Publications by authors named "Jeremiah Johnson"

222 Publications

Clip Chemistry: Diverse (Bio)(macro)molecular and Material Function through Breaking Covalent Bonds.

Chem Rev 2021 Apr 6. Epub 2021 Apr 6.

Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.

In the two decades since the introduction of the "click chemistry" concept, the toolbox of "click reactions" has continually expanded, enabling chemists, materials scientists, and biologists to rapidly and selectively build complexity for their applications of interest. Similarly, selective and efficient covalent bond reactions have provided and will continue to provide transformative advances. Here, we review key examples and applications of efficient, selective covalent bond cleavage reactions, which we refer to herein as "clip reactions." The strategic application of clip reactions offers opportunities to tailor the compositions and structures of complex (bio)(macro)molecular systems with exquisite control. Working in concert, click chemistry and clip chemistry offer scientists and engineers powerful methods to address next-generation challenges across the chemical sciences.
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http://dx.doi.org/10.1021/acs.chemrev.0c01282DOI Listing
April 2021

Crossing the Carotid Siphon: Techniques to Facilitate Distal Access in Tortuous Anatomy: 2-Dimensional Operative Video.

Oper Neurosurg (Hagerstown) 2021 Apr 2. Epub 2021 Apr 2.

Department of Neurosurgery, University of Texas Medical Branch, Galveston, Texas, USA.

As capabilities for endovascular treatment of intracranial vascular pathologies continue to expand, the need for access to the distal internal carotid artery with rigid support catheter systems continues to increase. One of the dominant factors limiting this access is patient anatomy, specifically vessel tortuosity. Increased tortuosity of the carotid siphon is a frequently encountered anatomic variant and may complicate endovascular procedures in adults and children.1,2 Failed attempts to navigate the carotid siphon with a distal access catheter carry a risk of vessel injury and treatment failure. For this reason, techniques that aid in supporting safe advancement of a distal access catheter across a tortuous carotid siphon are essential.3,4 In this video, we demonstrate 2 ways in which this may be accomplished. The first technique uses a larger diameter microcatheter, such as the AXS Offset catheter (Stryker, Kalamazoo, Michigan), to increase support for the distal access catheter, while the second uses a buddy wire technique to accomplish this increased support. Both of these techniques can help increase the safety of navigating a tortuous carotid siphon and increase the likelihood of successful treatment.  The procedures shown were performed with the informed consent of the patients.
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http://dx.doi.org/10.1093/ons/opab084DOI Listing
April 2021

Molecular Characterization of Polymer Networks.

Chem Rev 2021 Apr 1. Epub 2021 Apr 1.

Marsico Lung Institute, University of North Carolina, Chapel Hill, North Carolina 27599, United States.

Polymer networks are complex systems consisting of molecular components. Whereas the properties of the individual components are typically well understood by most chemists, translating that chemical insight into polymer networks themselves is limited by the statistical and poorly defined nature of network structures. As a result, it is challenging, if not currently impossible, to extrapolate from the molecular behavior of components to the full range of performance and properties of the entire polymer network. Polymer networks therefore present an unrealized, important, and interdisciplinary opportunity to exert molecular-level, chemical control on material macroscopic properties. A barrier to sophisticated molecular approaches to polymer networks is that the techniques for characterizing the molecular structure of networks are often unfamiliar to many scientists. Here, we present a critical overview of the current characterization techniques available to understand the relation between the molecular properties and the resulting performance and behavior of polymer networks, in the absence of added fillers. We highlight the methods available to characterize the chemistry and molecular-level properties of individual polymer strands and junctions, the gelation process by which strands form networks, the structure of the resulting network, and the dynamics and mechanics of the final material. The purpose is not to serve as a detailed manual for conducting these measurements but rather to unify the underlying principles, point out remaining challenges, and provide a concise overview by which chemists can plan characterization strategies that suit their research objectives. Because polymer networks cannot often be sufficiently characterized with a single method, strategic combinations of multiple techniques are typically required for their molecular characterization.
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http://dx.doi.org/10.1021/acs.chemrev.0c01304DOI Listing
April 2021

Pro-organic radical contrast agents ("pro-ORCAs") for real-time MRI of pro-drug activation in biological systems.

Polym Chem 2020 Aug 26;11(29):4768-4779. Epub 2020 Jun 26.

Department of Chemistry, Massachusetts Institute of Technology (MIT).

Nitroxide-based organic-radical contrast agents (ORCAs) are promising as safe, next-generation magnetic resonance imaging (MRI) tools. Nevertheless, stimuli-responsive ORCAs that enable MRI monitoring of prodrug activation have not been reported; such systems could open new avenues for prodrug validation and image-guided drug delivery. Here, we introduce a novel "pro-ORCA" concept that addresses this challenge. By covalent conjugation of nitroxides and drug molecules (doxorubicin, DOX) to the same brush-arm star polymer (BASP) through chemically identical cleavable linkers, we demonstrate that pro-ORCA and prodrug activation, , ORCA and DOX release, leads to significant changes in MRI contrast that correlate with cytotoxicity. This approach is shown to be general for a range of commonly used linker cleavage mechanisms (, photolysis and hydrolysis) and release rates. Pro-ORCAs could find applications as research tools or clinically viable "reporter theranostics" for and MRI-correlated prodrug activation.
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http://dx.doi.org/10.1039/d0py00558dDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009311PMC
August 2020

Double-barrel STA-MCA bypass for cerebral revascularization: lessons learned from a 10-year experience.

J Neurosurg 2021 Mar 19:1-9. Epub 2021 Mar 19.

4St. Luke's Health System, Boise, Idaho.

