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Abstract Background Defects in the ataxin-2 (ATXN-2) protein and CAG trinucleotide repeat expansion in its coding gene, Atxn-2, cause the neurodegenerative disorder spinocerebellar ataxia type 2 (SCA2). While clinical studies suggest potential benefits of human-derived mesenchymal stem cells (hMSCs) for treating various ataxias, the exact mechanisms underlying their therapeutic effects and interaction with host tissue to stimulate neurotrophin expression remain unclear specifically in the context of SCA2. Methods Human bone marrow-derived MSCs (hMSCs) were injected into the cisterna magna of 26-week-old wild-type and SCA2 mice. Mice were assessed for impaired motor coordination using the accelerating rotarod, open field test, and composite phenotype scoring. At 50 weeks, the cerebellum vermis was harvested for protein assessment and immunohistochemical analysis. Results Significant loss of NeuN and calbindin was observed in 25-week-old SCA2 mice. However, after receiving multiple injections of hMSCs starting at 26 weeks of age, these mice exhibited a significant improvement in abnormal motor performance and a protective effect on Purkinje cells. This beneficial effect persisted until the mice reached 50 weeks of age, at which point they were sacrificed to study further mechanistic events triggered by the administration of hMSCs. Calbindin-positive cells in the Purkinje cell layer expressed bone-derived neurotrophic factor after hMSC administration, contributing to the protection of cerebellar neurons from cell death. Conclusion In conclusion, repeated administration of hMSCs shows promise in alleviating SCA2 symptoms by preserving Purkinje cells, improving neurotrophic support, and reducing inflammation, ultimately leading to the preservation of locomotor function in SCA2 mice.

Abstract The bioinspired camera, comprising a single lens and a curved image sensor—a photodiode array on a curved surface—, was born of flexible electronics. Its economical build lends itself well to space-constrained machine vision applications. The curved sensor, much akin to the retina, helps image focusing, but the curvature also creates a problem of image distortion, which can undermine machine vision tasks such as object recognition. Here we report an anti-distortion single-lens camera, where 4096 silicon photodiodes arrayed on a curved surface in a nonuniform pattern assimilated to the distorting optics are the key to anti-distortion engineering. That is, the photo-pixel distribution pattern itself is warped in the same manner as images are warped, which correctively reverses distortion. Acquired images feature no appreciable distortion across a 120° horizontal view, as confirmed by their neural-network recognition accuracies. This distortion correction via photo-pixel array reconfiguration is a form of in-sensor computing.

Organic matter is crucial in aerosol–climate interactions, yet the physicochemical properties and origins of organic aerosols remain poorly understood. Here we show the seasonal characteristics of submicron organic aerosols in Arctic Svalbard during spring and summer, emphasizing their connection to transport patterns and particle size distribution. Microbial-derived organic matter (MOM) and terrestrial-derived organic matter (TOM) accounted for over 90% of the total organic mass in Arctic aerosols during these seasons, comprising carbohydrate/protein-like and lignin/tannin-like compounds, respectively. In spring, aerosols showed high TOM and low MOM intensities due to biomass-burning influx in the central Arctic. In contrast, summer exhibited elevated MOM intensity, attributed to the shift in predominant atmospheric transport from the central Arctic to the biologically active Greenland Sea. MOM and TOM were associated with Aitken mode particles (100 nm diameter), respectively. This association is linked to the molecular size of biomolecules, impacting the number concentrations of corresponding aerosol classes. These findings highlight the importance of considering seasonal atmospheric transport patterns and organic source-dependent particle size distributions in assessing aerosol properties in the changing Arctic.

Abstract We explored the genomic events underlying central neurocytoma (CN), a rare neoplasm of the central nervous system, via multiomics approaches, including whole-exome sequencing, bulk and single-nuclei RNA sequencing, and methylation sequencing. We identified FGFR3 hypomethylation leading to FGFR3 overexpression as a major event in the ontogeny of CN that affects crucial downstream events, such as aberrant PI3K-AKT activity and neuronal development pathways. Furthermore, we found similarities between CN and radial glial cells based on analyses of gene markers and CN tumor cells and postulate that CN tumorigenesis is due to dysregulation of radial glial cell differentiation into neurons. Our data demonstrate the potential role of FGFR3 as one of the leading drivers of tumorigenesis in CN.

