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Background/Objectives: Artificial intelligence (AI)-based volumetric measurements for assessing sarcopenia are expected to offer comprehensive insight into three-dimensional muscle volume and distribution. Therefore, we investigated the role of sarcopenia using computed tomography (CT)-based automated AI volumetric muscle measurements in predicting neoadjuvant chemoradiotherapy (nCRT) response and prognosis in patients with rectal cancer who underwent nCRT. Methods: We retrospectively analyzed the data of patients who underwent nCRT followed by curative resection between March 2010 and August 2021. Sarcopenia was defined using the Q1 cutoff value of the volumetric skeletal muscle index (SMI). The association between pre-nCRT volumetric sarcopenia and nCRT response was analyzed using logistic regression. A Cox proportional hazards model was used to identify the prognostic value of the pre- and post-nCRT volumetric SMIs. Results: Notably, 22 (25.6%) of the 86 patients had volumetric sarcopenia. The sarcopenia group showed a poorer nCRT response than the non-sarcopenia group. Pre-nCRT sarcopenia was a significant predictor of poor nCRT response (OR, 0.34 [95% CI, 0.12-0.96]; p = 0.041). Furthermore, an increased volumetric SMI during nCRT was a more significant prognostic factor on recurrence-free survival (aHR, 0.26 [95% CI, 0.08-0.83]; p = 0.023) and overall survival (aHR, 0.41 [95% CI, 0.17-0.99]; p = 0.049) than a decreased SMI. Conclusions: Volumetric sarcopenia can be used to predict poor nCRT response. A reduction in volumetric sarcopenia can be a poor prognostic factor in patients with rectal cancer who undergo nCRT.

Purpose: This study aimed to explore traumatic experiences and posttraumatic growth among Korean veterans., Methods: A qualitative study was conducted using photovoice. Purposive sampling strategies yielded five veterans who had experienced traumatic events. Participants engaged in three discussion sessions between August 5, 2023, and October 28, 2023. The collected data were analyzed using photovoice document analysis and thematic analysis., Results: Study results identified the following themes: 'The collapse of my life as a result massive trauma,' 'Sinking into endless isolation and disconnection,' 'The process of finding myself through reflection,' and 'My life journey moving forward together.' Despite the irreversible damage caused by traumatic experiences during military service, the participants continuously reflected on the meaning of their trauma and posttraumatic growth, thereby recovering their authentic selves., Conclusion: Veterans who have experienced traumatic events face severe difficulties, however through their efforts at recovery, they recognize the individuals they are now. This study suggests the need for social support and highlights the necessity of providing various opportunities and policy assistance to traumatized veterans., Competing Interests: Choi, Heeseung has been the Associate Editor of JKAN since 2022 but has no role in the review process. Except for that, no potential conflict of interest relevant to this article was reported., (© 2024 Korean Society of Nursing Science.)

Background: The efficacy of cell implantation via 3D-spheroids to treat basal tone in fecal incontinence remains unclear. To address this, in this study, we aimed to identify cell differentiation and assess the development of a contractile phenotype corresponding to smooth muscle cells (SMCs) following implantation of 3D-spheroid and 2D-cultured human adipose stem cells (hASCs) in an in vivo internal anal sphincter (IAS)-targeted mouse model., Methods: We developed an IAS-targeted in vivo model via rapid freezing (at - 196 °C) of the dorsal layers of the region of interest (ROI) of the IAS ring posterior quarter, between the submucosal and muscular layers, following submucosal dissection (n = 60 rats). After implantation of tetramethylindocarbocyanine perchlorate (Dil)-stained 3D and 2D-cells into randomly allocated cryoinjured rats, the entire sphincter ring or only the cryoinjured ROI was harvested. Expression of SMC markers, RhoA/ROCKII and its downstream molecules, and fibrosis markers was analyzed. Dil, α-smooth muscle actin (α-SMA), and RhoA signals were used for cell tracking., Results: In vitro, 3D-spheroids exhibited higher levels of SMC markers and RhoA/ROCKII-downstream molecules than 2D-hASCs. The IAS-targeted cryoinjured model exhibited substantial loss of SMC layers of the squamous epithelium lining of the anal canal, as well as reduced expression of SMC markers and RhoA-related downstream molecules. In vivo, 3D-spheroid implantation induced SMC markers and contractile molecules weakly at 1 week. At 2 weeks, the mRNA expression of aSma, Sm22a, Smoothelin, RhoA, Mypt1, Mlc 20 , Cpi17, and Pp1cd increased, whereas that of fibrosis markers reduced significantly in the 3D-spheroid implanted group compared to those in the sham, non-implanted, and 2D-hASC implanted groups. Protein levels of RhoA, p-MYPT1, and p-MLC 20 were higher in the 3D-spheroid-implanted group than in the other groups. At 2 weeks, in the implanted groups, the cryoinjured tissues (which exhibited Dil, α-SMA, and RhoA signals) were restored, while they remained defective in the sham and non-implanted groups., Conclusions: These findings demonstrate that, compared to 2D-cultured hASCs, 3D-spheroids more effectively induce a contractile phenotype that is initially weak but subsequently improves, inducing expression of RhoA/ROCKII-downstream molecules and SMC differentiation associated with IAS basal tone., (© 2024. The Author(s).)

Synthesizing perceivable artificial neural inputs independent of typical sensory channels remains a fundamental challenge in the development of next-generation brain-machine interfaces. Establishing a minimally invasive, wirelessly effective, and miniaturized platform with long-term stability is crucial for creating a clinically meaningful interface capable of mediating artificial perceptual feedback. In this study, we demonstrate a miniaturized fully implantable wireless transcranial optogenetic encoder designed to generate artificial perceptions through digitized optogenetic manipulation of large cortical ensembles. This platform enables the spatiotemporal orchestration of large-scale cortical activity for remote perception genesis via real-time wireless communication and control, with optimized device performance achieved by simulation-guided methods addressing light and heat propagation during operation. Cue discrimination during operant learning demonstrates the wireless genesis of artificial percepts sensed by mice, where spatial distance across large cortical networks and sequential order-based analyses of discrimination performance reveal principles that adhere to general perceptual rules. These conceptual and technical advancements expand our understanding of artificial neural syntax and its perception by the brain, guiding the evolution of next-generation brain-machine communication.

Biologically inspired artificial vision research has led to innovative robotic vision systems with low optical aberration, wide field of view, and compact form factor. However, challenges persist in object detection and recognition against complex backgrounds and varied lighting. Inspired by the feline eye, which features a vertically elongated pupil and tapetum lucidum, this study introduces an artificial vision system designed for superior object detection and recognition in a monocular framework. Using a slit-like elliptical aperture and a patterned metal reflector beneath a hemispherical silicon photodiode array, the system reduces excessive light and enhances photosensitivity. This design achieves clear focus under bright light and enhanced sensitivity in dim conditions. Theoretical and experimental analyses demonstrate the system's ability to filter redundant information and detect camouflaged objects in diverse lighting, representing a substantial advancement in monocular camera technology and the potential of biomimicry in optical innovations.

