Functional-hydrogel-based electronic-skin patch for accelerated healing and monitoring of skin wounds.

Conductive hydrogels feature reasonable electrical performance as well as tissue-like mechanical softness, thus positioning them as promising material candidates for soft bio-integrated electronics. Despite recent advances in materials and their processing technologies, however, facile patterning and monolithic integration of functional hydrogels (e.g., conductive, low-impedance, adhesive, and insulative hydrogels) for all-hydrogel-based soft bioelectronics still poses significant challenges. Here, we report material design, fabrication, and integration strategies for an electronic-skin (e-skin) patch based on functional hydrogels. The e-skin patch was fabricated by using photolithography-compatible functional hydrogels, such as poly(2-hydroxyethyl acrylate) (PHEA) hydrogel (substrate), Ag flake hydrogel (interconnection; conductivity: ∼571.43 S/cm), poly(3,4-ethylenedioxythiophene:polystyrene) (PEDOT:PSS) hydrogel (working electrode; impedance: ∼69.84 Ω @ 1 Hz), polydopamine (PDA) hydrogel (tissue adhesive; shear strength: ∼725.1 kPa), and poly(vinyl alcohol) (PVA) hydrogel (encapsulation). The properties of these functional hydrogels closely resemble those of human tissues in terms of water content and Young's modulus, enabling stable tissue-device interfacing in dynamically changing physiological environments. We demonstrated the efficacy of the e-skin patch through its application to accelerated healing and monitoring of skin wounds in mouse models - efficient fibroblast migration, proliferation, and differentiation promoted by electric field (EF) stimulation and iontophoretic drug delivery, and monitoring of the accelerated healing process through impedance mapping. The all-hydrogel-based e-skin patch is expected to create new opportunities for various clinically-relevant tissue interfacing applications.

Quality Characteristics of Meat Analogs through the Incorporation of Textured Vegetable Protein and Tenebrio molitor Larvae in the Presence of Transglutaminase.

Alternative protein sources with greater nutritional value and a lower environmental footprint have recently attracted interest in the production of meat substitutes. However, it is required that these alternatives mimic the texture and structure of meat. This study investigated varying ratios of textured vegetable proteins (TVP) to Tenebrio molitor larvae (brown mealworm; TM) with the addition of transglutaminase (TG) to determine the quality characteristics of these emulsions. The results demonstrated low protein solubility of the emulsions as TVP content increased. Furthermore, when the proportion of TM was high, the TG-treated emulsion had a low pH. Additionally, when there was a high TM ratio to TVP in the TG treatment, the emulsions demonstrated better thermal stability and water holding capacity. Regarding the rheological properties of the emulsion, both the frequency-dependent storage modulus (G') and loss modulus (G'') increased as the proportion of TVP in the emulsion increased with and without the addition of TG. Differential scanning calorimetry analyses demonstrated two protein denaturation peaks in all treatments, with high peak temperatures for both treatments with a high proportion of TM. The hardness and chewiness of the emulsion were highest in the treatment (T6 and T8) with TG, and the gumminess of the emulsion was greatest when TM only or when equal ratios of TVP and TM were treated with TG, respectively. In conclusion, the addition of TM to TVP with TG improves the overall texture of the protein mixture, making it a suitable meat alternative.

Urethral diverticulum in pregnancy: Rare case report and brief literature review.

OBJECTIVE: Female urethral diverticulum (UD), an evagination of the urethral mucosa into the surrounding connective tissue, is extremely rare in pregnancy. No clear guidelines on the optimal management of UD have been established, except for a common conservative approach. Here, we discuss how to manage UD with pregnancy. CASE REPORT: A 39-year-old gravida 4, para 0, abortion 3 (G4P0A3) woman at 34+0 gestational weeks (GW) visited our outpatient department with a 6-cm septate vaginal mass. Transvaginal ultrasound sonography (TVUS) revealed a 5.5 x 4.9-cm multicystic mass, which was confirmed as UD with pelvic MRI. She was admitted because of preterm labor. A cesarean section was performed at 36+5 GW due to a previous myomectomy, and a healthy male baby was born. UD was still observed in the patient two months after delivery. Periurethral diverticulectomy was performed, and pathological analysis revealed UD with chronic inflammation and edema. CONCLUSION: Previous reports and our case report show that UD can develop during pregnancy and that pelvic MRI is suitable for its accurate diagnosis. Vaginal delivery is possible in pregnant women with the small size of the UD. UD aspiration can permit vaginal delivery in a few cases; however, pus can occur at the aspirated site after the operation. If UD is still observed after delivery, urethral diverticulectomy is recommended.

