A proposed stratification system to address the heterogeneity of Subdural Hematoma Outcome reporting in the literature.

A major challenge within the academic literature on SDHs has been inconsistent outcomes reported across studies. Historically, patients have been categorized by the blood-product age identified on imaging (i.e., acute, subacute, or chronic). However, this schematic has likely played a central role in producing the heterogeneity encountered in the literature. In this investigation, a total of 494 patients that underwent SDH evacuation at a tertiary medical center between November 2013-December 2021 were retrospectively identified. Mechanism of injury was reviewed by the authors and categorized as either positive or negative for a high-velocity impact (HVI) injury. Any head strike injury leading to the formation of a SDH while traveling at a velocity beyond that of normal locomotion or daily activities was categorized as an HVI. Patients were subsequently stratified by those with an acute SDHs after a high-velocity impact (aSDHHVI), those with an acute SDH without a high-velocity impact injury (aSDHWO), and those with any combination of subacute or chronic blood products (mixed-SDH [mSDH]). Nine percent (n = 44) of patients experienced an aSDHHVI, 23% (n = 113) aSDHWO, and 68% (n = 337) mSDH. Between these groups, highly distinct patient populations were identified using several metrics for comparison. Most notably, aSDHHVI had a significantly worse neurological status at discharge (50% vs. 23% aSDHWO vs. 8% mSDH; p < 0.001) and mortality (25% vs. 8% aSDHWO vs. 4% mSDH; p < 0.001). Controlling for gender, midline shift (mm), and anticoagulation use in the acute SDH population, multivariable logistic regression revealed a 6.85x odds ratio (p < 0.001) for poor outcomes in those with a positive history for a high-velocity impact injury. As such, the distribution of patients that suffer an HVI related acute SDH versus those that do not can significantly affect the outcomes reported. Adoption of this stratification system will help address the heterogeneity of SDH reporting in the literature while still closely aligning with conventional reporting.

The Relationship of low-serum Vitamin D and Early Dental Implant Failure.

The aim of this study was to assess the effects of serum vitamin D levels and its relationship to early dental implant failures. A total of 174 implants in 109 patients were placed and serum vitamin D levels of those patients were noted the day of implant placement. Implants were followed up until restoration, approximately 3-6 months later, and any implant failure was noted based on 50% or more bone loss or implant mobility. Eight individuals had an implant fail early and their vitamin D levels had a mean of 42.54 ng/ml compared to the successful patients' levels of 31.92 ng/ml. Although not statistically significant, there was no correlation with low serum vitamin D levels of patients and early implant failure. Keywords: dental implant, implant failure, vitamin D.

Conservative Management of Acute Sports-Related Concussions: A Narrative Review.

This review explores the application of the conservative management model for pain to sports-related concussions (SRCs), framing concussions as a distinct form of pain syndrome with a pathophysiological foundation in central sensitization. Drawing parallels with proven pain management models, we underscore the significance of a proactive approach to concussion management. Recognizing concussions as a pain syndrome allows for the tailoring of interventions in alignment with conservative principles. This review first covers the epidemiology and controversies surrounding prolonged concussion recovery and persistent post-concussion symptoms (PPCS). Next, the pathophysiology of concussions is presented within the central sensitization framework, emphasizing the need for early intervention to mitigate the neuroplastic changes that lead to heightened pain sensitivity. Five components of the central sensitization process specific to concussion injuries are highlighted as targets for conservative interventions in the acute period: peripheral sensitization, cerebral metabolic dysfunction, neuroinflammation, glymphatic system dysfunction, and pain catastrophizing. These proactive interventions are emphasized as pivotal in accelerating concussion recovery and reducing the risk of prolonged symptoms and PPCS, in line with the philosophy of conservative management.

Extreme-aged patients (≥ 85 years) experience similar outcomes as younger geriatric patients following chronic subdural hematoma evacuation: a matched cohort study.