Objective: In select patients, extracranial-intracranial (EC-IC) bypass remains an important tool for cerebral revascularization. Traditionally, superficial temporal artery-middle cerebral artery (STA-MCA) bypass was performed using one limb of the STA only. In an attempt to augment flow and to direct flow to different ischemic areas of the brain, the authors adopted a "double-barrel" technique in which both branches of the STA are used to revascularize distinct MCA territories.

Methods: A series of consecutive double-barrel STA-MCA bypasses performed between 2010 and 2020 were reviewed. Each anastomosis was directed to augment flow to a territory most at risk based on preoperative perfusion studies, cerebral angiography, and intraoperative indocyanine green data. CT perfusion and CTA were routinely used to evaluate postoperative augmentation and graft patency. Patient perioperative outcomes, surgical complications, and modified Rankin Scale (mRS) scores at the last follow-up were reported.

Results: Forty-four patients (16 males, 28 females) successfully underwent double-barrel STA-MCA bypass on 54 cerebral hemispheres: 28 operations were for moyamoya disease, 23 for atherosclerotic disease refractory to medical therapy, 2 for complex cerebral aneurysms, and 1 for carotid occlusion as a sequela of cavernous meningioma growth. Ten patients underwent multiple operations, 9 of whom had moyamoya disease/syndrome, with the subsequent operation on the contralateral hemisphere. The average patient age at surgery was 45.1 years (range 14-73 years), with a mean follow-up time of 22.1 months. Intraoperative graft patency was confirmed in 100% of cases, and 101 (98.1%) of the 103 anastomoses with imaging follow-up were patent. Perfusion to the revascularized hemisphere was improved in 88.2% of cases. Perioperative ischemic and hemorrhagic complications occurred in 8 procedures (2 were asymptomatic), whereas remote ischemic and hemorrhagic events occurred in 7 cases. There was no mortality in the series, and the mean patient mRS scores were 1.72 at presentation and 1.15 at the last follow-up.

Conclusions: The high rates of intraoperative and postoperative patency support the feasibility of dual-anastomosis STA-MCA bypass for revascularization. The perioperative complication rate is not significantly different from that of single-anastomosis bypass. The functional outcomes at follow-up and perfusion improvement postoperatively support the efficacy and safety of this method as a treatment strategy.
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http://dx.doi.org/10.3171/2020.9.JNS201976DOI Listing
March 2021

Design of BET Inhibitor Bottlebrush Prodrugs with Superior Efficacy and Devoid of Systemic Toxicities.

J Am Chem Soc 2021 Mar 19;143(12):4714-4724. Epub 2021 Mar 19.

XTuit Pharmaceuticals, 35 Gatehouse Drive, Waltham, Massachusetts 02451, United States.

Prodrugs engineered for preferential activation in diseased versus normal tissues offer immense potential to improve the therapeutic indexes (TIs) of preclinical and clinical-stage active pharmaceutical ingredients that either cannot be developed otherwise or whose efficacy or tolerability it is highly desirable to improve. Such approaches, however, often suffer from trial-and-error design, precluding predictive synthesis and optimization. Here, using bromodomain and extra-terminal (BET) protein inhibitors (BETi)-a class of epigenetic regulators with proven anticancer potential but clinical development hindered in large part by narrow TIs-we introduce a macromolecular prodrug platform that overcomes these challenges. Through tuning of traceless linkers appended to a "bottlebrush prodrug" scaffold, we demonstrate correlation of prodrug activation kinetics with tumor pharmacokinetics, enabling the predictive design of novel BETi prodrugs with enhanced antitumor efficacies and devoid of dose-limiting toxicities in a syngeneic triple-negative breast cancer murine model. This work may have immediate clinical implications, introducing a platform for predictive prodrug design and potentially overcoming hurdles in drug development.
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http://dx.doi.org/10.1021/jacs.1c00312DOI Listing
March 2021

Generation Why: Neurosurgery and the Millennial Moment.

World Neurosurg 2021 Feb 20;149:8-10. Epub 2021 Feb 20.

Department of Neurosurgery, Baylor College of Medicine, Houston, Texas, USA. Electronic address:

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http://dx.doi.org/10.1016/j.wneu.2021.02.070DOI Listing
February 2021

PolyDAT: A Generic Data Schema for Polymer Characterization.

J Chem Inf Model 2021 Mar 22;61(3):1150-1163. Epub 2021 Feb 22.

Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.

Polymers are stochastic materials that represent distributions of different molecules. In general, to quantify the distribution, polymer researchers rely on a series of chemical characterizations that each reveal partial information on the distribution. However, in practice, the exact set of characterizations that are carried out, as well as how the characterization data are aggregated and reported, is largely nonstandard across the polymer community. This scenario makes polymer characterization data highly disparate, thereby significantly slowing down the development of polymer informatics. In this work, a proposal on how structural characterization data can be organized is presented. To ensure that the system can apply universally across the entire polymer community, the proposed schema, PolyDAT, is designed to embody a minimal congruent set of vocabulary that is common across different domains. Unlike most chemical schemas, where only data pertinent to the species of interest are included, PolyDAT deploys a multi-species reaction network construct, in which every characterization on relevant species is collected to provide the most comprehensive profile on the polymer species of interest. Instead of maintaining a comprehensive list of available characterization techniques, PolyDAT provides a handful of generic templates, which align closely with experimental conventions and cover most types of common characterization techniques. This allows flexibility for the development and inclusion of new measurement methods. By providing a standard format to digitalize data, PolyDAT serves not only as an extension to BigSMILES that provides the necessary quantitative information but also as a standard channel for researchers to share polymer characterization data.
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http://dx.doi.org/10.1021/acs.jcim.1c00028DOI Listing
March 2021

Metal homeostasis in pathogenic Epsilonproteobacteria: mechanisms of acquisition, efflux, and regulation.

Metallomics 2021 01;13(1)

Department of Microbiology, University of Tennessee, Knoxville, TN, USA.

