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Abstract Antimicrobials reserved for human medicines are permitted for companion animals and it is important to understand multidrug-resistant pathogens recovered from companion animals in terms of epidemiological correlation with human pathogens and possibility of transmission to human-beings. Seventeen of each CTX-M-type extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) and Klebsiella pneumoniae (ESBL-KP) canine isolates were assessed. Entire genomes of the 34 isolates were sequenced. Plasmid transfer and relative growth rates were assessed at differed temperature conditions indicating the body temperature of dogs, that of human-beings, and environment. ESBL-ECs were clonally diverse, while ESBL-KPs were not. The ESBL-ECs carried the bla CTX−M−15 gene in plasmids and the bla CTX−M−14-like gene either in chromosomes or in plasmids. The ESBL-KPs possessed the bla CTX−M−15 gene in plasmids (n = 15). One of the isolates carried another bla CTX−M−15 gene in a chromosome simultaneously and the other isolate had an additional bla CTX−M−9 gene-harbouring plasmid, together. Two ESBL-KP isolates carried the bla CTX−M−14 gene in plasmids. Plasmid transfer ESBL-EC to K. pneumoniae was efficient and the differed biological costs by temperature was much more in ESBL-EC than in ESBL-KP. Intersectoral dissemination of ESBL-ECs occurred mainly by horizontal gene transfer, while that of ESBL-KPs occurred by clonal dissemination.

Abstract Background Lymph node (LN) metastasis is an established prognostic factor for patients with surgically resected ampulla of Vater (AoV) cancer. The standard procedure for radical resection, including removal of regional LNs, is pancreaticoduodenectomy (PD); however, local excision has been considered as an alternative option for patients in the early stage cancer with significant comorbidities. In the present study, we elucidated the preoperative factors associated with LN metastasis to determine the appropriate surgical extent for T1 AoV cancer. Methods We included patients who underwent surgery for T1 AoV cancer at Samsung Medical Center and Severance Hospital between 2000 and 2019. Risk factors were analyzed to identify the preoperative parameters associated with LN metastasis or regional LN recurrence during follow-up. Finally, using the identified risk factors, a prediction model was constructed. Results Among 342 patients, 311 patients underwent PD, whereas 31 patients underwent transduodenal ampullectomy. Fourty-eight patients had LN metastasis according to pathology report, and two patients presented with regional LN recurrence. Age, carbohydrate antigen 19 − 9 (CA 19 − 9), and tumor differentiation were identified as factors associated with the increased risk of LN metastasis or regional LN recurrence. The area under the curve of the prediction model with these three factors was 0.728. Conclusion Our newly developed prediction model using age, CA 19 − 9, and tumor differentiation can help select patients who require PD over local excision. Nevertheless, additional in-depth analysis is warranted to select appropriate surgical extent for patients with presumed T1 AoV cancer.