Abstract In this multi-center, assessor-blinded pilot study, the diagnostic efficacy of cCeLL-Ex vivo, a second-generation confocal laser endomicroscopy (CLE), was compared against the gold standard frozen section analysis for intraoperative brain tumor diagnosis. The study was conducted across three tertiary medical institutions in the Republic of Korea. Biopsy samples from newly diagnosed brain tumor patients were categorized based on location and divided for permanent section analysis, frozen section analysis, and cCeLL-Ex vivo imaging. Of the 74 samples from 55 patients, the majority were from the tumor core (74.3%). cCeLL-Ex vivo exhibited a relatively higher diagnostic accuracy (89.2%) than frozen section analysis (86.5%), with both methods showing a sensitivity of 92.2%. cCeLL-Ex vivo also demonstrated higher specificity (70% vs. 50%), positive predictive value (PPV) (95.2% vs. 92.2%), and negative predictive value (NPV) (58.3% vs. 50%). Furthermore, the time from sample preparation to diagnosis was notably shorter with cCeLL-Ex vivo (13 min 17 s) compared to frozen section analysis (28 min 28 s) (p-value

Reducing atmospheric CO2 levels to combat global warming is a pressing concern today. Numerous methods have been employed to capture CO2 from flue gases. One particularly promising approach is the use of carbonic anhydrases (CAs) as biocatalysts for the rapid conversion of CO2 to H2CO3. However, the widespread application of CAs for CO2 capture has been hampered by their inherent instability under real-world conditions. In this study, we have successfully engineered a chimeric carbonic anhydrase with vastly improved physicochemical properties, particularly with respect to its resilience to high temperatures, alkaline pH, and saline environments. Using computational design, we created various hybrid CAs with enhanced resistance to elevated temperatures. Among them, a chimeric CA known as SPS, generated by domain exchange between SazCA and PmCA, exhibited superior heat stability compared to its parent CAs. SPS showed 10 % higher enzymatic activity and retained 80–13 % of its activity during a period of 3 h to 24 h of incubation at 100℃. SPS's apparent kcat and Km values were 4.84 × 108 s−1 and 13.7 mM, respectively. Structural analysis revealed that SPS forms dimers, which contributes to its robustness. Furthermore, we introduced modifications in the form of SPS_1 and SPS_2 variants by incorporating one or two loop sequences from the halotolerant dCAII into SPS. These modifications significantly improved the stability of the CA in alkaline and saline conditions. In particular, SPS showed remarkable efficiency in hydrating CO2 in seawater. Given these compelling results, we propose that hybrid CAs such as SPS, SPS_1, and SPS_2 hold great promise for facilitating CO2 hydration in a wide range of applications. Synopsis: Greenhouse gas sequestration is an immediate need. This study reports an engineered and highly stable carbonic anhydrase for CO2 sequestration and greenhouse gas reduction.

The International Maritime Organization has adopted a revision to the 2023 International Maritime Organization biofouling guidelines and has been discussing the development of guidelines for evaluating the efficacy of in-water cleaning systems. In hull cleaning, which involves aquatic invasive species removal, capture is considered very important in preventing the release of by-products. However, capture efficacy is difficult to evaluate due to the absence of unified evaluation guidelines or standardized methods. Here, we describe a new test method for evaluating the capture efficacy of in-water cleaning systems, using artificial barnacles that simulate the physical characteristics of actual barnacles. The test was designed to evaluate the impact of in-water cleaning on biocide release and biofouling organisms in the marine environment. We used a test plate with artificial barnacles attached to evaluate the capture efficacy with respect to the fouling rating. This test overcomes limitations in the evaluation of the capture efficacy of in-water cleaning systems and provides a reference for the development of more comprehensive tests and in-water cleaning regulation in the future.