Role of NOX1 and NOX5 in protein kinase C/reactive oxygen species­mediated MMP­9 activation and invasion in MCF­7 breast cancer cells.

NADPH oxidases (NOXs) are a family of membrane proteins responsible for intracellular reactive oxygen species (ROS) generation by facilitating electron transfer across biological membranes. Despite the established activation of NOXs by protein kinase C (PKC), the precise mechanism through which PKC triggers NOX activation during breast cancer invasion remains unclear. The present study aimed to investigate the role of NOX1 and NOX5 in the invasion of MCF­7 human breast cancer cells. The expression and activity of NOXs and matrix metalloprotease (MMP)­9 were assessed by reverse transcription­quantitative PCR and western blotting, and the activity of MMP­9 was monitored using zymography. Cellular invasion was assessed using the Matrigel invasion assay, whereas ROS levels were quantified using a FACSCalibur flow cytometer. The findings suggested that NOX1 and NOX5 serve crucial roles in 12­O­tetradecanoylphorbol­13­acetate (TPA)­induced MMP­9 expression and invasion of MCF­7 cells. Furthermore, a connection was established between PKC and the NOX1 and 5/ROS signaling pathways in mediating TPA­induced MMP­9 expression and cellular invasion. Notably, NOX inhibitors (diphenyleneiodonium chloride and apocynin) significantly attenuated TPA­induced MMP­9 expression and invasion in MCF­7 cells. NOX1­ and NOX5­specific small interfering RNAs attenuated TPA­induced MMP­9 expression and cellular invasion. In addition, knockdown of NOX1 and NOX5 suppressed TPA­induced ROS levels. Furthermore, a PKC inhibitor (GF109203X) suppressed TPA­induced intracellular ROS levels, MMP­9 expression and NOX activity in MCF­7 cells. Therefore, NOX1 and NOX5 may serve crucial roles in TPA­induced MMP­9 expression and invasion of MCF­7 breast cancer cells. Furthermore, the present study indicated that TPA­induced MMP­9 expression and cellular invasion were mediated through PKC, thus linking the NOX1 and 5/ROS signaling pathways. These findings offer novel insights into the potential mechanisms underlying their anti­invasive effects in breast cancer.

Guidelines for Antibacterial Treatment of Carbapenem-Resistant Enterobacterales Infections.

This guideline aims to promote the prudent use of antibacterial agents for managing carbapenem-resistant Enterobacterales (CRE) infections in clinical practice in Korea. The general section encompasses recommendations for the management of common CRE infections and diagnostics, whereas each specific section is structured with key questions that are focused on antibacterial agents and disease-specific approaches. This guideline covers both currently available and upcoming antibacterial agents in Korea.

Polaribacter ponticola sp. nov., isolated from seawater, reclassification of Polaribacter undariae as a later heterotypic synonym of Polaribacter sejongensis, and emended description of Polaribacter sejongensis Kim et al. 2013.

A Gram-stain-negative, yellow-pigmented, and strictly aerobic bacterium, designated as strain MSW5T, was isolated from seawater of the Yellow Sea in South Korea. The cells were non-motile rods exhibiting oxidase- and catalase-positive activities. Growth was observed at 15-25 °C (optimum, 25 °C) and pH 5.0-9.0 (optimum, pH 7.0-8.0) and in the presence of 1.0-5.0% (w/v) NaCl (optimum, 2.0%). Menaquinone-6 was the sole respiratory quinone, and iso-C15 : 0, summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c), iso-C15 : 0 3-OH, and C15 : 1 ω6c were the major cellular fatty acids. Major polar lipids included phosphatidylethanolamine, two unidentified aminolipids, and three unidentified lipids. Phylogenetic analyses based on 16S rRNA gene sequences and 92 concatenated core protein sequences revealed that strain MSW5T formed a distinct lineage within the genus Polaribacter. The genome of strain MSW5T was 3582 kb in size with a 29.1 mol% G+C content. Strain MSW5T exhibited the highest similarity to Polaribacter atrinae WP25T, with a 97.9% 16S rRNA gene sequence similarity. However, the average nucleotide identity and digital DNA-DNA hybridization values were 79.4 and 23.3%, respectively, indicating that strain MSW5T represents a novel species. Based on its phenotypic, chemotaxonomic, and phylogenetic characteristics, strain MSW5T is proposed to represent a novel species, with the name Polaribacter ponticola sp. nov. The type strain is MSW5T (=KACC 22340T=NBRC 116025T). In addition, whole genome sequence comparisons and phenotypic features suggested that Polaribacter sejongensis and Polaribacter undariae belong to the same species, with P. undariae proposed as a later heterotypic synonym of P. sejongensis. An emended description of Polaribacter sejongensis is also proposed.

