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Ototoxicity is the drug-induced damage of the inner ear, causing bilateral irreversible sensorineural hearing loss. Cisplatin is a widely used chemotherapeutic agent which causes ototoxicity as its side effect. Pretreatment with metformin prior to the application of cisplatin significantly decreased the late apoptosis and attenuated the cisplatin-induced increase in ROS. To understand the molecular mechanisms that are involved in the preventive effect of metformin, we evaluated the change of gene expression induced by cisplatin at several different time points (0 h, 6 h, 15 h, 24 h and 48 h) and the alteration of gene expression according to pretreatment with metformin in HEI-OC1 cells through microarray analysis. Cisplatin exposure induced a total of 89 DEGs (differentially expressed genes) after 6 h, with a total of 433 DEGs after 15 h, a total of 941 DEGs after 24 h, and a total of 2764 DEGs after 48 h. When cells were pretreated with metformin for 24 h, we identified a total of 105 DEGs after 6 h of cisplatin exposure, a total of 257 DEGs after 15 h, a total of 1450 DEGs after 24 h, and a total of 1463 DEGs after 48 h. The analysis was performed based on the gene expression, network analyses, and qRT-PCR, and we identified several genes (CSF2, FOS, JUN, TNFα, NFκB, Txnip, ASK1, TXN2, ATF3, TP53, IL6, and IGF1) as metformin-related preventive biomarkers in cisplatin ototoxicity.

Autoimmune limbic encephalitis (LE) is a rare, but devastating complication of allogeneic hem-atopoietic stem cell transplantation (HSCT). There is currently limited evidence describing the risk factors, laboratory features, and underlying mechanisms of this neurologic adverse event. We retrospectively reviewed available clinical, imaging, and laboratory data from adult patients with hematological malignancies who underwent haploidentical HSCT with cyclophosphamide (PTCy) at Chungnam National University Hospital from June 2016 to May 2020. Patients who developed LE were compared to those who did not based on clinical assessment, serum inflam-matory biomarkers, and reconstitution of various T cell populations. Of 35 patients, four devel-oped LE. There were no differences in patient demographics, donor demographics, or treatment conditions between patients that did and did not develop LE. Overall, patients with LE had worse clinical outcomes and overall survival than those without. In addition, they tended to have higher markers of systemic inflammation in the early post-transplant period, including fever, C-reactive protein (CRP), and cytokines. Remarkably, baseline interleukin-6 levels before HSCT were found to be higher in patients who developed LE than those who did not. In addition, analysis of T cell subsets showed impaired expansion of CD25+FOXP3+ regulatory T (Treg) cells in LE compared to non-LE patients despite appropriate reconstitution of the total CD4+ T cell population. Patients that developed LE within the first 30 days of HSCT were likely to have high serum IL-6 among other inflammatory cytokines coupled with suppression of regulatory T cell differentiation. Further work is needed on the mechanisms underlying impaired Treg expansion following HSCT and potential therapies.

Iron accumulation in the brain accelerates Alzheimer’s disease progression. To cure iron toxicity, we assessed the therapeutic effects of noncontact transcranial electric field stimulation to the brain on toxic iron deposits in either the Aβ fibril structure or the Aβ plaque in a mouse model of Alzheimer’s disease (AD) as a pilot study. A capacitive electrode-based alternating electric field (AEF) was applied to a suspension of magnetite (Fe3O4) to measure field-sensitized reactive oxygen species (ROS) generation. The increase in ROS generation compared to the untreated control was both exposure-time and AEF-frequency dependent. The frequency-specific exposure of AEF to 0.7–1.4 V/cm on a magnetite-bound Aβ-fibril or a transgenic Alzheimer’s disease (AD) mouse model revealed the degradation of the Aβ fibril or the removal of the Aβ-plaque burden and ferrous magnetite compared to the untreated control. The results of the behavioral tests show an improvement in impaired cognitive function following AEF treatment on the AD mouse model. Tissue clearing and 3D-imaging analysis revealed no induced damage to the neuronal structures of normal brain tissue following AEF treatment. In conclusion, our results suggest that the effective degradation of magnetite-bound amyloid fibrils or plaques in the AD brain by the electro-Fenton effect from electric field-sensitized magnetite offers a potential electroceutical treatment option for AD.

Foot-and-mouth disease (FMD) vaccines must be produced in a biosafety level 3 facility, so the FMD virus (FMDV) must be completely inactivated after amplification. The inactivation kinetics of FMDV during vaccine antigen production were assessed by evaluating whether the viral titer dropped below 10−7 TCID50/mL within 24 h of binary ethyleneimine (BEI) treatment. This study dealt with four FMD vaccine candidate strains for the efficacy of BEI treatment at different concentrations and temperatures to determine the optimal inactivation condition of each virus. Two domestic isolates, O/SKR/Boeun/2017 (O BE) and A/SKR/Yeoncheon/2017 (A YC), and two recombinant viruses, PAK/44/2008 (O PA-2) and A22/Iraq/24/64 (A22 IRQ), were investigated. The O BE and A22 IRQ required 2 mM BEI at 26 °C and 0.5 mM BEI at 37 °C for complete inactivation. The O PA-2 and A YC required 2 mM BEI at 26 °C and 1 mM BEI at 37 °C. Crucially, the yield of FMD virus particles (146S) in the viral infection supernatant was higher (>4.0 µg/mL) than those previously reported; additionally, there was little antigen loss, even after 24 h of treatment with 3 mM BEI. Overall, it is considered economical to produce FMD vaccines using these four kinds of viruses; therefore, these candidate strains will be prioritized for the manufacture of FMD vaccines in South Korea.

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Oxidative catabolism of monoamine neurotransmitters by monoamine oxidases (MAOs) produces reactive oxygen species (ROS), which contributes to neuronal cells’ death and also lowers monoamine neurotransmitter levels. In addition, acetylcholinesterase activity and neuroinflammation are involved in neurodegenerative diseases. Herein, we aim to achieve a multifunctional agent that inhibits the oxidative catabolism of monoamine neurotransmitters and, hence, the detrimental production of ROS while enhancing neurotransmitter levels. Such a multifunctional agent might also inhibit acetylcholinesterase and neuroinflammation. To meet this end goal, a series of aminoalkyl derivatives of analogs of the natural product hispidol were designed, synthesized, and evaluated against both monoamine oxidase-A (MAO-A) and monoamine oxidase-B (MAO-B). Promising MAO inhibitors were further checked for the inhibition of acetylcholinesterase and neuroinflammation. Among them, compounds 3aa and 3bc were identified as potential multifunctional molecules eliciting submicromolar selective MAO-B inhibition, low-micromolar AChE inhibition, and the inhibition of microglial PGE2 production. An evaluation of their effects on memory and cognitive impairments using a passive avoidance test confirmed the in vivo activity of compound 3bc, which showed comparable activity to donepezil. In silico molecular docking provided insights into the MAO and acetylcholinesterase inhibitory activities of compounds 3aa and 3bc. These findings suggest compound 3bc as a potential lead for the further development of agents against neurodegenerative diseases.