Abstract Background Repetitive transcranial magnetic stimulation (rTMS) is one of the non-invasive brain stimulations that modulate cortical excitability through magnetic pulses. However, the effects of rTMS on Parkinson’s disease (PD) have yielded mixed results, influenced by factors including various rTMS stimulation parameters as well as the clinical characteristics of patients with PD. There is no clear evidence regarding which patients should be applied with which parameters of rTMS. The study aims to investigate the efficacy and safety of personalized rTMS in patients with PD, focusing on individual functional reserves to improve ambulatory function. Methods This is a prospective, exploratory, multi-center, single-blind, parallel-group, randomized controlled trial. Sixty patients with PD will be recruited for this study. This study comprises two sub-studies, each structured as a two-arm trial. Participants are classified into sub-studies based on their functional reserves for ambulatory function, into either the motor or cognitive priority group. The Timed-Up and Go (TUG) test is employed under both single and cognitive dual-task conditions (serial 3 subtraction). The motor dual-task effect, using stride length, and the cognitive dual-task effect, using the correct response rate of subtraction, are calculated. In the motor priority group, high-frequency rTMS targets the primary motor cortex of the lower limb, whereas the cognitive priority group receives rTMS over the left dorsolateral prefrontal cortex. The active comparator for each sub-study is bilateral rTMS of the primary motor cortex of the upper limb. Over 4 weeks, the participants will undergo 10 rTMS sessions, with evaluations conducted pre-intervention, mid-intervention, immediately post-intervention, and at 2-month follow-up. The primary outcome is a change in TUG time between the pre- and immediate post-intervention evaluations. The secondary outcome variables are the TUG under cognitive dual-task conditions, Movement Disorder Society-Unified Parkinson’s Disease Rating Scale Part III, New Freezing of Gait Questionnaire, Digit Span, trail-making test, transcranial magnetic stimulation-induced motor-evoked potentials, diffusion tensor imaging, and resting state functional magnetic resonance imaging. Discussion The study will reveal the effect of personalized rTMS based on functional reserve compared to the conventional rTMS approach in PD. Furthermore, the findings of this study may provide empirical evidence for an rTMS protocol tailored to individual functional reserves to enhance ambulatory function in patients with PD. Trial registration ClinicalTrials.gov NCT06350617. Registered on 5 April 2024.

Objective To determine the normative values of the Korean version of the Modified Barthel Index (K-MBI) score for typically developing children in Korea and assess its suitability for use in children. Methods Rehabilitation physicians and occupational therapists with children were invited through an online platform to participate in a survey assessing their children’s performance of activity of daily living (ADL) using the K-MBI. The questionnaire encompassed queries on sociodemographic information of children and the assessment criteria outlined in the K-MBI. The standardized K-MBI scores by age were estimated using the nonlinear least squares method. Results The analysis incorporated responses from a total of 206 individuals. K-MBI total scores showed a rapid increase over the first 8 years of life, with 99% of children achieving a score of 90 or higher by age 8. Mobility scores exhibited a swift increase during early childhood, surpassing 90% of the maximum score at 3 years of age and nearing 100% at 7 years of age. In contrast, self-care scores demonstrated a more gradual advancement, achieving approximately 100% of the maximum score by the age of 10 years. Conclusion Age-specific normative values for K-MBI scores of typically developing children were established, which can be used as a reference in clinical care. While the K-MBI captured the overall trajectory of children’s ADL development, it did not discern subtle differences across various developmental stages. There is a need for the development of more refined assessment tools tailored specifically to children.

Abstract Conventional open laminectomy has long been considered one of the important surgical options for lumbar central stenosis owing to its positive outcomes. However, newer approaches have emerged as alternatives, including full-endoscopic and biportal endoscopic laminectomy. Therefore, a comparison of the outcomes that are associated with each of these surgical methods is warranted. This prospective multicenter trial, initiated in February 2019, compared the outcomes of three lumbar central stenosis surgical approaches: open laminectomy (OPEN), uniportal endoscopy (UNIPORT), and biportal endoscopy (BIPORT). Among 115 participants from seven centers, one-year follow-ups assessed laboratory, radiological, and clinical outcomes. Despite all groups showing adequate decompression and clinical improvement, the OPEN group exhibited less improvement in Visual analog scale (VAS) for back pain scores (p

