friendly discharge summaries (81% vs 13%; P &amp;amp;lt; .001). Two physicians reviewed each patient-friendly discharge summary for accuracy on a 6-point scale, with 54 of 100 reviews (54.0%) giving the best possible rating of 6. Summaries were rated entirely complete in 56 reviews (56.0%). Eighteen reviews noted safety concerns, mostly involving omissions, but also several inaccurate statements (termed hallucinations). Conclusions and Relevance The findings of this cross-sectional study of 50 discharge summaries suggest that LLMs can be used to translate discharge summaries into patient-friendly language and formats that are significantly more readable and understandable than discharge summaries as they appear in electronic health records. However, implementation will require improvements in accuracy, completeness, and safety. Given the safety concerns, initial implementation will require physician review.
Inconclusive Findings in Non-Vitamin K Antagonist Oral Anticoagulants Study—In Reply
Authors: Tou-Yuan Tsai, Yu-Chang Liu, Huei-Kai Huang
Journal: JAMA Internal Medicine (2024)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 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 Internal Medicine journal
Inconclusive Findings in Non-Vitamin K Antagonist Oral Anticoagulants Study
Authors: Faizan Khan, Ronda Lun, Michael D. Hill
Journal: JAMA Internal Medicine (2024)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 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 Internal Medicine journal
Programming Error and Incorrect Denominators in a Study of Low-Value Health Services
Authors: Thomas R. Radomski
Journal: JAMA Internal Medicine (2024)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 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 Internal Medicine journal
Clopidogrel Plus Aspirin vs Aspirin Alone in Patients With Acute Mild to Moderate Stroke
Authors: Hui-Sheng Chen, Yu Cui, Xin-Hong Wang, Yu-Tong Ma, Jing Han, Ying-Jie Duan, Jiang Lu, Li-Ying Shen, Yong Liang, Wei-Zhong Wang, Hui Wang, Yong Zhao, Jin-Tao Zhang, Yu-Lin Song, Xiao-Mei He, Run-Hui Li, Ding-Bo Tao, Jing Li, Shu-Man Huang, Ni Wang, Mei Hong, Chong Meng, Wei Zhang, Duo-Lao Wang, Thanh N. Nguyen, Shao-Yuan Chen, Li-Hong Zhao, Hong-Bo Xiao, Bing Han, Ying Hai, Zhong-Lian He, Li-Yang Zhang, Lian-Qiang Wang, Ping-Kang Pan, Dong-Qun Li, Yu-Tao Zhang, Dong-Yu Wang, Jing-Yu Li, Hong-Li Zhang, Xiao-Feng Qiu, Fu-Sheng Bai, Xu-Hai Gong, Jun Xu, Cheng-Guang Song, Zhi-Mei Yuan, Yan Du, Ping Zhang, Bao-Ying Sheng, Xiao-Hua Ju, Xin-Chen Zhu, Xiao-Hong Song, Ya-Jun Liu, Yan-Qin Guo, Hui-Ru Chen, Yong-Zhong Lin, Wei-Shu Xue, Zhao-Min Meng, Li-Yan Jiang, Qing-Hua Zhang, Hui-Min Liu, Zhong-Xin Xu, Chuan-Yu Liu, Ren-Lin Zou, Chun-Gang Zhao, Hui Li, Shuang-Yan Zhang, Zeng-Bao Wang, Ya-Fen Wei, Xue-Rong Qiu, Chang-Hao Jiang
Journal: JAMA Neurology (2024)

Dual antiplatelet therapy has been demonstrated to be superior to single antiplatelet in reducing recurrent stroke among patients with transient ischemic attack or minor stroke, but robust evidence for its effect in patients with mild to moderate ischemic stroke is lacking.
Clinical Decision Support for Hypertension Management in Chronic Kidney Disease
Authors: Lipika Samal, John L. Kilgallon, Stuart Lipsitz, Heather J. Baer, Allison McCoy, Michael Gannon, Sarah Noonan, Ryan Dunk, Sarah W. Chen, Weng Ian Chay, Richard Fay, Pamela M. Garabedian, Edward Wu, Matthew Wien, Saul Blecker, Hojjat Salmasian, Joseph V. Bonventre, Gearoid M. McMahon, David W. Bates, Sushrut S. Waikar, Jeffrey A. Linder, Adam Wright, Patricia Dykes
Journal: JAMA Internal Medicine (2024)