Epsilonproteobacteria are a diverse class of eubacteria within the Proteobacteria phylum that includes environmental sulfur-reducing bacteria and the human pathogens, Campylobacter jejuni and Helicobacter pylori. These pathogens infect and proliferate within the gastrointestinal tracts of multiple animal hosts, including humans, and cause a variety of disease outcomes. While infection of these hosts provides nutrients for the pathogenic Epsilonproteobacteria, many hosts have evolved a variety of strategies to either sequester metals from the invading pathogen or exploit the toxicity of metals and drive their accumulation as an antimicrobial strategy. As a result, C. jejuni and H. pylori have developed mechanisms to sense changes in metal availability and regulate their physiology in order to respond to either metal limitation or accumulation. In this review, we will discuss the challenges of metal availability at the host-pathogen interface during infection with C. jejuni and H. pylori and describe what is currently known about how these organisms alter their gene expression and/or deploy bacterial virulence factors in response to these environments.
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http://dx.doi.org/10.1093/mtomcs/mfaa002DOI Listing
January 2021

Distal Access Catheters for Coaxial Radial Access for Posterior Circulation Interventions.

World Neurosurg 2021 Jan 21. Epub 2021 Jan 21.

Department of Neurosurgery, Baylor College of Medicine, Houston, Texas, USA.

Background: The neurointerventional field is moving towards transradial access (TRA). Among the favorable indications for TRA is for posterior circulation/vertebrobasilar interventions. For some neurointerventions, a triaxial system (guide catheter, distal access catheter [DAC], and microcatheter) is typically used for optimal support. We describe application of a new technique in which we forgo use of the guide catheter, using the DAC only for coaxial access via the radial approach and its potential advantages.

Methods: A retrospective review was performed of our institutional database for cases using our coaxial distal access catheter technique for posterior circulation interventions. Patient characteristics and radiographic and clinical information were reviewed. All reviews were approved by institutional review board and ethics committee, and all patient identifiers were removed.

Results: A total of 12 patients were found that met our criteria. Successful access and procedural completion was achieved in 11 of 12 (92%). Mechanical thrombectomy accounted for 7 cases; 2 of these patients were also stented via the same approach/technique. Other cases included 2 successful aneurysm treatments (1 flow diverter, 1 coil embolization), a balloon test occlusion for a cervical chordoma, and an arteriovenous malformation embolization.

Conclusions: TRA with a distal access catheter provides support equivalent to a triaxial system with a coaxial construct in the posterior circulation. This has the advantage of using a smaller system in the radial and vertebrobasilar artery without losing stability. This technique can be used effectively and safely for a variety of posterior circulation neuroendovascular interventions.
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http://dx.doi.org/10.1016/j.wneu.2021.01.048DOI Listing
January 2021

Students from a large Australian university use Twitter to identify difficult course concepts to review during face-to-face lectorial sessions.

Adv Physiol Educ 2021 Jan;45(1):10-17

School of Health and Biomedical Science within the College of Science, Engineering and Health, RMIT University, Bundoora, Melbourne, Victoria, Australia.

Engaging undergraduate students in large classes is a constant challenge for many lecturers, as student participation and engagement can be limited. This is a concern since there is a positive correlation between increased engagement and student success. The lack of student feedback on content delivery prevents lecturers from identifying topics that would benefit students if reviewed. Implementing novel methods to engage the students in course content and create ways by which they can inform the lecturer of the difficult concepts is needed to increase student success. In the present study, we investigated the use of Twitter as a scalable approach to enhance engagement with course content and peer-to-peer interaction in a large course. In this pilot study, students were instructed to tweet the difficult concepts identified from content delivered by videos. A software program automatically collected and parsed the tweets to extract summary statistics on the most common difficult concepts, and the lecturer used the information to prepare face-to-face (F2F) lectorial sessions. The key findings of the study were ) the uptake of Twitter (i.e., registration on the platform) was similar to the proportion of students who participated in F2F lectorials, ) students reviewed content soon after delivery to tweet difficult concepts to lecturer, ) Twitter increased engagement with lecturers, ) the difficult concepts were similar to previous years, yet the automated gathering of Twitter data was more efficient and time saving for the lecturer, and ) students found the lectorial review sessions very valuable.
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http://dx.doi.org/10.1152/advan.00147.2020DOI Listing
January 2021

Forming the Simmons Catheter for Cerebral Angiography and Neurointerventions via the Transradial Approach-Techniques and Operative Videos.

World Neurosurg 2021 Mar 17;147:e351-e353. Epub 2020 Dec 17.

Department of Neurosurgery, University of Texas Medical Branch, Galveston, Texas, USA. Electronic address:

Objective: Transradial access has been used increasingly for diagnostic cerebral angiography and neurointerventions. This requires development of a new skillset. Forming the Simmons catheter to catheterize the cerebral vessels is the most fundamental. Patient anatomy can complicate the formation of the Simmons catheter and the success of the procedure. The aim of this paper is to identify and describe the techniques that can be used transradially to facilitate the formation of the Simmons catheter for catheterization of the cerebral vessels.

Methods: We reviewed our series of 85 cerebral angiograms performed via a transradial approach at our institution between 2018 and 2019. We identified the techniques employed to form the Simmons catheter and compiled operative videos demonstrating each technique and its nuances.

Results: We have identified 7 techniques used to form the Simmons catheter from a right radial approach: in the ascending aorta, in the descending aorta, in the aortic arch, by deflecting the catheter off of the aortic valve with the glidewire in the common carotid artery, by deflecting the catheter off of the aortic valve with the glidewire in the descending aorta, and directly in the right or left common carotid arteries. We have identified that formation of the Simmons catheter from a left radial approach is most easily done in the descending aorta.

