Injectable composite hydrogels embedded with gallium-based liquid metal particles for solid breast cancer treatment via chemo-photothermal combination.

Photothermal therapy (PTT) holds great promise as a cancer treatment modality by generating localized heat at the tumor site. Among various photothermal agents, gallium-based liquid metal (LM) has been widely used as a new photothermal-inducible metallic compound due to its structural transformability. To overcome limitations of random aggregation and dissipation of administrated LM particles into a human body, we developed LM-containing injectable composite hydrogel platforms capable of achieving spatiotemporal PTT and chemotherapy. Eutectic gallium-indium LM particles were first stabilized with 1,2-Distearoyl-sn­glycero-3-phosphoethanolamine (DSPE) lipids. They were then incorporated into an interpenetrating hydrogel network composed of thiolated gelatin conjugated with 6-mercaptopurine (MP) chemodrug and poly(ethylene glycol)-diacrylate. The resulted composite hydrogel exhibited sufficient capability to induce MDA-MB-231 breast cancer cell death through a multi-step mechanism: (1) hyperthermic cancer cell death due to temperature elevation by near-infrared laser irradiation via LM particles, (2) leakage of glutathione (GSH) and cleavage of disulfide bonds due to destruction of cancer cells. As a consequence, additional chemotherapy was facilitated by GSH, leading to accelerated release of MP within the tumor microenvironment. The effectiveness of our composite hydrogel system was evaluated both in vitro and in vivo, demonstrating significant tumor suppression and killing. These results demonstrate the potential of this injectable composite hydrogel for spatiotemporal cancer treatment. In conclusion, integration of PTT and chemotherapy within our hydrogel platform offers enhanced therapeutic efficacy, suggesting promising prospects for future clinical applications. STATEMENT OF SIGNIFICANCE: Our research pioneers a breakthrough in cancer treatments by developing an injectable hydrogel platform incorporating liquid metal (LM) particle-mediated photothermal therapy and 6-mercaptopurine (MP)-based chemotherapy. The combination of gallium-based LM and MP achieves synergistic anticancer effects, and our injectable composite hydrogel acts as a localized reservoir for specific delivery of both therapeutic agents. This platform induces a multi-step anticancer mechanism, combining NIR-mediated hyperthermic tumor death and drug release triggered by released glutathione from damaged cancer populations. The synergistic efficacy validated in vitro and in vivo studies highlights significant tumor suppression. This injectable composite hydrogel with synergistic therapeutic efficacy holds immense promise for biomaterial-mediated spatiotemporal treatment of solid tumors, offering a potent targeted therapy for triple negative breast cancers.

Corrigendum: Korean Ginseng Berry Extract Enhances the Male Steroidogenesis Enzymes In Vitro and In Vivo.

This corrects the article on p. 446 in vol. 41, PMID: 36649918.

Optimized Design of Hyaluronic Acid-Lipid Conjugate Biomaterial for Augmenting CD44 Recognition of Surface-Engineered NK Cells.

Triple-negative breast cancer (TNBC) presents treatment challenges due to a lack of detectable surface receptors. Natural killer (NK) cell-based adaptive immunotherapy is a promising treatment because of the characteristic anticancer effects of killing malignant cells directly by secreting cytokines and lytic granules. To maximize the cancer recognition ability of NK cells, biomaterial-mediated ex vivo cell surface engineering has been developed for sufficient cell membrane immobilization of tumor-targeting ligands via hydrophobic anchoring. In this study, we optimized amphiphilic balances of NK cell coating materials composed of CD44-targeting hyaluronic acid (HA)-poly(ethylene glycol) (PEG)-lipid to improve TNBC recognition and the anticancer effect. Changes in the modular design of our material by differentiating hydrophilic PEG length and incorporating lipid amount into HA backbones precisely regulated the amphiphilic nature of HA-PEG-lipid conjugates. The optimized biomaterial demonstrated improved anchoring into NK cell membranes and facilitating the surface presentation level of HA onto NK cell surfaces. This led to enhanced cancer targeting via increasing the formation of immune synapse, thereby augmenting the anticancer capability of NK cells specifically toward CD44-positive TNBC cells. Our approach addresses targeting ability of NK cell to solid tumors with a deficiency of surface tumor-specific antigens while offering a valuable material design strategy using amphiphilic balance in immune cell surface engineering techniques.

