Educational Limitations of ChatGPT in Neurosurgery Board Preparation.

Objective This study evaluated the potential of Chat Generative Pre-trained Transformer (ChatGPT) as an educational tool for neurosurgery residents preparing for the American Board of Neurological Surgery (ABNS) primary examination. Methods Non-imaging questions from the Congress of Neurological Surgeons (CNS) Self-Assessment in Neurological Surgery (SANS) online question bank were input into ChatGPT. Accuracy was evaluated and compared to human performance across subcategories. To quantify ChatGPT's educational potential, the concordance and insight of explanations were assessed by multiple neurosurgical faculty. Associations among these metrics as well as question length were evaluated. Results ChatGPT had an accuracy of 50.4% (1,068/2,120), with the highest and lowest accuracies in the pharmacology (81.2%, 13/16) and vascular (32.9%, 91/277) subcategories, respectively. ChatGPT performed worse than humans overall, as well as in the functional, other, peripheral, radiology, spine, trauma, tumor, and vascular subcategories. There were no subjects in which ChatGPT performed better than humans and its accuracy was below that required to pass the exam. The mean concordance was 93.4% (198/212) and the mean insight score was 2.7. Accuracy was negatively associated with question length (R2=0.29, p=0.03) but positively associated with both concordance (p<0.001, q<0.001) and insight (p<0.001, q<0.001). Conclusions The current study provides the largest and most comprehensive assessment of the accuracy and explanatory quality of ChatGPT in answering ABNS primary exam questions. The findings demonstrate shortcomings regarding ChatGPT's ability to pass, let alone teach, the neurosurgical boards.

The Evolution of Hand Injuries at a State's Only Level I Trauma Center: A Look From the 1980s Through the Global Pandemic.

BACKGROUND: The purpose of this study is to evaluate any changes to hand trauma in the past three decades and through the COVID-19 pandemic. We hypothesized that improved consumer safety regulations, changes in access to care, and the impact of a global pandemic, among other variables, have significantly influenced the mechanisms and treatment of hand injuries between the 1980s, 2010s (pre-COVID-19), and 2020s (post-COVID-19). METHODS: A retrospective single-center review was performed at the only level I trauma center in Mississippi, identifying all hand trauma consultations between 2012-2019 and 2020-2021, compared to aggregated data from 1989. RESULTS: Car accidents, gunshots, saw injuries, door injuries, and falls increased in 2012-2019 and 2020-2021 compared to 1989, whereas knife injuries, glass injuries, industrial injuries, and burns decreased. Crush injuries, de-gloving injuries, and lacerations with irregular edges were increased in recent cohorts, corresponding with increased amputations and tissue loss. Skin and subcutaneous injuries decreased in modern cohorts, corresponding with a decreased ability for primary skin repair and the need for more flaps. Additionally, while hospitalizations have increased, patients have improved follow-up. CONCLUSIONS: The nature of hand trauma has changed significantly over the past three decades. Increased numbers of cars and greater access to firearms might have led to increased rates of high-energy trauma, whereas burn and industrial injuries have decreased, potentially secondary to improved safety efforts. Despite increased overall hand trauma, time to treatment and follow-up have improved. Through this study, we can be more cognizant of the evolution of hand trauma in the modern era. This can allow improved access to care and further refine management to optimize functionality for hand injuries.

Characteristics and Risk Factors for Rhegmatogenous Retinal Detachment Related to Endophthalmitis.

Purpose: To evaluate the risk factors for the development of concurrent or delayed-onset rhegmatogenous retinal detachment (RRD) related to endophthalmitis as well as the anatomic and visual outcomes with subsequent RRD repair. Methods: In this retrospective case study, a 2-tailed t test (continuous) and Fisher exact test were used to determine statistical significance of the observed findings. The relative risk (RR) and 95% CIs were calculated to assess statistical significance. Results: Of the 170 patients included, 22 were found to have a concurrent or subsequent RRD. Initial treatment with pars plana vitrectomy (PPV) (RR, 3.544; 95% CI, 1.650-7.614), aphakia (RR, 4.150; 95% CI, 1.434-12.011), endogenous endophthalmitis (RR, 2.684; 95% CI, 1.065-6.764), and posterior synechiae (RR, 3.026; 95% CI, 1.408-6.505) were statistically significant risk factors for RRD. Anatomically successful repair was achieved in 77.7% of patients. Conclusions: In addition to preexisting risk factors, the initial treatment of endophthalmitis may be a significant risk factor for RRD development, with a higher incidence of subsequent RRD in patients who have PPV as the initial treatment for endophthalmitis.