Several cameras are mounted on navigation aid buoys and these cameras can be used for accident prevention systems by processing the images captured. The currently existing image processing algorithms were originally designed for accident prevention on land—for example, CCTV (closed-circuit television)—which are performance oriented. However, when it comes to ocean-based images, navigation aids are usually located at sea and the cameras must be battery operated, and consequently, the energy efficiency of image processing is a major concern. Therefore, this paper proposed a novel approach to the detection of images in an ocean environment with a significantly lower computation. The new algorithm clustered pixels to grids and dealt with grids using greyscale rather than the particular color values of each pixel. Simulation-based experiments demonstrated that the grid-based algorithm provided five-times faster image processing in order to detect an object and achieved an up to 2.5 higher detection rate when compared with existing algorithms using ocean images.

Capacitive DACs (C-DACs) are widely used as stand-alone DACs or in an ADC as auxiliary DACs. An important performance metric of a C-DAC is its energy consumption and the linearity between the digital input and the analog output. In multi-bit C-DACs, the mismatch between the capacitors can degrade linearity, which can be important in high-resolution applications. In this work, we analyze the power consumption and linearity performance of a class of C-DACs called split-array C-DACs. We show that the simple element rotation technique, which is widely used to suppress the mismatch error of DACs, cannot be used with the power-efficient three-level switching scheme to effectively suppress the mismatch error. Then, we propose a switching scheme which can be used with the power efficient three-level switching and can suppress the in-band mismatch error effectively.

Background: Although there is limited literature on medication adherence (including HIV care engagement) and COVID-19 vaccine hesitancy in general populations (i.e., non-sexual or gender minority populations), even less is known about whether HIV care engagement correlates with COVID-19 vaccine hesitancy among sexual and gender minorities, especially those from intersectional backgrounds. The objective of the current study was to examine if an association exists between HIV status neutral care (i.e., current pre-exposure prophylaxis [PrEP] or antiretroviral therapy [ART] use) and COVID-19 vaccination hesitancy among Black cisgender sexual minority men and transgender women at the initial peak of the pandemic. Methods: We conducted the N2 COVID Study in Chicago from 20 April 2020 to 31 July 2020 (analytic n = 222), including Black cisgender sexual minority men and transgender women who were vulnerable to HIV as well as those who were living with HIV. The survey included questions regarding HIV care engagement, COVID-19 vaccination hesitancy and COVID-19 related socio-economic hardships. Multivariable associations estimated adjusted risk ratios (ARRs) using modified Poisson regressions for COVID vaccine hesitancy adjusting for baseline socio-demographic characteristics and survey assessment time period. Results: Approximately 45% of participants reported COVID-19 vaccine hesitancy. PrEP and ART use were not associated with COVID-19 vaccine hesitancy when examined separately or combined (p > 0.05). There were no significant multiplicative effects of COVID-19 related socio-economic hardships and HIV care engagement on COVID-19 vaccine hesitancy. Conclusions: Findings suggest no association between HIV care engagement and COVID-19 vaccine hesitancy among Black cisgender sexual minority men and transgender women at the initial peak of the pandemic. It is therefore essential that COVID-19 vaccine promotion interventions focus on all Black sexual and gender minorities regardless of HIV care engagement and COVID-19 vaccine uptake is likely related to factors other than engagement in HIV status neutral care.

This case report presents the non-surgical orthodontic camouflage treatment of an 18-year-old male patient with skeletal Class III asymmetry and severe anterior open bite. The anterior open bite was corrected by extrusion of the maxillary and mandibular anterior teeth and clockwise and counterclockwise rotation of the maxillary and mandibular occlusal plane, respectively, using intermaxillary Class III elastics between the maxillary posterior buccal miniscrews and mandibular canines and anterior vertical elastics between the maxillary and mandibular canines. Class III dental relationships and dental asymmetry were corrected via unilateral distalization of the mandibular dentition on the left side using a closed coil spring between the buccal shelf screw and hook. The patient’s smile esthetics and dental relationship were improved with a more favorable facial profile, and facial asymmetry was slightly alleviated after orthodontic camouflage treatment. The total treatment time was 15 months. A modified wraparound retainer with a scalloped labial bow, tongue crib, and tooth positioner was used simultaneously to prevent the potential relapse.

We examined whether recombinant human bone morphogenetic protein-2 (rhBMP-2) when applied to collagen membranes, would reinforce them during guided bone regeneration. Four critical cranial bone defects were created and treated in 30 New Zealand white rabbits, including a control group, critical defect only; group 1, collagen membrane only; group 2, biphasic calcium phosphate (BCP) only; group 3, collagen membrane + BCP; group 4, collagen membrane with rhBMP-2 (1.0 mg/mL); group 5, collagen membrane with rhBMP-2 (0.5 mg/mL); group 6, collagen membrane with rhBMP-2 (1.0 mg/mL) + BCP; and group 7, collagen membrane with rhBMP-2 (0.5 mg/mL) + BCP. After a 2-, 4-, or 8-week healing period, the animals were sacrificed. The combination of collagen membranes with rhBMP-2 and BCP yielded significantly higher bone formation rates compared to the other groups (control group and groups 1–5 < groups 6 and 7; p < 0.05). A 2-week healing period yielded significantly lower bone formation than that at 4 and 8 weeks (2 < 4 = 8 weeks; p < 0.05). This study proposes a novel GBR concept in which rhBMP-2 is applied to collagen membranes outside instead of inside the grafted area, thereby inducing quantitatively and qualitatively enhanced bone regeneration in critical bone defects.