Subdural hematoma (SDH) evacuation represents one of the most frequently performed neurosurgical procedures. Several reports cite a rise in both the age and number of patient's requiring treatment, due in part to an aging population and expanded anticoagulation use. However, limited data and conflicting conclusions exist on extreme-aged geriatric patients (≥ 85 years of age) after undergoing surgery. Patients undergoing SDH evacuation at a tertiary academic medical center between November 2013-December 2021 were retrospectively identified. The study group consisted of patients ≥ 85 years (Group 1) diagnosed with a chronic SDH surgically evacuated. A control group was created matching patients by 70-84 years of age, gender, and anticoagulation use (Group 2). Multiple metrics were evaluated between the two including length-of hospital-stay, tracheostomy/PEG placement, reoperation rate, complications, discharge location, neurological outcome at the time of discharge, and survival. A total of 130 patients were included; 65 in Group 1 and 65 in Group 2. Patient demographics, medical comorbidities, SDH characteristics, international normalized ratio, partial thromboplastin time, and use of blood thinning agents were similar between the two groups. Kaplan Meier survival analysis at one-year was 80% for Group 1 and 76% for Group 2. No significant difference was identified using the log-rank test for equality of survivor functions (p = 0.26). All measured outcomes including GCS at time of discharge, length of stay, rate of reoperations, and neurological outcome were statistically similar between the two groups. Backwards stepwise conditional logistic regression revealed no significant association between poor outcomes at the time of discharge and age. Alternatively, anticoagulation use was found to be associated with poor outcomes (OR 3.55, 95% CI 1.08-11.60; p = 0.036). Several outcome metrics and statistical analyses were used to compare patients ≥ 85 years of age to younger geriatric patients (70-84 years) in a matched cohort study. Adjusting for age group, gender, and anticoagulation use, no significant difference was found between the two groups including neurological outcome at discharge, reoperation rate, and survival.

Tolerability, safety, and immunogenicity of the novel oral polio vaccine type 2 in children aged 6 weeks to 59 months in an outbreak response campaign in The Gambia: an observational cohort study.

BACKGROUND: Novel oral polio vaccine type 2 (nOPV2) has been used to interrupt circulating vaccine-derived poliovirus type 2 outbreaks following its WHO emergency use listing. This study reports data on the safety and immunogenicity of nOPV2 over two rounds of a campaign in The Gambia. METHODS: This observational cohort study collected baseline symptoms (vomiting, diarrhoea, irritability, reduced feeding, and reduced activity) and axillary temperature from children aged 6 weeks to 59 months in The Gambia before a series of two rounds of a nOPV2 campaign that took place on Nov 20-26, 2021, and March 19-22, 2022. Serum and stool samples were collected from a subset of the participants. The same symptoms were re-assessed during the week following each dose of nOPV2. Stool samples were collected on days 7 and 28, and serum was collected on day 28 following each dose. Adverse events, including adverse events of special interest, were documented for 28 days after each campaign round. Serum neutralising antibodies were measured by microneutralisation assay, and stool poliovirus excretion was measured by real-time RT-PCR. FINDINGS: Of the 5635 children eligible for the study, 5504 (97·7%) received at least one dose of nOPV2. There was no increase in axillary temperature or in any of the baseline symptoms following either rounds of the campaigns. There were no adverse events of special interest and no other safety signals of concern. Poliovirus type 2 seroconversion rates were 70% (95% CI 62 to 78; 87 of 124 children) following one dose of nOPV2 and 91% (85 to 95; 113 of 124 children) following two doses. Poliovirus excretion on day 7 was lower after the second round (162 of 459 samples; 35·3%, 95% CI 31·1 to 39·8) than after the first round (292 of 658 samples; 44·4%, 40·6 to 48·2) of the campaign (difference -9·1%; 95% CI -14·8 to -3·3), showing the induction of mucosal immunity. INTERPRETATION: In a campaign in west Africa, nOPV2 was well tolerated and safe. High rates of seroconversion and evidence of mucosal immunity support the licensure and WHO prequalification of this vaccine. FUNDING: Bill & Melinda Gates Foundation.

Are Medical School Curricula Adapting With Their Students? A Survey on How Medical Students Study and How it Relates to USMLE Step 1 Scores.

