bluuebunny/crossref_metadata_2025 huggingface dataset:
462 RNA-Based Therapeutics Targeting the Oncogenic Splicing Factor TRA2β Rewire Glioblastoma Cell Transcriptomes and Inhibit Their Proliferation
Authors: Leclair Nathan , Park Sunghee , Brugiolo Mattia , Angarola Brittany , Urbanski Laura , Yurieva Marina , Anczukow Olga
Published: March 2023

INTRODUCTION:

Glioblastomas are an aggressive brain tumor that, despite current treatment paradigms, carry a poor prognosis. Novel therapies aimed at specific glioblastoma alterations are needed. Alternative RNA splicing is a critical step in gene expression that allows a single gene to encode multiple RNA and subsequently protein isoforms. Alternative splicing becomes dysregulated in human tumors, including glioblastoma, through alterations in upstream regulatory splicing factor proteins such as TRA2β, an oncogene that enhances glioma cell proliferation. Despite these known alterations, targeting alternative splicing in glioblastomas has not been leveraged therapeutically.

METHODS:

U87MG glioblastoma cells were treated with splice-switching antisense oligonucleotides (ASOs) targeting the TRA2β transcript (ASO-1570) or non-targeting control (ASO-CTL). Cancer-relevant phenotypes, including proliferation and apoptosis, were measured using high-content imaging. Transcriptomic splicing signatures were defined using high-depth RNA-sequencing with computational tools that quantify percent splicing event inclusion (PSI) and validated using RT-PCR and western blotting.

RESULTS:

ASO-1570 treatment increased inclusion of a poison-exon in TRA2β leading to decreased coding transcripts and subsequent reductions in TRA2β protein expression compared to ASO-CTL. ASO-1570 significantly decreased cell proliferation and increased apoptosis. Mechanistically, ASO-1570 treated cells exhibited significant differences in alternatively spliced events, impacting genes involved in cancer-relevant pathways such as p53 and mTOR signaling. For example, ASO-1570 led to increased exon skipping in MDM2 leading to decreased MDM2 protein expression and increased p53 wild-type expression. ASO-1570 treatment also impacted growth of U87MG 3D-neurospheres, suggesting efficacy in advanced models that better capture in vivo conditions.

CONCLUSIONS:

Glioblastoma cells are sensitive to ASO-mediated TRA2β knockdown, which mechanistically induced transcriptome wide changes that impact cancer-related pathways. Further testing of this ASO in vivo may open novel avenues for its use as a targeted glioblastoma therapeutic.
472 Low-Field Portable Magnetic Resonance Imaging for Bedside Evaluation of Ischemic Stroke in Post-Thrombectomy Patients
Authors: Sujijantarat Nanthiya , Koo Andrew B. , Jambour Ivan , Malhotra Ajay , Crawford Anna , Mazurek Mercy , Parasuram Nethra , Chavva Isha , Sze Gordon , Renado Daniela , Antonios Joseph Paul , Elsamadicy Aladine A. , Hebert Ryan Matthew , Petersen Nils , Sheth Kevin , Matouk Charles Christian
Published: March 2023

INTRODUCTION:

Timely brain imaging is an essential component in clinical decision-making for patients undergoing mechanical thrombectomy (MT). The requirement for controlled access suites for high-field conventional MRI (cMRI) precludes rapid access for examination. In this study, we examined the use of low-field portable MRI (pMRI) in the post-thrombectomy setting.

METHODS:

Low-field pMRI was used to obtain bedside imaging in patients who underwent MT between December 2021 to April 2022 at Yale-New Haven Hospital.All pMRI exams were conducted in the standard ferromagnetic environment of the IR suite, with clinical and research staff present. Clinical, procedural, and pMRI details were collected. Two neuroradiologists served as blinded raters and evaluated pMRIs and cMRIs independently. If cMRI was not available for comparison, a post-thrombectomy CT was used.

RESULTS:

A total of 18 patients (61% females, median age 77 years-old [IQR 70-84]) underwent pMRIs in the IR suite after MT. MT was performed with a median access to revascularization time of 15 minutes [IQR 8-19], and with a TICI score of 2B and above in all patients. The median pMRI examination time was 30 minutes [IQR 13-32]. Thirteen patients (72.2%) had cMRI within 72 hours post-thrombectomy, while 4 who did not have cMRI (80%) underwent CT. Blinded raters correctly identified the presence of stroke on pMRI in all cases. Intracranial hemorrhage was identified on pMRI in 33.3% of the cases. The median infarct volume was 5.7 cc [IQR 3.83-15.43] on pMRI and 4.37 cc [IQR 0.66-16.5] on cMRI or post-thrombectomy CT. There were no adverse events related to the examination.

CONCLUSIONS:

The use of low-field pMRI is feasible in a post-thrombectomy setting and can enable timely identification of ischemic changes at bedside. Low-field pMRI may be helpful in acquiring time-sensitive brain imaging which may impact clinical decision-making post-thrombectomy.
481 Troubleshooting the Bypass: Intraoperative Management of Initially Failed Anastomosis in Cerebral Extracranial – Intracranial Direct Revascularization Surgery
Authors: Doron Omer , Langer David J. , Nossek Erez Zeev
Published: March 2023

INTRODUCTION:

Direct cerebral revascularization is considered one the most technically challenging operations in neurosurgery. Technical errors are often not identified during the completion of the anastomosis. Initial assessment and management at this moment can determine the success of the entire case, making re-circulation one of the most stressful moments in the procedure.

