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Circular RNAs (circRNAs) are noncoding RNAs abundant in brain tissue, and many are derived from activity-dependent, linear mRNAs encoding for synaptic proteins, suggesting that circRNAs may directly or indirectly play a role in regulating synaptic development, plasticity, and function. However, it is unclear if the circular forms of these RNAs are similarly regulated by activity and what role these circRNAs play in developmental plasticity. Here, we employed transcriptome-wide analysis comparing differential expression of both mRNAs and circRNAs in juvenile mouse primary visual cortex (V1) following monocular deprivation (MD), a model of developmental plasticity. Among the differentially expressed mRNAs and circRNAs following 3-day MD, the circular and the activity-dependent linear forms of the Homer1 gene, circHomer1 and Homer1a respectively, were of interest as their expression changed in opposite directions: circHomer1 expression increased while the expression of Homer1a decreased following MD. Knockdown of circHomer1 prevented the depression of closed-eye responses normally observed after 3-day MD. circHomer1 -knockdown led to a reduction in average dendritic spine size prior to MD, but critically there was no further reduction after 3-day MD, consistent with impaired structural plasticity. circHomer1 -knockdown also prevented the reduction of surface AMPA receptors after 3-day MD. Synapse-localized puncta of the AMPA receptor endocytic protein Arc increased in volume after MD but were smaller in circHomer1 -knockdown neurons, suggesting that circHomer1 regulates plasticity through mechanisms of activity-dependent AMPA receptor endocytosis. Thus, activity-dependent circRNAs regulate developmental synaptic plasticity, and our findings highlight the essential role of circHomer1 in V1 plasticity induced by short-term MD., Competing Interests: Competing Interest Statement N.M. is CSO of Circular Genomics Inc, Albuquerque, NM.

Understanding cellular architectures and their connectivity is essential for interrogating system function and dysfunction. However, we lack technologies for mapping the multiscale details of individual cells and their connectivity in the human organ-scale system. We developed a platform that simultaneously extracts spatial, molecular, morphological, and connectivity information of individual cells from the same human brain. The platform includes three core elements: a vibrating microtome for ultraprecision slicing of large-scale tissues without losing cellular connectivity (MEGAtome), a polymer hydrogel-based tissue processing technology for multiplexed multiscale imaging of human organ-scale tissues (mELAST), and a computational pipeline for reconstructing three-dimensional connectivity across multiple brain slabs (UNSLICE). We applied this platform for analyzing human Alzheimer's disease pathology at multiple scales and demonstrating scalable neural connectivity mapping in the human brain.

Background: One in two ventral and incisional hernia repair (VIHR) patients have preoperative opioid prescription within a year before procedure. The study's aim was to investigate risk factors of increased postoperative prescription filling in patients with or without preoperative opioid prescription., Methods: VIHR cases from 2013 to 2017 were reviewed. State prescription drug monitoring program data were linked to patient records. The primary endpoint was cumulative opioid dose dispensed through post-discharge day 45. Morphine milligram equivalent (MME) was used for uniform comparison., Results: 205 patients were included in the study (average age 53.5 years; 50.7% female). Over 35% met criteria for preoperative opioid use. Preoperative opioid tolerance, superficial wound infection, current smoking status, and any dispensed opioids within 45 days of admission were independent predictors for increased postoperative opioid utilization (p < 0.001)., Conclusion: Preoperative opioid use during 45-day pre-admission correlated strongly with postoperative prescription filling in VIHR patients, and several independent risk factors were identified., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Intravital fluorescence imaging of functional osteoclasts within their intact disease context provides valuable insights into the intricate biology at the microscopic level, facilitating the development of therapeutic approaches for osteoclast-associated bone diseases. However, there is a lack of studies investigating osteoclast activity within deep-seated bone lesions using appropriate fluorescent probes, despite the advantages offered by the multi-photon excitation system in enhancing deep tissue imaging resolution. In this study, we report on the intravital tracking of osteoclast activity in three distinct murine bone disease models. We utilized a cathepsin K (CatK)-responsive two-photon fluorogenic probe (CatKP1), which exhibited a notable fluorescence turn-on response in the presence of active CatK. By utilizing CatKP1, we successfully monitored a significant increase in osteoclast activity in hindlimb long bones and its attenuation through pharmacological intervention without sacrificing mice. Thus, our findings highlight the efficacy of CatKP1 as a valuable tool for unraveling pathological osteoclast behavior and exploring novel therapeutic strategies., (© 2023 Wiley-VCH GmbH.)

Immunogenic cell death (ICD) has emerged as a promising approach to cancer immunotherapy. During ICD, cancer cell death and the release of damage-associated molecular pattern (DAMP) signals occur simultaneously. Increased production of reactive oxygen species (ROS) and severe endoplasmic reticulum stress are necessary for enhanced ICD. Furthermore, the levels of ROS and reduced glutathione (GSH) are involved in various cell death mechanisms. The thiazole ring structure has gained considerable interest as a functional moiety for anticancer agents. This study designed and synthesized a positively charged cell-penetrating polypeptide with a thiazole functional moiety (NS). The NS internalizes into the cancer cells through direct penetration and endo-lysosomal escape. The NS induces mitochondrial depolarization and ER stress in a concentration-dependent manner, leading to a significant ROS production and GSH depletion. Consequently, the ICD of cancer cells is activated, resulting in the release of DAMP signals. Furthermore, NS causes a shift in the cell death pathway from apoptosis to necroptosis as the concentration increases. In this study, we confirmed the possibility of NS as a promising ICD inducer that can be used while varying the concentration according to the cancer type.

5 V-class LiNi 0.5 Mn 1.5 O 4 (LNMO) with its spinel symmetry is a promising cathode material for lithium-ion batteries. However, the high-voltage operation of LNMO renders it vulnerable to interfacial degradation involving electrolyte decomposition, which hinders long-term and high-rate cycling. Herein, this longstanding challenge presented by LNMO is overcome by incorporating a sacrificial binder, namely, λ-carrageenan (CRN), a sulfated polysaccharide. This binder not only uniformly covers the LNMO surface via hydrogen bonding and ion-dipole interaction but also offers an ionically conductive cathode-electrolyte interphase layer containing LiSO x F, a product of the electrochemical decomposition of the sulfate group. Taking advantage of these two auspicious properties, the CRN-based electrode exhibits cycling and rate performance far superior to that of its counterparts based on the conventional poly(vinylidene difluoride) and sodium alginate binders. This study introduces a new concept, namely "sacrificial" binder, for battery electrodes known to deliver superior electrochemical performance but be adversely affected by interfacial instability., (© 2023 Wiley-VCH GmbH.)

