SMO-CRISPR-mediated apoptosis in CD133-targeted cancer stem cells and tumor growth inhibition.

Cancer stem cells (CSCs) possess the ability to indefinitely proliferate and resist therapy, leading to cancer relapse and metastasis. To address this, we aimed to develop a CSC-inclusive therapy that targets both CSCs and non-CSC glioblastoma (GBM) cells. We accomplished this by using a smoothened (SMO) CRISPR/Cas9 plasmid to suppress the hedgehog pathway in CSCs, in combination with inhibiting the serine hydroxymethyl transferase 1 (SHMT1)-driven thymidylate biosynthesis pathway in non-CSC GBM cells using SHMT1 siRNA (siSHMT1). We targeted CSCs using a CD133 peptide attached to an osmotically active vitamin B6-coupled polydixylitol vector (VPX-CD133) by a photoactivatable heterobifunctional linker. VPX-CD133 nanocomplexes in comparison to VPX complexes remarkably targeted and transfected CSCs both in vitro and in subcutaneous tumor. The VPX-CD133-mediated targeted delivery of SMO CRISPR in CSCs led to SMO suppression that negatively affected its growth. Next, we performed comprehensive therapy in xenograft mice using VPX-CD133, which delivered SMO-CRISPR to CSCs, and VPX, which delivered siSHMT1 to non-CSC GBM cells. The combined treatment induced apoptosis in a large number of cells, reduced tumor volume by up to 81%, and improved the health of treated mice significantly. By eliminating CSCs together with the non-CSC GBM cells, the combined study paves the way for developing CSC-inclusive therapies for GBM.

Investigation of optimal convolutional neural network conditions for thyroid ultrasound image analysis.

Neural network models have been used to analyze thyroid ultrasound (US) images and stratify malignancy risk of the thyroid nodules. We investigated the optimal neural network condition for thyroid US image analysis. We compared scratch and transfer learning models, performed stress tests in 10% increments, and compared the performance of three threshold values. All validation results indicated superiority of the transfer learning model over the scratch model. Stress test indicated that training the algorithm using 3902 images (70%) resulted in a performance which was similar to the full dataset (5575). Threshold 0.3 yielded high sensitivity (1% false negative) and low specificity (72% false positive), while 0.7 gave low sensitivity (22% false negative) and high specificity (23% false positive). Here we showed that transfer learning was more effective than scratch learning in terms of area under curve, sensitivity, specificity and negative/positive predictive value, that about 3900 images were minimally required to demonstrate an acceptable performance, and that algorithm performance can be customized according to the population characteristics by adjusting threshold value.

Effects of 3D virtual reality motionless imagery training program with an avatar.

The present study aimed to explore the effects of motionless imagery training with an avatar in virtual reality (VR) on emotion, cognition, and physiological response changes in healthy adults. Participants were 30 healthy adults aged between 19 and 35 years. All participants were randomly divided into the experimental group (n = 18), which executed the imagery training with an avatar in VR, or the control group (n = 12), which merely experienced the VR without an avatar. Both groups underwent the intervention, a 20-min session, 3 times a week for 6 weeks. VR experience questionnaires and physiological response changes were measured at pre- and post-test and emotional states and cognition tests were measured at pre-, post-, and follow-up test. The experimental group showed no significant changes in the Presence Questionnaire (PQ) and the Simulator Sickness Questionnaire (SSQ) after the intervention while the control group showed a significant decrease in the PQ after the intervention. In all emotional states, there were no significant differences in the interaction between times and groups. A significant main effect of time was revealed in all cognition tests except the delayed recall and the delayed recognition in K-Auditory Verbal Learning Test (K-AVLT). In physiological response changes, the experimental group showed significant improvements in the electromyogram (EMG) at rectus femoris on the left side after the intervention. Thus, imagery training with an avatar in VR can be considered to be effective for enhancements of cognitions and physiological response changes.

A Very Simple Suture Technique for Correction of Primary Multiple Folds in Asian Eyelids.

