The efficacy of adipose stem cell-derived exosomes in hair regeneration based on a preclinical and clinical study.

BACKGROUND: Androgenetic alopecia (AGA) is a prevalent hair loss disorder with psychological repercussions. Traditional treatments have limitations, leading to the exploration of regenerative therapies such as exosomes derived from adipose tissue stem cells (ASC-Exosomes). METHODS: First, using human hair follicle (HF) dermal papilla cells (hDPCs) treated with ASC-Exosomes, ALP, VCAN, ß-catenin, and LEF-1 levels with RT-PCR and p-GSK3ß, GSK3ß, ß-catenin, ALP, and ß-actin levels with western blot analysis were assessed. Hair shaft elongation test and assay for ALP, Ki-67, and ß-catenin were done using human HF organ culture. Patients with AGA had ASC-Exosomes treatment and were evaluated for hair counts, photographic assessments, subjective satisfaction, and safety profiles. RESULTS: ASC-Exosomes impact hDPCs, increasing proliferation and the upregulation of hair growth-related genes, including ALP, VCAN, ß-catenin, and LEF-1. The Wnt/ß-catenin pathway was activated, indicating their role in promoting hair growth. ASC-Exosomes also promoted hair shaft elongation and ALP activity, suggesting a potential for hair regeneration. Thirty participants with AGA enrolled and treated over 24 weeks. The subjects experienced a significant increase in total hair density, improved global photographic assessments, and reported higher subjective satisfaction without severe adverse reactions. CONCLUSION: This research contributes to the growing body of evidence supporting the use of exosomes in hair loss treatment, offering a safe and effective alternative for individuals with AGA.

Effect of epinephrine-mixed fascia iliaca compartment block on bleeding in total hip arthroplasty: A single-center retrospective study.

Fascia iliaca compartment block (FICB) reduces opioid consumption and pain scores after total hip arthroplasty (THA), and has recently been widely applied. We investigated whether FICB could also reduce postoperative bleeding. One hundred and fifteen consecutive patients who underwent elective THA under general anesthesia over 5 months were retrospectively analyzed. They were divided into 2 groups: the FICB group received an epinephrine-mixed FICB procedure and the control group did not receive any block. Using the hematocrit measured at 4 different time points (preoperative and 1, 24, and 48 hours after surgery), the estimated blood loss (EBL) was calculated for 3 different time periods (0-1, 1-24, 24-48 hours after surgery). EBL at 1 to 24 hours (226 vs 398 mL, P = .008) was significantly lower in the FICB group than in the control group. Additionally, the number of packed red cell (PRC) units transfused per patient over 48 hours was 0.38 units in the FICB group, which was significantly lower than the 0.70 units used in the control group (P = .040). Epinephrine-mixed FICB in THA has the potential to reduce postoperative bleeding in the first 24 hours after surgery as well as reduce PRC transfusion requirements.

Severe acquired hemophilia A associated with COVID-19 vaccination: A case report and literature review.

RATIONALE: Acquired hemophilia A (AHA) is a rare autoimmune disease caused by an antibody that inhibits coagulation factor VIII activity. More than half of patients with AHA cannot identify underlying disorders. The remaining patients are associated with malignancies, autoimmune diseases, skin diseases, infections, and medications. Here, we present a case of 56-year-old Korean man with underlying hypertension, dyslipidemia, and diabetes mellitus who developed AHA following the second dose of BNT162b2 COVID-19 vaccination. PATIENT CONCERNS: He presented with a large 20 × 30 cm-sized hematoma along the psoas muscle and intracranial hemorrhage, necessitating intensive care with mechanical ventilation and continuous renal replacement therapy. Laboratory testing demonstrated that activated partial thromboplastin time and prothrombin times were 74.7 seconds (normal range 29-43 seconds) and 17.2 seconds (normal range 12.5-14.7 seconds), respectively. DIAGNOSES: Laboratory tests confirmed AHA with undetectable factor VIII activity (<1.5%) and a positive factor VIII antibody with a titer of 8.49 Bethesda units/mL. INTERVENTIONS: Recombinant factor VIIa (NovoSeven®) was administered every 2 hours to control the bleeding, alongside immunosuppression with methylprednisolone 1 mg/kg daily and cyclophosphamide 2 mg/kg daily to eliminate the autoantibody. OUTCOMES: Despite the treatments, the patient developed sepsis and succumbed 14 weeks after admission. LESSONS: This rare case underscores the importance of monitoring for AHA following COVID-19 vaccination. Although the benefits outweigh the risks of vaccination, AHA should be considered in the differential diagnosis of unusual bleeding following the vaccinations. Early diagnosis and management before severe bleeding are critical for successfully controlling life-threatening bleeding.