Association between sleep and myopia in children and adolescents: a systematic review and meta-analysis.

PURPOSE: There is a scarcity of literature focusing on sleep's impact on myopia in children despite an epidemic rise of myopia among the age group and the importance of early prevention. As such, this systematic review-meta-analysis aims to evaluate the association between various aspects of sleep and myopia in children and adolescents aged 0-19 years. METHODS: We searched PubMed, EMBASE, and Cochrane Library on 08/12/2022 for studies reporting sleep in relation to myopia among children and adolescents. Myopia was defined as spherical equivalent refraction < -0.5 diopter. The primary outcome was the relationship between sleep duration and myopia prevalence. Secondary outcomes include the effect of sleep quality, bedtime, and waketime on myopia prevalence, incidence, and progression. Odds ratio (OR) was estimated with a 95% confidence interval (95% CI). RESULTS: Eighteen studies (49,277 participants) were included in the review, and six studies (14,116 participants) were included in the meta-analysis for the primary outcome. There was no significant correlation between sleep and myopia prevalence (OR = 0.905, 95% CI = 0.782 to 1.047). Some studies suggested that better sleep quality (2 of 6 studies), earlier bedtime (3 of 5 studies), and later waketimes (2 of 3 studies) had protective effects on myopia. CONCLUSION: Sleep duration did not affect myopia prevalence in children, while other aspects of sleep had plausible but inconclusive impacts on myopia development and progression. More research with diverse populations and standardized methods of reporting is needed.

Tailoring tumor-recognizable hyaluronic acid-lipid conjugates to enhance anticancer efficacies of surface-engineered natural killer cells.

Natural killer (NK) cells have clinical advantages in adoptive cell therapy owing to their inherent anticancer efficacy and their ability to identify and eliminate malignant tumors. However, insufficient cancer-targeting ligands on NK cell surfaces often inhibit their immunotherapeutic performance, especially in immunosuppressive tumor microenvironment. To facilitate tumor recognition and subsequent anticancer function of NK cells, we developed hyaluronic acid (HA, ligands to target CD44 overexpressed onto cancer cells)-poly(ethylene glycol) (PEG, cytoplasmic penetration blocker)-Lipid (molecular anchor for NK cell membrane decoration through hydrophobic interaction) conjugates for biomaterial-mediated ex vivo NK cell surface engineering. Among these major compartments (i.e., Lipid, PEG and HA), optimization of lipid anchors (in terms of chemical structure and intrinsic amphiphilicity) is the most important design parameter to modulate hydrophobic interaction with dynamic NK cell membranes. Here, three different lipid types including 1,2-dimyristoyl-sn-glycero-3-phosphati-dylethanolamine (C14:0), 1,2-distearoyl-sn-glycero-3-phosphatidylethanolamine (DSPE, C18:0), and cholesterol were evaluated to maximize membrane coating efficacy and associated anticancer performance of surface-engineered NK cells (HALipid-NK cells). Our results demonstrated that NK cells coated with HA-PEG-DSPE conjugates exhibited significantly enhanced anticancer efficacies toward MDA-MB-231 breast cancer cells without an off-target effect on human fibroblasts specifically via increased NK cell membrane coating efficacy and prolonged surface duration of HA onto NK cell surfaces, thereby improving HA-CD44 recognition. These results suggest that our HALipid-NK cells with tumor-recognizable HA-PEG-DSPE conjugates could be further utilized in various cancer immunotherapies.

Ex Vivo Peptide Decoration Strategies on Stem Cell Surfaces for Augmenting Endothelium Interaction.