Abstract Background COVID-19 pandemic has led to psychological concerns, the distribution of which across populations may differ depending on whether pandemic-related damage is direct or indirect. This study aims to investigate concerns associated with direct and indirect damage according to population characteristics, and identify relatively vulnerable groups that are particularly affected by concerns. Method This cross-sectional study used data from the 2020 Korea Community Health Survey, which collected data based on a complex sampling design. A total of 208,106 responses from individuals aged ≥ 19 were collected via in-person interviews. The items related to COVID-19 concerns were measured by Likert scales ranging from 1 to 5 and categorized into two types: direct concerns, which pertained to infection or death, and indirect concerns, which pertained to criticism, vulnerability, and economic damage, through factor analysis. We compared the means and effect size of direct concerns, indirect concerns, and overall concerns using weighted mean, ANOVA, and multiple regression analysis. Results Exploratory and confirmatory factor analyses supported a two-factor structure for psychological concerns about COVID-19 (CFI = 0.99, TLI = 0.97, SRMR = 0.02, RMSEA = 0.06), which were divided into direct and indirect concerns. Mean scores were 3.62 for direct concerns and 4.07 for indirect concerns. Direct concerns were higher in females (B = .26); the elderly (B = .15); those diagnosed with hypertension or diabetes (B = .04; B = .06); those with few assistants during quarantine (B = .15); and those whose neighbors responded inappropriately to COVID-19 (B = .07). Indirect concerns were lower among the elderly (B = -.04), and higher among young; married (B = .25); pink- or blue-collar workers (B = .08; B = .06); and those who felt that the city responded inappropriately to COVID-19 (B = .02). Conclusion The prevalence of concerns regarding direct and indirect damage caused by the COVID-19 pandemic differed according to population characteristics. Some factors had a marked influence on direct and indirect concerns. Our findings could inform psychological interventions and policies for future pandemics. Customized interventions are needed to prevent negative psychological concerns and improve mental health.

Robots epitomize one of the most popular human imaginations that are evolving to become reality in the most pervasive way. Especially with the rise of artificial intelligence, it is more hopeful than ever that robots one day will be the interactive companions with some degree of emotion. A variety of robots in different forms with considerable mobility are available today. Among them, legged robots are the most attractive due to their dexterity, traversal versatility, functional modularity, and locomotive stability. Legged robots like robotic dogs can survey unchartered territories in uncertain environments. In this comprehensive review article, the status quo of this emerging and exciting field and how electronics of various form factors can functionalize them in an unbiased manner are surveyed and discussed. Different accessories currently available for quadrupedal robots, wearable devices potentially integratable with these robots, data management/integration strategies for reliable interfacing, and future outlook are discussed.

Purpose This study aimed to evaluate the predictive value of lymph node yield (LNY) for survival outcomes according to tumor response after preoperative chemoradiotherapy (PCRT) in patients with rectal cancer. Methods This study was a retrospective study conducted in a tertiary center. A total of 1,240 patients with clinical stage II or III rectal cancer who underwent curative resection after PCRT between 2007 and 2016 were included. Patients were categorized into the good response group (tumor regression grade [TRG], 0–1) or poor response group (TRG, 2–3). Propensity score matching was performed for age, sex, and pathologic stage between LNY of ≥12 and LNY of

Tungsten oxide (WO3) is known for its photochromic properties, making it useful for smart windows, displays, and sensors. However, its small bandgap leads to rapid recombination of electron–hole pairs, resulting in poor photochromic performance. This study aims to enhance the photochromic properties of WO3 by synthesizing hexagonal tungsten oxide via hydrothermal synthesis, which increases surface area and internal hydrates. Titanium oxide (TiO2) was adsorbed onto the tungsten oxide to inject additional charges and reduce electron–hole recombination. Additionally, polyvinylpyrrolidone (PVP) was used to improve dispersion in organic solvents, allowing for the fabrication of high-quality films using the doctor blade method. Characterization confirmed the enhanced surface area, crystal structure, and dispersion stability. Reflectance and transmittance measurements demonstrated significant improvements in photochromic properties due to the composite structure. These findings suggest that the introduction of TiO2 and PVP to tungsten oxide effectively enhances its photochromic performance, broadening its applicability in various advanced photochromic applications.