The trajectory prediction of a vehicle emerges as a pivotal component in Intelligent Transportation Systems. On urban roads where external factors such as intersections and traffic control devices significantly affect driving patterns along with the driver's intrinsic habits, the prediction task becomes much more challenging. Furthermore, long-term forecasting of trajectories accumulates prediction errors, leading to substantially inaccurate predictions that may deviate from the actual road. As a solution to these challenges, we propose a long-term vehicle trajectory prediction method that is robust to error accumulation and prevents off-road predictions. In this study, the Transformer model is utilized to analyze and forecast vehicle trajectories. In addition, we propose an extra encoding network to precisely capture the effect of the external factors on the driving pattern by producing an abstract representation of the situation nearby the driver. To avoid off-road predictions, we propose a post-processing method, called link projection, which projects predictions onto the road geometry. Moreover, to overcome the limitations of Euclidean distance-based evaluation metrics in evaluating the accuracy of the entire trajectory, we propose a new metric called area-between-curves (ABC). It measures the similarity between two trajectories, and thus the accordance between the two can be effectively evaluated. Extensive evaluations are conducted using real-world datasets against widely-used methods to demonstrate the effectiveness of the proposed approach. The results show that the proposed approach outperforms the conventional deep learning models by up to 65.74% (RMSE), 60.13% (MAE) and 91.45% (ABC).

Chimeric antigen receptor (CAR)-engineered natural killer (NK) cells are a promising immunotherapy for solid cancers; however, their effectiveness against pancreatic cancer is limited by the immunosuppressive tumor microenvironment. In particular, low NK cell infiltration poses a major obstacle that reduces cytotoxicity. The current study aimed to enhance the tumor-homing capacity of CAR-NK cells by targeting the chemokine-chemokine receptor axis between NK and pancreatic cancer cells. To this end, data from a chemokine array and The Cancer Genome Atlas pan-cancer cohort were analyzed. Pancreatic cancer cells were found to secrete high levels of ligands for C-X-C motif receptor 1 (CXCR1) and CXCR2. Subsequently, we generated anti-mesothelin CAR-NK cells incorporating CXCR1 or CXCR2 and evaluated their tumor-killing abilities in 2D cancer cell co-culture and 3D tumor-mimetic organoid models. CAR-NK cells engineered with CXCR2 demonstrated enhanced tumor killing and strong infiltration of tumor sites. Collectively, these findings highlight the potential of CXCR2-augmented CAR-NK cells as a clinically relevant modality for effective pancreatic cancer treatment. By improving their infiltration and tumor-killing capabilities, these CXCR2-augmented CAR-NK cells have the potential to overcome the challenges posed by the immunosuppressive tumor microenvironment, providing improved therapeutic outcomes., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Purpose: The integration of artificial intelligence (AI) and magnetic resonance imaging in rectal cancer has the potential to enhance diagnostic accuracy by identifying subtle patterns and aiding tumor delineation and lymph node assessment. According to our systematic review focusing on convolutional neural networks, AI-driven tumor staging and the prediction of treatment response facilitate tailored treat-ment strategies for patients with rectal cancer., Methods: This paper summarizes the current landscape of AI in the imaging field of rectal cancer, emphasizing the performance reporting design based on the quality of the dataset, model performance, and external validation., Results: AI-driven tumor segmentation has demonstrated promising results using various convolutional neural network models. AI-based predictions of staging and treatment response have exhibited potential as auxiliary tools for personalized treatment strategies. Some studies have indicated superior performance than conventional models in predicting microsatellite instability and KRAS status, offer-ing noninvasive and cost-effective alternatives for identifying genetic mutations., Conclusion: Image-based AI studies for rectal can-cer have shown acceptable diagnostic performance but face several challenges, including limited dataset sizes with standardized data, the need for multicenter studies, and the absence of oncologic relevance and external validation for clinical implantation. Overcoming these pitfalls and hurdles is essential for the feasible integration of AI models in clinical settings for rectal cancer, warranting further research.

Introduction: We aimed to evaluate the difference in intraoperative oxygen reserve index (ORi) between the sedatives remimazolam (RMMZ) and dexmedetomidine (DEX)., Methods: Seventy-eight adult patients scheduled for sedation under regional anesthesia were randomly assigned to either the DEX ( n = 39) or RMMZ ( n = 39) group. The primary outcome was the difference in perioperative ORi between the groups. The secondary outcomes included respiratory depression, hypo- or hypertension, heart rate (HR), blood pressure, respiratory rate and postoperative outcomes. Additionally, the number of patients who experienced a decrease in intraoperative ORi to < 50% and the associated factors were analyzed., Results: The ORi was significantly higher in the RMMZ group at 15 min after sedation maintenance. There were no significant differences in respiratory depression between the two groups. The intraoperative HR was significantly higher in the RMMZ group after the induction of sedation, 15 min after sedation maintenance, and at the end of surgery. No other results were significantly different between the two groups. The incidence of a decrease in intraoperative ORi to < 50% was significantly higher in the DEX group. Factors associated with a decrease in the intraoperative ORi to < 50% were diabetes mellitus, low baseline peripheral oxygen saturation (SpO 2 ), and DEX use. In the receiver operating characteristic curve analysis for a decrease in the intraoperative ORi to < 50%, the cutoff baseline SpO 2 was 97%., Conclusion: RMMZ is recommended as a sedative for patients with a low baseline SpO 2 and intraoperative bradycardia. Further studies should be conducted to establish the criteria for a significant ORi reduction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lee, Kim, Kang, Choi, Kim and You.)

Background: Oncologic impact of genetic alteration across synchronous colorectal cancer (CRC) still remains unclear. This study aimed to compare the oncologic relevance according to genetic alteration between synchronous and solitary CRC with performing systematic review., Methods: Multicenter retrospective analysis was performed for CRC patients with curative resection. Genetic profiling was consisted of microsatellite instability (MSI) testing, RAS (K-ras, and N-ras), and BRAF (v-Raf murine sarcoma viral oncogene homolog B1) V600E mutation. Multivariate analyses were conducted using logistic regression for synchronicity, and Cox proportional hazard model with stage-adjusting for overall survival (OS) and disease-free survival (DFS)., Results: It was identified synchronous (n = 36) and solitary (n = 579) CRC with similar base line characteristics. RAS mutation was associated to synchronous CRC with no relations of MSI and BRAF. During median follow up of 77.8 month, Kaplan-meier curves showed significant differences according to MSI-high for OS, and in RAS, and BRAF mutation for DFS, respectively. In multivariable analyses, RAS and BRAF mutation were independent factors (RAS, HR = 1.808, 95% CI = 1.18-2.77, p = 0.007; BRAF, HR = 2.417, 95% CI = 1.32-4.41, p = 0.004). Old age was independent factor for OS (HR = 3.626, 95% CI = 1.09-12.00, p = 0.035)., Conclusion: This study showed that oncologic outcomes might differ according to mutation burden characterized by RAS, BRAF, and MSI between synchronous CRC and solitary CRC. In addition, our systematic review highlighted a lack of data and much heterogeneity in genetic characteristics and survival outcomes of synchronous CRC relative to that of solitary CRC., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: The prognostic value of the volume and density of skeletal muscles in the abdominal waist of patients with colon cancer remains unclear. This study aimed to investigate the association between the automated computed tomography (CT)-based volume and density of the muscle in the abdominal waist and survival outcomes in patients with colon cancer., Materials and Methods: We retrospectively evaluated 474 patients with colon cancer who underwent surgery with curative intent between January 2010 and October 2017. Volumetric skeletal muscle index and muscular density were measured at the abdominal waist using artificial intelligence (AI)-based volumetric segmentation of body composition on preoperative pre-contrast CT images. Patients were grouped based on their skeletal muscle index (sarcopenia vs. not) and muscular density (myosteatosis vs. not) values and combinations (normal, sarcopenia alone, myosteatosis alone, and combined sarcopenia and myosteatosis). Postsurgical disease-free survival (DFS) and overall survival (OS) were analyzed using univariable and multivariable analyses, including multivariable Cox proportional hazard regression., Results: Univariable analysis showed that DFS and OS were significantly worse for the sarcopenia group than for the non-sarcopenia group ( P = 0.044 and P = 0.003, respectively, by log-rank test) and for the myosteatosis group than for the non-myosteatosis group ( P < 0.001 by log-rank test for all). In the multivariable analysis, the myosteatotic muscle type was associated with worse DFS (adjusted hazard ratio [aHR], 1.89 [95% confidence interval, 1.25-2.86]; P = 0.003) and OS (aHR, 1.90 [95% confidence interval, 1.84-3.04]; P = 0.008) than the normal muscle type. The combined muscle type showed worse OS than the normal muscle type (aHR, 1.95 [95% confidence interval, 1.08-3.54]; P = 0.027)., Conclusion: Preoperative volumetric sarcopenia and myosteatosis, automatically assessed from pre-contrast CT scans using AI-based software, adversely affect survival outcomes in patients with colon cancer., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2023 The Korean Society of Radiology.)