Conclusions: Transradial artery access has become increasingly common in cerebral angiography and neurointerventions. We describe techniques used for the formation of the Simmons catheter, a fundamental skill necessary for transradial cerebral angiogram or neurointervention.
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http://dx.doi.org/10.1016/j.wneu.2020.12.054DOI Listing
March 2021

Ambulatory neurosurgery in the COVID-19 era: patient and provider satisfaction with telemedicine.

Neurosurg Focus 2020 12;49(6):E13

2Department of Neurosurgery, University of Texas Medical Branch, Galveston, Texas.

Objective: Telemedicine has rapidly expanded in the recent years as technologies have afforded healthcare practitioners the ability to diagnose and treat patients remotely. Due to the COVID-19 pandemic, nonessential clinical visits were greatly limited, and much of the outpatient neurosurgical practice at the authors' institution was shifted quickly to telehealth. Although there are prior data suggesting that the use of telemedicine is satisfactory in other surgical fields, data in neurosurgery are limited. This study aimed to investigate both patient and provider satisfaction with telemedicine and its strengths and limitations in outpatient neurosurgery visits.

Methods: This quality improvement study was designed to analyze provider and patient satisfaction with telemedicine consultations in an outpatient neurosurgery clinic setting at a tertiary care, large-volume, academic center. The authors designed an 11-question survey for neurosurgical providers and a 13-question survey for patients using both closed 5-point Likert scale responses and multiple choice responses. The questionnaires were administered to patients and providers during the period when the clinic restricted in-person visits. At the conclusion of the study, the overall data were analyzed qualitatively and quantitatively.

Results: During the study period, 607 surveys were sent out to patients seen by telehealth at the authors' academic center, and 122 responses were received. For the provider survey, 85 surveys were sent out to providers at the authors' center and other academic centers, and 40 surveys were received. Ninety-two percent of patients agreed or strongly agreed that they were satisfied with that particular telehealth visit. Eighty-eight percent of patients agreed that their telehealth visit was more convenient for them than an in-person visit, but only 36% of patients stated they would like their future visits to be telehealth. Sixty-three percent of providers agreed that telehealth visits were more convenient for them than in-person visits, and 85% of responding providers stated that they wished to incorporate telehealth into their future practice.

Conclusions: Although the authors' transition to telehealth was both rapid and unexpected, most providers and patients reported positive experiences with their telemedicine visits and found telemedicine to be an effective form of ambulatory neurosurgical care. Not all patients preferred telemedicine visits over in-person visits, but the high satisfaction with telemedicine by both providers and patients is promising to the future expansion of telehealth in ambulatory neurosurgery.
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http://dx.doi.org/10.3171/2020.9.FOCUS20596DOI Listing
December 2020

Endovascular Selective Intra-Arterial Infusion of Mesenchymal Stem Cells Loaded With Delta-24 in a Canine Model.

Neurosurgery 2020 12;88(1):E102-E113

Department of Neurosurgery, Baylor College of Medicine, Houston, Texas.

Background: Delta-24-RGD, an oncolytic adenovirus, shows promise against glioblastoma. To enhance virus delivery, we recently demonstrated that human bone marrow-derived mesenchymal stem cells loaded with Delta-24-RGD (hMSC-D24) can eradicate glioblastomas in mouse models. There are no studies examining the safety of endovascular selective intra-arterial (ESIA) infusions of MSC-D24 in large animals simulating human clinical situations.

Objective: To perform canine preclinical studies testing the feasibility and safety of delivering increasing doses of hMSCs-D24 via ESIA infusions.

Methods: ESIA infusions of hMSC-D24 were performed in the cerebral circulation of 10 normal canines in the target vessels (internal carotid artery [ICA]/P1) via transfemoral approach using commercially available microcatheters. Increasing concentrations of hMSC-D24 or particles (as a positive control) were injected into 1 hemisphere; saline (negative control) was infused contralaterally. Toxicity (particularly embolic stroke) was assessed on postinfusion angiography, diffusion-weighted magnetic resonance imaging, clinical exam, and necropsy.

Results: ESIA injections were performed in the ICA (n = 7) or P1 (n = 3). In 2 animals injected with particles (positive control), strokes were detected by all assays. Of 6 canines injected with hMSC-D24 through the anterior circulation, escalating dose from 2 × 106 cells/20 mL to 1 × 108 cells/10 mL resulted in no strokes. Two animals had ischemic and hemorrhagic strokes after posterior cerebral artery catheterization. A survival experiment of 2 subjects resulted in no complications detected for 24-h before euthanization.

Conclusion: This novel study simulating ESIA infusion demonstrates that MSCs-D24 can be infused safely at least up to doses of 1 × 108 cells/10 mL (107 cells/ml) in the canine anterior circulation using commercially available microcatheters. These findings support a clinical trial of ESIA infusion of hMSCs-D24.
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http://dx.doi.org/10.1093/neuros/nyaa470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735865PMC
December 2020

Whole-Genome Sequencing and Bioinformatic Analysis of Environmental, Agricultural, and Human Isolates From East Tennessee.

Front Microbiol 2020 5;11:571064. Epub 2020 Nov 5.

Department of Microbiology, The University of Tennessee, Knoxville, Knoxville, TN, United States.

As a leading cause of bacterial-derived gastroenteritis worldwide, has a significant impact on human health in both the developed and developing worlds. Despite its prevalence as a human pathogen, the source of these infections remains poorly understood due to the mutation frequency of the organism and past limitations of whole genome analysis. Recent advances in both whole genome sequencing and computational methods have allowed for the high-resolution analysis of intraspecies diversity, leading multiple groups to postulate that these approaches may be used to identify the sources of infection. To address this hypothesis, our group conducted a regionally and temporally restricted sampling of agricultural and environmental sources and compared isolated genomes to those that caused human infections in the same region during the same time period. Through a network analysis comparing genomes from various sources, we found that human isolates clustered with those isolated from cattle and chickens, indicating these as potential sources of human infection in the region.
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http://dx.doi.org/10.3389/fmicb.2020.571064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674308PMC
November 2020

A national survey on the impact of the COVID-19 pandemic upon burnout and career satisfaction among neurosurgery residents.