Chronic kidney disease (CKD) affects 37 million adults in the United States, and for patients with CKD, hypertension is a key risk factor for adverse outcomes, such as kidney failure, cardiovascular events, and death.
Mesoporous zinc oxide-based drug delivery system offers an antifungal and immunoregulatory strategy for treating keratitis
Authors: Lingwen Gu, Jing Lin, Qian Wang, Fanyue Meng, Geng Niu, Hao Lin, Menghui Chi, Zhuhui Feng, Hengrui Zheng, Daohao Li, Guiqiu Zhao, Cui Li
Journal: Journal of Controlled Release (2024)
Inconclusive Findings in Non-Vitamin K Antagonist Oral Anticoagulants Study
Authors: Ching-Fang Tiffany Tzeng, Ming-Jen Tsai
Journal: JAMA Internal Medicine (2024)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 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 Internal Medicine journal
Rate of Deceased Kidney Donation From Potential In-Hospital Deaths in the US, 2003-2021
Authors: Jennifer Bragg-Gresham, Ana Laura Licon, Jenna Kiryakos, Rajiv Saran, John P. Roberts
Journal: JAMA Network Open (2024)

This cross-sectional study calculates deceased kidney donation rates in the US using deaths compatible with donation as the metric’s denominator.
An accessible deep learning tool for voxel-wise classification of brain malignancies from perfusion MRI
Authors: Alonso Garcia-Ruiz, Albert Pons-Escoda, Francesco Grussu, Pablo Naval-Baudin, Camilo Monreal-Aguero, Gretchen Hermann, Roshan Karunamuni, Marta Ligero, Antonio Lopez-Rueda, Laura Oleaga, M. Álvaro Berbís, Alberto Cabrera-Zubizarreta, Teodoro Martin-Noguerol, Antonio Luna, Tyler M. Seibert, Carlos Majos, Raquel Perez-Lopez
Journal: Cell Reports Medicine (2024)

Noninvasive differential diagnosis of brain tumors is currently based on the assessment of magnetic resonance imaging (MRI) coupled with dynamic susceptibility contrast (DSC). However, a definitive diagnosis often requires neurosurgical interventions that compromise patients' quality of life. We apply deep learning on DSC images from histology-confirmed patients with glioblastoma, metastasis, or lymphoma. The convolutional neural network trained on ∼50,000 voxels from 40 patients provides intratumor probability maps that yield clinical-grade diagnosis. Performance is tested in 400 additional cases and an external validation cohort of 128 patients. The tool reaches a three-way accuracy of 0.78, superior to the conventional MRI metrics cerebral blood volume (0.55) and percentage of signal recovery (0.59), showing high value as a support diagnostic tool. Our open-access software, Diagnosis In Susceptibility Contrast Enhancing Regions for Neuro-oncology (DISCERN), demonstrates its potential in aiding medical decisions for brain tumor diagnosis using standard-of-care MRI.
Synthetic PET from CT improves diagnosis and prognosis for lung cancer: Proof of concept
Authors: Morteza Salehjahromi, Tatiana V. Karpinets, Sheeba J. Sujit, Mohamed Qayati, Pingjun Chen, Muhammad Aminu, Maliazurina B. Saad, Rukhmini Bandyopadhyay, Lingzhi Hong, Ajay Sheshadri, Julie Lin, Mara B. Antonoff, Boris Sepesi, Edwin J. Ostrin, Iakovos Toumazis, Peng Huang, Chao Cheng, Tina Cascone, Natalie I. Vokes, Carmen Behrens, Jeffrey H. Siewerdsen, John D. Hazle, Joe Y. Chang, Jianhua Zhang, Yang Lu, Myrna C.B. Godoy, Caroline Chung, David Jaffray, Ignacio Wistuba, J. Jack Lee, Ara A. Vaporciyan, Don L. Gibbons, Gregory Gladish, John V. Heymach, Carol C. Wu, Jianjun Zhang, Jia Wu
Journal: Cell Reports Medicine (2024)

[18F]Fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT) are indispensable components in modern medicine. Although PET can provide additional diagnostic value, it is costly and not universally accessible, particularly in low-income countries. To bridge this gap, we have developed a conditional generative adversarial network pipeline that can produce FDG-PET from diagnostic CT scans based on multi-center multi-modal lung cancer datasets (n = 1,478). Synthetic PET images are validated across imaging, biological, and clinical aspects. Radiologists confirm comparable imaging quality and tumor contrast between synthetic and actual PET scans. Radiogenomics analysis further proves that the dysregulated cancer hallmark pathways of synthetic PET are consistent with actual PET. We also demonstrate the clinical values of synthetic PET in improving lung cancer diagnosis, staging, risk prediction, and prognosis. Taken together, this proof-of-concept study testifies to the feasibility of applying deep learning to obtain high-fidelity PET translated from CT.
Pneumorrhachis With FDG Uptake Cervical Lesions on PET/CT of a Patient With Suspected Recurrent Hypopharyngeal Cancer
Authors: Yu-Erh Huang, Chih-Lin Chuang, Shang-Heng Wu, Yu-Ming Chang, Pan-Fu Kao
Journal: Clinical Nuclear Medicine (2024)

