Clinical evaluation of noninvasive prenatal testing for sex chromosome aneuploidies in 9,176 Korean pregnant women: a single-center retrospective study.

BACKGROUND: To evaluate the clinical significance of noninvasive prenatal testing (NIPT) for detecting fetal sex chromosome aneuploidies (SCAs) in Korean pregnant women. METHODS: We retrospectively analyzed NIPT data from 9,176 women with singleton pregnancies referred to the CHA Biotech genome diagnostics center. Cell-free fetal DNA (cffDNA) was extracted from maternal peripheral blood, and high-throughput massively parallel sequencing was conducted. Subsequently, the positive NIPT results for SCA were validated via karyotype and chromosomal microarray analyses. RESULTS: Overall, 46 cases were SCA positive after NIPT, including 20, 12, 8, and 6 for Turner, triple X, Klinefelter, and Jacob syndromes, respectively. Among 37 women with invasive prenatal diagnosis, 19 had true positive NIPT results. The overall positive predictive value (PPV) of NIPT for detecting SCAs was 51.35%. The PPV was 18.75% for Turner, 88.89% for triple X, 71.43% for Klinefelter, and 60.00% for Jacob's syndromes. NIPT accuracy for detecting sex chromosome trisomies was higher than that for sex chromosome monosomy (P = 0.002). No significant correlation was observed between fetal SCA incidence and maternal age (P = 0.914), except for the borderline significance of Jacob's syndrome (P = 0.048). No significant differences were observed when comparing NIPT and karyotyping validation for fetal SCA according to pregnancy characteristics. CONCLUSION: Our data suggest that NIPT can reliably screen for SCAs, and it performed better in predicting sex chromosome trisomies compared with monosomy X. No correlation was observed between maternal age and fetal SCA incidence, and no association was observed between different pregnancy characteristics. The accuracy of these findings requires improvements; however, our study provides an important reference for clinical genetic counseling and further management. Larger scale studies, considering confounding factors, are required for accurate evaluation.

Fc-fused IL-7 provides broad antiviral effects against respiratory virus infections through IL-17A-producing pulmonary innate-like T cells.

Repeated pandemics caused by the influenza virus and severe acute respiratory syndrome coronavirus (SARS-CoV) have resulted in serious problems in global public health, emphasizing the need for broad-spectrum antiviral therapeutics against respiratory virus infections. Here, we show the protective effects of long-acting recombinant human interleukin-7 fused with hybrid Fc (rhIL-7-hyFc) against major respiratory viruses, including influenza virus, SARS-CoV-2, and respiratory syncytial virus. Administration of rhIL-7-hyFc in a therapeutic or prophylactic regimen induces substantial antiviral effects. During an influenza A virus (IAV) infection, rhIL-7-hyFc treatment increases pulmonary T cells composed of blood-derived interferon γ (IFNγ)+ conventional T cells and locally expanded IL-17A+ innate-like T cells. Single-cell RNA transcriptomics reveals that rhIL-7-hyFc upregulates antiviral genes in pulmonary T cells and induces clonal expansion of type 17 innate-like T cells. rhIL-7-hyFc-mediated disease prevention is dependent on IL-17A in both IAV- and SARS-CoV-2-infected mice. Collectively, we suggest that rhIL-7-hyFc can be used as a broadly active therapeutic for future respiratory virus pandemic.

Analysis of clinical factors and ultrasound features associated with COVID-19 vaccine-related axillary lymphadenopathy: A large group study.

