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Hyuck Min Kwon, Chang Dong Han, Ick-Hwan Yang, Woo-Suk Lee, Chan Woo Kim, Kwan Kyu Park Department of Orthopedic Surgery, Yonsei University College of Medicine, Seoul, KoreaCorrespondence: Kwan Kyu ParkDepartment of Orthopedic Surgery, Yonsei University, College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, KoreaTel +82 2-2228-2180Fax +82 2-363-1139Email kkpark@yuhs.acPurpose: Being underweight has never been studied in relation to the radiologic and clinical outcomes of total knee arthroplasty (TKA) in elderly patients. The aim of this study was to determine the effect of being underweight on TKA radiological and clinical outcomes and to investigate whether being underweight influences postoperative complications compared to normal body mass index (BMI) in elderly patients.Patients and Methods: A total of 118 female patients aged 65 years or older with BMI < 25 kg/m2 who underwent primary TKA were divided into two groups based on BMI: group A: 18.5 kg/m2 < BMI < 25 kg/m2; group B: BMI < 18.5 kg/m2. The radiologic and clinical outcomes were evaluated at follow-up of 6, 12, and 24 months after surgery such as the hip-knee-ankle angle, the American Knee Society (AKS) score, Western Ontario and McMaster University score (WOMAC), and patellofemoral (PF) scale. Moreover, postoperative complications during follow-up were investigated.Results: Preoperative clinical scores did not differ significantly between the two groups. Postoperative WOMAC pain (1.8 ± 1.9 versus 3.4 ± 2.6, p = 0.02), WOMAC function (12.4 ± 8.1 versus 16.5 ± 8.5, p = 0.012) and PF scales (26.1 ± 3.6 versus 23.7 ± 4.1, p = 0.002) were worse in the underweight group at 12 and 24 months after surgery. The frequency of postoperative complications did not differ significantly between groups. In multivariate linear regression analysis, underweight patient group was significantly associated with worse postoperative WOMAC and PF scores (p = 0.002, 0.005).Conclusion: Although postoperative complications of TKA did not differ between groups, underweight patients had worse clinical outcomes of TKA compared to patients with normal BMI in elderly patients. Therefore, care should be taken when performing TKA in elderly underweight patients.Keywords: total knee arthroplasty, clinical outcome, body mass index, underweight

Ceramic additive manufacturing currently relies on binders or high-energy lasers, each with limitations affecting final product quality and suitability for medical applications. To address these challenges, our laboratory has devised a surface activation technique for ceramic particles that eliminates the necessity for polymer binders or high-energy lasers in ceramic additive manufacturing. We utilized this method to 3D print bioactive SiC orthopedic screws and evaluated their properties. The study's findings reveal that chemical oxidation of SiC activated its surface, enabling 3D printing of orthopedic screws in a binder jet printer. Post-processing impregnation with NaOH and/or NH 4 OH strengthened the scaffold by promoting silica crystallization or partial conversion of silicon oxide into silicon nitride. The silica surface of the SiC 3D printed orthopedic screws facilitated osteoblast and neuron adhesion and extensive axon synthesis. The silicate ions released from the 3D printed SiC screws favorably modulated macrophage immune responses toward an M1 phenotype as indicated by the inhibition of TNFα secretions and of reactive oxygen species (ROS) expression along with the promotion of IL6R shedding. In contrast, under the same experimental conditions, Ti ions released from Ti6Al4V discs promoted macrophage TNFα secretion and ROS expression. In vivo tests demonstrated direct bone deposition on the SiC scaffold and a strong interfacial bond between the implanted SiC and bone. Immunostaining showed innervation, mineralization, and vascularization of the newly formed bone at the interface with SiC. Taken altogether, the 3D printed SiC orthopedic screws foster a favorable environment for wound healing and bone regeneration. The novel 3D printing method, based on ceramic surface activation represents a significant advancement in ceramic additive manufacturing and is applicable to a wide variety of materials., (© 2024 The Author(s). Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.)

Background : The role of treadmill stress echocardiography (TSE) in symptomatic patients may be limited. We evaluated whether carotid intima-media thickness (cIMT) and coronary artery calcium (CAC) scores can predict cardiovascular (CV) outcomes in patients with negative TSE. Methods : Patients who had negative TSE and measured cIMT or CAC scoring were enrolled and followed up. The primary CV outcome was defined as a composite of acute coronary syndrome, coronary revascularization, heart failure, stroke, and CV death. Results : Overall, 1095 patients participated. The median follow-up duration was 5.8 years. Patients with increased cIMT and CAC scores experienced a high incidence of primary CV outcomes (normal vs. increased group on cIMT and CAC scoring: 4.4% vs. 20.0% and 0.4% vs. 25.0%, respectively, p < 0.001). In the Cox proportional hazard model, increased cIMT and CAC scores were associated with increased primary CV outcomes (adjusted hazard ratio [95% confidence interval], p -value for increased cIMT and increased CAC scores = 2.939 [1.241-6.960], p = 0.014 and 45.192 [5.497-371.505], p < 0.001, respectively). Conclusions : Patients with increased cIMT and CAC scores have poor CV outcomes even though they have negative TSE results, and therefore, they should be carefully monitored.

