Choline kinase alpha 2 acts as a protein kinase to promote lipolysis of lipid droplets.

Lipid droplets are important for cancer cell growth and survival. However, the mechanism underlying the initiation of lipid droplet lipolysis is not well understood. We demonstrate here that glucose deprivation induces the binding of choline kinase (CHK) α2 to lipid droplets, which is sequentially mediated by AMPK-dependent CHKα2 S279 phosphorylation and KAT5-dependent CHKα2 K247 acetylation. Importantly, CHKα2 with altered catalytic domain conformation functions as a protein kinase and phosphorylates PLIN2 at Y232 and PLIN3 at Y251. The phosphorylated PLIN2/3 dissociate from lipid droplets and are degraded by Hsc70-mediated autophagy, thereby promoting lipid droplet lipolysis, fatty acid oxidation, and brain tumor growth. In addition, levels of CHKα2 S279 phosphorylation, CHKα2 K247 acetylation, and PLIN2/3 phosphorylation are positively correlated with one another in human glioblastoma specimens and are associated with poor prognosis in glioblastoma patients. These findings underscore the role of CHKα2 as a protein kinase in lipolysis and glioblastoma development.

The gluconeogenic enzyme PCK1 phosphorylates INSIG1/2 for lipogenesis.

Cancer cells increase lipogenesis for their proliferation and the activation of sterol regulatory element-binding proteins (SREBPs) has a central role in this process. SREBPs are inhibited by a complex composed of INSIG proteins, SREBP cleavage-activating protein (SCAP) and sterols in the endoplasmic reticulum. Regulation of the interaction between INSIG proteins and SCAP by sterol levels is critical for the dissociation of the SCAP-SREBP complex from the endoplasmic reticulum and the activation of SREBPs1,2. However, whether this protein interaction is regulated by a mechanism other than the abundance of sterol-and in particular, whether oncogenic signalling has a role-is unclear. Here we show that activated AKT in human hepatocellular carcinoma (HCC) cells phosphorylates cytosolic phosphoenolpyruvate carboxykinase 1 (PCK1), the rate-limiting enzyme in gluconeogenesis, at Ser90. Phosphorylated PCK1 translocates to the endoplasmic reticulum, where it uses GTP as a phosphate donor to phosphorylate INSIG1 at Ser207 and INSIG2 at Ser151. This phosphorylation reduces the binding of sterols to INSIG1 and INSIG2 and disrupts the interaction between INSIG proteins and SCAP, leading to the translocation of the SCAP-SREBP complex to the Golgi apparatus, the activation of SREBP proteins (SREBP1 or SREBP2) and the transcription of downstream lipogenesis-related genes, proliferation of tumour cells, and tumorigenesis in mice. In addition, phosphorylation of PCK1 at Ser90, INSIG1 at Ser207 and INSIG2 at Ser151 is not only positively correlated with the nuclear accumulation of SREBP1 in samples from patients with HCC, but also associated with poor HCC prognosis. Our findings highlight the importance of the protein kinase activity of PCK1 in the activation of SREBPs, lipogenesis and the development of HCC.

EGFR-Phosphorylated Platelet Isoform of Phosphofructokinase 1 Promotes PI3K Activation.

EGFR activates phosphatidylinositide 3-kinase (PI3K), but the mechanism underlying this activation is not completely understood. We demonstrated here that EGFR activation resulted in lysine acetyltransferase 5 (KAT5)-mediated K395 acetylation of the platelet isoform of phosphofructokinase 1 (PFKP) and subsequent translocation of PFKP to the plasma membrane, where the PFKP was phosphorylated at Y64 by EGFR. Phosphorylated PFKP binds to the N-terminal SH2 domain of p85α, which is distinct from binding of Gab1 to the C-terminal SH2 domain of p85α, and recruited p85α to the plasma membrane resulting in PI3K activation. PI3K-dependent AKT activation results in enhanced phosphofructokinase 2 (PFK2) phosphorylation and production of fructose-2,6-bisphosphate, which in turn promotes PFK1 activation. PFKP Y64 phosphorylation-enhanced PI3K/AKT-dependent PFK1 activation and GLUT1 expression promoted the Warburg effect, tumor cell proliferation, and brain tumorigenesis. These findings underscore the instrumental role of PFKP in PI3K activation and enhanced glycolysis through PI3K/AKT-dependent positive-feedback regulation.

Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy.

Overcoming metabolic stress is a critical step in tumor growth. Acetyl coenzyme A (acetyl-CoA) generated from glucose and acetate uptake is important for histone acetylation and gene expression. However, how acetyl-CoA is produced under nutritional stress is unclear. We demonstrate here that glucose deprivation results in AMP-activated protein kinase (AMPK)-mediated acetyl-CoA synthetase 2 (ACSS2) phosphorylation at S659, which exposed the nuclear localization signal of ACSS2 for importin α5 binding and nuclear translocation. In the nucleus, ACSS2 binds to transcription factor EB and translocates to lysosomal and autophagy gene promoter regions, where ACSS2 incorporates acetate generated from histone acetylation turnover to locally produce acetyl-CoA for histone H3 acetylation in these regions and promote lysosomal biogenesis, autophagy, cell survival, and brain tumorigenesis. In addition, ACSS2 S659 phosphorylation positively correlates with AMPK activity in glioma specimens and grades of glioma malignancy. These results underscore the significance of nuclear ACSS2-mediated histone acetylation in maintaining cell homeostasis and tumor development.

Phosphoglycerate Kinase 1 Phosphorylates Beclin1 to Induce Autophagy.

Autophagy is crucial for maintaining cell homeostasis. However, the precise mechanism underlying autophagy initiation remains to be defined. Here, we demonstrate that glutamine deprivation and hypoxia result in inhibition of mTOR-mediated acetyl-transferase ARD1 S228 phosphorylation, leading to ARD1-dependent phosphoglycerate kinase 1 (PGK1) K388 acetylation and subsequent PGK1-mediated Beclin1 S30 phosphorylation. This phosphorylation enhances ATG14L-associated class III phosphatidylinositol 3-kinase VPS34 activity by increasing the binding of phosphatidylinositol to VPS34. ARD1-dependent PGK1 acetylation and PGK1-mediated Beclin1 S30 phosphorylation are required for glutamine deprivation- and hypoxia-induced autophagy and brain tumorigenesis. Furthermore, PGK1 K388 acetylation levels correlate with Beclin1 S30 phosphorylation levels and poor prognosis in glioblastoma patients. Our study unearths an important mechanism underlying cellular-stress-induced autophagy initiation in which the protein kinase activity of the metabolic enzyme PGK1 plays an instrumental role and reveals the significance of the mutual regulation of autophagy and cell metabolism in maintaining cell homeostasis.

A New Back-End-Of-Line Ferroelectric Field-Effect Transistor Platform via Laser Processing.

The discovery of ferroelectricity in hafnia-based materials has revitalized interest in realizing ferroelectric field-effect transistors (FeFETs) due to its compatibility with modern microelectronics. Furthermore, low-temperature processing by atomic layer deposition offers promise for realizing monolithic three-dimensional (M3D) integration toward energy- and area-efficient computing paradigms. However, integrating ferroelectrics with channel materials in FeFETs for M3D integration remains challenging due to the dual requirement of a high-quality ferroelectric-channel interface and low-power operation, all while maintaining back-end-of-line (BEOL)-compatible fabrication temperatures. Recent studies on 2D semiconductors and metal oxide channels highlight these challenges. Polycrystalline silicon (poly-Si), a channel material long integrated into the semiconductor industry, presents a promising alternative; however, its high fabrication temperature has hindered its applications to M3D integration. To overcome this challenge, we demonstrates a BEOL-compatible FeFET platform using poly-Si channels fabricated via locally-confined laser thermal processing and hafnia-based ferroelectrics by low-temperature atomic layer deposition with wafer-scale uniformity. The local nature of the laser processing mitigates the trade-off between the high-temperature crystallization for the quality of the interface and BEOL thermal budget constraints. The laser-processed FeFETs boast the largest effective memory widow for all BEOL-compatible FeFETs. Moreover, the fabricated FeFETs are integrated into wafer-scale synaptic arrays for neuromorphic computing, achieving record-high energy efficiency. Therefore, this work establishes a promising BEOL-compatible FeFET materials platform toward M3D integration.

