Tumor immune microenvironment lncRNAs.

Long non-coding ribonucleic acids (RNAs) (lncRNAs) are key players in tumorigenesis and immune responses. The nature of their cell type-specific gene expression and other functional evidence support the idea that lncRNAs have distinct cellular functions in the tumor immune microenvironment (TIME). To date, the majority of lncRNA studies have heavily relied on bulk RNA-sequencing data in which various cell types contribute to an averaged signal, limiting the discovery of cell type-specific lncRNA functions. Single-cell RNA-sequencing (scRNA-seq) is a potential solution for tackling this limitation despite the lack of annotations for low abundance yet cell type-specific lncRNAs. Hence, updated annotations and further understanding of the cellular expression of lncRNAs will be necessary for characterizing cell type-specific functions of lncRNA genes in the TIME. In this review, we discuss lncRNAs that are specifically expressed in tumor and immune cells, summarize the regulatory functions of the lncRNAs at the cell type level and highlight how a scRNA-seq approach can help to study the cell type-specific functions of TIME lncRNAs.

Shifting perspectives: From "Epilepsy" to "Cerebroelectric Disorder".

BACKGROUND & OBJECTIVE: Epilepsy has long been associated with stigma and misconceptions. In response, the Korean Epilepsy Society initiated the Epilepsy Renaming project in 2008 to replace the stigmatizing term with a neutral and scientifically grounded name, "cerebroelectric disorder". This study explores the impact of changing terminology on the public discourse surrounding epilepsy. METHODS: Online news articles from distinct time periods (2001-2003, 2011-2014, 2017-2018, and 2020-2022) were analyzed using text data analysis techniques, including Latent Dirichlet Allocation topic modeling, frequency analysis, and sentiment analysis. The inclusion of data from 2017 to 2018 allowed for an examination of discourse trends independent of the COVID-19 pandemic's influence. Correlation of words in each period was visualized via network maps. Migraine was set as control term to highlight changes in perception devoid of significant stigma intervention efforts. RESULTS: The analysis revealed a significant shift in terminology preference, with cerebroelectric disorder gradually replacing epilepsy in news articles. The discourse surrounding epilepsy evolved over time from focusing on healthcare and economic aspects to patient-centered discussions, emphasizing the daily lives of individuals with epilepsy. This shift towards more empathetic and less stigmatized language was contrasted against the discourse on migraine, highlighting the specific impact of the terminological change on epilepsy's perception. CONCLUSION: The adoption of the neutral term "cerebroelectric disorder" in South Korea has influenced the discourse surrounding epilepsy, leading to more patient-centered discussions and a reduction in stigma. This study highlights the importance of terminology in shaping public perceptions of diseases and suggests that changing terminology can positively impact the understanding and destigmatization of epilepsy.

Advancements in Flexible Nanogenerators: Polyvinylidene Fluoride-Based Nanofiber Utilizing Electrospinning.

With the gradual miniaturization of electronic devices and the increasing interest in wearable devices, flexible microelectronics is being actively studied. Owing to the limitations of existing battery systems corresponding to miniaturization, there is a need for flexible alternative power sources. Accordingly, energy harvesting from surrounding environmental systems using fluorinated polymers with piezoelectric properties has received significant attention. Among them, polyvinylidene fluoride (PVDF) and PVDF co-polymers have been researched as representative organo-piezoelectric materials because of their excellent piezoelectric properties, mechanical flexibility, thermal stability, and light weight. Electrospinning is an effective method for fabricating nanofibrous meshes with superior surface-to-volume ratios from polymer solutions. During electrospinning, the polymer solution is subjected to mechanical stretching and in situ poling, corresponding to an external strong electric field. Consequently, the fraction of the piezoelectric ß-phase in PVDF can be improved by the electrospinning process, and enhanced harvesting output can be realized. An overview of electrospun piezoelectric fibrous meshes composed of PVDF or PVDF co-polymers to be utilized is presented, and the recent progress in enhancement methods for harvesting output, such as fiber alignment, doping with various nanofillers, and coaxial fibers, is discussed. Additionally, other applications of these meshes as sensors are reviewed.