Ischemic vascular diseases remain leading causes of disability and death. Although various clinical therapies have been tried, reperfusion injury is a major issue, occurring when blood recirculates at the damaged lesion. As an alternative approach, cell-based therapy has emerged. Mesenchymal stem cells (MSCs) are attractive cellular candidates due to their therapeutic capacities, including differentiation, safety, angiogenesis, and tissue repair. However, low levels of receptors/ligands limit targeted migration of stem cells. Thus, it is important to improve homing efficacy of transplanted MSCs toward damaged endothelium. Among various MSC modulations, ex vivo cell surface engineering could effectively augment homing efficiency by decorating MSC surfaces with alternative receptors/ligands, thereby facilitating intercellular interactions with the endothelium. Especially, exogenous decoration of peptides onto stem cell surfaces could provide appropriate functional signaling moieties to achieve sufficient MSC homing. Based on their protein-like functionalities, high modularity in molecular design, and high specific affinities and multivalency to target receptors, peptides could be representative surface-presentable moieties. Moreover, peptides feature a mild synthetic process, enabling precise control of amino acid composition and sequence. Such ex vivo stem cell surface engineering could be achieved primarily by hydrophobic interactions of the cellular bilayer with peptide-conjugated anchor modules and by covalent conjugation between peptides and available compartments in membranes. To this end, this review provides an overview of currently available peptide-mediated, ex vivo stem cell surface engineering strategies for enhancing MSC homing efficiency by facilitating interactions with endothelial cells. Stem cell surface engineering techniques using peptide-based bioconjugates have the potential to revolutionize current vascular disease treatments while addressing their technical limitations.

Molecular detection of Bartonella and Borrelia in pet dogs in Metro Manila and Laguna, Philippines.

Background and Aim: Bartonella and Borrelia are zoonotic vector-borne pathogens that can infect dogs and humans. Data on Bartonella and Borrelia in dogs in the Philippines are lacking. This study was conducted to validate previous reports and further investigate the occurrence of Bartonella and Borrelia spp. in cities of Metro Manila. Materials and Methods: A total of 182 canine blood samples were acquired with DNA using a commercial extraction kit from selected veterinary clinics in the cities of Metro Manila and Laguna, Philippines. The mammalian actin was amplified through polymerase chain reaction (PCR), followed by PCR assays targeting Bartonella gltA and Borrelia flaB. Further PCR assays targeting 16S of Borrelia and ospA and ospC of Borrelia burgdorferi were performed for those that showed flaB bands. Results: A positive band for gltA of Bartonella was observed in 9 (4.95%) samples, whereas a positive band for flaB of Borrelia was observed in 15 (8.24%) samples. Subsequent PCR assays for other genes of Borrelia were negative. Conclusion: These results confirmed the presence of Bartonella and warranted further investigation for the possible presence of other Borrelia species.

Immunogenic cell death in cancer immunotherapy.

Cancer immunotherapy has been acknowledged as a new paradigm for cancer treatment, with notable therapeutic effects on certain cancer types. Despite their significant potential, clinical studies over the past decade have revealed that cancer immunotherapy has low response rates in the majority of solid tumors. One of the key causes for poor responses is known to be the relatively low immunogenicity of solid tumors. Because most solid tumors are immune desert 'cold tumors' with antitumor immunity blocked from the onset of innate immunity, combination therapies that combine validated T-based therapies with approaches that can increase tumor-immunogenicity are being considered as relevant therapeutic options. This review paper focuses on immunogenic cell death (ICD) as a way of enhancing immunogenicity in tumor tissues. We will thoroughly review how ICDs such as necroptosis, pyroptosis, and ferroptosis can improve anti-tumor immunity and outline clinical trials targeting ICD. Finally, we will discuss the potential of ICD inducers. as an adjuvant for cancer immunotherapy.[BMB Reports 2023; 56(5): 275-286].

Current progress in gallium-based liquid metals for combinatory phototherapeutic anticancer applications.

A variety of therapeutic approaches using liquid metal (LM) have been intensively investigated, due to its unique physico-chemical properties that include high surface tension, fluidity, shape deformability, thermal conductivity, and electrical conductivity. Among a series of LMs, the relatively lower toxicity and minimal volatility of gallium (Ga)-based LMs (GaLMs) enables their usage in a series of potential biomedical applications, especially implantable platforms, to treat multiple diseases. In addition, the highly efficient conversion of light energy into thermal or chemical energy via GaLMs has led to recent developments in photothermal and photodynamic applications for anticancer treatments. As attractive photothermal agents or photosensitizers, a systematic interpretation of the structural characteristics and photo-responsive behaviors of GaLMs is necessary to develop effective anticancer engineering applications. Therefore, the aim of this review is to provide a comprehensive summary of currently suggested GaLM-mediated photo-therapeutic cancer treatments. In particular, the review summarizes (1) surface coating techniques to form stable and multifunctional GaLM particulates, (2) currently investigated GaLM-mediated photothermal and photodynamic anticancer therapies, (3) synergistic efficacies with the aid of additional interventions, and (4) 3D composite gels embedded with GaLMs particles, to convey the potential technological advances of LM in this field.

