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Abstract The hypothalamus plays an important role in aging, but it remains unclear regarding the underlying epigenetics and whether this hypothalamic basis can help address aging-related diseases. Here, by comparing mouse hypothalamus with two other limbic system components, we show that the hypothalamus is characterized by distinctively high-level DNA methylation during young age and by the distinct dynamics of DNA methylation and demethylation when approaching middle age. On the other hand, age-related DNA methylation in these limbic system components commonly and sensitively applies to genes in hypothalamic regulatory pathways, notably oxytocin (OXT) and gonadotropin-releasing hormone (GnRH) pathways. Middle age is associated with transcriptional declines of genes which encode OXT, GnRH and signaling components, which similarly occur in an Alzheimer’s disease (AD)-like model. Therapeutically, OXT-GnRH combination is substantially more effective than individual peptides in treating AD-like disorders in male 5×FAD model. In conclusion, the hypothalamus is important for modeling age-related DNA methylation and developing hypothalamic strategies to combat AD.

Abstract This paper proposes a new method for predicting the stage of osteoporosis by estimating bone-density parameters using an ultrasonic-bone densitometer. Using the developed ultrasonic bone densitometer, the ultrasonic signal passing through the phalanx of the finger was measured, and the measured signal was preprocessed to generate input data for parameter estimation. The Nakagami probability-density function was used for modeling this data, and optimal bone-density parameters were estimated using an optimization problem – to predict the stage of osteoporosis. The proposed method was verified through in vitro and in vivo experiments. In phantom experiments, cubes with different materials (ABS plastic, PLA plastic, Nylon) were used, and each cube had a different density through internal density so that it could mimic bones. The experiments were conducted using them and the results were compared. The experimental results confirmed that there was a correlation between the density and estimated parameters for all three materials. In the in vivo experiment, the osteoporosis stages were classified as normal, osteopenia, and osteoporosis, and the bone-density parameters were estimated for the participants of each group. Thus, a basis for predicting the stage of osteoporosis was created, and data from new participants were collected and verified as test data. As a result, normal and abnormal groups (osteopenia and osteoporosis) were predicted.

Common carotid artery occlusion (CCAO) is a very rare disorder that has rarely been studied. CCAO causes several neurological symptoms but can sometimes be asymptomatic due to the development of various anastomoses. Herein, we report the case of a 70-year-old male patient diagnosed with asymptomatic CCAO due to anastomotic flow. The patient underwent transfemoral cerebral angiography (TFCA) and was found to have CCAO with two collateral pathways, including an occipital arteryvertebral artery anastomosis. We emphasize the importance of TFCA when CCAO is suspected and review the types and anastomotic pathways of CCAO.

Abstract Background Pneumocephalus may be responsible for post-craniotomy headache but is easily overlooked in the clinical situation. In the present study, the relationship between the amount of intracranial air and post-craniotomy headache was investigated. Methods A retrospective observational study was performed on 79 patients who underwent minimal invasive craniotomy for unruptured cerebral aneurysms. Those who had undergone previous neurosurgery, neurological deficit before and after surgery were excluded The amount of air in the cranial cavity was measured using brain computed tomography (CT) taken within 6 h after surgery. To measure the degree of pain due to intracranial air, daily and total analgesic administration amount were used as a pain index. Correlation between intracranial air volume and total consumption of analgesic during hospitalization was tested using Spearman rank correlation coefficients. Receiver operating characteristics (ROC) analysis was used to determine the amount of air associated with increased analgesic consumption over 72 h postoperatively. Results The mean amount of intracranial air was 15.6 ± 9.1 mL. Total administration of parenteral and oral analgesics frequency were 6.5 ± 4.5, 13.2 ± 7.9 respectively. A statically significant correlation was observed between daily and total parenteral analgesic consumption after surgery and the amount of intracranial air at followed-up brain CT postoperatively within 24 h (r = 0.69, p