Development of a New Electrochemical Atomic Force Microscopy Tool for Obtaining Surface Morphology Through Electrochemical Reaction.

Electrochemical atomic force microscopy is a complex electrochemical analysis method that has been applied in many fields. Electrochemical atomic force microscopy consists of an electrochemical cell, electrochemical analysis system, and atomic force microscopy. To simultaneously analyze the electrochemical system and the atomic force microscopy, an electrochemical cell with a suitable structure is needed. We developed the electrochemical atomic force microscopy analysis system using a self-developed electrochemical cell. To confirm the in-situ analytical ability of the developed electrochemical atomic force microscopy analysis system, we observed the electrochemical corrosion process of copper with respect to changes in pH of a sulfuric acid solution. The operation of the electrochemical atomic force microscopy tool was verified by experiments on the electrochemical corrosion of copper, and the factors affecting the corrosion process were examined. It was confirmed that electrochemical atomic force microscopy can perform electrochemical analysis and atomic force microscopy image analysis at the same time.

Skin Metabolism: Relevance of Skin Enzymes for Rational Drug Design.

Transdermal therapeutic systems (TTS) have numerous pharmacological benefits. Drug release, for example, is independent of whether a patient is in a fed or a fasted state, and lower doses can be given as gastrointestinal and hepatic first-pass metabolism is avoided. In addition, inter- and intrapatient variability is minimized as the release of the drug is mainly controlled by the system. This makes TTS interesting as alternative systems to the most common dosage form of oral tablets. The difficulty with the dermal administration route is transporting the drug through the skin, since the skin is an efficient barrier against foreign bodies. Various strategies have been reported in the literature of how drug penetration can be improved. Most of them, however, focus on overcoming the stratum corneum as the first (mechanical) skin barrier. However, penetration is much more complex, and the skin's barrier function does not only depend on the stratum corneum; what has been underestimated is the second (biological) skin barrier formed of enzymes. Compared to the stratum corneum, very little is known about these enzymes, e.g., which enzymes are present in the skin and where exactly they are localized. Hence, very few strategies can be found for how to bypass or even use the skin enzyme barrier for TTS development. This review article provides an overview of the skin enzymes considered to be relevant for the biotransformation of dermally applied drugs. Also, we discuss the use of dermal prodrugs and soft drugs and give the stereoselectivity of skin metabolism careful consideration. Finally, we provide suggestions on how to make use of the current knowledge about skin enzymes for rational TTS design.

Supplemental Method for Reduction of Irreducible Mallet Finger Fractures by the 2-Extension Block Technique: The Dorsal Counterforce Technique.

PURPOSE: We suggest a method to achieve anatomical reduction in mallet finger fractures that are insufficiently treated by the 2-extension block wire technique. METHODS: We performed a retrospective review of 18 patients who were found to have an irreducible dorsal fragment and distal interphalangeal joint incongruence owing to rotation of the dorsal fragment in the sagittal plane. In these cases, we additionally employed a dorsal counterforce technique to supplement the 2-extension block technique. An additional K-wire was used to apply counterforce against the distal part of the dorsal fragment and control rotation in the sagittal plane. RESULTS: All 18 fractures united. Congruent joint surfaces and anatomical reduction were seen in all cases. The mean active flexion of the distal interphalangeal joints was 83.8° (range, 79°-88°) and the mean extension loss was 0.4° (range, 0°-4°). CONCLUSIONS: We believe that the dorsal counterforce technique effectively supplements the 2-extension block K-wire technique and aids control of dorsal fragment rotation in the sagittal plane. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Effect of Raloxifene Administration on Bone Response Around Implant in the Maxilla of Osteoporotic Rats.

