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  1. Book ; Online: Trainability, Expressivity and Interpretability in Gated Neural ODEs

    Kim, Timothy Doyeon / Can, Tankut / Krishnamurthy, Kamesh

    2023  

    Abstract: Understanding how the dynamics in biological and artificial neural networks implement the computations required for a task is a salient open question in machine learning and neuroscience. In particular, computations requiring complex memory storage and ... ...

    Abstract Understanding how the dynamics in biological and artificial neural networks implement the computations required for a task is a salient open question in machine learning and neuroscience. In particular, computations requiring complex memory storage and retrieval pose a significant challenge for these networks to implement or learn. Recently, a family of models described by neural ordinary differential equations (nODEs) has emerged as powerful dynamical neural network models capable of capturing complex dynamics. Here, we extend nODEs by endowing them with adaptive timescales using gating interactions. We refer to these as gated neural ODEs (gnODEs). Using a task that requires memory of continuous quantities, we demonstrate the inductive bias of the gnODEs to learn (approximate) continuous attractors. We further show how reduced-dimensional gnODEs retain their modeling power while greatly improving interpretability, even allowing explicit visualization of the structure of learned attractors. We introduce a novel measure of expressivity which probes the capacity of a neural network to generate complex trajectories. Using this measure, we explore how the phase-space dimension of the nODEs and the complexity of the function modeling the flow field contribute to expressivity. We see that a more complex function for modeling the flow field allows a lower-dimensional nODE to capture a given target dynamics. Finally, we demonstrate the benefit of gating in nODEs on several real-world tasks.
    Keywords Computer Science - Machine Learning ; Quantitative Biology - Neurons and Cognition
    Subject code 612
    Publishing date 2023-07-12
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Intradural cyst: intramedullary or extramedullary? Illustrative case.

    Kim, Timothy / Judy, Brendan / Witham, Timothy

    Journal of neurosurgery. Case lessons

    2021  Volume 2, Issue 3, Page(s) CASE21327

    Abstract: Background: Intradural spinal cord cysts are uncommon and generally benign. It can be difficult to determine whether the cyst is intramedullary or extramedullary on preoperative imaging, and the location of the cyst may be determined intraoperatively. ... ...

    Abstract Background: Intradural spinal cord cysts are uncommon and generally benign. It can be difficult to determine whether the cyst is intramedullary or extramedullary on preoperative imaging, and the location of the cyst may be determined intraoperatively. This patient presented with intractable back pain associated with imbalance and was found to have a cystic lesion of the ventriculus terminalis (VT).
    Observations: The patient was found to have a cystic lesion of the VT that was intramedullary rather than extramedullary, as initially expected based on preoperative imaging.
    Lessons: VT is a rare cystic expansion of the conus medullaris that can appear extramedullary on preoperative imaging. Intraoperatively, this lesion was found to be intramedullary and was successfully treated with fenestration.
    Language English
    Publishing date 2021-07-19
    Publishing country United States
    Document type Case Reports
    ISSN 2694-1902
    ISSN (online) 2694-1902
    DOI 10.3171/CASE21327
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Rhomboencephalosynapsis: Review of the Literature.

    Fouda, Mohammed A / Kim, Timothy Y / Cohen, Alan R

    World neurosurgery

    2021  Volume 159, Page(s) 48–53

    Abstract: Rhombencephalosynapsis is a rare congenital anomaly, characterized by partial or total agenesis of the cerebellar vermis with midline fusion of the cerebellar hemispheres, dentate nuclei, and the superior cerebellar peduncles, creating the distinctive ... ...