Recommended implementation of quantitative susceptibility mapping for clinical research in the brain: A consensus of the ISMRM electro-magnetic tissue properties study group.

This article provides recommendations for implementing QSM for clinical brain research. It is a consensus of the International Society of Magnetic Resonance in Medicine, Electro-Magnetic Tissue Properties Study Group. While QSM technical development continues to advance rapidly, the current QSM methods have been demonstrated to be repeatable and reproducible for generating quantitative tissue magnetic susceptibility maps in the brain. However, the many QSM approaches available have generated a need in the neuroimaging community for guidelines on implementation. This article outlines considerations and implementation recommendations for QSM data acquisition, processing, analysis, and publication. We recommend that data be acquired using a monopolar 3D multi-echo gradient echo (GRE) sequence and that phase images be saved and exported in Digital Imaging and Communications in Medicine (DICOM) format and unwrapped using an exact unwrapping approach. Multi-echo images should be combined before background field removal, and a brain mask created using a brain extraction tool with the incorporation of phase-quality-based masking. Background fields within the brain mask should be removed using a technique based on SHARP or PDF, and the optimization approach to dipole inversion should be employed with a sparsity-based regularization. Susceptibility values should be measured relative to a specified reference, including the common reference region of the whole brain as a region of interest in the analysis. The minimum acquisition and processing details required when reporting QSM results are also provided. These recommendations should facilitate clinical QSM research and promote harmonized data acquisition, analysis, and reporting.

Comparison between R2'-based and R2*-based χ-separation methods: A clinical evaluation in individuals with multiple sclerosis.

Susceptibility source separation, or χ-separation, estimates diamagnetic (χdia) and paramagnetic susceptibility (χpara) signals in the brain using local field and R2' (= R2* - R2) maps. Recently proposed R2*-based χ-separation methods allow for χ-separation using only multi-echo gradient echo (ME-GRE) data, eliminating the need for additional data acquisition for R2 mapping. Although this approach reduces scan time and enhances clinical utility, the impact of missing R2 information remains a subject of exploration. In this study, we evaluate the viability of two previously proposed R2*-based χ-separation methods as alternatives to their R2'-based counterparts: model-based R2*-χ-separation versus χ-separation and deep learning-based χ-sepnet-R2* versus χ-sepnet-R2'. Their performances are assessed in individuals with multiple sclerosis (MS), comparing them with their corresponding R2'-based counterparts (i.e., R2*-χ-separation vs. χ-separation and χ-sepnet-R2* vs. χ-sepnet-R2'). The evaluations encompass qualitative visual assessments by experienced neuroradiologists and quantitative analyses, including region of interest analyses and linear regression analyses. Qualitatively, R2*-χ-separation tends to report higher χpara and χdia values compared with χ-separation, leading to less distinct lesion contrasts, while χ-sepnet-R2* closely aligns with χ-sepnet-R2'. Quantitative analysis reveals a robust correlation between both R2*-based methods and their R2'-based counterparts (r ≥ 0.88). Specifically, in the whole-brain voxels, χ-sepnet-R2* exhibits higher correlation and better linearity than R2*-χ-separation (χdia/χpara from R2*-χ-separation: r = 0.88/0.90, slope = 0.79/0.86; χdia/χpara from χ-sepnet-R2*: r = 0.90/0.92, slope = 0.99/0.97). In MS lesions, both R2*-based methods display comparable correlation and linearity (χdia/χpara from R2*-χ-separation: r = 0.90/0.91, slope = 0.98/0.91; χdia/χpara from χ-sepnet-R2*: r = 0.88/0.88, slope = 0.91/0.95). Notably, χ-sepnet-R2* demonstrates negligible offsets, whereas R2*-χ-separation exhibits relatively large offsets (0.02 ppm in the whole brain and 0.01 ppm in the MS lesions), potentially indicating the false presence of myelin or iron in MS lesions. Overall, both R2*-based χ-separation methods demonstrated their viability as alternatives to their R2'-based counterparts. χ-sepnet-R2* showed better alignment with its R2'-based counterpart with minimal susceptibility offsets, compared with R2*-χ-separation that reported higher χpara and χdia values compared with R2'-based χ-separation.