Postoperative tissue adhesion and poor tendon healing are major clinical problems associated with tendon surgery. To avoid postoperative adhesion and promote tendon healing, we developed and synthesized a membrane to wrap the surgical site after tendon suturing. The bilayer-structured porous membrane comprised an outer layer [1,4-butanediol diglycidyl ether cross-linked with carboxymethyl cellulose (CX)] and an inner layer [1,4-butanediol diglycidyl ether cross-linked with Bletilla striata polysaccharides and carboxymethyl cellulose (CXB)]. The morphology, chemical functional groups, and membrane structure were determined. In vitro experiments revealed that the CX/CXB membrane demonstrated good biosafety and biodegradability, promoted tenocyte proliferation and migration, and exhibited low cell attachment and anti-inflammatory effects. Furthermore, in in vivo animal study, the CX/CXB membrane effectively reduced postoperative tendon-peripheral tissue adhesion and improved tendon repair, downregulating inflammatory cytokines in the tendon tissue at the surgical site, which ultimately increased tendon strength by 54% after 4 weeks.

Achieving high cell transfection efficiency is essential for various cell types in numerous disease applications. However, the efficient introduction of genes into natural killer (NK) cells remains a challenge. In this study, we proposed a design strategy for delivering exogenous genes into the NK cell line, NK-92, using a modified non-viral gene transfection method. Calcium phosphate/DNA nanoparticles (pDNA-CaP NPs) were prepared using co-precipitation methods and combined with low-voltage pulse electroporation to facilitate NK-92 transfection. The results demonstrated that the developed pDNA-CaP NPs exhibited a uniform diameter of approximately 393.9 nm, a DNA entrapment efficiency of 65.8%, and a loading capacity of 15.9%. Furthermore, at three days post-transfection, both the transfection efficiency and cell viability of NK-92 were significantly improved compared to standalone plasmid DNA (pDNA) electroporation or solely relying on the endocytosis pathway of pDNA-CaP NPs. This study provides valuable insights into a novel approach that combines calcium phosphate nanoparticles with low-voltage electroporation for gene delivery into NK-92 cells, offering potential advancements in cell therapy., Competing Interests: The authors have no conflicts to disclose., (© 2024 Author(s).)

The study aimed to investigate the extended effects and interrelations of corneal biomechanics, corneal optical density (COD), corneal thickness (CT), and intraocular pressure (IOP) following cataract surgery. Sixteen eyes were analyzed prospectively. The Corneal Visualization Scheimpflug Technology (Corvis ST) device assessed corneal biomechanics, while the Pentacam AxL ® (Pentacam) measured COD and CT. Postoperative data were collected around six months after surgery, with a subgroup analysis of data at nine months. The Pearson correlation was used to examine the relationship between surgical-induced changes in corneal biomechanics and COD. At six months, significant postoperative differences were observed in various biomechanical indices, including uncorrected IOP (IOPuct) and biomechanics-corrected IOP (bIOP). However, many indices lost statistical significance by the nine-month mark, suggesting the reversibility of postoperative corneal changes. Postoperative COD increased at the anterior layer of the 2-6 mm annulus and incision site. The changes in COD correlated with certain biomechanical indices, including maximal (Max) deformative amplitude (DA) and stiffness parameter (SP). In conclusion, despite significant immediate postoperative changes, corneal biomechanics, COD, and IOP experienced a gradual recovery process following cataract surgery. Clinicians should maintain vigilance for any unusual changes during the short-term observation period to detect abnormalities early.