BACKGROUND: Upper blepharoplasty is 1 of the most popular cosmetic procedures in Asia. As people become older, they develop soft tissue atrophy and multiple folds due to a sunken upper eyelid. Furthermore, people with thin upper eyelid skin are more likely to develop multiple folds, even at a young age. The authors investigated the effectiveness of a transverse mattress suture technique to prevent recurrence during upper blepharoplasty in patients with primary multiple folds. PATIENTS/METHODS: Data on 656 patients with primary multiple folds who underwent upper blepharoplasty from March 2017 to January 2020 were retrospectively reviewed. The authors compared the operative time, patients' satisfaction, panel assessment, and complications according to whether the suture technique was used. RESULTS: Among 656 patients, 228 were lost to follow-up or had incomplete data; therefore, the files of 428 patients were analyzed. In total, 199 patients did not undergo the suture technique, whereas 229 patients did. Statistically significant differences were found between the 2 groups in patients' satisfaction, aesthetic results, and recurrence. However, between-group difference was not significant in terms of symmetry or complications such as hematoma and swelling. CONCLUSIONS: People with thin upper eyelid skin or slightly protruding eyes are more likely to develop multiple folds at a young age, even in their teens or 20s. The authors performed a skin suture during upper blepharoplasty, and then performed a transverse mattress suture on the spots where multiple folds are expected. Patients who underwent the suture technique showed better aesthetic results and a significantly lower recurrence rate.

Scalp reconstruction using the reverse temporalis muscle flap: a case report.

The scalp is the thickest skin in the body and protects the intracranial structures. The coverage of a large scalp defect is a difficult surgical procedure, the full details of which must be considered prior to the procedure, such as defect size and depth, and various factors related to the patient's general condition. Although a free flap is the recommended surgical procedure to cover large scalp defects, it is a high-risk operation that is not appropriate for all patients. As such, other surgical options must be explored. We present the case of a patient with an ulcer on the scalp after wide excision and split-thickness skin graft for squamous cell cancer. We successfully performed a reverse temporalis muscle flap for this patient.

Comparative Study of Gasless Transaxillary, Bilateral Axillo-Breast, Unilateral Axillo-Breast With Carbon Dioxide Insufflation, Retroauricular, and Transoral Vestibular Endoscopic Thyroidectomy Approaches at a Single Institution: A Retrospective Analysis and Lessons Learned.

OBJECTIVES: This study aimed to present our experiences with various approaches for endoscopic thyroidectomy (ET) and to offer lessons for choosing an approach. METHODS: The medical records of 701 patients who underwent ET via the transaxillary (TA), bilateral axillo-breast (BABA), unilateral axillo-breast with carbon dioxide insufflation (UABA), retroauricular (RA), or transoral vestibular (TO) approach between May 2008 and March 2020 were retrospectively reviewed. Postoperative pain and cosmetic outcomes were evaluated using visual analog scales. RESULTS: The mean operative time of UABA was the shortest among the five approaches (TA, 194.65±51.13 minutes; BABA, 189.11±61.53 minutes; UABA, 118.62±30.23 minutes; RA, 168.22±45.63 minutes; TO, 196.10±40.19 minutes; P=0.02). BABA was the most painful approach, while TO was the least painful on postoperative day 1 (TA, 3.09±0.96; BABA, 3.59±0.92; UABA, 2.39±0.54; RA, 3.49±0.93; TO, 2.01±0.37; P=0.04) and day 3 (TA, 2.10±0.77; BABA, 2.59±0.88; UABA, 1.84±0.37; RA, 3.01±0.67; TO, 1.49±0.45; P=0.04). The TO group had the best cosmetic outcomes at 3 months (TA, 3.91±1.21; BABA, 4.52±1.13; UABA, 4.49±0.74; RA, 4.28±0.74; TO, 4.81±0.48; P=0.04). CONCLUSION: We present a single-surgeon experience of five distinctive ET approaches and the lessons from each approach, together with a literature review. This data may aid endoscopic thyroid surgeons in choosing from various ET approaches.

Treatment of a naso-orbito-ethmoid fracture using open reduction and suspension sutures: a case report.

