A virtual memory CD8+ T cell-originated subset causes alopecia areata through innate-like cytotoxicity.

Virtual memory T (TVM) cells are a T cell subtype with a memory phenotype but no prior exposure to foreign antigen. Although TVM cells have antiviral and antibacterial functions, whether these cells can be pathogenic effectors of inflammatory disease is unclear. Here we identified a TVM cell-originated CD44super-high(s-hi)CD49dlo CD8+ T cell subset with features of tissue residency. These cells are transcriptionally, phenotypically and functionally distinct from conventional CD8+ TVM cells and can cause alopecia areata. Mechanistically, CD44s-hiCD49dlo CD8+ T cells could be induced from conventional TVM cells by interleukin (IL)-12, IL-15 and IL-18 stimulation. Pathogenic activity of CD44s-hiCD49dlo CD8+ T cells was mediated by NKG2D-dependent innate-like cytotoxicity, which was further augmented by IL-15 stimulation and triggered disease onset. Collectively, these data suggest an immunological mechanism through which TVM cells can cause chronic inflammatory disease by innate-like cytotoxicity.

Giant modulation of optical nonlinearity by Floquet engineering.

Strong periodic driving with light offers the potential to coherently manipulate the properties of quantum materials on ultrafast timescales. Recently, strategies have emerged to drastically alter electronic and magnetic properties by optically inducing non-trivial band topologies1-6, emergent spin interactions7-11 and even superconductivity12. However, the prospects and methods of coherently engineering optical properties on demand are far less understood13. Here we demonstrate coherent control and giant modulation of optical nonlinearity in a van der Waals layered magnetic insulator, manganese phosphorus trisulfide (MnPS3). By driving far off-resonance from the lowest on-site manganese d-d transition, we observe a coherent on-off switching of its optical second harmonic generation efficiency on the timescale of 100 femtoseconds with no measurable dissipation. At driving electric fields of the order of 109 volts per metre, the on-off ratio exceeds 10, which is limited only by the sample damage threshold. Floquet theory calculations14 based on a single-ion model of MnPS3 are able to reproduce the measured driving field amplitude and polarization dependence of the effect. Our approach can be applied to a broad range of insulating materials and could lead to dynamically designed nonlinear optical elements.

Coherent many-body exciton in van der Waals antiferromagnet NiPS3.

An exciton is the bosonic quasiparticle of electron-hole pairs bound by the Coulomb interaction1. Bose-Einstein condensation of this exciton state has long been the subject of speculation in various model systems2,3, and examples have been found more recently in optical lattices and two-dimensional materials4-9. Unlike these conventional excitons formed from extended Bloch states4-9, excitonic bound states from intrinsically many-body localized states are rare. Here we show that a spin-orbit-entangled exciton state appears below the Néel temperature of 150 kelvin in NiPS3, an antiferromagnetic van der Waals material. It arises intrinsically from the archetypal many-body states of the Zhang-Rice singlet10,11, and reaches a coherent state assisted by the antiferromagnetic order. Using configuration-interaction theory, we determine the origin of the coherent excitonic excitation to be a transition from a Zhang-Rice triplet to a Zhang-Rice singlet. We combine three spectroscopic tools-resonant inelastic X-ray scattering, photoluminescence and optical absorption-to characterize the exciton and to demonstrate an extremely narrow excitonic linewidth below 50 kelvin. The discovery of the spin-orbit-entangled exciton in antiferromagnetic NiPS3 introduces van der Waals magnets as a platform to study coherent many-body excitons.

Compatibility Review for Object Detection Enhancement through Super-Resolution.

With the introduction of deep learning, a significant amount of research has been conducted in the field of computer vision in the past decade. In particular, research on object detection (OD) continues to progress rapidly. However, despite these advances, some limitations need to be overcome to enable real-world applications of deep learning-based OD models. One such limitation is inaccurate OD when image quality is poor or a target object is small. The performance degradation phenomenon for small objects is similar to the fundamental limitations of an OD model, such as the constraint of the receptive field, which is a difficult problem to solve using only an OD model. Therefore, OD performance can be hindered by low image quality or small target objects. To address this issue, this study investigates the compatibility of super-resolution (SR) and OD techniques to improve detection, particularly for small objects. We analyze the combination of SR and OD models, classifying them based on architectural characteristics. The experimental results show a substantial improvement when integrating OD detectors with SR models. Overall, it was demonstrated that, when the evaluation metrics (PSNR, SSIM) of the SR models are high, the performance in OD is correspondingly high as well. Especially, evaluations on the MS COCO dataset reveal that the enhancement rate for small objects is 9.4% higher compared to all objects. This work provides an analysis of SR and OD model compatibility, demonstrating the potential benefits of their synergistic combination. The experimental code can be found on our GitHub repository.