Purpose: To compare corneal haze between active ulcer and healed scarring using a Scheimpflug densitometry., Materials and Methods: A prospective longitudinal study enrolled 30 patients (30 eyes) with ulcerative keratitis (UK). Each subject's corneal optical density (COD) was measured with a Scheimpflug corneal densitometry, Pentacam® AXL (Oculus GmbH, Wetzlar, Germany), at the active ulcerative and complete scarring stage. The COD data were analyzed through distinct methods (inbuilt, sorted annular partitions, and ulcer-matching densitometric maps). We compared different CODs to select the better index for clinically monitoring the transition from corneal ulceration to healed scar., Results: The CODs of the periphery (P = 0.0024) and outside of the active ulcer (P = 0.0002) significantly decreased after scarring. Partitioning the cornea into different depths and annular zones, the anterior layer, center layer, and the 2-6 mm annular zone had a more remarkable COD decrease after scar formation. The 3rd-sorted COD in the anterior layer revealed the highest area under the receiver-operating characteristic curves (0.709), in which 90% of subjects had COD reduction during the ulcer-to-scar transition., Conclusions: Aside from subjective judgment based on clinical signs, the Scheimpflug tomography-based densitometry could provide objective and efficient monitoring of the corneal opacity evolution in UK patients. Because the 3rd-sorted annular COD is a better index than the inbuilt or mapping CODs in differentiating active ulcers from healed scars, this COD could be a clinically promising parameter to monitor the progression of UK patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To investigate the growth patterns of the maxillomandibular complex in preadolescent patients with Pierre-Robin sequence (PRS)., Methods: The samples consisted of 20 preadolescent PRS patients who had cleft palate and did not undergo growth-modification therapy or surgical intervention [6 boys and 14 girls; mean age of lateral cephalograms taken, 8.8 y (T1) and 13.7 y (T2)]. According to k-means cluster analysis, four clusters were defined over 3 major groups at T1: (1) Both very retrusive maxilla and mandible group: Cluster-4 [n=4, very large gonial angle, very low facial height ratio (FHR)] and Cluster-1 (n=5, small gonial angle, normal FHR); (2) Retrusive maxilla and very retrusive mandible group (Cluster-3, n=7, normal gonial angle, very low FHR); and (3) Both normal maxilla and mandible group (Cluster-2, n=4, very large gonial angle, low FHR). Seven angular and ratio variables [sella-nasion-A point (SNA), sella-nasion-B point (SNB), A point-nasion-B point (ANB), saddle angle, gonial angle, mandibular-body-length/anterior-cranial-base-length (MBL/ACBL), and FHR] at T1 and T2 and growth change from T1 to T2 were investigated., Results: At T1, SNA, SNB, saddle angle, gonial angle (all P<0.05), and FHR (P<0.01) showed significant difference among 4 clusters. At T2, SNA, SNB and gonial angle (all P<0.05) still showed significant difference among 4 clusters. During T1 to T2, there was no significant change in variables at each cluster except an increase in MBL/ACBL in Cluster-1 and FHR in Cluster-3 (all P<0.05)., Conclusions: Preadolescent PRS patients exhibited diverse skeletal phenotypes at T1, which did not change significantly from their original skeletal patterns by growth during T1 to T2., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Graphene oxide quantum dots (GOQDs) are promising candidates for biomedical applications since they have lower toxicity and higher biocompatibility than traditional semiconductor quantum dots. However, oxygen functional groups such as epoxy and hydroxyl groups usually induce nonradiative relaxation, which leads to GOQDs exhibiting nonemissive properties. For the enhancement of the emission efficiency of GOQDs, the number of nonradiative relaxation sites should be reduced. This paper reports the synthesis of highly luminescent reduced GOQDs prepared by liquid-phase photoreduction (LPP-rGOQDs). First, GOQDs was fabricated from single-walled carbon nanotubes through chlorate-based oxidation and separation after acoustic cavitation. Subsequently, LPP-rGOQDs were obtained by liquid-phase photoreduction of the GOQD suspension under intense pulsed light irradiation. Liquid-phase photoreduction selectively reduced epoxy groups present on the basal plane of GOQDs, and hydrogenated the basal plane without removal of carbonyl and carboxyl groups at the edges of the GOQDs. Such selective removal of oxidative functional groups was used to control the reduction degree of GOQDs, closely related to their optical properties. The optimized LPP-rGOQDs were bright blue in color and showed quantum yields up to about 19.7%, which was 10 times the quantum yield of GOQDs. Furthermore, the LPP-rGOQDs were utilized to image a human embryonic kidney (HEK293A), and a low cytotoxicity level and satisfactory cell imaging performance were observed., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Phytic acid (PA) has been reported to possess anti-inflammatory and antioxidant properties that are critical for neuroprotection in neuronal disorders. This raises the question of whether PA can effectively protect sensory neurons against chemotherapy-induced peripheral neuropathy (CIPN). Peripheral neuropathy is a dose-limiting side effect of chemotherapy treatment often characterized by severe and abnormal pain in hands and feet resulting from peripheral nerve degeneration. Currently, there are no effective treatments available that can prevent or cure peripheral neuropathies other than symptomatic management. Herein, we aim to demonstrate the neuroprotective effects of PA against the neurodegeneration induced by the chemotherapeutics cisplatin (CDDP) and oxaliplatin. Further aims of this study are to provide the proposed mechanism of PA-mediated neuroprotection. The neuronal protection and survivability against CDDP were characterized by axon length measurements and cell body counting of the dorsal root ganglia (DRG) neurons. A cellular phenotype study was conducted microscopically. Intracellular reactive oxygen species (ROS) was estimated by fluorogenic probe dichlorofluorescein. Likewise, mitochondrial membrane potential (MMP) was assessed by fluorescent MitoTracker Orange CMTMRos. Similarly, the mitochondria-localized superoxide anion radical in response to CDDP with and without PA was evaluated. The culture of primary DRG neurons with CDDP reduced axon length and overall neuronal survival. However, cotreatment with PA demonstrated that axons were completely protected and showed increased stability up to the 45-day test duration, which is comparable to samples treated with PA alone and control. Notably, PA treatment scavenged the mitochondria-specific superoxide radicals and overall intracellular ROS that were largely induced by CDDP and simultaneously restored MMP. These results are credited to the underlying neuroprotection of PA in a platinum-treated condition. The results also exhibited that PA had a synergistic anticancer effect with CDDP in ovarian cancer in vitro models. For the first time, PA's potency against CDDP-induced PN is demonstrated systematically. The overall findings of this study suggest the application of PA in CIPN prevention and therapeutic purposes.