Cancer-cell-derived exosomes confer oncogenic properties in their tumor microenvironment and to other cells; however, the exact mechanism underlying this process is unclear. Here, we investigated the roles of cancer-cell-derived exosomes in colon cancer. Exosomes were isolated from colon cancer cell lines, HT-29, SW480, and LoVo, using an ExoQuick-TC kit, identified using Western blotting for exosome markers, and characterized using transmission electron microscopy and nanosight tracking analysis. The isolated exosomes were used to treat HT-29 to evaluate their effect on cancer progression, specifically cell viability and migration. Cancer-associated fibroblasts (CAFs) were obtained from patients with colorectal cancer to analyze the effect of the exosomes on the tumor microenvironment. RNA sequencing was performed to evaluate the effect of the exosomes on the mRNA component of CAFs. The results showed that exosome treatment significantly increased cancer cell proliferation, upregulated N-cadherin, and downregulated E-cadherin. Exosome-treated cells exhibited higher motility than control cells. Compared with control CAFs, exosome-treated CAFs showed more downregulated genes. The exosomes also altered the regulation of different genes involved in CAFs. In conclusion, colon cancer-cell-derived exosomes affect cancer cell proliferation and the epithelial-mesenchymal transition. They promote tumor progression and metastasis and affect the tumor microenvironment.

Several Kalanchoë species reproduce asexually by forming plantlets in the leaf crenulations. Some species produce plantlets incessantly via somatic embryogenesis and organogenesis, whereas others exclusively develop plantlets after leaf detachment, presumably through organogenesis. SHOOT MERISTEMLESS ( STM ), which mediates SAM functions, appears to be involved in Kalanchoë plantlet formation, suggesting that meristem genes may be essential for plantlet formation. However, the genetic regulatory network for establishing and maintaining plantlet primordia in Kalanchoë remains elusive. Here, we showed that meristem genes were differentially expressed in the leaf crenulations of K. pinnata during plantlet development after leaf detachment. The regulatory interactions among these meristem genes are largely conserved in K. pinnata crenulations. Moreover, transgenic antisense (AS) plants with lower expression of these key meristem genes formed significantly fewer plantlets with some morphological defects, suggesting that the meristem genes play an important role in plantlet formation and development. Our research revealed that key meristem genetic pathways were co-opted to the leaf margin to facilitate the unique asexual reproduction mechanism in K. pinnata . This also highlights how evolutionary tinkering invents new structures such as epiphyllous buds and plantlets by rewiring pre-existing genetic pathways., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jácome-Blásquez and Kim.)

The development of organoid culture technologies has triggered industrial interest in ex vivo drug test-guided clinical response prediction for precision cancer therapy. The three-dimensional culture encapsulated with basement membrane (BM) components is extremely important in establishing ex vivo organoids and drug sensitivity tests because the BM components confer essential structures resembling tumor histopathology. Although numerous studies have demonstrated three-dimensional culture-based drug screening methods, establishing a large-scale drug-screening platform with matrix-encapsulated tumor cells is challenging because the arrangement of microspots of a matrix-cell droplet onto each well of a microwell plate is inconsistent and difficult to standardize. In addition, relatively low scales and lack of reproducibility discourage the application of three-dimensional organoid-based drug screening data for precision treatment or drug discovery. To overcome these limitations, we manufactured an automated organospotter-integrated high-throughput organo-on-pillar (high-TOP) drug-screening platform. Our system is compatible with various extracellular matrices, including BM extract, Matrigel, collagen, and hydrogel. In addition, it can be readily utilized for high-content analyses by simply exchanging the bottom plates without disrupting the domes. Our system demonstrated considerable robustness, consistency, reproducibility, and biological relevancy in three-dimensional drug sensitivity analyses using Matrigel-encapsulated ovarian cancer cell lines. We also demonstrated proof-of-concept cases representing the clinical feasibility of high-TOP-assisted ex vivo drug tests linked to clinical chemo-response in ovarian cancer patients. In conclusion, our platform provides an automated and standardized method for ex vivo drug-sensitivity-guided clinical response prediction, suggesting effective chemotherapy regimens for patients with cancer., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Bosung Ku has patent pending to Licensee. Sang Youl Jeon has patent pending to Licensee. None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

With the rise of mobile robotics, including self-driving automobiles and drones, developing artificial vision for high-contrast and high-acuity imaging in vertically uneven illumination conditions has become an important goal. In such situations, balancing uneven illumination, improving image contrast for facile object detection, and achieving high visual acuity in the main visual fields are key requirements. Meanwhile, in nature, cuttlefish (genus Sepia ) have evolved an eye optimized for vertically uneven illumination conditions, which consists of a W-shaped pupil, a single spherical lens, and a curved retina with a high-density photoreceptor arrangement and polarized light sensitivity. Here, inspired by the cuttlefish eye, we report an artificial vision system consisting of a W-shaped pupil, a single ball lens, a surface-integrated flexible polarizer, and a cylindrical silicon photodiode array with a locally densified pixel arrangement. The W-shaped pupil integrated on the ball lens balances vertically uneven illumination, and the cylindrical silicon photodiode array integrated with the flexible polarizer enables high-contrast and high-acuity imaging.

Objective: Studies on development of an anal incontinence (AI) model targeting smooth muscle cells (SMCs) of the internal anal sphincter (IAS) have not been reported. The differentiation of implanted human adipose-derived stem cells (hADScs) into SMCs in an IAS-targeting AI model has also not been demonstrated. We aimed to develop an IAS-targeting AI animal model and to determine the differentiation of hADScs into SMCs in an established model., Materials and Methods: The IAS-targeting AI model was developed by inducing cryoinjury at the inner side of the muscular layer via posterior intersphincteric dissection in Sprague-Dawley rats. Dil-stained hADScs were implanted at the IAS injury site. Multiple markers for SMCs were used to confirm molecular changes before and after cell implantation. Analyses were performed using H&E, immunofluorescence, Masson's trichrome staining, and quantitative RT-PCR., Results: Impaired smooth muscle layers accompanying other intact layers were identified in the cryoinjury group. Specific SMC markers, including SM22α, calponin, caldesmon, SMMHC, smoothelin, and SDF-1 were significantly decreased in the cryoinjured group compared with levels in the control group. However, CoL1A1 was increased significantly in the cryoinjured group. In the hADSc-treated group, higher levels of SMMHC, smoothelin, SM22α, and α-SMA were observed at two weeks after implantation than at one week after implantation. Cell tracking revealed that Dil-stained cells were located at the site of augmented SMCs., Conclusions: This study first demonstrated that implanted hADSc restored impaired SMCs at the injury site, showing stem cell fate corresponding to the established IAS-specific AI model.