OBJECTIVES: Over the years, medical schools have evolved their curricula in response to the medical field, faculty, and students. The current study aims to examine how medical students study, what resources they most commonly use, and how it relates to United States Medical Licensing Examination (USMLE) Step 1 scores. METHODS: A cross-sectional survey study of United States medical students was distributed via social media, GroupMe school chats, and school listservs from September 8, 2020, to December 12, 2020. The survey gathered data including, demographic and school information, resources students, time spent using each resource, and USMLE Step 1 scores. RESULTS: The survey was completed by 560 students from 102 different United States medical schools. Study guides as online resources (83.2%) were mostly used, lecture (82.5%), Anki (spaced repetition flashcards, 68.3%), and school-organized sessions (workshops, labs, and small groups) (60.7%). Of the students surveyed, 90% attended schools with a recorded lecture option. Only 54% of these students watched their lectures live. When watched online, the average watching speed was 1.75 ± 0.4× with a mode of 2× speed. In examining different medical school styles, schools with a 1.5-year preclinical curriculum had higher USMLE Step 1 scores (244.5 ± 15.6 vs 236.9 ± 16.2, P-score = .024) compared to schools that did not (1- or 2-year preclinical curriculum). CONCLUSION: Medical students seem to be using third-party resources in addition to their medical school curriculums. Because students are already broadly using these, medical schools could allow their curriculums to reference, require, or complement third-party online resources. Additionally, because of their increased cost, medical schools could consider ways to alleviate the cost on medical students as a means of equitable support. Lastly, Step 1 scores significantly correlated with schools with a 1.5-year preclinical curriculum, although the exact reasoning for this remains uncertain.

Federalism for Bioethics?

In the wake of the Dobbs decision withdrawing federal constitutional protection for reproductive rights, the United States is in the throes of federalist conflicts. Some states are enacting draconian prohibitions of abortion or gender-affirming care, whereas other states are attempting to shield providers and their patients seeking care. This article explores standard arguments supporting federalism, including that it allows for cultural differences to remain along with a structure that provides for the advantages of common security and commerce, that it provides a laboratory for confined experiments, that it is government closer to the people and thus more informed about local needs and preferences, and that it creates layers of government that can constrain one another and thus doubly protect rights. We contend that these arguments do not justify significant differences among states with respect to the recognition of important aspects of well-being; significant injustices among subnational units cannot be justified by federalism. However, as nonideal theorists, we also observe that federalism presents the possibility of some states protecting rights that others do not. Assuming that movement among subnational units is protected, those who are fortunate enough to be able to travel will be able to access rights they cannot access at home. Nonetheless, movement may not be readily available to minors, people without documentation, people with disabilities, people who lack economic resources, or people who have responsibilities that preclude travel. Only rights protection at the federal level will suffice in such cases.

Unsupervised feature extraction of aerial images for clustering and understanding hazardous road segments.

Aerial image data are becoming more widely available, and analysis techniques based on supervised learning are advancing their use in a wide variety of remote sensing contexts. However, supervised learning requires training datasets which are not always available or easy to construct with aerial imagery. In this respect, unsupervised machine learning techniques present important advantages. This work presents a novel pipeline to demonstrate how available aerial imagery can be used to better the provision of services related to the built environment, using the case study of road traffic collisions (RTCs) across three cities in the UK. In this paper, we show how aerial imagery can be leveraged to extract latent features of the built environment from the purely visual representation of top-down images. With these latent image features in hand to represent the urban structure, this work then demonstrates how hazardous road segments can be clustered to provide a data-augmented aid for road safety experts to enhance their nuanced understanding of how and where different types of RTCs occur.

Circadian therapy interventions for glymphatic dysfunction in concussions injuries: A narrative review.

There are two primary threats to the brain after concussion. The first is a buildup of neurotoxic proteins in the brain. The second, a partial consequence of the first, is a sustained neuroinflammatory response that may lead to central sensitization and the development of persistent post-concussive symptoms. These threats make neurotoxin clearance a high clinical priority in the acute period after injury. The glymphatic system is the brain's primary mechanism for clearing neurotoxic waste. The glymphatic system is intimately tied to the sleep cycle and circadian dynamics. However, glymphatic dysfunction and sleep disturbances are nearly ubiquitous in the acute period after concussion injury. Because of this, sleep optimization via circadian therapy is a time-sensitive and critical tool in acute concussion management.

Factors influencing intention to plagiarize among nursing students in the Philippines.