Ultrasonic standing waves with specific wavelengths generated in the multi-layered micro-resonators were numerically and experimentally analyzed. Using a three-dimensional scanning fluorescence microscope, the acoustophoretic motion of fluorescent microparticles within the micro-resonators was carefully and accurately measured. The manufactured micro-resonators were validated by comparing the location of the acoustic pressure nodal plane and the average energy density curves derived from numerical and experimental results. Results confirmed that the acoustic radiation force of the induced ultrasonic standing waves drives the microparticles vertically within the micro-resonators and their average energy density increases as the sinusoidal voltage applied to the piezoelectric transducer increases. Semi-empirical correlations were developed for the average energy density, based on experimental results for a wide range of the applied voltage amplitudes. The correlations were in good agreement, within less than 20 % of the experimental values measured for both the half-wavelength and quarter-wavelength micro-resonators., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: In-Hwan Yang reports financial support was provided by National Research Foundation of Korea. In-Hwan Yang reports a relationship with National Research Foundation of Korea that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Although blood pressure variability (BPV) and reperfusion are associated with parenchymal hematoma (PH) after stroke, the relationship between BPV and PH in atrial fibrillation (AF) patients who are at risk of reperfusion injury with frequent spontaneous recanalization is unknown. This study aimed to investigate whether BPV within the first 48 h is associated with PH within 72 h in patients with AF and stroke in terms of major vessel occlusion status. A total of 131 patients with AF that were admitted within 24 h after stroke onset were enrolled. PH was defined as a confluent hemorrhage with mass effect. The maximum (max), minimum (min), and average blood pressure (BP) during the first 48 h after admission were calculated. BPV was analyzed by using range between maximum and minimum (max-min), successive variation (SV), standard deviation (SD), and coefficient of variation (CV). All parameters were applied for systemic (SBP), diastolic (DBP), and pulse pressure (PP). After adjusting for confounding variables, various BPV parameters were associated with PH, including SBP max (p = 0.0426), SBP SV (p = 0.0006), DBP max-min (p = 0.0437), DBP SV (p = 0.0358), DBP SD (p = 0.0393), PP max-min (p = 0.0478), PP SV (p < 0.0001), PP SD (p = 0.0034), and PP CV (p = 0.0120). The relationship remained significant in patients with a patent major vessel responsible for infarction but not in patients with an occluded major vessel. In conclusion, this study revealed that high BPV was associated with PH in patients with AF and acute stroke, particularly for those with a patent major vessel. The control of BP and BPV after stroke may be considered in patients with AF., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Electrical stimulation (ESTIM) has shown to be an effective symptomatic treatment to treat pain associated with peripheral nerve damage. However, the neuroprotective mechanism of ESTIM on peripheral neuropathies is still unknown. In this study, we identified that ESTIM has the ability to enhance mitochondrial trafficking as a neuroprotective mechanism against chemotherapy-induced peripheral neuropathies (CIPNs). CIPN is a debilitating and painful sequalae of anti-cancer chemotherapy treatment which results in degeneration of peripheral nerves. Mitochondrial dynamics were analyzed within axons in response to two different antineoplastic mechanisms by chemotherapy drug treatments paclitaxel and oxaliplatin in vitro . Mitochondrial trafficking response to chemotherapy drug treatment was observed to decrease in conjunction with degeneration of distal axons. Using low-frequency ESTIM, we observed enhanced mitochondrial trafficking to be a neuroprotective mechanism against CIPN. This study confirms ESTIM enhances regeneration of peripheral nerves by increased mitochondrial trafficking., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

The analysis of nerve regeneration in the chemotherapy-induced peripheral neuropathy (CIPN) model can be achieved using the compartmentalized culture system. This system enables us to isolate the cell body from the axon physically and fluidically, therefore allowing for the independent manipulation of the cell body and axons. Compartmentalized chambers mimic the human body conditions, and can be used to study axonal degeneration, disease modeling, and drug screening. This culture system is applied to the CIPN model to study and analyze axonal behavior in response to paclitaxel (PTX) with and without fluocinolone acetonide (FA) and to better understand the site-specific target of PTX. Therefore, this compartmentalized system allows for the independent treatment of chemotherapy drugs to the cell body or axonal side which enables monitoring their reaction as a result of the treatment., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: This study aimed to propose a revision of the evaluation objectives of the Korean Dentist Clinical Skill Test by analyzing the opinions of those involved in the examination after a review of those objectives., Methods: The clinical skill test objectives were reviewed based on the national-level dental practitioner competencies, dental school educational competencies, and the third dental practitioner job analysis. Current and former examinees were surveyed about their perceptions of the evaluation objectives. The validity of 22 evaluation objectives and overlapping perceptions based on area of specialty were surveyed on a 5-point Likert scale by professors who participated in the clinical skill test and dental school faculty members. Additionally, focus group interviews were conducted with experts on the examination., Results: It was necessary to consider including competency assessments for “emergency rescue skills” and “planning and performing prosthetic treatment.” There were no significant differences between current and former examinees in their perceptions of the clinical skill test’s objectives. The professors who participated in the examination and dental school faculty members recognized that most of the objectives were valid. However, some responses stated that “oromaxillofacial cranial nerve examination,” “temporomandibular disorder palpation test,” and “space management for primary and mixed dentition” were unfeasible evaluation objectives and overlapped with dental specialty areas., Conclusion: When revising the Korean Dentist Clinical Skill Test’s objectives, it is advisable to consider incorporating competency assessments related to “emergency rescue skills” and “planning and performing prosthetic treatment.”

Few studies have reported a complete quantitative database of cranial growth, from infancy to adulthood, as a reference through three-dimensional analysis. Our study aimed to characterize cranial growth patterns using craniometric parameters by establishing sex- and age-specific norms. In total, 1009 Korean patients (male-to-female ratio, 2:1; age range, 0-18 years) who underwent thin-slice computed tomography (CT) scans for head trauma were divided into 20 age groups, with a 6-month interval for those under 2 years and a 1-year interval for those over 2 years. After four reference planes [Frankfurt horizontal (FH), midsagittal, and two coronal planes passing the sella (S) and basion (B)] had been established, intracranial volume (ICV), anteroposterior diameter (APD), biparietal diameter (BPD), cranial heights (CHs), cephalic index (CI, BPD/APD), and height index (HI, CH-B/APD) were measured using Mimics software. Best-fit logarithmic curves were derived using a linear regression model. The best-fit curves for ICV (cm 3 ) were y = 785.6 + 157*ln(age) for males (R 2  = 0.5752) and y = 702 + 150.5*ln(age) for females (R 2  = 0.6517). After adjustment for age, males had higher values of ICV, APD, BPD, and CHs than females (all p < 0.0001). ICV, APD, BPD, and CHs demonstrated a rapid increase during the first few months of life, reaching 90-95% of the adult size by 5-6 years of age, while CI and HI showed a continuous decline by 4%, regardless of sex. This study presented cranial growth references for more than 1000 of the Korean population aged up to 18 years. This might help to provide guidelines for diagnosis and treatment (including timing, amount, and direction) for cranial reconstruction in pediatric patients with craniosynostosis., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023. Published by Elsevier Ltd.)