A human brain atlas of χ-separation for normative iron and myelin distributions.

Iron and myelin are primary susceptibility sources in the human brain. These substances are essential for a healthy brain, and their abnormalities are often related to various neurological disorders. Recently, an advanced susceptibility mapping technique, which is referred to as χ-separation (pronounced as "chi"-separation), has been proposed, successfully disentangling paramagnetic iron from diamagnetic myelin. This method provided a new opportunity for generating high-resolution iron and myelin maps of the brain. Utilizing this technique, this study constructs a normative χ-separation atlas from 106 healthy human brains. The resulting atlas provides detailed anatomical structures associated with the distributions of iron and myelin, clearly delineating subcortical nuclei, thalamic nuclei, and white matter fiber bundles. Additionally, susceptibility values in a number of regions of interest are reported along with age-dependent changes. This atlas may have direct applications such as localization of subcortical structures for deep brain stimulation or high-intensity focused ultrasound and also serve as a valuable resource for future research.

Multifunctional HfAlO thin film: Ferroelectric tunnel junction and resistive random access memory.

This study presents findings indicating that the ferroelectric tunnel junction (FTJ) or resistive random-access memory (RRAM) in one cell can be intentionally selected depending on the application. The HfAlO film annealed at 700 °C shows stable FTJ characteristics and can be converted into RRAM by forming a conductive filament inside the same cell, that is, the process of intentionally forming a conductive filament is the result of defect generation and redistribution, and applying compliance current prior to a hard breakdown event of the dielectric film enables subsequent RRAM operation. The converted RRAM demonstrated good memory performance. Through current-voltage fitting, it was confirmed that the two resistance states of the FTJ and RRAM had different transport mechanisms. In the RRAM, the 1/f noise power of the high-resistance state (HRS) was about ten times higher than that of the low-resistance state (LRS). This is because the noise components increase due to the additional current paths in the HRS. The 1/f noise power according to resistance states in the FTJ was exactly the opposite result from the case of the RRAM. This is because the noise component due to the Poole-Frenkel emission is added to the noise component due to the tunneling current in the LRS. In addition, we confirmed the potentiation and depression characteristics of the two devices and further evaluated the accuracy of pattern recognition through a simulation by considering a dataset from the Modified National Institute of Standards and Technology.

Enhancing deep learning classification performance of tongue lesions in imbalanced data: mosaic-based soft labeling with curriculum learning.