Cell-penetrating peptides (CPPs) have great potential to deliver bioactive agents into cells. Although there have been many recent advances in CPP-related research, it is still important to develop more efficient CPPs. The development of CPPs by in silico methods is a very useful addition to experimental methods, but in many cases it can lead to a large number of false-positive results. In this study, we developed a deep-learning-based CPP prediction method, AiCPP, to develop novel CPPs. AiCPP uses a large number of peptide sequences derived from human-reference proteins as a negative set to reduce false-positive predictions and adopts a method to learn small-length peptide sequence motifs that may have CPP tendencies. Using AiCPP, we found that short peptide sequences derived from amyloid precursor proteins are efficient new CPPs, and experimentally confirmed that these CPP sequences can be further optimized.

We examined how dietary and physical activity behaviors influence fluctuations in blood glucose levels over a seven-day period in people at high risk for diabetes. Twenty-eight participants underwent a mixed meal tolerance test to assess glucose homeostasis at baseline. Subsequently, they wore an accelerometer to assess movement behaviors, recorded their dietary intakes through a mobile phone application, and wore a flash glucose monitoring device that measured glucose levels every 15 min for seven days. Generalized estimating equation models were used to assess the associations of metabolic and lifestyle risk factors with glycemic variability. Higher BMI, amount of body fat, and selected markers of hyperglycemia and insulin resistance from the meal tolerance test were associated with higher mean glucose levels during the seven days. Moderate- to vigorous-intensity physical activity and polyunsaturated fat intake were independently associated with less variation in glucose levels (CV%). Higher protein and polyunsaturated fatty acid intakes were associated with more time-in-range. In contrast, higher carbohydrate intake was associated with less time-in-range. Our findings suggest that dietary composition (a higher intake of polyunsaturated fat and protein and lower intake of carbohydrates) and moderate-to-vigorous physical activity may reduce fluctuations in glucose levels in persons at high risk of diabetes.

Cardiovascular diseases are a global health burden with an increasing prevalence. In addition, various metabolic diseases, such as obesity, diabetes, and hypertension are associated with a higher risk of cardiovascular diseases. Dietary strategies based on healthy foods have been suggested for the prevention or improvement of cardiovascular and metabolic diseases. Grains are the most widely consumed food worldwide, and the preventive effects of whole grains (e.g., oats, barley, and buckwheat) on metabolic diseases have been reported. The germ and bran of grains are rich in compounds, including phytochemicals, vitamins, minerals, and dietary fiber, and these compounds are effective in preventing and improving cardiovascular and metabolic diseases. Thus, this review describes the characteristics and functions of bioactive ingredients in whole grains, focusing on mechanisms by which polyphenols, antioxidants, and dietary fiber contribute to cardiovascular and metabolic diseases, based on preclinical and clinical studies. There is clear evidence for the broad preventive and therapeutic effects of whole grains, supporting the value of early dietary intervention.

Background: The CHADS2, CHA2DS2-VASc, ATRIA, and Essen scores have been developed for predicting vascular outcomes in stroke patients. We investigated the association between these stroke risk scores and unsuccessful recanalization after endovascular thrombectomy (EVT). Methods: From the nationwide multicenter registry (Selection Criteria in Endovascular Thrombectomy and Thrombolytic therapy (SECRET)) (Clinicaltrials.gov NCT02964052), we consecutively included 501 patients who underwent EVT. We identified pre-admission stroke risk scores in each included patient. Results: Among 501 patients who underwent EVT, 410 (81.8%) patients achieved successful recanalization (mTICI ≥ 2b). Adjusting for body mass index and p < 0.1 in univariable analysis revealed the association between all stroke risk scores and unsuccessful recanalization (CHADS2 score: odds ratio (OR) 1.551, 95% confidence interval (CI) 1.198–2.009, p = 0.001; CHA2DS2VASc score: OR 1.269, 95% CI 1.080–1.492, p = 0.004; ATRIA score: OR 1.089, 95% CI 1.011–1.174, p = 0.024; and Essen score: OR 1.469, 95% CI 1.167–1.849, p = 0.001). The CHADS2 score had the highest AUC value and differed significantly only from the Essen score (AUC of CHADS2 score; 0.618, 95% CI 0.554–0.681). Conclusion: All stroke risk scores were associated with unsuccessful recanalization after EVT. Our study suggests that these stroke risk scores could be used to predict recanalization in stroke patients undergoing EVT.

The posture-analyzing and virtual reconstructing device (PAViR) used a Red Green Blue-Depth camera as a sensor and skeleton reconstruction images were produced. This PAViR quickly analyzed the whole posture from multiple repetitive shots without radiation exposure in clothes and provided a virtual skeleton within seconds. This study aims to evaluate the reliability when shooting repeatedly and to assess the validity compared to parameters of full-body, low-dose X-rays (EOSs) when applied as diagnostic imaging. As a prospective and observational study, 100 patients with musculoskeletal pain underwent an EOS to obtain whole body coronal and sagittal images. The outcome measures were human posture parameters, which were divided by the standing plane in both EOSs and PAViRs as follows: (1) a coronal view (asymmetric clavicle height, pelvic oblique, bilateral Q angles of the knee, and center of seventh cervical vertebra-central sacral line (C7-CSL)) and (2) a sagittal view (forward head posture). A validation of the PAViR compared to the EOSs revealed that C7-CSL showed a moderate positive correlation with that of the EOS (r = 0.42, p < 0.01). The forward head posture (r = 0.39, p < 0.01), asymmetric clavicle height (r = 0.37, p < 0.01), and pelvic oblique (r = 0.32, p < 0.01) compared to those of the EOS had slightly positive correlations. The PAViR has excellent intra-rater reliability in people with somatic dysfunction. Except for both Q angles, the PAViR has fair-to-moderate validation when compared to EOS diagnostic imaging in the parameter representing coronal and sagittal imbalance. Although the PAViR system is not yet available in the medical field, it has the potential to become a radiation-free, accessible, and cost-effective postural analysis diagnostic tool after the EOS era.