PURPOSE: To investigate factors that distinguish COVID-19 vaccine-related axillary lymphadenopathy from malignancy or other etiologies. METHODS: From June 2021 to April 2022, 3859 consecutive female patients had breast and axillary ultrasound (US) at our institution. After exclusions, 592 patients were included in the study. We retrospectively reviewed clinical history and US features of enlarged axillary lymph nodes. Assessed clinical factors included age, vaccination type, dose and vaccination date, and ultrasound features included cortical thickness, shape, marginal irregularity, focal cortical thickening, fatty hilum, and number and anatomic location of enlarged lymph nodes. The seven US features were used to score the severity of lymphadenopathy. Binary logistic models and independent two-sample t-tests were used for statistical analysis. RESULTS: Among 592 patients (mean age 49.3 ± 10.3 years), 406(68.6%), 90(15.2%), 42(7.1), 4(0.7%) and 50(8.4%) patients received Pfizer, AstraZeneca, Moderna, Janssen and cross inoculation of more than one type, respectively. 185(31.3%), 376(63.5%) and 31(5.2%) patients received a first, second and third dose, respectively. The interval between vaccination and US was 30.9 ± 21.5 days. US showed axillary lymphadenopathy (LAP) in 113 patients (19.1%). Clinical factors associated with LAP were age younger than 50 years, mRNA vaccine, first dose and shorter interval(P < 0.05). US features associated with LAP were mean cortical thickness of 4.6 ± 1.63 mm, oval shape (70.8%), smooth margin (53.1%), focal cortical thickening (62.8%) and preserved fatty hilum (84.1%). Using our scoring method, the mean overall score for vaccine-related LAP was 2.45 ± 1.51 points. CONCLUSION: Awareness of influencing factors and sonographic features can help differentiate COVID-19 vaccine-related adenopathy from other etiologies.

Pharmaceutical and Immunological Evaluation of Cholera Toxin A1 Subunit as an Adjuvant of Hepatitis B Vaccine Microneedles.

PURPOSE: For successful delivery of a solid vaccine formulation into the skin using microneedles, the solubility of an adjuvant should be considered because the decrease in the dissolution rate by the addition of adjuvant decreases the delivery efficiency of the vaccine. METHODS: In this study, cholera toxin A subunit 1 (CTA1) was examined as an adjuvant to Hepatitis B vaccine (HBV) microneedles because of its good water solubility, improved safety, and positive effect as shown in intramuscular administration of a liquid vaccine. RESULTS: All solid formulations with CTA 1 dissolved in in vivo mouse skin within 30 min, and they were successfully delivered into the skin. In experiments with mice, the addition of CTA1 led to improved IgG immune response compared to the use of an aluminum hydroxide-based formulation and intramuscular administration of HBV. In addition, CTA1 induced CD8 + T cell response as much as in which the aluminum hydroxide-based formulation induced. CONCLUSIONS: CTA1 is an adjuvant that satisfies both the delivery efficiency and the immunological characteristics required for vaccine microneedles. CTA1 will be used as a potential adjuvant through vaccine microneedles.

High-Resolution Finger MRI: What Should You Look for in Trauma of the Fingers?

The fingers are among the most commonly injured structures in traumatic injuries resulting from sports and work. Finger injuries encompass a broad spectrum of injuries to bone and soft tissues, including tendons, ligaments, and cartilage. The high resolution of 3T MRI with dedicated surface coils allows for optimal assessment of the intricate soft tissue structures of the fingers. There have been several reports on detailed MRI features of the basic anatomy and common pathological findings of the finger and hand. Understanding the normal anatomy and familiarization with common traumatic lesions of the ligaments, tendons, and pulleys of the fingers on high-resolution MRI will allow radiologists to perform accurate preoperative evaluations of traumatic hand lesions. The purpose of this study is to review the normal hand anatomy and common traumatic lesions of the finger on high-resolution MRI and correlate them with surgical findings.

Nonclinical safety assessment and immunogenicity of rVSVInd(GML)-mspSGtc vaccine for SARS-CoV-2 in rabbits.

The worldwide health, economic, and societal consequences of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic have been devastating. The primary strategy to prevent new infectious diseases is to vaccinate the majority of people worldwide. However, the significant hurdles that are faced include vaccine safety concerns and vaccine reluctance. Among the various types of vaccines, the recombinant vesicular stomatitis virus (rVSV) is a promising candidate owing to its safety and efficacy. Therefore, we investigated the toxicity, immunogenicity, and local tolerance of the rVSVInd(GML)-mspSGtc vaccine against SARS-CoV-2. New Zealand White (NZW) rabbits were administered single or three repeated intramuscular injections of rVSVInd(GML)-mspSGtc every 2 weeks, followed by a 4-week recovery period. Male and female rabbits were randomly assigned into three groups: a control group and two dose-level groups (1 × 109 and 4 × 109 PFU/mL). Treatment-related changes included a temporary increase in body temperature and local inflammation at the injection site. These findings indicated recovery or a trend toward recovery, with no overt systemic toxicity. Immunogenicity analysis results suggested that rVSVInd(GML)-mspSGtc elicited a robust dose-dependent immune response in terms of neutralizing antibodies and IgG antibodies against the SARS-CoV-2 spike protein. In addition, the immune response intensity was increased by repeated vaccine administration. In conclusion, both the approximate lethal dose and the no observed adverse effect level for rVSVInd(GML)-mspSGtc exceeded 4 × 109 PFU/mL in NZW rabbits. Overall, rVSVInd(GML)-mspSGtc induced no adverse effects at the maximum dosage tested; however, its efficacy warrants further clinical evaluation.