Mast cells are an important component of immune responses. Immunoglobulin (Ig) E-sensitized mast cells release substances within minutes of allergen exposure, triggering allergic responses. Until now, numerous pharmacological effects of wheatgrass and aronia have been verified, but the effects of wheatgrass and aronia (TAAR)-mixed extract on allergic reactions have not been identified. Therefore, the aim of this study was to demonstrate the anti-allergic effect of TAAR extract on mast cell activation and cutaneous anaphylaxis. In this study, we investigated the anti-allergic effects and related mechanisms of TAAR extract in IgE-activated mast cells in vitro. We also assessed the ameliorating effect of TAAR extract on IgE-mediated passive cutaneous anaphylaxis mice in vivo. The TAAR extract significantly reduced the expression of β-hexosaminidase, histamine, and pro-inflammatory cytokines, which are mediators related to mast cell degranulation, via the regulation of various signaling pathways. The TAAR extract also regulated oxidative-stress-related factors through the Nrf2 signaling pathway. Additionally, treatment of TAAR extract to the passive cutaneous anaphylaxis mouse model improved ear thickness and local ear pigmentation. Taken together, our results suggest that TAAR extract is a potential candidate natural product to treat overall IgE-mediated allergic inflammation and oxidative-stress-related diseases by suppressing mast cell activity.

Atopic dermatitis is regulated by the production of pro-inflammatory cytokines and chemokines via the nuclear factor kappa B or mitogen-activated protein kinase signaling pathways, as well as, the release of oxidative stress-related factors via the NF-E2 p45-related factor 2 signaling pathway. Both wheatgrass ( Triticum aestivum L., TA) and aronia ( Aronia melanocarpa , AR) are known for their anti-inflammatory and antioxidant properties, however, the anti-inflammatory and antioxidant effects of TA and AR (TAAR) mixture extract have not been elucidated in an atopic dermatitis model. In this study, we assessed the inhibitory effects and underlying molecular mechanism of TAAR extract against lipopolysaccharide-induced inflammation and tumor necrosis factor-α/interferon-γ-induced inflammation and oxidative stress in vitro. We also investigated the alleviating effect of TAAR extract on DNCB-induced atopic dermatitis-like skin lesions in mice in vivo. We found that TAAR extract treatment inhibited inflammatory mediators in both RAW 264.7 cells and HaCaT cells, and increased the expression of oxidative stress defense enzymes in HaCaT cells. Furthermore, treatment of the DNCB-induced mouse model with TAAR extract ameliorated the overall symptoms of atopic dermatitis. Therefore, TAAR extract as a novel natural therapeutic agent may be used for the treatment of atopic dermatitis.

Cognitive impairment is observed in 12% to 56% of stroke patients, and screening for cognitive impairment is often complex and time-consuming, with results dependent on patient compliance. Therefore, there is a need for an objective method to assess cognitive impairment regardless of patient compliance. Objective evaluation methods include electroencephalogram (EEG) and event-related potential (ERP). This study was conducted to assess intra-tester reliability of resting EEG-based spectral features and auditory/visual P300 latency/amplitude in patients with subacute ischemic stroke. Twenty patients with subacute ischemic stroke were included in the study. The resting EEG and P300 wave using an auditory and visual oddball paradigm were measured at baseline and once again in 24 hours. The following electrode positions (10-20 system) were constantly recorded: F3 (Frontal), Fz, F4, C3 (Central), Cz, C4, P3 (Parietal), Pz, P4. DAR (delta/alpha ratio) and BSI (brain symmetry index) were determined using EEG data. F3 and F4, C3 and C4 and P3 and P4 were switched according to the stroke side and classified as affected hemisphere (AH) and unaffected hemisphere (UH) after the evaluation. In ERP, the amplitude and latency of P300 were obtained. In reliability analysis of EEG-based spectral characteristics, significant reliability was observed for DAR (ICC = 0.447), BSldir (ICC = 0.713) and BSIdirtheta (ICC = 0.724) (Table 4). DAR was showed a poor ICC level, and BSIdir and BSIdirtheta had a moderate ICC level. Visual P300 latency showed excellent intraclass correlation coefficient (ICC) in several montages (PUH = 0.972, Pz = 0.945). In 6 montages, auditory P300 latency was reliable, while in 9 montages, visual P300 latency was reliable. In 4 montages, auditory P300 amplitude was reliable, while visual P300 amplitude was reliable in 7. The visual P300 was more reliable than the auditory P300. The ICC values for P300 latency were greater than those for amplitude. Therefore, when ERP is performed on subacute stroke patients, visual has higher reliability than auditory., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To evaluate the relationship between femoral muscle volume (FMV) and physiological outcomes after trans-femoral amputations (TFAs) affecting overall locomotor function in patients., Methods: Seven individuals who underwent TFA and had been using a prosthesis participated in this cross-sectional study. Gait and balance were assessed using clinical tests, such as 10-m walk test, 6-minute walk test, Berg Balance Scale, and automatic balance system. Respiratory gas analysis was performed to check oxygen consumption rate. Five participants were evaluated for bilateral FMV by MR imaging and FMV was reconstructed using three-dimentional remodeling., Results: In five participants, significant differences were found between the non-involved and involved sides in femur length, total FMV, and functional muscle volume (all p<0.01) in all groups except for the hip adductor volume. The %mean difference between the non-involved and involved sides was 30% for femur length, 52.55% for hip flexor volume, 26.55% for hip adductor volume, 51.86% for hip extensor volume, and 60.21% for knee extensor volume. The hip flexor volume to hip extensor volume ratio in the involved limb and oxygen consumption rate during comfortable gait were negatively correlated (r=-0.96, p=0.04)., Conclusion: In individuals who underwent unilateral TFA, hip girdle muscle imbalance in the involved limbs may be associated with oxygen consumption rate while using a prosthesis.

We attempted to improve the photon absorption of the photoactive layer in organic photovoltaic (OPV) devices by device engineering without changing their thickness. Soft nanoimprinting lithography was used to introduce a 1D grating pattern into the photoactive layer. The increase in photocurrent caused by the propagating surface plasmon-polariton mode was quantitatively analyzed by measuring the external quantum efficiency in transverse magnetic and transverse electric modes. In addition, the introduction of an ultrathin substrate with a refractive index of 1.34 improved photon absorption by overcoming the mismatched optical impedance at the air/substrate interface. As a result, the power conversion efficiency (PCE) of an ultrathin OPV with a 400 nm grating period was 8.34%, which was 11.6% higher than that of an unpatterned ultrathin OPV, and the PCE was 3.2 times higher at a low incident light angle of 80°, indicating very low incident light angle dependence.