ABSTRACT Aim To compare nurse work hours and nursing activities between high‐staffed and low‐staffed general wards to examine the effects of increased staffing on nurse workload and nursing care. Design A secondary analysis was conducted using cross‐sectional data collected at a tertiary teaching hospital in South Korea in January 2020. Methods Nursing activities provided by 350 nurses were observed every 10 min during their shifts for three observation days in four high‐ and four low‐staffed wards. Nurse‐to‐patient ratios, nurse work hours, nursing activities and the composition of nursing hours (direct care, indirect care and associated work) were analysed. Results After excluding non‐productive personal time, nurses in the low‐staffed wards worked 9.28 h, which indicates 1.28 h of overtime work on average, while the high‐staffed wards recorded 7.90 h of productive work time. The nurse‐to‐patient ratio in the high‐staffed wards was 1:4.73, whereas that in the low‐staffed wards was 1:8.87. The proportion of direct care hours out of nurse work hours was higher in the low‐staffed wards (30.9%) than in the high‐staffed wards (25.7%). Nurses in the low‐staffed wards provided a greater number of direct care hours, and the largest difference in direct care hours between the two groups was found on night shifts. Nurses in the high‐staffed wards spent more time communicating with patients and charting, whereas nurses in the low‐staffed wards spent more time on vital signs and medications. Conclusion Improved staffing had positive impacts on patients and nurses. Patients benefited from better staffing through increased communication with nurses. Better staffing also reduced overtime work and activities conducted during night shifts. Implications for the Profession and Patient Care Adequate staffing is essential to improve patient care quality and reduce nurse workload. Nursing activities must be prioritised and redesigned to maximise the benefits of increased staffing on patient and nurse outcomes. Reporting Method We have adhered to the STROBE reporting guidelines. No Patient or Public Contribution The aim of this study was to compare nurse work hours and nursing activities between high‐staffed and low‐staffed wards.

Background and Purpose In young patients (aged 18–60 years) with patent foramen ovale (PFO)-associated stroke, percutaneous closure has been found to be useful for preventing recurrent ischemic stroke or transient ischemic attack (TIA). However, it remains unknown whether PFO closure is also beneficial in older patients. Methods Patients aged ≥60 years who had a cryptogenic stroke and PFO from ten hospitals in South Korea were included. The effect of PFO closure plus medical therapy over medical therapy alone was assessed by a propensity-score matching method in the overall cohort and in those with a high-risk PFO, characterized by the presence of an atrial septal aneurysm or a large shunt. Results Out of the 437 patients (mean age, 68.1), 303 (69%) had a high-risk PFO and 161 (37%) patients underwent PFO closure. Over a median follow-up of 3.9 years, recurrent ischemic stroke or TIA developed in 64 (14.6%) patients. In the propensity score-matched cohort of the overall patients (130 pairs), PFO closure was associated with a significantly lower risk of a composite of ischemic stroke or TIA (hazard ratio [HR]: 0.45; 95% confidence interval [CI]: 0.24–0.84; P=0.012), but not for ischemic stroke. In a subgroup analysis of confined to the high-risk PFO patients (116 pairs), PFO closure was associated with significantly lower risks of both the composite of ischemic stroke or TIA (HR: 0.40; 95% CI: 0.21–0.77; P=0.006) and ischemic stroke (HR: 0.47; 95% CI: 0.23–0.95; P=0.035). Conclusion Elderly patients with cryptogenic stroke and PFO have a high recurrence rate of ischemic stroke or TIA, which may be significantly reduced by device closure.

Background Perfusion imaging (PI) serves as a valuable tool for triaging patients with acute ischemic stroke for endovascular treatment (EVT). This study aims to investigate trends in PI use and its impacts on EVT rates and clinical outcomes, particularly focusing on variations across different time windows. Methods Data from a prospective, nationwide, acute stroke registry in South Korea were analyzed retrospectively. PI was regarded as treatment‐decision imaging when conducted either (1) prior to EVT, or (2) within 3 hours from hospital arrival in patients not receiving EVT. The study spanned 3 epochs: 2011–2014, 2015–2017, and 2018–2021. Based on the time from onset to arrival, patients were categorized into 2 time windows: early (0–6 hours) and late (6–24 hours). We evaluated EVT rates and clinical outcomes in patients with anterior large vessel occlusion. Results From 2011 to 2021 among 49 449 patients with acute ischemic stroke presenting within 24 hours of onset, PI use rates declined from 36.9% to 30.1%. In the early window, rates dropped from 48.4% to 32.4%, whereas in the late window, they increased from 23.5% to 27.8%. Factors such as older age, atrial fibrillation, anterior large vessel occlusion, and severe stroke were associated with higher rates in the late window. Conversely, younger age and male sex were associated with higher rates in the early window. For patients with anterior large vessel occlusion, PI use increased the likelihood of receiving EVT in the late window and minimized the risk of symptomatic intracranial hemorrhage in the early window. However, 3‐month functional outcomes and mortality were. unaffected. Conclusion The study revealed distinct trends in PI use across early and late time windows, indicating varying roles of PI in these time frames. However, the definitive value and necessity of PI in guiding EVT decision‐making remain unclear, underscoring the need for further research