Establishment of multicenter COVID-19 therapeutics preclinical test system in Republic of Korea.

Throughout the recent COVID-19 pandemic, South Korea led national efforts to develop vaccines and therapeutics for SARS-CoV-2. The project proceeded as follows: 1) evaluation system setup (including Animal Biosafety Level 3 (ABSL3) facility alliance, standardized nonclinical evaluation protocol, and laboratory information management system), 2) application (including committee review and selection), and 3) evaluation (including expert judgment and reporting). After receiving 101 applications, the selection committee reviewed pharmacokinetics, toxicity, and efficacy data and selected 32 final candidates. In the nonclinical efficacy test, we used golden Syrian hamsters and human angiotensin-converting enzyme 2 transgenic mice under a cytokeratin 18 promoter to evaluate mortality, clinical signs, body weight, viral titer, neutralizing antibody presence, and histopathology. These data indicated eight new drugs and one repositioned drug having significant efficacy for COVID-19. Three vaccine and four antiviral drugs exerted significant protective activities against SARS-CoV-2 pathogenesis. Additionally, two anti-inflammatory drugs showed therapeutic effects on lung lesions and weight loss through their mechanism of action but did not affect viral replication. Along with systematic verification of COVID-19 animal models through large-scale studies, our findings suggest that ABSL3 multicenter alliance and nonclinical evaluation protocol standardization can promote reliable efficacy testing against COVID-19, thus expediting medical product development.

Novel MRI signs of ruptured disc in the cervical spine with intraoperative comparisons.

OBJECTIVES: To evaluate the diagnostic performance of two novel MRI signs for extruded disc (ED) and uncontained ED (ruptured disc, RD) in the cervical spine using intraoperative findings as reference. METHODS: This retrospective study included patients who underwent cervical spine MRI and surgery for disc pathology with intraoperative confirmation of RD from September 1, 2016, to January 31, 2021. Two radiologists determined whether the disc was extruded or ruptured with and without the aid of two novel MRI signs suggesting RD (sign 1: blurred margin of the disc; sign 2: mushroom-shaped disc). The diagnostic performance was analyzed using surgical findings as reference. Intra- and interobserver agreements were measured for each MRI sign. RESULTS: A total of 91 patients totaling 131 discs were enrolled (mean age: 56.02 ± 12.93; range: 26-88; 62 men and 29 women), of whom 62 were surgically confirmed with RD. When the diagnosis was based exclusively on existing ED definitions, ED was diagnosed with 62.9-79.0% sensitivity and 80.2% accuracy, whereas RD was diagnosed with 35.5-45.2% sensitivity and 67.9-71.0% accuracy. However, when the two novel MRI signs were used as an aid in the diagnosis, ED was diagnosed with 95.2-96.8% sensitivity and 84.0-88.5% accuracy, while RD was diagnosed with 95.2-96.8% sensitivity and 84.0-89.3% accuracy. Intra- and interobserver agreement was substantial (k = 00.77-0.86, 0.69-0.79, respectively, p < 0.001). CONCLUSIONS: The detection of two novel MRI signs on preoperative MRI can lead to a more accurate RD diagnosis. KEY POINTS: • The diagnostic sensitivity of MRI for cervical ruptured disc is very low (about 35-45 %) using the standardized definition of lumbar disc nomenclature. • Two novel MRI signs can lead to a more accurate diagnosis of the surgically confirmed ruptured disc in the cervical spine. • These two novel MRI signs showed substantial intra-and interobserver reliabilities.