J Clin Neurosci 2020 Oct 19;80:137-142. Epub 2020 Aug 19.

Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address:

The coronavirus disease 2019 (COVID-19) pandemic has posed significant changes to resident education and workflow. However, the impact of the pandemic on U.S. neurosurgery residents has not been well characterized. We investigated the impact of the COVID-19 pandemic on U.S. neurosurgery resident workflow, burnout, and career satisfaction. In 2020, a survey evaluating factors related to career satisfaction and burnout was emailed to 1,374 American Association of Neurological Surgeons (AANS) residents. Bivariate and multivariate (logistic) analyses were performed to characterize predictors of burnout and career satisfaction. 167 survey responses were received, with a response rate (12.2%) comparable to that of similar studies. Exclusion of incomplete responses yielded 111complete responses. Most respondents were male (65.8%) and White (75.7%). Residents reported fewer work hours (67.6%) and concern that COVID-19 would impair theirachievement of surgical milestones (65.8%). Burnout was identified in 29 (26.1%) respondents and career satisfaction in 82 (73.9%) respondents. In multivariate analysis, burnout was significantly associated with alterations in elective rotation/vacation schedules (p = .013) and the decision to not pursue neurosurgery again if given the choice (p < .001). Higher post-graduate year was associated with less burnout (p = .011). Residents displayed greater career satisfaction when focusing their clinical work upon neurosurgical care (p = .065). Factors related to COVID-19 have contributed to workflow changes among U.S. neurosurgery residents. We report a moderate burnout rate and a paradoxically high career satisfaction rate among neurosurgery residents. Understanding modifiable stressors during the COVID-19pandemic may help to formulate interventions to mitigate burnout and improve career satisfaction among residents.
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http://dx.doi.org/10.1016/j.jocn.2020.08.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438065PMC
October 2020

Middle Meningeal Artery Embolization for Chronic Subdural Hematoma: A Multi-Center Experience of 154 Consecutive Embolizations.

Neurosurgery 2021 01;88(2):268-277

Neurosurgical Service, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.

Background: Middle meningeal artery (MMA) embolization has emerged as a promising treatment for chronic subdural hematoma (cSDH).

Objective: To determine the safety and efficacy of MMA embolization.

Methods: Consecutive patients who underwent MMA embolization for cSDH (primary treatment or recurrence after conventional surgery) at 15 centers were included. Clinical details and follow-up were collected prospectively. Primary clinical and radiographic outcomes were the proportion of patients requiring additional surgical treatment within 90 d after index treatment and proportion with > 50% cSDH thickness reduction on follow-up computed tomography imaging within 90 d. National Institute of Health Stroke Scale and modified Rankin Scale were also clinical outcomes.

Results: A total of 138 patients were included (mean age: 69.8, 29% female). A total of 15 patients underwent bilateral interventions for 154 total embolizations (66.7% primary treatment). At presentation, 30.4% and 23.9% of patients were on antiplatelet and anticoagulation therapy, respectively. Median admission cSDH thickness was 14 mm. A total of 46.1% of embolizations were performed under general anesthesia, and 97.4% of procedures were successfully completed. A total of 70.2% of embolizations used particles, and 25.3% used liquid embolics with no significant outcome difference between embolization materials (P > .05). On last follow-up (mean 94.9 d), median cSDH thickness was 4 mm (71% median thickness reduction). A total of 70.8% of patients had >50% improvement on imaging (31.9% improved clinically), and 9 patients (6.5%) required further cSDH treatment. There were 16 complications with 9 (6.5%) because of continued hematoma expansion. Mortality rate was 4.4%, mostly unrelated to the index procedure but because of underlying comorbidities.

Conclusion: MMA embolization may provide a safe and efficacious minimally invasive alternative to conventional surgical techniques.
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http://dx.doi.org/10.1093/neuros/nyaa379DOI Listing
January 2021

Trends in academic productivity in the COVID-19 era: analysis of neurosurgical, stroke neurology, and neurointerventional literature.

J Neurointerv Surg 2020 Nov 30;12(11):1049-1052. Epub 2020 Sep 30.

Department of Neurosurgery, University of Texas Medical Branch, Galveston, Texas, USA

Background: Academic physicians aim to provide clinical and surgical care to their patients while actively contributing to a growing body of scientific literature. The coronavirus disease 2019 (COVID-19) pandemic has resulted in procedural-based specialties across the United States witnessing a sharp decline in their clinical volume and surgical cases.

Objective: To assess the impact of COVID-19 on neurosurgical, stroke neurology, and neurointerventional academic productivity.

Methods: The study compared the neurosurgical, stroke neurology, and neurointerventional academic output during the pandemic lockdown with the same time period in previous years. Editors from a sample of neurosurgical, stroke neurology, and neurointerventional journals provided the total number of original manuscript submissions, broken down by months, from the year 2016 to 2020. Manuscript submission was used as a surrogate metric for academic productivity.

Results: 8 journals were represented. The aggregated data from all eight journals as a whole showed that a combined average increase of 42.3% was observed on original submissions for 2020. As the average yearly percent increase using the 2016-2019 data for each journal exhibited a combined average increase of 11.2%, the rise in the yearly increase for 2020 in comparison was nearly fourfold. For the same journals in the same time period, the average percent of COVID-19 related publications from January to June of 2020 was 6.87%.

Conclusion: There was a momentous increase in the number of original submissions for the year 2020, and its effects were uniformly experienced across all of our represented journals.
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http://dx.doi.org/10.1136/neurintsurg-2020-016710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7528313PMC
November 2020

Profile of Data Sharing in the Clinical Neurosciences.