Management of chalazion, characterized by noninfectious chronic granulomatous inflammation of the meibomian glands (MGs), remains challenging in ophthalmic practice, particularly because of its propensity for recurrence even after surgical intervention. This study aimed to evaluate the combined efficacy of doxycycline and intense pulsed light (IPL) therapy for treating intractable recurrent chalazion, focusing on reducing recurrence rates and improving MG status. This retrospective study included patients with intractable recurrent chalazion refractory to conventional treatments including surgical intervention and antibiotics. All patients were treated with a combination of doxycycline and IPL therapy. Clinical assessments included best-corrected visual activity, intraocular pressure, and MG evaluations using slit-lamp biomicroscopy and Keratograph 5 M topography. The study included 12 patients (5 male and 7 female) with an average age of 36.3 years. Treatment outcomes were categorized as ‘success’ (83.3%), ‘stationary’ (8.3%), and ‘failure’ (8.3%). Significant improvements were noted in the MG expression scores (p = 0.038), MG quality scores (p = 0.045), and lid margin telangiectasia scores (p = 0.002). In addition, significant improvement in meiboscores was observed (p = 0.002). The combination of doxycycline and IPL therapy demonstrated promising efficacy in treating intractable recurrent chalazion, with significant improvements in MG function and reduced recurrence rates. This treatment approach offers a viable alternative for patients with recurrent chalazions, particularly for those who are unresponsive to conventional treatments.

BackgroundThe mesocircuit model describes a complex network that includes the prefrontal cortical-striatopallidal-thalamo-cortical loop systems and is involved in the mechanism underlying consciousness in patients with disorders of consciousness (DoC). Inhibitory signals to the thalamus become hyperactive in DoC patients, leading to a loss of consciousness. Reactivating this mesocircuit system is important for recovering consciousness in these patients. We investigated how the residual integrity of the thalamo-dorsolateral prefrontal cortex tract (TDLPFCT) influences consciousness in patients with DoC.MethodsThis retrospective case–control study included three groups: prolonged DoC (n = 20), stroke without DoC (n = 20), and healthy controls (n = 20). Diffusion tensor imaging (DTI) was performed at least 4 weeks after the onset. Thalamo-DLPFC tracts were reconstructed using diffusion tensor tractography, and fractional anisotropy (FA) and tract volume (TV) were measured for each hemisphere. Consciousness was assessed using the revised coma recovery scale (CRS-R) within a week of brain imaging.ResultsSignificant differences in DLPFCT TV were observed across all three groups, in both affected and less-affected lobes, with the DoC group showing the greatest reduction. A significant correlation was found between the TV of the less-affected TDLPFCT and CRS-R score.ConclusionThe integrity of the TDLPFCT, particularly in the less affected hemisphere, is associated with consciousness levels in patients with prolonged DoC. This finding suggests its potential importance in assessing prognosis and further developing therapeutic strategies for patients with DoC.