Correction: A vesicular stomatitis virus-based prime-boost vaccination strategy induces potent and protective neutralizing antibodies against SARS-CoV-2.

[This corrects the article DOI: 10.1371/journal.ppat.1010092.].

Temporal Transcriptome Analysis of SARS-CoV-2-Infected Lung and Spleen in Human ACE2-Transgenic Mice.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and potentially fatal virus. So far, most comprehensive analyses encompassing clinical and transcriptional manifestation have concentrated on the lungs. Here, we confirmed evident signs of viral infection in the lungs and spleen of SARS-CoV-2-infected K18-hACE2 mice, which replicate the phenotype and infection symptoms in hospitalized humans. Seven days post viral detection in organs, infected mice showed decreased vital signs, leading to death. Bronchopneumonia due to infiltration of leukocytes in the lungs and reduction in the spleen lymphocyte region were observed. Transcriptome profiling implicated the meticulous regulation of distress and recovery from cytokine-mediated immunity by distinct immune cell types in a time-dependent manner. In lungs, the chemokine-driven response to viral invasion was highly elevated at 2 days post infection (dpi). In late infection, diseased lungs, post the innate immune process, showed recovery signs. The spleen established an even more immediate line of defense than the lungs, and the cytokine expression profile dropped at 7 dpi. At 5 dpi, spleen samples diverged into two distinct groups with different transcriptome profile and pathophysiology. Inhibition of consecutive host cell viral entry and massive immunoglobulin production and proteolysis inhibition seemed that one group endeavored to survive, while the other group struggled with developmental regeneration against consistent viral intrusion through the replication cycle. Our results may contribute to improved understanding of the longitudinal response to viral infection and development of potential therapeutics for hospitalized patients affected by SARS-CoV-2.

Preclinical assessment and randomized Phase I study of CT-P63, a broadly neutralizing antibody targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in significant morbidity and mortality worldwide. Despite a successful vaccination programme, the emergence of mutated variants that can escape current levels of immunity mean infections continue. Herein, we report the development of CT-P63, a broad-spectrum neutralizing monoclonal antibody. In vitro studies demonstrated potent neutralizing activity against the most prevalent variants, including Delta and the BA.1 and BA.2 sub-lineages of Omicron. In a transgenic mouse model, prophylactic CT-P63 significantly reduced wild-type viral titres in the respiratory tract and CT-P63 treatment proved efficacious against infection with Beta, Delta, and Omicron variants of SARS-CoV-2 with no detectable infectious virus in the lungs of treated animals. A randomized, double-blind, parallel-group, placebo-controlled, Phase I, single ascending dose study in healthy volunteers (NCT05017168) confirmed the safety, tolerability, and pharmacokinetics of CT-P63. Twenty-four participants were randomized and received the planned dose of CT-P63 or placebo. The safety and tolerability of CT-P63 were evaluated as primary objectives. Eight participants (33.3%) experienced a treatment-emergent adverse event (TEAE), including one grade ≥3 (blood creatine phosphokinase increased). There were no deaths, treatment-emergent serious adverse events, TEAEs of special interest, or TEAEs leading to study drug discontinuation in the CT-P63 groups. Serum CT-P63 concentrations rapidly peaked before declining in a biphasic manner and systemic exposure was dose proportional. Overall, CT-P63 was clinically safe and showed broad-spectrum neutralizing activity against SARS-CoV-2 variants in vitro and in vivo.

Does the Suprascapular Nerve Move within the Suprascapular Notch? Biomechanical Perspective Using the Finite Element Method.