Abstract Nephritis is common in systemic lupus erythematosus patients and is associated with hyper-activation of immune and renal cells. Although mesenchymal stem cells (MSCs) ameliorate nephritis by inhibiting T and B cells, whether MSCs directly affect renal cells is unclear. To address this issue, we examined the direct effect of MSCs on renal cells with a focus on chemokines. We found that expression of CCL2, CCL3, CCL4, CCL5, CCL8, CCL19, and CXCL10 increased 1.6–5.6-fold in the kidney of lupus-prone MRL.Fas lpr mice with advancing age from 9 to 16 weeks. Although MSCs inhibited the increase in the expression of most chemokines by 52–95%, they further increased CCL8 expression by 290%. Using renal cells, we next investigated how MSCs enhanced CCL8 expression. CCL8 was expressed by podocytes, but not by tubular cells. MSCs enhanced CCL8 expression by podocytes in a contact-dependent manner, which was proved by transwell assay and blocking with anti-VCAM-1 antibody. Finally, we showed that CCL8 itself activated MSCs to produce more immunosuppressive factors (IL-10, IDO, TGF-β1, and iNOS) and to inhibit more strongly IFN-γ production by T cells. Taken together, our data demonstrate that MSCs activate podocytes to produce CCL8 in a contact-dependent manner and conversely, podocyte-derived CCL8 might potentiate immunosuppressive activity of MSCs in a paracrine fashion. Our study documents a previously unrecognized therapeutic mechanism of MSCs in nephritis.

Radiotherapy is commonly used to treat solid cancers located in the pelvis. A considerable number of patients experience proctitis of varying severity, even for a considerable period after radiotherapy. These side effects are often long-lasting or progressively worsen despite multiple therapeutic efforts and are a primary cause of an unexpectedly low quality of life, even after successful cancer treatment. Therefore, this study evaluated the individual and combined efficacy of ginsenoside, curcumin, butyric acid, and sucralfate compounds in treating radiation-induced proctitis. While the candidate compounds did not affect the proliferation and migration of cancer cells, they promoted the recovery of cell activity, including motility. They exhibited anti-inflammatory effects on human dermal fibroblasts or human umbilical vein endothelial cells within in vitro disease models. When each compound was tested, curcumin and ginsenoside were the most effective in cell recovery and promoted the migration of human dermal fibroblasts and cell restoration of human umbilical vein endothelial cells. The combination of ginsenoside and curcumin resulted in cell migration recovery of approximately 54%. In addition, there was a significant improvement in the length of the endothelial tube, with an increase of approximately 25%, suggesting that the ginsenoside-curcumin-containing combination was the most effective against radiation-induced damage. Furthermore, studies evaluating the effects of combined treatments on activated macrophages indicated that the compounds effectively reduced the secretion of inflammatory cytokines, including chemokines, and alleviated radiation-induced inflammation. In conclusion, our study provides valuable insights into using curcumin and ginsenoside as potential compounds for the effective treatment of radiation-induced injuries and highlights the promising therapeutic benefits of combining these two compounds.

ABSTRACT Microbial interactions are determined by competition, cooperation, and inaction, depending on the transcriptional response to the metabolites secreted by each other. The consequence of these interactions is reflected in the cell phenotype by the composition of cell materials, including lipids, nucleotides, and proteins. We studied the phenotypic plasticity of single cells involved in microbial interactions using Raman spectroscopy and evaluated the types of interactions by linking phenotypes to transcriptional profiles. We used a membrane-based co-culture system to induce chemical interactions between skin-dominant bacteria and fungi, Staphylococcus and Malassezia. Staphylococcus species exhibited an amensalism interaction with Malassezia based on growth and cell viability. Malassezia co-cultured with S. epidermidis and S. aureus resulted in significant changes in the Raman spectra of nucleic acids and proteins in the Raman phenotypes, respectively. The observed differences in phenotypes during co-culture with Malassezia were significantly associated with changes in transcriptomic profiles, which demonstrated variations in the defense/resistance and biofilm-formation mechanisms of S. epidermidis, whereas no meaningful changes were observed for the transcriptome of S. aureus. These approaches provide a robust, simple, and reproducible method for comprehending bacterial–fungal interactions. IMPORTANCE Evaluating bacterial–fungal interactions is important for understanding ecological functions in a natural habitat. Many studies have defined bacterial–fungal interactions according to changes in growth rates when co-cultivated. However, the current literature lacks detailed studies on phenotypic changes in single cells associated with transcriptomic profiles to understand the bacterial-fungal interactions. In our study, we measured the single-cell phenotypes of bacteria co-cultivated with fungi using Raman spectroscopy with its transcriptomic profiles and determined the consequence of these interactions in detail. This rapid and reliable phenotyping approach has the potential to provide new insights regarding bacterial–fungal interactions.

