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BackgroundAmblyopia is the most common developmental vision disorder in children. The initial treatment consists of refractive correction. When insufficient, occlusion therapy may further improve visual acuity. However, the challenges and compliance issues associated with occlusion therapy may result in treatment failure and residual amblyopia. Virtual reality (VR) games developed to improve visual function have shown positive preliminary results. The aim of this study is to determine the efficacy of these games to improve vision, attention, and motor skills in patients with residual amblyopia and identify brain-related changes. We hypothesize that a VR-based training with the suggested ingredients (3D cues and rich feedback), combined with increasing the difficulty level and the use of various games in a home-based environment is crucial for treatment efficacy of vision recovery, and may be particularly effective in children.MethodsThe AMBER study is a randomized, cross-over, controlled trial designed to assess the effect of binocular stimulation (VR-based stereoptic serious games) in individuals with residual amblyopia (n = 30, 6-35 years of age), compared to refractive correction on vision, selective attention and motor control skills. Additionally, they will be compared to a control group of age-matched healthy individuals (n = 30) to account for the unique benefit of VR-based serious games. All participants will play serious games 30 min per day, 5 days per week, for 8 weeks. The games are delivered with the Vivid Vision Home software. The amblyopic cohort will receive both treatments in a randomized order according to the type of amblyopia, while the control group will only receive the VR-based stereoscopic serious games. The primary outcome is visual acuity in the amblyopic eye. Secondary outcomes include stereoacuity, functional vision, cortical visual responses, selective attention, and motor control. The outcomes will be measured before and after each treatment with 8-week follow-up.DiscussionThe VR-based games used in this study have been conceived to deliver binocular visual stimulation tailored to the individual visual needs of the patient, which will potentially result in improved basic and functional vision skills as well as visual attention and motor control skills.Trial registrationThis protocol is registered on ClinicalTrials.gov (identifier: NCT05114252) and in the Swiss National Clinical Trials Portal (identifier: SNCTP000005024).

Associations between human genetic variation and clinical phenotypes have become a foundation of biomedical research. Most repositories of these data seek to be disease-agnostic and therefore lack disease-focused views. The Type 2 Diabetes Knowledge Portal (T2DKP) is a public resource of genetic datasets and genomic annotations dedicated to type 2 diabetes (T2D) and related traits. Here, we seek to make the T2DKP more accessible to prospective users and more useful to existing users. First, we evaluate the T2DKP's comprehensiveness by comparing its datasets with those of other repositories. Second, we describe how researchers unfamiliar with human genetic data can begin using and correctly interpreting them via the T2DKP. Third, we describe how existing users can extend their current workflows to use the full suite of tools offered by the T2DKP. We finally discuss the lessons offered by the T2DKP toward the goal of democratizing access to complex disease genetic results.

Polygenic scores (PGSs) combine the effects of common genetic variants1,2 to predict risk or treatment strategies for complex diseases3-7. Adding rare variation to PGSs has largely unknown benefits and is methodically challenging. Here, we developed a method for constructing rare variant PGSs and applied it to calculate genetically modified hemoglobin A1C thresholds for type 2 diabetes (T2D) diagnosis7-10. The resultant rare variant PGS is highly polygenic (21,293 variants across 154 genes), depends on ultra-rare variants (72.7% observed in fewer than three people) and identifies significantly more undiagnosed T2D cases than expected by chance (odds ratio = 2.71; P = 1.51 × 10-6). A PGS combining common and rare variants is expected to identify 4.9 million misdiagnosed T2D cases in the United States-nearly 1.5-fold more than the common variant PGS alone. These results provide a method for constructing complex trait PGSs from rare variants and suggest that rare variants will augment common variants in precision medicine approaches for common disease.

We investigate the extent to which human genetic data are incorporated into studies that hypothesize novel links between genes and metabolic disease. To lower the barriers to using genetic data, we present an approach to enable researchers to evaluate human genetic support for experimentally determined hypotheses.