Naso-orbito-ethmoidal (NOE) fractures are complicated fractures of the mid-face. The treatment of NOE fractures is challenging and a comprehensive treatment strategy is required. We introduce a case of NOE fracture treated with open reduction and suspension sutures. A 28-year-old woman presented with a unilateral NOE fracture. To reduce the frontal process of the maxilla, a suspension suture was made by pulling the fragment using a double arm suture via a transcaruncular incision. The suture thread was placed in the horizontal plane. Another suspension suture on the inferior orbital rim assisted reduction procedure, and they passed through the overlying skin. The reduction alignment could be finely adjusted by tightening the transcutaneous suture threads while checking the degree of bone alignment through the subciliary incision. The two suture threads were suspended using a thermoplastic nasal splint. An additional skin incision on the medial canthal area, which would have resulted in a scar, could be avoided. Four months postoperatively, computed tomography showed an accurate and stable reduction. The patient was satisfied with her aesthetic appearance, and functional deficits were not present.

Phylogeography and Antioxidant Activity of Proso Millet (Panicum miliaceum L.).

Proso millet (Panicum miliaceum L.) or broomcorn millet is among the most important food crops to be domesticated by humans; it is widely distributed in America, Europe, and Asia. In this study, we genotyped 578 accessions of P. miliaceum using 37 single-sequence repeat (SSR) markers, to study the genetic diversity and population structure of each accession. We also investigated total phenolic content (TPC) and superoxide dismutase (SOD) activity and performed association analysis using SSR markers. The results showed that genetic diversity and genetic distance were related to geographic location and the fixation index (Fst). Population structure analysis divided the population into three subpopulations. Based on 3 subpopulations, the population is divided into six clusters in consideration of geographical distribution characteristics and agronomic traits. Based on the genetic diversity, population structure, pairwise Fst, and gene flow analyses, we described the topological structure of the six proso millet subpopulations, and the geographic distribution and migration of each cluster. Comparison of the published cluster (cluster 1) with unique germplasms in Japan and South Korea suggested Turkey as a possible secondary center of origin and domestication (cluster 3) for the cluster. We also discovered a cluster domesticated in Nepal (cluster 6) that is adapted to high-latitude and high-altitude cultivation conditions. Differences in phenotypic characteristics, such as TPC, were observed between the clusters. The association analysis showed that TPC was associated with SSR-31, which explained 7.1% of the total variance, respectively. The development of markers associated with TPC and SOD will provide breeders with new tools to improve the quality of proso millet through marker-assisted selection.

Primary cutaneous CD4+ small/medium T-cell lymphoma: a case report.

Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder is a rare disease characterized by a single mass on the face or upper part of the trunk. It usually presents an asymptomatic and favorable progression, and its histopathologic findings include small and medium-sized lymphoid cells. The authors report a case of primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder on the forehead. A 51-year-old man presented with a protruding mass on his forehead that the patient had noted 1 month previously. Surgical excision and a permanent biopsy were performed under local anesthesia. Based on the biopsy results, the mass was diagnosed as a primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder. There was no evidence of recurrence at a 15-month follow-up visit.

Federated Learning for Thyroid Ultrasound Image Analysis to Protect Personal Information: Validation Study in a Real Health Care Environment.

BACKGROUND: Federated learning is a decentralized approach to machine learning; it is a training strategy that overcomes medical data privacy regulations and generalizes deep learning algorithms. Federated learning mitigates many systemic privacy risks by sharing only the model and parameters for training, without the need to export existing medical data sets. In this study, we performed ultrasound image analysis using federated learning to predict whether thyroid nodules were benign or malignant. OBJECTIVE: The goal of this study was to evaluate whether the performance of federated learning was comparable with that of conventional deep learning. METHODS: A total of 8457 (5375 malignant, 3082 benign) ultrasound images were collected from 6 institutions and used for federated learning and conventional deep learning. Five deep learning networks (VGG19, ResNet50, ResNext50, SE-ResNet50, and SE-ResNext50) were used. Using stratified random sampling, we selected 20% (1075 malignant, 616 benign) of the total images for internal validation. For external validation, we used 100 ultrasound images (50 malignant, 50 benign) from another institution. RESULTS: For internal validation, the area under the receiver operating characteristic (AUROC) curve for federated learning was between 78.88% and 87.56%, and the AUROC for conventional deep learning was between 82.61% and 91.57%. For external validation, the AUROC for federated learning was between 75.20% and 86.72%, and the AUROC curve for conventional deep learning was between 73.04% and 91.04%. CONCLUSIONS: We demonstrated that the performance of federated learning using decentralized data was comparable to that of conventional deep learning using pooled data. Federated learning might be potentially useful for analyzing medical images while protecting patients' personal information.