METHODS:

A retrospective analysis of direct bypass cases based on operative reports and available videos, were studied in detai. A case was defined as an “initially failed bypass”, irrespective of its final result, if after removal of the temporary clips, the bypass was not patent, or significant leak was encountered.

RESULTS:

138 cases were included (109 being STA-MCA) done for flow replacement (n = 49), or for flow augmentation (n = 89). 45 initially failed anastomosis, out of which 37 were the result of a technical error encounterd. Causes were clot(n = 10), vessel kinking(n = 5), spasm(n = 6), inappropriate donor(n = 3) or recipient(n = 2), competitive flow(n = 6) or a leak(n = 5). 31/37 cases were troubleshooted successfully resulting in a working bypass. Rescue maneuvers included: Partial re-opening of the suture line and irrigation for clot, graft repositioning for kinking, papaverine-vessel massage for spasm, and partial vessel cut at the donor site for anastomosis inspection. In “local” lack of demand, a new anastomosis was done by the same donor. 30-days follow-up showed similar rates of patency between successfully troubleshooted patients and the rest of the patients (82% vs 85%, p = 0.35).

CONCLUSIONS:

A comprehensive approach detailing technical “corrections”, describing maneuvers and the sequence of actions done in order to “revive” the bypass, as well as their prevalence, was not previously well described. In this study we present 3 of initial failure types: a leak, acute occlusion or delayed occlusion, presenting an algorithm for intra-operative management in these cases.
487 Clinical Outcomes of Decompressive Spine Surgery for Painless Cervical Myelopathy: An Analysis of the Michigan Spine Surgery Improvement Collaborative (MSSIC) Registry
Authors: Deshpande Nachiket , Fadel Hassan Ali , Schultz Lonni , Abdulhak Muwaffak , Chang Victor W. , Schwalb Jason M.
Published: March 2023

INTRODUCTION:

Cervical myelopathy (CM) is the occurrence of neurologic dysfunction secondary to any etiology that results in direct cervical spinal cord compression. Although axial neck pain and radicular arm pain are common presenting features in CM, some patients present atypically with myelopathic symptoms in the absence of neck or arm pain. To date, little is known regarding the outcomes of surgical decompression in these patients.

METHODS:

This is a retrospective study of prospectively collected data from the Michigan Spine Surgery Improvement Collaborative (MSSIC) registry. A total of 340 patients undergoing spine surgery for painless CM were analyzed. Surgical and patient reported outcomes, including minimal clinically important difference (MCID) in modified Japanese Orthopedic Association (mJOA) scores and Patient-Reported Outcomes Measurement Information System Physical Function (PROMIS PF) scores, were assessed at 90 days, 1 year, and 2 years postoperatively.

RESULTS:

At 90 days following surgery, a MCID in PROMIS PF and mJOA scores was seen in 42% and 36% of patients, respectively. The proportion of patients with MCID in mJOA scores remained stable at 1- and 2-year follow-up, while the percentage of patients with MCID in PROMIS PF scores decreased to 22% at two years post-operatively. When stratifying by pre-operative CM severity, patient reported outcomes and surgical complications did not significantly vary. Importantly, patient satisfaction remained above 80% at 90 days, 1 year, and 2 years after surgery.

CONCLUSIONS:

Following surgical intervention, clinically significant improvement was seen in a modest number of patients. The high degree of sustained patient satisfaction suggests that our measured outcomes may not accurately capture the degree of improvement that is important to patients, or it may represent happiness from not experiencing further functional decline.
518 Identification of Tumor Infiltrating Leukocytes in Glioblastoma and Clinical Outcomes
Authors: Orozco Andres Restrepo , Goodyke Austin , Zagorski Joseph , Vitaz Todd
Published: March 2023

INTRODUCTION:

Glioblastoma (GBM) accounts for 60% of all malignant brain tumors in adults with a dismal 5-year survival rate of 5%. Treatment challenges stem from GBM’s intricate biology, therapy-resistant tumor cells, favorable milieu, invasive properties, and immunosuppressive tumor-infiltrating leukocytes (TIL). These cells are pro-repair and provide an immune inhibitory function, thereby conferring an elusive and protective phenotype to malignant cells. The clinical association with outcomes and response of these cell types to chemotherapeutics remains largely uncharacterized.

METHODS:

Fresh GBM tumor samples were collected. Using flow cytometry, tumor-specific and TIL-specific antibodies are used to label these cells. GBM and TIL phenotype within each sample is correlated to patient outcome to understand how those are related to the successes and failures of treatment. In addition, these cells are subjected to a different chemotherapeutics to assess their response to therapy.

RESULTS:

Patients’ mean age was 66.3 y, 15 patients (62%) were female. There was variable expression of EFGR and PDFRA within and between tumors. TIL represent approximately 20% of the cells in the samples. Myeloid cells represent most TIL (86%) in most samples. MGMT promoter un-methylated status was associated with high proportion of MDSC (34%) and poor survival. Correlations between TIL and GBM immunophenotypes were observed such as an inverse correlation between EGFR expression and MDSCs. Drug-screening is currently underway.