Evidence is growing to support minimally invasive surgical evacuation of intraparenchymal hematomas, particularly those with minimal residual hematoma volumes following evacuation. To maximize the potential for neurologic recovery, it is imperative that the trajectory for access to the hematoma minimizes disruption of normal parenchyma. Flat panel detector CT-based navigation and needle guidance software provides a platform that uses flat panel detector CT imaging obtained on the angiography table to aid reliable and safe access to the hematoma. In addition to providing a high degree of accuracy, this method also allows convenient and rapid re-imaging to assess navigation accuracy and the degree of hematoma evacuation prior to procedural completion. We provide a practical review of the syngo iGuide needle guidance software and the methodology for incorporating its use, and the software of other vendors, in a variety of minimally invasive methods for evacuation of intraparenchymal hematomas.

Hundreds of thousands of genetic variants have been reported to cause severe monogenic diseases, but the probability that a variant carrier develops the disease (termed penetrance) is unknown for virtually all of them. Additionally, the clinical utility of common polygenetic variation remains uncertain. Using exome sequencing from 77,184 adult individuals (38,618 multi-ancestral individuals from a type 2 diabetes case-control study and 38,566 participants from the UK Biobank, for whom genotype array data were also available), we apply clinical standard-of-care gene variant curation for eight monogenic metabolic conditions. Rare variants causing monogenic diabetes and dyslipidemias display effect sizes significantly larger than the top 1% of the corresponding polygenic scores. Nevertheless, penetrance estimates for monogenic variant carriers average 60% or lower for most conditions. We assess epidemiologic and genetic factors contributing to risk prediction in monogenic variant carriers, demonstrating that inclusion of polygenic variation significantly improves biomarker estimation for two monogenic dyslipidemias.

• Webinar increased insight into neurosurgery and the path to become a neurosurgeon. • There is a substantial appetite for virtual content related to neurosurgery. • USMSs, IMSs, and undergraduates have different motivations for webinar attendance. • Webinar format may effectively provide international exposure to neurosurgery. During the COVID-19 pandemic, the American Association of Neurological Surgeons (AANS) Young Neurosurgeons Committee (YNC) and Neurosurgery Research & Education Foundation (NREF) launched the YNC-NREF Webinar Series to provide young and aspiring neurosurgeons with timely information, education, and inspiration in the absence of in-person programming. Five 90-minute Zoom webinars were evaluated, each including 1–2 keynote speakers, a panel discussion, and an audience question-and-answer section. Topics included overviews of neurosurgery, the match, subspecialties, and inspirational career stories. Optional pre- and post-webinar surveys with 11-point Likert-type scores were distributed to attendees. We compared groups using chi-squared and Kruskal-Willis tests, and perceptions pre- and post-webinar using Mann-Whitney tests. The webinars were live using Zoom, and the recordings were published on NREF's YouTube channel. The webinar series targeted young neurosurgeons. The first five episodes had a particular focus on medical students and undergraduates. A total of 673 unique participants attended the webinar series; 257 (38%) and 78 (11%) attendees completed the pre- and post-webinar survey, respectively. Respondents had high baseline interest in neurosurgery and were motivated to learn about the match and training in the US, understand neurosurgeons' day-to-day lives, and ask questions. There were significant differences in perceptions between USMSs, IMSs, and undergraduate students. The webinar improved attendees' knowledge about neurosurgical specialties, the match, and US neurosurgery training. The YNC and NREF effectively engaged a large, diverse audience through an online webinar series, building a foundation for future virtual programming by organized neurosurgery. ACGME competencies. 1. Medical Knowledge. 2. Professionalism. 3. Interpersonal Skills and Communication. [ABSTRACT FROM AUTHOR]