Discovery of novel disease-causing mutation in SSBP1 and its correction using adenine base editor to improve mitochondrial function.

Mutations in nuclear genes regulating mitochondrial DNA (mtDNA) replication are associated with mtDNA depletion syndromes. Using whole-genome sequencing, we identified a heterozygous mutation (c.272G>A:p.Arg91Gln) in single-stranded DNA-binding protein 1 (SSBP1), a crucial protein involved in mtDNA replisome. The proband manifested symptoms including sensorineural deafness, congenital cataract, optic atrophy, macular dystrophy, and myopathy. This mutation impeded multimer formation and DNA-binding affinity, leading to reduced efficiency of mtDNA replication, altered mitochondria dynamics, and compromised mitochondrial function. To correct this mutation, we tested two adenine base editor (ABE) variants on patient-derived fibroblasts. One variant, NG-Cas9-based ABE8e (NG-ABE8e), showed higher editing efficacy (≤30%) and enhanced mitochondrial replication and function, despite off-target editing frequencies; however, risks from bystander editing were limited due to silent mutations and off-target sites in non-translated regions. The other variant, NG-Cas9-based ABE8eWQ (NG-ABE8eWQ), had a safer therapeutic profile with very few off-target effects, but this came at the cost of lower editing efficacy (≤10% editing). Despite this, NG-ABE8eWQ-edited cells still restored replication and improved mtDNA copy number, which in turn recovery of compromised mitochondrial function. Taken together, base editing-based gene therapies may be a promising treatment for mitochondrial diseases, including those associated with SSBP1 mutations.

Internal quality prediction technology for 'Sulhyang' strawberry fruit using organic analysis and hyperspectral imaging.

In recent years, hyperspectral imaging combined with machine learning techniques has garnered significant attention for its potential in assessing fruit maturity. This study proposes a method for predicting strawberry fruit maturity based on the harvest time. The main features of this study are as follows. 1) Selection of wavelength band associated with strawberry growth season; 2) Extraction of efficient parameters to predict strawberry maturity 3) Prediction of internal quality attributes of strawberries using extracted parameters. In this study, experts cultivated strawberries in a controlled environment and performed hyperspectral measurements and organic analyses on the fruit with minimal time delay to facilitate accurate modeling. Data augmentation techniques through cross-validation and interpolation were effective in improving model performance. The four parameters included in the model and the cumulative value of the model were available for quality prediction as additional parameters. Among these five parameter candidates, two parameters with linearity were finally identified. The predictive outcomes for firmness, soluble solids content, acidity, and anthocyanin levels in strawberry fruit, based on the two identified parameters, are as follows: The first parameter, ps, demonstrated RMSE performances of 1.0 N, 2.3 %, 0.1 %, and 2.0 mg per 100 g fresh fruit for firmness, soluble solids content, acidity, and anthocyanin, respectively. The second parameter, p3, showed RMSE performances of 0.6 N, 1.2 %, 0.1 %, and 1.8 mg per 100 g fresh fruit, respectively. The proposed non-destructive analysis method shows the potential to overcome the challenges associated with destructive testing methods for assessing certain internal qualities of strawberry fruit.

A novel treatment strategy targeting cellular pathways with natural products to alleviate sarcopenia.