An electrodiagnostic test is more useful than the lower extremity isometric strength test for objectively determining the degree of nerve damage and prognosis in cauda equina syndromes (CES). This study evaluated the correlation between nerve conduction study (NCS) parameters and the lower extremity isometric strength and manual muscle test (MMT) grades. The isometric strengths of knee extension (KE), ankle dorsiflexion (ADF), and ankle plantarflexion (APF) were measured. NCS parameters, MMT, and isometric strength of femoral, peroneal, and tibial nerves were evaluated, including their correlations with each other. A regression equation between the isometric strength and compound muscle action potential (CMAP) amplitudes was derived and cutoff values were used to confirm boundary values of strength and amplitude between the MMT grades. KE isometric strength and femoral nerve CMAP amplitude were significantly correlated (r = 0.738, P < .001). ADF isometric strength and peroneal nerve CMAP amplitude were significantly correlated (tibialis anterior, r = 0.707, P < .001). KE (r = 0.713, P < .001), ADF (r = 0.744, P < .001), and APF (r = 0.698, P < .001) isometric strengths were correlated with the MMT grades. For the regression curve, the second-order curve was more reasonable than the first-order curve. Cutoff femoral nerve CMAP amplitude and isometric strength cutoff values were ≥2.05 mV and 17.3, respectively, for MMT grades 2 to 3 and 2.78 ± 1.08 and 20.8 ± 9.33, respectively, for grade 3. The isometric strengths of the KE, ADF, and APF and the CMAP amplitude of the electrophysiologic parameters were correlated in CES patients and a significant correlation with MMT grade was also identified. Accordingly, it is possible to identify the precise neurological condition, objectively evaluate the degree of paralysis and disability, and determine the quantitative muscle strength from MMT in order to establish an appropriate rehabilitation treatment plan., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Neuromorphic devices have been extensively studied to overcome the limitations of a von Neumann system for artificial intelligence. A synaptic device is one of the most important components in the hardware integration for a neuromorphic system because a number of synaptic devices can be connected to a neuron with compactness as high as possible. Therefore, synaptic devices using silicon-based memory, which are advantageous for a high packing density and mass production due to matured fabrication technologies, have attracted considerable attention. In this study, a segmented transistor devoted to an artificial synapse is proposed for the first time to improve the linearity of the potentiation and depression (P/D). It is a complementary metal oxide semiconductor (CMOS)-compatible device that harnesses both non-ohmic Schottky junctions of the source and drain for improved weight linearity and double-layered nitride for enhanced speed. It shows three distinct and unique segments in drain current-gate voltage transfer characteristics induced by Schottky junctions. In addition, the different stoichiometries of Si x N y for a double-layered nitride is utilized as a charge trap layer for boosting the operation speed. This work can bring the industry potentially one step closer to realizing the mass production of hardware-based synaptic devices in the future.

Signal transduction pathways post-translationally regulating nucleotide metabolism remain largely unknown. Guanosine monophosphate reductase (GMPR) is a nucleotide metabolism enzyme that decreases GTP pools by converting GMP to IMP. We observed that phosphorylation of GMPR at Tyr267 is critical for its activity and found that this phosphorylation by ephrin receptor tyrosine kinase EPHA4 decreases GTP pools in cell protrusions and levels of GTP-bound RAC1. EPHs possess oncogenic and tumor-suppressor activities, although the mechanisms underlying switches between these two modes are poorly understood. We demonstrated that GMPR plays a key role in EPHA4-mediated RAC1 suppression. This supersedes GMPR-independent activation of RAC1 by EPHA4, resulting in a negative overall effect on melanoma cell invasion and tumorigenicity. Accordingly, EPHA4 levels increase during melanoma progression and inversely correlate with GMPR levels in individual melanoma tumors. Therefore, phosphorylation of GMPR at Tyr267 is a metabolic signal transduction switch controlling GTP biosynthesis and transformed phenotypes., Competing Interests: Declaration of interests The authors declare no competing financial interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Synaptic NMDA receptors can produce powerful dendritic supralinearities that expand the computational repertoire of single neurons and their respective circuits. This form of supralinearity may represent a general principle for synaptic integration in thin dendrites. However, individual cortical neurons receive many diverse classes of input that may require distinct postsynaptic decoding schemes. Here, we show that sensory, motor, and thalamic inputs preferentially target basal, apical oblique, and distal tuft dendrites, respectively, in layer 5b pyramidal neurons of the mouse retrosplenial cortex, a visuospatial association area. These dendritic compartments exhibited differential expression of NMDA receptor-mediated supralinearity due to systematic changes in the AMPA-to-NMDA receptor ratio. Our results reveal a new schema for integration in cortical pyramidal neurons, in which dendrite-specific changes in synaptic receptors support input-localized decoding. This coexistence of multiple modes of dendritic integration in single neurons has important implications for synaptic plasticity and cortical computation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Stroke-related disabilities cause poor physical performance, especially among older adults, and can lead to sarcopenia. Functional electrical stimulation (FES) has been used to improve physical performance in individuals with neurological disorders and increase muscle mass and strength to counteract muscle atrophy. This review covers the principles, underlying mechanisms, and therapeutic effects of FES on physical performance and skeletal muscle function in post-stroke older adults. We found that FES restored weakened dorsiflexor and hip abductor strength during the swing and stance phases of gait, respectively, to help support weight-bearing and upright posture and facilitate static and dynamic balance in this population. FES may also be effective in improving muscle mass and strength to prevent muscle atrophy. However, previous studies on this topic in post-stroke older adults are scarce, and further studies are needed to confirm this supposition.

An outbreak of SARS CoV-2 infection occurred in an infantry battalion from Joint Base Lewis-McChord following participation in a field training exercise in the vicinity of Yakima, WA in February of 2021. Extreme weather during the exercise disrupted planned COVID-19 mitigation measures and caused 110 soldiers to be sheltered in a small aircraft hangar for several nights. The probable index case reported to sick call with symptoms compatible with COVID-19, but the soldier was not diagnosed with COVID-19, was returned to duty, and was allowed to remain in the enclosed hangar for 3 additional days. In total, 143 individuals with epidemiologic ties to the field training exercise tested positive for SARS-CoV-2 during the outbreak. Nine samples sent for sequencing were determined to be the SARS-CoV-2 Beta variant. This report illustrates important lessons learned whose implementation in the future will enable better protection of service members from COVID-19 and similar health risks associated with training.

Vitamin B12 (B12) is involved as a cofactor in the synthesis of myelin. A lack of B12 impairs peripheral nerve production, which can contribute to sarcopenia. In this cross-sectional study, we aimed to investigate the relationship between B12 insufficiency and sarcopenia in community-dwelling older Korean adults. A total of 2325 (1112 men; 1213 women) adults aged 70-84 years were recruited. The tools used for sarcopenia were based on the Asian Working Group for Sarcopenia (AWGS) guidelines. Individuals with low appendicular skeletal muscle mass index (ASMI) (<7.0 kg/m 2 for men; <5.4 kg/m 2 for women) and low hand grip strength (HGS) (<28 kg for men; <18 kg for women) were defined as the sarcopenia group. Among this group, those who showed low physical performance (≤9 points on the Short Physical Performance Battery (SPPB)) were defined as the severe sarcopenia group. B12 concentrations were classified into insufficient (<350 pg/mL) and sufficient (≥350 pg/mL). Univariate and multivariate logistic regression analyses were used to evaluate the relationship between sarcopenia and B12 levels. Low ASMI showed a high incidence in the B12-insufficient group. However, HGS, SPPB, and the severity of sarcopenia showed no correlation with B12. Further, insufficient B12 may affect muscle quantity rather than muscle strength or physical performance.