Controlled active exercise after open reduction and internal fixation of hand fractures.

BACKGROUND: Hand fractures can be treated using various operative or nonoperative methods. When an operative technique utilizing fixation is performed, early postoperative mobilization has been advocated. We implemented a protocol involving controlled active exercise in the early postoperative period and analyzed the outcomes. METHODS: Patients who were diagnosed with proximal phalangeal or metacarpal fractures of the second to fifth digits were included (n=37). Minimally invasive open reduction and internal fixation procedures were performed. At 3 weeks postoperatively, controlled active exercise was initiated, with stress applied against the direction of axial loading. The exercise involved pain-free active traction in three positions (supination, neutral, and pronation) between 3 and 5 weeks postoperatively. Postoperative radiographs and range of motion (ROM) in the interphalangeal and metacarpophalangeal joints were analyzed. RESULTS: Significant improvements in ROM were found between 6 and 12 weeks for both proximal phalangeal and metacarpal fractures (P<0.05). At 12 weeks, 26 patients achieved a total ROM of more than 230° in the affected finger. Postoperative radiographic images demonstrated union of the affected proximal phalangeal and metacarpal bones at a 20-week postoperative follow-up. CONCLUSIONS: Minimally invasive open reduction and internal fixation minimized periosteal and peritendinous dissection in hand fractures. Controlled active exercise utilizing pain-free active traction in three different positions resulted in early functional exercise with an acceptable ROM.

The Influence of Non-Linear Frequency Compression on the Perception of Speech and Music in Patients with High Frequency Hearing Loss.

BACKGROUND AND OBJECTIVES: Non-linear frequency compression (NLFC) technology compresses and shifts higher frequencies into a lower frequency area that has better residual hearing. Because consonants are uttered in the high-frequency area, NLFC could provide better speech understanding. The aim of this study was to investigate the clinical effectiveness of NLFC technology on the perception of speech and music in patients with high-frequency hearing loss. SUBJECTS AND METHODS: Twelve participants with high-frequency hearing loss were tested in a counter-balanced order, and had two weeks of daily experience with NLFC set on/off prior to testing. Performance was repeatedly evaluated with consonant tests in quiet and noise environments, speech perception in noise, music perception and acceptableness of sound quality rating tasks. Additionally, two questionnaires (the Abbreviated Profile of Hearing Aid Benefit and the Korean version of the International Outcome Inventory-Hearing Aids) were administered. RESULTS: Consonant and speech perception improved with hearing aids (NLFC on/off conditions), but there was no significant difference between NLFC on and off states. Music perception performances revealed no notable difference among unaided and NLFC on and off states. The benefits and satisfaction ratings between NLFC on and off conditions were also not significantly different, based on questionnaires, however great individual variability preferences were noted. CONCLUSIONS: Speech perception as well as music perception both in quiet and noise environments was similar between NLFC on and off states, indicating that real world benefits from NLFC technology may be limited in Korean adult hearing aid users.

Retroauricular thyroidectomy with a single-arm robotic surgical system: Preclinical cadaveric study.

BACKGROUND: In this study, we evaluate a new flexible, single-arm robotic system in performing thyroidectomy via a retroauricular approach. METHODS: Four fresh cadavers were used. Technical details of the new system are discussed, and the comprehensive surgical procedures are described step by step. RESULTS: This single-port flexible system could be used to successfully perform retroauricular thyroidectomy. The ideal angle to dock the patient-side cart was at a 90° angle to the operating table. When the cannula tip was placed 10 to 15 cm away from the skin incision, positioning and full movement of all four instruments without collisions were possible. Three flexible instruments and an endoscope made the robotic dissection more efficient. CONCLUSIONS: We describe the first preclinical evaluation of an innovative, flexible, single-arm robotic surgical system for retroauricular thyroidectomy.

Juvenile psammomatoid ossifying fibroma of the maxilla.