Cureus 2020 Aug 21;12(8):e9927. Epub 2020 Aug 21.

Department of Neurosurgery, Baylor College of Medicine, Houston, USA.

Importance:  In today's climate of high healthcare costs and limited research resources, much attention has been given to inefficiency in research. Open access to research data has been proposed as a way to pool resources and make the most of research funding while also promoting transparency and scientific rigor.  Objective: The clinical neurosciences stand to benefit greatly from the potential opportunities afforded by open data, and we sought to evaluate the current state of publicly available research findings and data sharing policies within the clinical neurosciences.  Design: The Clarivate Analytics Web of Science journal citation reports for 2017 were used to sort journals in the category 'Clinical Neurosciences' by impact factor. The top 50 journals were selected and reviewed, but data was only collected from journals focused on original research (42/50). For each journal we reviewed the 10 most recent original research articles for 2016, 2017, and 2018 as designated by Scopus.  Results: A data sharing policy existed for 60% (25/42) of the journals reviewed. Of the articles studied 41% (517/1255) contained source data, and the amount of articles with available source data increased from 2016 to 2018. Of all the articles reviewed, 49.4% (620/1255) were open access. Overall, 6.9% (87/1255) of articles had their source data accessible outside of the manuscript (e.g. registries, databases, etc.) and 8.9% (112/1255) addressed the availability of their source data within the publication itself. The availability of source data outside the manuscript and in-article discussion of source data availability both increased from 2016 to 2018. Only 3.9% (49/1255) of articles reviewed reported negative results for their primary outcome, and 7.6% (95/1255) of the articles could not be defined as primarily reporting positive or negative findings (characterization studies, census reporting, etc.). The distribution of negative versus positive results reported showed no significant trend over the years studied.  Conclusion and Relevance: Our results demonstrate an opportunity for increased data sharing in neuroscience original research. These findings also suggest a trend towards increased adoption of open data sharing policies among journals and increased availability of unprocessed data in publications. This can increase the quality and speed at which new research is developed in the clinical neurosciences.
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http://dx.doi.org/10.7759/cureus.9927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505642PMC
August 2020

Burnout and career satisfaction among attending neurosurgeons during the COVID-19 pandemic.

Clin Neurol Neurosurg 2020 11 1;198:106193. Epub 2020 Sep 1.

Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States. Electronic address:

Objective: The novel coronavirus SARS-CoV-2 (COVID-19) pandemic has posed significant changes to physician workflow and healthcare delivery. This national survey investigated the impact of the pandemic on burnout and career satisfaction among U.S. attending neurosurgeons.

Methods: A 24-question survey was sent electronically to all American Association of Neurological Surgeons (AANS) attending members. The abbreviated Maslach Burnout Inventory (aMBI) was used to measure the following burnout and career satisfaction indices: emotional exhaustion, depersonalization, and personal accomplishment. Bivariate analyses were conducted and multivariate analyses were performed using logistic regression models.

Results: 407 attending neurosurgeons were included in the present study, with an overall response rate of 17.7 %. The majority of respondents were male (88.7 %), White (84.3 %), and in practice for 15 years or more (64.6 %). The majority reported a decrease in work hours due to the pandemic (82.6 %), uncertainty about future earnings (80.3 %), and uncertainty regarding future healthcare reform (84.5 %). Burnout was identified in 83 (20.4 %) respondents, whereas career satisfaction was identified in 316 (77.6 %) respondents. Rate of burnout was decreased when compared to rates reported in the pre-COVID era. In multivariate analysis, burnout was associated with working in a hostile or difficult environment since the rise of COVID-19 (OR = 2.534, p = 0.008), not having children (OR = 3.294, p = 0.011), being in practice for 5-15 years (vs. < 5 years) (OR = 4.568, p = 0.014), spending increased time conducting non-neurosurgical medical care due to COVID-19 (OR = 2.362, p = 0.019), feeling uncertain about future earnings due to COVID-19 (OR = 4.031, p = 0.035), and choosing not to pursue or feeling uncertain about pursuing neurosurgery again if given the choice (OR = 7.492, p < 0.001). Career satisfaction was associated with cerebrovascular subspecialty training (OR = 2.614, p = 0.046) and a willingness to pursue neurosurgery again if given the choice (OR = 2.962, p < 0.001).

Conclusion: Factors related to the novel COVID-19 pandemic have contributed to changes in workflow among U.S. attending neurosurgeons. Despite these changes, we report decreased burnout and high career satisfaction among U.S. neurosurgeons. Understanding modifiable stressors among neurosurgeons during the pandemic may help to identify effective future interventions to mitigate burnout and improve career satisfaction.
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http://dx.doi.org/10.1016/j.clineuro.2020.106193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462441PMC
November 2020

Comparison of First-Pass Efficacy Among Four Mechanical Thrombectomy Techniques: A Single-Center Experience.

World Neurosurg 2020 Dec 3;144:e533-e540. Epub 2020 Sep 3.

Department of Neurology, Baylor College of Medicine, Houston, Texas, USA.

Background: First-pass efficacy (FPE) is an established marker of technical and clinical efficacy among mechanical thrombectomy (MT) techniques. It is unclear what the optimal approach is in achieving FPE. We present a single-center experience comparing rates of FPE among 2 MT techniques and evaluate the potential predictors of FPE among other outcomes.

Methods: A single-center retrospective analysis was carried out of patients with consecutive large-vessel occlusion strokes (LVOS) of anterior circulation from September 2015 to April 2019 who underwent MT and for whom data were available on the status of FPE. Four MT techniques were identified: ADAPT (a direct first-pass aspiration), SrADAPT (stent retriever with aspiration), SRBG (stent retriever with balloon guide catheter), and STRAP (stent retriever-aspiration and proximal flow arrest). The primary outcome was FPE and secondary outcomes included the rate of successful reperfusion.