Background As pilomatricoma is a common adnexal skin tumor often occurring in exposed areas, dermatologists focus on minimizing postsurgical scarring. Methods This retrospective study included patients aged

Dear Editor, Pyoderma gangrenosum(PG) is a rare neutrophilic dermatosis that causes the development of painful ulcers on the skin, initially starting with nodules or abscesses, and quickly progressing at the peripheral regions into ulcers.1 The exact cause is not yet known, and 20-30% of patients are said to experience a pathergy phenomenon in which lesions occur in the sites of previous trauma.2 In addition, pyoderma gangrenosum is accompanied by systemic diseases, such as Crohn's disease or inflammatory colitis, rheumatoid arthritis, and hyperthyroidism.3 Although numerous reports indicate that pyoderma gangrenosum is associated with systemic diseases,4 case reports on the association of pyoderma gangrenosum with skin diseases, especially blistering disorders, are very rare. [...]

Abstract 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.

Abstract Background A single cycle (two repeated treatments) with intrathecal autologous bone marrow-derived mesenchymal stem cells (BM-MSCs, 26-day interval) showed safety and provided therapeutic benefit lasting 6 months in patients with ALS but did not demonstrate long-term efficacy. This phase III clinical trial (ALSUMMIT) protocol was developed to evaluate the long-term efficacy and safety of the combined protocol of single-cycle intrathecal therapy and three additional booster injections of BM-MSC (Lenzumestrocel) treatment in patients with ALS. Methods ALSUMMIT is a multicentre, randomized, double-blind, parallel-group, sham procedure-controlled, phase III trial for ALS. The 115 subjects will be randomized (1:2:2) into three groups: (1) study Group 1 (single-cycle, two repeated injections with 26-day interval), (2) study Group 2 (single-cycle + three additional booster injections at 4, 7, and 10 months), and (3) the control group. Participants who have an intermediate rate of disease progression will be included in this trial to reduce clinical heterogeneity. The primary endpoint will be evaluated by combined assessment of function and survival (CAFS), also known as joint rank scores (JRS), at 6 months (study Group 1 vs. control) and 12 months (study Group 2 vs. control) after the first Lenzumestrocel or placebo administration. Safety assessment will be performed throughout the study period. Additionally, after the 56-week main study, a long-term follow-up observational study will be conducted to evaluate the long-term efficacy and safety up to 36 months. Discussion Lenzumestrocel is the orphan cell therapy product for ALS conditionally approved by the South Korea Ministry of Food and Drug Safety (MFDS). This ALSUMMIT protocol was developed for the adoption of enrichment enrolment, add-on design, and consideration of ethical issues for the placebo group. Trial registration ClinicalTrials.gov NCT04745299 . Registered on Feb 9, 2021. Clinical Research Information Service (CRIS) KCT0005954 . Registered on Mar 4, 2021.

Abstract Augmented reality (AR) offers a new medical treatment approach. We aimed to evaluate frameless (mask) fixation navigation using a 3D-printed patient model with fixed-AR technology for gamma knife radiosurgery (GKRS). Fixed-AR navigation was developed using the inside-out method with visual inertial odometry algorithms, and the flexible Quick Response marker was created for object-feature recognition. Virtual 3D-patient models for AR-rendering were created via 3D-scanning utilizing TrueDepth and cone-beam computed tomography (CBCT) to generate a new GammaKnife Icon™ model. A 3D-printed patient model included fiducial markers, and virtual 3D-patient models were used to validate registration accuracy. Registration accuracy between initial frameless fixation and re-fixation navigated fixed-AR was validated through visualization and quantitative method. The quantitative method was validated through set-up errors, fiducial marker coordinates, and high-definition motion management (HDMM) values. A 3D-printed model and virtual models were correctly overlapped under frameless fixation. Virtual models from both 3D-scanning and CBCT were enough to tolerate the navigated frameless re-fixation. Although the CBCT virtual model consistently delivered more accurate results, 3D-scanning was sufficient. Frameless re-fixation accuracy navigated in virtual models had mean set-up errors within 1 mm and 1.5° in all axes. Mean fiducial marker differences from coordinates in virtual models were within 2.5 mm in all axes, and mean 3D errors were within 3 mm. Mean HDMM difference values in virtual models were within 1.5 mm of initial HDMM values. The variability from navigation fixed-AR is enough to consider repositioning frameless fixation without CBCT scanning for treating patients fractionated with large multiple metastases lesions (> 3 cm) who have difficulty enduring long beam-on time. This system could be applied to novel GKRS navigation for frameless fixation with reduced preparation time.