Microfluidic preconcentration enables the collection or extraction of low-abundance analytes at specific locations. It has attracted considerable attention as an essential technology in bioengineering, particularly for detection and diagnosis. Herein, we investigated the key parameters in the preconcentration of fluorescent dyes based on electrophoresis in a microfluidic electromembrane system. Commercial ion-exchange membrane (IEM)-integrated polydimethylsiloxane microfluidic devices were fabricated, and Alexa Fluor 488 and Rhodamine 6G were used as fluorescent dyes for sample preconcentration. Through experimental studies, the effect of the channel concentration ratio (CCR, concentration ratio of the main and buffer channels) on the performance of the sample preconcentration was studied. The results show that the preconcentration of the target sample occurs more effectively for a high CCR or high salt concentration of the main channel when the CCR is constant. We also demonstrate a phenomenon that the salt concentration in the electrolyte solution increases as the preconcentration progresses. Our results provide consolidated conditions for electrophoresis-based sample preconcentration in electromembrane systems.

Optical neuroimaging provides an effective neuroscience tool for multi-scale investigation of the neural structures and functions, ranging from molecular, cellular activities to the inter-regional connectivity assessment. Amongst experimental preparations, the implementation of an artificial window to the central nervous system (CNS) is primarily required for optical visualization of the CNS and associated brain activities through the opaque skin and bone. Either thinning down or removing portions of the skull or spine is necessary for unobstructed long-term in vivo observations, for which types of the cranial and spinal window and applied materials vary depending on the study objectives. As diversely useful, a window can be designed to accommodate other experimental methods such as electrophysiology or optogenetics. Moreover, auxiliary apparatuses would allow the recording in synchrony with behavior of large-scale brain connectivity signals across the CNS, such as olfactory bulb, cerebral cortex, cerebellum, and spinal cord. Such advancements in the cranial and spinal window have resulted in a paradigm shift in neuroscience, enabling in vivo investigation of the brain function and dysfunction at the microscopic, cellular level. This Review addresses the types and classifications of windows used in optical neuroimaging while describing how to perform in vivo studies using rodent models in combination with other experimental modalities during behavioral tests. The cranial and spinal window has enabled longitudinal examination of evolving neural mechanisms via in situ visualization of the brain. We expect transformable and multi-functional cranial and spinal windows to become commonplace in neuroscience laboratories, further facilitating advances in optical neuroimaging systems.

The microspheres for 1-month (PLGA-based) and 3-month (PLA-based) drug releases of leuprolide were manufactured using an IVL-DrugFluidic™ system and their morphology, particle size and distribution, and encapsulation efficiency were compared with the commercialized products. In vivo test was also conducted to monitor the amount of leuprolide and testosterone in plasma after a single subcutaneous injection in male Sprague-Dawley (SD) rats and male Beagle dogs. The median diameter, span value, drug loading, and encapsulation efficiency of PLGA-based microspheres (63.29 μm, 0.26, 13.15%, and 78.90%, respectively) and PLA-based microspheres (80.28 μm, 0.21, 14.42%, and 86.50%, respectively) demonstrated narrow particle size distribution (monodispersed) and efficient drug loading/encapsulation efficiency. Both the microspheres exhibited a desired time-dependent drug release profile and reduced initial burst release by 16-fold in SD rats and 240-fold in Beagle dogs compared to Leuplin DPS®. Moreover, the testosterone level in plasma was suppressed to < 0.50 ng/mL after 28 days with a steady plasma drug concentration. The results suggested that newly developed leuprolide-loaded microspheres produced by the IVL-DrugFluidic™ system could provide extended drug release with advantages such as reduced initial burst release and testosterone level suppression, along with steady plasma drug concentration, over the existing products., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Few species in the Kalanchoë genus form plantlets on their leaf margins as an asexual reproduction strategy. The limited molecular studies on plantlet formation show that an organogenesis ortholog, SHOOTMERISTEMLESS ( STM ) and embryogenesis genes, such as LEAFY COTYLEDON1 ( LEC1 ) and FUSCA3 are recruited during plantlet formation. To understand the mechanisms of two Kalanchoë plantlet-forming species with different modes of plantlet formation, RNA-sequencing analysis was performed. Differentially expressed genes between the developmental stages were clustered in K. daigremontiana (Raym.-Hamet and H. Perrier) and K. pinnata (Lam. Pers.), respectively. Of these gene clusters, GO terms that may be involved in plantlet formation of both species, such as signaling, response to wounding, reproduction, regulation of hormone level, and response to karrikin were overrepresented. Compared with the common GO terms, there were more unique GO terms overrepresented during the plantlet formation of each species. A more in-depth investigation is required to understand how these pathways are participating in plantlet formation. Nonetheless, this transcriptome analysis is presented as a reliable basis for future studies on plantlet formation and development in two Kalanchoë plantlet-forming species.

An obstacle to effective uniform treatment of glioblastoma, especially at recurrence, is genetic and cellular intertumoral heterogeneity. Hence, personalized strategies are necessary, as are means to stratify potential targeted therapies in a clinically relevant timeframe. Functional profiling of drug candidates against patient-derived glioblastoma organoids (PD-GBO) holds promise as an empirical method to preclinically discover potentially effective treatments of individual tumors. Here, we describe our establishment of a PD-GBO-based functional profiling platform and the results of its application to four patient tumors. We show that our PD-GBO model system preserves key features of individual patient glioblastomas in vivo. As proof of concept, we tested a panel of 41 FDA-approved drugs and were able to identify potential treatment options for three out of four patients; the turnaround from tumor resection to discovery of treatment option was 13, 14, and 15 days, respectively. These results demonstrate that this approach is a complement and, potentially, an alternative to current molecular profiling efforts in the pursuit of effective personalized treatment discovery in a clinically relevant time period. Furthermore, these results warrant the use of PD-GBO platforms for preclinical identification of new drugs against defined morphological glioblastoma features.

The complexity in the molecular mechanism of the internal anal sphincter (IAS) limits preclinical or clinical outcomes of fecal incontinence (FI) treatment. So far, there are no systematic reviews of IAS translation and experimental studies that have been reported. This systematic review aims to provide a comprehensive understanding of IAS critical role in FI. Previous studies revealed the key pathway for basal tone and relaxation of IAS in different properties as follows; calcium, Rho-associated, coiled-coil containing serine/threonine kinase, aging-associated IAS dysfunction, oxidative stress, renin-angiotensin-aldosterone, cyclooxygenase, and inhibitory neurotransmitters. Previous studies have reported improved functional outcomes of cellular treatment for regeneration of dysfunctional IAS, using various stem cells, but did not demonstrate the interrelationship between those results and basal tone or relaxation-related molecular pathway of IAS. Furthermore, these results have lower specificity for IAS-incontinence due to the included external anal sphincter or nerve injury regardless of the cell type. An acellular approach using bioengineered IAS showed a physiologic response of basal tone and relaxation response similar to human IAS. However, in both cellular and acellular approaches, the lack of human IAS data still hampers clinical application. Therefore, the IAS regeneration presents more challenges and warrants more advances.