OBJECTIVES: To determine the effect of raloxifene (RAL) on bone response around implants in the maxilla of osteoporotic rats. MATERIALS AND METHODS: Forty-five female rats at 8 weeks-old were divided into 3 groups: (1) control group, sham-operated rats, (2) ovariectomized group (OVX), and (3) ovariectomized and raloxifene-administered group (RAL). Eight weeks after the ovariectomy, upper right molar was extracted and an implant was placed at 4 weeks post-extraction. The RAL group was administered with 1 mg/kg/d of raloxifene via gavage while the OVX group and the control group received saline only. Three rats in each group were sacrificed at 1, 4, 7, 14, and 28 days and histologic sections were evaluated by hematoxylin and eosin staining and micro-computerized tomography was taken. RESULTS: The RAL group showed faster bone formation around the implant than the OVX group. At 4 weeks after implantation, newly formed bone close to implant threads was mature with considerable quantity of bone marrow in the RAL group. CONCLUSION: Raloxifene showed increased bone formation around implant. This might have clinical implications in prosthetic restoration by dental implants for patients with poor bone quality.

Azithromycin nanocrystals for dermal prevention of tick bite infections.

Azithromycin was optimized as nanocrystals with a drug content of 10.0 % (w/w) and a surfactant D-α -tocopheryl polyethylenglycol 1000 succinate (TPGS) content of 1.0 % (w/w) using bead milling for 10 min. The photon correlation spectroscopy (PCS) diameter of the bulk population was 189 nm, laser diffraction (LD) diameter 90 % was 370 nm. Spherical morphology of the optimal nanocrystals was observed by transmission electron microscope (TEM). They were stable over 1 year of storage at 4 °C with the particle size within the nanometer range which was confirmed by PCS, LD and light microscope. An acceptable physical stability of 2 years was also obtained when stored at 4 °C. No microbial attack to the nanocrystals was observed before 3 years storage at 4 °C. The saturation solubility of the nanocrystals was up to triple compared to the raw drug powder (RDP) in water. When incorporated into the gel base, highest penetration efficacy was achieved by the optimal nanocrystals compared to 1) the clinically effective ethanol-solution-gel, 2) the gel with propylene glycol and 3) the gel with RDP in the ex vivo porcine ear penetration study. Even though propylene glycol improved saturation solubility of nanocrystals, it could not bring benefit to nanocrystals in the penetration study. Based on these optimized azithromycin nanocrystals, topical administration for enhanced dermal bioavailability of azithromycin seems to be feasible.

Maximum Loaded Amorphous Azithromycin Produced Using the Wetness Impregnation Method with Fractional Steps for Dermal Prophylaxis Against Lyme Disease.

Azithromycin was loaded onto the µm-sized mesoporous silica Davisil® SP53D-11920 using the wetness impregnation method with fractional steps (WIFS) and further incorporated into a 5 % hydroxypropyl cellulose gel to prevent Lyme disease. Maximum loadings (32.0 % w/w and 33.2 % w/w) were produced by different concentrated loading solutions and determined by X-ray diffraction (XRD). A total of 24 months stability of the amorphous azithromycin state in the silica (33.2 % loading) and 18 months stability in the gel (33.2 % loading) at 4 °C were also confirmed by XRD. The higher kinetic solubility at 40 min (1,300 µg/mL versus 93 µg/mL) and higher porcine ear skin penetration compared to the raw drug powder indicated higher dermal bioavailability of the azithromycin-loaded silica (32.0 % loading), even when compared to the "gold standard" nanocrystals and another clinical effective azithromycin formulation with ethanol. In summary, maximum loaded silicas with azithromycin by WIFS is a promising dermal formulation for prophylaxis against Lyme disease.

One-Barrel Microsurgical Fibula Flap for Reconstruction of Large Defects of the Femur.

Various methods for reconstructing large femur bone defects after tumor resection have been introduced. In this study, we reviewed the clinical outcomes of using a 1-barrel free vascularized fibular graft (FVFG) protected by a lateral locking plate for large femoral defects not involving the knee joint.Between August 2007 and August 2013, we treated 7 patients with large femoral bone defects after tumor resection. The mean age of the patients was 19 years (range, 12-36 years), and 3 were women. All defects were free of infection before the procedure. Femoral bone defects were reconstructed using a 1-barrel FVFG protected by a lateral locking plate. The mean bone defect size was 10.5 cm (range, 6-16 cm). We reviewed clinical outcomes at the last follow-up.All patients survived beyond the last follow-up; the mean follow-up period was 54 months (range, 26-100 months). Two patients sustained stress fractures of the FVFG, but the lateral locking plate protected the fractured graft until in situ bone healing obtained. Mean time to bone union of both host-graft junctions was 24 months (range, 18-31 months). The mean Musculoskeletal Tumor Society score (%) was 85.8% (range, 80-95%).A 1-barrel FVFG protected by a lateral locking plate maintained a stable graft-host bone construct, successfully leading to bone healing, even in cases of stress fractures of the graft, and appears to be a good option for large femur bone defects.