Background: Amylin, a 37‐residue amyloidogenic peptide, is co‐secreted with insulin by pancreatic beta‐cells (Verma et al. 2020). Vascular deposition of amylin has been noted in patients with diabetes and neurocognitive disorders (Ly et al., 2017) Emergent large vessel occlusions (ELVOs) result in severe ischemic strokes without appropriate treatment. Growth factors, including erythropoietin (EPO), are involved in post‐stroke recovery as a potential neuroprotectant target, inhibiting apoptosis and decreasing inflammation (Jerndal et al., 2010). Here, amylin accumulation in plasma, red blood cells (RBCs), and ELVOs (where available) and plasma EPO levels were compared between stroke and control patients. Due to amylin's amyloidogenic propensity, we hypothesized that there would be an association between amylin uptake and stroke incidence. Method: A prospective registry (Blood and Clot Thrombectomy Registry and Collaboration; BACTRAC) was developed to analyze blood and thrombus directly in patients presenting with an ELVO. Total protein concentration and amylin concentrations of clot lysates, plasma, and RBC lysates were obtained via bicinchoninic acid assay (BCA) and competitive enzyme‐linked immunosorbent assay (ELISA), respectively. Plasma EPO concentrations were obtained via ELISA. An amylin uptake coefficient (the level of amylin in RBC lysates divided by the sum of amylin present in RBC lysates and plasma) was calculated to determine the degree to which circulating amylin is depositing on RBCs. Result: Due to a significant difference between control and stroke RBCs (p = 0.0012, Figure 1) in total protein concentration, all downstream analyses were normalized to respective protein concentrations. A significant difference in amylin uptake by RBCs between stroke and control patients is shown in Figure 2 (p = 0.0073). An uptake coefficient greater than 0.50 indicates uptake of amylin by RBCs. Finally, a significant difference in plasma EPO concentration was observed between stroke and control (p = 0.0017; Figure 3). Conclusion: Consistent with our hypotheses, the present data indicates that amylin uptake by RBCs is significantly increased in stroke patients than in control patients. However, both groups show evidence of accumulation, as indicated by uptake coefficients greater than 0.50. Further, levels of erythropoietin are significantly increased in stroke patients. Further investigation into whether amylin may be thrombogenic is warranted. [ABSTRACT FROM AUTHOR]

Background and Purpose: Quantitative electroencephalogram (QEEG) parameters have been previously utilized in prognosis following acute ischemic stroke (AIS). However, the use and interpretation of QEEG parameters remain scarce following endovascular treatment (EVT) of AIS. Methods: AIS patients were prospectively enrolled following EVT, and 24-hour EEG monitoring was conducted. Global delta/alpha ratio (DAR), (delta + theta)/(alpha + beta) ratio (DTABR), and relative band power were analyzed. Primary outcome was a poor outcome (modified Rankin Scale ≥4 at 90-day follow-up). Multivariate logistic regression and diagnostic analyses were performed. Results: Poor outcome was seen in 35.5% (11/31) of enrolled patients. Multivariable logistic regression identified that higher DAR (OR 1.10, 95% CI 1.02–1.18, p = 0.02) and higher DTABR (OR 1.13, 95% CI 1.01–1.27, p = 0.02) were associated with poor outcome. DAR ≥14.3 demonstrated high sensitivity (90.9%), specificity (90.0%) and accuracy (90.3%) for poor outcome. Conclusions: Early evidence of elevated DAR and DTABR on quantitative EEG was associated with poor outcome at 90 days following EVT for AIS. [ABSTRACT FROM AUTHOR]

Intravenous thrombolysis elevates the prognostic level of acute ischemic stroke (AIS) patients. Normobaric hyperoxia (NBO) delays the progression of the infarct core and promotes neurological recovery. However, it is uncertain whether NBO can further raise the prognostic level of AIS patients based on intravenous thrombolysis. To explore the efficacy and safety of NBO combined with intravenous thrombolysis on AIS patients. This observational study included anterior circulation stroke patients who received intravenous thrombolysis within 4.5 h after stroke onset. These patients were divided into two groups based on whether or not they received NBO therapy. The baseline data and the prognosis of the two groups were compared. The primary outcome was the proportion of functional independence (modified Rankin Scale 0–2) at 90 days post discharge. A total of 227 patients were included in this study. 125 patients received NBO therapy combined with intravenous thrombolysis, while 102 patients received intravenous thrombolysis only. Overall, the rate of recanalization was 83.3%. Consequently, 101 patients (80.8%) who received NBO combined with intravenous thrombolysis and 63 patients (61.8%) in the control group achieved functional independence (P = 0.002). Multivariable logistic regression analysis showed that NBO combined with intravenous thrombolysis over intravenous thrombolysis alone was associated with 90-day functional independence (OR: 2.318; 95% CI: 1.226–4.381; P = 0.01). This study verified the efficacy and safety of NBO combined with intravenous thrombolysis in AIS patients. Prospective study is needed to further substantiate these findings. [ABSTRACT FROM AUTHOR]