Activities in the digital economy driven by information technology have rapidly increased in scope and speed in the aftermath of COVID-19. Meanwhile, social isolation accelerated by quarantine measures has increased concerns about individuals’ mental health. However, little is known about the specific consequences of online interactions, especially when applied in online fan community-based relationships. Therefore, we examined the impact of loneliness in the context of COVID-19 on online interaction with other fans and parasocial relationships with celebrities on the Weverse platform. We also examined how these interactions influence mental well-being and the sense of virtual community. With 202 valid data samples acquired from global BTS fandom, this study conducted a partial least squares–structural equation modeling analysis. The empirical results demonstrate a significant positive relationship between loneliness and the extent of online interaction, while no significant impact on parasocial relationships was observed. Both online interaction and parasocial relationships were found to enhance both well-being and SOVC. However, these results were observed to differ between Weverse paid subscribers and free users.

Prurigo pigmentosa is a rare inflammatory skin disease characterized by an unexpected onset of diffuse erythematous papules and macules usually on the chest, neck, and back. These generally resolve, leaving reticular hyperpigmentation. Rarely, vesicular or bullous forms have been reported. We present a case of exfoliative vesiculobullous prurigo pigmentosa in a 13-year-old boy. He presented with symmetrical eruption of papules and vesicles on his back, neck, and chest in the last 10 days, causing pruritis and prickling sensation. Within a few days, the bullous lesions and all affected areas of the skin showed exfoliation. Histological study and clinical findings indicated the condition to be vesiculobullous prurigo pigmentosa with exfoliation. Treatment with doxycycline 200 mg/day and topical tacrolimus ointment showed a good response. The lesions resolved, leaving a light-brown reticulated hyperpigmentation. In conclusion, this was a case of exfoliative vesiculobullous prurigo pigmentosa in an adolescent man successfully treated with doxycycline and topical tacrolimus as an effective and safe treatment option.

Abstract The metacommunity approach provides insights into how the biological communities are assembled along the environmental variations. The current study presents the importance of water quality on the metacommunity structure of algal communities in six river-connected lakes using long-term (8 years) monitoring datasets. Elements of metacommunity structure were analyzed to evaluate whether water quality structured the metacommunity across biogeographic regions in the riverine ecosystem. The algal community in all lakes was found to exhibit Clementsian or quasi-Clementsian structure properties such as significant turnover, grouped and species sorting indicating that the communities responded to the environmental gradient. Reciprocal averaging clearly classified the lakes into three clusters according to the geographical region in river flow (upstream, midstream, and downstream). The dispersal patterns of algal genera, including Aulacoseira, Cyclotella, Stephanodiscus, and Chlamydomonas across the regions also supported the spatial-based classification results. Although conductivity, chemical oxygen demand, and biological oxygen demand were found to be important variables (loading > |0.5|) of the entire algal community assembly, water temperature was a critical factor in water quality associated with community assembly in each geographical area. These results support the notion that the structure of algal communities is strongly associated with water quality, but the relative importance of variables in structuring algal communities differed by geological regions.

