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Article: "Timing of percutaneous endoscopic gastrostomy tube placement in post-stroke patients does not impact mortality, complications, or outcomes": Commentary.

Willman, Jonathan / Lucke-Wold, Brandon

World journal of gastrointestinal pharmacology and therapeutics

2023 Volume 14, Issue 1, Page(s) 1–3

Abstract: In this commentary, we summarize some of the key points of the original paper "Timing of percutaneous endoscopic gastrostomy tube placement in post-stroke patients does not impact mortality, complications, or outcomes" and offer support for the proposed ... ...

Abstract	In this commentary, we summarize some of the key points of the original paper "Timing of percutaneous endoscopic gastrostomy tube placement in post-stroke patients does not impact mortality, complications, or outcomes" and offer support for the proposed results. Specifically, we address how early percutaneous endoscopic gastrostomy (PEG) tube placement may reduce hospital length of stay and costs. We also discuss topics related to the article including PEG weaning and post-stroke nutritional formulation. However, we note that concerns purported by previous studies that early PEG placement may worsen outcomes are not fully addressed, and further research is needed.
Language	English
Publishing date	2023-01-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	2583480-0
ISSN	2150-5349
ISSN	2150-5349
DOI	10.4292/wjgpt.v14.i1.1
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Article ; Online: Commentary: "Inflammation and the role of infection: Complications and treatment options following neurotrauma".

Willman, Jonathan / Lucke-Wold, Brandon

Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia

2023 Volume 113, Page(s) 147–148

MeSH term(s)	Humans ; Brain Injuries, Traumatic/complications ; Brain Injuries, Traumatic/therapy ; Inflammation
Language	English
Publishing date	2023-01-19
Publishing country	Scotland
Document type	Letter ; Comment
ZDB-ID	1193674-5
ISSN	1532-2653 ; 0967-5868
ISSN (online)	1532-2653
ISSN	0967-5868
DOI	10.1016/j.jocn.2023.01.005
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Zs.A 3999: Show issues

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Article ; Online: Endocrine resistant breast cancer: brain metastasis.

Willman, Matthew / Willman, Jonathan / Lucke-Wold, Brandon

Exploration of targeted anti-tumor therapy

2022 Volume 3, Issue 2, Page(s) 240–251

Abstract: Endocrine resistant breast cancer metastasis continues to serve as a significant clinical challenge with high morbidity and mortality for patients. As the number of breast cancer cases continues to rise, the rate of brain metastasis has also increased. ... ...

Abstract	Endocrine resistant breast cancer metastasis continues to serve as a significant clinical challenge with high morbidity and mortality for patients. As the number of breast cancer cases continues to rise, the rate of brain metastasis has also increased. For single lesions or a large symptomatic lesion with other smaller lesions, surgical resection is a viable option in non-eloquent regions. Stereotactic radiosurgery is a great option for post-operative therapy or for 10 or fewer small lesions (< 3 cm in size). Whole-brain radiation can be used sparingly for large tumor burdens but should encompass hippocampus sparing techniques. Chemotherapy options have remained relatively limited due to decreased permeability of the blood-brain barrier. Emerging monoclonal antibody treatments have offered initial promise, especially for endocrine resistant breast cancer metastasis.
Language	English
Publishing date	2022-04-26
Publishing country	United States
Document type	Journal Article
ISSN	2692-3114
ISSN (online)	2692-3114
DOI	10.37349/etat.2022.00081
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Article: Secondary Mechanisms of Neurotrauma: A Closer Look at the Evidence.

Aghili-Mehrizi, Sina / Williams, Eric / Yan, Sandra / Willman, Matthew / Willman, Jonathan / Lucke-Wold, Brandon

Diseases (Basel, Switzerland)

2022 Volume 10, Issue 2

Abstract: Traumatic central nervous system injury is a leading cause of neurological injury worldwide. While initial neuroresuscitative efforts are focused on ameliorating the effects of primary injury through patient stabilization, secondary injury in neurotrauma ...

Abstract	Traumatic central nervous system injury is a leading cause of neurological injury worldwide. While initial neuroresuscitative efforts are focused on ameliorating the effects of primary injury through patient stabilization, secondary injury in neurotrauma is a potential cause of cell death, oxidative stress, and neuroinflammation. These secondary injuries lack defined therapy. The major causes of secondary injury in neurotrauma include endoplasmic reticular stress, mitochondrial dysfunction, and the buildup of reactive oxygen or nitrogenous species. Stress to the endoplasmic reticulum in neurotrauma results in the overactivation of the unfolded protein response with subsequent cell apoptosis. Mitochondrial dysfunction can lead to the release of caspases and the buildup of reactive oxygen species; several characteristics make the central nervous system particularly susceptible to oxidative damage. Together, endoplasmic reticulum, mitochondrial, and oxidative stress can have detrimental consequences, beginning moments and lasting days to months after the primary injury. Understanding these causative pathways has led to the proposal of various potential treatment options.
Language	English
Publishing date	2022-05-23
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720869-2
ISSN	2079-9721
ISSN	2079-9721
DOI	10.3390/diseases10020030
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Article ; Online: Neutrophil to Lymphocyte Ratio and Periprosthetic Joint Infection: A Systematic Review and Meta-Analysis.