Highly efficient adsorbents are needed to remove uremic toxins and reduce the economic and societal burden of the current dialysis treatments in resource-limited environments. In this study, nanostructured porous carbon nanofibers with nitrogen-doped zeolites (NZ-PCNF) were prepared, by electrospinning zeolites with chitosan-poly(ethylene oxide) blends, followed by a one-step carbonization process, without further activation steps or aggressive chemical additives for N-doping. The results showed that N-zeolites were successfully integrated into an ultrafine carbon nanofiber network, with a uniform nanofiber diameter of approximately 25 nm, hierarchical porous structure (micro- and mesopores), and high specific surface area (639.29 m 2 /g), facilitating uremic toxin diffusion and adsorption. The self-N-doped structure in the NZ-PCNF removed more creatinine (∼1.8 times) than the porous carbon nanofibers when using the same weight of precursor materials. Cytotoxicity and hemolysis tests were performed to verify the safety of NZ-PCNF. This study provides a novel strategy for transforming chitosan-based materials into state-of-the-art porous carbon nanofiber/zeolite self-N-doped composites, affording an efficient bioderived adsorbent for the removal of uremic toxins in patients with chronic kidney disease., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aims: Chemotherapy induced peripheral neuropathy (CIPN) is a common side effect seen in patients who have undergone most chemotherapy treatments to which there are currently no treatment methods. CIPN has been shown to cause axonal degeneration leading to Peripheral Neuropathy (PN), which can lead to major dosage reduction and may prevent further chemotherapy treatment due to oftentimes debilitating pain. Previously, we have determined the site-specific action of Paclitaxel (PTX), a microtubule targeting agent, as well as the neuroprotective effect of Fluocinolone Acetonide (FA) against Paclitaxel Induced Peripheral Neuropathy (PIPN)., Main Methods: Mitochondrial trafficking analysis was determined for all sample sets, wherein FA showed enhanced anterograde (axonal) mitochondrial trafficking leading to neuroprotective effects for all samples., Key Findings: Using this system, we demonstrate that PTX, Monomethyl auristatin E (MMAE), and Vincristine (VCR), are toxic at clinically prescribed levels when treated focally to axons. However, Cisplatin (CDDP) was determined to have a higher toxicity when treated to cell bodies. Although having different targeting mechanisms, the administration of FA was determined to have a significant neuroprotective effect for against all chemotherapy drugs tested., Significance: This study identifies key insights regarding site of action and neuroprotective strategies to further development as potential therapeutics against CIPN. FA was treated alongside each chemotherapy drug to identify the neuroprotective effect against CIPN, where FA was found to be neuroprotective for all drugs tested. This study found that treatment with FA led to an enhancement in the anterograde movement of mitochondria based on fluorescent imaging., Competing Interests: Declaration of competing interest There are no conflicts of interests among authors., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The purpose of this study was to characterize the spheno-occipital synchondrosis fusion (SOSF) from preadolescents to young adults. A total of 630 Korean subjects (308 men, 322 women; age range, 6-18 y) were divided into 26 groups according to sex and age. After 3-dimensional computed tomography (CT) images were reoriented using the Frankfort horizontal (FH) plane, mid-sagittal plane, and frontal plane via ON3D software (3DONS), the cervical vertebrae maturation index (CVMI) and SOSF stages were identified using 6-stage and 5-stage scoring systems, respectively. The distributions of stage in each group were statistically investigated. Women showed early appearance and a short range of onset (CVMI stage 2, SOSF stage 2), middle (CVMI stage 4, SOSF stage 3 and stage 4), and completion (CVMI stage 6, SOSF stage 5), indicating rapid skeletal maturation compared with men. In both males and females, there were strong positive correlations between age and CVMI stage (rs=0.902, rs=0.890), between age and SOSF stage (rs=0.887, rs=0.885), and between CVMI and SOSF stages (rs=0.955, rs=0.964) (all P<0.001). The mean ages at SOSF stage 3 and stage 4 (12.7~13.9 y in males and 11.0~12.5 y in females) could be used as indicators of the pubertal growth peak. Regression equations for SOSF stage (y), age (a), and CVMI stage (b) were as follows: y=1.355-(0.133×a)+(0.29007×b)+(0.041×a×b) for males (r2=0.9496); y=1.305-(0.158×a)+(0.455×b)+(0.036×a×b) for females (r2=0.9606). Ordinal logistic regression analyses with the proportional odds model showed that females had more advanced SOSF stages than males (odds ratio: 1.972; 95% CI: 1.063-3.658, P<0.05). Our findings may provide basic references for CVMI and SOSF from preadolescents to young adults., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