CONCLUSIONS:

The MDSC and EGFR inverse correlation suggests a possible relationship between tumor cells and TIL, supported by studies showing a release of pro-repair cytokines with EGFR signaling. Similarly, T-cells were positively correlated with EGFR expression. These findings strengthen the evidence of the protective role of TIL in GBM. Chemotherapeutics are being currently studied to assess impact on tumor viability.
552 Quantifying the Blood-Brain Barrier in Acute Ischemic Stroke Using Novel MR Imaging
Authors: Mouchtouris Nikolaos , Alizadeh Mahdi , Ailes Isaiah , Piper Keenan , Gooch M. Reid , Tjoumakaris Stavropoula I. , Rosenwasser Robert H. , Wu Chengyuan , Jabbour Pascal
Published: March 2023

INTRODUCTION:

Acute ischemic stroke causes endothelial cell and tight junction damage, resulting in blood-brain barrier (BBB) disruption. BBB disruption is a significant risk factor for hemorrhagic conversion, which is seen in up to 20-40% of patients, increasing mortality by 7.9-fold. A number of processes, such as reperfusion injury, neuroinflammation, and neoangiogenesis impact the BBB permeability, which can fluctuate for several weeks after stroke. Despite its significance, BBB permeability is not taken into consideration in the management of this patient population.

METHODS:

We used two MRI sequences, diffusion-prepared pseudocontinuous arterial spin labeling (DP-pCASL) and Neurite Orientation Dispersion and Density Imaging (NODDI) to scan patients greater than 18 years old who presented with acute ischemic stroke. DP-pCASL generates cerebral blood flow, arterial transit time (ATT), and BBB permeability. NODDI generates neurite dispersion index (NDI), orientation dispersion index (ODI), and free water index (ISO) maps. Normalized BBB permeability above the 75th percentile of the vascular territories was defined as high permeability.

RESULTS:

Ten patients were enrolled with a mean age of 66.8 ± 13.9 and NIHSS of 15.8 ± 8.0. Patients were scanned at a mean 83.4 ± 78.8 hours from symptom onset. Two patients had received alteplase and 6 patients underwent mechanical thrombectomy. Multivariable logistic regression showed that increasing ATT (p <0.001), decreasing ODI signal (p = 0.001), increasing relative monocyte count (p = 0.001) were significant predictors of increased BBB permeability. Intubation/general anesthesia decreased the odds of high BBB permeability (OR 0.072, p < 0.001).

CONCLUSIONS:

Higher ATT, higher monocyte count, lower ODI, and lack of anesthesia were significant predictors of high BBB permeability in stroke patients. We provide a detailed account of our addition of DP-pCASL and NODDI into the stroke imaging protocol.
563 Post-Approval Three Year Outcomes Study of the Neuroform Atlas Stent for Treatment of Wide-Neck Intracranial Aneurysms
Authors: Jankowitz Brian , Swanson Thomas , Zaidat Osama O.
Published: March 2023

INTRODUCTION:

Favorable safety and effectiveness outcomes were presented previously for the Neuroform Atlas Stent following the completion of its pre-market study (ATLAS trial [Safety and Effectiveness of the Treatment of Wide Neck, Saccular, Intracranial Aneurysms with the Neuroform Atlas Stent System]) in anterior and posterior cohorts.

METHODS:

The ATLAS post-approval study was a multicenter, prospective, single-arm, open-label study of wide neck (neck ≥ 4mm or dome-to-neck ratio <2) intracranial aneurysms in the anterior and posterior circulations treated with the Neuroform Atlas Stent and approved coils. The primary effectiveness endpoint was complete occlusion (Raymond-Roy class 1) on angiography in the absence of retreatment or significant parent artery stenosis (>50%) through 3 years post-procedure. The primary safety endpoint was occurrence of major stroke, ipsilateral stroke, or neurological death through 3 years post-procedure. Independent adjudication of primary endpoint outcomes was completed by an Imaging Core Laboratory and Clinical Events Committee.

RESULTS:

A total of 146 anterior and 101 posterior cohort subjects from the pre-market study population were enrolled for continued follow-up. Subject demographics and aneurysm anatomy were representative of pivotal trial findings. For anterior subjects, the mean aneurysm size was 6.1±2.4 mm and the mean dome-to-neck ratio was 1.2±0.3 mm. In posterior subjects, the mean aneurysm size was 7±2.7 mm and the mean dome-to-neck ratio was 1.2±0.4 mm. At 3-year follow-up, the percent of target aneurysm progressive occlusion rated the same or better was 84.4% (95% CI, 67.2% - 94.7%) of anterior subjects and 90.0% (95% CI, 73.5% - 97.9%) of posterior subjects. A primary safety event was reported in 0.7% (1/146) of anterior and 1.0% (1/101) of posterior subjects, respectively, with no neurological deaths.

CONCLUSIONS:

The results of the ATLAS post-approval study demonstrate durable treatment effectiveness and favorable safety outcomes.
567 Drivers of 30-day Readmission, Drivers of 30-day Readmission, Reoperation, and Length of Stay Following Clipping Surgery of Unruptured Aneurysms in Elderly: A National Surgical Quality Improvement Program (NSQIP) Study
Authors: Ghaith Abdul Karim , Ghanem Marc , Bendok Bernard R. , Bydon Mohamad
Published: March 2023

INTRODUCTION:

Elderly population is increasing worldwide with a consistent increase in the incidence of aneurysms. There are limited data evaluating the rate and predictors of reoperation and readmission after microsurgical clipping of unruptured aneurysms in elderly.