Dielectric constant (DC, ε) is a fundamental parameter in material sciences to measure polarizability of the system. In industrial processes, its value is an imperative indicator, which demonstrates the dielectric property of material and compiles information including separation information, chemical equilibrium, chemical reactivity analysis, and solubility modeling. Since, the available ε-prediction models are fairly primitive and frequently suffer from serious failures especially when deals with strong polar compounds. Therefore, we have developed a novel data-driven system to improve the efficiency and wide-range applicability of ε using in material sciences. This innovative scheme adopts the correlation distance and genetic algorithm to discriminate features’ combination and avoid overfitting. Herein, the prediction output of the single ML model as a coding to estimate the target value by simulating the layer-by-layer extraction in deep learning, and enabling instant search for the optimal combination of features is recruited. Our model established an improved correlation value of 0.956 with target as compared to the previously available best traditional ML result of 0.877. Our framework established a profound improvement, especially for material systems possessing ε value >50. In terms of interpretability, we have derived a conceptual computational equation from a minimum generating tree. Our innovative data-driven system is preferentially superior over other methods due to its application for the prediction of dielectric constants as well as for the prediction of overall micro and macro-properties of any multi-components complex.

Abstract The usefulness of 3-dimensional (3D)-printed disease models has been recognized in various medical fields. This study aims to introduce a production platform for patient-specific 3D-printed brain tumor model in clinical practice and evaluate its effectiveness. A full-cycle platform was created for the clinical application of a 3D-printed brain tumor model (3D-printed model) production system. Essential elements included automated segmentation software, cloud-based interactive communication tools, customized brain models with exquisite expression of brain anatomy in transparent material, adjunctive devices for surgical simulation, and swift process cycles to meet practical needs. A simulated clinical usefulness validation was conducted in which neurosurgeons assessed the usefulness of the 3D-printed models in 10 cases. We successfully produced clinically applicable patient-specific models within 4 days using the established platform. The simulated clinical usefulness validation results revealed the significant superiority of the 3D-printed models in surgical planning regarding surgical posture (p = 0.0147) and craniotomy design (p = 0.0072) compared to conventional magnetic resonance images. The benefit was more noticeable for neurosurgeons with less experience. We established a 3D-printed brain tumor model production system that is ready to use in daily clinical practice for neurosurgery.

Abstract Background The impact of adjuvant radiotherapy (RT) on atypical meningioma (AM) underwent a gross total resection (GTR) remains unclear, showing conflicting results from various studies. The objective of this study was to perform an updated meta-analysis for observational studies to determine the effect of adjuvant RT after GTR on local recurrence and survival outcomes compared to observation after GTR. Methods PubMed, Embase, and Web of Science were searched to identify comparative studies that reported outcomes of adjuvant RT versus observation for AM patients after GTR. Local recurrence rate, progression-free survival (PFS), overall survival (OS), and toxicities related to RT were considered as outcomes of interest. Differences between two cohorts were estimated by calculating odds ratios (OR) for LR rate and hazard ratios (HR) for survival outcomes with 95% confidence intervals (CIs) for meta-analysis, using R version 4.0.3 software. Included studies were appraised with the Risk of Bias Assessment tool for Non-Randomized Studies. Outcome ratios were combined with the Mantel–Haenszel method and the inverse variance-weighted method, appropriately. Results Data from 30 studies involving 2904 patients (adjuvant RT: n = 737; observation: n = 2167) were eventually included. Significant reduction of local recurrence rate was seen in the adjuvant RT cohort compare to that in the observation cohort (OR 0.50; 95% CI 0.36–0.68; p 5-year revealed that adjuvant RT was superior to observation. There was no significant difference in OS between the two cohorts during any period. Most toxicities were tolerable with grade 1 or 2. There was no documented grade 5 toxicity. Conclusions For AM patients who underwent GTR, evidence suggested that adjuvant RT could potentially decrease local recurrence and improve PFS better than observation.

Designing efficient bio-inspired visual recognition system remains a challenge. Here the authors present a curved neuromorphic image sensor array based on a heterostructure of MoS2 and pV3D3 integrated with a plano-convex lens for efficient image acquisition and data pre-processing.

Cryptococcus neoformans is an encapsulated yeast that can be found in pigeon droppings, hay, and dust. Primary cutaneous cryptococcosis (PCC) without systemic involvement is recognized as a distinct clinical condition and is rarely reported in immunocompetent patients. A 78-year-old woman with no history of other diseases except for hypertension presented with a painful diffuse erythematous plaque along with oozing on left forearm that had lasted for 7 weeks. She was treated with cefoperazone/sulbactam for 3 weeks under suspicion of bacterial cellulitis, although the lesions aggravated without any improvement. We performed bacterial and fungal cultures as well as incisional biopsy. The pathogen was identified as Cryptococcus neoformans following sequence analysis of the internal transcribed spacer gene. The patient was treated with fluconazole 400 mg/day for 3 months, and there was no evidence of recurrence after 3 months of follow-up.