BACKGROUND: Oral potentially malignant disorders (OPMDs) are associated with an increased risk of cancer of the oral cavity including the tongue. The early detection of oral cavity cancers and OPMDs is critical for reducing cancer-specific morbidity and mortality. Recently, there have been studies to apply the rapidly advancing technology of deep learning for diagnosing oral cavity cancer and OPMDs. However, several challenging issues such as class imbalance must be resolved to effectively train a deep learning model for medical imaging classification tasks. The aim of this study is to evaluate a new technique of artificial intelligence to improve the classification performance in an imbalanced tongue lesion dataset. METHODS: A total of 1,810 tongue images were used for the classification. The class-imbalanced dataset consisted of 372 instances of cancer, 141 instances of OPMDs, and 1,297 instances of noncancerous lesions. The EfficientNet model was used as the feature extraction model for classification. Mosaic data augmentation, soft labeling, and curriculum learning (CL) were employed to improve the classification performance of the convolutional neural network. RESULTS: Utilizing a mosaic-augmented dataset in conjunction with CL, the final model achieved an accuracy rate of 0.9444, surpassing conventional oversampling and weight balancing methods. The relative precision improvement rate for the minority class OPMD was 21.2%, while the relative [Formula: see text] score improvement rate of OPMD was 4.9%. CONCLUSIONS: The present study demonstrates that the integration of mosaic-based soft labeling and curriculum learning improves the classification performance of tongue lesions compared to previous methods, establishing a foundation for future research on effectively learning from imbalanced data.

Depth-wise profiles of iron and myelin in the cortex and white matter using χ-separation: A preliminary study.

The in-vivo profiling of iron and myelin across cortical depths and underlying white matter has important implications for advancing knowledge about their roles in brain development and degeneration. Here, we utilize χ-separation, a recently-proposed advanced susceptibility mapping that creates positive (χpos) and negative (χneg) susceptibility maps, to generate the depth-wise profiles of χpos and χneg as surrogate biomarkers for iron and myelin, respectively. Two regional sulcal fundi of precentral and middle frontal areas are profiled and compared with findings from previous studies. The results show that the χpos profiles peak at superificial white matter (SWM), which is an area beneath cortical gray matter known to have the highest accumulation of iron within the cortex and white matter. On the other hand, the χneg profiles increase in SWM toward deeper white matter. These characteristics in the two profiles are in agreement with histological findings of iron and myelin. Furthermore, the χneg profiles report regional differences that agree with well-known distributions of myelin concentration. When the two profiles are compared with those of QSM and R2*, different shapes and peak locations are observed. This preliminary study offers an insight into one of the possible applications of χ-separation for exploring microstructural information of the human brain, as well as clinical applications in monitoring changes of iron and myelin in related diseases.

χ-Separation Imaging for Diagnosis of Multiple Sclerosis versus Neuromyelitis Optica Spectrum Disorder.

Background Use of χ-separation imaging can provide surrogates for iron and myelin that relate closely to abnormal changes in multiple sclerosis (MS) lesions. Purpose To evaluate the appearances of MS and neuromyelitis optica spectrum disorder (NMOSD) brain lesions on χ-separation maps and explore their diagnostic value in differentiating the two diseases in comparison with previously reported diagnostic criteria. Materials and Methods This prospective study included individuals with MS or NMOSD who underwent χ-separation imaging from October 2017 to October 2020. Positive (χpos) and negative (χneg) susceptibility were estimated separately by using local frequency shifts and calculating R2' (R2' = R2* - R2). R2 mapping was performed with a machine learning approach. For each lesion, presence of the central vein sign (CVS) and paramagnetic rim sign (PRS) and signal characteristics on χneg and χpos maps were assessed and compared. For each participant, the proportion of lesions with CVS, PRS, and hypodiamagnetism was calculated. Diagnostic performances were assessed using receiver operating characteristic (ROC) curve analysis. Results A total of 32 participants with MS (mean age, 34 years ± 10 [SD]; 25 women, seven men) and 15 with NMOSD (mean age, 52 years ± 17; 14 women, one man) were evaluated, with a total of 611 MS and 225 NMOSD brain lesions. On the χneg maps, 80.2% (490 of 611) of MS lesions were categorized as hypodiamagnetic versus 13.8% (31 of 225) of NMOSD lesions (P < .001). Lesion appearances on the χpos maps showed no evidence of a difference between the two diseases. In per-participant analysis, participants with MS showed a higher proportion of hypodiamagnetic lesions (83%; IQR, 72-93) than those with NMOSD (6%; IQR, 0-14; P < .001). The proportion of hypodiamagnetic lesions achieved excellent diagnostic performance (area under the ROC curve, 0.96; 95% CI: 0.91, 1.00). Conclusion On χ-separation maps, multiple sclerosis (MS) lesions tend to be hypodiamagnetic, which can serve as an important hallmark to differentiate MS from neuromyelitis optica spectrum disorder. © RSNA, 2022 Supplemental material is available for this article.

