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1.
J Neurooncol ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38958849

ABSTRACT

PURPOSE: Artificial Intelligence (AI) has become increasingly integrated clinically within neurosurgical oncology. This report reviews the cutting-edge technologies impacting tumor treatment and outcomes. METHODS: A rigorous literature search was performed with the aid of a research librarian to identify key articles referencing AI and related topics (machine learning (ML), computer vision (CV), augmented reality (AR), virtual reality (VR), etc.) for neurosurgical care of brain or spinal tumors. RESULTS: Treatment of central nervous system (CNS) tumors is being improved through advances across AI-such as AL, CV, and AR/VR. AI aided diagnostic and prognostication tools can influence pre-operative patient experience, while automated tumor segmentation and total resection predictions aid surgical planning. Novel intra-operative tools can rapidly provide histopathologic tumor classification to streamline treatment strategies. Post-operative video analysis, paired with rich surgical simulations, can enhance training feedback and regimens. CONCLUSION: While limited generalizability, bias, and patient data security are current concerns, the advent of federated learning, along with growing data consortiums, provides an avenue for increasingly safe, powerful, and effective AI platforms in the future.

2.
Nat Commun ; 15(1): 4945, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38858386

ABSTRACT

Single administration of low-dose ketamine has both acute and sustained anti-depressant effects. Sustained effect is associated with restoration of glutamatergic synapses in medial prefrontal cortic (mFPC) neurons. Ketamine induced profound changes in a number of molecular pathways in a mouse model for chronic stress. Cell-cell communication analyses predicted that planar-cell-polarity (PCP) signaling was decreased after chronic administration of corticosterone but increased following ketamine administration in most of the excitatory neurons. Similar decrease of PCP signaling in excitatory neurons was predicted in dorsolateral prefrontal cortical (dl-PFC) neurons of patients with major depressive disorder (MDD). We showed that the basolateral amygdala (BLA)-projecting infralimbic prefrontal cortex (IL PFC) neurons regulate immobility time in the tail suspension test and food consumption. Conditionally knocking out Celsr2 and Celsr3 or Prickle2 in the BLA-projecting IL PFC neurons abolished ketamine-induced synapse restoration and behavioral remission. Therefore, PCP proteins in IL PFC-BLA neurons mediate synapse restoration induced by of low-dose ketamine.


Subject(s)
Disease Models, Animal , Ketamine , Neurons , Prefrontal Cortex , Synapses , Animals , Ketamine/pharmacology , Prefrontal Cortex/metabolism , Prefrontal Cortex/drug effects , Synapses/drug effects , Synapses/metabolism , Neurons/metabolism , Neurons/drug effects , Mice , Male , Humans , Cell Polarity/drug effects , Depressive Disorder, Major/metabolism , Depressive Disorder, Major/drug therapy , Mice, Knockout , Stress, Psychological , Corticosterone , Basolateral Nuclear Complex/metabolism , Basolateral Nuclear Complex/drug effects , Mice, Inbred C57BL , LIM Domain Proteins/metabolism , LIM Domain Proteins/genetics , Glutamic Acid/metabolism , Antidepressive Agents/pharmacology
3.
Front Immunol ; 15: 1368572, 2024.
Article in English | MEDLINE | ID: mdl-38698852

ABSTRACT

Introduction: Interferon-gamma (IFN-γ) is pivotal in orchestrating immune responses during healthy pregnancy. However, its dysregulation, often due to autoimmunity, infections, or chronic inflammatory conditions, is implicated in adverse reproductive outcomes such as pregnancy failure or infertility. Additionally, the underlying immunological mechanisms remain elusive. Methods: Here, we explore the impact of systemic IFN-γ elevation on cytotoxic T cell responses in female reproduction utilizing a systemic lupus-prone mouse model with impaired IFN-γ degradation. Results: Our findings reveal that heightened IFN-γ levels triggered the infiltration of CD8+T cells in the pituitary gland and female reproductive tract (FRT), resulting in prolactin deficiency and subsequent infertility. Furthermore, we demonstrate that chronic IFN-γ elevation increases effector memory CD8+T cells in the murine ovary and uterus. Discussion: These insights broaden our understanding of the role of elevated IFN-γ in female reproductive dysfunction and suggest CD8+T cells as potential immunotherapeutic targets in female reproductive disorders associated with chronic systemic IFN-γ elevation.