Exploring the association between campus environment of higher education and student health: A systematic review of findings and measures.

Numerous studies have investigated the relationship between the neighborhood environments and residents' health. However, other important settings, such as university campuses, have received little attention. This paper conducted a systematic review and synthesized existing empirical works examining the association between the university/college campuses built and natural environments and students' health. Following the PRISMA guidelines, we searched nine databases using keywords related to higher-education campuses and health-related outcomes. A total of 19 articles were identified, including fifteen cross-sectional studies, three experimental studies, and one longitudinal study. The majority of the studies were conducted in Asian countries and published in the past five years. The findings indicate that active transportation infrastructure, such as increased road intersections and better walkability, were found to be positively associated with students' physical activity. The natural environments, including perceived naturalness, blue space, and greenness was shown to support student's mental health and quality of life. Specifically, blue space was found to be the most preferred place for mental restoration, and scattered trees demonstrated a supportive effect in reducing depression symptoms. Even just viewing virtual trees had a restorative effect and feel less anxiety. Additionally, during the summer, tree shadows were identified as the most important factors for enhancing thermal comfort. This review emphasizes the crucial role of campus environments in promoting college students' health. Future longitudinal studies and investigations using multiple campuses would provide a more comprehensive understanding of this relationship. Such endeavors can contribute to the development of evidence-based strategies for designing and planning healthy campus environments that optimize students' well-being.

Clinical utility of response time in speech audiometry in elderly with mild cognitive impairment.

OBJECTIVES: This study investigated whether verbal response time (RT) as a measure of listening effort in speech audiometry could be an indicator for identifying elderly individuals with mild cognitive impairment (MCI). DESIGN: Korean sentence recognition tests were conducted in favourable (+5 dB signal-to-noise ratio [SNR]) and adverse (-5 dB SNR) conditions in the presence of noise. Sentence recognition scores (SRSs) and RTs for the two groups were measured and analysed with other demographic variables. STUDY SAMPLES: Fourteen elderly adults who were diagnosed with MCI and 14 age-matched adults with normal cognition participated in this study. RESULTS: No statistical difference was found between the SRSs of the two groups. RTs for the MCI elderly were significantly longer than the control group. We found significant correlations of RTs with SRSs, Korean Mini-Mental State Examination (K-MMSE) scores, and age at -5 dB SNR. Only the SRSs were correlated with the RTs at +5 dB SNR. CONCLUSIONS: This study found that elderly individuals with MCI need a longer time for sentence recognition in noise. These findings suggest that measuring RT in speech audiometry could potentially be a cost-effective and time-saving method that could characterise elderly with MCI at hearing-care clinics.

Street environments and crime around low-income and minority schools: Adopting an environmental audit tool to assess crime prevention through environmental design (CPTED).

Crime prevention through environmental design (CPTED) suggests an association between micro-scale environmental conditions and crime, but little empirical research exists on the detailed street-level environmental features associated with crime near low-income and minority schools. This study focuses on the neighborhoods around 14 elementary schools serving lower income populations in Seattle, WA to assess if the distribution of crime incidences (2013-2017) is linked with the street-level environmental features that reflect CPTED principles. We used a total of 40 audit variables that were included in the four domains derived from the broken windows theory and CPTED principles: natural surveillance (e.g., number of windows, balconies, and a sense of surveillance), territoriality (e.g., crime watch signs, trees), image/maintenance (e.g., graffiti and a sense of maintenance/cleanness), and geographical juxtaposition (e.g., bus stops, presence of arterial). We found that multiple crime types had significant associations with CPTED components at the street level. Among the CPTED domains, two image/maintenance features (i.e., maintenance of streets and visual quality of buildings) and two geographical juxtaposition features (i.e., being adjacent to multi-family housing and bus stops) were consistently associated with both violent and property crime. The findings suggest that local efforts to improve maintenance of streets and visual quality of buildings and broader planning efforts to control specific land uses near schools are important to improve safety in marginalized neighborhoods near schools that tend to be more vulnerable to crime. Our research on micro-scale environmental determinants of crime can also serve as promising targets for CPTED research and initiatives.

