Publications by authors named "Keith Murphy"

Introduction: Opioid use disorder (OUD) is a serious and persistent problem in the United States with limited non-pharmacological treatment options, especially for the concomitant sleep disorders experienced by most individuals with addiction. While new, non-invasive interventions such as low-intensity focused ultrasound (LIFU) have shown promise in targeting the brain regions impacted throughout addiction and recovery, the devices used are not amenable to outpatient treatment in their current form factor and cannot be used at night during sleep. To bridge this gap and provide a much-needed treatment option for repeated, at-home use, we developed a wearable LIFU device out-of-clinic use.

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Our understanding of brain circuit operations and disorders has rapidly outpaced our ability to intervene and restore them. Developing technologies that can precisely interface with any brain region and circuit may combine diagnostics with therapeutic intervention, expediting personalised brain medicine. Transcranial ultrasound stimulation (TUS) is a promising noninvasive solution to this challenge, offering focal precision and scalability.

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Article Synopsis
  • The brain uses a process called hippocampal neuronal plasticity to help us learn and remember things, which involves changes in how brain cells connect with each other.
  • A protein called midkine (Mdk) is important for the brain's development and memory, and when it's missing, some types of memory can be affected.
  • In experiments with rats, scientists found that learning activities caused Mdk levels to rise quickly and that adding more Mdk helped improve their memory in tests, showing that Mdk plays a helpful role in how we learn and remember.
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Focused ultrasound can non-invasively modulate neural activity, but whether effective stimulation parameters generalize across brain regions and cell types remains unknown. We used focused ultrasound coupled with fiber photometry to identify optimal neuromodulation parameters for four different arousal centers of the brain in an effort to yield overt changes in behavior. Applying coordinate descent, we found that optimal parameters for excitation or inhibition are highly distinct, the effects of which are generally conserved across brain regions and cell types.

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Sleep and feeding are vital homeostatic behaviors, and disruptions in either can result in substantial metabolic consequences. Distinct neuronal manipulations in can dissociate sleep loss from subsequent homeostatic rebound, offering an optimal platform to examine the precise interplay between these fundamental behaviors. Here, we investigate concomitant changes in sleep and food intake in individual animals, as well as respiratory metabolic expenditure, that accompany behavioral and genetic manipulations that induce sleep loss in .

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Rapid conversion of force into a biological signal enables living cells to respond to mechanical forces in their environment. The force is believed to initially affect the plasma membrane and then alter the behavior of membrane proteins. Phospholipase D2 (PLD2) is a mechanosensitive enzyme that is regulated by a structured membrane-lipid site comprised of cholesterol and saturated ganglioside (GM1).

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Nonalcoholic steatohepatitis (NASH) is an inflammatory and fibrotic liver disease that has reached epidemic proportions and has no approved pharmacologic therapies. Research and drug development efforts are hampered by inadequate preclinical models. This research describes a three-dimensional bioprinted liver tissue model of NASH built using primary human hepatocytes and nonparenchymal liver cells (hepatic stellate cells, liver sinusoidal endothelial cells, and Kupffer cells) from either healthy or NASH donors.

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Neuropeptide S (NPS) is a highly conserved peptide found in all tetrapods that functions in the brain to promote heightened arousal; however, the subpopulations mediating these phenomena remain unknown. We generated mice expressing Cre recombinase from the Nps gene locus (Nps) and examined populations of NPS+ neurons in the lateral parabrachial area (LPBA), the peri-locus coeruleus (peri-LC) region of the pons, and the dorsomedial thalamus (DMT). We performed brain-wide mapping of input and output regions of NPS+ clusters and characterized expression patterns of the NPS receptor 1 (NPSR1).

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Transcranial ultrasound neuromodulation is a promising potential therapeutic tool for the noninvasive treatment of neuropsychiatric disorders. However, the expansive parameter space and difficulties in controlling for peripheral auditory effects make it challenging to identify ultrasound sequences and brain targets that may provide therapeutic efficacy. Careful preclinical investigations in clinically relevant behavioral models are critically needed to identify suitable brain targets and acoustic parameters.

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Endotherms can survive low temperatures and food shortage by actively entering a hypometabolic state known as torpor. Although the decrease in metabolic rate and body temperature (Tb) during torpor is controlled by the brain, the specific neural circuits underlying these processes have not been comprehensively elucidated. In this study, we identify the neural circuits involved in torpor regulation by combining whole-brain mapping of torpor-activated neurons, cell-type-specific manipulation of neural activity, and viral tracing-based circuit mapping.