    Abstract Rhombencephalosynapsis is a rare congenital anomaly, characterized by partial or total agenesis of the cerebellar vermis with midline fusion of the cerebellar hemispheres, dentate nuclei, and the superior cerebellar peduncles, creating the distinctive keyhole appearance of the fourth ventricle. Rhombencephalosynapsis can be isolated or can occur in association with other congenital anomalies and syndromes such as Gómez-López-Hernández syndrome (GLHS) or VACTERL: vertebral anomalies (V), anal atresia (A), cardiovascular defects (C), esophageal atresia and/or tracheoesophageal fistula (TE), and renal (R) and limb/radial (L) anomalies. Recent advances in prenatal imaging have resulted in an increasing rate of prenatal diagnosis of abnormalities of the posterior fossa including rhombencephalosynapsis. Patients with rhombencephalosynapsis may present with motor developmental delay, ataxia, swallowing difficulties, muscular hypotonia, spastic quadriparesis, abnormal eye movements, and a characteristic "figure-of-eight" head shaking. Cognitive outcome varies from severe intellectual disability to normal intellectual function. Rhombencephalosynapsis with VACTERL is often associated with severe cognitive disabilities, whereas patients with GLHS may have better cognitive function. The most common associated findings with rhombencephalosynapsis include hydrocephalus, mesencephalosynapsis, holoprosencephaly, pontocerebellar hypoplasia, corpus callosum dysgenesis, and absence of septum pellucidum. Patients can be categorized into 4 groups: 1) rhombencephalosynapsis associated with GLHS; 2) rhombencephalosynapsis with VACTERL; 3) rhombencephalosynapsis with atypical holoprosencephaly, and 4) isolated rhomboencephalosynapsis. The etiology of rhombencephalosynapsis is unknown. Here, we discuss several hypotheses about its etiology.
    MeSH term(s) Abnormalities, Multiple/diagnosis ; Alopecia ; Cerebellum/abnormalities ; Craniofacial Abnormalities/diagnosis ; Female ; Growth Disorders ; Holoprosencephaly ; Humans ; Neurocutaneous Syndromes ; Pregnancy ; Rhombencephalon
    Language English
    Publishing date 2021-12-22
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2534351-8
    ISSN 1878-8769 ; 1878-8750
    ISSN (online) 1878-8769
    ISSN 1878-8750
    DOI 10.1016/j.wneu.2021.12.062
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Nuanced Management of a Skull Base Tumor in the Setting of Relapsed Acute Lymphoblastic Leukemia.

    Jung, Geena / Buckner-Wolfson, Emery / Tal, Adit / Fatemi, Ryan / Kim, Timothy / Liriano, Genesis / Kobets, Andrew

    Journal of neurological surgery reports

    2024  Volume 85, Issue 2, Page(s) e48–e52

    Abstract: ... ...

    Abstract Introduction
    Language English
    Publishing date 2024-04-30
    Publishing country Germany
    Document type Case Reports
    ZDB-ID 2653397-2
    ISSN 2193-6366 ; 2193-6358
    ISSN (online) 2193-6366
    ISSN 2193-6358
    DOI 10.1055/a-2297-4265
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Flow-field inference from neural data using deep recurrent networks.

    Kim, Timothy Doyeon / Luo, Thomas Zhihao / Can, Tankut / Krishnamurthy, Kamesh / Pillow, Jonathan W / Brody, Carlos D

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Computations involved in processes such as decision-making, working memory, and motor control are thought to emerge from the dynamics governing the collective activity of neurons in large populations. But the estimation of these dynamics remains a ... ...

    Abstract Computations involved in processes such as decision-making, working memory, and motor control are thought to emerge from the dynamics governing the collective activity of neurons in large populations. But the estimation of these dynamics remains a significant challenge. Here we introduce Flow-field Inference from Neural Data using deep Recurrent networks (FINDR), an unsupervised deep learning method that can infer low-dimensional nonlinear stochastic dynamics underlying neural population activity. Using population spike train data from frontal brain regions of rats performing an auditory decision-making task, we demonstrate that FINDR outperforms existing methods in capturing the heterogeneous responses of individual neurons. We further show that FINDR can discover interpretable low-dimensional dynamics when it is trained to disentangle task-relevant and irrelevant components of the neural population activity. Importantly, the low-dimensional nature of the learned dynamics allows for explicit visualization of flow fields and attractor structures. We suggest FINDR as a powerful method for revealing the low-dimensional task-relevant dynamics of neural populations and their associated computations.
    Language English
    Publishing date 2023-11-16
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.11.14.567136
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Emerging Technologies for Non-invasive Monitoring of Treatment Response to Immunotherapy for Brain Tumors.

    Mathios, Dimitrios / Srivastava, Siddhartha / Kim, Timothy / Bettegowda, Chetan / Lim, Michael

    Neuromolecular medicine

    2021  Volume 24, Issue 2, Page(s) 74–87

    Abstract: Glioblastoma is the most common primary malignant brain tumor and one of the most aggressive tumors across all cancer types with remarkable resistance to any treatment. While immunotherapy has shown a robust clinical benefit in systemic cancers, its ... ...