Sarcopenia is a condition marked by a significant reduction in muscle mass and strength, primarily due to the aging process, which critically impacts muscle protein dynamics, metabolic functions, and overall physical functionality. This condition leads to increased body fat and reduced daily activity, contributing to severe health issues and a lower quality of life among the elderly. Recognized in the ICD-10-CM only in 2016, sarcopenia lacks definitive treatment options despite its growing prevalence and substantial social and economic implications. Given the aging global population, addressing sarcopenia has become increasingly relevant and necessary. The primary causes include aging, cachexia, diabetes, and nutritional deficiencies, leading to imbalances in protein synthesis and degradation, mitochondrial dysfunction, and hormonal changes. Exercise remains the most effective intervention, but it is often impractical for individuals with limited mobility, and pharmacological options such as anabolic steroids and myostatin inhibitors are not FDA-approved and are still under investigation. This review is crucial as it examines the potential of natural products as a novel treatment strategy for sarcopenia, targeting multiple mechanisms involved in its pathogenesis. By exploring natural products' multi-targeted effects, this study aims to provide innovative and practical solutions for sarcopenia management. Therefore, this review indicates significant improvements in muscle mass and function with the use of specific natural compounds, suggesting promising alternatives for those unable to engage in regular physical activity.

The Ray Method: Aesthetic and Simple Technique for Prosthesis Coverage in Prepectoral Breast Reconstruction.

In prepectoral breast reconstruction, the acellular dermal matrix (ADM) is commonly used to envelop breast implants. Various wrapping methods have been proposed. We present a simple but aesthetic method (ie, the ray method) for wrapping in prepectoral breast reconstruction. Without any complicated design, we folded the four corners of one large ADM and sewed them together to completely envelop the implant. Then, the 6 o'clock corner of the ADM envelope was folded up and sutured to make a pentagonal shape. The other corners of the ADM envelope were quilted to determine the position and movement of the internal implant. Additional sutures were placed on the ADM envelope to separate the implant from the host tissue. The folded 6 o'clock corner was cut to a convex contour and had a diagonal gap to prevent the collection of fluid in the ADM envelope. Finally, the wrapped implant was inserted in the postmastectomy space, and the ADM envelope was spread widely to support soft tissue effectively. This simple design is straightforward for inexperienced surgeons and reduces operation time. The position and movement of the breast implant in the ADM envelope can be easily controlled by using quilted sutures. Subclavian depression and step-off deformities can be minimized by this wide-stretched ADM. By total coverage with a large ADM, the breast implant is separated from the surrounding tissue, and foreign body reactions are reduced. This method is reliable for maximizing the aesthetic advantages of prepectoral direct-to-implant breast reconstruction.

Alveolar Microdynamics during Tidal Ventilation in Live Animals Imaged by SPring-8 Synchrotron.

It is self-evident that our chests expand and contract during breathing but, surprisingly, exactly how individual alveoli change shape over the respiratory cycle is still a matter of debate. Some argue that all the alveoli expand and contract rhythmically. Others claim that the lung volume change is due to groups of alveoli collapsing and reopening during ventilation. Although this question might seem to be an insignificant detail for healthy individuals, it might be a matter of life and death for patients with compromised lungs. Past analyses were based on static post-mortem preparations primarily due to technological limitations, and therefore, by definition, incapable of providing dynamic information. In contrast, this study provides the first comprehensive dynamic data on how the shape of the alveoli changes, and, further, provides valuable insights into the optimal lung volume for efficient gas exchange. It is concluded that alveolar micro-dynamics is nonlinear; and at medium lung volume, alveoli expand more than the ducts.

Compensatory strategies of dysphagia after anterior cervical spinal surgery: A case report.