Background: Plagiarism is an ethical concern among students but is insufficiently discussed and acknowledged in some educational institutions. Determining what factors influence plagiarism can help the academic community manage its incidence. Objective: This study determined the factors affecting the intention to plagiarize among Filipino nursing students. Methods: Utilizing a cross-sectional research design, data were gathered from 304 nursing students last June 2021 using valid instruments administered online. Regression analysis identified influencing factors of intention to plagiarize. Results: Findings indicated a generally low intention (M = 1.47, SD = 0.74) to plagiarize among nursing students. Internet literacy (B = -0.314, p <0.001), attitude (B = 0.257, p <0.001), moral obligation (B = -0.236, p <0.001), past behavior (B = 0.139, p <0.001), and subjective norm (B = -0.095, p = -0.001) influenced nursing students' plagiarism intention. Conclusion: Several interrelated factors play major roles in nursing students' tendency to plagiarize. Creating an educational environment that does not favor the unethical practice of plagiarism is recommended for nursing schools.

Evaluation of Latex Immunoturbidimetric Assay Thresholds and HIT in Cardiothoracic Surgery.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a common differential diagnosis in cardiothoracic surgery. The latex immunoturbidimetric assay (LIA) is an enhanced immunoassay that has recently been introduced for the detection of total HIT immunoglobulin and retains a higher specificity of 95% compared to the enzyme-linked immunosorbent assay. OBJECTIVES: To investigate if a semiquantitative relationship exists between increasing LIA levels beyond the current positivity threshold and its correlation to positive serotonin release assay results in cardiothoracic surgery. METHODS: This was a multicenter, observational cohort of cardiothoracic surgery patients initiated on anticoagulation with heparin-based products. To conduct sensitivity and specificity analysis of LIA values, HIT positive was defined as a LIA value ≥1 unit/mL and HIT negative was defined as a LIA level <1 unit/mL. A receiver operating characteristic (ROC) analysis was utilized to evaluate the predictive performance of the LIA. RESULTS: At manufactures' cutoffs of ≥1.0 unit/mL, LIA sensitivity and specificity was 93.8% and 22%, respectively, yielding a false positive rate of 78%. At a higher cutoff of 4.5 units/mL, LIA sensitivity and specificity was 75% and 71%, respectively, yielding a false positive rate of 29% and an area under the ROC curve of 0.75 (P = .01; 95% confidence interval: 0.621-0.889). Bivalirudin was initiated in 84.6% of false positive LIA results. CONCLUSION: This study suggests that the diagnostic accuracy of the LIA can be optimized by increasing the LIA positivity threshold. Proposing a higher LIA cutoff, may mitigate unwarranted anticoagulation and bleeding outcomes.

Cholinergic and noradrenergic axonal activity contains a behavioral-state signal that is coordinated across the dorsal cortex.

Fluctuations in brain and behavioral state are supported by broadly projecting neuromodulatory systems. In this study, we use mesoscale two-photon calcium imaging to examine spontaneous activity of cholinergic and noradrenergic axons in awake mice in order to determine the interaction between arousal/movement state transitions and neuromodulatory activity across the dorsal cortex at distances separated by up to 4 mm. We confirm that GCaMP6s activity within axonal projections of both basal forebrain cholinergic and locus coeruleus noradrenergic neurons track arousal, indexed as pupil diameter, and changes in behavioral engagement, as reflected by bouts of whisker movement and/or locomotion. The broad coordination in activity between even distant axonal segments indicates that both of these systems can communicate, in part, through a global signal, especially in relation to changes in behavioral state. In addition to this broadly coordinated activity, we also find evidence that a subpopulation of both cholinergic and noradrenergic axons may exhibit heterogeneity in activity that appears to be independent of our measures of behavioral state. By monitoring the activity of cholinergic interneurons in the cortex, we found that a subpopulation of these cells also exhibit state-dependent (arousal/movement) activity. These results demonstrate that cholinergic and noradrenergic systems provide a prominent and broadly synchronized signal related to behavioral state, and therefore may contribute to state-dependent cortical activity and excitability.

Diagnosing Oral Granulomatous Lesions: A Case Report.

The diagnosis of oral granulomatous lesions raises many challenges for the clinician. This article, which includes a case report, describes a process to formulate differential diagnoses by identifying distinguishing characteristics of an entity and applying that information to attain understanding of the ongoing pathophysiological process. Relevant clinical, radiographic, and histologic findings of common disease entities that can mimic clinical and radiographic presentation of this case are discussed to aid dental clinicians in identifying and diagnosing similar lesions in their practice.

Direct Uptake of Nutrition and Caffeine Study (DUNCS): biscuit based comparative study.