The purpose of this study was to classify the skeletal phenotypes of adult patients with skeletal class III (C-III) malocclusion and unilateral or bilateral cleft lip and palate using principal component analysis and cluster analysis. The samples consisted of 81 adult C-III patients with cleft lip and palate (CLP) who underwent orthognathic surgery (OGS) or distraction osteogenesis (59 males and 22 females; 50 unilateral cleft lip and palate and 31 bilateral cleft lip and palate; mean age when lateral cephalograms were taken, 22.2±4.6 y). Thirteen angular and one ratio cephalometric variables were measured. Using 4 representative variables obtained from principal component analysis (SNA, SNB, Gonial angle, and Bjork sum), K-means cluster analysis was performed to classify the phenotypes. Then, statistical analysis was conducted to characterize the differences in the variables among the clusters. Five clusters were obtained from 3 groups: severely retrusive maxilla and moderately retrusive mandible group: cluster-1 (23.5%, severely hyperdivergent pattern), cluster-4 (27.2%, moderately hyperdivergent pattern), and cluster-5 (11.1%, normodivergent pattern); moderately retrusive maxilla and normal mandible group: cluster-2 (30.9%, normodivergent pattern); normal maxilla and moderately protrusive mandible group: cluster-3 (7.4%, normodivergent pattern). Although skeletal phenotypes were diverse, distribution of sex and cleft type did not differ among 5 clusters ( P >0.05). Sixty-two percent of cleft patients showed a severely retrusive maxilla and moderately retrusive mandible (cluster-1, cluster-4, and cluster-5), which indicated that these are the main cause of skeletal C-III malocclusion in CLP patients who were treated with OGS. Therefore, it is necessary to consider presurgical orthodontic treatment and surgical planning based on the skeletal phenotypes of CLP patients., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

This study aimed to classify the skeletal phenotypes of preadolescent patients with isolated cleft palate using principal component analysis and cluster analysis. Sixty-four preadolescent female patients with isolated cleft palate (incomplete hard palate and complete soft palate cleft group, n=51; complete cleft of the hard and soft palate group, n=13; the mean age when lateral cephalograms were taken, 7.08±0.76 y) were included. Ten angular and 2 ratio cephalometric variables were measured on a lateral cephalogram. Cluster analysis was performed using 3 representative variables obtained from principal component analysis (SN-GoMe, SNA, and SNB). The differences in the variables among the clusters were characterized using the Kruskal-Wallis test. As a result of the analysis, 6 clusters were obtained from 3 groups: the retrusive maxilla and mandible group: cluster 3 (14.1%, moderately hyperdivergent pattern), cluster 5 (17.2%, severely hyperdivergent pattern); the normal maxilla and mandible group: cluster 1 (23.4%, normodivergent pattern), cluster 4 (12.5%, moderately hyperdivergent pattern), cluster 6 (20.3%, severely hyperdivergent pattern); the normal maxilla and protrusive mandible group: cluster 2 (12.5%, normodivergent pattern). The distribution of isolated cleft palate types did not differ among the 6 clusters ( P >0.05). Two thirds of the patients (68.7%, clusters 1, 2, 4, and 6) had a normal anteroposterior position of the maxilla, while one third of the patients (31.3%, clusters 3 and 5) showed a retrusive mandible. These results indicate that isolated cleft palate patients have diverse maxillo-mandibular growth patterns compared with patients with cleft lip and palate., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

The purpose of this study was to investigate the distribution and phenotype of Goldenhar syndrome (GS) and its association with other anomalies. The samples consisted of 18 GS patients (6 males and 12 females; mean age at investigation, 7.4 ± 4.8 y) who were treated or followed up at the Department of Orthodontics, Seoul National University Dental Hospital between 1999 and 2021. The prevalence of side involvement and degree of mandibular deformity (MD), midface anomalies, and association with other anomalies were evaluated using statistical analysis. The prevalence of unilateral and bilateral MD did not differ (55.6% versus 44.4%). In unilateral MD cases, there was a tendency for higher prevalence of more severe Pruzansky-Kaban types than mild ones (type I, 10%; type IIa, 10%; type IIb, 50%; type III, 30%). Despite hypoplasia of the condyle/ramus complex, compensatory mandibular body growth occurred in 33.3% of GS patients (more severe side in bilateral MD cases, 37.5%, and ipsilateral side in unilateral MD cases, 30%). Class II molar relation was more prevalent than class I and class III molar relations (72.2% versus 11.1% versus 16.7%, P <0.01). Al total of 38.9% of patients had congenitally missing tooth. #7 facial cleft was found in 44.4% of patients. In midface anomalies, ear problem was the most common anomaly, followed by hypoplasia/absence of zygomatic arch and eye problem (88.9% versus 64.3% versus 61.1%, P <0.01). Association with the midface, spine, cardiovascular, and limb anomalies did not differ between unilateral and bilateral MD cases. These results might provide a basic guideline for diagnosis and treatment planning for GS patients., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