    Abstract Glioblastoma is the most common primary malignant brain tumor and one of the most aggressive tumors across all cancer types with remarkable resistance to any treatment. While immunotherapy has shown a robust clinical benefit in systemic cancers, its benefit is still under investigation in brain cancers. The broader use of immunotherapy in clinical trials for glioblastoma has highlighted the challenges of traditional methods of monitoring progression via imaging. Development of new guidelines, advanced imaging techniques, and immune profiling have emerged to counter premature diagnoses of progressive disease. However, these approaches do not provide a timely diagnosis and are costly and time consuming. Surgery is currently the standard of care for diagnosis of pseudoprogression in cases where MRI is equivocal. However, it is invasive, risky, and disruptive to patient's lives and their oncological treatment. With its increased vascularity, glioblastoma is continually shedding tumor components into the vasculature including tumor cells, genetic material, and extracellular vesicles. These elements can be isolated from routine blood draws and provide a real-time non-invasive indicator of tumor progression. Liquid biopsy therefore presents as an attractive alternative to current methods to guide treatment. While the initial evaluation of liquid biopsy for brain tumors via identification of mutations in the plasma was disappointing, novel technologies and use of alternatives to plasma cell-free DNA analytes provide promise for an effective liquid biopsy approach in brain tumors. This review aims to summarize developments in the use of liquid biopsy to monitor glioblastoma, especially in the context of immunotherapy.
    MeSH term(s) Biomarkers, Tumor/genetics ; Biomarkers, Tumor/therapeutic use ; Brain Neoplasms/drug therapy ; Glioblastoma/pathology ; Glioblastoma/therapy ; Humans ; Immunotherapy ; Liquid Biopsy/methods ; Magnetic Resonance Imaging
    Chemical Substances Biomarkers, Tumor
    Language English
    Publishing date 2021-07-23
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2077809-0
    ISSN 1559-1174 ; 1535-1084
    ISSN (online) 1559-1174
    ISSN 1535-1084
    DOI 10.1007/s12017-021-08677-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Transitions in dynamical regime and neural mode underlie perceptual decision-making.

    Luo, Thomas Zhihao / Kim, Timothy Doyeon / Gupta, Diksha / Bondy, Adrian G / Kopec, Charles D / Elliot, Verity A / DePasquale, Brian / Brody, Carlos D

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Perceptual decision-making is the process by which an animal uses sensory stimuli to choose an action or mental proposition. This process is thought to be mediated by neurons organized as attractor ... ...

    Abstract Perceptual decision-making is the process by which an animal uses sensory stimuli to choose an action or mental proposition. This process is thought to be mediated by neurons organized as attractor networks
    Language English
    Publishing date 2023-11-20
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.10.15.562427
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Case Report: Treatment of the rare B-cell lymphoblastic lymphoma with scalp lesion using rotation flap.

    Kim, Timothy / Jung, Geena / Buckner-Wolfson, Emery / Fatemi, Ryan / Liriano, Genesis / Tal, Adit / Wang, Yanhua / Tepper, Oren / Kobets, Andrew

    Frontiers in oncology

    2023  Volume 13, Page(s) 1252512

    Abstract: Introduction: Leukemia is the most frequently occurring cancer in children, and lymphoblastic lymphoma (LBL) is a rare subtype. LBL are lymphoid neoplasms of B or T cell origin and are primarily treated with chemotherapy. Although cure rates among ... ...

    Abstract Introduction: Leukemia is the most frequently occurring cancer in children, and lymphoblastic lymphoma (LBL) is a rare subtype. LBL are lymphoid neoplasms of B or T cell origin and are primarily treated with chemotherapy. Although cure rates among children are excellent, these patients must be monitored for relapse. Cutaneous lesions involving B-cell LBL (B-LBL) are extremely rare and here we present a patient with a worsening B-LBL scalp mass who required radical surgical excision.
    Case report: A 6-year-old female patient with a history of a nontender scalp mass discovered at approximately 2-3 years of age was evaluated for resection of the nodule due to its size and treatment history. The patient was originally diagnosed with follicular lymphoma by punch biopsy; excision was successfully performed on this 4 cm lesion and upon examination of the skin biopsy did we get a diagnosis of B-LBL. Reconstruction of the scalp was done through the rotation flap method. The patient's scalp healed well, and adjuvant chemotherapy was continued. There has been no reoccurrence.
    Discussion: Here we report the rarity of B-LBL cases involving extranodal involvement in the scalp. The most common reconstruction of scalp lesions has been using free flap from the anterolateral thigh (ALT) and latissimus dorsi (LD). Our case used the rotation flap, which has its functional and cosmetic benefits. The importance of monitoring this patient is emphasized due to the dangerous consequences of B-LBL relapse. Ultimately, our successful treatment and care of this rare case can be used as guidance for similar patients in the future.
    Language English
    Publishing date 2023-10-20
    Publishing country Switzerland
    Document type Case Reports
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2023.1252512
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Nuanced Management of a Skull Base Tumor in the Setting of Relapsed Acute Lymphoblastic Leukemia