Periodontitis and rheumatoid arthritis (RA) are inflammatory diseases that share many similarities. We aimed to investigate the associations of periodontitis and oral hygiene status and behaviors with RA in a nationwide general population cohort. Participants from the National Health Screening cohort database of Korea who underwent oral health screening by dentists between 2003 and 2004 were included. The occurrence of RA was analyzed according to the presence of periodontitis, oral health examination findings, and behaviors. Overall, 2,239,586 participants were included. During a median of 16.7 years, RA occurred in 27,029 (1.2%) participants. The risk for incident RA was higher when participants had periodontitis (hazard ratio (HR) 1.2, 95% confidence interval (CI), 1.08−1.24) and an increased number of missing teeth (HR 1.5, 95% CI, 1.38−1.69). In contrast, better oral hygiene behaviors, such as a higher frequency of daily tooth brushing (HR 0.76, 95% CI 0.73–0.79, p for trend

Inotodiol, an oxysterol found only in Chaga mushroom, has received attention from the pharmaceutical industry due to its strong antioxidant and anti-allergic activities. However, the production of inotodiol is still challenging, and its fundamental properties have yet to be investigated. This study aims to develop an efficient method to produce high-purity inotodiol from Chaga mushroom. Then, pure inotodiol was used to assess its physicochemical properties and biological activities. By optimizing the solvent used for extraction and purification, a new method to produce inotodiol was developed with high purity (>97%) and purification yield (33.6%). Inotodiol exhibited a melting point (192.06 °C) much higher than lanosterol and cholesterol. However, the solubility of inotodiol in organic solvents was notably lower than those of the other two sterols. The difference in the hydroxyl group at C-22 of inotodiol has shown the distinctive physicochemical properties of inotodiol compared with cholesterol and lanosterol. Based on those findings, a nonionic surfactant-based delivery system for inotodiol was developed to improve its bioavailability. The inotodiol microemulsion prepared with 1–2% Tween-80 exhibited homogenous droplets with an acceptable diameter (354 to 217 nm) and encapsulation efficiency (85.6–86.9%). The pharmacokinetic analysis of inotodiol microemulsion in oral administration of 4.5 mg/kg exhibited AUC0–24h = 341.81 (ng·h/mL), and Cmax = 88.05 (ng/mL). Notably, when the dose increased from 4.5 to 8.0 mg/kg, the bioavailability of inotodiol decreased from 41.32% to 33.28%. In a mouse model of sepsis, the serum level of interleukin-6 significantly decreased, and the rectal temperature of mice was recovered in the inotodiol emulsion group, indicating that inotodiol microemulsion is an effective oral delivery method. These results could provide valuable information for applying inotodiol in functional food, cosmetic, and pharmaceutical industries.

Each individual has a unique skin tone based on the types and quantities of melanin pigment, and oxidative stress is a key element in melanogenesis regulation. This research sought to understand the in vitro and in vivo antioxidant and depigmenting properties of betel leaves (Piper betle L.) extract (PBL) and the underlying mechanism. Ethyl acetate fractions of PBL (PBLA) demonstrated excellent phenolic content (342 ± 4.02 mgGAE/g) and strong DPPH, ABTS radicals, and nitric oxide (NO) scavenging activity with an IC50 value of 41.52 ± 1.02 μg/mL, 45.60 ± 0.56 μg/mL, and 51.42 ± 1.25 μg/mL, respectively. Contrarily, ethanolic extract of PBL (PBLE) showed potent mushroom, mice, and human tyrosinase inhibition activity (IC50 = 7.72 ± 0.98 μg/mL, 20.59 ± 0.83 μg/mL and 24.78 ± 0.56 μg/mL, respectively). According to gas chromatography–mass spectrometry, PBL is abundant in caryophyllene, eugenol, O-eugenol, 3-Allyl-6-methoxyphenyl acetate, and chavicol. An in vitro and in vivo investigation showed that PBLE suppressed tyrosinase (Tyr), tyrosinase-related protein-1 and -2 (Trp-1 and Trp-2), and microphthalmia-associated transcription factors (MITF), decreasing the formation of melanin in contrast to the untreated control. PBLE reduced the cyclic adenosine monophosphate (cAMP) response to an element-binding protein (CREB) phosphorylation by preventing the synthesis of cAMP. Additionally, it activates c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases (p38), destroying Tyr and MITF and avoiding melanin production. Higher levels of microtubule-associated protein-light chain 3 (LC3-II), autophagy-related protein 5 (Atg5), Beclin 1, and lower levels of p62 demonstrate that PBLE exhibits significant anti-melanogenic effects via an autophagy-induction mechanism, both in vitro and in vivo. Additionally, PBLE significantly reduced the amount of lipid peroxidation while increasing the activity of several antioxidant enzymes in vivo, such as catalase, glutathione, superoxide dismutase, and thioredoxin. PBLE can therefore be employed in topical formulations as a potent skin-whitening agent.

Since conventional ecological remediation technologies are often unreliable and inefficient, the use of phytoremediation, which uses plants to restore damaged or polluted environments, has been actively developed. In particular, phytoremediation for the management of abandoned mines has gained public acceptance due to its aesthetic advantages, environmental friendliness, use of solar energy, and low remediation costs. In this article, we review the current status of the phytoremediation of abandoned mines in Korea and the challenges that are faced. The technical and policy challenges that need to be overcome for the successful application of phytoremediation in Korea are discussed, along with its potential for use in sustainable ecosystem management. To fully deploy phytoremediation technology in old mining areas, further basic and applied research are required.

Although clinical studies have demonstrated that prior use of antiplatelets was associated with decreased blood viscosity (BV) in patients with acute ischemic stroke, the impact of previous anticoagulant use on blood viscosity in cardioembolic stroke with non-valvular AF (NVAF) has not yet been clearly studied. This single-center retrospective observational study aimed to determine the impact of prior antithrombotic (antiplatelet and anticoagulant) use on BV in patients with cardioembolic stroke (CES) due to NVAF. Patients with CES and NVAF were analyzed with the following inclusion criteria: (1) patients over 20 years of age admitted within five days of stroke onset; (2) ischemic stroke presumably due to an NVAF-derived embolus; (3) compatible cortical/subcortical lesion on brain computed tomography or magnetic resonance imaging; (4) hemoglobin level of 10–18 mg/dL; and (5) receiving antiplatelets within five days or anticoagulants within two days if previously medicated. From the screening of 195 patients (22% of the total stroke population during the study period) who had experienced ischemic stroke with AF, 160 were included for the final analysis. Eighty-nine patients (56%) were taking antithrombotics (antiplatelet, 57%; warfarin, 13%; NOACs, 30%) regularly. Compared to patients without previous antithrombotic use, those with previous antithrombotic use (antiplatelets, warfarin, and NOACs) were significantly associated with decreased systolic BV (SBV) and diastolic BV (DBV) (p < 0.036). In multiple linear regression analysis, hematocrit (Hct) level and prior antithrombotic use were significantly associated with decreased SBV and DBV. Hct was positively correlated with increased SBV and DBV. In Hct-adjusted partial correlation analysis, prior uses of any antithrombotic agents were associated with decreased SBV (r < −0.270, p < 0.015) and DBV (r < −0.183, p < 0.044). In conclusion, this study showed that prior antithrombotic use (antiplatelets, VKAs, and NOACs) was associated with decreased SBV and DBV in patients presenting with acute CES secondary to NVAF. Our results indicated that previous use of NOACs may be a useful hemorheological parameter in patients with acute CES due to NVAF. Accumulation of clinical data from a large number of patients with the risk of stroke occurrence, initial stroke severity, and functional outcome is necessary to assess the usefulness of BV.