Osteopontin (OPN) is an extracellular matrix protein with a diverse range of functions, including roles in cell adhesion, migration, and immunomodulation, which are associated with the modulation of neuroinflammation in the central nervous system. The present study was performed to evaluate the involvement of OPN in the eyes of an experimental autoimmune uveoretinitis (EAU) model. The EAU model was developed by immunization of Lewis rats with interphotoreceptor retinoid-binding protein. The results showed the OPN level was remarkably upregulated in the eye of EAU rats on day 9 post-immunization. The level of CD44, a ligand of OPN, was increased in the ciliary body of EAU rats. Furthermore, OPN was also detected in the ciliary body and activated microglia/macrophages in the EAU retina. The results suggest that OPN was significantly upregulated in the eyes of EAU rats, and that it may be useful as an early biomarker of ocular autoimmune diseases. All animal experiments were approved by the Institutional Animal Care and Use Committee of Jeju National University (approval No. 2020-0012) on March 11, 2020.

Objectives This study aims to examine the effects of the July 2018 worldwide valsartan recall and shortage on global trends of antihypertensive medication use in 83 countries.Methods A time-series analysis of monthly purchases of valsartan, other angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) across 83 countries from January 2017 to July 2020 was conducted using the IQVIA MIDAS database. Trends in outcomes were investigated globally and by economic level (developed vs developing economies). The valsartan recall’s impact on antihypertensive use was assessed with interventional autoregressive integrated moving average modelling.Results Global valsartan utilisation trends decreased significantly by 15.7% (−61 166 515 SU; p

BackgroundThe globus pallidus is a highly mitochondria-rich metabolic structure that is particularly sensitive to metabolic disturbances and hypoxia. Symmetric lesions of globus pallidus and delayed diffuse leukoencephalopathy were documented in toxic–metabolic disorders, hypoxia, a neurodegenerative disorder, and mitochondrial encephalopathies. Similar changes are also reported in individuals with active COVID-19 infections with associated hypoxia or critical illness.Case informationWe describe a patient with post–COVID-19 infection who presented with rapid cognitive and neurological decline associated with similar neuroimaging structural changes but without toxic–metabolic changes or hypoxia. Despite multiple non-inflammatory cerebrospinal fluid studies, mechanisms involving post–COVID-19 inflammation and immune dysregulation are suspected, given the unexplained continued decline in the neurological status, lack of concurrent hypoxia or antecedent respiratory difficulties, and after a reasonable exclusion of alternative etiologies. Hypermetabolism of both anteromedial temporal structures and diffuse hypometabolism predominantly in the frontal region on PET scan provided indirect support for possible inflammatory mechanisms after reasonable exclusion of alternative etiologies, such as direct CNS infection, among others. The patient's neurological impairment improved substantially after treatment with pulse steroids, plasmapheresis, and rituximab.ConclusionTo the best of our knowledge, this is the first report of post–COVID-19 with bilateral symmetric contrast-enhancing necrotic lesions of globus pallidus with delayed diffuse supratentorial leukoencephalopathy with microhemorrhages without concurrent hypoxia or reported preceding symptoms suggestive of hypoxia. We suspect that these inflammatory mechanisms might be triggered by prior COVID-19 exposure/infection. Furthermore, the role of the cross-talk between inflammation and clinically mild or silent hypoxia linked to prior COVID-19 infection cannot be excluded. Awareness of these post–COVID-19 neurological sequelae and their potential pathophysiology among those with no known antecedent significant hypoxia are important for early recognition and treatment.

Abstract In this study, preclinical experiments were performed with an in-house developed prototypal photon-counting detector computed tomography (PCD CT) system. The performance of the system was compared with the conventional energy-integrating detector (EID)-based CT, concerning the basic image quality biomarkers and the respective capacities for material separation. The pre- and the post-contrast axial images of a canine brain captured by the PCD CT and EID CT systems were found to be visually similar. Multi-energy images were acquired using the PCD CT system, and machine learning-based material decomposition was performed to segment the white and gray matters for the first time in soft tissue segmentation. Furthermore, to accommodate clinical applications that require high resolution acquisitions, a small, native, high-resolution (HR) detector was implemented on the PCD CT system, and its performance was evaluated based on animal experiments. The HR acquisition mode improved the spatial resolution and delineation of the fine structures in the canine’s nasal turbinates compared to the standard mode. Clinical applications that rely on high-spatial resolution expectedly will also benefit from this resolution-enhancing function. The results demonstrate the potential impact on the brain tissue segmentation, improved detection of the liver tumors, and capacity to reconstruct high-resolution images both preclinically and clinically.