Synthetic tissue-hydrogel methods have enabled superresolution investigation of biological systems using diffraction-limited microscopy. However, chemical modification by fixatives can cause loss of antigenicity, limiting molecular interrogation of the tissue gel. Here, we present epitope-preserving magnified analysis of proteome (eMAP) that uses purely physical tissue-gel hybridization to minimize the loss of antigenicity while allowing permanent anchoring of biomolecules. We achieved success rates of 96% and 94% with synaptic antibodies for mouse and marmoset brains, respectively. Maximal preservation of antigenicity allows imaging of nanoscopic architectures in 1000-fold expanded tissues without additional signal amplification. eMAP-processed tissue gel can endure repeated staining and destaining without epitope loss or structural damage, enabling highly multiplexed proteomic analysis. We demonstrated the utility of eMAP as a nanoscopic proteomic interrogation tool by investigating molecular heterogeneity in inhibitory synapses in the mouse brain neocortex and characterizing the spatial distributions of synaptic proteins within synapses in mouse and marmoset brains.

Wheat ( Triticum aestivum L.) is the oldest known food crop, and many studies have reported that wheat shoots (i.e., wheatgrass) possess anti-cancer, anti-inflammatory, and antioxidant activities. However, the potentially ameliorative effect of wheat shoots on hepatotoxicity caused by high doses of N -acetyl-para-aminophenol (acetaminophen, APAP) has yet to be reported. C57BL/6 mice received daily oral TAE (100 or 200 mg/kg), positive control (silymarin 100 mg/kg), or negative control (saline vehicle) treatments for 7 days prior to intraperitoneal APAP injection. Histological, serum (ELISA), Western blotting, and quantitative PCR analyses of excised liver tissues were then performed. Pre-treatment with TAE (100 or 200 mg/kg) ameliorated APAP-induced pathological damage (i.e., hepatotoxic lesions), reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and also ameliorated APAP-induced increases in oxidative stress, thereby inhibiting oxidative liver damage and reducing the expression of inflammatory cytokines. In addition, TAE pre-treatment inhibited the expression of Cytochrome P4502E1 (CYP2E1), which is a key enzyme in the onset of APAP-induced hepatotoxicity, suppressed the expression of the target proteins regulated by the antioxidant enzyme Nrf2, and suppressed hepatocyte apoptosis. These findings suggest that TAE is an attractive therapeutic candidate that exhibits potential hepatoprotective activity by inhibiting oxidative stress, inflammation, apoptosis, and liver damage.

Physiological changes in GTP levels in live cells have never been considered a regulatory step of RAC1 activation because intracellular GTP concentration (determined by chromatography or mass spectrometry) was shown to be substantially higher than the in vitro RAC1 GTP dissociation constant (RAC1-GTP Kd). Here, by combining genetically encoded GTP biosensors and a RAC1 activity biosensor, we demonstrated that GTP levels fluctuating around RAC1-GTP Kd correlated with changes in RAC1 activity in live cells. Furthermore, RAC1 co-localized in protrusions of invading cells with several guanylate metabolism enzymes, including rate-limiting inosine monophosphate dehydrogenase 2 (IMPDH2), which was partially due to direct RAC1-IMPDH2 interaction. Substitution of endogenous IMPDH2 with IMPDH2 mutants incapable of binding RAC1 did not affect total intracellular GTP levels but suppressed RAC1 activity. Targeting IMPDH2 away from the plasma membrane did not alter total intracellular GTP pools but decreased GTP levels in cell protrusions, RAC1 activity, and cell invasion. These data provide a mechanism of regulation of RAC1 activity by local GTP pools in live cells., (© 2021. The Author(s).)

Resistance to the proteasome inhibitor bortezomib (BTZ) represents a major obstacle in the treatment of multiple myeloma (MM). The contribution of lipid metabolism in the resistance of MM cells to BTZ is mostly unknown. Here we report that levels of fatty acid elongase 6 (ELOVL6) were lower in MM cells from BTZ-nonresponsive vs BTZ-responsive patients and in cultured MM cells selected for BTZ resistance compared with parental counterparts. Accordingly, depletion of ELOVL6 in parental MM cells suppressed BTZ-induced endoplasmic reticulum (ER) stress and cytotoxicity, whereas restoration of ELOVL6 levels in BTZ-resistant MM cells sensitized them to BTZ in tissue culture settings and, as xenografts, in a plasmacytoma mouse model. Furthermore, for the first time, we identified changes in the BTZ-induced lipidome between parental and BTZ-resistant MM cell lines underlying a functional difference in their response to BTZ. We demonstrated that restoration of ELOVL6 levels in BTZ-resistant MM cells resensitized them to BTZ largely via upregulation of ELOVL6-dependent ceramide species, which was a prerequisite for BTZ-induced ER stress and cell death in these cells. Our data characterize ELOVL6 as a major clinically relevant regulator of MM cell resistance to BTZ, which can emerge from the impaired ability of these cells to alter ceramide composition in response to BTZ., (© 2021 by The American Society of Hematology.)

Background: Nodakenin, a coumarin glucoside isolated from the roots of Angelica biserrata, has been reported to have anti-inflammatory, antibacterial, anticancer effects. However, despite these studies, the potential liver protective effects of nodakenin in inflammatory liver injury models have not been reported., Methods: A mouse model of inflammatory liver injury was induced by injection of lipopolysaccharide (LPS) (15 mg/kg, intraperitoneally (i.p)). Liver tissue AST, ALT, ROS, T-GSH and T-SOD were analyzed by ELISA. The concentrations of TNF-α, IL-6, and IL-1β in serum of LPS-induced inflammatory liver injury mice were analyzed. The mRNA expression levels of GPx1, catalase, SOD1, SOD2, TNF-α, IL-6, IL-1β, iNOS and COX-2 were analyzed using real-time PCR. The expressions of MAPK, IRF3, NF-κB, Nrf2, HO-1, caspase-3 and caspase-7 were analyzed using western blotting. Liver tissue was stained with IHC to confirm NF-κB, Nrf-2, HO-1, caspase-3, Bax, and Bcl2. Tunnel analysis was performed to confirm the fragmented nuclear DNA characteristics of apoptosis., Results: The administration of nodakenin (10 and 30 mg/kg) reduced serum aminotransferase levels compared to LPS-induced liver damage and significantly improved the oxidative state of liver tissue and pathological damage. Moreover, inhibited the phosphorylation of transforming growth factor beta (TGF-β)-activated kinase (TAK)-1 in LPS-induced inflammatory liver injury model, and significantly inhibited the transcriptional of nuclear factor-kappa B (NF-kB) and the secretion of pro-inflammatory mediators. In addition nodakenin pre-treatment also attenuated hepatocyte death by regulating apoptosis-related mitochondrial proteins, such as cysteinyl aspartate specific proteinase 3 (caspase 3), poly (ADP-ribose) polymerase (PARP), B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X (Bax)., Conclusion: Our findings suggest that nodakenin has anti-inflammatory, anti-oxidant and anti-apoptotic activity and may be an adjunctive prevention agent for liver injury., (Copyright © 2020. Published by Elsevier GmbH.)