Background: Lymph node (LN)-related risk factors have been updated to predict long-term outcomes in patients with papillary thyroid carcinoma (PTC). However, those factors’ analytic appropriateness and general applicability must be validated. This study aimed to assess LN-related risk factors, and suggest new LN-related risk categories. Methods: This multicenter observational cohort study included 1232 patients with PTC with N1 disease treated with a total thyroidectomy and neck dissection followed by radioactive iodine remnant ablation. Results: The median follow-up duration was 117 months. In the follow-up period, structural recurrence occurred in 225 patients (18.3%). Among LN-related variables, the presence of extranodal extension (p < 0.001), the maximal diameter of metastatic LN foci (p = 0.029), the number of retrieved LNs (p = 0.003), the number of metastatic LNs (p = 0.003), and the metastatic LN ratio (p < 0.001) were independent risk factors for structural recurrence. Since these factors showed a nonlinear association with the hazard ratio of recurrence-free survival (RFS) rates, we calculated their optimal cutoff values using the K-means clustering algorithm, selecting 0.2 cm and 1.1 cm for the maximal diameter of metastatic LN foci, 4 and 13 for the number of metastatic LN, and 0.28 and 0.58 for the metastatic LN ratio. The RFS curves of each subgroup classified by these newly determined cutoff values showed significant differences (p < 0.001). Each LN risk group also showed significantly different RFS rates from the others (p < 0.001). Conclusions: In PTC patients with an N1 classification, our novel LN-related risk estimates may help predict long-term outcomes and design postoperative management and follow-up strategies. After further validation studies based on independent datasets, these risk categories might be considered when redefining risk stratification or staging systems.

The development of short-wave infrared photodetectors based on various two-dimensional (2D) materials has recently attracted attention because of the ability of these devices to operate at room temperature. Although van der Waals heterostructures of 2D materials with type-II band alignment have significant potential for use in short-wave infrared photodetectors, there is a need to develop photodetectors with high photoresponsivity. In this study, we investigated the photogating of graphene using a monolayer-MoS2/monolayer-MoTe2 van der Waals heterostructure. By stacking MoS2/MoTe2 on graphene, we fabricated a broadband photodetector that exhibited a high photoresponsivity (>100 mA/W) and a low dark current (60 nA) over a wide wavelength range (488–1550 nm).

The residual strength of denting- and fracture-damaged box girders were experimentally and numerically investigated. The experiments were conducted under a pure bending moment using the four-point bending test method. The load, deflection, and strain were measured. The strains of the extension structures were also measured, and the frictional forces between the model and the supported round bar were estimated. Test models consisting of two groups were fabricated. These groups were designed to estimate the residual strength of denting- and fracture-damaged models. The damage was induced by releasing a striker using a drop-testing machine to consider the dynamic effect. Additionally, numerical analyses were performed via a nonlinear finite element analysis, where the measured initial imperfection data and welding residual stresses were considered. The ultimate longitudinal moments that considered the frictional force of the round bars were reduced by 12% (on average) compared with those obtained by neglecting the frictional forces.

Sargassum thunbergii has been traditionally used as an edible and medicinal material in oriental countries. However, the skin-whitening and anti-wrinkling effects of S. thunbergii have not yet been investigated. This study was conducted to establish optimal extraction conditions for the production of bioactive compounds with antioxidant activity as well as skin-whitening and anti-wrinkle effects using ultrasound-assisted extraction (UAE) in S. thunbergii. The extraction time (5.30~18.7 min), extraction temperature (22.4~79.6 °C), and ethanol concentration (0.0~99.5%), which are the main variables of the UAE, were optimized using a central composite design. Quadratic regression equations were derived based on experimental data and showed a high coefficient of determination (R2 > 0.85), demonstrating suitability for prediction. The optimal UAE condition for maximizing all dependent variables, including radical scavenging activity (RSA), tyrosinase inhibitory activity (TIA), and collagenase inhibitory activity (CIA), was identified as an extraction time of 12.0 min, an extraction temperature of 65.2 °C, and ethanol of 53.5%. Under these conditions, the RSA, TIA, and CIA of S. thunbergii extract were 86.5%, 88.3%, and 91.4%, respectively. We also confirmed S. thunbergii extract had inhibitory effects on the mRNA expression of tyrosinase-related protein-1, matrix metalloproteinase-1, and matrix metalloproteinase-9, which are the main genes of melanin synthesis and collagen hydrolysis. Liquid chromatography-tandem mass spectrometry was used to identify the main phenolic compounds in S. thunbergii extract, and caffeic acid was identified as a major peak, demonstrating that high value-added ingredients with skin-whitening and anti-wrinkling effects can be produced from S. thunbergii and used for developing cosmetic materials.

Owing to the hasty growth of communication technologies in the Underwater Internet of Things (UIoT), many researchers and industries focus on enhancing the existing technologies of UIoT systems for developing numerous applications such as oceanography, diver networks monitoring, deep-sea exploration and early warning systems. In a constrained UIoT environment, communication media such as acoustic, infrared (IR), visible light, radiofrequency (RF) and magnet induction (MI) are generally used to transmit information via digitally linked underwater devices. However, each medium has its technical limitations: for example, the acoustic medium has challenges such as narrow-channel bandwidth, low data rate, high cost, etc., and optical medium has challenges such as high absorption, scattering, long-distance data transmission, etc. Moreover, the malicious node can steal the underwater data by employing blackhole attacks, routing attacks, Sybil attacks, etc. Furthermore, due to heavyweight, the existing privacy and security mechanism of the terrestrial internet of things (IoT) cannot be applied directly to UIoT environment. Hence, this paper aims to provide a systematic review of recent trends, applications, communication technologies, challenges, security threats and privacy issues of UIoT system. Additionally, this paper highlights the methods of preventing the technical challenges and security attacks of the UIoT environment. Finally, this systematic review contributes much to the profit of researchers to analyze and improve the performance of services in UIoT applications.