PURPOSE: We aimed to analyze changes in suprascapular nerve (SSN) position within the suprascapular notch during in vivo shoulder abduction. MATERIALS AND METHODS: Three-dimensional models of the shoulder complex were constructed based on magnetic resonance imaging of the brachial plexus (BP-MR) in a patient diagnosed with SSN dysfunction but normal scapular movement. Using BP-MR in neutral position and computed tomography data on shoulder abduction, shoulder abduction was simulated as the transition between two positions of the shoulder complex with overlapping of a neutral and abducted scapula. SSN movement during abduction was evaluated using the finite element method. Contact stress on the SSN was measured in the presence and absence of the transverse scapular ligament (TSL). RESULTS: In the neutral position, the SSN ran almost parallel to the front of the TSL until entering the suprascapular notch and slightly contacted the anterior-inferior border of the TSL. As shoulder abduction progressed, contact stress decreased due to gradual loss of contact with the TSL. In the TSL-free scapula, there was no contact stress on the SSN in the neutral position. Towards the end of shoulder abduction, contact stress increased again as the SSN began to contact the base of the suprascapular notch in both TSL conditions. CONCLUSION: We identified changes in the position of the SSN path within the suprascapular notch during shoulder abduction. The SSN starts in contact with the TSL and moves toward the base of the suprascapular notch with secondary contact. These findings may provide rationale for TSL release in SSN entrapment.

Laboratory information management system for COVID-19 non-clinical efficacy trial data.

BACKGROUND: As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. RESULTS: In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. CONCLUSIONS: This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.

Acute to Subacute Spinal Cord Infarction Mimicking Acute Multiple Sclerosis: Usefulness of Diffusion-weighted MRI for Diagnosis.

BACKGROUND: Spinal Cord Infarction (SCI) is difficult to diagnose because of its rarity, unknown etiology, and unestablished diagnostic criteria. Additionally, the timeline of SCI has not been studied in detail, as few studies using Diffusion-Weighted Image (DWI) sequences of the spine of a small target population have been previously conducted. CASE STUDY: A 56-year-old male with underlying arrhythmia suddenly developed visual field defects on the right side, pain in the left upper extremity, and a tingling sensation in the left hand. Brain Magnetic resonance imaging (MRI) revealed acute to subacute stages of multifocal brain infarction. On additional cervical spinal MRI, it showed atypical MRI findings of SCI, considered late acute to early subacute phase, which were similar to those seen in the acute phase of multiple sclerosis (MS). Additional DWI revealed restricted diffusion. From these findings, it could be inferred that the patient's SCI occurred at the same time as the multifocal brain infarctions caused by atrial fibrillation. CONCLUSION: A DWI sequence of spine MRI could be helpful in the diagnosis of acute to subacute phase SCI and in differentiating with acute MS.

Middle East Respiratory Syndrome coronavirus vaccine development: updating clinical studies using platform technologies.

Middle East Respiratory Syndrome coronavirus (MERS-CoV), a contagious zoonotic virus, causes severe respiratory infection with a case fatality rate of approximately 35% in humans. Intermittent sporadic cases in communities and healthcare facility outbreaks have continued to occur since its first identification in 2012. The World Health Organization has declared MERS-CoV a priority pathogen for worldwide research and vaccine development due to its epidemic potential and the insufficient countermeasures available. The Coalition for Epidemic Preparedness Innovations is supporting vaccine development against emerging diseases, including MERS-CoV, based on platform technologies using DNA, mRNA, viral vector, and protein subunit vaccines. In this paper, we review the usefulness and structure of a spike glycoprotein as a MERS-CoV vaccine candidate molecule, and provide an update on the status of MERS-CoV vaccine development. Vaccine candidates based on both DNA and viral vectors coding MERS-CoV spike gene have completed early phase clinical trials. A harmonized approach is required to assess the immunogenicity of various candidate vaccine platforms. Platform technologies accelerated COVID-19 vaccine development and can also be applied to developing vaccines against other emerging viral diseases.

Utility of Preoperative Shear-Wave Elastography of the Supraspinatus Muscle for Predicting Successful Rotator Cuff Repair: A Prospective Observational Study With MRI Correlation.