Exsolution of Ru Nanoparticles on BaCe0.9 Y0.1 O3-δ Modifying Geometry and Electronic Structure of Ru for Ammonia Synthesis Reaction Under Mild Conditions.

Green ammonia is an efficient, carbon-free energy carrier and storage medium. The ammonia synthesis using green hydrogen requires an active catalyst that operates under mild conditions. The catalytic activity can be promoted by controlling the geometry and electronic structure of the active species. An exsolution process is implemented to improve catalytic activity by modulating the geometry and electronic structure of Ru. Ru nanoparticles exsolved on a BaCe0.9 Y0.1 O3-δ support exhibit uniform size distribution, 5.03 ± 0.91 nm, and exhibited one of the highest activities, 387.31 mmolNH3  gRu -1  h-1 (0.1 MPa and 450 °C). The role of the exsolution and BaCe0.9 Y0.1 O3-δ support is studied by comparing the catalyst with control samples and in-depth characterizations. The optimal nanoparticle size is maintained during the reaction, as the Ru nanoparticles prepared by exsolution are well-anchored to the support with in-plane epitaxy. The electronic structure of Ru is modified by unexpected in situ Ba promoter accumulation around the base of the Ru nanoparticles.

KAT2A coupled with the α-KGDH complex acts as a histone H3 succinyltransferase.

Histone modifications, such as the frequently occurring lysine succinylation, are central to the regulation of chromatin-based processes. However, the mechanism and functional consequences of histone succinylation are unknown. Here we show that the α-ketoglutarate dehydrogenase (α-KGDH) complex is localized in the nucleus in human cell lines and binds to lysine acetyltransferase 2A (KAT2A, also known as GCN5) in the promoter regions of genes. We show that succinyl-coenzyme A (succinyl-CoA) binds to KAT2A. The crystal structure of the catalytic domain of KAT2A in complex with succinyl-CoA at 2.3 Å resolution shows that succinyl-CoA binds to a deep cleft of KAT2A with the succinyl moiety pointing towards the end of a flexible loop 3, which adopts different structural conformations in succinyl-CoA-bound and acetyl-CoA-bound forms. Site-directed mutagenesis indicates that tyrosine 645 in this loop has an important role in the selective binding of succinyl-CoA over acetyl-CoA. KAT2A acts as a succinyltransferase and succinylates histone H3 on lysine 79, with a maximum frequency around the transcription start sites of genes. Preventing the α-KGDH complex from entering the nucleus, or expression of KAT2A(Tyr645Ala), reduces gene expression and inhibits tumour cell proliferation and tumour growth. These findings reveal an important mechanism of histone modification and demonstrate that local generation of succinyl-CoA by the nuclear α-KGDH complex coupled with the succinyltransferase activity of KAT2A is instrumental in histone succinylation, tumour cell proliferation, and tumour development.

Surgical management and final outcomes of chondrosarcoma of the temporomandibular joint: case series and comprehensive literature review.