Inadvertent arterial placement of central venous catheters carries serious sequelae, including pseudoaneurysm development and stroke. Although numerous strategies for therapeutic repair after arterial injury have been employed, no treatment provides a definitive standard of care. All articles published between January 2000 and July 2018 involving the placement of central venous catheters in the brachiocephalic or subclavian arteries, carotid artery, vertebral artery, and aortic arch and subsequent treatment were systematically reviewed. Arterial repair consisted of manual pressure, endovascular techniques (balloon tamponade, percutaneous closure devices, and covered stent placement), and open surgery. Success rates favored endovascular techniques and surgery over manual compression. [ABSTRACT FROM AUTHOR]

• U.S. neurosurgery residents report moderate burnout during the COVID-19 pandemic. • Neurosurgery residents report uncertainty about future healthcare reform & earnings. • The COVID-19 pandemic may impair residents' achievement of surgical milestones. • Burnout is associated with altered rotation or vacation schedules and lower PGY. • Career satisfaction is associated with delivery of neurosurgical patient care. 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 111 complete 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 their achievement 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-19 pandemic may help to formulate interventions to mitigate burnout and improve career satisfaction among residents. [ABSTRACT FROM AUTHOR]

• Anatomic risk factors increased post-operative stroke and MI risk. • Contralateral ICA stenosis increased post-operative stroke and MI risk. • Physiologic risk factors increased post-operative MI and arrhythmia risk. • Severe contralateral ICA stenosis increased postoperative carotid restenosis rate. Carotid artery stenosis accounts for up to 20% of ischemic strokes. Since the 1950 s, one of the primary surgical treatment for this condition is carotid endarterectomy (CEA). Because of improvement of medical therapy for carotid artery atherosclerosis and the increased use of carotid artery stents, CEA is indicated if the risk of stroke and death are low. The goal of this study is to characterize the impact of pre-operative stroke and stroke risk factors on post-operative CEA patient outcomes, using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) Targeted Vascular Module on CEA. Using the Targeted Vascular Module of the ACS-NSQIP, 22,116 patients who underwent CEA were identified from 2011 to 2016. Univariate analysis and multivariable logistic regression analyses were conducted to identify significant risk factors that predispose patients to stroke. Patients with pre-operative stroke comprise 42.1% of the group, with post-operative stroke being the second most common complication (2.1%). Pre-operative stroke patients were also at a higher risk for transient ischemic attacks, post-operative restenosis, post-operative distal embolization, and other complications. Patients with pre-operative risk factors, including stroke or stroke-like symptoms, high risk physiologic factors, high risk anatomic factors, and contralateral internal carotid artery stenosis were at a higher risk of developing post-operative stroke and other complications. Patients with these pre-operative risk factors should be closely monitored for post-operative complications in an effort to improve patient outcomes. [ABSTRACT FROM AUTHOR]

• Common buckthorn assimilates carbon faster than glossy in high light intensities. • Hawthorn assimilated carbon faster than both buckthorn species in moderate light. • Shade acclimated hawthorn was inferior to buckthorn at higher light intensities. • Gray dogwood assimilated carbon and used water less efficiently than buckthorn. Common buckthorn (Rhamnus cathartica L.) and glossy buckthorn (Frangula alnus Mill.; or, Rhamnus frangula L.) are non-native, invasive plant species invading U.S. Midwest natural areas. Both are ubiquitous on the Calvin College campus in Southwest Michigan where they compete with native plants for light, water, and nutrients exceptionally well. We hypothesize that common buckthorn will assimilate carbon faster and use water more efficiently than glossy buckthorn and native co-habiting shrubs in relatively dry and bright edge and meadow habitats whereas glossy buckthorn will thrive in moist and thin forest canopies. These are habitats in which each buckthorn species is abundant and colonizes rapidly. The objective of this project was to compare light use efficiency (LUE), water use efficiency (WUE), chlorophyll content and stomatal characteristics of both buckthorn species with two locally common co-habiting native species, hawthorn (Crataegus spp.) and gray dogwood (Cornus racemosa Lam.), acclimated to forest edge and understory environments on the Calvin campus in 2016 and 2017. Between 380 and 480 light use efficiency curves were measured with a LI-6400XT Portable Photosynthesis System using common and glossy buckthorn, hawthorn and gray dogwood leaves during two growing seasons from plants acclimated to edge and understory habitats. Common buckthorn assimilated carbon faster than glossy buckthorn when leaves were exposed to moderate or high light intensities. Water use efficiency was advantageous to glossy buckthorn at low to moderate light intensities, potentially enabled by the high density of stomates on lower leaf surfaces. Shade-acclimated common buckthorn displayed only minor decreases in photosynthesis rate relative to leaves in sun-acclimated plants after exposure to a wide range of light intensities possibly because of its higher leaf chlorophyll content. Sun-acclimated hawthorn grew faster than both buckthorn species when exposed to higher light intensities and produced comparable growth rates to buckthorn species in the shaded understory. Gray dogwood produced the slowest growth rate of the four species in all environments. Restoration of buckthorn infested areas is problematic in both sunny edge and shaded understory habitats and will require continuous mitigation of common and glossy buckthorn along with the concomitant establishment of more competitive native species like hawthorn. [ABSTRACT FROM AUTHOR]