Brain organoids grown from human pluripotent stem cells self-organize into cytoarchitectures resembling the developing human brain. These three-dimensional models offer an unprecedented opportunity to study human brain development and dysfunction. Characterization currently sacrifices spatial information for single-cell or histological analysis leaving whole-tissue analysis mostly unexplored. Here, we present the SCOUT pipeline for automated multiscale comparative analysis of intact cerebral organoids. Our integrated technology platform can rapidly clear, label, and image intact organoids. Algorithmic- and convolutional neural network-based image analysis extract hundreds of features characterizing molecular, cellular, spatial, cytoarchitectural, and organoid-wide properties from fluorescence microscopy datasets. Comprehensive analysis of 46 intact organoids and ~ 100 million cells reveals quantitative multiscale "phenotypes" for organoid development, culture protocols and Zika virus infection. SCOUT provides a much-needed framework for comparative analysis of emerging 3D in vitro models using fluorescence microscopy.

We investigated the relationship between blood pressure (BP) and mortality in patients taking antihypertensive medications in the Korean using data from the 2007-2015 Korean National Health and Nutrition Examination Surveys. A total of 6601 patients aged 30-74 years were included. Systolic BP (SBP) and diastolic BP (DBP) were both divided into four groups as follows: SBP < 120, 120 ≤ SBP ≤ 129 130 ≤ SBP ≤ 139, and SBP ≥ 140; DBP < 70, 70 ≤ DBP ≤ 79, 80 ≤ DBP ≤ 89, and DBP ≥ 90. The survival rates and hazard ratios were evaluated using Kaplan-Meier curves and multivariable Cox regression analyses. To evaluate the predictability of all-cause mortality according to SBP and/or DBP, we calculated Harrell's concordance-index. The lowest DBP group had a high risk of mortality regardless of the SBP status. The group with DBP < 70 mm Hg and SBP ≥ 140 mm Hg showed the highest mortality. The discriminatory ability calculated using Harrell's C-indexes was greater for the combination of SBP and DBP compared to DBP or SBP alone. These results suggest that it is more effective to simultaneously evaluate the effect of SBP and DBP to predict mortality; clinicians should manage DBP < 70 mm Hg when treating hypertensive patients., (© 2020 Wiley Periodicals LLC.)

LIL (laser interference lithography), which does not require a mask, is an effective way to create a wide variety of periodic patterns by exposing two laser beams on a specimen. The LIL method can be used for a wide range of nano-pattern spacing by adjusting the laser intensity, exposure time, and development time. In addition, it has been used in many studies due to its advantage with regard to the forming of nanostructures over a large area in a short period of time. However, the existing LIL technique requires demanding precision levels to align the laser beam. In this paper, we attempt to solve this problem by using a prism laser interferometer to complement the complicated beam alignment of LIL. In this study, ma-p1205 PR-coated silicon wafers were exposed to a CW laser with 360 nm wavelength using a contact-type and a non-contact prism interferometer. A rectangular triangular prism and an equilateral triangular prism of N-BK7 were used, and periods of 300 nm and 260 nm were fabricated, respectively. The MATLAB and COMSOL programs were used to compare the theoretical values and fabricated patterns.

Background: Dysphagia and dysarthria tend to coexist in stroke patients. Dysphagia can reduce patients' quality of life, cause aspiration pneumonia and increased mortality., Objective: To evaluate correlations among swallowing function parameters and acoustic vowel space values in patients with stroke., Methods: Data from stroke patients with dysarthria and dysphagia were collected. The formant parameter representing the resonance frequency of the vocal tract as a two-dimensional coordinate point was measured for the /a/, /ae/, /i/, and /u/vowels, and the quadrilateral vowel space area (VSA) and formant centralization ratio (FCR) were measured. Swallowing function was evaluated by a videofluoroscopic swallowing study (VFSS) using the videofluoroscopic dysphagia scale (VDS) and penetration aspiration scale (PAS). Pearson's correlation and linear regression analyses were used to assess the correlation of VSA and FCR to VDS and PAS scores., Results: Thirty-one stroke patients with dysphagia and dysarthria were analyzed. VSA showed a negative correlation to VDS and PAS scores, while FCR showed a positive correlation to VDS score, but not to PAS score. VSA and FCR were significant factors for assessing dysphagia severity., Conclusions: VSA and FCR values were correlated with swallowing function and may be helpful in predicting dysphagia severity associated with stroke.

Recent studies have explored the association between single-nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) and ischemic stroke (IS). In particular, the associations of rs2910164 (miRNA-146A), rs11614913 (miRNA-196A2), and rs3746444 (miRNA-499A) were intensively studied in IS. In this study, we investigated the associations between SNPs in miRNAs and IS including rs2910164, rs11614913, and rs3746444 in a Korean population. For a pilot study, we selected 19 SNPs in pre-miRNA region (including mature miRNA region) and genotyped in 140 IS patients and 240 control subjects using the Fluidigm Dynamic Array. Our pilot study showed a weak association of rs79402775 in miRNA-933 ( p = 0.044) and a relatively strong association of rs35196866 in miRNA-4669 ( p = 0.016) with IS. From the pilot study, we selected rs79402775, rs35196866, and rs7202008 (miRNA-2117; p = 0.055) as candidate miRNA SNPs on IS and further genotyped these SNPs in 264 IS patients and 455 control subjects using direct sequencing. In addition, we further analyzed the associations of rs2910164, rs11614913, and rs3746444 that have been intensively studied in previous studies. In the further analysis, we found the significant association between rs35196866 and IS ( p = 0.0014 in additive model and p = 0.00015 in dominant model; p = 0.00037 in allele frequency analysis). However, the association between rs2910164, rs11614913, rs3746444, rs79402775, and rs7202008 and IS was not shown. These results suggest that miRNA-4669 may be involved in the susceptibility of IS., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2019 Seoung-Jin Hong et al.)

Although antioxidants promote melanoma metastasis, the role of reactive oxygen species (ROS) in other stages of melanoma progression is controversial. Moreover, genes regulating ROS have not been functionally characterized throughout the entire tumor progression in mouse models of cancer. To address this question, we crossed mice-bearing knock-out of Klf9, an ubiquitous transcriptional regulator of oxidative stress, with two conditional melanocytic mouse models: Braf CA mice, where Braf V600E causes premalignant melanocytic hyperplasia, and Braf CA /Pten -/- mice, where Braf V600E and loss of Pten induce primary melanomas and metastases. Klf9 deficiency inhibited premalignant melanocytic hyperplasia in Braf CA mice but did not affect formation and growth of Braf CA /Pten -/- primary melanomas. It also, as expected, promoted Braf CA /Pten -/- metastasis. Treatment with antioxidant N-acetyl cysteine phenocopied loss of Klf9 including suppression of melanocytic hyperplasia. We were interested in a different role of Klf9 in regulation of cell proliferation in Braf CA and Braf CA /Pten -/- melanocytic cells. Mechanistically, we demonstrated that BRAF V600E signaling transcriptionally upregulated KLF9 and that KLF9-dependent ROS were required for full-scale activation of ERK1/2 and induction of cell proliferation by BRAF V600E . PTEN depletion in BRAF V600E -melanocytes did not further activate ERK1/2 and cell proliferation, but rendered these phenotypes insensitive to KLF9 and ROS. Our data identified an essential role of KLF9-dependent ROS in BRAF V600E signaling in premalignant melanocytes, offered an explanation to variable role of ROS in premalignant and transformed melanocytic cells and suggested a novel mechanism for suppression of premalignant growth by topical antioxidants.