Abstract The wearable electronics integrated with textile-based devices is a promising strategy to meet the requirements of human comfort as well as electrical performances. This research presents a design and development framework for a seamless glove sensor system using digital knitting fabrication. Based on the performance requirements of glove sensors for controlling a prosthetic hand, desirable design components include electrical conductivity, comfort, formfit, electrical sensitivity, and customizable design. These attributes are determined and achieved by applying appropriate materials and fabrication technologies. In this study, a digital knitting CAD/CAM system is utilized to meet the desired performance criteria, and two prototypes of the seamless glove sensor systems are successfully developed for the detection of both human and robotic finger motions. This digital knitting system will provide considerable potential for customized design development as well as a sustainable production process. This structured, systematic approach could be adapted in the future development of wearable electronic textile systems.

Previous studies have shown that Ninjurin-1 participates in cell trafficking and axonal growth following central and peripheral nervous system neuroinflammation. But its precise roles in these processes and involvement in spinal cord injury pathophysiology remain unclear. Western blot assay revealed that Ninjurin-1 levels in rats with spinal cord injury exhibited an upregulation until day 4 post-injury and slightly decreased thereafter compared with sham controls. Immunohistochemistry analysis revealed that Ninjurin-1 immunoreactivity in rats with spinal cord injury sharply increased on days 1 and 4 post-injury and slightly decreased on days 7 and 21 post-injury compared with sham controls. Ninjurin-1 immunostaining was weak in vascular endothelial cells, ependymal cells, and some glial cells in sham controls while it was relatively strong in macrophages, microglia, and reactive astrocytes. These findings suggest that a variety of cells, including vascular endothelial cells, macrophages, and microglia, secrete Ninjurin-1 and they participate in the pathophysiology of compression-induced spinal cord injury. All experimental procedures were approved by the Care and Use of Laboratory Animals of Jeju National University (approval No. 2018-0029) on July 6, 2018.

Abstract Manganese oxide (MnO) nanocubes were fabricated and their surface were modified by ligand encapsulation or ligand exchange, to render them water-soluble. And then, MnO formed the hollow structure by etching using acidic solution (phthalate buffer, pH 4.0). Depending on the ligand of the MnO surface, it increases the interaction between MnO and water molecules. Also, the hollow structure of MnO, as well as the ligand, can greatly enhance the accessibility of water molecules to metal ions by surface area-to-volume ratio. These factors provide high R1 relaxation, leading to strong T1 MRI signal. We have confirmed T1-weighted MR contrast effect using 4-kinds of MnO nanocubes (MnOEn, MnOEnHo, MnOEx and MnOExHo). They showed enough a MR contrast effect and biocompatibility. Especially, among them, MnOExHo exhibited high T1 relaxivity (r1) (6.02 mM−1 s−1), even about 1.5 times higher sensitivity than commercial T1 MR contrast agents. In vitro/in vivo studies have shown that MnOExHo provides highly sensitive T1-weighted MR imaging, thereby improving diagnostic visibility at the disease site.