METHODS:

Data on elderly patients (≥65 years) who underwent surgical clipping of an unruptured aneurysm between 2016 and 2020 were extracted from the prospective National Surgical Quality Improvement Program registry (NSQIP). Multivariable logistic regression evaluated the independent predictors of nonroutine hospital discharge, length of stay (LOS), 30-day reoperation, and readmission. Shapley additive explanations (SHAP) were calculated for feature importance using the best-performing model.

RESULTS:

A total of 367 elderly patients underwent surgical clipping for both ruptured (N = 142) and unruptured aneurysms (N = 225). Among the 225 unruptured cases, 11.6% (N=26) were readmitted and 6.2% (N = 14) were reoperated after 30 days. The mean LOS is 6.53 days (± 7.15). Most patients were discharged home (N = 160; 71.1%). Morbidity and morbidity probabilities were 2.15% and 3.8%, respectively. Male sex; preoperative BUN; preoperative creatinine and preoperative platelet count (p < 0.05) are more likely to predict 30-day readmission. Male sex, history of cancer , and history of COPD (p < 0.05) are more likely to predict reoperation. LOS was predicted with simple aneurysm , history of sepsis; history of COPD; elective surgery; operative time and days till the operation (p < 0.05). Machine learning using SHAP showed that BUN, platelet count, and sex had the highest impact on readmission; WBC, hematocrit, and sodium levels had the highest impact on reoperation; while operative time and history of sepsis had the highest impact on LOS.

CONCLUSIONS:

Our predictive model validates risk stratification of outcomes of patients undergoing microsurgical clipping of unruptured cerebral aneurysms in the elderly.
749 Medical Student Milestones for Neurosurgery Sub-Interns: A Pilot Study of a Novel Competency-Based Evaluation Tool to Quantitatively Differentiate Residency Applicants
Authors: Bowden Stephen , Tan Hao , Rothbaum Michael , Cook Steven H. , Hanft Simon Jeremy , Heth Jason , Mullin Jeffrey Paul , Orina Josiah N. , Wilson Jonathan Lee , Winer Jesse , Wolfe Stacey Q. , Selden Nathan R. , Chambless Lola Blackwell
Published: March 2023

INTRODUCTION:

Resident selection is guided by few objective, quantitative datapoints. Utility of a standardized letter of recommendation (SLOR) has been limited by “grade inflation”. The Milestones program in neurosurgery residency standardizes “competence” definitions, recognizes domains of competence beyond patient care and medical knowledge, and highlights deficient areas. A similar approach for neurosurgery sub-interns could provide objective performance data to aid applicant evaluation.

METHODS:

Medical student milestones were adapted from the residency milestones or newly created according to group consensus of relevant competencies. Competency levels were graded ordinally 1 (level of 3rd-year medical student) to 4 (2nd-year resident). Faculty and self-evaluations were completed for 35 sub-interns across eight programs. Evaluators were surveyed on its usefulness. Average and cumulative milestone scores (CMS) within and across programs were evaluated using descriptive statistics. Kendall’s W tested inter-rater agreement. CMS were compared against percentile assignments on LOR using analysis of variance with post-hoc testing.

RESULTS:

The average faculty rating overall was 3.20, similar to that expected of an intern. Students scored highest in coachability and feedback (3.49; 3.67) and lowest in bedside procedural aptitude (2.90; 2.85) in faculty and self-evaluations. Median CMS was 26.5 (IQR 21.75-29.75; range 14-32). CMS in four programs evaluating at least five students ranged at least 11 points. A program with three faculty raters demonstrated scoring agreement across five students (p = 0.024). CMS differed significantly between SLOR percentile assignments, despite 25% of students assigned to top 5%ile while CMS-driven assignment of percentiles significantly differentiated quartiles of students. Faculty and students strongly endorsed the milestones form.

CONCLUSIONS:

The medical student milestones form was well-received and considered useful in objectively differentiating students within and across programs.
771 Levetiracetam Dosing for Seizure Prophylaxis in Neurocritical Care Patients
Authors: Findlay Matt , Hedges Ashley , Menacho Sarah Tamara , Ansari Safdar , Hawryluk Gregory W. J. , Davis Gary , Wolfe Brianne , Lingenfelter Erin
Published: March 2023

INTRODUCTION:

Levetiracetam has emerged as a safer alternative to phenytoin for seizure prophylaxis in patients presenting with subarachnoid hemorrhage (SAH) or traumatic brain injury (TBI). However, it remains unclear which Levetiracetam dosing regimen is most effective at preventing seizures.

METHODS:

A retrospective cohort study captured adult patients at a quaternary care center presenting with SAH or TBI who received levetiracetam as a total daily dose (TDD) equivalent to or greater than 1000 mg. The primary outcome was the combined seizure incidence, including clinical and subclinical seizures.

RESULTS:

Among the 139 patients identified, 49.6% were male, and the mean age was 53 years. For patients receiving 1000 mg TDD levetiracetam, the administration was 500 mg twice daily. For patients receiving >1000 mg TDD, 77/78 patients received 1000 mg twice daily, and the remaining patient received 750 mg twice daily. A higher seizure incidence was observed, 11.5% vs 1.3%, in patients receiving 1000 mg TDD compared with doses >1000 mg TDD, respectively (p = 0.01), despite no difference in examined confounders, including history of alcoholism (14.8% vs. 19.2%, p = 0.49), benzodiazepine use (65.6% vs. 73.1%, p = 0.28), or propofol use (62.3% vs. 62.8%, p = 0.17). No difference in adverse effects were observed (anemia 1.6% vs. 3.8%, p = 0.44; leukopenia 6.6% vs. 9.0%, p = 0.60; thrombocytopenia 1.6% vs. 1.3%, p = 0.86).