Introduction: Sleep disruption is a characteristic of Alzheimer's disease (AD) that may exacerbate disease progression. This study tested whether a dual orexin receptor antagonist (DORA) would enhance sleep and attenuate neuropathology, neuroinflammation, and cognitive deficits in an AD-relevant mouse model, 5XFAD., Methods: Wild-type (C57Bl6/SJL) and 5XFAD mice received chronic treatment with vehicle or DORA-22. Piezoelectric recordings monitored sleep and spatial memory was assessed via spontaneous Y-maze alternations. Aβ plaques, Aβ levels, and neuroinflammatory markers were measured by immunohistochemistry, enzyme-linked immunosorbent assay, and real-time polymerase chain reaction, respectively., Results: In 5XFAD mice, DORA-22 significantly increased light-phase sleep without reducing Aβ levels, plaque density, or neuroinflammation. Effects of DORA-22 on cognitive deficits could not be determined because the 5XFAD mice did not exhibit deficits., Discussion: These findings suggest that DORAs may improve sleep in AD patients. Further investigations should optimize the dose and duration of DORA-22 treatment and explore additional AD-relevant animal models and cognitive tests.

Understanding complex biological systems requires the system-wide characterization of both molecular and cellular features. Existing methods for spatial mapping of biomolecules in intact tissues suffer from information loss caused by degradation and tissue damage. We report a tissue transformation strategy named stabilization under harsh conditions via intramolecular epoxide linkages to prevent degradation (SHIELD), which uses a flexible polyepoxide to form controlled intra- and intermolecular cross-link with biomolecules. SHIELD preserves protein fluorescence and antigenicity, transcripts and tissue architecture under a wide range of harsh conditions. We applied SHIELD to interrogate system-level wiring, synaptic architecture, and molecular features of virally labeled neurons and their targets in mouse at single-cell resolution. We also demonstrated rapid three-dimensional phenotyping of core needle biopsies and human brain cells. SHIELD enables rapid, multiscale, integrated molecular phenotyping of both animal and clinical tissues.

Polyamine inhibition for cancer therapy is, conceptually, an attractive approach but has yet to meet success in the clinical setting. The aryl hydrocarbon receptor (AHR) is the central transcriptional regulator of the xenobiotic response. Our study revealed that AHR also positively regulates intracellular polyamine production via direct transcriptional activation of 2 genes, ODC1 and AZIN1, which are involved in polyamine biosynthesis and control, respectively. In patients with multiple myeloma (MM), AHR levels were inversely correlated with survival, suggesting that AHR inhibition may be beneficial for the treatment of this disease. We identified clofazimine (CLF), an FDA-approved anti-leprosy drug, as a potent AHR antagonist and a suppressor of polyamine biosynthesis. Experiments in a transgenic model of MM (Vk*Myc mice) and in immunocompromised mice bearing MM cell xenografts revealed high efficacy of CLF comparable to that of bortezomib, a first-in-class proteasome inhibitor used for the treatment of MM. This study identifies a previously unrecognized regulatory axis between AHR and polyamine metabolism and reveals CLF as an inhibitor of AHR and a potentially clinically relevant anti-MM agent.

Oncogenic transcription factor FOXQ1 has been implicated in promotion of multiple transformed phenotypes in carcinoma cells. Recently, we have characterized FOXQ1 as a melanoma tumor suppressor that acts via repression of N-cadherin gene, and invasion and metastasis. Here we report that FOXQ1 induces differentiation in normal and transformed melanocytic cells at least partially via direct transcriptional activation of MITF gene, melanocytic lineage-specific regulator of differentiation. Importantly, we demonstrate that pigmentation induced in cultured melanocytic cells and in mice by activation of cAMP/CREB1 pathway depends in large part on FOXQ1. Moreover, our data reveal that FOXQ1 acts as a critical mediator of BRAF V600E -dependent regulation of MITF levels, thus providing a novel link between two major signal transduction pathways controlling MITF and differentiation in melanocytic cells.

Objective: To evaluate the association between balance function and asymmetry of knee extension strength in an elderly Korean population., Methods: The strength of the knee extensors in each leg was measured in 306 community-dwelling elderly subjects (age, 76.70±4.85 years) and 25 young healthy subjects (age, 34.23±8.93 years). Based on the difference in strength of both legs, the elderly subjects were divided into symmetric (n=128) and asymmetric (n=178) strength groups using an asymmetry cutoff 20%. We determined the postural control ability of the subjects using InBody posturography, Berg Balance Scale (BBS), Timed Up and Go test (TUG) and Short Physical Performance Battery (SPPB). The sway index (SI) of the subjects in four positions was assessed using posturography., Results: The group with asymmetric strength presented a significantly higher SI than the group with symmetric strength, in the normal position with eyes open and eyes open on pillows. In the normal position with the eyes closed and in postures with the eyes closed on pillows, the statistical analysis revealed no significant differences between the two groups. The three tests for physical performance (BBS, TUG, and SPPB) show no statistically significant difference between the two groups., Conclusion: The asymmetric strength group showed a significantly lower balance than the group with symmetric strength based on several posturographic parameters. Ambulatory elderly individuals with asymmetry in knee extension strength, showed deficits in balance control even in normal clinical tests., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported.

Objective: To investigate the differences in biomechanical parameters measured by gait analysis systems between healthy subjects and subjects with plantar fasciitis (PF), and to compare biomechanical parameters between 'normal, barefooted' gait and arch building gait in the participants., Methods: The researchers evaluated 15 subjects (30 feet) with bilateral foot pain and 15 subjects (15 feet) with unilateral foot pain who had a clinical diagnosis of PF. Additionally, 17 subjects (34 feet) who had no heel pain were recruited. Subjects were excluded if they had a traumatic event, prior surgery or fractures of the lower limbs, a leg length discrepancy of 1 cm or greater, a body mass index greater than 35 kg/m 2 , or had musculoskeletal disorders. The participants were asked to walk with an arch building gait on a treadmill at 2.3 km/hr for 5 minutes. Various gait parameters were measured., Results: With the arch building gait, the PF group proved that gait line length and single support line were significantly decreased, and lateral symmetry of the PF group was increased compared to that of the control group. The subjects with bilateral PF displayed significantly increased maximum pressure over the heel and the forefoot during arch building gait. In addition, the subjects with unilateral PF showed significantly increased maximum pressure over the forefoot with arch building gait., Conclusion: The researchers show that various biomechanical differences exist between healthy subjects and those with PF. Employing an arch building gait in patients with PF could be helpful in changing gait patterns to normal biomechanics., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported.