RATIONALE: Dysphagia after anterior cervical discectomy and fusion (ACDF) is a common postoperative complication. However, information regarding rehabilitation strategies for postoperative dysphagia is limited. Herein, we report a compensatory strategy for treating dysphagia after ACDF. PATIENT CONCERNS: A 65-year-old Asian male presented with left arm pain and weakness for more than 1 month. Magnetic resonance imaging of the cervical spine revealed degenerative disc lesions and spinal stenosis at the C3 to C7 levels. The patient underwent ACDF at the C3 to C5 levels and artificial disc replacement at the C5 to C7 levels by right side approach. After surgery, the patient complained of difficulty swallowing. A video fluoroscopic swallowing study (VFSS) detected swallowing dysfunction in the pharyngeal phase, revealing an asymmetric pharyngeal residue in the anterior-posterior view. DIAGNOSIS: The patient was diagnosed with dysphagia after ACDF. INTERVENTIONS: Based on the VFSS findings, the patient underwent swallowing rehabilitation therapy and compensatory techniques, such as head rotation to the weak right side and head tilting to the robust left side. OUTCOMES: After 2 months of rehabilitation with compensatory techniques, food moved smoothly towards the robust side, and the subjective symptoms of dysphagia improved. LESSONS: Consequently, swallowing function post-ACDF surgery must be assessed; if unilateral dysphagia is detected, compensatory techniques may prove beneficial. This case study showed that, based on the objective findings of the VFSS, an effective swallowing compensation strategy can be established and applied to patients with postoperative dysphagia.

Neuron-Specific Enolase as a Predictor of Neurologic Outcomes in Extracorporeal Cardiopulmonary Resuscitation Patients.

Background: Neuron-specific enolase (NSE) has traditionally been used as a biomarker to predict neurologic outcomes after cardiac arrest. This study aimed to evaluate the utility of NSE in predicting neurologic outcomes in patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR). Methods: This observational cohort study included 47 consecutive adult ECPR patients (median age, 59.0 years; 74.5% males) treated between January 2018 and December 2021 at a tertiary extracorporeal life support center. The primary outcome was a poor neurologic outcome, defined as a Cerebral Performance Category score of 3-5 at hospital discharge. Results: Twelve (25.5%) patients had abnormal findings on computed tomography of the brain. A poor neurologic outcome was demonstrated in 22 (46.8%) patients. The NSE level at 72 h after ECPR showed the best prediction power for a poor neurologic outcome compared with NSE at 24 and 48 h. A cutoff value exceeding 61.9 µg/L for NSE at 72 h yielded an area under the curve (AUC) of 0.791 for predicting poor neurologic outcomes and exceeding 62.1 µg/L with an AUC of 0.838 for 30-day mortality. Conclusions: NSE levels at 72 h after ECPR appear to be a reliable biomarker for predicting poor neurologic outcomes and 30-day mortality in ECPR patients.

Polyacrylamide/Gel-Based Self-Healing Artificial Tympanic Membrane for Drug Delivery of Otitis Treatment.

One of the bacterial infections caused by tympanic membrane perforation is otitis media (OM). Middle ear inflammation causes continuous pain and can be accompanied by aftereffects such as facial nerve paralysis if repeated chronically. Therefore, it is necessary to develop an artificial tympanic membrane (TM) that can effectively regenerate the eardrum due to the easy implantation and removal of OM inflammation. In this study, we synthesized hydrogel by mixing gelatin and polyacrylamide. Cefuroxime sodium salt was then incorporated into this hydrogel to both regenerate the TM and treat OM. Cytotoxicity experiments confirmed the biocompatibility of hydrogels equipped with antibiotics, and we conducted drug release and antibacterial experiments to examine continuous drug release. Through experiments, we have verified the excellent biocompatibility, drug release ability, and antibacterial effectiveness of hydrogel. It holds the potential to serve as an effective strategy for treating OM and regenerating TM as a drug delivery substance.

Effect of a Combination of Lactiplantibacillus plantarum KC3 and Leonurus japonicus Extracts in Respiratory Discomfort: A Randomized, Double-Blind, Placebo-Controlled Trial.