CONCLUSIONS:

Patients may experience a reduced incidence of clinical and electroencephalographic seizures with levetiracetam dosing greater than 1000 mg TDD.
805 External Validation of the McGovern Score for Predicting Pediatric Blunt Cerebrovascular Injury
Authors: Venkataraman Sidish Srinivas , Herbert Joseph , Ravindra Vijay , Bollo Robert John , Cox Charles S. , Gannon Stephen , Limbrick David Delmar , Naftel Robert Partlow , Ugalde Irma , Weiner Howard , Yorkgitis Brian , Shah Manish N.
Published: March 2023

INTRODUCTION:

Blunt cerebrovascular injury (BCVI) is defined as blunt trauma to the head and neck leading to damage to the vertebral and/or carotid arteries. The risk factors for pediatric BCVI have not been clearly described and which pediatric patients are considered “high-risk” and in need of angiographic/vessel imaging is largely based on clinical and institutional treatment patterns. Our group previously proposed a screening tool, the McGovern score, to identify pediatric trauma patients at high risk for BCVI.

METHODS:

This multicenter, retrospective, hospital-based, cohort study involved data collected for all pediatric (<16 years) trauma patients who presented to the emergency department between 2003 and 2017 at 6 level 1 pediatric trauma centers. This trauma registry was then queried for patients who received a CTA as a screening method for BCVI. Patient age, arrival date, length of follow-up, and MOI were recorded. Glasgow Coma Scale (GCS) on arrival and the presence or absence of a focal neurological deficit. The obtained radiological variables included the presence or absence of a carotid canal fracture, petrous temporal bone fracture, and cerebral infarction as determined on CT scanning. Patients who were found to have BCVI were queried for mode of treatment, type of intracranial injury, artery damaged, and BCVI injury grade. The McGovern score was calculated for all patients who underwent CTA across all data groups.

RESULTS:

1012 patients underwent CTA. 72 of these patients were found to have BCVI, 51 of which were in the external cohort. Across all data groups, the McGovern score has a >80% sensitivity and >98% NPV.

CONCLUSIONS:

The McGovern score is an effective and generalizable screening tool for pediatric BCVI.
865 Survival Benefit of Stereotactic Laser Ablation (SLA) in Newly Diagnosed Glioblastoma Patients: A Matched Cohort Analysis
Authors: Bartek Jiri , Dhawan Sanjay , Chen Clark C C.
Published: March 2023

INTRODUCTION:

Post-hoc analysis of a previously published matched cohort study suggests improved survival for glioblastoma patients who underwent stereotactic laser ablation (SLA) relative those who underwent a biopsy, particularly for tumors where contrast enhancing (CE) regions were completely covered by thermal ablation.

METHODS:

Thirteen patients with newly diagnosed isocitrate dehydrogenase (IDH) wild type glioblastomas (without H3K27 mutation) who underwent SLA with ablation coverage of >90% of the contrast enhancing region were identified. Control cohort was generated by screening patients who underwent stereotactic biopsy for a newly diagnosed tumor matched for: age (+/- 10 years), location, tumor volume (+/- 30% of CE volume), and methyl-guanine methyl-transferase (MGMT promoter methylation status). Post-operative course, complications, 30-day readmission, and overall survival data were collected.

RESULTS:

The mean KPS for the SLA and biopsy cohorts were comparable (SLA: 90+14; biopsy: 87+16). One patient (8%) in the SLA cohort experienced new-onset diplopia, and one biopsy-only patient (8%) suffered hemi-sensory alteration. There were no 30-day readmissions for either cohort. With a median follow-up of 283 days, the median survival (mOS) for 375 days (∼13 mo) for the SLA treated patient cohort and 264 days (∼ 9 mo) for the biopsy cohort (p = 0.026). To exclude the possibility that this survival difference was due to selection of prognostically favorable patients for SLA, the survival benefit was confirmed by comparison to a second matched biopsy-only glioblastoma cohort from another institution without capacity for SLA. When stratified by MGMT promoter methylation, SLA survival benefit was significant in only patients with methylated tumors (SLA mOS: 620 days (21 mo); biopsy mOS: 171 days (5.7 mo), p = 0.007)

CONCLUSIONS:

For MGMT promoter methylated glioblastomas, SLA treatment was associated with improved survival relative to biopsy-treated patients. Validation of this finding in a prospective study is warranted.
888 Artificial Neural Network Analysis of Evoked Auditory Brainstem Responses for Prediction of Active Auditory Brainstem Implant (ABI) Electrodes in Patients With Neurofibromatosis Type II
Authors: Fatima Nida , Rock Jordan , Galvin John , Peng Kevin , Barnard Zachary , Lekovic Gregory
Published: March 2023

INTRODUCTION:

Auditory brainstem implantation (ABI) is used to provide auditory sensations through electric stimulation of the cochlear nucleus and is a key strategy for hearing rehabilitation in patients with neurofibromatosis type II (NF2). The exact position of the 3 by 7 electrode array with respect to the cochlear nucleus is not known, due to complex anatomy following tumor removal, procedures during surgery, potential distortions to the anatomy, and post-operative array migration, and other factors.