Abstract Background Gastric cancer is a considerable burden for worldwide patients. And diffuse gastric cancer is the most insidious subgroup with poor survival. The phenotypic characterization of the diffuse gastric cancer cell line can be useful for gastric cancer researchers. In this article, we aimed to characterize the diffuse gastric cancer cells with MRI and transcriptomic data. We hypothesized that gene expression pattern is associated with the phenotype of the cells and that the heterogeneous enhancement pattern and the high tumorigenicity of SNU484 can be modulated by the perturbation of the highly expressed gene. Methods We evaluated the 9.4 T magnetic resonance imaging and transcriptomic data of the orthotopic mice models from diffuse gastric cancer cells such as SNU484, Hs746T, SNU668, and KATO III. We included MKN74 as an intestinal cancer control cell. After comprehensive analysis integrating MRI and transcriptomic data, we selected CD34 and validated the effect by shRNA in the BALB/c nude mice models. Results SNU484, SNU668, Hs746T, and MKN74 formed orthotopic tumors by the 5 weeks after cell injection. The diffuse phenotype was found in the SNU484 and Hs746T. SNU484 was the only tumor showing the heterogeneous enhancement pattern on T2 images with a high level of CD34 expression. Knockdown of CD34 decreased the round-void shape in the H&E staining (P = 0.028), the heterogeneous T2 enhancement, and orthotopic tumorigenicity (100% vs 66.7%). The RNAseq showed that the suppressed CD34 is associated with the downregulated gene-sets of the extracellular matrix remodeling. Conclusion Suppression of CD34 in the human-originated gastric cancer cell suggests that it is important for the round-void histologic shape, heterogeneous enhancement pattern on MRI, and the growth of gastric cancer cell line.

This study investigated the effects of whey bioconversion products (WBPs) produced by lactic acid bacteria on periodontal disease. WBPs were prepared by fermenting whey with seven lactic acid bacteria, Limosilactobacillus fermentum SMFM2017-CK1 (LF-CK1), L. plantarum SMFM2017-NK2 (LP-NK2), Pediococcus pentosaceus SMFM2017-NK1 (PP-NK1), L. plantarum SMFM2017-NK1 (LP-NK1), L. paraplantarum SMFM2017-YK1 (LPP-YK1), L. plantarum SMFM2017-YK1 (LP-YK1), and L. fermentum SMFM2017-NK1 (LF-NK1)]; the pH of the fermented whey was adjusted to 6.5, followed by centrifugation. WBPs were examined for their effect on cell viability and antimicrobial activity against periodontal pathogens. The selected WBPs were used in animal experiments. After inducing periodontitis through right mandibular first molar ligation, WBPs were administered orally for 8 weeks. After sacrifice, gene and protein expression analyses of genes related to inflammatory and oxidative stress were performed, and histopathological analysis of gingival tissue was conducted. Our results showed that LP-YK1 WBP (WBP produced by LP-YK1) and LF-NK1 WBP (WBP produced by LF-NK1) groups exerted higher anti-inflammatory and antioxidant effects compared to the control group (p < 0.05). Histopathological analysis revealed that infiltration of inflammatory cells and epithelial cell proliferation were reduced in the LP-YK1 WBP group. These results indicate that WBPs prepared with LP-YK1 can be used as a postbiotic to alleviate periodontitis.

Metal artifacts are considered a major challenge in computed tomography (CT) as these adversely affect the diagnosis and treatment of patients. Several approaches have been developed to address this problem. The present study explored the clinical potential of a novel photon-counting detector (PCD) CT system in reducing metal artifacts in head CT scans. In particular, we studied the recovery of an oral tumor region located under metal artifacts after correction. Three energy thresholds were used to group data into three bins (bin 1: low-energy, bin 2: middle-energy, and bin 3: high-energy) in the prototype PCD CT system. Three types of physical phantoms were scanned on the prototype PCD CT system. First, we assessed the accuracy of iodine quantification using iodine phantoms at varying concentrations. Second, we evaluated the performance of material decomposition (MD) and virtual monochromatic images (VMIs) using a multi-energy CT phantom. Third, we designed an ATOM phantom with metal insertions to verify the effect of the proposed metal artifact reduction. In particular, we placed an insertion-mimicking an iodine-enhanced oral tumor in the beam path of metallic objects. Normalized metal artifact reduction (NMAR) was performed for each energy bin image, followed by an image-based MD and VMI reconstruction. Image quality was analyzed quantitatively by contrast-to-noise ratio (CNR) measurements. The results of iodine quantification showed a good match between the true and measured iodine concentrations. Furthermore, as expected, the contrast between iodine and the surrounding material was higher in bin 1 image than in bin 3 image. On the other hand, the bin 3 image of the ATOM phantom showed fewer metal artifacts than the bin 1 image because of the higher photon energy. The result of quantitative assessment demonstrated that the 40-keV VMI (CNR: 20.6 ± 1.2) with NMAR and MD remarkably increased the contrast of the iodine-enhanced region compared with that of the conventional images (CNR: 10.4 ± 0.5) having 30 to 140 keV energy levels. The PCD-based multi-energy CT imaging has immense potential to maximize the contrast of the target tissue and reduce metal artifacts simultaneously. We believe that it would open the door to novel applications for the diagnosis and treatment of several diseases.