Abstract Genome-wide association studies have identified several genetic variants associated with nonalcoholic fatty liver disease. To emphasize metabolic abnormalities in fatty liver, metabolic (dysfunction)-associated fatty liver disease (MAFLD) has been introduced; thus, we aimed to investigate single-nucleotide polymorphisms related to MAFLD and its subtypes. A genome-wide association study was performed to identify genetic factors related to MAFLD. We used a Korean population-based sample of 2282 subjects with MAFLD and a control group of 4669. We replicated the results in a validation sample which included 639 patients with MAFLD and 1578 controls. Additionally, we categorized participants into three groups, no MAFLD, metabolic dysfunction (MD)-MAFLD, and overweight/obese-MAFLD. After adjusting for age, sex, and principal component scores, rs738409 [risk allele G] and rs3810622 [risk allele T], located in the PNPLA3 gene, showed significant associations with MAFLD (P-values, discovery set = 1.60 × 10–15 and 4.84 × 10–10; odds ratios, 1.365 and 1.284, validation set = 1.39 × 10–4, and 7.15 × 10–4, odds ratios, 1.299 and 1.264, respectively). An additional SNP rs59148799 [risk allele G] located in the GATAD2A gene showed a significant association with MAFLD (P-values, discovery set = 2.08 × 10–8 and validation set = 0.034, odds ratios, 1.387 and 1.250). rs738409 was significantly associated with MAFLD subtypes ([overweight/obese-MAFLD; odds ratio (95% confidence interval), P-values, 1.515 (1.351–1.700), 1.43 × 10–12 and MD-MAFLD: 1.300 (1.191–1.416), 2.90 × 10–9]. There was a significant relationship between rs3810622 and overweight/obese-MAFLD and MD-MAFLD [odds ratios (95% confidence interval), P-values, 1.418 (1.258, 1.600), 1.21 × 10–8 and 1.225 (1.122, 1.340), 7.06 × 10–6, respectively]; the statistical significance remained in the validation set. PNPLA3 was significantly associated with MAFLD and MAFLD subtypes in the Korean population. These results indicate that genetic factors play an important role in the pathogenesis of MAFLD.

Purpose Cutting balloon-percutaneous transluminal angioplasty (CB-PTA) is a feasible treatment option for in-stent restenosis (ISR) after carotid artery stenting (CAS). However, the longterm durability and safety of CB-PTA for ISR after CAS have not been well established. Materials and Methods We retrospectively reviewed medical records of patients with ISR after CAS who had been treated with CB-PTA from 2012 to 2021 in our center. Detailed information of baseline characteristics, periprocedural and long-term outcomes, and follow-up imaging was collected. Results During 2012–2021, a total of 301 patients underwent CAS. Of which, CB-PTA was performed on 20 lesions exhibiting severe ISR in 18 patients following CAS. No patient had any history of receiving carotid endarterectomy or radiation therapy. These lesions were located at the cervical segment of the internal carotid artery (n=16), proximal external carotid artery (n=1), and distal common carotid artery (n=1). The median time interval between initial CAS and detection of ISR was 390 days (interquartile range 324–666 days). The follow-up period ranged from 9 months to 9 years with a median value of 21 months. Four patients (22.2%) were symptomatic. The average of stenotic degree before and after the procedure was 79.2% and 34.7%, respectively. Out of the 18 patients receiving CB-PTA, 16 (88.9%) did not require additional stenting, and 16 (88.9%) did not experience recurrent ISR during the follow-up period. Two patients who experienced recurrent ISR were successfully treated with CB-PTA and additional stenting. No periprocedural complication was observed in any case. Conclusion Regarding favorable periprocedural and long-term outcomes in our single-center experience, CB-PTA was a feasible and safe option for the treatment of severe ISR after CAS.