The increased global prevalence of chronic respiratory diseases in recent years has caused a substantial public health burden. Lactiplantibacillus plantarum KC3 and Leonurus japonicus Houtt. (LJH) extracts can alleviate respiratory symptoms and improve lung function in vitro and in vivo. However, the clinical efficacy and safety profile of this combination in patients with respiratory diseases remain unclear. Therefore, this multicenter, randomized, double-blind, placebo-controlled clinical trial aimed to evaluate the efficacy and safety of L. plantarum KC3 and LJH extracts in adults with respiratory discomfort. This mixture was termed 'CKDB-315'. Participants, randomly assigned to the CKDB-315 or placebo groups, were treated for 12 weeks. Assessments included the St. George's Respiratory Questionnaire (SGRQ) and the Chronic Obstructive Pulmonary Disease Assessment Test (CAT). The CKDB-315 group showed considerably improved SGRQ and CAT scores compared with the placebo group. Secondary outcomes, including dyspnea, pulmonary function, total antioxidant status, and inflammatory cytokine levels, were consistent with the primary outcomes. Exploratory analyses of the gut microbiota and short-chain fatty acid contents revealed the potential mechanisms underlying the effects of CKDB-315. Finally, safety analysis indicated that CKDB-315 was well tolerated and caused few adverse events. Our findings indicate that CKDB-315 is a promising therapeutic option for respiratory discomfort in adults.

Clinicopathological Characteristics and Lymph Node Metastasis Rates in Early Gastric Lymphoepithelioma-Like Carcinoma: Implications for Endoscopic Resection.

Background/Aims: Lymphoepithelioma-like carcinoma (LELC) is a rare subtype of gastric cancer. We aimed to identify the clinicopathological features and rate of lymph node metastasis (LNM) to investigate the feasibility of endoscopic submucosal dissection for early gastric LELC confined to the mucosa or submucosa. Methods: We compared the clinicopathological characteristics of 116 early gastric LELC patients and 5,753 early gastric well- or moderately differentiated (WD or MD) tubular adenocarcinoma patients treated by gastrectomy. Results: Compared to WD or MD early gastric cancer (EGC) patients, early LELC patients were younger and had a higher prevalence of proximally located tumors. Despite more frequent deep submucosal invasion (86.2% vs 29.8%), lymphatic invasion was less frequent (6.0% vs 16.2%) in early LELC patients than in WD or MD EGC patients. Among tumors with deep submucosal invasion, the tumor size was smaller, lymphatic invasion was less frequent (6.0% vs 40.2%) and the rate of LNM was lower (10.0% vs 19.4%) in patients with LELC than in those with WD or MD EGC. The overall rate of LNM in early LELC patients was 8.6% (10/116). The risk of LNM in patients with mucosal, shallow submucosal invasive, or deep submucosal invasive LELC was 0% (0/6), 0% (0/10), and 10% (10/100), respectively. Conclusions: Early LELC is a distinct subtype of EGC with more frequent deep submucosal invasion but less lymphatic invasion and LNM than WD or MD EGCs. Endoscopic submucosal dissection may be considered curative for patients with early LELC confined to the mucosa or shallow submucosa, given its negligible rate of LNM.

Associations between tinnitus and body composition: a cross-sectional study.

The relationship between tinnitus and body composition in specific regions has not been extensively investigated. This study aimed to identify associations between tinnitus and body composition. Individuals with data on physical and otological examination findings, and bioelectrical impedance analysis were included from the ninth Korea National Health and Nutritional Examination Survey. They were divided into a tinnitus group and a non-tinnitus group. Participants with tinnitus were further classified into acute or chronic tinnitus group. The tinnitus group showed significantly higher body fat percentages in each region (arms: P = 0.014; legs: P = 0.029; trunk: P = 0.008; whole body: P = 0.010) and waist circumference (P = 0.007) than the non-tinnitus group, and exhibited lower leg muscle percentage (P = 0.038), total body fluid percentage (P = 0.010), and intracellular fluid percentage (P = 0.009) than the non-tinnitus group in men. Furthermore, men with chronic tinnitus showed a significantly higher trunk fat percentage (P = 0.015) and waist circumference (P = 0.043), and lower intracellular fluid percentage (P = 0.042) than their counterparts without tinnitus. No significant differences in body composition were observed among the groups in the female population. In men, body composition may be associated with tinnitus.

Higher exposure to 1,3-butadiene is associated with more severe hearing loss.