Radiographic and neurological outcomes of Gamma Knife radiosurgery for lower cranial nerve schwannomas: a single-institution experience.

OBJECTIVE: Gamma Knife radiosurgery (GKRS) is widely used for treating small- to medium-sized or postoperative residual, recurrent lower cranial nerve schwannomas (LCNSs). This study aimed to evaluate the radiographic and neurological outcomes of GKRS for LCNS. METHODS: A total of 60 patients with 47 jugular foramen schwannomas (JFSs) and 13 hypoglossal nerve schwannomas (HNSs) who underwent GKRS were included. Dysphagia (40.4%) and hoarseness (23.4%) were the most common preexisting symptoms associated with JFS, whereas tongue deviation (53.8%) was prevalent in HNS. The median tumor volumes were 3.2 cm3 and 2.2 cm3 for JFSs and HNSs, respectively. The median marginal dose administered to the tumor was 13 Gy (range 12-15 Gy). The median follow-up duration was 52.8 months. RESULTS: Local tumor control was achieved in 91.5% of JFSs and 92.3% of HNSs. The preexisting neurological symptoms improved in 48.9% of patients with JFS and remained stable in 29.8%. However, 10 patients (21.3%) experienced exacerbation of symptoms associated with cranial nerves VII, VIII, IX, X, and XI. Among these, 3 patients (6.4%) exhibited persistent symptomatic deterioration. Patients with HNSs demonstrated a stable trajectory without symptom aggravation. Larger tumor volume and cystic portion were significantly associated with tumor progression (p = 0.017 and 0.003, respectively), and post-GKRS transient swelling was associated with neurological deterioration (p = 0.044). CONCLUSIONS: GKRS is an alternative treatment option for LCNS that reduces surgical morbidity and enhances tumor control. However, GKRS can potentially lead to neurological deterioration, necessitating extreme caution throughout the procedure, specifically for JFSs.

Deciphering the links: Fragmented polystyrene as a driver of skin inflammation.

Nano- and microplastics (NMPs), ubiquitous in the environment, pose significant health risks. We report for the first time a comprehensive study using in-vitro, in-vivo, and ex-vivo models to investigate the penetration and inflammatory effects of fragmented polystyrene (fPS) on human skin, including the analysis of both penetration depth and fPS amounts that penetrate the skin. Human keratinocyte (HaCaT) and human dermal fibroblast (HDF) cells exposed to fPS exhibited notable internalization and cytotoxicity. In a 3D human skin model, fPS particles penetrated the dermal layer within one hour, with an average maximum penetration of 4.7 µg for particles smaller than 2 µm. Similarly, mouse dorsal skin and human abdominal skin models confirmed fPS penetration. RNA sequencing revealed substantial upregulation of inflammatory genes, including IL-1α, IL-1ß, IL-18, IL-6, IL-8, ICAM-1, FOS, and JUN, following fPS exposure. These findings were validated at both the mRNA and protein levels, indicating a robust inflammatory response. Notably, the inflammatory response in both the 3D human skin and mouse models increased in a dose-dependent manner, underscoring the toxicological impact of fPS on skin health. This study provides crucial insights into the mechanisms through which NMPs affect human health and underscores the need for further research to develop effective mitigation strategies.

Epidemiologic characteristics and risk factors of Clostridioides difficile infection in patients with active tuberculosis in the Republic of Korea: A nationwide population-based study.