Abstract A 57-year-old man presented with odynophagia for 1 week was referred for FDG PET/CT scan to rule out recurrent hypopharyngeal cancer. The FDG PET/CT showed hypermetabolic lesions in hypopharyngeal area and adjacent cervical spine with pneumorrhachis, the presence of intraspinal air, on attenuation CT images, which might indicate a life-threatening infection. An emergency MRI confirmed the presence of cervical spondylodiscitis with an epidural abscess. The patient rapidly progressed to quadriplegia and difficulty voiding on the same day as the PET/CT scan, leading to emergent operation. The patient received antibiotics treatment and discharged 4 months later without evidence of cancer recurrence.
Different Ectopic Endocrine Tumors on Renal Hilum Detected by 68Ga-DOTATATE PET
Authors: Yuhu Lv, Xiaoli Lan, Chunxia Qin
Journal: Clinical Nuclear Medicine (2024)

Abstract Renal hilum is a very rare location for primary adrenocortical adenoma or pheochromocytoma. We report 68 Ga-DOTATATE PET/CT findings of primary renal hilar adrenocortical adenoma in one patient and 68 Ga-DOTATATE PET/MR findings of pheochromocytoma in another patient.
68Ga-DOTA–Ibandronic Acid PET/CT in a Patient With Chemotherapy-Induced Salivary Gland Hypofunction
Authors: Ya Liu, Haoyuan Ding, Ting Zhang, Yue Chen, Zhanwen Huang
Journal: Clinical Nuclear Medicine (2024)

Abstract DOTA–ibandronic acid (IBA) is a novel precursor targeting bone metastasis. It can be radiolabeled with 68 Ga for the diagnosis of bone metastases. However, extraosseous lesions can also show increased DOTA-IBA uptake. We report the 68 Ga-DOTA-IBA PET/CT findings in a case with cholangiocarcinoma with multiple bone metastases. 68 Ga-DOTA-IBA PET/CT revealed increased uptake of DOTA-IBA in bone metastases. Besides, symmetrical and diffuse increased DOTA-IBA uptake in bilateral salivary glands was observed. 99m TcO 4 − salivary gland scintigraphy showed impaired salivary gland function.
Label‐Free Single Microparticles and Cell Aggregates Sorting in Continuous Cell‐Based Manufacturing
Authors: Lingyan Gong, Linwei He, Nan Lu, Chayakorn Petchakup, King Ho Holden Li, Chor Yong Tay, Han Wei Hou
Journal: Advanced Healthcare Materials (2024)

There is a paradigm shift in biomanufacturing toward continuous bioprocessing but cell-based manufacturing using adherent and suspension cultures, including microcarriers, hydrogel microparticles, and 3D cell aggregates, remains challenging due to the lack of efficient in-line bioprocess monitoring and cell harvesting tools. Herein, a novel label-free microfluidic platform for high throughput (≈50 particles/sec) impedance bioanalysis of biomass, cell viability, and stem cell differentiation at single particle resolution is reported. The device is integrated with a real-time piezo-actuated particle sorter based on user-defined multi-frequency impedance signatures. Biomass profiling of Cytodex-3 microcarriers seeded with adipose-derived mesenchymal stem cells (ADSCs) is first performed to sort well-seeded or confluent microcarriers for downstream culture or harvesting, respectively. Next, impedance-based isolation of microcarriers with osteogenic differentiated ADSCs is demonstrated, which is validated with a twofold increase of calcium content in sorted ADSCs. Impedance profiling of heterogenous ADSCs-encapsulated hydrogel (alginate) microparticles and 3D ADSC aggregate mixtures is also performed to sort particles with high biomass and cell viability to improve cell quality. Overall, the scalable microfluidic platform technology enables in-line sample processing from bioreactors directly and automated analysis of cell quality attributes to maximize cell yield and improve the control of cell quality in continuous cell-based manufacturing.
Diffusion Kurtosis Imaging and Radiomics in Diffuse Axonal Injury
Authors: R. M. Afandiev, N. E. Zakharova, G. V. Danilov, E. L. Pogosbekyan, S. A. Goryaynov, Ya. A. Latyshev, A. V. Kosyr’kova, A. D. Kravchuk, D. Yu. Usachev, I. N. Pronin
Journal: Radiology - Practice (2024)