Salimi, Maryam / Karam, Joseph Albert / Willman, Matthew / Willman, Jonathan / Lucke-Wold, Brandon / Khanzadeh, Shokoufeh / Mirghaderi, Peyman / Parvizi, Javad

The Journal of arthroplasty

2023 Volume 39, Issue 3, Page(s) 831–838

Abstract: Background: The neutrophil-to-lymphocyte ratio (NLR) has shown promising results as a diagnostic tool for periprosthetic joint infection (PJI) after total joint arthroplasty. We conducted a systematic review and meta-analysis to determine the utility of ...

Abstract	Background: The neutrophil-to-lymphocyte ratio (NLR) has shown promising results as a diagnostic tool for periprosthetic joint infection (PJI) after total joint arthroplasty. We conducted a systematic review and meta-analysis to determine the utility of NLR in the diagnosis of PJI. Methods: We searched PubMed, Scopus, and Web of Science from inception up to 2022 and evaluated the quality of the included literature. Results: Based on the 12 eligible studies, NLR levels were significantly higher in patients who had PJI compared to those who had aseptic loosening (standard mean difference (SMD) = 1.05, 95% Confidence Interval (CI) = 0.71 to 1.40, P < .001). In the subgroup analysis according to type of PJI, NLR levels were significantly higher in patients who had either acute (SMD = 1.04, 95% CI = 0.05 to 2.03, P < .001) or chronic PJI (SMD = 1.08, 95% CI = 0.55 to 1.61, P < .001), compared to those who had aseptic loosening. According to type of arthroplasty, NLR levels were significantly higher in patients who had either total knee arthroplasty (SMD = 1.81, 95% CI = 1.48 to 2.13, P < .001) or total hip arthroplasty (SMD = 1.76, 95% CI = 1.54 to 1.98, P < .001) compared to aseptic loosening. The pooled sensitivity of the 12 studies was 0.73 (95% CI, 0.65 to 0.79), and the pooled specificity was 0.75 (95% CI, 0.71 to 0.78). The pooled positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of NLR were 2.94 (95% CI = 2.44 to 3.54), 0.35 (95% CI = 0.27 to 0.46), and 8.26 (95% CI = 5.42 to 12.58), respectively. Conclusion: In summary, this meta-analysis indicates that NLR is a reliable marker in the diagnosis of PJI.
MeSH term(s)	Humans ; Prosthesis-Related Infections/diagnosis ; Neutrophils ; Arthroplasty, Replacement, Knee/adverse effects ; Arthroplasty, Replacement, Hip/adverse effects ; Arthritis, Infectious/diagnosis ; Biomarkers/analysis ; Sensitivity and Specificity
Chemical Substances	Biomarkers
Language	English
Publishing date	2023-08-24
Publishing country	United States
Document type	Meta-Analysis ; Systematic Review ; Journal Article
ZDB-ID	632770-9
ISSN	1532-8406 ; 0883-5403
ISSN (online)	1532-8406
ISSN	0883-5403
DOI	10.1016/j.arth.2023.08.067
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Article ; Online: Extreme Metastability of Diamond and its Transformation to the BC8 Post-Diamond Phase of Carbon.

Nguyen-Cong, Kien / Willman, Jonathan T / Gonzalez, Joseph M / Williams, Ashley S / Belonoshko, Anatoly B / Moore, Stan G / Thompson, Aidan P / Wood, Mitchell A / Eggert, Jon H / Millot, Marius / Zepeda-Ruiz, Luis A / Oleynik, Ivan I

The journal of physical chemistry letters

2024 Volume 15, Issue 4, Page(s) 1152–1160

Abstract: Diamond possesses exceptional physical properties due to its remarkably strong carbon-carbon bonding, leading to significant resilience to structural transformations at very high pressures and temperatures. Despite several experimental attempts, ... ...