OBJECTIVES: To identify the time required to achieve optimal palatability of a cup of tea without risk of harm (oral scalding) using the resources available in a standard hospital staff room, and to identify the best accompanying biscuit for nutritional content, crunchiness, and integrity when dunking. DESIGN: Prospective, non-masked, biscuit based, comparative study. SETTING: Staff room in the surgery department of a UK hospital. PARTICIPANTS: Four different varieties of round, non-chocolate biscuit: oat, digestive, rich tea, and shortie. A standardised cup of tea was determined on the basis of the investigators' preference for colour and palatability and pragmatic tea making methods. MAIN OUTCOME MEASURES: The main outcome was time to achieve a safe temperature for consumption of tea, and the best biscuit to pair with the tea on the basis of nutritional content, absorptive ability, crunchiness, and integrity after dunking. Biscuits were ranked first to last (according to scores 1-4), with penalty points given for adverse events such as scalds and breakability. RESULTS: Baseline data suggested that after adding 240 mL of freshly boiled water to an unwarmed mug containing a tea bag, the median temperature of a standard cup of tea was 82ºC (range 81-84ºC). Optimal palatability and agreed universal drinking temperature of 61ºC was achieved at 400 (range 360-420) seconds with 30 mL of cow's milk and 370 (330-450) seconds with 40 mL of milk. The investigators considered tea colour preferable with 40 mL of milk. CONCLUSION: Healthcare workers can safely consume a cup of tea after less than 10 minutes, especially if enjoyed with a biscuit. Making time for a cup of tea may help healthcare workers avoid their break point.

Feasibility of gabapentin as an intervention for neurorecovery after an acute spinal cord injury: Protocol.

Introduction: This protocol is describing the first ever prospective, mock-efficacy, dose exploration trial design testing the feasibility of administering gabapentin in the acute setting as an intervention for neurorecovery. Gabapentin is an FDA-approved medication for treating seizures and postherpetic neuralgia and is used broadly off-label for neuropathic pain management for many conditions, including spinal cord injury. Emerging data suggests that when given early after spinal cord injury onset and in low-medium doses, gabapentin may have properties that promote recovery of neurological function. The objective of this trial is to assess the feasibility of conducting an efficacy trial in which gabapentin is started early after injury, is restricted in its dose, and is not used for pain management. Methods and analysis: Forty-two people aged 18 years or older with any level and any severity of spinal cord injury induced by a trauma will be enrolled, randomized, and have the first dose of study medication by 120 h post-injury onset. Participants will be randomly assigned to one of three groups: 600, 1,800 mg/day gabapentin, or placebo. Study medication will be given for a 90-day duration. Blinded assessments will be obtained at 7 days post-injury (baseline), 30 days post-injury (interim), after the 90-day treatment duration/approximately 3 months post-injury (end of treatment), and at 6 months post-injury (end of study). The key analysis parameters will evaluate feasibility of recruitment of target population, delivery of drug treatment protocol, maintenance of blinding, and retention of participants. Discussion: Outputs from this trial will inform research and clinical practice on the effects of manipulating gabapentin for non-pain management purposes in the acute setting and will guide the development of a properly powered efficacy trial of gabapentin as an intervention for neurorecovery in spinal cord injury. Ethics and dissemination: The study was approved by the MetroHealth Institutional Review Board (IRB21-00609) and registered at clinicaltrials.gov prior to enrolling any participants. Dissemination will include peer-reviewed publications, presentations at professional conferences and in the community, and through other healthcare and public venues. Clinical trial registration: www.ClinicalTrials.gov, identifier: NCT05302999; protocol version 1.1 approved 05/23/2022. Trial funding: National Institute on Disability, Independent Living and Rehabilitation Research.

Auto-segmentation and time-dependent systematic analysis of mesoscale cellular structure in ß-cells during insulin secretion.

The mesoscale description of the subcellular organization informs about cellular mechanisms in disease state. However, applications of soft X-ray tomography (SXT), an important approach for characterizing organelle organization, are limited by labor-intensive manual segmentation. Here we report a pipeline for automated segmentation and systematic analysis of SXT tomograms. Our approach combines semantic and first-applied instance segmentation to produce separate organelle masks with high Dice and Recall indexes, followed by analysis of organelle localization based on the radial distribution function. We demonstrated this technique by investigating the organization of INS-1E pancreatic ß-cell organization under different treatments at multiple time points. Consistent with a previous analysis of a similar dataset, our results revealed the impact of glucose stimulation on the localization and molecular density of insulin vesicles and mitochondria. This pipeline can be extended to SXT tomograms of any cell type to shed light on the subcellular rearrangements under different drug treatments.