BACKGROUND: The relationship between anti-tuberculosis (TB) agents and Clostridioides difficile infection (CDI) remains unclear. This study aimed to investigate the epidemiological characteristics and risk factors for CDI in patients with TB. METHODS: This nationwide, population-based cohort study was conducted in the Republic of Korea (ROK) between January 2018 and December 2022. Data were extracted from the National Health Insurance Service (NHIS) National Health Information Database. The risk factors for CDI in patients with TB were identified through multivariate logistic regression analysis using a 1:4 greedy matching method based on age and sex. RESULTS: During the study period, CDI developed in 2,901 of the 131,950 patients with TB who were prescribed anti-TB agents. The incidence of CDI in patients with TB has increased annually in the ROK from 12.31/1000 in 2018 to 33.51/1000 in 2022. Oral metronidazole (81.94%) was the most common first-line treatment for CDI. The in-hospital mortality rate of patients with concomitant CDI and tuberculosis was 9.9% compared with 6.9% in those with TB alone (P<0.0001). Multivariate logistic regression analysis found intensive care unit admission, Charlson Comorbidity Index ≥3, antibiotics exposure, standard regimen, multidrug resistant TB, and extrapulmonary TB as significant risk factors for development of CDI in patients with TB. CONCLUSION: CDI is uncommon in patients with TB, but it results in a significantly increased mortality rate. Patients being treated for TB should be carefully monitored for the development of CDI. Further clinical research is warranted to identify effective interventions for preventing and controlling CDI during TB treatment.

Therapeutic single-cell landscape: methotrexate exacerbates interstitial lung disease by compromising the stemness of alveolar epithelial cells under systemic inflammation.

BACKGROUND: Interstitial lung disease (ILD) poses a serious threat in patients with rheumatoid arthritis (RA). However, the impact of cornerstone drugs, including methotrexate (MTX) and TNF inhibitor, on RA-associated ILD (RA-ILD) remains controversial. METHODS: Using an SKG mouse model and single-cell transcriptomics, we investigated the effects of MTX and TNF blockade on ILD. FINDINGS: Our study revealed that MTX exacerbates pulmonary inflammation by promoting immune cell infiltration, Th17 activation, and fibrosis. In contrast, TNF inhibitor ameliorates these features and inhibits ILD progression. Analysis of data from a human RA-ILD cohort revealed that patients with ILD progression had persistently higher systemic inflammation than those without progression, particularly among the subgroup undergoing MTX treatment. INTERPRETATION: These findings highlight the need for personalized therapeutic approaches in RA-ILD, given the divergent outcomes of MTX and TNF inhibitor. FUNDING: This work was funded by GENINUS Inc., and the National Research Foundation of Korea, and Seoul National University Hospital.

Masticatory Function, Sex, and Risk of Dementia Among Older Adults: A Population-Based Cohort Study.

BACKGROUND: A decline in masticatory function may indicate brain dysfunction related to dementia, but the relationship between masticatory function and dementia risk remains unclear. This study aimed to investigate whether masticatory function is associated with the risk of cognitive decline and dementia. METHODS: Data were obtained from the nationwide prospective cohort study of randomly sampled community-dwelling Koreans aged ≥ 60 years. The 5,064 non-demented participants, whose number of chewing cycles per bite was assessed by clinical interview, were followed for 8 years with biennial assessments of cognitive performance and clinical diagnoses of all-cause dementia and Alzheimer's disease (AD). Structural brain magnetic resonance imaging was collected from a subset of cohort participants and their spouses for imaging analyses. RESULTS: Males who chewed ≥ 30 cycles/bite had faster decline in global cognition and memory function and were at higher risk for incident all-cause dementia (hazard ratio [HR], 2.91; 95% confidence interval [CI], 1.18-7.18) and AD (HR, 3.22; 95% CI, 1.14-9.11) compared to males with less than 10 cycles/bite. Additionally, increased chewing cycles in males were associated with reduced brain volume, particularly in regions involved in compensatory cognitive control of mastication. There was no significant association between chewing cycles and the risk of dementia or brain volume in females. CONCLUSION: Older men who frequently chew their meals could be considered a notable population at risk for dementia who should be carefully assessed for their cognitive trajectories.

Diagnostic Utility of Whole Genome Sequencing After Negative Karyotyping/Chromosomal Microarray in Infants Born With Multiple Congenital Anomalies.