Results: Among 226 patients with LVOS of the anterior circulation who underwent MT, data were available for 164 on FPE for the 4 MT techniques. SRBG was the most prevalent technique. No significant difference was found in rates of FPE among the 4 MT techniques (P = 0.332). No independent predictors of FPE were identified on multivariable analysis. STRAP had the highest rate of successful reperfusion compared with the other techniques (P = 0.049) and was the only independent predictor of that outcome (P = 0.027).

Conclusions: Among patients with LVOS of the anterior circulation, the rate of FPE did not differ among the 4 MT techniques. There were no predictors of FPE among the studied variables. STRAP was the only predictor of successful reperfusion.
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http://dx.doi.org/10.1016/j.wneu.2020.08.209DOI Listing
December 2020

Molecular Design of Stable Sulfamide- and Sulfonamide-based Electrolytes for Aprotic Li-O Batteries.

Chem 2019 Oct 25;5(10):2630-2641. Epub 2019 Jul 25.

Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Electrolyte instability is one of the most challenging impediments to enabling Lithium-Oxygen (Li-O) batteries for practical use. The use of physical organic chemistry principles to rationally design new molecular components may enable the discovery of electrolytes with stability profiles that cannot be achieved with existing formulations. Here, we report on the development of sulfamide- and sulfonamide-based small molecules that are liquids at room temperature, capable of dissolving reasonably high concentration of Li salts (e.g., LiTFSI), and are exceptionally stable under the harsh chemical and electrochemical conditions of aprotic Li-O batteries. In particular, ,-dimethyl-trifluoromethanesulfonamide was found to be highly resistant to chemical degradation by peroxide and superoxide, stable against electrochemical oxidation up to 4.5 V, and stable for > 90 cycles in a Li-O cell when cycled at < 4.2 V. This study provides guiding principles for the development of next-generation electrolyte components based on sulfamides and sulfonamides.
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http://dx.doi.org/10.1016/j.chempr.2019.07.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442112PMC
October 2019

Intra-Arterial Glycoprotein IIb/IIIa Inhibitor Treatment for Symptomatic Intracranial Atherosclerotic Stenosis Presenting as Large Vessel Occlusions.

Cureus 2020 Jul 17;12(7):e9243. Epub 2020 Jul 17.

Neurosurgery, Baylor College of Medicine, Houston, USA.

Introduction There is no consensus on the optimal treatment for acute ischemic stroke (AIS) large vessel occlusions (LVOs) or near-occlusions with underlying intracranial atherosclerotic stenosis (ICAS). We report the first American series using intra-arterial (IA) glycoprotein IIb/IIIa inhibitors (GPIs) as a stand-alone revascularization technique for ICAS presenting with large vessel ischemic syndromes. Methods Records at two centers of 140 patients presenting with AIS undergoing stroke intervention from January 2017 to June 2019 were retrospectively reviewed. Patients treated with IA GPIs were identified, and baseline factors, imaging, procedural characteristics, hospital course, and outcomes were collected. Six patients with ICAS underlying their acute symptomatic near occlusion or LVO were treated with IA GPI. Four near-occlusions were treated with IA GPI as the first-line therapy, while two LVOs were treated with IA GPI as an adjunct therapy to thrombectomy. Results The mean age was 61.3 years (range 36-79), presentation National Institute of Health Stroke Scale (NIHSS) was 10 (4-18), time from last seen well to treatment was 434.5 minutes (164-1290), and time from groin puncture to revascularization was 67.3 minutes (26-94). Three patients received intravenous (IV) tissue plasminogen activator (tPA), and all patients received an IA weight-based GPI infusion. Five patients had thrombolysis in cerebral ischemia (TICI) 3, and one patient had TICI 2b. The mean discharge NIHSS was 2.5 (0-8). The mean modified Rankin scale was 1.3 (range 0-4) at discharge and .8 at three months. No patients had a postprocedural symptomatic hemorrhage. Conclusion Our results highlight the utility of IA GPI administration as the first-line therapy for symptomatic ICAS near occlusions or as a rescue technique after failed thrombectomy for LVO patients suspected of underlying ICAS.
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http://dx.doi.org/10.7759/cureus.9243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430682PMC
July 2020

Publisher Correction: Cleavable comonomers enable degradable, recyclable thermoset plastics.

Nature 2020 Sep;585(7823):E4

Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41586-020-2660-7DOI Listing
September 2020

Canine Model for Selective and Superselective Cerebral Intra-Arterial Therapy Testing.

Neurointervention 2020 Nov 11;15(3):107-116. Epub 2020 Aug 11.

Department of Neurosurgery, Baylor College of Medicine, Houston, TX, USA.

Purpose: With advancing endovascular technology and increasing interest in minimally invasive intra-arterial therapies such as stem cell and chemotherapy for cerebral disease, the establishment of a translational model with cerebral circulation accessible to microcatheters is needed. We report our experience catheterizing canine cerebral circulation with microcatheters, present high-resolution angiographic images of the canine vascular anatomy, describe arterial branch flow patterns and provide measurements of canine arterial conduits.

Materials And Methods: Angiograms were performed on 10 intact purpose-bred hounds. Angiography, measurements of arterial conduits and catheterization information for intracranial arterial branches were obtained.

Results: Selective and superselective cerebral angiography was successful in all subjects. Relevant arterial mean diameters include the femoral (4.64 mm), aorta (9.38 mm), external carotid (3.65 mm), internal carotid arteries (1.6 mm), vertebrobasilar system and Circle of Willis branches. Catheterization of the Circle of Willis was achieved via the posterior circulation in all subjects tested (n=3) and the use of flow directed microcatheters resulted in reduced arterial tree deformation and improved superselection of intracranial vessels. Catheterization of the intracranial circulation was attempted but not achieved via the internal carotid artery (n=7) due to its tortuosity and subsequent catheter related vasospasm.