METHODS:

A retrospective study of a prospectively maintained database of ABI users with evoked brainstem responses was carried out at an academic institution. Multi-class classification was conducted using the multilayer perceptron (MLP) feed forward neural network model (FF-NN) to classify and predict the post-operative active electrodes.

RESULTS:

1,177 electrodes were stimulated intraoperatively among 85 patients [females, n = 48 (56.6%)]. ABI was implanted to the right and left side in 44 patients (51.7%) and 43 patients (48.3%) respectively. The mean follow-up of ABI was 29.6 months (range, 18-33.4 months). Notably, the heat map showed that electrodes at the center and the medial end (E9-16) of the array showed higher likelihoods of being active, irrespective of right or left side. The network was trained for 500 epochs with a learning rate of 0.3 and achieved a mean classification of about 92.3%. The open accessible software for predicting the monopolar electrode stimulation postoperatively based on bipolar intraoperative stimulation can be found here at: https://hifla.org/abi

CONCLUSIONS:

An ideal MLP FF-NN structure was achieved and hence may result in understanding more precisely about the ABI stimulation and bringing consistency among the neurosurgeons and audiologists worldwide.
Softball Pitchers’ Body Segment Girths Are Associated with Varied Biomechanics at Ball Release of the Pitch
Authors: FRIESEN KENZIE B. , OLIVER GRETCHEN D.
Published: March 2023

Purpose

The purpose of this study was to examine the relationships between pitcher trunk and throwing arm girth with kinematics at ball release of the softball pitch. Softball pitchers can be of various shapes and sizes; however, it is unknown if segment girth might influence pitch biomechanics. Because of the importance of body positioning at ball release of the windmill pitch, this study examined the relationship between segment girth and pitch biomechanics at ball release.

Methods

Forty-two pitchers volunteered to participate (1.706 ± 0.061 m, 74.98 ± 15.94 kg, 15.5 ± 1.7 yr). Participants’ throwing upper arm, chest, waist, and hip girth were measured. Participants then pitched fastballs to a catcher (43 ft) while an electromagnetic motion capture system synced with a force plate and motion analysis software collected kinematic data (sampled at 240 Hz).

Results

Linear regressions revealed that upper arm, chest, and waist girth were associated with throwing arm shoulder horizontal abduction. Greater segment girth was associated with less horizontal abduction at ball release of the pitch.

Conclusions

Segment girth is related to pitch biomechanics and may influence body positions at crucial softball pitch events such as ball release.

Clinical Relevance

Understanding biomechanical differences according to body segment girth is important for safe and optimal player development and performance.
The West Africa Lassa fever Consortium pre-positioned protocol for a Phase II/III adaptive, randomised, controlled, platform trial to evaluate multiple Lassa fever therapeutics
Authors: Bourner Josephine , Salam Alex Paddy , Jaspard Marie , Olayinka Adebola , Fritzell Camille , Goncalves Bronner , Vaillant Michel , Edwards Tansy , Erameh Cyril , Ajayi Nnennaya , Ramharter Michael , Olliaro Piero ,   The WALC Work Package 2 Working Group
Published: March 2023

Background: This is a standardized, pre-positioned protocol for the coordinated evaluation of Lassa fever therapeutics. The protocol is the product of discussions that took place in 2021 and 2022 among international investigators from a wide range of scientific and medical disciplines working together within the West Africa Lassa fever Consortium (WALC).

Methods: This is a clinical Phase II/III multicentre randomised controlled platform trial using a superiority framework with an equal allocation ratio and a composite primary endpoint of all-cause mortality OR new onset of i) acute kidney failure (AKF), OR ii) acute respiratory failure (ARF), OR iii) shock assessed from enrolment (D0) to D28.

Discussion: This pre-positioned protocol was developed by the WALC and made available for adaptation and implementation by the wider Lassa fever research community in order to generate efficient, reliable, and comparable evidence for Lassa fever therapeutics.
ASSESSING THE IMPACT AND EFFECTIVENESS OF A COMMUNITY LEADERSHIP DEVELOPMENT PROGRAM ON BLACK LEADERS
Authors: Fix Rebecca L. , Atnafou-Boyer Rebkha
Published: March 2023

Community leaders working in Black communities are faced with countless challenges yet require unique skills for which evidence-based training is often limited or difficult to find. The current study employed a mixed- methods approach using archival data to evaluate a promising and much needed neighborhood leadership program for Black community leaders, the Bunting Neighborhood Leadership Program. The three primary foci of the program were to examine who were selected as fellows, the goals fellows presented with upon entering the program, and the primary outcomes following immediate program completion and follow-up. Nineteen fellows have matriculated through the program, and all completed pre- and post-surveys, and were each contacted about current awards and other leadership successes. Additionally, seven fellows were interviewed about their experiences with and outcomes following the program. Surveys demonstrated important gains in knowledge and skill development for fellows. Following participation, many fellows developed their own organizations, and some secured funding and received awards for their community leadership work. Three key themes emerged from coded interviews, namely (1) characteristics of those who seek a community leadership training, (2) successes in community impact and activities observed among fellows following program completion, and (3) skills-based outcomes for fellows following program completion. The COVID-19 pandemic and killings of Black civilians by police also impacted participants’ responses. The role of blackness in Black community leadership was observed across themes that emerged. Overall, this is a promising community leadership program with important implications for leaders who serve Black communities.
ACTIVIST MUSICIANS: A FRAMEWORK FOR LEADERS OF SOCIAL CHANGE
Authors: Hill John C.
Published: March 2023