BACKGROUND: Achieving a definitive genetic diagnosis of unexplained multiple congenital anomalies (MCAs) in neonatal intensive care units (NICUs) infants is challenging because of the limited diagnostic capabilities of conventional genetic tests. Although the implementation of whole genome sequencing (WGS) has commenced for diagnosing MCAs, due to constraints in resources and faculty, many NICUs continue to utilize chromosomal microarray (CMA) and/or karyotyping as the initial diagnostic approach. We aimed to evaluate the diagnostic efficacy of WGS in infants with MCAs who have received negative results from karyotyping and/or CMA. METHODS: In this prospective study, we enrolled 80 infants with MCAs who were admitted to a NICU at a single center and had received negative results from CMA and/or karyotyping. The phenotypic characteristics were classified according to the International Classification of Diseases and the Human Phenotype Ontology. We assessed the diagnostic yield of trio-WGS in infants with normal chromosomal result and explored the process of diagnosing by analyzing both phenotype and genotype. Also, we compared the phenotype and clinical outcomes between the groups diagnosed with WGS and the undiagnosed group. RESULTS: The diagnostic yield of WGS was 26% (21/80), of which 76% were novel variants. There was a higher diagnostic yield in cases of craniofacial abnormalities, including those of the eye and ear, and a lower diagnostic yield in cases of gastrointestinal and genitourinary abnormalities. In addition, higher rates of rehabilitation therapy and gastrostomy were observed in WGS-diagnosed infants than in undiagnosed infants. CONCLUSION: This prospective cohort study assessed the usefulness of trio-WGS following chromosomal analysis for diagnosing MCAs in the NICU and revealed improvements in the diagnostic yield and clinical utility of WGS.

Caregiving-Related Depression Increases Neuroinflammation in Spousal Caregivers to Individuals with Cognitive Impairment: A Longitudinal Study.

BACKGROUND: The caregiving burden of the spousal caregivers (SCGs) to individuals with cognitive impairment poses public health challenges with adverse psychosocial and physiological effects. However, few studies have investigated the neurobiological impact of caregiving, particularly through the investigation of neuroinflammation and neurodegeneration. METHODS: Using data from a longitudinal cohort at Chungnam National University Hospital, the relationship between caregiving burden, neuroinflammation and neurodegeneration was examined in 38 older adult couples over a 16-month period. Caregiving burden was assessed through a multifaceted approach. For factors related to the care recipient, we assessed cognitive function and neuropsychiatric symptoms. Factors regarding the SCGs included the measurement of perceived depression. Glial fibrillary acidic protein (GFAP) was used as a plasma biomarker for neuroinflammation and neurofilament light chain (NfL) for neurodegeneration. Regression analyses were adjusted for age, sex, apolipoprotein E status, follow-up interval, vascular risk factors, and physical activity. RESULTS: Changes in depression among SCGs were significantly correlated with increased GFAP levels (p = 0.003), indicating that greater depressive symptoms during caregiving are associated with increased neuroinflammation. In contrast, no significant correlations were found between changes in cognitive function or neuropsychiatric symptoms in care recipients and the plasma biomarker levels of SCGs. Additionally, there was no significant association between changes in depression and NfL levels in SCGs. CONCLUSIONS: The psychological stress experienced by SCGs while caring for partners with cognitive impairment actively contributes to neuroinflammation, a well-known risk factor for various diseases. This study emphasizes the need to address psychological stress experienced by older adult caregivers.

Progress of Metal Chalcogenides as Catalysts for Efficient Electrosynthesis of Hydrogen Peroxide.

Hydrogen peroxide (H2O2) is a high-demand chemical, valued as a powerful and eco-friendly oxidant for various industrial applications. The traditional industrial method for producing H2O2, known as the anthraquinone process, is both costly and environmentally problematic. Electrochemical synthesis, which produces H2O2 using electricity, offers a sustainable alternative, particularly suited for small-scale, continuous on-site H2O2 generation due to the portability of electrocatalytic devices. For efficient H2O2 electrosynthesis, electrocatalysts must exhibit high selectivity, activity, and stability for the two-electron pathway-oxygen reduction reaction (2e- ORR). Transition-metal chalcogenide (TMC)-based materials have emerged as promising candidates for effective 2e- ORR due to their high activity in acidic environments and the abundance of their constituent elements. This review examines the potential of TMC-based catalysts in H2O2 electrosynthesis, categorizing them into noble-metal and non-noble-metal chalcogenides. It underscores the importance of achieving high selectivity, activity, and stability in 2e- ORR. By reviewing recent advancements and identifying key challenges, this review provides valuable insights into the development of TMC-based electrocatalysts for sustainable H2O2 production.