Conclusion: The canine cerebral vasculature is posterior circulation dominant. Anterior circulation angiography is achievable via the internal carotid artery, but direct cerebral arterial access is best achieved via the posterior circulation using flow-directed microcatheters. It is feasible to deliver intra-arterial therapies to selective vascular territories within the canine cerebral circulation, thus making it a viable animal model for testing novel intra-arterial cerebral treatments.
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http://dx.doi.org/10.5469/neuroint.2020.00150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608496PMC
November 2020

Marketing of Tenofovir Disoproxil Fumarate (TDF) Lawsuits and Social Media Misinformation Campaigns' Impact on PrEP Uptake Among Gender and Sexual Minority Individuals.

AIDS Behav 2021 May;25(5):1396-1404

New York City Department of Health and Mental Hygiene, New York, NY, USA.

There has been an influx of ads on social media seeking plaintiffs in lawsuits for harms/side-effects caused by tenofovir disoproxil fumarate/Emtricitabine (TDF/FTC, Truvada) for PrEP. Community groups and researchers have suggested these ads may be undermining efforts to disseminate PrEP to key populations. In October 2019, we began assessing the impact of injury lawsuit ads on social media platforms in an ongoing U.S. national cohort study of HIV-negative cis men, trans men, and trans women who have sex with men. Although assessments are ongoing, given the alarming nature of our findings, we report data collected as of March 2020 (n = 2078). Most (59.9%) said they had seen ads for TDF-related lawsuits on social media. Twenty-eight percent said they would probably or definitely not start PrEP and 22.1% said they would not stay on PrEP (were they on it) as a result of seeing these ads. Next, 38.2% agreed or strongly agreed that seeing these ads made them think that TDF/FTC for PrEP was not safe. Black, Latinx, and/or multiracial individuals were most likely to be negatively impacted by the ads including perceptions that these ads made them think PrEP is not safe. In contrast, past year experience taking PrEP was positively associated with intentions to start and/or stay on PrEP despite seeing the ads. Due to forthcoming affordable/generic options, TDF/FTC is projected to become the most scalable option for disseminating PrEP to key populations. Results suggest that ads for TDF lawsuits on social media are having a negative impact on individual PrEP decision-making. Our findings highlight the urgency for accurate and balanced messaging on the benefits and risks of PrEP, so that individuals can make informed choices about whether PrEP is right for them.
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http://dx.doi.org/10.1007/s10461-020-02977-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854969PMC
May 2021

Quantitative Mapping of Molecular Substituents to Macroscopic Properties Enables Predictive Design of Oligoethylene Glycol-Based Lithium Electrolytes.

ACS Cent Sci 2020 Jul 18;6(7):1115-1128. Epub 2020 Jun 18.

Department of Chemistry, Research Laboratory of Electronics, Department of Materials Science and Engineering, Department of Mechanical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.

Molecular details often dictate the macroscopic properties of materials, yet due to their vastly different length scales, relationships between molecular structure and bulk properties can be difficult to predict , requiring Edisonian optimizations and preventing rational design. Here, we introduce an easy-to-execute strategy based on linear free energy relationships (LFERs) that enables quantitative correlation and prediction of how molecular modifications, i.e., substituents, impact the ensemble properties of materials. First, we developed substituent parameters based on inexpensive, DFT-computed energetics of elementary pairwise interactions between a given substituent and other constant components of the material. These substituent parameters were then used as inputs to regression analyses of experimentally measured bulk properties, generating a predictive statistical model. We applied this approach to a widely studied class of electrolyte materials: oligo-ethylene glycol (OEG)-LiTFSI mixtures; the resulting model enables elucidation of fundamental physical principles that govern the properties of these electrolytes and also enables prediction of the properties of novel, improved OEG-LiTFSI-based electrolytes. The framework presented here for using context-specific substituent parameters will potentially enhance the throughput of screening new molecular designs for next-generation energy storage devices and other materials-oriented contexts where classical substituent parameters (e.g., Hammett parameters) may not be available or effective.
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http://dx.doi.org/10.1021/acscentsci.0c00475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379101PMC
July 2020

Cleavable comonomers enable degradable, recyclable thermoset plastics.

Nature 2020 07 22;583(7817):542-547. Epub 2020 Jul 22.

Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.

Thermosets-polymeric materials that adopt a permanent shape upon curing-have a key role in the modern plastics and rubber industries, comprising about 20 per cent of polymeric materials manufactured today, with a worldwide annual production of about 65 million tons. The high density of crosslinks that gives thermosets their useful properties (for example, chemical and thermal resistance and tensile strength) comes at the expense of degradability and recyclability. Here, using the industrial thermoset polydicyclopentadiene as a model system, we show that when a small number of cleavable bonds are selectively installed within the strands of thermosets using a comonomer additive in otherwise traditional curing workflows, the resulting materials can display the same mechanical properties as the native material, but they can undergo triggered, mild degradation to yield soluble, recyclable products of controlled size and functionality. By contrast, installation of cleavable crosslinks, even at much higher loadings, does not produce degradable materials. These findings reveal that optimization of the cleavable bond location can be used as a design principle to achieve controlled thermoset degradation. Moreover, we introduce a class of recyclable thermosets poised for rapid deployment.
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http://dx.doi.org/10.1038/s41586-020-2495-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384294PMC
July 2020

Stepping Up: How U.S. Neurosurgery Training Programs Can Innovatively Assess Resident Applicants in a Post-Step 1 World.

World Neurosurg 2020 10 16;142:291-293. Epub 2020 Jul 16.

Department of Neurosurgery, Baylor College of Medicine, Houston, Texas, USA.

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http://dx.doi.org/10.1016/j.wneu.2020.07.078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365120PMC
October 2020