A proposition offered in this manuscript is that activist musicians use their musical competencies to enhance their social change strategies within the local community. However, it is unclear what strategies are being utilized by local activist musicians in order to reach collective action and achieve social and political change. A self-developed framework, the Framework for Activist Musicians (FAM), portrays how an activist musician utilizes their social experiences, behaviors, and influence to enact social change. The framework delineates how a musician utilizes their music-making involvement and status to enhance their charisma and authenticity as an activist to establish social change. Additionally, the framework outlines the unique qualities of a musician and activist which make them well-prepared to be an influential community leader.
MEET OUR LEADERSHIP STUDENTS: An Online Exercise to Develop Personas Application Manuscript
Authors: Winton Steven L. , Cornelius Andrea M. , Devany Katie L. , Hughes Patrick J.
Published: March 2023

Using an exploratory multi-case study approach, we examined student perceptions of leadership through analysis of introductory discussion board forums in online undergraduate and graduate leadership courses to formulate leadership student personas. A review of related literature reveals that leadership’s broad application results in a vast array of interests and motivations related to pursuit of a leadership degree. To that end, development of student personas provides leadership program administrators and faculty with a better understanding of their needs and characteristics. In this application paper, we will share qualitative data compiled from four online leadership courses. Our preliminary findings identified data-driven personas that showcase how leadership students with varying backgrounds and aspirations envision knowing our leadership students, as well as recommending future research that can help advance the field of leadership education.
TRAINING LEADERSHIP TRAINERS: Cultivating the Next Generation of Leadership Educators in Nicaragua
Authors: Kroll Jonathan , Moreno Manuel
Published: March 2023

Although the leadership training and development industry generates billions of dollars each year, some countries lag behind. This article explores one program’s attempt to expand leadership training and development opportunities in Nicaragua. The Leadership Trainer Certification Program (LTCP) is designed to prepare those who are responsible for the leadership development of others with the knowledge, skills, and facilitation techniques to effectively train others in leadership. In this article, we detail qualitative narrative data from one participant’s experience to share how he translated his learning into his leadership training and development practice. This article illuminates how leadership train-the-trainer programming can re-shape the leadership landscape, especially in places like Nicaragua and throughout the Global South.
LEARNING FROM LEADERSHIP CAPSTONE PROJECTS
Authors: Wefald Andrew J. , Benavides Mac T. , Seay Aliah K. Mestrovich
Published: March 2023

Using a qualitative grounded theory approach, student guided leadership capstone projects were examined using a thematic analysis to determine the categories of projects students chose. The research sought to answer two research questions: 1) What areas of leadership development do students seek out through capstone projects for a four-year leadership studies minor? 2) What can this tell us about the program from an evaluation perspective? The analysis found four categories: self-care, application and understanding of leadership, interpersonal skills, and intercultural development skills. The implications for leadership educators are discussed as well as how capstone projects can be utilized in other leadership programs.
DEVELOPING STUDENTS WHO LEAD IN THEIR COMMUNITIES: A Mixed Methods Case Study of Three Municipal-Based Leadership Programs in the United States
Authors: Crocco Oliver , Stojanović Maja , Whitley Melissa , Davis Kimberly , Climek Michael , Costello Gina , Henry Rachel , Braud Vani’Tra , Tepe Andrea , Bryant De’Jerra , Molleno Catherine
Published: March 2023

While many studies investigate student leadership development in educational contexts or curriculum-based programs, little is known about the efficacy of leadership development programs that emerge in municipalities. This mixed methods case study explored the leadership development of participants in three nine-month youth leadership programs at a municipal-based prevention, treatment, and outreach center in the United States. Qualitative focus groups and quantitative surveys using the Student Leadership Practices Inventory (SLPI) were used to collect data at the beginning and end of the three programs along with a post-program evaluative survey. Findings from the qualitative and quantitative analyses are first presented individually and then expressed using a joint display table to visually represent the integrated results. Findings showed that the programs positively influenced participants’ perceptions, characteristics, and behaviors as youth leaders in their communities. Participants not only indicated improvements in their leadership practices according to the SLPI from pre- to post-program, but also demonstrated more complex understandings of leadership and what it means to be a leader in one’s community. These findings are useful for individuals and organizations planning student leadership development programs and should inform future research in the field.
REFLECTING BACK AND GOING FORWARD: Promising Pedagogical Practices for Culturally Relevant/Sustaining and Equitable Online Leadership Education
Authors: McCarron Graziella Pagliarulo , Yamanaka Aoi
Published: March 2023

According to the U.S. Department of Education’s National Center for Education Statistics, in the fall of 2020, 72.8% of U.S. postsecondary students were enrolled in distance education courses—up from 36.3% in the fall of 2019. While this surge may be explained by a number of factors, one of the most significant factors is the COVID-19-induced pivot to online learning. The rapid and intense expansion in distance education due to COVID-19 offered learners some sense of continuity in their studies, but it also revealed stark inequities in learner resources and access—especially for students of Color and students from lower-income households. Further, as COVID-19 spread, the U.S. roiled in a “twin pandemic” of racial injustice that continued to metastasize—spawning more pain-points such as online environments where racism became unmasked when face-to-face norms were abandoned. These revelations about the shadow side of online learning are particularly concerning in the context of leadership education and its commitment to inclusion, collaboration, and holism. Given this new context for online leadership education, the purpose of this piece is to reflect on how the Journal of Leadership Education has shepherded the journey of online leadership education and what the future of this journey might look like for online leadership educators committed to change. Scaffolded by the Community of Inquiry model, we offer promising practices that address cognitive, social, teaching, and learner presence in the pursuit of culturally relevant/sustaining and equitable online leadership education.
EXPLORING STOICISM IN LEADERSHIP: A Comparison with Emotional Intelligence in Undergraduate Leadership Students
Authors: Brown Amy M. C. , Sowcik Matthew , Stedman Nicole L. P. , Bunch James C.
Published: March 2023