BACKGROUND: Surgical management for chondrosarcoma of the temporomandibular joint (TMJ) is challenging due to the anatomical location involving the facial nerve and the functional joint. The purpose of this case series was to analyze the largest number of TMJ chondrosarcoma cases reported from a single institution and to review the literature about chondrosarcoma involving the TMJ. METHODS: Ten TMJ chondrosarcoma patients at Seoul National University Dental Hospital were included in this study. Radiographic features, surgical approaches, histopathologic subtypes, and treatment modalities were evaluated. All case reports of TMJ chondrosarcoma published in English from 1954 to 2021 were collected under PRISMA guidelines and comprehensively reviewed. RESULTS: The lesions were surgically resected in all 10 patients with efforts to preserve facial nerve function. Wide excision including margins of normal tissue was performed to ensure adequate resection margins. All TMJs were reconstructed with a metal condyle except one, which was reconstructed with vascularized costal bone. At last follow-up, all patients were still alive, and there had been no recurrence. Among 47 cases (patients from the literature and our cases), recurrence was specified in 43 and occurred in four (9.5%). CONCLUSIONS: For surgical management of TMJ chondrosarcoma, wide excision must consider preservation of the facial nerve. Reconstruction using a metal condyle prosthesis and a vascularized free flap is reliable. A more conservative surgical approach correlates with a favorable prognosis for facial nerve recovery. Nevertheless, wide excision is imperative to prevent tumor recurrence. In cases in which the glenoid fossa is unaffected by the tumor, it is deemed unnecessary to reconstruct the glenoid fossa within an oncological setting.

Active photonic wireless power transfer into live tissues.

Recent advances in soft materials and mechanics activate development of many new types of electrical medical implants. Electronic implants that provide exceptional functions, however, usually require more electrical power, resulting in shorter period of usages although many approaches have been suggested to harvest electrical power in human bodies by resolving the issues related to power density, biocompatibility, tissue damage, and others. Here, we report an active photonic power transfer approach at the level of a full system to secure sustainable electrical power in human bodies. The active photonic power transfer system consists of a pair of the skin-attachable photon source patch and the photovoltaic device array integrated in a flexible medical implant. The skin-attachable patch actively emits photons that can penetrate through live tissues to be captured by the photovoltaic devices in a medical implant. The wireless power transfer system is very simple, e.g., active power transfer in direct current (DC) to DC without extra circuits, and can be used for implantable medical electronics regardless of weather, covering by clothes, in indoor or outdoor at day and night. We demonstrate feasibility of the approach by presenting thermal and mechanical compatibility with soft live tissues while generating enough electrical power in live bodies through in vivo animal experiments. We expect that the results enable long-term use of currently available implants in addition to accelerating emerging types of electrical implants that require higher power to provide diverse convenient diagnostic and therapeutic functions in human bodies.

Classification of Skeletal Phenotypes of Adult Patients With Cleft Skeletal Class III Malocclusion Using Principal Component Analysis and Cluster Analysis.

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.

Facial Asymmetry Phenotypes in Adult Patients With Unilateral Cleft Lip and Palate and Skeletal Class III Malocclusion Using Principal Component Analysis and Cluster Analysis.

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.

Analysis of Differences in Single-Joint Movement of Dominant and Non-Dominant Hands for Human-like Robotic Control.

Although several previous studies on laterality of upper limb motor control have reported functional differences, this conclusion has not been agreed upon. It may be conjectured that the inconsistent results were caused because upper limb motor control was observed in multi-joint tasks that could generate different inter-joint motor coordination for each arm. Resolving this, we employed a single wrist joint tracking task to reduce the effect of multi-joint dynamics and examined the differences between the dominant and non-dominant hands in terms of motor control. Specifically, we defined two sections to induce feedback (FB) and feedforward (FF) controls: the first section involved a visible target for FB control, and the other section involved an invisible target for FF control. We examined the differences in the position errors of the tracer and the target. Fourteen healthy participants performed the task. As a result, we found that during FB control, the dominant hand performed better than the non-dominant hand, while we did not observe significant differences in FF control. In other words, in a single-joint movement that is not under the influence of the multi-joint coordination, only FB control showed laterality and not FF control. Furthermore, we confirmed that the dominant hand outperformed the non-dominant hand in terms of responding to situations that required a change in control strategy.