Effectiveness of individualized 3D titanium-printed Orthognathic osteotomy guides and custom plates.

BACKGROUND: Computer-aided design/manufacturing (CAD/CAM) technology was developed to improve surgical accuracy and minimize errors in surgical planning and orthognathic surgery. However, its accurate implementation during surgery remains a challenge. Hence, we compared the accuracy and stability of conventional orthognathic surgery and the novel modalities, such as virtual simulation and three-dimensional (3D) titanium-printed customized surgical osteotomy guides and plates. METHODS: This prospective study included 12 patients who were willing to undergo orthognathic surgery. The study group consisted of patients who underwent orthognathic two-jaw surgery using 3D-printed patient-specific plates processed by selective laser melting and an osteotomy guide; orthognathic surgery was also performed by the surgeon directly bending the ready-made plate in the control group. Based on the preoperative computed tomography images and intraoral 3D scan data, a 3D virtual surgery plan was implemented in the virtual simulation module, and the surgical guide and bone fixation plate were fabricated. The accuracy and stability were evaluated by comparing the results of the preoperative virtual simulation (T0) to those at 7 days (T1) and 6 months (T2) post-surgery. RESULT: The accuracy (ΔT1‒T0) and stability (ΔT2‒T1) measurements, using 11 anatomical references, both demonstrated more accurate results in the study group. The mean difference of accuracy for the study group (0.485 ± 0.280 mm) was significantly lower than in the control group (1.213 ± 0.716 mm) (P < 0.01). The mean operation time (6.83 ± 0.72 h) in the control group was longer than in the study group (5.76 ± 0.43 h) (P < 0.05). CONCLUSION: This prospective clinical study demonstrated the accuracy, stability, and effectiveness of using virtual preoperative simulation and patient-customized osteotomy guides and plates for orthognathic surgery.

Automatic Detection and Segmentation of Thrombi in Abdominal Aortic Aneurysms Using a Mask Region-Based Convolutional Neural Network with Optimized Loss Functions.

The detection and segmentation of thrombi are essential for monitoring the disease progression of abdominal aortic aneurysms (AAAs) and for patient care and management. As they have inherent capabilities to learn complex features, deep convolutional neural networks (CNNs) have been recently introduced to improve thrombus detection and segmentation. However, investigations into the use of CNN methods is in the early stages and most of the existing methods are heavily concerned with the segmentation of thrombi, which only works after they have been detected. In this work, we propose a fully automated method for the whole process of the detection and segmentation of thrombi, which is based on a well-established mask region-based convolutional neural network (Mask R-CNN) framework that we improve with optimized loss functions. The combined use of complete intersection over union (CIoU) and smooth L1 loss was designed for accurate thrombus detection and then thrombus segmentation was improved with a modified focal loss. We evaluated our method against 60 clinically approved patient studies (i.e., computed tomography angiography (CTA) image volume data) by conducting 4-fold cross-validation. The results of comparisons to multiple other state-of-the-art methods suggested the superior performance of our method, which achieved the highest F1 score for thrombus detection (0.9197) and outperformed most metrics for thrombus segmentation.

Abdominal Aortic Thrombus Segmentation in Postoperative Computed Tomography Angiography Images Using Bi-Directional Convolutional Long Short-Term Memory Architecture.