Trends in Demographic and Geographic Disparities in Stroke Mortality Among Older Adults in the United States.

BACKGROUND: Stroke is a leading cause of morbidity and mortality in the United States among older adults. However, the impact of demographic and geographic risk factors remains ambiguous. A clear understanding of these associations and updated trends in stroke mortality can influence health policies and interventions. METHODS: This study characterizes stroke mortality among older adults (age ≥55) in the US from January 1999 to December 2020, sourcing data from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research. Segmented regression was used to analyze trends in crude mortality rate and age-adjusted mortality rate (AAMR) per 100,000 individuals stratified by stroke subcategory, sex, ethnicity, urbanization, and state. RESULTS: A total of 3,691,305 stroke deaths occurred in older adults in the US between 1999 and 2020 (AAMR = 233.3), with an overall decrease in AAMR during these years. The highest mortality rates were seen in nonspecified stroke (AAMR = 173.5), those 85 or older (crude mortality rate1276.7), men (AAMR = 239.2), non-Hispanic African American adults (AAMR = 319.0), and noncore populations (AAMR = 276.1). Stroke mortality decreased in all states from 1999 to 2019 with the greatest and least decreases seen in California (-61.9%) and Mississippi (-35.0%), respectively. The coronavirus pandemic pandemic saw increased stroke deaths in most groups. CONCLUSIONS: While there's a decline in stroke-related deaths among US older adults, outcome disparities remain across demographic and geographic sectors. The surge in stroke deaths during coronavirus pandemic reaffirms the need for policies that address these disparities.

Unsupervised machine learning models reveal predictive clinical markers of glioblastoma patient survival using white blood cell counts prior to initiating chemoradiation.

Background: Glioblastoma is a malignant brain tumor requiring careful clinical monitoring even after primary management. Personalized medicine has suggested the use of various molecular biomarkers as predictors of patient prognosis or factors utilized for clinical decision-making. However, the accessibility of such molecular testing poses a constraint for various institutes requiring identification of low-cost predictive biomarkers to ensure equitable care. Methods: We collected retrospective data from patients seen at Ohio State University, University of Mississippi, Barretos Cancer Hospital (Brazil), and FLENI (Argentina) who were managed for glioblastoma-amounting to 581 patient records documented using REDCap. Patients were evaluated using an unsupervised machine learning approach comprised of dimensionality reduction and eigenvector analysis to visualize the inter-relationship of collected clinical features. Results: We discovered that the serum white blood cell (WBC) count of a patient during baseline planning for treatment was predictive of overall survival with an over 6-month median survival difference between the upper and lower quartiles of WBC count. By utilizing an objective PD-L1 immunohistochemistry quantification algorithm, we were further able to identify an increase in PD-L1 expression in glioblastoma patients with high serum WBC counts. Conclusions: These findings suggest that in a subset of glioblastoma patients the incorporation of WBC count and PD-L1 expression in the brain tumor biopsy as simple biomarkers predicting glioblastoma patient survival. Moreover, machine learning models allow the distillation of complex clinical data sets to uncover novel and meaningful clinical relationships.

Plastic Surgery: Beware the Candle Burning at Both Ends.