The unique mechanism by which leaf margin cells regain potency and then form a plantlet in Kalanchoë spp. remains elusive but involves organogenesis and embryogenesis in response to age, day length, nutrient availability, and drought stress. In light of this, we investigated whether TARGET OF RAPAMYCIN (TOR), a conserved protein kinase in eukaryotes that controls cell growth and metabolism in response to nutrient and energy availability, may regulate plantlet formation. Kalanchoë daigremontiana TOR (KdTOR) was expressed in the leaf margin at the site of plantlet initiation, in the early plantlet cotyledons, and in the root tip of the developed plantlet. Both chemical and genetic inhibition of TOR Kinase activity in Kalanchoë daigremontiana leaves disrupted plantlet formation. Furthermore, downregulation of KdTOR in transgenic plants led to wide-ranging transcriptional changes, including decreased K. daigremontiana SHOOTMERISTEMLESS and K. daigremontiana LEAFYCOTYLEDON1 expression, whereas auxin treatments induced KdTOR expression in the plantlet roots. These results suggest that the KdTOR pathway controls plantlet development in cooperation with auxin, organogenesis, and embryogenesis pathways. The ancient and highly conserved TOR Kinase therefore controls diverse and unique developmental pathways, such as asexual reproduction within the land plant lineage., (© The Author(s) 2021. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Interest in resistive random access memory (RRAM) has grown rapidly in recent years for realizing ultrahigh density data storage devices. However, sneak currents in these devices can result in misreading of the data, thus limiting the applicability of RRAM. Complementary resistive switching (CRS) memory consisting of two antiserial RRAMs can considerably reduce sneak currents; however, complicated device architectures and manufacturing processes still remain as challenges. Herein, an effective and simple approach for fabricating CRS memory devices using self-assembled block copolymer micelles is reported. Cu ions are selectively placed in the core of polystyrene-block-poly(2-vinylpyridine) spherical micelles, and a hexagonally packed micelle monolayer is prepared through spin-coating. The micelle monolayer can be a symmetrical resistive switching layer, because the micelles and Cu act as dielectric and active metals in memory devices, respectively. The locally enhanced electric field and Joule heating achieved by the structured Cu atoms inside the micelles promote metal ionization and ion migration in a controlled manner, thus allowing for position selectivity during resistive switching. The micelle-based memory device exhibits stable and reliable CRS behavior, with a nonoverlapping and narrow distribution of threshold voltages. Therefore, this approach is promising for fabricating CRS memory devices for high-performance and ultrahigh-density RRAM applications., (© 2022 Wiley-VCH GmbH.)

Electrodialysis using anion-exchange membranes (AEMs) and cation-exchange membranes (CEMs) has been widely used for water desalination and the management of various ionic species. During commercial electrodialysis, the available area of an ion-exchange membrane is reduced by a non-conductive spacer that is in contact with the AEM/CEM. Although multiple reports have described the advantages or disadvantages of spacers, fewer studies have explored the effects of spacers on the mass transport effect of the reduced membrane area excluding the fluid flow change. In this paper, we present our experimental studies concerning mass transport in microfluidic electrodialysis systems with partially masked ion-exchange membranes. Six different types of masking membranes were prepared by the deposition of non-conductive films on parts of the membranes. The experimental results showed that the overlapped types (in which masking was vertically aligned in the AEM/CEM) exhibited a larger electrical conductance and better current/energy efficiency, compared with the non-overlapped types (in which masking was vertically dislocated in the AEM/CEM). We also observed that a reduction in the unit length of the unmasked ion-exchange membrane enhanced overall mass transport. Our results demonstrate the effects of patterned membranes on electrical resistance and desalination performance; they also identify appropriate arrangements for electromembrane systems.

Background: The purpose of this study was to evaluate the characteristics and prognosis of de novo CRC patients who underwent liver or kidney transplantation., Methods: We retrospectively reviewed the medical records of 66 de novo CRC patients selected from 8,734 liver transplant (LT) or kidney transplant (KT) recipients. We analyzed characteristics and survival outcomes of de novo CRC patients and sporadic CRC patients who underwent radical surgery with stage I-III in Asan Medical Center between 2005 and 2016. Survival outcomes were analyzed via the 1:4 matching method., Results: The standard incidence ratio (SIR) of de novo CRC in KT recipients is 1.67 in men and 2.54 in women. That in LT recipients is 3.10 in men and 2.25 in women. Compared with sporadic CRC patients, de novo CRC patients had more colon cancer than rectal cancer (p=0.041). In 9 patients (13.6%), CRC was diagnosed within one year after transplantation, 21 patients (31.8%) were diagnosed between 1-5 years, and the remaining 36 patients (54.6%) were diagnosed thereafter. There were no significant differences in recurrence-free survival and overall survival between the two groups (p=0.211 and p=0.324, respectively)., Conclusions: The risk of developing de novo CRC in transplant recipients was higher than in the general population. The survival outcome of de novo CRC was no different compared with the sporadic CRC. Therefore, regular surveillance is essential for timely diagnosis and treatment for transplantation patients. A large prospective study for an intense CRC surveillance program in transplantation patients is needed., (© 2021. Société Internationale de Chirurgie.)

Background: Optimal surveillance strategies for stage III colorectal cancer (CRC) are lacking, and intensive surveillance has not conferred a significant survival benefit., Aim: To examine the association between surveillance intensity and recurrence and survival rates in patients with stage III CRC., Methods: Data from patients with pathologic stage III CRC who underwent radical surgery between January 2005 and December 2012 at Asan Medical Center, Seoul, Korea were retrospectively reviewed. Surveillance consisted of abdominopelvic computed tomography (CT) every 6 mo and chest CT annually during the 5 year follow-up period, resulting in an average of three imaging studies per year. Patients who underwent more than the average number of imaging studies annually were categorized as high intensity (HI), and those with less than the average were categorized as low intensity (LI)., Results: Among 1888 patients, 864 (45.8%) were in HI group. Age, sex, and location were not different between groups. HI group had more advanced T and N stage ( P = 0.002, 0.010, each). Perineural invasion (PNI) was more identified in the HI group (21.4% vs 30.3%, P < 0.001). The mean overall survival (OS) and recurrence-free interval (RFI) was longer in the LI group ( P < 0.001, each). Multivariate analysis indicated that surveillance intensity [odds ratio (OR) = 1.999; 95% confidence interval (CI): 1.680-2.377; P < 0.001], pathologic T stage (OR = 1.596; 95%CI: 1.197-2.127; P = 0.001), PNI (OR = 1.431; 95%CI: 1.192-1.719; P < 0.001), and circumferential resection margin (OR = 1.565; 95%CI: 1.083-2.262; P = 0.017) in rectal cancer were significantly associated with RFI. The mean post-recurrence survival (PRS) was longer in patients who received curative resection ( P < 0.001). Curative resection rate of recurrence was not different between HI (29.3%) and LI (23.8%) groups ( P = 0.160). PRS did not differ according to surveillance intensity ( P = 0.802)., Conclusion: Frequent surveillance with CT scan do not improve OS in stage III CRC patients. We need to evaluate role of other surveillance method rather than frequent CT scans to detect recurrence for which curative treatment was possible because curative resection is the important to improve post-recurrence survival., Competing Interests: Conflict-of-interest statement: We have no financial relationships to disclose., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