Comparative analysis of body composition using torso CT from PET/CT with bioelectrical impedance and muscle strength in healthy adults.

The role of torso computed tomography (CT) in evaluating body composition has been unexplored. This study assessed the potential of low-dose torso CT from positron emission tomography (PET)/CT for analyzing body composition and its relation to muscle strength. We retrospectively recruited 384 healthy Korean adults (231 men, 153 women) who underwent torso 18F-FDG PET/CT, bioelectrical impedance analysis (BIA), and muscle strength tests (handgrip strength [HGS] and knee extension strength [KES]). CT images were segmented into three compartments: torso volumetric, abdominal volumetric, and abdominal areal. Muscle amounts from each compartment were indexed to height (m2). BIA and HGS served as reference standards, with correlation coefficients (r) calculated. Torso muscle volumetric index (TorsoMVI) had the strongest correlations with BIA-derived values (r = 0.80 for men; r = 0.73 for women), surpassing those from the abdominal compartments. TorsoMVI was also correlated significantly with HGS (r = 0.39, p < 0.01) and differentiated between normal and possible sarcopenia in men (n = 225, 5960 ± 785 cm3/m2 vs. n = 6, 5210 ± 487 cm3/m2, p = 0.02). In women, KES correlated more strongly with muscle parameters than HGS. Despite gender-specific variations, torso CT-derived parameters show promise for evaluating body composition and sarcopenia.

Clinical feasibility of deep learning-accelerated single-shot turbo spin echo sequence with enhanced denoising for pancreas MRI at 3 Tesla.

PURPOSE: To assess the feasibility of the single-shot turbo spin echo sequence using deep learning-based reconstruction (DLR) (HASTEDL) with enhanced denoising for pancreas MRI. METHODS: Patients who underwent pancreas MRI from March to April 2021 were included. Four T2-weighted images (non-FS conventional HASTE vs. HASTEDL with enhanced denoising and FS HASTEDL with enhanced denoising vs. HASTEDL) were acquired. Two readers independently assessed the image quality parameters of the two non-FS image sets using a 4-point Likert scale. The signal-to-noise ratio (SNR) of the cystic lesions and pancreatic parenchyma and the contrast-to-noise ratio between the cystic lesion and pancreatic parenchyma were calculated for all four image sets. The size of the largest cystic lesion and the diameter of pancreatic duct were measured. RESULTS: A total of 63 patients were included, 48 (76.2 %) of whom had 136 pancreatic cystic lesion(s). The acquisition times of conventional HASTE and HASTEDL were 69 and 18 sec, respectively. All image quality parameters except artifacts for reader 2 were significantly better for HASTEDL with enhanced denoising. Those images also received scores for overall image quality that were significantly higher than those for the conventional HASTE (3.26 ±â€¯0.54 vs. 2.47 ±â€¯0.56, p < 0.001). The SNR of the pancreatic cystic lesion and pancreatic parenchyma was significantly higher in the HASTEDL with enhanced denoising (p < 0.001 for both). Inter-reader variability for measuring the pancreatic cyst size (ICC, 0.999 vs. 0.995; 95 % LoA, -0.13481 to 0.14743 vs. -0.24097 to 0.27404) and duct diameter (ICC, 0.994 vs. 0.969; 95 % LoA, -0.11684 to 0.36026 vs. -0.45544 to 0.44664) was lower in HASTEDL with enhanced denoising than in the conventional HASTE. CONCLUSION: HASTEDL with enhanced denoising could be useful for reducing the acquisition time of pancreas MRI while improving the image quality for the evaluation of pancreatic cystic lesions.

Dynamics of SARS-CoV-2 variants during the XBB wave in the Republic of Korea.

As COVID-19 has become endemic, SARS-CoV-2 variants are becoming increasingly diverse, underscoring the escalating importance of global genomic surveillance. This study analyzed 86,762 COVID-19 samples identified in the Republic of Korea from September 2022 to November 2023. The results revealed a consistent increase in the prevalence of the XBB variants following the dominance of BN.1, with various XBB sub-lineages co-circulating in the Republic of Korea. The overall nucleotide diversity (π) among the SARS-CoV-2 genomes was 0.00155. Evolutionary analysis revealed that the average time interval between the first detection and estimated date of the most recent common ancestor of Korean XBB sub-lineages was 47 d, suggesting that the novel variants were efficiently identified in the Korean surveillance system. The mutation rate was determined to be in the range of 5.6 × 10-4 to 9.1 × 10-4 substitutions/site/year. In conclusion, this study provides insights into the genetic diversity and evolutionary interpretation of the XBB sub-lineages during the XBB wave in the Republic of Korea, highlighting the importance of continued genomic surveillance for emerging variants.