Association of temporomandibular disorder and high frequency of suicide ideation in Korean adolescents: a cross-sectional survey.

BACKGROUND: This study investigated the association between psychological factors and temporomandibular disorder (TMD) in a representative sample using data from the Korean nationwide survey. METHODS: The study included 1337 adolescents. Participants provided demographic, socio-economic and behavioural information, and responses to questionnaires assessing their mental health status including perceived stress, depressed mood and suicidal ideation in the presence of TMD. In univariate analysis, t-test was used to test the association between TMD and risk factors by gender in a complex sampling design. Multivariate logistic regression analyses were used to examine the association between TMD and psychological factors. RESULTS: Male adolescents with TMD were highly engaged with depressed mood and suicidal ideation (p = .0006, p = .0223), however, no psychological factors were significant in female adolescents (p < .05). Male adolescents with both depressed mood and suicidal ideation had significantly high rates of TMD (p = .0024). The risks for experiencing depressed mood (OR: 3.07) and suicidal ideation (OR: 2.564) were significantly associated with TMD in male adolescents after adjusting confounders. CONCLUSIONS: The results provide evidence that the depressed mood and suicidal ideation were associated with TMD in male adolescents. This study has important implications for enhanced screening and evaluation of mental health among patients with TMD according to gender.

Direct Synthesis of Carbon Sheathed Tungsten Oxide Nanoparticles via Self-Assembly Route for High Performance Electrochemical Charge Storage Electrode.

Using a stabilizing agent-assisted co-assembly method, a novel nanocomposite of mesoporous carbon embedded with uniform tungsten oxide nanorods is obtained, which is converted into carbon-sheathed tungsten oxide nanoparticles by delicate calcination and further reduction. Through optimization of tungsten content, it is found that highly crystalline tungsten oxide nanoparticles are uniformly coated with an ultra-thin carbon layer. When applied into electrochemical charge-storage electrodes for supercapacitor and lithium-ion battery, an excellent average capacitance (129 F g−1, above 400 F cm−3), higher rate performance and significantly advanced cycle stability are observed. These improved charge storage properties are attributed to improved electrical conductivity and enhanced structural stability, which is induced by uniform carbon coating on partially reduced tungsten oxide nanoparticles.

Ascending Facial Necrotizing Fasciitis in a Patient Taking a Bisphosphonate.

Facial necrotizing fasciitis (NF) is a rare fulminant infection of the soft and connective tissues that spreads along the fascial planes of the face. Its origins most commonly involve odontogenic infection and it is usually associated with a history of dentoalveolar surgery, such as tooth extraction or implant placement. We present a case of ascending facial NF with odontogenic origin in a patient taking a bisphosphonate.

Improved Bone Regeneration With Multiporous PLGA Scaffold and BMP-2-Transduced Human Adipose-Derived Stem Cells by Cell-Permeable Peptide.

OBJECTIVE: Currently, much work has focused on the engineering of bone using adipose-derived stem cells (ADSCs), which differentiate into osteogenic cells. This study was conducted to assess the bone-regenerating capacity of ADSCs with genetic modification. MATERIALS AND METHODS: ADSCs were cultured and transduced with recombinant adenovirus-expressing bone morphogenetic protein-2 (rAd/BMP-2). Two 5-mm full-thickness bone defects were created on the parietal bones of 24 rats. The defects were left empty (n = 12), restored with a scaffold alone (n = 12), transplanted with ADSCs in osteogenic media (n = 12), or transplanted with rAd/BMP-2-transduced ADSCs (n = 12). Six defects from each group were assessed by histologic observation, histomorphometric analysis, and microcomputed tomography (micro-CT) imaging at 4 and 8 weeks after transplantation. RESULTS: Increased new bone formation was observed in the rAd/BMP-2-transduced ADSC groups, compared with the other groups. On micro-CT, significant differences were noted in bone volume-to-tissue volume ratios between rAd/BMP-2-transduced ADSCs group and the other groups at both time points (P < 0.05). CONCLUSION: The result demonstrates that transferring BMP-2 promotes the osteogenic differentiation of ADSCs and enhances bone regeneration. Under limitation of this study, genetic modification of ADSCs with BMP-2 could be adopted in clinical application.