A combination of BR101801 and venetoclax enhances antitumor effect in DLBCL cells via c-Myc/Bcl-2/Mcl-1 triple targeting.

Double hit diffuse large B-cell lymphoma (DLBCL) with rearrangement and overexpression of both c-Myc and Bcl-2 responds poorly to standard R-CHOP therapy. In a recent phase I study, Venetoclax (ABT-199) targeting Bcl-2 also exhibited disappointing response rates in patients with relapsed/refractory DLBCL, suggesting that targeting only Bcl-2 is not sufficient for achieving successful efficacy due to the concurrent oncogenic function of c-Myc expression and drug resistance following an increase in Mcl-1. Therefore, co-targeting c-Myc and Mcl-1 could be a key combinatorial strategy to enhance the efficacy of Venetoclax. In this study, BR101801 a novel drug for DLBCL, effectively inhibited DLBCL cell growth/proliferation, induced cell cycle arrest, and markedly inhibited G0/G1 arrest. The apoptotic effect of BR101801 was also observed by increased Cytochrome C, cleaved PARP, and Annexin V-positive cell populations. This anti-cancer effect of BR101801 was confirmed in animal models, where it effectively inhibited tumor growth by reducing the expression of both c-Myc and Mcl-1. Furthermore, BR101801 exhibited a significant synergistic antitumor effect even in late xenograft models when combined with Venetoclax. Our data strongly suggest that c-Myc/Bcl-2/Mcl-1 triple targeting through a combination of BR101801 and Venetoclax could be a potential clinical option for double-hit DLBCL.

Association between polycystic ovary syndrome and non-infectious uveitis.

Polycystic ovary syndrome (PCOS) is a common endocrine disease in young women. It has been reported that increased proinflammatory cytokines can induce systemic inflammation. However, the association between PCOS and uveitis remains elusive. In this study, we investigate the possible association between PCOS and uveitis using Korean National Health Insurance Service-National Sample Cohort. The incidence of non-infectious uveitis was compared between patients with and without PCOS before and after propensity score matching. Hazard ratios were determined using univariate and multivariate Cox regression models. Of 558,302 female participants, 2039 had PCOS and 8122 had non-infectious uveitis. The incidence of non-infectious uveitis was 35.1 per 10,000 person-years in the PCOS patients compared to 16.6 in non-patients (P < .001). This tendency remained after 1:3 propensity score matching. The hazard ratio of PCOS using a multivariate Cox regression model was 2.79 (95% CI, 1.92-4.05; P < .001) and 2.87 (95% CI, 1.77-4.67; P < .001) before and after matching, respectively. Our results suggests that PCOS is associated with non-infectious uveitis, particularly in women of reproductive age. This may be due to hormonal changes and proinflammatory factors. Future investigations should examine the clinical features and underlying mechanisms.

Korean Ginseng Berry Extract Enhances the Male Steroidogenesis Enzymes In Vitro and In Vivo.