BACKGROUND. After rotator cuff tear, properties of the torn muscle predict failed surgical repair. OBJECTIVE. The purpose of our study was to explore the utility of preoperative shear-wave elastography (SWE) measurements of the supraspinatus muscle to predict successful rotator cuff repair, including comparison with MRI-based measures. METHODS. This prospective study included 74 patients (37 men, 37 women; mean age, 63.9 ± 10.0 [SD] years) who underwent rotator cuff repair between May 2019 and January 2021. Patients underwent preoperative clinical shoulder MRI and investigational shoulder ultrasound including SWE using shear modulus. The mean elasticity values of the supraspinatus and trapezius muscles were measured, and the elasticity ratio (i.e., ratio of mean elasticity of supraspinatus muscle to mean elasticity of trapezius muscle) was calculated. The muscular fatty infiltration score (1-3 scale) was recorded on gray-scale ultrasound. On MRI, muscular fatty infiltration was assessed by Goutallier grade (0-4 scale), and muscular atrophy was assessed by the occupation ratio (ratio of cross-sectional areas of supraspinatus muscle and supraspinatus fossa) and by the muscle atrophy grade (0-3 scale). After rotator cuff repair, the surgeon classified procedures as achieving sufficient (n = 60) or insufficient (n = 14) repair. RESULTS. Patients with insufficient repair, versus those with sufficient repair, more commonly exhibited a large (3-5 cm) tear (100.0% vs 50.0%). Patients with insufficient, versus sufficient, repair exhibited higher mean Goutallier grade (3.8 ± 0.4 vs 1.9 ± 1.1), mean muscle atrophy grade (2.0 ± 0.8 vs 0.5 ± 0.7), mean supraspinatus elasticity (44.15 ± 8.06 vs 30.84 ± 7.89 kPa), mean elasticity ratio (3.66 ± 0.66 vs 1.83 ± 0.58), and mean gray-scale fatty infiltration grade (2.86 ± 0.36 vs 1.63 ± 0.66) and showed lower mean occupation ratio (0.3 ± 0.1 vs 0.6 ± 0.1) (all, p < .001). AUC for predicting insufficient repair was 0.945 for Goutallier grade, 0.961 for occupation ratio, 0.900 for muscle atrophy grade, 0.874 for mean elasticity, 0.971 for elasticity ratio, and 0.912 for gray-scale fatty infiltration grade. Elasticity ratio (cutoff ≥ 2.51) achieved sensitivity of 100.0% and specificity of 90.0% for insufficient repair. At multivariable analysis including tear size, the three MRI measures, elasticity ratio, and gray-scale fatty infiltration grade, the only independent predictors of insufficient repair were muscle atrophy grade of 2-3 (odds ratio [OR] = 9.3) and elasticity ratio (OR = 15.7). CONCLUSION. SWE-derived elasticity is higher in patients with insufficient rotator cuff repair; the elasticity ratio predicts insufficient repair independent of tear size and muscle characteristics. CLINICAL IMPACT. Preoperative SWE may serve as a prognostic marker in patients with rotator cuff tear.

A vesicular stomatitis virus-based prime-boost vaccination strategy induces potent and protective neutralizing antibodies against SARS-CoV-2.

The development of safe and effective vaccines to prevent SARS-CoV-2 infections remains an urgent priority worldwide. We have used a recombinant vesicular stomatitis virus (rVSV)-based prime-boost immunization strategy to develop an effective COVID-19 vaccine candidate. We have constructed VSV genomes carrying exogenous genes resulting in the production of avirulent rVSV carrying the full-length spike protein (SF), the S1 subunit, or the receptor-binding domain (RBD) plus envelope (E) protein of SARS-CoV-2. Adding the honeybee melittin signal peptide (msp) to the N-terminus enhanced the protein expression, and adding the VSV G protein transmembrane domain and the cytoplasmic tail (Gtc) enhanced protein incorporation into pseudotype VSV. All rVSVs expressed three different forms of SARS-CoV-2 spike proteins, but chimeras with VSV-Gtc demonstrated the highest rVSV-associated expression. In immunized mice, rVSV with chimeric S protein-Gtc derivatives induced the highest level of potent neutralizing antibodies and T cell responses, and rVSV harboring the full-length msp-SF-Gtc proved to be the superior immunogen. More importantly, rVSV-msp-SF-Gtc vaccinated animals were completely protected from a subsequent SARS-CoV-2 challenge. Overall, we have developed an efficient strategy to induce a protective response in SARS-CoV-2 challenged immunized mice. Vaccination with our rVSV-based vector may be an effective solution in the global fight against COVID-19.

Vitamin D deficiency and associated factors in south Korean childbearing women: a cross-sectional study.