Objective: To assess the cross-sectional area (CSA) of the muscles for investigating the occurrence of asymmetry of the paraspinal (multifidus and erector spinae) and psoas muscles and its relation to the chronicity of unilateral lumbar radiculopathy using magnetic resonance imaging (MRI)., Methods: This retrospective study was conducted between January 2012 to December 2014. Sixty one patients with unilateral L5 radiculopathy were enrolled: 30 patients had a symptom duration less than 3 months (group A) and 31 patients had a symptom duration of 3 months or more (group B). Axial MRI measured the CSA of the paraspinal and psoas muscles at the middle between the lower margin of the upper vertebra and upper margin of the lower vertebra, and obtained the relative CSA (rCSA) which is the ratio of the CSA of muscles to that of the lower margin of L4 vertebra., Results: There were no differences in the demographics between the two groups. In group B, rCSA of the erector spinae at the L4-5 level, and that of multifidus at the L4-5 and L5-S1 levels, were significantly smaller on the involved side as compared with the uninvolved side. In contrast, no significant muscle asymmetry was observed in group A. The rCSA of the psoas was not affected in either group., Conclusion: The atrophy of the multifidus and erector spinae ipsilateral to the lumbar radiculopathy was observed only in patients suffering from unilateral radiculopathy for 3 months or more., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported.

Lineage-specific regulation of tumor progression by the same transcription factor is understudied. We find that levels of the FOXQ1 transcription factor, an oncogene in carcinomas, are decreased during melanoma progression. Moreover, in contrast to carcinomas, FOXQ1 suppresses epithelial-to-mesenchymal transition, invasion, and metastasis in melanoma cells. We find that these lineage-specific functions of FOXQ1 largely depend on its ability to activate (in carcinomas) or repress (in melanoma) transcription of the N-cadherin gene (CDH2). We demonstrate that FOXQ1 interacts with nuclear β-catenin and TLE proteins, and the β-catenin/TLE ratio, which is higher in carcinoma than melanoma cells, determines the effect of FOXQ1 on CDH2 transcription. Accordingly, other FOXQ1-dependent phenotypes can be manipulated by altering nuclear β-catenin or TLE proteins levels. Our data identify FOXQ1 as a melanoma suppressor and establish a mechanism underlying its inverse lineage-specific transcriptional regulation of transformed phenotypes., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To investigate whether the polymorphisms of CASP3 gene (rs4647602, intron A/C and rs1049216, UTR C/T) and CASP9 gene (rs1052576, Gln/Arg G/A and rs1052571, Ser/Val T/C) were associated with the development, and clinical severity of ischemic stroke and functional consequences after stroke., Methods: Genomic DNA from 121 ischemic stroke patients and 201 healthy control subjects were extracted, and polymerase chain reaction products were sequenced. To investigate the association of polymorphisms and the development, and National Institutes of Health Stroke Scale (K-NIHSS), logistic regression models were analyzed., Results: Polymorphism of the untranslational region of CASP3 (rs1049216, UTR C/T) has been associated with the development of ischemic stroke-in codominant1 model (odds ratio [OR], 0.51; 95% confidence interval [CI], 0.29-0.88; p=0.017), in dominant model (OR, 0.57; 95% CI, 0.34-0.97; p=0.034), and in the overdominant model (OR, 0.50; 95% CI, 0.29-0.87; p=0.011). A missense SNP of CASP9 gene (rs1052571, Ser/Val T/C) was associated with the development of ischemic stroke (OR, 1.93; 95% CI, 1.05-3.55; p=0.034 in recessive model)., Conclusion: These results indicate the possibility that CASP3 and CASP9 genes are markers for the development of ischemic stroke., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported.

Objective: To evaluate the relationships between tongue pressure and different aspects of the oral-phase swallowing function., Methods: We included 96 stroke patients with dysphagia, ranging in age from 40 to 88 years (mean, 63.7 years). Measurements of tongue pressure were obtained with the Iowa Oral Performance Instrument, a device with established normative data. Three trials of maximum performance were performed for lip closure pressure (LP), anterior hard palate-to-tongue pressure (AP), and posterior hard palate-to-tongue pressure (PP); buccal-to-tongue pressures on both sides were also recorded (buccal-to-tongue pressure, on the weak side [BW]; buccal-to-tongue pressure, on the healthy side [BH]). The average pressure in each result was compared between the groups. Clinical evaluation of the swallowing function was performed with a videofluoroscopic swallowing study., Results: The average maximum AP and PP values in the intact LC group were significantly higher than those in the inadequate lip closure group (AP, p=0.003; PP, p<0.001). AP and PP showed significant relationships with bolus formation (BF), mastication, premature bolus loss (PBL), tongue to palate contact (TP), and oral transit time (OTT). Furthermore, LP, BW, and BH values were significantly higher in the groups with intact mastication, without PBL and intact TP., Conclusion: These findings indicate that the tongue pressure appears to be closely related to the oral-phase swallowing function in post-stroke patients, especially BF, mastication, PBL, TP and OTT., Competing Interests: No potential conflict of interest relevant to this article was reported.

Objective: To investigate whether baculoviral inhibitor of apoptosis (IAP) repeat containing 5 gene (BIRC5) polymorphisms are associated with the development and clinical phenotypes of ischemic stroke in Korea population., Methods: We enrolled 121 ischemic stroke patients and 291 control subjects. Ischemic stroke patients were divided into subgroups according to the scores of National Institutes of Health Stroke Survey (<6 or ≥6) and Modified Barthel Index (<60 or ≥60). Single nucleotide polymorphisms (SNPs) of BIRC5 (rs3764383 and rs2071214) were selected and genotyped by direct sequencing for all subjects. Multiple logistic regression models (codominant 1 and 2, dominant, recessive, overdominant and log-additive) were used to estimate odds ratios (ORs), 95% confidence intervals (CIs), and p-values., Results: In analysis of stroke susceptibility, the genotype and allele frequencies of rs3764383 exhibited no difference between the control group and the ischemic stroke group. SNP rs2071214 was associated with ischemic stroke in the codominant (p=0.003), dominant (p=0.002), overdominant (p=0.005), and log-additive (p=0.008) models, respectively. The G allele frequency of rs2071214 was significantly (p=0.009) associated with susceptibility for ischemic stroke (OR, 1.57; 95% CI, 1.12-2.21). However, in the analysis for clinical phenotype, no SNP of the BIRC5 gene was found to be associated with ischemic stroke., Conclusion: These results suggest that a missense SNP (rs2071214) of BIRC5 may be associated with the development of ischemic stroke in the Korean population.