Background: Plastic surgery dates back to 800 BC, where forehead flaps were used to reconstruct noses in India. Today, it is one of the most romanticized fields in medicine. Due to the influence of social media, there has never been a larger spotlight. Ironically, this spotlight brings a narrowed perception of the scope of plastic surgery. This study aimed to assess the scope through the eyes of the average American to identify gaps in knowledge to better represent the field. Methods: A series of questions were developed under survey methodologists and administered by Qualtrics. Responses were gathered, and data were analyzed to assess the public's knowledge of plastic surgery's scope. Results: Two thousand five hundred responses were obtained, balanced across demographics similar to that of the United States. The US population has a poor understanding of the scope of plastic surgery and how to obtain board certification. Conclusions: This survey demonstrates a gap in awareness of plastic surgery as a field and the scope outside aesthetic procedures dramatized by the media. There remains no clear understanding of the qualifications of plastic surgeons or the provider makeup of the field of cosmetic surgery. Subspecialties proved to be overlooked, and knowledge of board certification was sparse. Further effort is needed to educate both the public and patients of the scope of plastic surgery, so that they might seek and gain access to appropriate treatment in the most efficient manner to optimize outcomes regarding the form and function of the body.

Subdermal Plexus Density as It Relates to Obesity and Wound Complications in Patients Undergoing Reduction Mammaplasty.

Background: Reduction mammaplasty is one of the most common reconstructive procedures performed in plastic surgery. Multiple comorbidities play a role in postoperative wound healing complications; however, there are insufficient data on the subdermal plexus (SDP) as it relates to these comorbidities. The purpose of this study is to evaluate the relationship between body mass index (BMI) and SDP of the superficial breast tissues and examine the association between SDP and postoperative complications. Methods: After Institutional Review Board approval, screening, and informed consent, patients undergoing reduction mammaplasty were selected. Tissue to be discarded was sent to pathology for analysis of immunohistochemistry directed against endothelial cells to determine the density of the SDP. Patients with BMI <35 and ≥35 kg/m2 were compared. Statistical analysis, including 2-tailed t test and Pearson correlation, was conducted. Results: A significant difference in SDP density (standard deviation) was identified between patients with a BMI ≥35 versus <35 kg/m2 (2.65 capillaries/mm2 ± 1.8 vs 1.56 capillaries/mm2 ± 1.2; P = .033). Patients with no historical use of tobacco versus those who used tobacco showed a significantly increased SDP (2.11 capillaries/mm2 ± 1.6 vs 1.20 capillaries/mm2 ± 0.5; P = .009). A significant relationship between postoperative infection (1.00 capillaries/mm2 ± 1.1; P = .041) and hematoma/seroma (0.788 capillaries/mm2 ± 0.1; P = .003) was identified. No significant relationship was found between SDP and delayed wound healing, nipple-areolar complex complications, fat/flap necrosis, or symptomatic scar occurrence. Conclusions: There is a statistically significant increase in SDP seen with increasing BMI, which does not explain the higher rate of wound healing complications after reduction mammaplasty typically seen in the higher BMI patient population. The association between BMI and complications after reduction mammaplasty remains unclear.

The association between bone mineral density and proximal junctional kyphosis in adult spinal deformity: a systematic review and meta-analysis.

OBJECTIVE: Proximal junctional kyphosis (PJK) is a complication of surgical management for adult spinal deformity (ASD) with a multifactorial etiology. Many risk factors are controversial, and their relative importance is not fully understood. The authors aimed to elucidate the association between bone mineral density (BMD) and PJK. METHODS: A systematic literature search was performed using PubMed and Web of Science keywords of "Proximal Junctional Kyphosis [MeSH] OR Proximal Junctional Failure [MeSH]" AND "Bone Mineral Density [MeSH] OR Hounsfield Units [MeSH] OR DEXA [MeSH]" set to the date range of January 2002 to July 2022. Studies required a minimum of 10 patients and 12 months of follow-up. Articles were included if they were in the English language and presented a primary retrospective cohort that included a comparison of patients with and without PJK, as well as a radiographic biomarker for BMD, such as Hounsfield units (HU) or T-score. RESULTS: A total of 18 unique studies with 2185 patients who underwent ASD surgery were identified. Of these, 537 patients (24.6%) developed PJK. Eight studies provided T-scores that were amenable to comparison, which found that patients who developed PJK were found to have lower BMD T-scores by a mean of -0.69 (95% CI -0.88 to -0.50; I2 = 63.9%, p < 0.001). The HU at the UIV among patients with the PJK group (n = 101) compared with the non-PJK group (n = 156) was found to be significantly lower (mean difference -32.35, 95% CI -46.05 to -18.65; I2 = 28.7%, p < 0.001). CONCLUSIONS: This meta-analysis suggests that low preoperative BMD as measured by T-score and a diagnosis of osteoporosis were associated with higher postoperative PJK. Additionally, lower HU on CT at the UIV were found to be significant risk factors for postoperative PJK as well. These findings suggest that more attention to preoperative BMD is a risk factor for PJK among ASD patients is warranted.