BACKGROUND: Adequate levels of vitamin D are important for women of childbearing age as vitamin D helps maintain the pregnancy and ensures proper maternal and fetal bone metabolism and fetal skeletal development. However, vitamin D deficiency is a health problem prevalent in women of all ages, worldwide. This study aimed to determine the current status of serum vitamin D levels and the risk factors for vitamin D deficiency among South Korean nurses of childbearing age. METHODS: Serum levels of 25-hydroxyvitamin D (25[OH]D) were measured in 1594 registered nurses aged 20 to 45 years who are participants in an ongoing prospective cohort study of the Korean Nurses' Health Study initiated in 2013. The participants completed surveys about demographic and occupational characteristics and physical and psychological health. We examined associations with vitamin D deficiency through multivariable logistic regression analysis. RESULTS: The average blood 25(OH) D concentration of the participants was 12.92 ng/mL (4.0-63.4 ng/mL), while the prevalence of vitamin D deficiency (< 20 ng/mL) was 89% (1419/1594). Multivariable logistic regression showed that significant risk factors for vitamin D deficiency included month of sampling (there was a lower level of vitamin D deficiency in winter than in spring, summer, or fall), age (women in their 20s had a lower vitamin D level than those in their 30s and 40s), and stress symptoms. Vitamin D levels were not associated with body mass index, physical activity, and depressive symptoms. CONCLUSIONS: This study showed a high prevalence of vitamin D deficiency in Korean female nurses. Serum levels of vitamin D were associated with age and season. Vitamin D deficiency should be recognized as one of the primary health concerns among young women. More proactive actions, such as vitamin D supplements and food fortification, are needed to improve vitamin D deficiency in high-risk groups.

COVID-19 vaccine-related axillary lymphadenopathy in breast cancer patients: Case series with a review of literature.

PURPOSE: Lymphadenopathy (LAP) after COVID-19 vaccination in patients with a diagnosis of cancer has been challenging. We analyzed imaging and clinical features from early cases of axillary LAP in six COVID-19 vaccine recipients with a history of breast cancer. METHOD: Among the patients with a history of breast cancer and recent COVID-19 vaccine administration, six patients who showed isolated axillary LAP were gathered. Radiologic features were reviewed from breast ultrasound, chest computed tomography, and breast magnetic resonance imaging. Clinical and pathological information were obtained for analysis. RESULTS: The interval between ultrasound detection of LAP and last COVID-19 vaccine administration ranged from 14 to 28 days (mean 21.67 days). Round shape of the lymph node and irregular cortex were noted in 2 and 0 cases, respectively. Mean maximum cortical thickness, length to width ratio and interval aggravation in maximum cortical thickening were 4.2 mm, 1.34, and 2.81-fold with cut-off value of 3 mm, 1.5, 2.0-fold, respectively. CONCLUSION: We observed axillary LAP ipsilateral to a recent vaccine administration persisting longer than what the Centers for Disease Control and Prevention announced. In our patients, COVID-19 vaccine-related LAP tended to show increased cortical thickness without cortical irregularity. Oncologist as well as radiologist should be familiar with the fact that COVID-19 vaccines, regardless of vaccine type or dosage, can frequently cause ipsilateral axillary LAP, showing some suspicious features more often than others, and can persist longer than anticipated so that both over- and underdiagnosis can be avoided. We report our observations in six patients and provide an exhaustive review of the published literature.

The in vitro and in vivo efficacy of CT-P59 against Gamma, Delta and its associated variants of SARS-CoV-2.

The SARS-CoV-2 variant is rapidly spreading across the world and causes to resurge infections. We previously reported that CT-P59 presented its in vivo potency against Beta variants, despite its reduced activity in cell experiments. Yet, it remains uncertain to exert the antiviral effect of CT-P59 on Gamma, Delta and its associated variants (L452R). To tackle this question, we carried out cell tests and animal studies. CT-P59 showed neutralization against Gamma, Delta, Epsilon, and Kappa variants in cells, with reduced susceptibility. The mouse challenge experiments with Gamma and Delta variants substantiated in vivo potency of CT-P59 showing symptom remission and virus abrogation in the respiratory tract. Collectively, cell and animal studies showed that CT-P59 is effective against Gamma and Delta variants infection, hinting that CT-P59 has therapeutic potential for patients infected with Gamma, Delta and its associated variants.