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Thoroughbred horses are bred for competitive racing and undergo intense training regimes. The maintenance of physical soundness and desirable behavioural characteristics are critical to the longevity of a racing career. Horses intended for Flat racing generally enter training as yearlings and undergo introductory training prior to exercise conditioning for racing.

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Behavioural plasticity enables horses entering an exercise training programme to adapt with reduced stress. We characterised SNPs associated with behaviour in yearling Thoroughbred horses using genomics analyses for two phenotypes: (1) handler-assessed coping with early training events [coping] (n = 96); and (2) variation in salivary cortisol concentration at the first backing event [cortisol] (n = 34). Using RNA-seq derived gene expression data for amygdala and hippocampus tissues from n = 2 Thoroughbred stallions, we refined the SNPs to those with functional relevance to behaviour by cross-referencing to the 500 most highly expressed genes in each tissue.

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Focused ultrasound (FUS) is a powerful tool for noninvasive modulation of deep brain activity with promising therapeutic potential for refractory epilepsy; however, tools for examining FUS effects on specific cell types within the deep brain do not yet exist. Consequently, how cell types within heterogeneous networks can be modulated and whether parameters can be identified to bias these networks in the context of complex behaviors remains unknown. To address this, we developed a fiber Photometry Coupled focused Ultrasound System (PhoCUS) for simultaneously monitoring FUS effects on neural activity of subcortical genetically targeted cell types in freely behaving animals.

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We determined baseline oral and cervicogenital human papillomavirus (HPV) prevalence and determinants of infection in the Michigan HPV and Oropharyngeal Cancer (MHOC) study. We enrolled 394 college-age and older participants of both sexes in Ann Arbor, Michigan and the surrounding area. All participants provided an oral sample at baseline, and 130 females provided a cervicogenital sample.

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Background: Minimally invasive surgery is gaining support for resection of gallbladder cancer (GBC). This study aims to compare operative and early outcomes of robotic resection (RR) to open resection (OR) from a single institution performing a high volume of robotic HPB surgery.

Methods: Twenty patients with GBC underwent RR from January 2013 to August 2019.

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Mathematical models are powerful tools to study COVID-19. However, one fundamental challenge in current modeling approaches is the lack of accurate and comprehensive data. Complex epidemiological systems such as COVID-19 are especially challenging to the commonly used mechanistic model when our understanding of this pandemic rapidly refreshes.

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Neurofibromatosis type 1 is a chronic multisystemic genetic disorder that results from loss of function in the neurofibromin protein. Neurofibromin may regulate metabolism, though the underlying mechanisms remain largely unknown. Here we show that neurofibromin regulates metabolic homeostasis in Drosophila via a discrete neuronal circuit.

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Importance: Image-based deep learning models (DLMs) have been used in other disciplines, but this method has yet to be used to predict surgical outcomes.

Objective: To apply image-based deep learning to predict complexity, defined as need for component separation, and pulmonary and wound complications after abdominal wall reconstruction (AWR).

Design, Setting, And Participants: This quality improvement study was performed at an 874-bed hospital and tertiary hernia referral center from September 2019 to January 2020.

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Background: Neoadjuvant therapy may improve survival of patients with pancreatic adenocarcinoma; however, determining response to therapy is difficult. Artificial intelligence allows for novel analysis of images. We hypothesized that a deep learning model can predict tumor response to NAC.

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Operative microwave ablation (MWA) is a safe modality for treating hepatic tumors. The aim of this study is to present our 10-year, single-center experience of operative MWA for neuroendocrine liver metastases (NLM). A single-institution retrospective review of patients who underwent operative MWA for NLM was performed (2008-2018).

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Background: Society consensus guidelines are commonly used to guide management of pancreatic cystic neoplasms (PCNs). However, downsides of these guidelines include unnecessary surgery and missed malignancy. The aim of this study was to use computed tomography (CT)-guided deep learning techniques to predict malignancy of PCNs.

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Background: Ruptured, or bleeding, hepatocellular carcinoma (rHCC) is a relatively rare disease presentation associated with high acute mortality rates. This study sought to evaluate outcomes following laparoscopic microwave ablation (MWA) and washout in rHCC.

Methods: A retrospective single-center review was performed to identify patients with rHCC (2008-2018).

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Background: Resection with trisectionectomy may necessitate liver molding for adequate future liver remnant (FLR), and subsequent complications can impact return to intended oncologic therapy (RIOT). This study evaluated whether a difference in RIOT exists with the use of molding and between liver molding techniques (associating liver partition and portal vein ligation for staged hepatectomy [ALPPS] and portal vein embolization [PVE]) with trisectionectomy.

Methods: A retrospective review evaluated trisectionectomies for malignancy.

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