Abdominal aortic aneurysm (AAA) is a fatal clinical condition with high mortality. Computed tomography angiography (CTA) imaging is the preferred minimally invasive modality for the long-term postoperative observation of AAA. Accurate segmentation of the thrombus region of interest (ROI) in a postoperative CTA image volume is essential for quantitative assessment and rapid clinical decision making by clinicians. Few investigators have proposed the adoption of convolutional neural networks (CNN). Although these methods demonstrated the potential of CNN architectures by automating the thrombus ROI segmentation, the segmentation performance can be further improved. The existing methods performed the segmentation process independently per 2D image and were incapable of using adjacent images, which could be useful for the robust segmentation of thrombus ROIs. In this work, we propose a thrombus ROI segmentation method to utilize not only the spatial features of a target image, but also the volumetric coherence available from adjacent images. We newly adopted a recurrent neural network, bi-directional convolutional long short-term memory (Bi-CLSTM) architecture, which can learn coherence between a sequence of data. This coherence learning capability can be useful for challenging situations, for example, when the target image exhibits inherent postoperative artifacts and noises, the inclusion of adjacent images would facilitate learning more robust features for thrombus ROI segmentation. We demonstrate the segmentation capability of our Bi-CLSTM-based method with a comparison of the existing 2D-based thrombus ROI segmentation counterpart as well as other established 2D- and 3D-based alternatives. Our comparison is based on a large-scale clinical dataset of 60 patient studies (i.e., 60 CTA image volumes). The results suggest the superior segmentation performance of our Bi-CLSTM-based method by achieving the highest scores of the evaluation metrics, e.g., our Bi-CLSTM results were 0.0331 higher on total overlap and 0.0331 lower on false negative when compared to 2D U-net++ as the second-best.

Angelica gigas NAKAI and Its Active Compound, Decursin, Inhibit Cellular Injury as an Antioxidant by the Regulation of AMP-Activated Protein Kinase and YAP Signaling.

Natural products and medicinal herbs have been used to treat various human diseases by regulating cellular functions and metabolic pathways. Angelica gigas NAKAI (AG) helps regulate pathological processes in some medical fields, including gastroenterology, gynecology, and neuropsychiatry. Although some papers have reported its diverse indications, the effects of AG against arachidonic acid (AA)+ iron and carbon tetrachloride (CCl4) have not been reported. In HepG2 cells, AA+ iron induced cellular apoptosis and mitochondrial damage, as assessed by mitochondrial membrane permeability (MMP) and the expression of apoptosis-related proteins. On the other hand, AG markedly inhibited these detrimental phenomena and reactive oxygen species (ROS) production induced by AA+ iron. AG activated the liver kinase B1 (LKB1)-dependent AMP-activated protein kinase (AMPK), which affected oxidative stress in the cells. Moreover, AG also regulated the expression of yes-associated protein (YAP) signaling as mediated by the AMPK pathways. In mice, an oral treatment of AG protected against liver toxicity induced by CCl4, as indicated by the plasma and histochemical parameters. Among the compounds in AG, decursin had antioxidant activity and affected the AMPK pathway. In conclusion, AG has antioxidant effects in vivo and in vitro, indicating that natural products such as AG could be potential candidate for the nutraceuticals to treat various disorders by regulating mitochondrial dysfunction and cellular metabolic pathways.

Enhancement of Cooperation and Reentrant Phase of Prisoner's Dilemma Game on Signed Networks.

We studied the prisoner's dilemma game as applied to signed networks. In signed networks, there are two types of links: positive and negative. To establish a payoff matrix between players connected with a negative link, we multiplied the payoff matrix between players connected with a positive link by -1. To investigate the effect of negative links on cooperating behavior, we performed simulations for different negative link densities. When the negative link density is low, the density of the cooperator becomes zero because there is an increasing temptation payoff, b. Here, parameter b is the payoff received by the defector from playing the game with a cooperator. Conversely, when the negative link density is high, the cooperator density becomes almost 1 as b increases. This is because players with a negative link will suffer more payoff damage if they do not cooperate with each other. The negative link forces players to cooperate, so cooperating behavior is enhanced.

Falls associated with indoor and outdoor environmental hazards among community-dwelling older adults between men and women.