Objective To investigate the prevalence of complex regional pain syndrome (CRPS), post-herpetic neuralgia (PHN), trigeminal neuralgia (TN), and diabetic neuropathy (DN), common causes of neuropathic pain encountered in pain clinics. Methods We investigated the period prevalence rate of CRPS, PHN, TN, and DN using data from a Korean national electronic database from 2009 to 2013. Results The prevalence of CRPS decreased slightly throughout the study period, while the prevalence of PHN increased from 2009 to 2013. The prevalence of TN was reduced over the same period. The prevalence of DN increased from 2009 to 2012 but decreased in 2013. All four neuropathic diseases were more prevalent in individuals aged over 70 years. The prevalence of CRPS, PHN, and TN were more common in women than in men, but DN showed no gender difference. Conclusion While the prevalence of CRPS and TN has decreased in Korea, that of PHN and DN has increased. With the exception of DN, the neuropathic diseases were more prevalent in women. Further studies are necessary to investigate the risk factors and socioeconomic burden for each disease, and national efforts are essential to limit the development of these preventable neuropathic diseases.

We examined the sea-breeze-initiated rainfall in the Seoul Metropolitan area (SMA) on 6 July 2017 using the weather research and forecasting (WRF) model. The model captures the arrival of the sea breeze front (SBF), the development of afternoon rainfall in the SMA, and the location of the sea-breeze-initiated maximum rainfall in the northeastern SMA reasonably well but overestimates the subsequent rainfall. We conducted sensitivity tests to better understand the urban effect on the sea-breeze-initiated rainfall event. Through factor separation analysis, we first examined the explicit role of sea and urban effect on sea-breeze-initiated rainfall. The results show that the interaction of sea and urban effects cause rainfall in the northwest and northeast of the SMA, indicating that both urban heat island circulation (UHIC) and sea breeze play an important role in the study case’s rainfall. We further examined the relative role of urban roughness and anthropogenic heat on the sea-breeze-initiated rainfall through factor separation analysis. Both anthropogenic heat and urban roughness play a role in increasing precipitation in the northeastern area of the SMA, with a larger contribution of anthropogenic heat than urban roughness. The relationship between low-level convergence at the SBF and urban factors is discussed.

An amendment to this paper has been published and can be accessed via the original article.

In recent years, flexible sensors for data gloves have been developed that aim to achieve excellent wearability, but they are associated with difficulties due to the complicated manufacturing and embedding into the glove. This study proposes a knitted glove integrated with strain sensors for pattern recognition of hand postures. The proposed sensing glove is fabricated at all once by a knitting technique without sewing and bonding, which is composed of strain sensors knitted with conductive yarn and a glove body with non-conductive yarn. To verify the performance of the developed glove, electrical resistance variations were measured according to the flexed angle and speed. These data showed different values depending on the speed or angle of movements. We carried out experiments on hand postures pattern recognition for the practicability verification of the knitted sensing glove. For this purpose, 10 able-bodied subjects participated in the recognition experiments on 10 target hand postures. The average classification accuracy of 10 subjects reached 94.17% when their own data were used. The accuracy of up to 97.1% was achieved in the case of grasp posture among 10 target postures. When all mixed data from 10 subjects were utilized for pattern recognition, the average classification expressed by the confusion matrix arrived at 89.5%. Therefore, the comprehensive experimental results demonstrated the effectiveness of the knitted sensing gloves. In addition, it is expected to reduce the cost through a simple manufacturing process of the knitted sensing glove.