While volatile organic compounds (VOCs) impair various organs, their influence on hearing loss (HL) has not been extensively researched. We aimed to identify the association between VOCs and HL or high-frequency hearing loss (HFHL). We extracted data on age, sex, pure tone audiometry, hypertension, occupational noise exposure, and creatinine-corrected urine VOC metabolite concentrations from the eighth Korea National Health and Nutrition Survey. Among the VOC metabolites, N-acetyl-S-(benzyl)-L-cysteine (BMA, P = 0.004), N-acetyl-S-(phenyl)-L-cysteine (SPMA, P = 0.027), and N-acetyl-S-(3,4-dihydroxybutyl)-L-cysteine (DHBMA, P < 0.001) showed associations with HL. Additionally, HFHL exhibited significant associations with BMA (P = 0.005), 3- and 4-methylhippuric acid (3, 4 MHA, P = 0.049), mandelic acid (MA, P = 0.015), SPMA (P < 0.001), N-acetyl-S-(3-hydroxypropyl)-L-cysteine (3-HPMA, P < 0.001), and DHBMA (P < 0.001). After controlling other factors, DHBMA were associated with HL (P = 0.021) and HFHL (P = 0.014) and exhibited a linear association with the mean hearing level (ß = 0.054, P = 0.024) and high-frequency hearing level (ß = 0.045, P = 0.037). Since 1,3-butadiene may act as an ototoxic material, early screening for workers exposed to 1,3-butadiene and reducing exposure to 1,3-butadiene in everyday life may be helpful to prevent further HL.

Glycaemic Status and Risk of Abdominal Aortic Aneurysm: A Nationwide Cohort Study of Four Million Adults using Korean National Health Screening Data.

OBJECTIVE: This retrospective cohort study aimed to confirm the previously reported inverse association between diabetes mellitus (DM) and abdominal aortic aneurysm (AAA) using large population based data. It also investigated the associations between AAA and impaired fasting glucose (IFG) and new onset DM (not yet treated). METHODS: A representative dataset was obtained from the Korean National Health Insurance Service. Participants who were aged ≥ 50 years and received a national health examination in 2009 were included and followed until 31 December 2019. Glycaemic status was defined based on fasting plasma glucose level and the relevant diagnostic codes. AAA was ascertained using medical facility use records with relevant diagnostic codes or aneurysm repair surgery. A Cox proportional hazards model was used to examine the association between glycaemic status and AAA, with adjustment for confounders. Additionally, the interactions between glycaemic status and subgroups based on baseline characteristics were examined. RESULTS: The study population comprised 4 162 640 participants. Participants with IFG or DM were significantly more likely to be male, older, and have comorbidities compared with normoglycaemic participants at baseline. The incidence of AAA was lower in participants with IFG or DM compared with normoglycaemic participants. The AAA risk was lower in patients with DM than in patients with IFG, and decreased linearly according to glycaemic status: the adjusted hazard ratio was 0.88 (95% confidence interval [CI] 0.85 - 0.91) for IFG, 0.72 (95% CI 0.67 - 0.78) for newly diagnosed DM, 0.65 (95% CI 0.61 - 0.69) for DM duration < 5 years, and 0.47 (95% CI 0.44 - 0.51) for DM duration ≥ 5 years compared with the normoglycaemia group. Both IFG and DM were related to reduced AAA risk in all subgroups, suggesting an independent association. CONCLUSION: Both IFG and DM, even when not treated with antihyperglycaemic medication, were associated with a lower incidence of AAA. The AAA risk decreased linearly according to DM duration.

Surgical outcome of mitral valve surgery in atrial functional mitral regurgitation compared with degenerative etiology.