Abstract	Diamond possesses exceptional physical properties due to its remarkably strong carbon-carbon bonding, leading to significant resilience to structural transformations at very high pressures and temperatures. Despite several experimental attempts, synthesis and recovery of the theoretically predicted post-diamond BC8 phase remains elusive. Through quantum-accurate multimillion atom molecular dynamics (MD) simulations, we have uncovered the extreme metastability of diamond at very high pressures, significantly exceeding its range of thermodynamic stability. We predict the post-diamond BC8 phase to be experimentally accessible only within a narrow high pressure-temperature region of the carbon phase diagram. The diamond to BC8 transformation proceeds through premelting followed by BC8 nucleation and growth in the metastable carbon liquid. We propose a double-shock compression pathway for BC8 synthesis, which is currently being explored in experiments at the National Ignition Facility.
Language	English
Publishing date	2024-01-25
Publishing country	United States
Document type	Journal Article
ISSN	1948-7185
ISSN (online)	1948-7185
DOI	10.1021/acs.jpclett.3c03044
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Article ; Online: Prognostic Role of Neutrophil to Lymphocyte Ratio in Contrast-Induced Nephropathy: A Systematic Review and Meta-analysis.

He, Tao / Mohammadpour, Behnood / Willman, Matthew / Yaghoobpoor, Shirin / Willman, Jonathan / Lucke-Wold, Brandon / Aminizadeh, Sarina / Khanzadeh, Shokoufeh / Bazrgar, Aida / Ghaedi, Arshin

Angiology

2024 , Page(s) 33197241238512

Abstract: This meta-analysis assessed the use of the neutrophil-to-lymphocyte ratio (NLR) as a means of early detection of contrast-induced nephropathy (CIN) following diagnostic or therapeutic procedures. We used Web of Science, PubMed, and Scopus to conduct a ... ...

Abstract	This meta-analysis assessed the use of the neutrophil-to-lymphocyte ratio (NLR) as a means of early detection of contrast-induced nephropathy (CIN) following diagnostic or therapeutic procedures. We used Web of Science, PubMed, and Scopus to conduct a systematic search. There was no limitation regarding language or date of publication. We reported standardized mean difference (SMD) with a 95% confidence interval (CI). Due to high heterogeneity, a random-effects model was used, and the Newcastle-Ottawa scale was used for quality assessment. Thirty-one articles were included in the analysis. Patients in the CIN group had elevated levels of NLR compared with those in the non-CIN group (SMD = 0.78, 95% CI = 0.52-1.04,
Language	English
Publishing date	2024-03-15
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	80040-5
ISSN	1940-1574 ; 0003-3197
ISSN (online)	1940-1574
ISSN	0003-3197
DOI	10.1177/00033197241238512
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Book ; Online: Extreme Metastability of Diamond and its Transformation to BC8 Post-Diamond Phase of Carbon

Nguyen-Cong, Kien / Willman, Jonathan T. / Gonzalez, Joseph M. / Williams, Ashley S. / Belonoshko, Anatoly B. / Moore, Stan G. / Thompson, Aidan P. / Wood, Mitchell A. / Eggert, Jon H. / Millot, Marius / Zepeda-Ruiz, Luis A. / Oleynik, Ivan I.

2024

Abstract	Diamond possesses exceptional physical properties due to its remarkably strong carbon-carbon bonding, leading to significant resilience to structural transformations at very high pressures and temperatures. Despite several experimental attempts, synthesis and recovery of the theoretically predicted post-diamond BC8 phase remains elusive. Through quantum accurate, multi-million atom molecular dynamics (MD) simulations, we have uncovered the extreme metastability of diamond at very high pressures, significantly exceeding its range of thermodynamic stability. We predict the post-diamond BC8 phase to be experimentally accessible only within a narrow high pressure-temperature region of the carbon phase diagram. The diamond to BC8 transformation proceeds through pre-melting followed by BC8 nucleation and growth in the metastable carbon liquid. We propose a double-shock compression pathway to achieve BC8 synthesis, which is currently being explored in theory-inspired experiments at the National Ignition Facility.
Keywords	Condensed Matter - Materials Science
Publishing date	2024-01-16
Publishing country	us
Document type	Book ; Online
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Article ; Online: Identification of UBE3A Protein in CSF and Extracellular Space of the Hippocampus Suggest a Potential Novel Function in Synaptic Plasticity.

Dodge, Andie / Willman, Jonathan / Willman, Matthew / Nenninger, Austin W / Morrill, Nicole K / Lamens, Kristina / Greene, Hayden / Weeber, Edwin J / Nash, Kevin R

Autism research : official journal of the International Society for Autism Research

2021 Volume 14, Issue 4, Page(s) 645–655

Abstract: Disruptions to the maternally inherited allele UBE3A, encoding for an E3 ubiquitin ligase, leads to the manifestation of Angelman Syndrome (AS). While this disorder is rare, the symptoms are severe and lifelong including but not limited to: intractable ... ...