BACKGROUND: Hazardous environmental exposures are recognized risk factors for falls among older adults. However, the gender differences in the associations of falls with indoor and outdoor environmental hazards are scarce. This study examined the indoor and outdoor environmental risk factors for falls and compared the data for men and women among U.S. older adults using nationally representative data. METHODS: We used the 2011 National Health and Aging Trends Study (NHATS) for a cross-sectional analysis of 6680 community-dwelling adults aged ≥65 years in the United States. A series of logistic regressions was used to identify the indoor and outdoor environmental hazards associated with falls stratified by gender after adjusting for sociodemographic, health, and behaviors. We also tested for significant interactions with gender. RESULTS: Compared to men, women had a higher prevalence of falls. In the model adjusted for sociodemographic, health, and behavioral conditions, there were gender differences in the association of falls with the presence of indoor and outdoor environmental hazards. Gender-specific analyses showed that women with the presence of indoor environmental hazards (OR = 1.37, 95% CI = 1.04.-1.79) had higher odds of falls, whereas for men, the presence of outdoor environmental hazards (OR = 1.34, 95% CI = 1.02-1.75) was associated with falls. We also found a significant interaction term between outdoor environmental hazards and gender (OR = 0.65, 95% CI = 0.47-0.90). The interaction plot indicated that the presence of outdoor environmental hazards increased the risks of falling in men but not in women. CONCLUSIONS: Significant gender differences exist in the association of falls with indoor and outdoor environmental hazards among older men and women. Our findings suggest that gender-tailored prevention programs to increase awareness of the environmental hazards and gender-specific environmental interventions are needed to help prevent falls.

Two-Dimensionally Stretchable Organic Light-Emitting Diode with Elastic Pillar Arrays for Stress Relief.

Recent advanced studies on flexible and stretchable electronic devices and optoelectronics have made possible a variety of soft and more functional electronic devices. With consumer demand for highly functional or free-form displays, high flexibility and stretchability in light-emitting devices are needed. Herein, we developed a unique structure of stretchable substrates with pillar arrays to reduce the stress on the active area of devices when strain is applied. We confirmed the advantages of the produced structures using mechanical simulation tools and determined that the structures effectively lessen the applied stress of interconnection as well as the active area in a stretched state. With this stress-relief stretchable substrate, we realized stretchable OLEDs that are compliant and maintain their performance under high strain deformation. Also, devices can be stretched in the biaxis, which is superior to only one-directional stretchable electronics; as such, devices can be used in practical applications like wearable electronics and health monitoring systems. We propose, for the first time, stretchable OLEDs patterned by the thermal evaporation fabrication process onto stress-relief substrates. These OLEDs can mitigate certain problems in previous studies of stretchable OLEDs without need to find new materials or to use a prestrained fabrication process.

BEX1 and BEX4 Induce GBM Progression through Regulation of Actin Polymerization and Activation of YAP/TAZ Signaling.

GBM is a high-grade cancer that originates from glial cells and has a poor prognosis. Although a combination of surgery, radiotherapy, and chemotherapy is prescribed to patients, GBM is highly resistant to therapies, and surviving cells show increased aggressiveness. In this study, we investigated the molecular mechanism underlying GBM progression after radiotherapy by establishing a GBM orthotopic xenograft mouse model. Based on transcriptomic analysis, we found that the expression of BEX1 and BEX4 was upregulated in GBM cells surviving radiotherapy. We also found that upregulated expression of BEX1 and BEX4 was involved in the formation of the filamentous cytoskeleton and altered mechanotransduction, which resulted in the activation of the YAP/TAZ signaling pathway. BEX1- and BEX4-mediated YAP/TAZ activation enhanced the tumor formation, growth, and radioresistance of GBM cells. Additionally, latrunculin B inhibited GBM progression after radiotherapy by suppressing actin polymerization in an orthotopic xenograft mouse model. Taken together, we suggest the involvement of cytoskeleton formation in radiation-induced GBM progression and latrunculin B as a GBM radiosensitizer.

Dual Specificity Kinase DYRK3 Promotes Aggressiveness of Glioblastoma by Altering Mitochondrial Morphology and Function.