SHORT syndrome is a rare autosomal dominant disorder characterized by multiple congenital defects and is historically defined by its acronym: s hort stature, hyperextensibility of joints and/or inguinal hernia, ocular depression, Rieger anomaly, and teething delay. Herein, we report a male infant with SHORT syndrome who presented with transient neonatal diabetes mellitus (TNDM) with insulin resistance. The proband was born at 38 weeks of gestation but displayed facial dysmorphic features. Intrauterine growth restriction (IUGR) was detected on a prenatal ultrasonography test. His birth weight was 1.8 kg (<3rd percentile), length 44 cm (<3rd percentile), and head circumference 31 cm (<3rd percentile). The patient's blood glucose level started to increase at 5 days of age (218-263 mg/dl) and remained high at 20 days of age (205-260 mg/dl). He was treated with subcutaneous insulin and the blood glucose level gradually stabilized. Blood glucose level was stabilized over time without insulin treatment at 6 weeks of age. Clinical exome sequencing showed a heterozygous pathogenic variant, NM&#95;181523.3:c.1945C>T (p.Arg649Trp) in exon 15 of the phosphoinositide-3-kinase regulatory subunit 1 ( PIK3R1 ) known as the causative gene for SHORT syndrome. Examination of the patient at 10 months of age revealed no hyperglycemic episode and glycated hemoglobin level was 5.2%. To the best of our knowledge, this is the first case of TNDM in SHORT syndrome due to a pathogenic variant of PIK3R1 . We believe that our case can aid in expanding the phenotypes of SHORT syndrome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kim, Kim, Yim, Kim and Jang.)

Since bromodomain containing 4 (brd4) has been considered as a prominent cancer target, numerous attempts have been made to develop potent brd4 bromodomain inhibitors. The present study provided a novel chemical scaffold which inhibited brd4 activity. Mid-throughput screening against brd4 bromodomain was performed using alpha-screen and homogeneous time-resolved fluorescence assays. Furthermore, cell cytotoxicity and xenograft assays were performed to examine if the compound was effective both in vitro and in vivo . As a result, it was revealed that compounds having naphthalene-1,4-dione scaffold inhibited the binding of bromodomain to acetylated histone. The compounds with naphthalene-1,4-dione had cytotoxic effects against the Ty82 cell line, a NUT midline carcinoma cell line, whose proliferation is dependent on brd4 activity. A10, one of the compounds with naphthalene-1,4-dione scaffold, also exhibited tumor growth inhibition effects in the xenograft assay. In addition, the compounds exhibited cytotoxic effects against gastric cancer cell lines which were resistant to I-BET-762, a BET bromodomain inhibitor. In conclusion, the novel scaffold to suppress brd4 activity was effective against cancer cells both in vitro and in vivo ., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Kim et al.)

The purpose of this study was to investigate the effect of the aliphatic moiety in the sulfonated poly(arylene ether sulfone) (SPAES) backbone. A new monomer (4,4'-dihydroxy-1,6-diphenoxyhexane) was synthesized and polymerized with other monomers to obtain partially alkylated SPAESs. According to differential scanning calorimetry analysis, the glass transition temperature (T g ) of these polymers ranged from 85 to 90 °C, which is 100 °C lower than that of the fully aromatic SPAES. Due to the low T g values obtained for the partially alkylated SPAESs, it was possible to prepare a hydrocarbon electrolyte membrane-based membrane electrode assembly (MEA) with Nafion ® binder in the electrode through the use of a decal transfer method, which is the most commercially suitable system to obtain an MEA of proton exchange membrane fuel cells (PEMFCs). A single cell prepared using this partially alkylated SPAES as an electrolyte membrane exhibited a peak power density of 539 mW cm -2 .

The present study examined the attitudes of Filipino middle school students toward physical education (PE) and the associations between PE attitude and various personal and external correlates of PE. In total, 659 middle school students, aged between 12 and 19 years (M = 14.55; SD = 1.14), participated in the study. The Physical Education Attitude Scale (PEAS) was used to measure affective, cognitive, and motivational/behavioral attitudes of adolescent students toward PE. Results showed that middle school students had moderate general attitudes toward PE. Female students had more favorable attitudes toward PE when their teacher was male than female. When the teacher was female, male students were more satisfied with the PE curriculum than female students. When the teacher was male, female students were more comfortable with the PE curriculum than male students. Finally, students' PE attitude did not decrease as they got older, regardless of student sex. The findings provide a different perspective for the field and underscore the importance of not only the PE curriculum but also the student-teacher relationship. To prevent the decline in students' positive attitude and encourage positive behaviors toward PE and activities, teachers should be very considerate about their interactions with students of the same sex; school administrators (e.g., principal and PE department head), meanwhile, should focus at providing PE teachers with special training courses to enhance both their teaching and communication capabilities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cruz, Kim and Kim.)

We created a new, 8-item scale called "Career Student Planning Scale (CSPS)" for a valid and reliable measure regarding college students' career planning during a traumatic event, such as a pandemic. CSPS is conceptually similar to the career decision-making difficulty questionnaire (CDDQ) and the career decision self-efficacy (CDSE) scale. CSPS leans towards questions about college students' perceptions about career planning, rather than intuitions about career decision-making; it also inquires about how participants conceptualize about their career plans to be correct, rather than the more extreme idea about how their intuitions are correct: we developed this scale to capture the latter construct. We included the coronavirus anxiety scale (CAS), CDDQ, the general procrastination scale (GPS), and the CDSE short form (CDSE-SF) as covariates to ensure that CSPS has distinct effects on their career paths. Our findings indicate the CSPS has acceptable psychometric properties and demonstrates a valuable input to those measures., (© The Author(s) 2021.)

Conventional imaging and recognition systems require an extensive amount of data storage, pre-processing, and chip-to-chip communications as well as aberration-proof light focusing with multiple lenses for recognizing an object from massive optical inputs. This is because separate chips (i.e., flat image sensor array, memory device, and CPU) in conjunction with complicated optics should capture, store, and process massive image information independently. In contrast, human vision employs a highly efficient imaging and recognition process. Here, inspired by the human visual recognition system, we present a novel imaging device for efficient image acquisition and data pre-processing by conferring the neuromorphic data processing function on a curved image sensor array. The curved neuromorphic image sensor array is based on a heterostructure of MoS 2 and poly(1,3,5-trimethyl-1,3,5-trivinyl cyclotrisiloxane). The curved neuromorphic image sensor array features photon-triggered synaptic plasticity owing to its quasi-linear time-dependent photocurrent generation and prolonged photocurrent decay, originated from charge trapping in the MoS 2 -organic vertical stack. The curved neuromorphic image sensor array integrated with a plano-convex lens derives a pre-processed image from a set of noisy optical inputs without redundant data storage, processing, and communications as well as without complex optics. The proposed imaging device can substantially improve efficiency of the image acquisition and recognition process, a step forward to the next generation machine vision.

A novel nanocomposite-based non-volatile resistance switching random access memory device introducing single-walled carbon nanotube (SWCNT)@TiO 2 core-shell wires was proposed for flexible electronics. The SWCNT was de-bundled by ultrasonication with sodium dodecylbenzene sulfonate (SDBS), and then the TiO 2 skin layer on the SWCNT surface was successfully introduced by adding benzyl alcohol as a weak surfactant. The nanocomposite resistance switching layer was composed of the SWCNT@TiO 2 core-shell wires and poly(vinyl alcohol) (PVA) matrix by a simple spin-coating method. The device exhibited reproducible resistance switching performance with a remarkably narrow distribution of operating parameters (V SET and V RESET were 2.63 ± 0.16 and 0.95 ± 0.11 V, respectively) with a large R ON /R OFF ratio of 10 5 for 200 consecutive switching cycles. Furthermore, the excellent resistance switching behavior in our device was maintained against mechanical stress up to 10 5 bending test. We believe that the nanocomposite memory device with SWCNT@TiO 2 core-shell wires would be a critical asset to realize practical application for a flexible non-volatile memory field.