Objective This study aimed to compare the accuracy of robotic spine surgery and conventional pedicle screw fixation in lumbar degenerative disease. We evaluated clinical and radiological outcomes to demonstrate the noninferiority of robotic surgery. Methods This study employed propensity score matching and included 3 groups: robot-assisted mini-open posterior lumbar interbody fusion (PLIF) (robotic surgery, RS), c-arm guided minimally invasive surgery transforaminal lumbar interbody fusion (C-arm guidance, CG), and freehand open PLIF (free of guidance, FG) (54 patients each). The mean follow-up period was 2.2 years. The preoperative spine condition was considered. Accuracy was evaluated using the Gertzbein-Robbins scale (GRS score) and Babu classification (Babu score). Radiological outcomes included adjacent segmental disease (ASD) and mechanical failure. Clinical outcomes were assessed based on the visual analogue scale, Oswestry Disability Index, 36-item Short Form health survey, and clinical ASD rate. Results Accuracy was higher in the RS group (p < 0.01) than in other groups. The GRS score was lower in the CG group, whereas the Babu score was lower in the FG group compared with the RS group. No significant differences were observed in radiological and clinical outcomes among the 3 groups. Regression analysis identified preoperative facet degeneration, GRS and Babu scores as significant variables for radiological and clinical ASD. Mechanical failure was influenced by the GRS score and patients’ age. Conclusion This study showed the superior accuracy of robotic spine surgery compared with conventional techniques. When combined with minimally invasive surgery, robotic surgery is advantageous with reduced ligament and muscle damage associated with traditional open procedures.

Abstract Transcranial Direct Current Stimulation (tDCS) has benefits for motor rehabilitation in stroke patients, but its clinical application is limited due to inter-individual heterogeneous effects. Recently, optimized tDCS that considers individual brain structure has been proposed, but the utility thereof has not been studied in detail. We explored whether optimized tDCS provides unique electrode positions for each patient and creates a higher target electric field than the conventional approach. A comparative within-subject simulation study was conducted using data collected for a randomized controlled study evaluating the effect of optimized tDCS on upper extremity function in stroke patients. Using Neurophet tES LAB 3.0 software, individual brain models were created based on magnetic resonance images and tDCS simulations were performed for each of the conventional and optimized configurations. A comparison of electrode positions between conventional tDCS and optimized tDCS was quantified by calculation of Euclidean distances. A total of 21 stroke patients were studied. Optimized tDCS produced a higher electric field in the hand motor region than conventional tDCS, with an average improvement of 20% and a maximum of 52%. The electrode montage for optimized tDCS was unique to each patient and exhibited various configurations that differed from electrode placement of conventional tDCS. Optimized tDCS afforded a higher electric field in the target of a stroke patient compared to conventional tDCS, which was made possible by appropriately positioning the electrodes. Our findings may encourage further trials on optimized tDCS for motor rehabilitation after stroke.

BackgroundRepetitive transcranial magnetic stimulation (rTMS) is widely used therapy to enhance motor deficit in stroke patients. To date, rTMS protocols used in stroke patients are relatively unified. However, as the pathophysiology of stroke is diverse and individual functional deficits are distinctive, more precise application of rTMS is warranted. Therefore, the objective of this study was to determine the effects of personalized protocols of rTMS therapy based on the functional reserve of each stroke patient in subacute phase.MethodsThis study will recruit 120 patients with stroke in subacute phase suffering from the upper extremity motor impairment, from five different hospitals in Korea. The participants will be allocated into three different study conditions based on the functional reserve of each participant, measured by the results of TMS-induced motor evoked potentials (MEPs), and brain MRI with diffusion tensor imaging (DTI) evaluations. The participants of the intervention-group in the three study conditions will receive different protocols of rTMS intervention, a total of 10 sessions for 2 weeks: high-frequency rTMS on ipsilesional primary motor cortex (M1), high-frequency rTMS on ipsilesional ventral premotor cortex, and high-frequency rTMS on contralesional M1. The participants of the control-group in all three study conditions will receive the same rTMS protocol: low-frequency rTMS on contralesional M1. For outcome measures, the following assessments will be performed at baseline (T0), during-intervention (T1), post-intervention (T2), and follow-up (T3) periods: Fugl-Meyer Assessment (FMA), Box-and-block test, Action Research Arm Test, Jebsen-Taylor hand function test, hand grip strength, Functional Ambulatory Category, fractional anisotropy measured by the DTI, and brain network connectivity obtained from MRI. The primary outcome will be the difference of upper limb function, as measured by FMA from T0 to T2. The secondary outcomes will be the differences of other assessments.DiscussionThis study will determine the effects of applying different protocols of rTMS therapy based on the functional reserve of each patient. In addition, this methodology may prove to be more efficient than conventional rTMS protocols. Therefore, effective personalized application of rTMS to stroke patients can be achieved based on their severity, predicted mechanism of motor recovery, or functional reserves.Clinical trial registrationhttps://clinicaltrials.gov/, identifier NCT06270238.