Genotype-Phenotype Correlations in 83 Korean X-linked Retinoschisis Patients: Impact of RS1 Secretion Profiles on Clinical Phenotypes.

PURPOSE: To assess the correlation between genotype and phenotype severity in X-linked juvenile retinoschisis (XLRS) by examining clinical and genetic features of a cohort of Korean XLRS patients. DESIGN: Retrospective, observational study. PARTICIPANTS: Data from 83 consecutive male patients with molecularly confirmed XLRS were collected retrospectively. METHODS: Clinical evaluation included best-corrected visual acuity (BCVA), fundus photography, spectral-domain optical coherence tomography (SD-OCT), and full-field electroretinography (ERG). MAIN OUTCOME MEASURES: The phenotypic characteristics of a cohort of pediatric Korean XLRS patients, based on mutation types (truncating versus missense) and secretory profile (secretion versus non-secretion), were assessed. RESULTS: One hundred sixty-six eyes of 83 patients were included. The mean age at diagnosis was 6.1 ± 8.8 years (range, 0.5-20.7 years), with a mean follow-up time of 9.2 ± 7.0 years (range, 0.6-24.3 years). The BCVA at first and last examination ranged from light perception to 0.1 logarithm of the minimum angle of resolution (mean ± SD, 0.75 ± 0.59 and 0.82 ± 0.65, respectively). There were no significant differences in the first and last BCVA measurements between the truncating (0.71 ± 0.51 and 0.75 ± 0.44) and missense (0.77 ± 0.59 and 0.84 ± 0.66) variants (P = 0.678 and 0.551, respectively). Additionally, there were no differences in clinical parameters from fundus photography, SD-OCT, and full-field ERG. However, the BCVA at the first and last measurement were better for patients in the secretion group (0.51 ± 0.24 and 0.61 ± 0.30) compared to patients in the non-secretion group (0.65 ± 0.71 and 0.87 ± 0.81). The last BCVA showed a statistically significant difference between the two groups (P = 0.021). In OCT findings, the frequency of ellipsoid zone disruption was higher in patients with non-secretion variants than those with secretion variants (P = 0.030), with no significant differences in other parameters. CONCLUSIONS: The secretion profile of RS1 could influence the severity of XLRS phenotypes. Patients with RS1-secreted mutants, particularly with intact octamerization, exhibit more homogeneous phenotypes and better visual acuity than the RS1-non-secreted group. This data provides insights for studying genotype and phenotype correlations in both clinical and research fields.

A comprehensive genotype-phenotype study in 203 individuals with retinoblastoma.

Retinoblastoma is the most common intraocular tumor in children and is caused by biallelic inactivation of the RB1 gene. The identification of RB1 germline variants in patients with retinoblastoma and their families is critical for early diagnosis and prevention. In this study, genetic testing was conducted on the genomic DNA of 203 patients with retinoblastoma using a combined approach of direct sequencing and multiplex ligation-dependent probe amplification (MLPA) assays for genotype-phenotype correlation studies. Sixty-five germline variants were identified in 80 of the 203 patients, with 67 bilateral and 13 unilateral retinoblastoma cases. The variant detection rates in the bilateral and unilateral cases were 88% and 10%, respectively. Eighteen novel variants were identified. Variants were classified according to their presence, mutation pattern, location, molecular consequences, and pathogenicity. Subsequently, the genotypes and phenotypes of the 203 patients were evaluated. Variants were associated with age at diagnosis (p < 0.001), laterality (p < 0.001), and tumor size (p = 0.010). The molecular consequences of the variants were related to laterality (p < 0.001) and tumor size (p = 0.001). The pathogenicity of the variants was associated with age at diagnosis (p = 0.001), laterality (p = 0.0212), treatment response (p = 0.0470), and tumor size (p = 0.002). These results suggest that patient phenotypes are associated with the inherent characteristics of germline RB1 variants. These findings indicate the potential application of genetic testing results in clinical practice.