Abstract	Disruptions to the maternally inherited allele UBE3A, encoding for an E3 ubiquitin ligase, leads to the manifestation of Angelman Syndrome (AS). While this disorder is rare, the symptoms are severe and lifelong including but not limited to: intractable seizures, abnormal EEG's, ataxic gait, lack of speech, and most notably an abnormally happy demeanor with easily provoked laughter. Currently, little is known about the neurophysiological underpinnings of UBE3A leading to such globally severe phenotypes. Utilizing the newest AS rat model, comprised of a full UBE3A deletion, we aimed to elucidate novel mechanistic actions and potential therapeutic targets. This report demonstrates for the first time that catalytically active UBE3A protein is detectable within cerebrospinal fluid (CSF) of wild type rats but distinctly absent in AS rat CSF. Microdialysis within the rat hippocampus also showed that UBE3A protein is located in the interstitial fluid of wild type rat brains but absent in AS animals. This protein maintains catalytic activity and appears to be regulated in a dynamic activity-dependent manner. LAY SUMMARY: Angelman syndrome (AS) is a rare genetic disorder caused by the loss of the UBE3A gene within the central nervous system. Although we have identified the gene responsible for AS, we still have a long way to go to fully understand its function in vivo. Here we report that UBE3A is present within normal cerebrospinal fluid (CSF) but distinctly absent in AS CSF. Furthermore, we demonstrate that UBE3A is secreted and that this may occur in a dynamic activity-dependent fashion. Extracellular UBE3A maintained its ubiquitinating activity, thus suggesting that UBE3A may have a novel role outside of neurons. Autism Res 2021, 14: 645-655. © 2021 International Society for Autism Research and Wiley Periodicals LLC.
MeSH term(s)	Angelman Syndrome/genetics ; Animals ; Autism Spectrum Disorder ; Extracellular Space ; Hippocampus ; Neuronal Plasticity ; Rats ; Ubiquitin-Protein Ligases/genetics
Chemical Substances	Ube3a protein, rat (EC 2.3.2.26) ; Ubiquitin-Protein Ligases (EC 2.3.2.27)
Language	English
Publishing date	2021-01-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2481338-2
ISSN	1939-3806 ; 1939-3792
ISSN (online)	1939-3806
ISSN	1939-3792
DOI	10.1002/aur.2475
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Article ; Online: Improving Gene Therapy for Angelman Syndrome with Secreted Human UBE3A.

Nenninger, Austin W / Willman, Matthew / Willman, Jonathan / Stewart, Emma / Mesidor, Philippe / Novoa, Michelle / Morrill, Nicole K / Alvarez, Luis / Joly-Amado, Aurélie / Peters, Melinda M / Gulick, Danielle / Nash, Kevin R

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics

2022 Volume 19, Issue 4, Page(s) 1329–1339

Abstract: The rare genetic neurodevelopmental disease Angelman syndrome (AS) is caused by the loss of function of UBE3A, a ubiquitin ligase. The disease results in a lifetime of severe symptoms, including intellectual disability and motor impairments for which ... ...

Abstract	The rare genetic neurodevelopmental disease Angelman syndrome (AS) is caused by the loss of function of UBE3A, a ubiquitin ligase. The disease results in a lifetime of severe symptoms, including intellectual disability and motor impairments for which there are no effective treatments. One avenue of treatment for AS is the use of gene therapy to reintroduce a functional copy of the UBE3A gene. Our group had previously shown that recombinant adeno-associated virus (rAAV) expressing mouse Ube3a could rescue deficits in a mouse model of AS. Here, we expand on this work and show that this approach could be successfully replicated in a second AS model using the human UBE3A gene. Furthermore, we address the challenge of limited vector distribution in the brain by developing a novel modified form of UBE3A. This modified protein, termed STUB, was designed with a secretion signal and a cell-penetrating peptide. This allowed transduced cells to act as factories for the production of UBE3A protein that could be taken up by neighboring non-transduced cells, thus increasing the number of neurons receiving the therapeutic protein. Combining this construct with intracerebroventricular injections to maximize rAAV distribution within the brain, we demonstrate that this novel approach improves the recovery of behavioral and electrophysiological deficits in the AS rat model. More importantly, a comparison of rAAV-STUB to a rAAV expressing the normal human UBE3A gene showed that STUB was a more effective therapeutic. These data suggest that rAAV-STUB is a new potential approach for the treatment of AS.
MeSH term(s)	Animals ; Humans ; Mice ; Rats ; Angelman Syndrome/genetics ; Angelman Syndrome/therapy ; Cell-Penetrating Peptides/genetics ; Genetic Therapy ; Ubiquitin-Protein Ligases/genetics ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitins/genetics
Chemical Substances	Cell-Penetrating Peptides ; UBE3A protein, human (EC 2.3.2.26) ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; Ubiquitins
Language	English
Publishing date	2022-05-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	2316693-9
ISSN	1878-7479 ; 1933-7213
ISSN (online)	1878-7479
ISSN	1933-7213
DOI	10.1007/s13311-022-01239-2
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