To investigate the association of the oral health parameters with Meniere’s disease in a nationwide population-based longitudinal cohort database. The data of the participants who underwent an oral health screening by dentists in 2003 (n = 2,415,963) were retrieved from the National Health Insurance Database of the Korean National Health Insurance Service. The main outcome was the occurrence of Meniere’s disease, defined as two or more claims of the diagnostic code H810 with a previous audiometric examination. The occurrence of Meniere’s disease was analyzed using a Cox proportional hazard model according to the presence of periodontitis and the oral health examination findings, including missing teeth, the frequency of tooth brushing and dental scaling. Overall, the analysis included 2,240,282 participants. During a median follow-up of 16.7 years, Meniere’s disease developed in 112,106 (5.0%) participants. Poor oral health status was characterized by the presence of periodontitis (adjusted hazard ratio [aHR]: 1.18, 95% confidence interval [CI]: 1.14–1.22, p < 0.001) and an increased number of missing teeth (≥15; aHR: 1.25, 95% CI: 1.18–1.32, p < 0.001) was associated with an increased risk of Meniere’s disease. Better oral hygiene behaviors, such as frequent tooth brushing (≥3 per day; aHR: 0.75, 95% CI: 0.73–0.76, p < 0.001) and dental scaling within 1 year (aHR: 0.98, 95% CI: 0.97–0.99, p = 0.003) were negatively associated with the occurrence of Meniere’s disease. The presence of periodontitis and an increased number of missing teeth may augment the risk of the occurrence of Meniere’s disease. However, maintaining good oral hygiene through tooth brushing and dental scaling may be associated with a decreased risk of Meniere’s disease. Further studies should confirm the association between oral health and Meniere’s disease.

Brain-derived extracellular vesicles (BDEVs) are released from the central nervous system. Brain-related research and diagnostic techniques involving BDEVs have rapidly emerged as a means of diagnosing brain disorders because they are minimally invasive and enable repeatable measurements based on body fluids. However, EVs from various cells and organs are mixed in the blood, acting as potential obstacles for brain diagnostic systems using BDEVs. Therefore, it is important to screen appropriate brain EV markers to isolate BDEVs in blood. Here, we established a strategy for screening potential BDEV biomarkers. To collect various molecular data from the BDEVs, we propose that the sensitivity and specificity of the diagnostic system could be enhanced using machine learning and AI analysis. This BDEV-based diagnostic strategy could be used to diagnose various brain diseases and will help prevent disease through early diagnosis and early treatment.

The purpose of this study was to enhance the accuracy of the calorific value estimation of coal by applying data preprocessing methods in laser-induced breakdown spectroscopy (LIBS). The Savitzky–Golay (SG)-smoothing and SG derivative preprocessing methods were adopted to improve the accuracy of the prediction model. The relationship among the original, SG-smoothing-pretreated, and SG derivative-pretreated LIBS data and their elemental concentrations were determined using the partial least squares regression (PLSR) model. In order to compare the reliability of each PLSR model, the coefficient of determination, root mean square error (RMSE), relative error, and RMSE average were used. As a result, the reliability of the PLSR model processed with the SG derivative method was the highest, and the root mean square average was the lowest among the three models. The predictability of the concentration of each element using the PLSR model pre-processed by the SG derivative was confirmed with the residual predictive deviation parameter. The predicted calorific value was estimated from the predicted concentrations of elements in coal using Dulong’s equation. The PLSR model pretreated by the SG derivative showed the lowest error compared to the calorific value of mixed coals obtained via the chemical analysis.

Background: We evaluated vaccine effectiveness (VE) against infections with SARS-CoV-2 variants of concern in Seoul, the capital of the Republic of Korea, having the highest population density in the country, under real-world conditions. Methods: We evaluated the reduction in the effectiveness of mRNA and viral-vector COVID-19 vaccines against infection by the SARS-CoV-2 delta variant in a subpopulation from April 2021 to July 2021 who visited screening clinics in Seoul using a test-negative case-control study design. Moreover, we conducted a case-control study matching the ten-year-old age group, sex, healthcare workers, and five districts of Seoul, which are considered confounding factors. Results: The full VE in the pre-delta-dominant period was 95.0% (95% confidence interval [CI]: 91.2–97.2); however, it decreased to 61.1% (95% CI: 53.2–67.6) during the delta-dominant period. Notably, we found that COVID-19 VE was significantly decreased in individuals aged ≥80 years (52.9%, 95% CI: −9.9–79.8), men (50.6 %, 95% CI: 39.4–59.8), and asymptomatic individuals (49.8%, 95% CI: 36.5–60.3) during the widespread SARS-CoV-2 delta variant circulation. Conclusions: Vaccine-mediated protection drastically declined during the delta-dominant period and in vulnerable groups. This study suggests the requirement for additional countermeasures, such as the administration of a booster vaccine, in vulnerable groups based on age, sex, and symptomatic manifestation.

This study aimed to examine the multi-faceted lifestyle profiles of community-dwelling middle- and older-aged adults based on their physical activity, participation in various activities, and nutrition. It identified the association of lifestyle profiles with demographic variables, quality of life, and mental health. The analysis included 569 participants (mean age = 60.2; SD = 4.3). Latent profile analysis identified three distinctive lifestyle profiles: “inactive and unbalanced” (36.4%), “basic life maintenance” (54.6%), and “active and balanced” (9.1%). Sex (p < 0.001), age (p < 0.001), and regular medication intake (p < 0.01) were statistically significantly different among the three profiles. Of the “inactive and unbalanced” lifestyle group, 63.3% of it was comprised of by females, and a relatively large distribution was aged over 65. In the “basic life maintenance” subgroup, males showed a relatively large distribution, and 92.6% of participants were aged 55–64. People with active and balanced lifestyles demonstrated high quality of life levels (p < 0.001) and low loneliness levels (p < 0.01). Multinomial logistic regression revealed a statistically significant positive association between lifestyle profiles and quality of life (p < 0.001) as well as mental health (p < 0.01). Therefore, health promotion that considers multi-faceted lifestyle factors would need to improve health and quality of life among community-dwelling middle- and older-aged adults in South Korea.