    Jung, Geena / Buckner-Wolfson, Emery / Tal, Adit / Fatemi, Ryan / Kim, Timothy / Liriano, Genesis / Kobets, Andrew

    Journal of Neurological Surgery Reports

    2024  Volume 85, Issue 02, Page(s) e48–e52

    Abstract: Introduction: Relapsed acute lymphoblastic leukemia (ALL) involving the central nervous system (CNS) is a significant issue that contributes to both morbidity and mortality. Given the poor outcomes in patients with CNS relapse, understanding how ALL ... ...

    Abstract Introduction: Relapsed acute lymphoblastic leukemia (ALL) involving the central nervous system (CNS) is a significant issue that contributes to both morbidity and mortality. Given the poor outcomes in patients with CNS relapse, understanding how ALL involving intracranial relapse presents and is treated is critical. Here, we present a complex case of relapsed recurrent ALL in a pediatric patient.
    Case Report: An 11-year-old patient presented with double relapse of ALL in the form of an extensive skull base lesion and again with leptomeningeal disease. For the skull base lesion, she was treated nonsurgically with chemotherapy and radiation, which led to a remarkable reduction in the size of the lesion. However, she was found to have early recurrence with leptomeningeal enhancement resulting in hydrocephalus 5 months after completing therapy. A shunt was placed successfully. Currently, she is being managed with monthly intrathecal chemotherapy with cerebrospinal fluid sampling and bone marrow biopsies every 2 months.
    Discussion: We report the significant effect of chemotherapy and radiotherapy in reducing the size of the extensive skull base lesion, saving the patient from the risks associated with surgery. This patient's initial relapse, with a large skull base lesion that had intracranial involvement, is an unusual presentation of relapsed ALL. The additional early recurrence of leptomeningeal disease further makes this case unique and the management even more nuanced. Here, we demonstrate a multidisciplinary approach for the successful treatment of our patient, which can help guide the management of similar patients in the future.
    Keywords skull base tumor ; acute lymphocytic leukemia
    Language English
    Publishing date 2024-04-01
    Publisher Georg Thieme Verlag KG
    Publishing place Stuttgart ; New York
    Document type Article
    ZDB-ID 2653397-2
    ISSN 2193-6366 ; 2193-6358
    ISSN (online) 2193-6366
    ISSN 2193-6358
    DOI 10.1055/a-2297-4265
    Database Thieme publisher's database

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  10. Article: Oxidative Stress in the Tumor Microenvironment and Its Relevance to Cancer Immunotherapy.

    Aboelella, Nada S / Brandle, Caitlin / Kim, Timothy / Ding, Zhi-Chun / Zhou, Gang

    Cancers

    2021  Volume 13, Issue 5

    Abstract: It has been well-established that cancer cells are under constant oxidative stress, as reflected by elevated basal level of reactive oxygen species (ROS), due to increased metabolism driven by aberrant cell growth. Cancer cells can adapt to maintain ... ...

    Abstract It has been well-established that cancer cells are under constant oxidative stress, as reflected by elevated basal level of reactive oxygen species (ROS), due to increased metabolism driven by aberrant cell growth. Cancer cells can adapt to maintain redox homeostasis through a variety of mechanisms. The prevalent perception about ROS is that they are one of the key drivers promoting tumor initiation, progression, metastasis, and drug resistance. Based on this notion, numerous antioxidants that aim to mitigate tumor oxidative stress have been tested for cancer prevention or treatment, although the effectiveness of this strategy has yet to be established. In recent years, it has been increasingly appreciated that ROS have a complex, multifaceted role in the tumor microenvironment (TME), and that tumor redox can be targeted to amplify oxidative stress inside the tumor to cause tumor destruction. Accumulating evidence indicates that cancer immunotherapies can alter tumor redox to intensify tumor oxidative stress, resulting in ROS-dependent tumor rejection. Herein we review the recent progresses regarding the impact of ROS on cancer cells and various immune cells in the TME, and discuss the emerging ROS-modulating strategies that can be used in combination with cancer immunotherapies to achieve enhanced antitumor effects.
    Language English
    Publishing date 2021-02-27
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers13050986
    Database MEDical Literature Analysis and Retrieval System OnLINE

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