Brain organoids are 3D cytoarchitectures resembling the embryonic human brain. This review focuses on current advancements in biomedical engineering methods to develop organoids such as pluripotent stem cells assemblies, quickly aggregated floating culture, hydrogel suspension, microfluidic systems (both photolithography and 3D printing), and brain organoids-on-a-chip. These methods have the potential to create a large impact on neurological disorder studies by creating a model of the human brain investigating pathogenesis and drug screening for individual patients. 3D brain organoid cultures mimic not only features of patients' unknown drug reactions, but also early human brain development at cellular, structural, and functional levels. The challenge of current brain organoids lies in the formation of distinct cortical neuron layers, gyrification, and the establishment of complex neuronal circuitry, as they are critically specialized, developmental aspects. Furthermore, recent advances such as vascularization and genome engineering are in development to overcome the barrier of neuronal complexity. Future technology of brain organoids is needed to improve tissue cross-communication, body axis simulation, cell patterning signals, and spatial-temporal control of differentiation, as engineering methods discussed in this review are rapidly evolving., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The rise of obesity and associated fatal diseases has taken a massive toll worldwide. Despite the existing pharmaceuticals and bariatric surgeries, these approaches manifest limited efficacy or accompany various side effects. Therefore, researchers seek to facilitate the prolonged and specific delivery of therapeutics. Or else, to mimic the essential part of "gastric bypass" by physically blocking excessive absorption via less invasive methods. To achieve these goals, polymeric biomaterials have gained tremendous interest recently. They are known for synthesizing hydrogels, microneedle patches, mucoadhesive coatings, polymer conjugates, and so forth. In this Review, we provide insights into the current studies of polymeric biomaterials in the prevention and treatment of obesity, inspiring future improvements in this regime of study.

Recanalization therapy is the most effective treatment for eligible patients with acute ischemic stroke (AIS). Gut microbiota are involved in the pathological mechanisms and outcomes of AIS. However, the association of gut microbiota features with adverse recanalization therapy outcomes remains unclear. Herein, we investigated gut microbiota features associated with neurological deficits in patients with AIS after recanalization therapy and whether they predict the patients' functional outcomes. We collected fecal samples from 51 patients with AIS who received recanalization therapy and performed 16S rRNA gene sequencing (V3-V4). We compared the gut microbiota diversity and community composition between mild to moderate and severe disability groups. Next, the characteristic gut microbiota was compared between groups, and we noted that the characteristic gut microbiota in patients with mild to moderate disability included Bilophila , Butyricimonas , Oscillospiraceae&#95; UCG-003 , and Megamonas . Moreover, the relative abundance of Bacteroides fragilis , Fusobacterium sp., and Parabacteroides gordonii was high in patients with severe disability. The characteristic gut microbiota was correlated with neurological deficits, and areas under the receiver operating characteristic curves confirmed that the characteristic microbiota predicted adverse recanalization therapy outcomes. In conclusion, gut microbiota characteristics are correlated with recanalization therapy outcomes in patients with AIS. Gut microbiota may thus be a promising biomarker associated with early neurological deficits and predict recanalization therapy outcomes.

Bidirectional communication of the microbiota-gut-brain axis is crucial in stroke. Recanalization therapy, namely intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT), are recommended for eligible patients with acute ischemic stroke (AIS). It remains unclear whether gut microbiota metabolites, namely trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFAs), can predict the prognosis after recanalization therapy. This prospective study recruited patients with AIS receiving IVT, EVT, or both. The National Institutes of Health Stroke Scale (NIHSS) and modified Rankin scale (mRS) scores were used to assess the severity and functional outcomes of AIS, respectively. A functional outcome of mild-to-moderate disability was defined as a mRS score of 0-3 at discharge. Plasma TMAO and SCFA levels were measured through liquid chromatography with triple-quadrupole mass spectrometry. Fifty-six adults undergoing recanalization therapy for AIS were enrolled. Results showed that TMAO levels were not associated with stroke severity and functional outcomes, while isovalerate levels (one of the SCFAs) were negatively correlated with NIHSS scores at admission and discharge. In addition, high isovalerate levels were independently associated with a decreased likelihood of severe disability. The study concluded that an elevated plasma isovalerate level was correlated with mild stroke severity and disability after recanalization therapy for AIS.

Paclitaxel (PTX)-induced peripheral neuropathy (PIPN) is a debilitating health condition which is a result of degeneration of peripheral nerves found in extremities. Currently, there are no established treatment methods that can prevent or protect from PIPN. Fluocinolone acetonide (FA) has been recently identified as a potential candidate for protection from PIPN. However, the fundamental mechanism of action is still unknown. In this study, we showed that enhanced anterograde mitochondrial movement in dorsal root ganglion (DRG) cells has a major role in FA-mediated neuroprotection in PIPN. In this study, cells were treated with PTX or FA along with their combination followed by mitochondrial fluorescence staining. Somal (proximal) and axonal (distal) mitochondria were selectively stained using a microfluidic compartmentalized chamber with different MitoTrackers blue and red, respectively, which we termed, the two-color staining approach. Results revealed that axons were protected from degeneration by the PTX effect when treated along with FA. PTX exposure alone resulted in low mitochondrial mobility in DRG cells. However, cotreatment with PTX and FA showed significant enhancement of anterograde trafficking of somal (proximal) mitochondria to distal axons. Similarly, cotreatment with FA restored mitochondrial mobility significantly. Overall, this study affirms that increasing mitochondrial recruitment into the axon by cotreatment with FA can be a worthwhile strategy to protect or prevent PIPN. The proposed two-color staining approach can be extended to study trafficking for other neuron-specific subcellular organelles.