Enhancing Effect of Intermittent Parathyroid Hormone Administration on Bone Formation After Titanium Implant Placement in an Ovariectomized Rat Maxilla.

OBJECTIVE: This study examined the effect of intermittent parathyroid hormone (PTH) administration on the bone response around implant on the maxilla of rats with ovariectomy-induced osteoporosis. MATERIAL AND METHODS: A total of 27 female Sprague-Dawley rats were divided into 3 groups (n = 9) and were ovariectomized (OVX). Eight weeks after, upper right molar was extracted and an implant was placed at 4 weeks after extraction. The PTH group received PTH, and the OVX group and the control group received vehicle only. Beginning after implant placement, 30 µg/kg of PTH was subcutaneously administered in the dorsum 3 times a week. Three rats in each group were killed at 1, 2, and 4 weeks and histologic sections were evaluated. RESULTS: After 4 weeks, the amount of newly formed bone around implants in the PTH group was comparable with the control group, with bone covering the implant surface in both groups. However, the OVX group displayed relatively small amount of new bone. CONCLUSION: Intermittent PTH has the potential to increase new bone formation around implant. These findings have clinical implications in prosthetic restoration by implants with poor bone quality.

Association between insulin resistance and periodontitis in Korean adults.

OBJECTIVE: Recent studies have proposed an association between periodontitis and metabolic abnormalities. We investigated the association between insulin resistance and periodontitis among Korean adults. METHODS: A cross-sectional analysis was conducted using the Korea National Health and Nutrition Examination Survey 2008-2010. A total of 16,720 non-diabetic subjects over 18 years old were evaluated (7060 men and 9660 women). Periodontal status was assessed by the Community Periodontal Index. Insulin resistance was measured using the homeostasis model assessment of insulin resistance (HOMA-IR). Participants in the highest and lowest quartile of HOMA-IR were defined as insulin-resistant and insulin-sensitive respectively. RESULTS: The prevalence of periodontitis increased significantly with higher HOMA-IR quartiles in post-menopausal women (p for linear association = 0.019). Among post-menopausal women, participants in the highest quartile of HOMA-IR were significantly more likely to have periodontitis compared to those in the lowest quartile [adjusted odds ratio (OR), 1.47; 95% confidence interval (CI), 1.07-2.01]. Moreover, obese post-menopausal women showed an increased association between insulin resistance and periodontitis (adjusted OR, 1.92; 95% CI,1.29-2.87). However, this association was not found in men or pre-menopausal women. CONCLUSIONS: Our results suggest that insulin resistance may be associated with periodontitis, especially when combined with obesity, among post-menopausal women in Korea.

Applications of scanning probe-atomic force microscopy in nanobioelectronics.

Scanning probe microscopy (SPM) is considered one of the most powerful tools for nanoscale studies that are becoming increasingly important, and SPM has shown rapid development. Atomic force microscopy (AFM), in particular, is the widely used SPM system. SPM, and especially AFM, has been used as a new measuring tool for phenomena that were earlier difficult to prove because of the limitations of earlier systems. In addition SPM allows acquiring nanoscale resolution images of the surface of materials. New applications are constantly being developed for SPM, and it is now used actively in material sciences and biological fields. The most important reason why SPM has attracted attention in the biological field is because it can be used in liquids as well. This allows the study of live cells and various other systems in nanoscale. Recently, there have been many advances in nanoscale studies, such as studies of cell interactions, cell changes according to environmental changes, and development of biosensors. This review is focused on applications in nanodevices, as well as on specific biological applications to discuss the development and opportunities of SPM in the biological field.

Development and applications of 3-dimensional integration nanotechnologies.