Side-firing intraoperative ultrasound applied to resection of pituitary macroadenomas and giant adenomas: A single-center retrospective case-control study.

Introduction: Multiple intraoperative navigation and imaging modalities are currently available as an adjunct to endoscopic transsphenoidal resection of pituitary adenomas, including intraoperative CT and MRI, fluorescence guidance, and neuronavigation. However, these imaging techniques have several limitations, including intraoperative tissue shift, lack of availability in some centers, and the increased cost and time associated with their use. The side-firing intraoperative ultrasound (IOUS) probe is a relatively new technology in endoscopic endonasal surgery that may help overcome these obstacles. Methods: A retrospective analysis was performed on patients admitted for resection of pituitary adenomas by a single surgeon at the University of Mississippi Medical Center. The control (non-ultrasound) group consisted of twelve (n=12) patients who received surgery without IOUS guidance, and the IOUS group was composed of fifteen (n=15) patients who underwent IOUS-guided surgery. Outcome measures used to assess the side-firing IOUS were the extent of tumor resection, postoperative complications, length of hospital stay (LOS) in days, operative time, and self-reported surgeon confidence in estimating the extent of resection intraoperatively. Results: Preoperative data analysis showed no significant differences in patient demographics or presenting symptoms between the two groups. Postoperative data revealed no significant difference in the rate of gross total resection between the groups (p = 0.716). Compared to the non-US group, surgeon confidence was significantly higher (p < 0.001), and operative time was significantly lower for the US group in univariate analysis (p = 0.011). Multivariate analysis accounting for tumor size, surgeon confidence, and operative time confirmed these findings. Interestingly, we noted a trend for a lower incidence of postoperative diabetes insipidus in the US group, although this did not quite reach our threshold for statistical significance. Conclusion: Incorporating IOUS as an aid for endonasal resection of pituitary adenomas provides real-time image guidance that increases surgeon confidence in intraoperative assessment of the extent of resection and decreases operative time without posing additional risk to the patient. Additionally, we identified a trend for reduced diabetes insipidus with IOUS.

Management of pediatric sternal wounds following congenital heart surgery: The role of the plastic surgeon in debridement and closure.

BACKGROUND: Management of sternal wound infections (SWIs) in pediatric patients following congenital heart surgery can be extremely difficult. Patients with congenital cardiac conditions are at risk for complications such as sternal dehiscence, infection, and cardiopulmonary compromise. In this study, we report a single-institution experience with pediatric SWIs. METHODS: Fourteen pediatric patients requiring plastic surgery consultation for complex sternal wound closure were included. A retrospective chart review was performed with the following variables of interest: demographic data, congenital cardiac condition, respective surgical palliations, development of mediastinitis, causative organism, number of debridements, presence of sternal wires, and choice of flap coverage. Primary endpoints included achieved chest wall closure and overall survival. RESULTS: Of the 14 patients, 8 (57%) were diagnosed with culture-positive mediastinitis. The sternum remained wired at the time of final flap closure in eight (57%) patients. All patients were reconstructed with pectoralis major flaps, except one (7%) who also received an omental flap and two (14%) who received superior rectus abdominis flaps. One patient (7%) was treated definitively with negative pressure wound therapy, and one (7%) was too unstable for closure. Six patients developed complications, including one (7%) with persistent mediastinitis, two (14%) with hematoma formation, one (7%) with abscess, and one (7%) with skin necrosis requiring subsequent surgical debridement. There were three (21%) mortalities. CONCLUSIONS: The management of SWI in congenital cardiac patients is challenging. The standard tenets for management of SWI in adults are loosely applicable, but additional considerations must be addressed in this unique subset population.