Small cell lung cancer (SCLC) is a neuroendocrine tumor noted for the rapid development of both metastases and resistance to chemotherapy. High mutation burden, ubiquitous loss of TP53 and RB1, and a mutually exclusive amplification of MYC gene family members contribute to genomic instability and make the development of new targeted agents a challenge. Previously, we reported a novel OCT4-induced MYC transcriptional activation pathway involving c-MYC, pOCT4 S111 , and MAPKAPK2 in progressive neuroblastoma, also a neuroendocrine tumor. Using tumor microarray analysis of clinical samples and preclinical models, we now report a correlation in expression between these proteins in SCLC. In correlating c-MYC protein expression with genomic amplification, we determined that some SCLC cell lines exhibited high c-MYC without genomic amplification, implying amplification-independent MYC activation. We then confirmed direct interaction between OCT4 and DNA-PKcs and identified specific OCT4 and DNA-PKcs binding sites. Knock-down of both POU5F1 (encoding OCT4) and PRKDC (encoding DNA-PKcs) resulted in decreased c-MYC expression. Further, we confirmed binding of OCT4 to the promoter/enhancer region of MYC. Together, these data establish the presence of a DNA-PKcs/OCT4/c-MYC pathway in SCLCs. We then disruptively targeted this pathway and demonstrated anticancer activity in SCLC cell lines and xenografts using both DNA-PKcs inhibitors and a protein-protein interaction inhibitor of DNA-PKcs and OCT4. In conclusion, we demonstrate here that DNA-PKcs can mediate high c-MYC expression in SCLCs, and that this pathway may represent a new therapeutic target for SCLCs with high c-MYC expression., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

This study developed an epoxy-type biomimic zwitterionic copolymer, poly(glycidyl methacrylate) (PGMA)-poly(sulfobetaine acrylamide) (SBAA) (poly(GMA-co-SBAA)), to modify the surface of polyamide elastic fabric using a hydroxylated pretreatment zwitterionic copolymer and dip-coating method. X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy confirmed successful grafting, while scanning electron microscopy revealed changes in the surface pattern. Optimization of coating conditions included controlling reaction temperature, solid concentration, molar ratio, and base catalysis. The modified fabric exhibited good biocompatibility and anti-biofouling performance, as evidenced by contact angle measurements and evaluation of protein adsorption, blood cell, and bacterial attachment. This simple, cost-effective zwitterionic modification technology has high commercial value and is a promising approach for surface modification of biomedical materials.

The purpose of this study was to classify and characterize facial asymmetry (FA) phenotypes in adult patients with unilateral cleft lip and palate (UCLP) and skeletal class III malocclusion. The samples comprised 52 adult UCLP patients (36 men and 16 women; mean age, 22.43 y) who had undergone orthognathic surgery for correction of class III malocclusion. After measurement of 22 cephalometric parameters in posteroanterior cephalograms taken 1 month before orthognathic surgery, principal component analysis was performed to obtain 5 representative parameters [deviation (mm) of ANS (ANS-dev), maxillary central incisor contact point (Mx1-dev), and menton (Me-dev); cant (degree) of the maxillary anterior occlusal plane (MxAntOP-cant) and mandibular border (MnBorder-cant)]. K-means cluster analysis was conducted using these representative parameters. The differences in cephalometric parameters among the clusters were statistically analyzed. The FA phenotypes were classified into 4 types: No-cant-and-No-deviation type (cluster-4, n=16, 30.8%); MxMn-cant-MxMn-dev to the cleft-side type (cluster-3, n=4, 7.7%); Mx-cant-Mn-shift to the cleft-side type (cluster-2, n=15, 28.8%); and Mn-cant-Mn-dev to the noncleft-side type (cluster-1, n=17, 32.7%). Asymmetry in the maxilla and/or mandible were observed in 70% of patients. One third of patients (cluster-2 and cluster-3; sum, 36.5%) exhibited significant cant of MxAntOP induced by cleft and cant or shift of the mandible to the cleft side. Another one third of patients (cluster-1, 32.7%) demonstrated significant deviation and cant of the mandible to the noncleft-side despite cleft in the maxilla. This FA phenotype classification might be a basic guideline for diagnosis and treatment planning for UCLP patients., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

Previous studies have highlighted the importance of outdoor time in reducing the risk of myopia progression. Although ultraviolet A (UVA) radiation dominates in terms of energy with respect to the UV radiation reaching the Earth's surface, its effects on the exposed anterior sclera have not been well studied. This study was designed to investigate the UVA-induced biological effects at peak sunlight levels in human scleral fibroblasts (HSFs). Using next-generation sequencing (NGS), we analyzed the differentially expressed genes (DEGs) in UVA-treated and normal HSFs. Further, we then identified the functions and key regulators of the DEGs using bioinformatics analysis, and verified the effects of UVA on gene and protein expression in HSFs using real-time PCR, western blotting, and immunofluorescence imaging. The highest level of solar UVA (365 nm) was 3.4 ± 0.18 (mW/cm 2 ). The results from the functional analysis of the DEGs were related to structural changes in the extracellular matrix (ECM) and protein metabolism. Transforming growth factor-β1 (TGF-β1) and Smad3 were predicted to be potential upstream regulators, associated with ECM organization. Exposure to a single wavelength of UVA (365 nm, 3 mW/cm 2 ) for 1 h for 5 consecutive days induced the downregulation of the mRNA of ECM genes including COL1A1, COL3A1, COL5A1, VCAN and collagen I protein in HSF. UVA downregulated Smad3 protein and reduced TGF-β-induced collagen I protein production following UVA exposure in HSF. In conclusion, high UVA exposure reduces TGF-β signaling and collagen I production by modulating Smad levels in HSF. The effects of overexposure to high-intensity UVA on myopia control require further investigations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)