This systematic review and meta-analysis aimed to investigate the status of emotional labor and its related factors among nurses in general hospital settings in Korea. A total of seven electronic databases were comprehensively searched to find relevant cross-sectional studies published up to 28 January 2021. The meta-analysis was performed using Stata version 13.1. In total, 131 studies were included. The population showed a standardized mean difference of 3.38 (95% confidence interval, 3.34 to 3.42) in emotional labor assessed by a 1–5 Likert scale. The level of emotional labor had significant negative correlations with job satisfaction, social support, organizational engagement, coworker support, resilience, and nurses’ work environment, while it had significant positive correlations with emotional labor and burnout, turnover intention, and job stress. Although the methodological quality of the included studies was generally good, 24 of the included studies (18.32%) were evaluated as lacking generalization potential or otherwise as unclear. In conclusion, nurses in general hospital settings in Korea experience mild-to-moderate levels of emotional labor. There is some evidence that the emotional labor of nurses and its detrimental effects can be buffered at both the individual and hospital levels, and future research should focus on developing targeted interventions and evaluating their effectiveness.

Terahertz (THz) imaging techniques are attractive for a wide range of applications, such as non-destructive testing, biological sensing, and security imaging. We investigate practical issues in THz imaging systems based on a solid immersion lens (SIL). The system stability in terms of longitudinal misalignment of the SIL is experimentally verified by showing that the diffraction-limited sub-wavelength beam size (0.7 λ) is maintained as long as the SIL is axially located within the depth-of-focus (~13 λ) of the objective lens. The origin of the fringe patterns, which are undesirable but inevitable in THz imaging systems that use continuous waves, is analytically studied, and a method for minimizing the interference patterns is proposed. By combining two THz images obtained at different axial positions of the object and separated by λ/4, the interference patterns are significantly reduced, and the information hidden under the interference patterns is unveiled. The broad applicability of the proposed method is demonstrated by imaging objects with different surface profiles. Our work proves that the resolution of conventional THz imaging systems can easily be enhanced by simply inserting a SIL in front of the object with high tolerance in the longitudinal misalignment and provides a method enabling THz imaging for objects with different surface profiles.

Social mixing is one of the key objectives of the housing policy in OECD countries. The Low-Income Housing Tax Credit (LIHTC) program, the largest affordable housing construction program in the US since 1986, has recently set creating mixed-income communities as one of the standards. As a project-based program, LIHTC developments are likely to influence residential mobility, however, little is known about its empirical effects. This study investigated whether new LIHTC projects are effective at attracting heterogeneous income groups to LIHTC neighborhoods, thereby contributing to creating mixed-income communities. Using unique individual-level household movement data combined with origin–destination neighborhood characteristics, we developed zero-inflated negative binomial (ZINB) models to analyze the LIHTC’s impact on residential mobility patterns in Franklin County, Ohio, US, from 2011 to 2015. The results suggest that the LIHTC attracts low-income households while deterring higher-income families, and therefore the program is not proved to be effective at creating mixed-income neighborhoods.

The ability to estimate stature can be important in the identification of skeletal remains. This study aims to develop a Korean-specific equation predicting stature using radiographic measurements in the contemporary Korean population. 200 healthy Korean adults, including 102 males and 98 females, were randomly selected (age, range 20–86 years). The first and second metatarsals of the foot were measured by a standing X-ray using a digital medical image viewer. The result showed a statistically significant correlation between metatarsal length and stature in Korean populations (male, R = 0.46, p &lt, 0.001, female, R = 0.454, p &lt, 0.001). Values of correlation coefficients (R) of the equations were 0.431 to 0.477. Compared to equations derived from other races, the Korean-specific equation showed significantly lower error values for estimating the actual height of Koreans through cross-validation. In conclusion, this study is the first to propose a Korean-specific regression formula for estimating stature using metatarsal length and a verified formula for precise application to the Korean population. However, given the relatively low correlation coefficient, the stature estimation formula derived from this study can be utilized when other bones that allow more accurate stature estimation are not available.

Reactive oxygen species (ROS) and intracellular iron levels are critical modulators of lipid peroxidation that trigger iron-dependent non-apoptotic ferroptosis in myocardial ischemia-reperfusion (I/R) injury. Histochrome (HC), with a potent antioxidant moiety and iron-chelating capacity, is now available in clinical practice. However, limited data are available about the protective effects of HC on ferroptotic cell death in myocardial I/R injury. In this study, we investigated whether the intravenous administration of HC (1 mg/kg) prior to reperfusion could decrease myocardial damage by reducing ferroptosis. Rats undergoing 60 min of ischemia and reperfusion were randomly divided into three groups as follows: (1) Sham, (2) I/R control, and (3) I/R + HC. Serial echocardiography up to four weeks after I/R injury showed that intravenous injection of HC significantly improved cardiac function compared to the I/R controls. In addition, the hearts of rats who received intravenous injection of HC exhibited significantly lower cardiac fibrosis and higher capillary density. HC treatment decreased intracellular and mitochondrial ROS levels by upregulating the expression of nuclear factor erythroid 2-related factor (Nrf2) and its downstream genes. HC also inhibited erastin- and RSL3-induced ferroptosis in rat neonatal cardiomyocytes by maintaining the intracellular glutathione level and through upregulated activity of glutathione peroxidase 4. These findings suggest that early intervention with HC before reperfusion rescued myocardium from I/R injury by preventing ferroptotic cell death. Therefore, HC is a promising therapeutic option to provide secondary cardioprotection in patients who undergo coronary reperfusion therapy.