What Role do Mitochondria Have in Diastolic Dysfunction? Implications for Diabetic Cardiomyopathy and Heart Failure With Preserved Ejection Function.

ABSTRACT: Diastolic dysfunction is common to both diabetic cardiomyopathy and heart failure with preserved ejection fraction (HFpEF). Although commonly attributed to increased fibrosis, alterations in mitochondrial function and associated Ca2+ handling may contribute to impaired cardiac function. With mitochondrial dysfunction, increased reactive oxygen species (ROS), inflammation, and decreased adenosine triphosphate/adenosine diphosphate ratio may lead to increased extracellular matrix and diminished contractile relaxation. In this article, we discuss recent research implicating deficient mitochondria-associated endoplasmic reticulum membranes (MAMs) as it relates to impaired metabolic function and what role that may have in diastolic dysfunction in diabetic cardiomyopathy. The contribution of mitochondrial dysfunction to diastolic dysfunction in HFpEF is less established, but equally credible based on preclinical studies. However, there are notable differences between diabetic cardiomyopathy and HFpEF. Recent evidence implicates impaired endoplasmic reticulum signaling, in particular the unfolded protein response (UPR), in the pathogenesis of HFpEF. With HFpEF, enhanced pressure on the mitochondrial "gas pedal" because of increased cytosolic Ca2+ may perturb mitochondrial homeostasis. For diabetic cardiomyopathy and HFpEF, a better understanding of how altered cellular ion and redox status affect mitochondrial function is needed. Finally, we discuss the implications that mitochondrial dysfunction may have in devising novel therapeutic strategies for diabetic cardiomyopathy and HFpEF.

Negative Pressure Wound Therapy in Facilitating Wound Healing After Surgical Decompression for Metastatic Spine Disease.

BACKGROUND: The risk of wound-related complications, including surgical site infections (SSIs), in patients undergoing surgery for metastatic spine disease (MSD) is high. Consequently, patients requiring wound revision surgery face delay in resuming oncological care and incur additional hospitalization. Recent reports suggest that negative pressure wound therapy (NPWT) applied on a closed wound at the time of surgery significantly reduces postoperative wound complications in degenerative spine disease and trauma setting. Here, we report a single institution experience with incisional NPWT in patients undergoing surgery for MSD. METHODS: We compared rates of wound complications requiring surgical revision in a surgical cohort of patients with or without NPWT from 2015 to 2020. Adult patients with radiographic evidence of MSD with mechanical instability and/or accelerated neurological decline were included in the study. NPWT was applied on a closed wound in the operating room and continued for 5 days or until discharge, whichever occurred first. RESULTS: A total of 42 patients were included: 28 with NPWT and 14 without. Patient demographics including underlying comorbidities were largely similar. NPWT patients had higher rates of prior radiation to the surgical site (36% vs. 0%, P = 0.017) and longer fusion constructs (6.7 vs. 3.9 levels, P < 0.001). Three patients (21%) from the control group and none from the NPWT group contracted SSI requiring wound washout (P = 0.032). CONCLUSIONS: Our data suggest that SSI and wound dehiscence are significantly reduced with the addition of incisional NPWT in this vulnerable population.