OBJECTIVE: To analyze and compare the outcomes of mitral valve surgery for atrial functional mitral regurgitation (AFMR) and for degenerative mitral regurgitation (DMR). METHODS: Patients with AFMR or DMR who underwent mitral valve repair/replacement at 2 institutions between January 2012 and December 2022 were included. Patients <18 years of age and patients undergoing concomitant cardiac surgery (except for the maze procedure or tricuspid annuloplasty) were excluded. Propensity score analysis was used to adjust for baseline differences. RESULTS: A total of 642 patients were enrolled. After propensity score analysis, 164 patients were classified into the DMR group, and 82 patients were classified into the AFMR group. All matched patients in both groups had atrial fibrillation. In DMR and AFMR, the 5-year freedom from readmission for heart failure and cardiac death was 96.3% in the DMR group versus 88.6% in the AFMR group (P = .045) and freedom from readmission for cardiac death in the 2 groups was 100% and 90.0%, respectively (P = .002). The recurrence rate of significant mitral regurgitation (MR) after mitral valve repair was not significantly different between the 2 groups (P = .699, log-rank test), and the 5-year freedom from MR recurrence (moderate or greater) was 89.8% and 93.0%, respectively. After the maze procedure, significantly more patients in the AFMR group than the DMR group were in junctional rhythm (49.1% vs 3.3%; P < .001) and required permanent pacemaker insertion during the follow-up period (11.4% vs 1.5% after 5 years; P = .041, log-rank test). CONCLUSIONS: AFMR was associated with acceptable outcomes of mitral valve surgery, and mitral valve repair is a good treatment option. However, significantly more patients were in junctional rhythm after the maze procedure, needing more permanent pacemaker insertion.

Long-term follow-up results of facial nerve schwannoma with good facial nerve function: a multicenter study.

PURPOSE: Facial nerve schwannomas (FNSs) are rare intracranial tumors, and the optimal management of these tumors remains unclear. We investigated the long-term follow-up results of FNS with good facial nerve function. METHODS: At nine medical centers in the Korean Facial Nerve Study Group, 43 patients undergoing observation periods longer than 12 months for FNS with good facial nerve function (House-Brackmann grade ≤ II) were enrolled, and clinical and radiographic data were obtained for these cases. RESULTS: The mean follow-up period was 63 months. In the majority of cases, tumors involved multiple segments (81.4%) and only eight cases were confined to a single site. There were no cases where the tumor was confined to the extratemporal region. Tumor size increased slightly, with an average estimated change of 0.48 mm/year. Twenty (46.5%) of 43 patients showed no change in tumor size. Seven patients (16.3%) showed worsening House-Brackmann (H-B) grade, of which two patients deteriorated from H-B grade I to II, four worsened to grade III, and one deteriorated to grade IV. The remaining 36 patients (83.7%) showed no change in facial nerve function. There was no difference in H-B grade according to tumor size at the time of diagnosis or change in tumor size. CONCLUSION: We conducted a large-scale observational study of FNS with good facial nerve function. Our study showed that many patients maintained facial nerve function during long-term follow-up. Conservative management with regular examination and imaging can be an appropriate option for managing FNS with good facial nerve function.

CRISPR-based editing strategies to rectify EYA1 complex genomic rearrangement linked to haploinsufficiency.

Pathogenic structure variations (SVs) are associated with various types of cancer and rare genetic diseases. Recent studies have used Cas9 nuclease with paired guide RNAs (gRNAs) to generate targeted chromosomal rearrangements, focusing on producing fusion proteins that cause cancer, whereas research on precision genome editing for rectifying SVs is limited. In this study, we identified a novel complex genomic rearrangement (CGR), specifically an EYA1 inversion with a deletion, implicated in branchio-oto-renal/branchio-oto syndrome. To address this, two CRISPR-based approaches were tested. First, we used Cas9 nuclease and paired gRNAs tailored to the patient's genome. The dual CRISPR-Cas9 system induced efficient correction of paracentric inversion in patient-derived fibroblast, and effectively restored the expression of EYA1 mRNA and protein, along with its transcriptional activity required to regulate the target gene expression. Additionally, we used CRISPR activation (CRISPRa), which leads to the upregulation of EYA1 mRNA expression in patient-derived fibroblasts. Moreover, CRISPRa significantly improved EYA1 protein expression and transcriptional activity essential for target gene expression. This suggests that CRISPRa-based gene therapies could offer substantial translational potential for approximately 70% of disease-causing EYA1 variants responsible for haploinsufficiency. Our findings demonstrate the potential of CRISPR-guided genome editing for correcting SVs, including those with EYA1 CGR linked to haploinsufficiency.