PURPOSE: Testosterone hormonal replacement is the most commonly prescribed solution for men with reproductive issues; however, this treatment has various drawbacks. Hence, the identification of a natural product that promotes steroidogenesis is urgently needed. Ginseng is a popular traditional medicine. This study aimed to investigate steroidogenic effects of Korean ginseng berry extract (GBE; Panax ginseng C.A. Meyer) in vitro and in vivo. MATERIALS AND METHODS: In vitro model, mouse Leydig cells were treated with varying concentrations of GBE, and the levels of steroidogenesis-related genes and proteins and testosterone were measured using western blotting, qRT-PCR, and enzyme-linked immunosorbent assay (ELISA). Similarly, in an in vivo model using lipopolysaccharide-injected C57BL/6J mice, expression of steroidogenesis-related genes and proteins and testosterone levels were analyzed. Additionally, sleep deprivation was used to simulate common life stressors related to late-onset hypogonadism (LOH) and the natural effects of aging. Mice were fed sham or GBE before being subjected to paradoxical sleep deprivation. RESULTS: In vitro, GBE induced steroidogenic effects by increasing the levels of enzymes associated with steroidogenesis, steroidogenic acute regulatory protein (STAR), CYP11A1, and CYP17A1. In vivo, GBE significantly increased mRNA and protein levels of steroidogenic enzymes. Furthermore, the synthetic testosterone levels in mouse Leydig cell supernatants and blood sera were increased. In the sleep deprivation study, mice fed GBE showed increased testosterone production and survival under such stressful conditions. CONCLUSIONS: GBE increased mRNA and protein levels of steroidogenesis-related enzymes STAR, CYP11A1, and CYP17A1. These key enzymes induced the increased production of testosterone both in vivo and in vitro. Thus, GBE might be a promising therapeutic or additive nutritional agent for improving men's health by increasing steroidogenesis or improving LOH.

Eco-Friendly Keratin-Based Additives in the Polymer Matrix to Enhance the Output of Triboelectric Nanogenerators.

A triboelectric nanogenerator (TENG) is an energy generator that converts mechanical energy into electrical energy using triboelectricity at a nanoscale. Given their potential application as power sources in electronic devices, various attempts have been made to improve their output performance. Here, we present an eco-friendly, low-cost, and facile fabrication method to enhance TENG characteristics with keratin protein additives. Keratin sources, human and cat hair, are processed into powder and added to the friction layer, which increases their positive charge affinity, thereby boosting the output performance of the TENG. The output performances of the keratin-added TENG (K-TENG) are measured in the vertical contact-separation mode, with both additives having the highest output values at 5 wt % load. The K-TENG generates more output voltage and current values than the pristine TENG by 90 and 208%, respectively. Hence, we conclude that this method would potentially promote TENG as a strong candidate for a competitive "green" energy harvesting device in future electronics applications.

Voxel-wise adversarial semi-supervised learning for medical image segmentation.

BACKGROUND AND OBJECTIVE: Semi-supervised learning for medical image segmentation is an important area of research for alleviating the huge cost associated with the construction of reliable large-scale annotations in the medical domain. Recent semi-supervised approaches have demonstrated promising results by employing consistency regularization, pseudo-labeling techniques, and adversarial learning. These methods primarily attempt to learn the distribution of labeled and unlabeled data by enforcing consistency in the predictions or embedding context. However, previous approaches have focused only on local discrepancy minimization or context relations across single classes. METHODS: In this paper, we introduce a novel adversarial learning-based semi-supervised segmentation method that effectively embeds both local and global features from multiple hidden layers and learns context relations between multiple classes. Our voxel-wise adversarial learning method utilizes a voxel-wise feature discriminator, which considers multilayer voxel-wise features (involving both local and global features) as an input by embedding class-specific voxel-wise feature distribution. Furthermore, our previous representation learning method is improved by overcoming information loss and learning stability problems, which enables rich representations of labeled data. RESULT: In the experiments, we used the Left Atrial Segmentation Challenge dataset and the Abdominal Multi-Organ dataset to prove the effectiveness of our method in both single class and multiclass segmentation. The experimental results demonstrate that our method outperforms current best-performing state-of-the-art semi-supervised learning approaches. Our proposed adversarial learning-based semi-supervised segmentation method successfully leveraged unlabeled data to improve the network performance by 2% in Dice score coefficient for multi-organ dataset. CONCLUSION: We compare our approach to a wide range of medical datasets, and showed our method can be adapted to embed class-specific features. Furthermore, visual interpretation of the feature space demonstrates that our proposed method enables a well-distributed and separated feature space from both labeled and unlabeled data, which improves the overall prediction results.

The telomere maintenance mechanism spectrum and its dynamics in gliomas.