This study was the first to examine two related constructs within the context of leadership. Stoicism is an ancient philosophy offering practical advice for a virtuous and eudaemonic life. As a method to examine one’s emotional experiences (Sellars, 2006), leaders such as Roman Emperor Marcus Aurelius and Teddy Roosevelt (Aurelius, ca. 160 A.D., 2002) practiced Stoicism, yet mentions of it within the field of leadership research have been scant. Leadership academics contrast desirable emotional intelligence behaviors with Stoicism (Grewal & Salovey, 2005; Mayer et al., 2008). Regardless, these two constructs are both concerned with effectively managing emotions, practicing self-awareness, high levels of motivation, and sensitivity to the expression of emotion in others (Goleman, 2005; Pigliucci, 2017; Salzgeber, 2019)

Undergraduate students in a leadership minor (_N_ = 445) at a public university completed the Emotional and Social Competency Inventory - University and the Liverpool Stoicism Scale. Analysis included a description of assessment results, an examination or the relationship between variables and differences in participant’s scores based on race, gender, and age. Stoicism and emotional self-awareness showed a moderate, statistically significant negative correlation (_r_ = - 0.391, _p_ = .05). A low, statistically significant negative relationship was reported between stoicism and the relationship management competency of teamwork (p = .003, r = -.018), and a low statistically significant positive relationship between self-management competencies, adaptability (p = .043, r = .189) and emotional self-control (p = .039, r = .192). Student’s Stoicism scores were significantly correlated with gender (_t_(113) = 2.479; _p_ = .015, _d_ = .564)

The research findings provided baseline statistics for continued exploration of Stoicism within the context of leadership. Future research that better aligns with the original doctrines of the philosophy is recommended, particularly in the interest of leadership development.
THE HIDDEN LEADERSHIP CURRICULUM: Alumni Perspectives on the Leadership Lessons Gained Through Co-Curricular Engagement
Authors: Rosch David M. , May Reuben A , Wilson Kevin D. , Spencer Gayle L.
Published: March 2023

Co-curricular engagement in postsecondary education provides students with a breadth of opportunity for leadership-focused developmental experiences. However, few studies have qualitatively examined in detail how alumni describe years later how formal co-curricular involvement contributes to their development. Such lack of attention has resulted in what we describe as a “hidden leadership curriculum” embedded in co-curricular engagement. To address this gap in the literature, we explored the leadership experiences of 25 recent alumni who were engaged within various co-curricular organizations, and the leadership lessons relevant to their professional success that they report learning as a direct result of their involvement. Findings from this study reveal how the inherent organizational challenges embedded within co-curricular engagements lead students to develop a more interdependent, relational conception of effective leadership behaviors. These conceptualizations place value on collective group engagement and decision-making, and help students recognize group needs over individual desires. In addition, many participants reported acquiring the value of generativity – building a leadership pipeline - within their respective co-curricular organizations. We discuss practical implications, such as the central role of challenging experiences within the co-curriculum, and suggest future research recommendations.
EFFECTIVENESS OF A STRENGTHS-BASED LEADERSHIP COACHING PROGRAM FOR WOMEN
Authors: Petrone Christina Glance , Luzynski Cheyenne , Petrone Ashley B. , Holmes Maja Husar , Dagen Allison Swan , Lockman Julie A.
Published: March 2023

Strengths-based coaching has emerged in past decades as an asset-based approach that can help individuals identify, harness, and leverage their strengths to achieve professional and personal goals. This paper shares the design and outcomes of a year-long strengths-based coaching program to support leadership development within the context of one university’s women’s leadership initiative.

Program outcomes and changes in participants’ perceived confidence in identifying and applying their strengths in different contexts were evaluated through an online survey using a Likert-based REDCap survey tool after participation in the program. Findings strongly suggest that most participants lacked the self-confidence and/or self-awareness to recognize their own strengths in a granular way prior to the program. Themes that emerged in the survey findings point to the following program outcomes: participants gained an increased ability to identify and value one’s own leadership strengths, an increased ability to recognize and value the strengths of others, and a supportive community of women leaders to share experiences and reflect on the application of their strengths as part of their leadership journey.

Further studies are needed to understand and measure how a program such as this can impact one’s leader identity, self-awareness, and self-confidence. Given the critical need for women’s leadership opportunities, this program shows promise as a means to strengthen women’s leadership across career stages and disciplines.
Posterior composite restorations including the Clark cavity design and superior Class II contacts using a novel matrix system: part 2
Authors: Burgess Claire , Hassall Dominic
Published: March 2023

In the second part of this series, we describe the use of the Bioclear Method for posterior composite restorations, including modern cavity design and techniques to achieve predictable contacts with Class II restorations.

CPD/Clinical Relevance: This article highlights a clinically relevant and modern method that can be used for placing anterior and posterior direct composite restorations.