To investigate the contribution of the interleukin-6 receptor (IL-6R) gene single nucleotide polymorphisms (SNPs) to the neurological status of Korean patients with ischemic stroke (IS), two SNPs of the IL-6R gene (rs4845617, 5 UTR; rs2228144, Ala31Ala) were selected. IS patients were classified into clinical phenotypes according to two well-defined scores: the National Institutes of Health Stroke Survey (NIHSS) and the Modified Barthel Index scores. There were 121 IS patients and 291 control subjects. The SNP rs4845617 significantly contributed to the neurological status of patients with IS (P = 0.011 in codominant model 2, P = 0.006 in recessive model, and P = 0.008 in log-additive model). Allele frequencies of rs4845617 and rs2228144 demonstrated no significant difference in IS patients and controls. The AG and GG haplotypes differed between the NIHSS 1 (NIHSS scores < 6) group and the NIHSS 2 (NIHSS scores ≥ 6) group in patients with IS (P = 0.014, P = 0.0024). These results suggest that rs4845617 of the IL-6R gene is associated with the neurologic status of Korean patients with IS.

Objective: To investigate whether four single nucleotide polymorphisms (SNPs) rs2293054 [Ile734Ile], rs1047735 [His902His], rs2293044 [Val1353Val], rs2682826 (3'UTR) of nitric oxide synthase 1 (NOS1) are associated with the development and clinical phenotypes of ischemic stroke., Methods: We enrolled 120 ischemic stroke patients and 314 control subjects. Ischemic stroke patients were divided into subgroups according to the scores of the National Institutes of Health Stroke Survey (NIHSS, <6 and ≥6) and Modified Barthel Index (MBI, <60 and ≥60). SNPStats, SNPAnalyzer, and HelixTree programs were used to calculate odds ratios (ORs), 95% confidence intervals (CIs), and p-values. Multiple logistic regression models were performed to analyze genetic data., Results: No SNPs of the NOS1 gene were found to be associated with ischemic stroke. However, in an analysis of clinical phenotypes, we found that rs2293054 was associated with the NIHSS scores of ischemic stroke patients in codominant (p=0.019), dominant (p=0.007), overdominant (p=0.033), and log-additive (p=0.0048) models. Also, rs2682826 revealed a significant association in the recessive model (p=0.034). In allele frequency analysis, we also found that the T alleles of rs2293054 were associated with lower NIHSS scores (p=0.007). Respectively, rs2293054 had a significant association in the MBI scores of ischemic stroke in codominant (p=0.038), dominant (p=0.031), overdominant (p=0.045), and log-additive (p=0.04) models., Conclusion: These results suggest that NOS1 may be related to the clinical phenotypes of ischemic stroke in Korean population.

The amorphous carbon layer (ACL), used as the hardmask for the etching of nanoscale semi-conductor materials, was etched using O2/CHF3 in addition to O2/N2 using pulsed dual-frequency capacitively coupled plasmas, and the effects of source power pulsing for different gas combinations on the characteristics of the plasmas and ACL etching were investigated. As the etch mask for ACL, a patterned SiON layer was used. The etch rates of ACL were decreased with the decrease of pulse duty percentage for both O2/N2 and O2/CHF3 due to decrease of the reactive radicals, such as F and O, with decreasing pulse duty percentage. In addition, at the same pulse duty percentage, the etch selectivity of ACL/SiON with O2/CHF3 was also significantly lower than that with O2/N2. However, the etch profiles of ACL with O2/CHF3 was more anisotropic and the etch profiles were further improved with decreasing the pulse duty percentage than those of ACL with O2/N2. The improved anisotropic etch profiles of ACL with decreasing pulse duty percentage for O2/CHF3 were believed to be related to the formation of a more effective passivation layer, such as a thick fluorocarbon layer, on the sidewall of the ACL during the etching with O2/CHF3, compared to the weak C-N passivation layer formed on the sidewall of ACL when using O2/N2.

Dystonia is a movement disorder characterized by involuntary muscle contractions. Patients with dystonia may experience uncontrollable twisting, repetitive movements, or abnormal posture. A 55-year-old man presented with an involuntary left forearm supination, which he had experienced for five years. There was no history of antecedent trauma to the wrist or elbow. Although conventional therapeutic modalities had been performed, the symptoms persisted. When he visited our hospital, electromyography was performed. Reduced conduction velocity was evident at the elbow-axilla segment of the left median nerve. We suspected that there was a problem on the median nerve between the elbow and the axilla. For this reason, we performed an ultrasonography and magnetic resonance imaging study. A spindle-shaped soft tissue mass was observed at the left median nerve that suggested the possibility of neurofibroma. Dystonia caused by traumatic or compressive peripheral nerve injury has often been reported, but focal dystonia due to a neurogenic tumor is extremely rare. Here, we report our case with a review of the literature.

Monomelic amyotrophy (MMA), also known as Hirayama disease, is a sporadic juvenile muscular atrophy in the distal upper extremities. This disorder rarely involves proximal upper extremities and presents minimal sensory symptoms with no upper motor neuron (UMN) signs. It is caused by anterior displacement of the posterior dural sac and compression of the cervical cord during neck flexion. An 18-year-old boy visited our clinic with a 5-year history of left upper extremity pain and slowly progressive weakness affecting the left shoulder. Atrophy was present in the left supraspinatus and infraspinatus. On neurological examination, positive UMN signs were evident in both upper and lower extremities. Electrodiagnostic study showed root lesion involving the fifth to seventh cervical segment of the cord with chronic and ongoing denervation in the fifth and sixth cervical segment innervated muscles. Cervical magnetic resonance imaging (MRI) showed asymmetric cord atrophy apparent in the left side and intramedullary high signal intensity along the fourth to sixth cervical vertebral levels. With neck flexion, cervical MRI revealed anterior displacement of posterior dural sac, which results in the cord compression of those segments. The mechanisms of myelopathy in our patient seem to be same as that of MMA. We report a MMA patient involving proximal limb with UMN signs in biomechanical concerns and discuss clinical importance of cervical MRI with neck flexion. The case highlights that clinical variation might cause misdiagnosis.

The magnetic tunnel junction (MTJ)-related materials such as CoFeB, CoPt, MgO, and Ru, and W were etched using CH3OH in a pulse-biased inductively coupled plasma system and the effect of bias pulsing (100% 30% duty percentage) on the etch characteristics of the MTJ-related materials was investigated at the substrate temperature of 200 degrees C. The etch selectivity of MTJ-related materials over W was improved by using pulse-biasing possibly due to the formation of more stable and volatile etch products during the pulse-off time and the removal of the compounds more easily on the etched CoFeB surface during the pulse-on time. X-ray photoelectron spectroscopy also showed that the use of lower duty percentage decreases the residue thickness remaining on the etched MTJ materials indirectly indicated the higher volatility of the etch products by the bias pulsing. The etching of nano-patterned CoFeB masked with W also showed more anisotropic etch profile by pulse-biasing probably due to the increased the etch selectivity of CoFeB over W and the decreased redeposition of etch products on the sidewall of the CoFeB features. The most anisotropic CoFeB etch profiles could be observed by using CH3OH gas in the pulse biasing of 30% duty ratio.