(Inverse) spinel-typed bimetallic sulfides are fascinating H 2 O 2 scissors because of the inclusion of S 2- , which can regenerate metals (M δ + , δ ≤ 2) used to produce • OH via H 2 O 2 dissection. These sulfides, however, were under-explored regarding compositional, structural, and electronic tunabilities based on the proper selection of metal constituents. Motivated by S-modified Ni δ + /Co δ + promising to H 2 O 2 cleavage, Ni 2 CoS 4 , NiCo 2 S 4 , NiS/CoS were synthesized and contrasted with regards to their catalytic traits. Ni 2 CoS 4 provided the greatest activity in dissecting H 2 O 2 among the catalysts. Nonetheless, Ni 2 CoS 4 catalyzed H 2 O 2 scission primarily via homogeneous catalysis mediated by leached Ni δ + /Co δ + . Conversely, NiCo 2 S 4 , NiS, and CoS catalyzed H 2 O 2 cleavage mainly via unleached Ni δ + /Co δ + -enabled heterogeneous catalysis. Of significance, NiCo 2 S 4 provided Lewis acidic strength favorable to adsorb H 2 O 2 and desorb • OH compared to NiS and CoS, respectively. Of additional significance, NiCo 2 S 4 provided S 2- with lesser energy required to reduce M ( δ +1)+ via e- transfer than NiS/CoS. Hence, NiCo 2 S 4 prompted H 2 O 2 scission cycle per unit time better than NiS/CoS, as evidenced by kinetic assessments. NiCo 2 S 4 was also superior to Ni 2 CoS 4 because of the elongated lifespan anticipated as • OH producer, resulting from heterogeneous catalysis with moderate Ni δ + /Co δ + leaching. Furthermore, NiCo 2 S 4 revealed the greatest recyclability and mineralization efficiency in decomposing recalcitrants via • OH-mediated oxidation., Competing Interests: Declaration of Competing Interest There are no conflicts to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: Adjuvant treatment for breast cancer in postmenopausal women is a risk factor for bone loss. However, the association between bone mineral density (BMD) changes in premenopausal breast cancer patients and various adjuvant treatment regimens is not well characterized. In this study, we evaluated the changes in BMD according to adjuvant treatment in premenopausal women with breast cancer., Methods: Between 2006 and 2010, BMD data of 910 premenopausal women with breast cancer before operation and 1, 2, 3.5, and 5 years post-operation were retrospectively analyzed. The patients were divided according to the type of treatment: observation (O), tamoxifen (T), chemotherapy (C), C followed by T (C → T), and gonadotropin-releasing hormone (GnRH) agonist with T (G + T)., Results: After 5 years of follow-up, BMD changes were similar between the T and O groups (all p > 0.05). Within 1 year of treatment, the C group showed the most significant BMD loss. The C → T and G + T groups showed more significant BMD loss in the lumbar spine and femur than the O and T groups (both p < 0.001, both). After 1 year of treatment, BMD loss in the lumbar spine was significantly greater in the C → T and G + T groups than in the T group; this tendency was maintained for 5 years of treatment (all p < 0.005)., Conclusion: Premenopausal women who received adjuvant treatment which induced menopause showed significant bone loss which lasted for 5 years. Although no significant difference was observed between the O and T groups, tamoxifen treatment during chemotherapy or GnRH agonist treatment might prevent bone loss.

TARGET OF RAPAMYCIN (TOR) kinase has been recognised as a key developmental regulator in both plants and animals. Despite their distinct developmental programmes, all eukaryotes studied possess a functional TOR kinase, which integrates environmental and nutrient signals to direct growth and development. This is particularly important in plants, as they are sessile and must sense and respond to external signals to coordinate multicellular growth appropriately. Thus, the investigation of TOR is essential for plant developmental studies in the context of the resources available for growth. Recently, links have been shown between TOR and plant development from embryogenesis through to senescence, however more investigation is crucial to fully elucidate TOR function in each developmental process., (Copyright © 2020 McCready, Spencer and Kim.)

Cancer immunotherapy, in the form of vaccination, adoptive cellular transfer, or immune checkpoint inhibitors, has emerged as a promising practice within the field of oncology. However, despite the developing field's potential to revolutionize cancer treatment, the presence of immunotherapeutic-resistant tumor cells in many patients present a challenge and limitation to these immunotherapies. These cells not only indicate immunotherapeutic resistance, but also show multi-modal resistance to conventional therapies, abnormal metabolism, stemness, and metastasis. How can immunotherapeutic-resistant tumor cells render multi-malignant phenotypes? We reasoned that the immune-refractory phenotype could be associated with multi-malignant phenotypes and that these phenotypes are linked together by a factor that acts as the master regulator. In this review, we discussed the role of the embryonic transcription factor NANOG as a crucial master regulator we named "common factor" in multi-malignant phenotypes and presented strategies to overcome multi-malignancy in immunotherapeutic-resistant cancer by restraining the NANOG-mediated multi-malignant signaling axis. Strategies that blunt the NANOG axis could improve the clinical management of therapy-refractory cancer., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interest., (Copyright © 2020. The Korean Association of Immunologists.)

Parking is a challenging task for autonomous vehicles and requires a centimeter level precision of distance measurement for safe parking at a destination to avoid collisions with nearby vehicles. In order to avoid collisions with parked vehicles while parking, real-time localization performance should be maintained even when loop closing occurs. This study proposes a simultaneous localization and mapping (SLAM) method, using around view monitor (AVM)/light detection and ranging (LiDAR) sensor fusion, that provides rapid loop closing performance. We extract the parking line features by utilizing the sensor fusion data for sparse feature-based pose graph optimization that boosts the loop closing speed. Hence, the proposed method can perform the loop closing within a few milliseconds to compensate for the accumulative errors even in a large-scale outdoor environment, which is much faster than other LiDAR-based SLAM algorithms. Therefore, it easily satisfies real-time localization performance. Furthermore, thanks to the parking line features, the proposed method can detect a parking space by utilizing the accumulated parking lines in the map. The experiment was performed in three outdoor parking lots to validate the localization performance and parking space detection performance. All of the proposed methods can be operated in real-time in a single-CPU environment.

Increasing concerns about musculoskeletal disorders in the upper back arising from excessive daily use of the smartwatch have been widely validated by the rising prevalence of discomfort. This study explored the smartwatch as a potential ergonomic intervention over the smartphone. Fourteen healthy participants completed five tasks (application setting, calling, message typing, message checking and vocal message entry) with smartphone and smartwatch in both sitting and standing postures. The neck-shoulder kinematics and muscle activation levels were monitored to assess the effects of the tasks, devices, and postures. The results indicated greater head flexion, head rotation and shoulder abduction and greater muscle activities for smartwatch use compared to smartphone use, but the performance measure (i.e., elapsed time) was superior for smartwatch use in all tasks except message typing. Collectively, only short and simple tasks such as message checking and application setting should be conducted with the smartwatch., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Nature often creates complex structures by rearranging pre-existing units. One such example is the flower head (capitulum) in daisies, where a group of flowers (florets) and phyllaries (modified bracts) are arranged to superficially mimic a single flower. The capitulum is a key taxonomical innovation that defines the daisy family (Asteraceae), the largest flowering plant group. However, patterning mechanisms underlying its structure remain elusive. Here, we show that auxin, a plant hormone, provides a developmental patterning cue for the capitulum. During capitulum development, a temporal auxin gradient occurs, regulating the successive and centripetal formation of distinct florets and phyllaries. Disruption of the endogenous auxin gradient led to homeotic conversions of florets and phyllaries in the capitulum. Furthermore, auxin regulates floral meristem identity genes, such as Matricaria inodora RAY2 and M inodora LEAFY , which determine floret and phyllary identity. This study reveals the mechanism of capitulum patterning and highlights how common developmental tools, such as hormone gradients, have independently evolved in plants and animals., (© 2019 The author(s). All Rights Reserved.)