Juvenile psammomatoid ossifying fibroma (JPOF) is a rare, benign, fibro-osseous variant of ossifying fibroma. It exhibits short-term rapid growth and has a high recurrence rate. Herein we describe a case of JPOF of the maxilla that was treated via complete excision utilizing an intraoral approach with immediate reconstruction using an iliac bone graft, in conjunction with a comprehensive review of the literature. A 20-year-old man presented with a mass on his right cheek that he reported had been growing over the last 10 months. In that cheek he had noticed fullness and experienced pressure, tenderness, and fluffiness, with no other ophthalmic or dental symptoms. After clinical, radiological, and histological examinations, the diagnosis was confirmed as JPOF. Surgical excision was performed, followed by immediate reconstruction with an autologous iliac cortical and cancellous bone graft harvested from the right iliac crest under general anesthesia. Good cicatrization of the intraoral surgical wounds and right iliac crest were evident. He was monitored for 6 months after the surgery and exhibited appropriate midfacial contour. There were no signs of recurrence or complications.

Ultrasonographic Thyroid Nodule Classification Using a Deep Convolutional Neural Network with Surgical Pathology.

Ultrasonography with fine-needle aspiration biopsy is commonly used to detect thyroid cancer. However, thyroid ultrasonography is prone to subjective interpretations and interobserver variabilities. The objective of this study was to develop a thyroid nodule classification system for ultrasonography using convolutional neural networks. Transverse and longitudinal ultrasonographic thyroid images of 762 patients were used to create a deep learning model. After surgical biopsy, 325 cases were confirmed to be benign and 437 cases were confirmed to be papillary thyroid carcinoma. Image annotation marks were removed, and missing regions were recovered using neighboring parenchyme. To reduce overfitting of the deep learning model, we applied data augmentation, global average pooling. And 4-fold cross-validation was performed to detect overfitting. We employed a transfer learning method with the pretrained deep learning model VGG16. The average area under the curve of the model was 0.916, and its specificity and sensitivity were 0.70 and 0.92, respectively. Positive and negative predictive values were 0.90 and 0.75, respectively. We introduced a new fine-tuned deep learning model for classifying thyroid nodules in ultrasonography. We expect that this model will help physicians diagnose thyroid nodules with ultrasonography.

Bipolar or monopolar electrosurgery in blepharoplasty: A comparison of surgical outcomes and patient satisfaction.

BACKGROUND: An electrosurgery unit (ESU) is the mainstay of bleeding control in blepharoplasty. There are two different types of ESUs: monopolar (m-ESU) and bipolar (b-ESU). AIMS: We used m- and b-ESUs in upper, lower, and combined blepharoplasty and compared their outcomes. PATIENTS/METHODS: In this retrospective file review of 292 blepharoplasty patients, we excluded 14 who were lost to follow-up or had missing data; among the 278 enrolled patients, we recorded operative time, a surgeon panel's score for edema and ecchymosis on the third postoperative day, patients' scores of their satisfaction and inconvenience, and postoperative complications. RESULTS: One hundred thirty-nine patients were included in the m-ESU and b-ESU group. Overall, 105 patients underwent upper blepharoplasty, 77 underwent lower blepharoplasty, and 96 underwent combined blepharoplasty. The total mean operative time in the m-ESU and b-ESU was 67.94 and 62.82 minutes, respectively. This difference was not significant (P > .05). The panel's edema and patient satisfaction and inconvenience scores were significantly better in the b-ESU group (P < .05). There were no significant differences in the panel's ecchymosis score and frequency as well as nature of complications between the m-ESU and b-ESU group (P > .05). CONCLUSIONS: In this cohort of blepharoplasty patients, minimally invasive b-ESUs were efficient in obtaining reliable surgical results with higher satisfaction and lower inconvenience rates of patients than m-ESUs. We would like to recommend the use of b-ESUs in blepharoplasty, especially for plastic surgeons inexperienced in periorbital esthetic surgery.

Factors that Predicts the Size of Autologous Hamstring Tendon Graft for Double-Bundle ACL Reconstruction.