The rapid diagnosis and effective inhibition of coronavirus using spike antibody attached gold nanoparticles.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of the coronavirus disease that began in 2019 (COVID-19), has been responsible for 1.4 million deaths worldwide as of 13 November 2020. Because at the time of writing no vaccine is yet available, a rapid diagnostic assay is very urgently needed. Herein, we present the development of anti-spike antibody attached gold nanoparticles for the rapid diagnosis of specific COVID-19 viral antigen or virus via a simple colorimetric change observation within a 5 minute time period. For rapid and highly sensitive identification, surface enhanced Raman spectroscopy (SERS) was employed using 4-aminothiophenol as a reporter molecule, which is attached to the gold nanoparticle via an Au-S bond. In the presence of COVID-19 antigen or virus particles, owing to the antigen-antibody interaction, the gold nanoparticles undergo aggregation, changing color from pink to blue, which allows for the determination of the presence of antigen or virus very rapidly by the naked eye, even at concentrations of 1 nanogram (ng) per mL for COVID-19 antigen and 1000 virus particles per mL for SARS-CoV-2 spike protein pseudotyped baculovirus. Importantly, the aggregated gold nanoparticles form "hot spots" to provide very strong SERS signal enhancement from anti-spike antibody and 4-aminothiophenol attached gold nanoparticles via light-matter interactions. Finite-difference time-domain (FDTD) simulation data indicate a 4-orders-of-magnitude Raman enhancement in "hot spot" positions when gold nanoparticles form aggregates. Using a portable Raman analyzer, our reported data demonstrate that our antibody and 4-aminothiophenol attached gold nanoparticle-based SERS probe has the capability to detect COVID-19 antigen even at a concentration of 4 picograms (pg) per mL and virus at a concentration of 18 virus particles per mL within a 5 minute time period. Using HEK293T cells, which express angiotensin-converting enzyme 2 (ACE2), by which SARS-CoV-2 enters human cells, we show that anti-spike antibody attached gold nanoparticles have the capability to inhibit infection by the virus. Our reported data show that antibody attached gold nanoparticles bind to SARS-CoV-2 spike protein, thereby inhibiting the virus from binding to cell receptors, which stops virus infection and spread. It also has the capability to destroy the lipid membrane of the virus.

Multifocal Xanthoma of Bone.

We report a case of a 40-year-old woman with hyperlipidemia and associated multifocal xanthoma of bone requiring prophylactic fixation of her bilateral femurs. Although xanthomas of bone are themselves a benign process, their presence may indicate that the patient has poorly controlled lipids and is at an increased risk of cardiovascular disease. Lytic lesions may require prophylactic fixation to prevent pathologic fracture.

Aptamer Conjugated Gold Nanostar-Based Distance-Dependent Nanoparticle Surface Energy Transfer Spectroscopy for Ultrasensitive Detection and Inactivation of Corona Virus.

The ongoing outbreak of the coronavirus infection has killed more than 2 million people. Herein, we demonstrate that Rhodamine 6G (Rh-6G) dye conjugated DNA aptamer-attached gold nanostar (GNS)-based distance-dependent nanoparticle surface energy transfer (NSET) spectroscopy has the capability of rapid diagnosis of specific SARS-CoV-2 spike recombinant antigen or SARS-CoV-2 spike protein pseudotyped baculovirus within 10 min. Because Rh-6G-attached single-stand DNA aptamer wrapped the GNS, 99% dye fluorescence was quenched because of the NSET process. In the presence of spike antigen or virus, the fluorescence signal persists because of the aptamer-spike protein binding. Specifically, the limit of detection for the NSET assay has been determined to be 130 fg/mL for antigen and 8 particles/mL for virus. Finally, we have demonstrated that DNA aptamer-attached GNSs can stop virus infection by blocking the angiotensin-converting enzyme 2 (ACE2) receptor binding capability and destroying the lipid membrane of the virus.

Effective Inhibition of SARS-CoV-2 Entry by Heparin and Enoxaparin Derivatives.

Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has caused a pandemic of historic proportions and continues to spread globally, with enormous consequences to human health. Currently there is no vaccine, effective therapeutic, or prophylactic. As with other betacoronaviruses, attachment and entry of SARS-CoV-2 are mediated by the spike glycoprotein (SGP). In addition to its well-documented interaction with its receptor, human angiotensin-converting enzyme 2 (hACE2), SGP has been found to bind to glycosaminoglycans like heparan sulfate, which is found on the surface of virtually all mammalian cells. Here, we pseudotyped SARS-CoV-2 SGP on a third-generation lentiviral (pLV) vector and tested the impact of various sulfated polysaccharides on transduction efficiency in mammalian cells. The pLV vector pseudotyped SGP efficiently and produced high titers on HEK293T cells. Various sulfated polysaccharides potently neutralized pLV-S pseudotyped virus with clear structure-based differences in antiviral activity and affinity to SGP. Concentration-response curves showed that pLV-S particles were efficiently neutralized by a range of concentrations of unfractionated heparin (UFH), enoxaparin, 6-O-desulfated UFH, and 6-O-desulfated enoxaparin with 50% inhibitory concentrations (IC50s) of 5.99 µg/liter, 1.08 mg/liter, 1.77 µg/liter, and 5.86 mg/liter, respectively. In summary, several sulfated polysaccharides show potent anti-SARS-CoV-2 activity and can be developed for prophylactic as well as therapeutic purposes.IMPORTANCE The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV-2) in Wuhan, China, in late 2019 and its subsequent spread to the rest of the world has created a pandemic situation unprecedented in modern history. While ACE2 has been identified as the viral receptor, cellular polysaccharides have also been implicated in virus entry. The SARS-CoV-2 spike glycoprotein (SGP) binds to glycosaminoglycans like heparan sulfate, which is found on the surface of virtually all mammalian cells. Here, we report structure-based differences in antiviral activity and affinity to SGP for several sulfated polysaccharides, including both well-characterized FDA-approved drugs and novel marine sulfated polysaccharides, which can be developed for prophylactic as well as therapeutic purposes.