Insulin-like growth factor-1 (IGF-1) primarily increases the release of gamma-aminobutyric acid (GABA) in neurons, moreover, it is responsible for the promotion of longitudinal growth in children and adolescents. Therefore, in this study, we investigated whether exogenous GABA supplementation activates IGF-mediated growth performance. Zebrafish larvae treated with GABA at three days post fertilization (dpf) showed a significant increase in the total body length from 6 to 12 dpf through upregulation of growth-stimulating genes, including IGF-1, growth hormone-1 (GH-1), growth hormone receptor-1 (GHR-1), and cholecystokinin A (CCKA). In particular, at 9 dpf, GABA increased total body length from 3.60 ± 0.02 to 3.79 ± 0.03, 3.89 ± 0.02, and 3.92 ± 0.04 mm at concentrations of 6.25, 12.5, and 25 mM, and the effect of GABA at 25 mM was comparable to 4 mM β-glycerophosphate (GP)-treated larvae (3.98 ± 0.02 mm). Additionally, the highest concentration of GABA (50 mM) -induced death in 50% zebrafish larvae at 12 dpf. GABA also enhanced IGF-1 expression and secretion in preosteoblast MC3T3-E1 cells, concomitant with high levels of the IGF-1 receptor gene (IGF-1R). In zebrafish larvae, the GABA-induced growth rate was remarkably decreased in the presence of an IGF-1R inhibitor, picropodophyllin (PPP), which indicates that GABA-induced IGF-1 enhances growth rate via IGF-1R. Furthermore, we investigated the effect of GABA receptors on growth performance along with IGF-1 activation. Inhibitors of GABAA and GABAB receptors, namely bicuculline and CGP 46381, respectively, considerably inhibited GABA-induced growth rate in zebrafish larvae accompanied by a marked decrease in the expression of growth-stimulating genes, including IGF-1, GH-1, GHR-1, and CCKA, but not with an inhibitor of GABAC receptor, TPMPA. Additionally, IGF-1 and IGF-1R expression was impaired in bicuculline and CGP 46381-treated MC3T3-E1 cells, but not in the cells treated with TPMPA. Furthermore, treatment with bicuculline and CGP 46381 significantly downregulated GABA-induced IGF-1 release in MC3T3-E1 cells. These data indicate that GABA stimulates IGF-1 release via GABAA and GABAB receptors and leads to growth promotion performance via IGF-1R.

A non-solvent synthesis of alkali metal-doped PdCu-Pd-Cu@C is presented that needs no mechanical grinding and utilizes heat treatment under an N2 gas flow. Pluronic® F127 is used to generate pores and a high surface area, and tannic acid is used as a carbon source for the PdCu-Pd-Cu@C nanocatalysts. Because some C is transferred to organic compounds during the nitrogen heat treatment, this demonstrated the advantage of raising the weight ratio of active metals comparatively. The PdCu-Pd-Cu@C nanocatalyst developed in this study outperformed commercial Pd/C catalysts by bimetallic PdCu-Pd-Cu nanoparticles and Pd nanoparticles in terms of catalytic activity (selectivity of commercial Pd/C: 45%, PdCu-Pd-Cu@C nanocatalyst: 76%). The alkali metal dopants increase the selectivity of the final product on the PdCu-Pd-Cu@C surface because they are electron-rich, which assists in the adsorption of the substrate (selectivity of PdCu-Pd-Cu@C nanocatalyst: 76%, K-doped PdCu-Pd-Cu@C nanocatalysts: 90%). Furthermore, even after being reused 5 times in this research, the final catalytic performance was comparable to that of the initial catalyst.

Accurate bracket placement is essential for successful orthodontic treatment. An indirect bracket bonding system (IDBS) has been developed to ensure proper bracket positioning with three-dimensional computer-aided transfer jigs. The purpose of this study was to investigate the accuracy of bracket positioning by a one-body transfer jig according to the tooth type and presence/absence of a resin base. In total, 506 teeth from 20 orthodontic patients were included in this study. After initial dental models were scanned, virtual setup and bracket positioning procedures were performed with 3D software. Transfer jigs and RP models were fabricated with a 3D printer, and brackets were bonded to the RP model with or without resin base fabrication. The best-fit method of 3D digital superimposition was used to evaluate the lineal and angular accuracy of the actual bracket position compared to a virtual bracket position. Although all the measurements showed significant differences in position, they were clinically acceptable. Regarding the tooth types, premolars and molars showed higher accuracy than anterior teeth. The presence or absence of a resin base did not consistently affect the accuracy. In conclusion, the proper application of IDBS should be performed considering the errors, and resin base fabrication might not be essential in ensuring high-accuracy IDBS.

Due to its high prevalence, screening for hepatic fibrosis in the low-risk population is called for action in the primary care clinic. However, current guidelines provide conflicting recommendations on populations to be screened. We aimed to identify the target populations that would most benefit from screening for hepatic fibrosis in clinical practice. This study examined 1288 subjects who underwent magnetic resonance elastography. The diagnostic performance of the Fibrosis-4 (FIB-4) index and NAFLD fibrosis score was compared in the following groups: (1) ultrasonography (USG)-diagnosed NAFLD, (2) elevated liver enzyme, (3) metabolic syndrome, (4) impaired fasting glucose, and (5) type 2 diabetes regardless of fatty liver. Decision curve analysis was performed to express the net benefit of groups over a range of probability thresholds (Pts). The diabetes group showed a better area under the receiver operating characteristic curve (AUROC: 0.69) compared with subjects in the USG-diagnosed NAFLD (AUROC: 0.57) and elevated liver enzyme (AUROC: 0.55) groups based on the FIB-4 index. In decision curve analysis, the diabetes group showed the highest net benefit for the detection of significant fibrosis across a wide range of Pts. Patients with diabetes, even in the absence of fatty liver, would be preferable for hepatic fibrosis screening in low-risk populations.

The orthodontic treatment of patients having temporomandibular disorders are some of the most complicated cases to treat. The positions of the mandibular condyles are often unstable, which means clinicians find it difficult to have definite criteria for making an accurate and reliable orthodontic diagnosis. This article reports the orthodontic treatment of a patient showing skeletal Class II and temporomandibular disorders with condylar resorption. To stabilize her condylar position and to relieve her symptoms in the temporomandibular joint, a stabilization splint was used before orthodontic tooth movement. After the splint therapy, the patient exhibited significantly increased open bite and a more severe Class II occlusal relationship as her mandibular condyles were seated anteriorly and superiorly in the articular fossae. The occlusion and facial esthetics of the patient were improved by orthodontic camouflage treatment with the proper use of temporary skeletal anchorage devices and treatment mechanics.

Protrusion can occur after correction of the anterior crossbite in Class III malocclusions. Four-premolar extractions might be indicated if the patients asked for a profile reduction. Two similar Class III anterior crossbite cases illustrate how the skeletal anchorage can prevent protrusion after anterior crossbite correction and the need for four- premolar extractions, as in the first case. The use of extra-radicular miniscrews at the infrazygomatic crest and buccal shelf are recommended for whole arch distalization of the maxillary and mandibular arches to reduce protrusion after anterior crossbite correction. It is an effective and efficient treatment alternative to extraction therapy for the protrusion after anterior crossbite correction. Long-term follow-up records show encouraging results supporting this paradigm shift in anterior crossbite correction with extra-radicular miniscrews.