BACKGROUND: The activation of the telomere maintenance mechanism (TMM) is one of the critical drivers of cancer cell immortality. In gliomas, TERT expression and TERT promoter mutation are considered to reliably indicate telomerase activation, while ATRX mutation and/or loss indicates an alternative lengthening of telomeres (ALT). However, these relationships have not been extensively validated in tumor tissues. METHODS: Telomerase repeated amplification protocol (TRAP) and C-circle assays were used to profile and characterize the TMM cross-sectionally (n = 412) and temporally (n = 133) across glioma samples. WES, RNA-seq, and NanoString analyses were performed to identify and validate the genetic characteristics of the TMM groups. RESULTS: We show through the direct measurement of telomerase activity and ALT in a large set of glioma samples that the TMM in glioma cannot be defined solely by the combination of telomerase activity and ALT, regardless of TERT expression, TERT promoter mutation, and ATRX loss. Moreover, we observed that a considerable proportion of gliomas lacked both telomerase activity and ALT. This telomerase activation-negative and ALT negative group exhibited evidence of slow growth potential. By analyzing a set of longitudinal samples from a separate cohort of glioma patients, we discovered that the TMM is not fixed and can change with glioma progression. CONCLUSIONS: This study suggests that the TMM is dynamic and reflects the plasticity and oncogenicity of tumor cells. Direct measurement of telomerase enzyme activity and evidence of ALT should be considered when defining TMM. An accurate understanding of the TMM in glioma is expected to provide important information for establishing cancer management strategies.

Soluble ACE2 and TMPRSS2 Levels in the Serum of Asthmatic Patients.

BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine subtype 2 (TMPRSS2) are key proteins mediating viral entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although gene expressions of ACE2 and TMPRSS2 have been analyzed in various organs and diseases, their soluble forms have been less studied, particularly in asthma. Therefore, we aimed to measure circulating ACE2 and TMPRSS2 in the serum of asthmatics and examine their relationship with clinical characteristics. METHODS: Clinical data and serum samples of 400 participants were obtained from an asthma cohort. The soluble ACE2 (sACE2) and soluble TMPRSS2 (sTMPRSS2) level was measured by enzyme-linked immunosorbent assay, and the values underwent a natural log transformation. Associations between sACE2 and TMPRSS2 levels and various clinical variables were analyzed. RESULTS: The patients younger than 70 years old, those with eosinophilic asthma (eosinophils ≥ 200 cells/µL), and inhaled corticosteroids (ICS) non-users were associated with higher levels of sACE2. Blood eosinophils and fractionated exhaled nitric oxide levels were positively correlated with serum ACE2. In contrast, lower levels of sTMPRSS2 were noted in patients below 70 years and those with eosinophilic asthma, while no association was noted between ICS use and sTMPRSS2. The level of sTMPRSS2 also differed according to sex, smoking history, coexisting hypertension, and forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio. The proportion of sputum neutrophils was positively correlated with sTMPRSS2, while the FEV1/FVC ratio reported a negative correlation with sTMPRSS2. CONCLUSION: The levels of ACE2 and TMPRSS2 were differently expressed according to age, ICS use, and several inflammatory markers. These findings suggest variable susceptibility and prognosis of SARS-CoV-2 infection among asthmatic patients.

Intaglio Contact Printing of Versatile Carbon Nanotube Composites and Its Applications for Miniaturizing High-Performance Devices.

Composites based on carbon nanotubes (CNTs) are promising patternable materials that can be engineered to incorporate the outstanding properties of CNTs into various applications via printing technologies. However, conventional printing methods for CNTs require further improvement to overcome the major drawbacks that limit the patterning resolution and target substrate. Herein, an intaglio contact printing method based on a CNT/paraffin composite is presented for realizing highly precise CNT network patterns without restrictions on the substrate. In this method, the CNT/paraffin composite can be patterned with a high resolution (<10 µm) and neatly transferred onto various substrates with a wide range of surface energies, including human skin. The patterned composite exhibits high durability against structural deformations, and structural damage caused by fatigue accumulation can be cured in a few seconds. In addition, miniaturized sensing and energy-harvesting applications are demonstrated with high performances. The present method facilitates the rapid fabrication of highly precise interdigitated electrodes via one-step printing, enabling high-performance operation and miniaturization of the devices. It is anticipated that these results will not only spur the further development of various applications of CNTs but also contribute to advances in soft lithography methods applicable to many fields of science and engineering.