A potential new clinical disorder is arising due to the addiction to cellphones called nomophobia-or feelings of discomfort or anxiety experienced by individuals when they are unable to use their mobile phones or utilize the conveniences these devices provide. However, before being able to officially classify this disorder as clinically relevant, more research needs to be conducted to determine how nomophobia relates to existing disorders. In a sample of 397 undergraduate students, the present study examined the relationship between the Nomophobia Questionnaire (NMP-Q) and the Obsessiveness Content Scale (OBS) of the Minnesota Multiphasic Personality Inventory-2 (the MMPI-2). Confirmatory factor analysis (CFA) was used to test whether the OBS Content Scale would be related to a one-factor NMP-Q solution (Fig. 1) or a four-factor NMP-Q solution (Fig. 2). Convergent and divergent validity were also investigated. The four-factor model was a better fit than the one-factor model as indicated by most fit indices. The findings showed that the OBS latent variable was correlated with all of the four NMP-Q latent variables. Mixed support was found for convergent validity, but high support was found for the divergent validity of the NMP-Q factors. This study contributes to a growing body of literature seeking to better understand the addictive nature of cellphones and takes a new perspective on addiction research and obsessiveness. These findings provide a better understanding between pre-existing assessments of personality disorders (e.g., obsessiveness) that are emerging from the overuse of mobile phones or the excessive fear of losing one's cell phone.

Bromodomain-containing protein 4 (Brd4) is known to play a key role in tumorigenesis. It binds acetylated histones to regulate the expression of numerous genes. Because of the importance of brd4 in tumorigenesis, much research has been undertaken to develop brd4 inhibitors with therapeutic potential. As a result, various scaffolds for bromodomain inhibitors have been identified. To discover new scaffolds, we performed mid-throughput screening using two different enzyme assays, alpha-screen and ELISA. We found a novel bromodomain inhibitor with a unique scaffold, aristoyagonine. This natural compound showed inhibitory activity in vitro and tumor growth inhibition in a Ty82-xenograft mouse model. In addition, we tested Brd4 inhibitors in gastric cancer cell lines, and found that aristoyagonine exerted cytotoxicity not only in I-BET-762-sensitive cancer cells, but also in I-BET-762-resistant cancer cells. This is the first paper to describe a natural compound as a Brd4 bromodomain inhibitor., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Flower forms are both highly diverse and multifaceted. As well as varying in colour, size, organ number, and much more, flowers show different types of symmetry. Floral symmetry can be grouped into three main categories: asymmetry, bilateral symmetry and radial symmetry, characterised by zero, one, and multiple planes of symmetry, respectively. This review will first explore floral symmetry from a classical morphological view, then from a modern molecular perspective. The recent molecular work on symmetry in monocots and eudicots will be discussed, followed by an in-depth discussion into the evolution of CYC genes, particularly in the capitulum of the sunflower family (Asteraceae). Whilst recent studies on non-model species are helping to bring new light to this field, more species coverage is required to understand how traits such as bilateral symmetry have evolved so many times, and whether the same molecular regulators were recruited for this function., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Gastric cancer is a malignancy that has a high mortality rate. Although progress has been made in the treatment of gastric cancer, many patients experience cancer recurrence and metastasis. Folate receptor 1 (FOLR1) is overexpressed on the cell surface in over one-third of gastric cancer patients, but rarely is expressed in normal tissue. This makes FOLR1 a potential target for chimeric antigen receptor (CAR) T cell immunotherapy, although the function of FOLR1 has not been elucidated. CAR are engineered fusion receptor composed of an antigen recognition region and signaling domains. T cells expressing CAR have specific activation and cytotoxic effects against cancer cells containing the target antigen. In this study, we generated a CAR that targets FOLR1 composed of a single-chain variable fragment (scFv) of FOLR1 antibody and signaling domains consisting of CD28 and CD3ζ. Both FOLR1-CAR KHYG-1, a natural killer cell line, and FOLR1-CAR T cells recognized FOLR1-positive gastric cancer cells in a MHC-independent manner and induced secretion of various cytokines and caused cell death. Conclusively, this is the first study to demonstrate that CAR KHYG-1/T cells targeting FOLR1 are effective against FOLR1-positive gastric cancer cells., Competing Interests: The authors have declared that no competing interests exist.

Fe-cluster-based crystal structures are predicted for chalcogenides Fe 3 X 4 (X = S, Se, Te) using an adaptive genetic algorithm. Topologically different from the well-studied layered structures of iron chalcogenides, the newly predicted structures consist of Fe clusters that are either separated by the chalcogen atoms or connected via sharing of the vertex Fe atoms. Using first-principles calculations, we demonstrate that these structures have competitive or even lower formation energies than the experimentally synthesized Fe 3 X 4 compounds and exhibit interesting magnetic and electronic properties. In particular, we show that Fe 3 Te 4 can be a good candidate as a rare-earth-free permanent magnet and Fe 3 S 4 can be a magnetic nodal-line topological material.

While the role of proteins in determining cell identity has been extensively studied, the contribution of small noncoding RNA molecules such as miRNAs and siRNAs has been also recognised. miRNAs bind to complementary sites in target mRNA molecules to trigger the degradation or translational inhibition of those targets. Recent studies have revealed that miRNAs play pivotal roles in key developmental processes such as patterning of the embryo, meristem, leaf, and flower. Furthermore, these miRNAs have been recruited throughout plant evolution into pathways that create diverse plant organ forms and shapes. This review focuses on the roles of miRNAs in establishing plant cell identity during key plant development processes and creating morphological diversity during plant evolution., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Bone morphogenetic protein 9 (BMP9), a member of the TGF-β superfamily, is considered a regulator of glucose homeostasis as well as a neuronal differentiation factor. BMP9 induces phosphorylation of Smad1/5 through activin receptor-like kinase 1 and 2 (ALK1 and ALK2). Recently, many studies have shown that BMP9 contributes to tumorigenesis, and aberrant ALK2 expression is involved in many diseases. To investigate the role of BMP9-ALK2 signaling in cancer cells, we used TF-1 cells that require granulocyte-macrophage colony-stimulating factor (GM-CSF) for cell proliferation. BMP9 promoted the proliferation of TF-1 cells in media lacking GM-CSF. TF-1 cells overexpressing ALK2 resulted in the autophosphorylation of Smad1/5, leading to consequent increase in cell growth. Through high-throughput screening (HTS), we found two ALK2-specific inhibitors, KRC203 and KRC360, with IC 50 values of 0.9 nM and 0.3 nM. These compounds were more potent and specific for the inhibition of ALK2 when compared to LDN193189. In cell-based assays, these compounds effectively inhibited the proliferation and migration of cancer cells induced by ALK2 and BMP9. Therefore, we propose that our compounds are promising candidates for the treatment of cancer or diseases with abnormal ALK2 or BMP9 signaling., (Copyright © 2017 Elsevier Inc. All rights reserved.)