Unlike conventional two-dimensional (2D) planar structures, signal or power is supplied through through-silicon via (TSV) in three-dimensional (3D) integration technology to replace wires for binding the chip/wafer. TSVs have becomes an essential technology, as they satisfy Moore's law. This 3D integration technology enables system and sensor functions at a nanoscale via the implementation of a highly integrated nano-semiconductor as well as the fabrication of a single chip with multiple functions. Thus, this technology is considered to be a new area of development for the systemization of the nano-bio area. In this review paper, the basic technology required for such 3D integration is described and methods to measure the bonding strength in order to measure the void occurring during bonding are introduced. Currently, CMOS image sensors and memory chips associated with nanotechnology are being realized on the basis of 3D integration technology. In this paper, we intend to describe the applications of high-performance nano-biosensor technology currently under development and the direction of development of a high performance lab-on-a-chip (LOC).

Clinical outcomes of patients with unilateral internal derangement of the temporomandibular joint following arthrocentesis and stabilization splint therapy.

BACKGROUND: The management of internal derangement (ID) of the TMJ is challenging because of multiple etiologic factors and varying degrees of severity. The aim of this study was to evaluate the clinical outcomes of patients with unilateral ID treated with arthrocentesis and stabilization splint therapy during a 6-month period. METHODS: A total of 105 patients (87 females, 18 males) with unilateral ID were included in this study. Patients were divided into unilateral anterior disc displacement with reduction (ADDwR) and unilateral anterior disc displacement without reduction (ADDwoR). Patients with ADDwoR were subdivided according to the erosive bone changes. Objective parameters on mandibular movement and subjective parameters on pain were obtained and assessed. Their clinical outcomes before and after arthrocentesis and stabilization splint therapy were compared with the chi-square, Fisher's exact test, paired t-test, or Wilcoxon singed-rank test. RESULTS: All objective parameters of unilateral ID patients significantly increased at the 6-month follow-up. The differences in mean visual analog scale (VAS) pain scores were statistically significant in all subjective variables (p < 0.01). In joints with ADDwoR, preoperative maximal mouth opening, and maximal protrusive movement in both groups, with erosive and non-erosive changes were significantly increased after 6 months (p < 0.01). However, right and left maximal lateral movement increased after treatment in both groups but without significant differences. All VAS pain scores on jaw movement and palpation of associated muscles showed a significant decrease regardless of erosive changes. CONCLUSIONS: The combination of arthrocentesis and subsequent stabilization splint therapy was shown to be highly effective in pain reduction and improvement of mandibular movements in both unilateral ADDwR and ADDwoR, as well as in cases with both erosive and non-erosive bony changes associated with unilateral ADDwoR.

Enhanced Hybrid Nanogenerator Based on PVDF-HFP and PAN/BTO Coaxially Structured Electrospun Nanofiber.

Nanogenerators have garnered significant interest as environmentally friendly and potential energy-harvesting systems. Nanogenerators can be broadly classified into piezo-, tribo-, and hybrid nanogenerators. The hybrid nanogenerator used in this experiment is a nanogenerator that uses both piezo and tribo effects. These hybrid nanogenerators have the potential to be used in wearable electronics, health monitoring, IoT devices, and more. In addition, the versatility of the material application in electrospinning makes it an ideal complement to hybrid nanogenerators. However, despite their potential, several experimental variables, biocompatibility, and harvesting efficiency require improvement in the research field. In particular, maximizing the output voltage of the fibers is a significant challenge. Based on this premise, this study aims to characterize hybrid nanogenerators (HNGs) with varied structures and material combinations, with a focus on identifying HNGs that exhibit superior piezoelectric- and triboelectric-induced voltage. In this study, several HNGs based on coaxial structures were fabricated via electrospinning. PVDF-HFP and PAN, known for their remarkable electrospinning properties, were used as the primary materials. Six combinations of these two materials were fabricated and categorized into homo and hetero groups based on their composition. The output voltage of the hetero group surpassed that of the homo group, primarily because of the triboelectric-induced voltage. Specifically, the overall output voltage of the hetero group was higher. In addition, the combination group with the most favorable voltage characteristics combined PVDF-HFP@PAN(BTO) and PAN hollow, boasting an output voltage of approximately 3.5 V.