Glioblastoma multiforme (GBM) is a malignant primary brain tumor with poor patient prognosis. Although the standard treatment of GBM is surgery followed by chemotherapy and radiotherapy, often a small portion of surviving tumor cells acquire therapeutic resistance and become more aggressive. Recently, altered kinase expression and activity have been shown to determine metabolic flux in tumor cells and metabolic reprogramming has emerged as a tumor progression regulatory mechanism. Here we investigated novel kinase-mediated metabolic alterations that lead to acquired GBM radioresistance and malignancy. We utilized transcriptomic analyses within a radioresistant GBM orthotopic xenograft mouse model that overexpresses the dual specificity tyrosine-phosphorylation-regulated kinase 3 (DYRK3). We find that within GBM cells, radiation exposure induces DYRK3 expression and DYRK3 regulates mammalian target of rapamycin complex 1 (mTORC1) activity through phosphorylation of proline-rich AKT1 substrate 1 (PRAS40). We also find that DYRK3 knockdown inhibits dynamin-related protein 1 (DRP1)-mediated mitochondrial fission, leading to increased oxidative phosphorylation (OXPHOS) and reduced glycolysis. Importantly, enforced DYRK3 downregulation following irradiation significantly impaired GBM cell migration and invasion. Collectively, we suggest DYRK3 suppression may be a novel strategy for preventing GBM malignancy through regulating mitochondrial metabolism.

Revisiting Platinum-Based Anticancer Drugs to Overcome Gliomas.

Although there are many patients with brain tumors worldwide, there are numerous difficulties in overcoming brain tumors. Among brain tumors, glioblastoma, with a 5-year survival rate of 5.1%, is the most malignant. In addition to surgical operations, chemotherapy and radiotherapy are generally performed, but the patients have very limited options. Temozolomide is the most commonly prescribed drug for patients with glioblastoma. However, it is difficult to completely remove the tumor with this drug alone. Therefore, it is necessary to discuss the potential of anticancer drugs, other than temozolomide, against glioblastomas. Since the discovery of cisplatin, platinum-based drugs have become one of the leading chemotherapeutic drugs. Although many studies have reported the efficacy of platinum-based anticancer drugs against various carcinomas, studies on their effectiveness against brain tumors are insufficient. In this review, we elucidated the anticancer effects and advantages of platinum-based drugs used in brain tumors. In addition, the cases and limitations of the clinical application of platinum-based drugs are summarized. As a solution to overcome these obstacles, we emphasized the potential of a novel approach to increase the effectiveness of platinum-based drugs.

Linear Magnetoelectric Phase in Ultrathin MnPS_{3} Probed by Optical Second Harmonic Generation.

The transition metal thiophosphates MPS_{3} (M=Mn, Fe, Ni) are a class of van der Waals stacked insulating antiferromagnets that can be exfoliated down to the ultrathin limit. MnPS_{3} is particularly interesting because its Néel ordered state breaks both spatial-inversion and time-reversal symmetries, allowing for a linear magnetoelectric phase that is rare among van der Waals materials. However, it is unknown whether this unique magnetic structure of bulk MnPS_{3} remains stable in the ultrathin limit. Using optical second harmonic generation rotational anisotropy, we show that long-range linear magnetoelectric type Néel order in MnPS_{3} persists down to at least 5.3 nm thickness. However an unusual mirror symmetry breaking develops in ultrathin samples on SiO_{2} substrates that is absent in bulk materials, which is likely related to substrate induced strain.

LDR-Induced miR-30a and miR-30b Target the PAI-1 Pathway to Control Adverse Effects of NSCLC Radiotherapy.

Radiotherapy has been a central part in curing non-small cell lung cancer (NSCLC). However, it is possible that not all of the tumor cells are destroyed by radiation; therefore, it is important to effectively control residual tumor cells that could become aggressive and resistant to radiotherapy. In this study, we aimed to investigate the molecular mechanism of decreased NSCLC radioresistance by low-dose radiation (LDR) pretreatment. The results indicated that miR-30a and miR-30b, which effectively inhibited plasminogen activator inhibitor-1 (PAI-1), were overexpressed by treatment of LDR to NSCLC cells. Phosphorylation of Akt and ERK, the downstream survival signals of PAI-1, was decreased by PAI-1 inhibition. Reduced cell survival and epithelial-mesenchymal transition by PAI-1 inhibition were confirmed in NSCLC cells. Moreover, in vivo orthotopic xenograft mouse models with 7C1 nanoparticles to deliver miRNAs showed that tumor growth and aggressiveness were efficiently decreased by LDR treatment followed by radiotherapy. Taken together, the present study suggested that PAI-1, whose expression is regulated by LDR, was critical for controlling surviving tumor cells after radiotherapy.