Subject(s)
CD8-Positive T-Lymphocytes , Interferon-gamma , Animals , Female , Mice , Pregnancy , CD8-Positive T-Lymphocytes/immunology , Disease Models, Animal , Infertility, Female/immunology , Interferon-gamma/metabolism , Lupus Erythematosus, Systemic/immunology , Mice, Inbred C57BL , Ovary/immunology , Pituitary Gland/immunology , Pituitary Gland/metabolism , Prolactin/metabolism , Uterus/immunology
4.
Public Policy Aging Rep ; 33(4): 113-119, 2023.
Article in English | MEDLINE | ID: mdl-38155935
5.
Exp Neurol ; 347: 113880, 2022 01.
Article in English | MEDLINE | ID: mdl-34597683

ABSTRACT

Epilepsy and autism spectrum disorders (ASD) frequently show comorbidity, suggesting shared or overlapping neurobiological basis underlying these conditions. R104Q is the first mutation in the PRICKLE 1(PK1) gene that was discovered in human patients with progressive myoclonus epilepsy (PME). Subsequently, a number of mutations in the PK1 gene were shown to be associated with either epilepsy, autism, or both, as well as other developmental disorders. Using CRISPR-Cas9-mediated gene editing, we generated a PK1R104Q mouse line. The mutant mice showed reduced density of excitatory synapses in hippocampus and impaired interaction between PK1 and the repressor element 1(RE-1) silencing transcription factor (REST). They also displayed reduced seizure threshold, impaired social interaction, and cognitive functions. Taken together, the PK1R104Q mice display characteristic behavioral features similar to the key symptoms of epilepsy and ASD, providing a useful model for studying the molecular and neural circuit mechanisms underlying the comorbidity of epilepsy and ASD.


Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Autism Spectrum Disorder/genetics , Disease Models, Animal , Epilepsy/genetics , LIM Domain Proteins/genetics , Animals , Gene Editing , Humans , Mice , Mutation , Phenotype
6.
Sci Adv ; 7(41): eabh2974, 2021 Oct 08.
Article in English | MEDLINE | ID: mdl-34613779

ABSTRACT

Whether there exists a common signaling mechanism that assembles all glutamatergic synapses is unknown. We show here that knocking out Prickle1 and Prickle2 reduced the formation of the PSD-95­positive glutamatergic synapses in the hippocampus and medial prefrontal cortex in postnatal development by 70­80%. Prickle1 and Prickle2 double knockout in adulthood lead to the disassembly of 70 to 80% of the postsynaptic-density(PSD)-95­positive glutamatergic synapses. PSD-95­positive glutamatergic synapses in the hippocampus of Prickle2E8Q/E8Q mice were reduced by 50% at postnatal day 14. Prickle2 promotes synapse formation by antagonizing Vangl2 and stabilizing the intercellular complex of the planar cell polarity (PCP) components, whereas Prickle2 E8Q fails to do so. Coculture experiments show that the asymmetric PCP complexes can determine the presynaptic and postsynaptic polarity. In summary, the PCP components regulate the assembly and maintenance of a large number of glutamatergic synapses and specify the direction of synaptic transmission.

7.
J Med Humanit ; 38(4): 445-457, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28589308

ABSTRACT

Qualitative and quantitative research on the impact of medical and health humanities teaching in baccalaureate education is sparse. This paper reviews recent studies of the impact of medical and health humanities coursework in pre-health professions education and describes a pilot study of baccalaureate students who completed semester-long medical humanities courses in the Division of Medical Humanities & Bioethics at the University of Rochester. The study format was an email survey. All participants were current or former baccalaureate students who had taken one or more courses in literature and narrative in medicine, bioethics, history of medicine, and/or visual arts and healthcare during the past four years. The survey gathered numerical data in several areas: demographic information, career plans, self-reported influence of coursework on educational and career plans, and self-reported influence of coursework on intellectual skills and abilities. It also gathered narrative commentary that elaborated on students' responses to the numerically-based questions. Notable findings from preliminary analysis of the data include higher scores of self-reported impact of the coursework on specific habits of mind and on preparedness for intended career rather than on gaining admission to future educational programs. Discussion of the results focuses on several potential future directions this type of study might take, including multi-center, longitudinal, and sequential approaches.