Latinos and the Pandemic: Results from the National Social Life, Health, and Aging Project-COVID-19 Study.

Pre-pandemic disparities placed Latinos at risk for COVID-19. This report describes the associations between increased viral exposure through social contact and material hardship and the uneven distribution of COVID-19 morbidity among Latino older adults using data from the recently released supplement to the National Social Life, Heath, and Aging Project (NSHAP) (N = 2672), a population-based panel study of adults born 1920-1965. Logistic regression revealed that material hardship and reliance on outside help were significantly correlated with COVID-19 infection, which may partially explain the disproportionate burden Latinos experience during the pandemic.

Mönckeberg Arteriosclerosis of the Facial Vasculature Presentation on CBCT: A Case Report.

Mönckeberg arteriosclerosis, also known as Mönckeberg sclerosis or Mönckeberg medial calcinosis, is a well-documented phenomenon in medicine due to its association with a number of serious systemic conditions and aging. This article presents a unique case of Mönckeberg arteriosclerosis in the oral facial region demonstrated clearly on cone-beam computed tomography (CBCT). The reporting of Mönckeberg arteriosclerosis in dental literature is uncommon even though the radiographic features of the head and neck on plain film and CBCT are unique to the condition. As dentistry and medicine strive to move toward an integrated one-health model, it will be important for dental practitioners to recognize this condition during dental radiographic evaluation. A practitioner's understanding of the potential medical implications and the need for appropriate referral to a medical colleague could be lifesaving for a dental patient.

Tumour Versus Germline BRCA Testing in Ovarian Cancer: A Single-Site Institution Experience in the United Kingdom.

The aim of this audit was to evaluate the usefulness and serviceability of testing for pathogenic mutations in BRCA1 or BRCA2 (BRCA1/2) genes in ovarian cancer (OC) patients. One hundred and thirty-five patients with more common histological sub-types of OC were retrospectively identified between 2011 and 2019. The fail rate of the molecular analysis was 7.4% (10/135). One hundred and twenty-five records were evaluated: 99 (79.2%) patients had wild-type BRCA (both somatic and germline); tumour BRCA1/2 (tBRCA1/2) pathogenic mutations were found in 20 (16%) patients with distribution between BRCA1 and BRCA2 being 40% and 60%, respectively; 13 (10.4%) patients with pathogenic variants had germline mutations; and tBRCA1/2 with variant of unknown significance (VUS), in the absence of pathogenic BRCA1 or BRCA2 variants, was detected in 6 (4.8%) patients. Our data show that expanding the molecular service to the routine first-tumour testing for patients with OC will potentially increase the detection rate of BRCA mutations, thereby providing early benefits of PARP inhibitors therapy. The tumour testing service should continue to be offered to newly diagnosed patients with high-grade epithelial cancers, including high-grade serous carcinoma, but also with carcinosarcomas and poorly-differentiated metastatic adenocarcinomas of unknown origin.

SARS-CoV-2 Spike receptor-binding domain with a G485R mutation in complex with human ACE2

Since SARS-CoV-2 emerged in 2019, genomic sequencing has identified mutations in the viral RNA including in the receptor-binding domain of the Spike protein. Structural characterisation of the Spike carrying point mutations aids in our understanding of how these mutations impact binding of the protein to its human receptor, ACE2, and to therapeutic antibodies. The Spike G485R mutation has been observed in multiple isolates of the virus and mutation of the adjacent residue E484 to lysine is known to contribute to antigenic escape. Here, we have crystallised the SARS-CoV-2 Spike receptor-binding domain with a G485R mutation in complex with human ACE2. The crystal structure shows that while the G485 residue does not have a direct interaction with ACE2, its mutation to arginine affects the structure of the loop made by residues 480-488 in the receptor-binding motif, disrupting the interactions of neighbouring residues with ACE2 and with potential implications for antigenic escape from vaccines, antibodies and other biologics directed against SARS-CoV-2 Spike.