This study aimed to assess the feasibility of radiomic features derived from diﬀusion kurtosis imaging (DK MRI) in identifying microstructural brain damage in diﬀuse axonal injury (DAI) and predicting its outcome. We hypothesized that radiomic features, computed from parametric DK MRI maps, may diﬀer between healthy individuals and those with trauma, and may be related to DAI outcomes. The study included 31 DAI patients and 12 healthy volunteers. A total of 342,300 radiomic features were calculated (2282 features for each combination of 10 parametric DK maps with 15 regions of interest). Our ﬁndings suggest that the set of radiomic features eﬀectively distinguishes between healthy and damaged brain tissues, and can predict DAI outcome. A broad spectrum of radiomic parameters based on DK MRI data showed high diagnostic and prognostic potential in DAI, presenting advantages beyond the traditionally used average values for the regions of interest on parametric DK MRI maps.
Aneurysm Wall Contrast on Magnetic Resonance Imaging: A New Predictor of Rupture of Saccular Intracranial Aneurysms
Authors: K. S. Semin, N. E. Zakharova, Sh. Sh. Eliava, A. N. Konovalov, A. S. Kheireddin, D. B. Kalaeva, A. I. Batalov, I. N. Pronin
Journal: Radiology - Practice (2024)

Background. Recent studies suggest that accumulation of contrast agent in the aneurysm’s wall may predict a high risk of aneurysm growth or rupture. Objective. To compare the enhancement of the aneurysm wall with other characteristics that affect at the risk of rupture. Materials and Methods. The study included 95 patients with 132 previously identified saccular aneurysms, who underwent magnetic resonance imaging (MRI) according to a specialized protocol using 3.0 Tesla MRI scanner. The presence or absence of aneurysm’s wall enhancement compared with the following characteristics: gender and age of the patient, the size and shape of the aneurysm, the presence of arterial hypertension, and the PHASES score. Results. Accumulation of contrast agent by the aneurysm’s wall was associated with the aneurysm dome size (p &lt; 0,001, Sp = 78,1 %, Se = 72,1 %) and PHASES score (p &lt; 0,001, Sp = 64,1 %, Se =57,1 %). No relationship between age, gender, arterial hypertension, shape, and aneurysm location and contrast enhancement was found (p &gt; 0,05). Conclusion. Contrast enhancement of the aneurysm wall on MRI can be considered an additional risk marker of its rupture.
Atypical case of glioblastoma localization: infratentorial localization (Clinical Case and the Review of the Literature)
Authors: R. S. Talybov, T. N. Trofimova, V. I. Pavlova, I. V. Shvetsov, V. V. Mochalov, M. E. Martirosyan, A. A. Prishchepov
Journal: Radiology - Practice (2024)

Glioblastoma is the most common high-grade primary brain tumor, occurring primarily in adults. This inﬁltrating tumor locates deep in the white matter, subcortical structures and thalamus. The typical localization of glioblastoma is supratentorial, accounting for more than 99% of cases. Primary infratentorial growth of glioblastomas involving the cerebellum is a very rare condition, occurring in less than 1 % of cases reported in the literature. The diﬀerential diagnosis consists mainly of solitary metastatic lesions and medulloblastoma. The clinical manifestations of cerebellar lesions are similar, but the methods of surgical and chemoradiotherapy treatment, prognosis and outcome in cases with various histologic types of the tumors are diﬀerent. Thus radiology, carried out using multiparametric MRI mapping, is an decision making procedure. In thus publication we present an atypical case of infratentorial glioblastoma in a 45-yearold patient.
Enhancer–promoter interactions become more instructive in the transition from cell-fate specification to tissue differentiation
Authors: Tim Pollex, Adam Rabinowitz, Maria Cristina Gambetta, Raquel Marco-Ferreres, Rebecca R Viales, Aleksander Jankowski, Christoph Schaub, Eileen E M Furlong
Journal: Nature Genetics (2024)

Abstract To regulate expression, enhancers must come in proximity to their target gene. However, the relationship between the timing of enhancer–promoter (E–P) proximity and activity remains unclear, with examples of uncoupled, anticorrelated and correlated interactions. To assess this, we selected 600 characterized enhancers or promoters with tissue-specific activity in Drosophila embryos and performed Capture-C in FACS-purified myogenic or neurogenic cells during specification and tissue differentiation. This enabled direct comparison between E–P proximity and activity transitioning from OFF-to-ON and ON-to-OFF states across developmental conditions. This showed remarkably similar E–P topologies between specified muscle and neuronal cells, which are uncoupled from activity. During tissue differentiation, many new distal interactions emerge where changes in E–P proximity reflect changes in activity. The mode of E–P regulation therefore appears to change as embryogenesis proceeds, from largely permissive topologies during cell-fate specification to more instructive regulation during terminal tissue differentiation, when E–P proximity is coupled to activation.