Subject(s)
Education, Medical, Undergraduate , Humanities/education , Students, Medical , Adolescent , Adult , Career Choice , Curriculum , Female , Humans , Job Application , Male , Pilot Projects , Surveys and Questionnaires , Young Adult
8.
IEEE Trans Biomed Eng ; 63(8): 1687-98, 2016 08.
Article in English | MEDLINE | ID: mdl-26560865

ABSTRACT

Surface electromyography (sEMG) has been the predominant method for sensing electrical activity for a number of applications involving muscle-computer interfaces, including myoelectric control of prostheses and rehabilitation robots. Ultrasound imaging for sensing mechanical deformation of functional muscle compartments can overcome several limitations of sEMG, including the inability to differentiate between deep contiguous muscle compartments, low signal-to-noise ratio, and lack of a robust graded signal. The objective of this study was to evaluate the feasibility of real-time graded control using a computationally efficient method to differentiate between complex hand motions based on ultrasound imaging of forearm muscles. Dynamic ultrasound images of the forearm muscles were obtained from six able-bodied volunteers and analyzed to map muscle activity based on the deformation of the contracting muscles during different hand motions. Each participant performed 15 different hand motions, including digit flexion, different grips (i.e., power grasp and pinch grip), and grips in combination with wrist pronation. During the training phase, we generated a database of activity patterns corresponding to different hand motions for each participant. During the testing phase, novel activity patterns were classified using a nearest neighbor classification algorithm based on that database. The average classification accuracy was 91%. Real-time image-based control of a virtual hand showed an average classification accuracy of 92%. Our results demonstrate the feasibility of using ultrasound imaging as a robust muscle-computer interface. Potential clinical applications include control of multiarticulated prosthetic hands, stroke rehabilitation, and fundamental investigations of motor control and biomechanics.


Subject(s)
Forearm/physiology , Hand/physiology , Image Processing, Computer-Assisted/methods , Muscle, Skeletal/physiology , Ultrasonography/methods , Algorithms , Female , Hand Strength/physiology , Humans , Male , Movement/physiology
9.
Annu Int Conf IEEE Eng Med Biol Soc ; 2016: 3219-3222, 2016 Aug.
Article in English | MEDLINE | ID: mdl-28268993

ABSTRACT

Advancements in multiarticulate upper-limb prosthetics have outpaced the development of intuitive, non-invasive control mechanisms for implementing them. Surface electromyography is currently the most popular non-invasive control method, but presents a number of drawbacks including poor deep-muscle specificity. Previous research established the viability of ultrasound imaging as an alternative means of decoding movement intent, and demonstrated the ability to distinguish between complex grasps in able-bodied subjects via imaging of the anterior forearm musculature. In order to translate this work to clinical viability, able-bodied testing is insufficient. Amputation-induced changes in muscular geometry, dynamics, and imaging characteristics are all likely to influence the effectiveness of our existing techniques. In this work, we conducted preliminary trials with a transradial amputee participant to assess these effects, and potentially elucidate necessary refinements to our approach. Two trials were performed, the first using a set of three motion types, and the second using four. After a brief training period in each trial, the participant was able to control a virtual prosthetic hand in real-time; attempted grasps were successfully classified with a rate of 77% in trial 1, and 71% in trial 2. While the results are sub-optimal compared to our previous able-bodied testing, they are a promising step forward. More importantly, the data collected during these trials can provide valuable information for refining our image processing methods, especially via comparison to previously acquired data from able-bodied individuals. Ultimately, further work with amputees is a necessity for translation towards clinical application.


Subject(s)
Amputees , Artificial Limbs , Computer Systems , Ultrasonography/methods , Electromyography , Humans , Image Processing, Computer-Assisted , Movement
12.
JAMA ; 305(11): 1095-6; author reply 1096, 2011 Mar 16.
Article in English | MEDLINE | ID: mdl-21406643
15.
J Gen Intern Med ; 25(9): 991-2, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20446050

ABSTRACT

In this short story, through a challenging case where his sound diagnostic work has seemingly gone unrecognized, an internist is reminded of what is most important in clinical care.


Subject(s)
Anecdotes as Topic , Epidural Abscess/diagnosis , Job Satisfaction , Primary Health Care , Humans , Physician-Patient Relations
16.
N Engl J Med ; 356(9): 966; author reply 966, 2007 Mar 01.
Article in English | MEDLINE | ID: mdl-17329712
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