Effective screening of SARS-CoV-2 neutralizing antibodies in patient serum using lentivirus particles pseudotyped with SARS-CoV-2 spike glycoprotein.

Pseuodotyped particles have significant importance and use in virology as tools for studying the biology of highly pathogenic viruses in a lower biosafety environment. The biological, chemical, and serological studies of the recently emerged SARS-CoV-2 will be greatly aided by the development and optimization of a suitable pseudotyping system. Here, we pseudotyped the SARS-CoV-2 Spike glycoprotein (SPG) on a traditional retroviral (MMLV) as well as a third generation lentiviral (pLV) vector and tested the transduction efficiency in several mammalian cell lines expressing SARS-CoV-2 receptor hACE2. While MMLV pseudotyped the vesicular stomatitis virus G glycoprotein (VSV-G) efficiently, it could not pseudotype the full-length SPG. In contrast, pLV pseudotyped both glycoproteins efficiently; however, much higher titers of pLV-G particles were produced. Among all the tested mammalian cells, 293Ts expressing hACE2 were most efficiently transduced using the pLV-S system. The pLV-S particles were efficiently neutralized by diluted serum (>:640) from recently recovered COVID-19 patients who showed high SARS-CoV-2 specific IgM and IgG levels. In summary, pLV-S pseudotyped virus provides a valid screening tool for the presence of anti SARS-CoV-2 specific neutralizing antibodies in convalescent patient serum.

The structure-activity relationship of the interactions of SARS-CoV-2 spike glycoproteins with glucuronomannan and sulfated galactofucan from Saccharina japonica.

The SARS-CoV-2 spike glycoproteins (SGPs) and human angiotensin converting enzyme 2 (ACE2) are the two key targets for the prevention and treatment of COVID-19. Host cell surface heparan sulfate (HS) is believed to interact with SARS-CoV-2 SGPs to facilitate host cell entry. In the current study, a series of polysaccharides from Saccharina japonica were prepared to investigate the structure-activity relationship on the binding abilities of polysaccharides (oligosaccharides) to pseudotype particles, including SARS-CoV-2 SGPs, and ACE2 using surface plasmon resonance. Sulfated galactofucan (SJ-D-S-H) and glucuronomannan (Gn) displayed strongly inhibited interaction between SARS-CoV-2 SGPs and heparin while showing negligible inhibition of the interaction between SARS-CoV-2 SGPs and ACE2. The IC50 values of SJ-D-S-H and Gn in blocking heparin SGP binding were 27 and 231 nM, respectively. NMR analysis showed that the structure of SJ-D-S-H featured with a backbone of 1, 3-linked α-L-Fucp residues sulfated at C4 and C2/C4 and 1, 3-linked α-L-Fucp residues sulfated at C4 and branched with 1, 6-linked ß-D-galacto-biose; Gn had a backbone of alternating 1, 4-linked ß-D-GlcAp residues and 1, 2-linked α-D-Manp residues. The sulfated galactofucan and glucuronomannan showed strong binding ability to SARS-CoV-2 SGPs, suggesting that these polysaccharides might be good candidates for preventing and/or treating SARS-CoV-2.