Voxel-level Siamese Representation Learning for Abdominal Multi-Organ Segmentation.

BACKGROUND AND OBJECTIVE: Recent works in medical image segmentation have actively explored various deep learning architectures or objective functions to encode high-level features from volumetric data owing to limited image annotations. However, most existing approaches tend to ignore cross-volume global context and define context relations in the decision space. In this work, we propose a novel voxel-level Siamese representation learning method for abdominal multi-organ segmentation to improve representation space. METHODS: The proposed method enforces voxel-wise feature relations in the representation space for leveraging limited datasets more comprehensively to achieve better performance. Inspired by recent progress in contrastive learning, we suppressed voxel-wise relations from the same class to be projected to the same point without using negative samples. Moreover, we introduce a multi-resolution context aggregation method that aggregates features from multiple hidden layers, which encodes both the global and local contexts for segmentation. RESULTS: Our experiments on the multi-organ dataset outperformed the existing approaches by 2% in Dice score coefficient. The qualitative visualizations of the representation spaces demonstrate that the improvements were gained primarily by a disentangled feature space. CONCLUSION: Our new representation learning method successfully encoded high-level features in the representation space by using a limited dataset, which showed superior accuracy in the medical image segmentation task compared to other contrastive loss-based methods. Moreover, our method can be easily applied to other networks without using additional parameters in the inference.

Current Stimulation of the Midbrain Nucleus in Pigeons for Avian Flight Control.

A number of research attempts to understand and modulate sensory and motor skills that are beyond the capability of humans have been underway. They have mainly been expounded in rodent models, where numerous reports of controlling movement to reach target locations by brain stimulation have been achieved. However, in the case of birds, although basic research on movement control has been conducted, the brain nuclei that are triggering these movements have yet to be established. In order to fully control flight navigation in birds, the basic central nervous system involved in flight behavior should be understood comprehensively, and functional maps of the birds' brains to study the possibility of flight control need to be clarified. Here, we established a stable stereotactic surgery to implant multi-wire electrode arrays and electrically stimulated several nuclei of the pigeon's brain. A multi-channel electrode array and a wireless stimulation system were implanted in thirteen pigeons. The pigeons' flight trajectories on electrical stimulation of the cerebral nuclei were monitored and analyzed by a 3D motion tracking program to evaluate the behavioral change, and the exact stimulation site in the brain was confirmed by the postmortem histological examination. Among them, five pigeons were able to induce right and left body turns by stimulating the nuclei of the tractus occipito-mesencephalicus (OM), nucleus taeniae (TN), or nucleus rotundus (RT); the nuclei of tractus septo-mesencephalicus (TSM) or archistriatum ventrale (AV) were stimulated to induce flight aviation for flapping and take-off with five pigeons.

Liver segmentation in abdominal CT images via auto-context neural network and self-supervised contour attention.

OBJECTIVE: Accurate image segmentation of the liver is a challenging problem owing to its large shape variability and unclear boundaries. Although the applications of fully convolutional neural networks (CNNs) have shown groundbreaking results, limited studies have focused on the performance of generalization. In this study, we introduce a CNN for liver segmentation on abdominal computed tomography (CT) images that focus on the performance of generalization and accuracy. METHODS: To improve the generalization performance, we initially propose an auto-context algorithm in a single CNN. The proposed auto-context neural network exploits an effective high-level residual estimation to obtain the shape prior. Identical dual paths are effectively trained to represent mutual complementary features for an accurate posterior analysis of a liver. Further, we extend our network by employing a self-supervised contour scheme. We trained sparse contour features by penalizing the ground-truth contour to focus more contour attentions on the failures. RESULTS: We used 180 abdominal CT images for training and validation. Two-fold cross-validation is presented for a comparison with the state-of-the-art neural networks. The experimental results show that the proposed network results in better accuracy when compared to the state-of-the-art networks by reducing 10.31% of the Hausdorff distance. Novel multiple N-fold cross-validations are conducted to show the best performance of generalization of the proposed network. CONCLUSION AND SIGNIFICANCE: The proposed method minimized the error between training and test images more than any other modern neural networks. Moreover, the contour scheme was successfully employed in the network by introducing a self-supervising metric.