The evolution of novel morphologies can signify expansion of a clade into new niches. This can be studied in the fossil record by investigating the morphospace occupancy of organisms, with small morphospaces signifying low morphological disparity and more diffuse morphospaces suggesting a broader range of morphologies adapted to different environments. Morphological disparity of many taxa (arthropods, crinoids, etc.) from the Cambrian to modern intervals have been studied in this manner. However, no study has investigated this in archaeocyaths, which, as reef builders, can have a disproportionate effect on early Cambrian biodiversity relative to their frequency. Here, we collect morphological data on archaeocyathan sponges, mostly from Laurentia. More than 600 museum specimens and 400 field samples were measured for traditional morphometric characters and discrete gross morphological characteristics. We find that archaeocyaths have an average cup/individual (body) diameter of 10.6 mm. This is significantly smaller than a selected group of modern demosponges and lithistid sponges that measure 94.1 mm and 66.8 mm in diameter, respectively, and each has a larger size variance. Archaeocyathan gross morphologies are also highly constrained to a few simple morphologies (three to six categories), while modern demosponges and lithistids are more diverse (nine categories each). These data indicate that Laurentian archaeocyaths were restricted in their morphological disparity, potentially due to limitations imposed by having a robust calcareous skeleton while still maintaining a large intervallum cavity space to facilitate passive entrainment. The fact that these Cambrian reef builders were restricted in their morphological complexity may have had a strong influence on the biodiversity of early Phanerozoic ecosystems. Furthermore, a clade limited to only a few specific morphologies is at an increased risk of extinction. [ABSTRACT FROM AUTHOR]

Objectives:Fractional flow reserve (FFR) accurately predicts the degree of stenosis and is now widely used to identify clinically significant severe coronary artery lesions. In the current study, we utilized a similar indicator, fractional flow (FF), to determine the hemodynamic impact of symptomatic intracranial atherosclerotic stenosis (ICAS) and to assess the correlation of FF with the severity of stenosis and collateral circulation. Methods:Patients with symptomatic ICAS (70–99% stenosis) confirmed on digital subtraction angiography (DSA) were consecutively recruited. FF was obtained during DSA examination with the use of pressure sensors and was measured as a ratio, comparing measurements distal to an ICAS lesion (Pd) and within the aorta (Pa). The degree of leptomeningeal collateralization was graded from zero (absent) to four (complete compensatory). The correlation between FF, anatomical stenosis, and collateral status was then analyzed. Results:Twenty-five patients with a mean age of 55.6 years were analyzed. The median percentage of stenosis and median FF were 82.3 and 0.68%, respectively. Eleven patients were found to have poor collateralization (grade 0-2), and fourteen patients were identified with good collateral circulation (grade 3-4). Overall, the hemodynamic impact of an atherosclerotic lesions worsened (decreased FF) as the percentage of stenosis increased, although this did not reach statistical significance (r = −0.398,p = 0.06). However, the status of collateralization significantly altered this correlation, worsening the hemodynamic impact in patients with poor collateral circulation (r = −0.677,p = 0.032). There was no difference in patients with good collateral circulation (r = −0.279,p = 0.356). Conclusion:An anatomically severe (70–99%) symptomatic ICAS lesion may generate significant hemodynamic stress downstream as assessed by the indicator FF, particularly in patients with poor collateral circulation. Further, good collateralization may mitigate this hemodynamic impact, partially explaining the protective effect of collateral circulation against recurrent stroke in such patients. [ABSTRACT FROM PUBLISHER]