BACKGROUND: To evaluate the effectiveness of demographic data and radiographic measurements for predicting the diameter and length of autologous semitendinosus (ST) and gracilis (GR) graft. MATERIALS AND METHODS: Fifty-four cases were included to measure the size of 3 or 4 strands of ST and GR tendons retrospectively. The hamstring length on radiograph was defined as the length from the lowest point of ischial tuberosity to intercondylar notch of the femur. The linear and logistic regression analysis was used to assess the roles of the predictor variables, as demographic and radiologic data, in the outcome variables, as diameter of tendon grafts. The cross-validation with hold-out samples and concordance correlation coefficient (CCC) were also calculated. RESULTS: The hamstring and leg length measurement and gender were associated with the diameter of 4-stranded ST tendon graft. The hamstring length measurement, age and BMI were the factors associated with the diameter of 3-stranded ST tendon graft. The hamstring length measurement was found as a common factor for predicting diameters of hamstring tendon with reliable predictability. Moreover, the equation of multivariate regression analysis for the diameter of 4-stranded ST tendon graft showed the most validated power of prediction. All of the cross-validated R 2 values were calculated as similar results of multivariate model, but CCC between the measured diameter and estimated value on the predictive equation showed moderate agreement only (CCC = 0.694). CONCLUSIONS: Combining radiographic length measurements with demographic data showed reliable prediction in identifying the risk of inappropriate graft diameters. LEVEL OF EVIDENCE: Level IV retrospective cohort study.

The Postoperative Changes of Nasal Septum and Maxilla After Alveolar Bone Grafts in Patients With Unilateral Alveolar Cleft.

BACKGROUND: Alveolar clefts give rise to many aesthetic and functional problems among affected patients. Therefore, surgical adjustments of the bony defective anomalies are important. The authors performed secondary bone grafts and analyzed the effects particularly on the nasal septum and maxillary area (midface). METHODS: The patients who had alveolar bone grafts were retrospectively reviewed with pre/postoperative 3-dimensional computed tomography; the measurements included distances between the anterior nasal spine (ANS) and the vertical midline, angles between the nasal septum and the transverse line, and angles between the floor of the pyriform aperture and the transverse line. RESULTS: A total number of 23 patients were finally included in the study. The mean age of the patients was 9.7 ±â€Š1.95 years (range, 7-14 years). The mean distance between the ANS and the vertical midline was 5.3 ±â€Š4.70 mm/4.9 ±â€Š4.15 mm pre/postoperatively, showing the mean paired difference of 0.4 ±â€Š0.89 mm (P < 0.05). The mean angles between the nasal septum and the transverse line and between the floor of the pyriform aperture and the transverse line were 64.5 ±â€Š14.69°/65.9 ±â€Š13.73° and 21.7 ±â€Š8.94°/11.5 ±â€Š7.03° pre/postoperatively, showing the mean paired differences of -1.4 ±â€Š2.78° and 10.1 ±â€Š8.20°, respectively (both P < 0.05). CONCLUSION: The results suggest that secondary alveolar bone grafting has expanded effects on the adjacent midfacial structures.

Clinical Efficacy of Acellular Dermal Matrix Paste in Treating Diabetic Foot Ulcers.

INTRODUCTION: Diabetic foot ulcers (DFUs) are slow to heal because of poor tissue vascularity and regenerative capacity, among various factors. OBJECTIVE: In this study, the authors evaluate the efficacy of applying a paste formulation of acellular dermal matrix (ADM) to DFUs. MATERIALS AND METHODS: Patients with Wagner grade 2 or 3 DFUs (N = 49) received either ADM paste (treatment group; n = 23) or conventional foam dressing (control group; n = 26). All chronic wounds were debrided and irrigated in an attempt to control infection. After paste application, mild compaction was undergone to fill ulcer cavities, and foam dressings were used to cover the surface to absorb any discharge. All DFUs were analyzed with regard to ulcer area, depth, progression, healing rate, and duration to complete healing. RESULTS: At the 60-day primary outcome mark, 56.52% (13/23) of the DFUs in the treatment group were healed, compared with 23.08% (6/26) of DFUs in the control group. Mean rates of wound area resolution in the treatment and control groups were 74.17% ± 30.84% and 51.87% ± 32.81%, respectively (P ⟨ .05), with mean times to heal (within 60 days) of 13.54 ± 9.18 days and 21.5 ± 11.98 days, respectively (P ⟨ .05). There were no serious adverse events in either group, and no complications related to ADM paste application. CONCLUSIONS: The ADM paste effectively enhanced tissue regeneration, shortening ulcer duration and preventing associated complications, while eliminating the need for supplemental ulcer management procedures. The paste formulation of ADM provides a matrix for tissue ingrowth, promoting the healing of DFUs.