BackgroundThe alpha-protein kinase 3 (ALPK3) gene (OMIM: 617608) is associated with autosomal recessive familial hypertrophic cardiomyopathy-27 (CMH27, OMIM: 618052). Recently, several studies have shown that monoallelic premature terminating variants (PTVs) in ALPK3 are associated with adult-onset autosomal dominant hypertrophic cardiomyopathy (HCMP). However, these studies were performed on patient cohorts mainly from European Caucasian backgrounds.MethodsTo determine if this finding is replicated in the Korean HCMP cohort, we evaluated 2,366 Korean patients with non-syndromic HCMP using exome sequencing and compared the cohort dataset with three independent population databases.ResultsWe observed that monoallelic PTVs in ALPK3 were also significantly enriched in Korean patients with HCMP with an odds ratio score of 10–21.ConclusionsWe suggest that ALPK3 PTV carriers be considered a risk group for developing HCMP and be monitored for cardiomyopathies.

Rho guanine nucleotide exchange factors (Rho GEFs) activate Rho GTPases, which act as molecular switches regulating various essential cellular functions. This study investigated the role of ARHGEF5, a Rho GEF known for its involvement in cell migration and invasion processes, in the context of brain development. We found that ARHGEF5 is essential for dendrite development during the early stages of neuronal growth. We also discovered that ARHGEF5 binds to Drebrin E, which is vital for coordinating actin and microtubule dynamics, and facilitates the interaction between Drebrin E and Cyclin-dependent kinase 5, which phosphorylates Drebrin E. Notably, ARHGEF5 deficiency resulted in a decrease in acetylated α-tubulin levels, and the expression of an α-tubulin acetylation mimetic mutant (K40Q) rescued the defects in dendrite development and neuronal migration, suggesting ARHGEF5’s role in modulating microtubule stability. Additionally, ARHGEF5 was shown to influence Golgi positioning in the leading processes of migrating cortical neurons during brain development. Our study suggests that ARHGEF5 plays a crucial role in integrating cytoskeletal dynamics with neuronal morphogenesis and migration processes during brain development.

Objective: EuCorVac-19 (ECV-19), an adjuvanted liposome-displayed receptor binding domain (RBD) COVID-19 vaccine, previously reported interim Phase 2 trial results showing induction of neutralizing antibodies 3 weeks after prime-boost immunization. The objective of this study was to determine the longer-term antibody response of the vaccine. Methods: To assess immunogenicity 6 and 12 months after vaccination, participants in the Phase 2 trial (NCT04783311) were excluded if they: 1) withdrew, 2) reported COVID-19 infection or additional vaccination, or 3) exhibited increasing Spike (S) antibodies (representing possible non-reported infection). Following exclusions, of the 197 initial subjects, anti-S IgG antibodies and neutralizing antibodies were further assessed in 124 subjects at the 6-month timepoint, and 36 subjects at the 12-month timepoint. Results: Median anti-S antibody half-life was 52 days (interquartile range [IQR]:42-70), in the “early” period from 3 weeks to 6 months, and 130 days (IQR:97-169) in the “late” period from 6 to 12 months. There was a negative correlation between initial antibody titer and half-life. Anti-S and neutralizing antibody responses were correlated. Neutralizing antibody responses showed longer half-lives; the early period had a median half-life of 120 days (IQR:81-207), and the late period had a median half-life of 214 days (IQR:140-550). Conclusion: These data establish antibody durability of ECV-19, using a framework to analyze COVID-19 vaccine-induced antibodies during periods of high infection.