More than half of post-operative complications can be prevented, and operation performances can be improved based on the feedback gathered from operations or notifications of the risks during operations in real time. However, existing surgical analysis methods are limited, because they involve time-consuming processes and subjective opinions. Therefore, the detection of surgical instruments is necessary for (a) conducting objective analyses, or (b) providing risk notifications associated with a surgical procedure in real time. We propose a new real-time detection algorithm for detection of surgical instruments using convolutional neural networks (CNNs). This algorithm is based on an object detection system YOLO9000 and ensures continuity of detection of the surgical tools in successive imaging frames based on motion vector prediction. This method exhibits a constant performance irrespective of a surgical instrument class, while the mean average precision (mAP) of all the tools is 84.7, with a speed of 38 frames per second (FPS).

We designed a high-sensitivity magnetic resonance imaging contrast agent that could be used to diagnose diseases. First, magnetic nanocrystals were synthesized by a thermal decomposition method on an organic solvent to obtain a high magnetism and methoxy poly(ethylene glycol)-poly(lactic acid) as an amphiphilic polymer using the ring-opening polymerization method to stably disperse the magnetic nanocrystals in an aqueous phase. Subsequently, the magnetic nanoclusters simultaneously self-assembled with methoxy poly(ethylene glycol)-poly(lactic acid) using the nano-emulsion method to form magnetic nanoclusters. Because their shape was similar to a raspberry, they were named PEGylated magnetic nano-assemblies. The PEGylated magnetic nano-assemblies were dispersed stably in the aqueous phase with a uniform size of approximately 65–70 nm for an extended period (0 days: 68.8 ± 5.1 nm, 33 days: 69.2 ± 2.0 nm, and 44 days: 63.2 ± 5.6). They exhibited both enough of a magnetic resonance (MR) contrast effect and biocompatibility. In an in vivo study, the PEGylated magnetic nano-assemblies provided a high contrast effect for magnetic resonance images for a long time after one treatment, thereby improving the diagnostic visibility of the disease site.

Interscapular brown adipose tissue (BAT) plays an important role in controlling glucose homeostasis. Increased glucose entry and glycolysis in BAT result in lactate production and release. The adipose tissue expresses the lactate receptor hydrocarboxylic acid receptor 1 (HCAR1), markedly downregulated in male diet-induced obese (DIO) and ob/ob mice. In this study, we examined the role of HCAR1 in BAT in controlling glucose homeostasis in male DIO mice. We overexpressed HCAR1 in BAT by injecting adeno-associated viruses (AAVs) expressing HCAR1 into the BAT pads of male DIO C57BL/6J mice. Overexpressing HCAR1 in BAT resulted in augmented glucose uptake by BAT in response to treatment with the HCAR1 agonist. HCAR1 overexpression elevated BAT temperature associated with increased thermogenic gene expression in BAT. HCAR1 overexpression prevented body weight gain in male DIO mice. Importantly, mice overexpressing HCAR1 in BAT exhibited improved glucose tolerance and insulin sensitivity. HCAR1 overexpression upregulated the Slc2a4 gene expression and promoted GLUT4 trafficking to the plasma membrane. In addition, mice overexpressing HCAR1 displayed a decrease in hormone-sensitive lipase (HSL) phosphorylation and increased lipogenic enzyme gene expression in BAT. Unlike DIO mice, overexpressing HCAR1 in BAT of mice fed a low-fat diet did not change body weight gain and glucose homeostasis. Taken together, our results support the interpretation that HCAR1 expressed in BAT promotes glucose entry and reduces lipolysis in BAT of male DIO mice. As activation of HCAR1 in BAT restores body weight, glucose tolerance, and insulin sensitivity in male DIO mice, our study suggests that interoceptive lactate detection via HCAR1 in BAT can regulate glucose and lipid substrate utilization and/or availability to promote healthy metabolism. [ABSTRACT FROM AUTHOR]