ABSTRACT Drought has become a major agricultural threat leading crop yield loss. Although a few species of rhizobacteria have the ability to promote plant growth under drought, the drought tolerance of the soil microbiome and its relationship with the promotion of plant growth under drought are scarcely studied. This study aimed to develop a novel approach for assessing drought tolerance in agricultural land by quantitatively measuring microbial phenotypes using stable isotopes and Raman spectroscopy. Raman spectroscopy with deuterium isotope probing was used to identify the Raman signatures of drought effects from drought-tolerant bacteria. Counting drought-tolerant cells by applying these phenotypic properties to agricultural samples revealed that 0% to 52.2% of all measured single cells had drought-tolerant properties, depending on the soil sample. The proportions of drought-tolerant cells in each soil type showed similar tendencies to the numbers of revived pea plants cultivated under drought. The phenotype of the soil microbiome and plant behavior under drought conditions therefore appeared to be highly related. Studying metagenomics suggested that there was a reliable link between the phenotype and genotype of the soil microbiome that could explain mechanisms that promote plant growth in drought. In particular, the proportion of drought-tolerant cells was highly correlated with genes encoding phytohormone production, including tryptophan synthase and isopentenyl-diphosphate delta-isomerase; these enzymes are known to alleviate drought stress. Raman spectroscopy with deuterium isotope probing shows high potential as an alternative technology for quantitatively assessing drought tolerance through phenotypic analysis of the soil microbiome. IMPORTANCE Soil microbiome has played a critical role in the plant survival during drought. However, the drought tolerance of soil microbiome and its ability to promote plant growth under drought is still scarcely studied. In this study, we identified the Raman signature (i.e., phenotype) of drought effects from drought-tolerant bacteria in agricultural soil samples using Raman-deuterium isotope probing (Raman-DIP). Moreover, the number of drought-tolerant cells measured by Raman-DIP was highly related to the survival rate of plant cultivation under drought and the abundance of genes encoding phytohormone production alleviating drought stress in plant. These results suggest Raman-DIP is a promising technology for measuring drought tolerance of soil microbiome. This result give us important insight into further studies of a reliable link between phenotype and genotype of soil microbiome for future plant-bacteria interaction research.

Summary: Early quantitative structure-activity relationship (QSAR) technologies have unsatisfactory versatility and accuracy in fields such as drug discovery because they are based on traditional machine learning and interpretive expert features. The development of Big Data and deep learning technologies significantly improve the processing of unstructured data and unleash the great potential of QSAR. Here we discuss the integration of wet experiments (which provide experimental data and reliable verification), molecular dynamics simulation (which provides mechanistic interpretation at the atomic/molecular levels), and machine learning (including deep learning) techniques to improve QSAR models. We first review the history of traditional QSAR and point out its problems. We then propose a better QSAR model characterized by a new iterative framework to integrate machine learning with disparate data input. Finally, we discuss the application of QSAR and machine learning to many practical research fields, including drug development and clinical trials.

Abstract Background Massive intraluminal bleeding requires urgent intervention and management. However, the source of bleeding on the small intestine is difficult to determine. Intestinal tumor with intussusception is a rare and normally not an urgent condition. Herein, we present a rare case of intestinal intussusception with massive bleeding due to jejunal gastrointestinal stromal tumor (GIST) that required emergency surgical treatment. Case presentation A 51-year-old male was admitted to the emergency department complaining of abdominal pain and acute hematochezia. Esophagogastroduodenoscopy (EGD) and colonoscopy could not determine the source of the bleeding site. Abdominal pelvic computed tomography (AP-CT) revealed GIST with intussusception, strongly suggestive of distal jejunal bleeding. Unresponsive transfusion with low blood pressure and continuous hematochezia led to emergency laparotomy. GIST, which was the leading point for intussusception, was located in the jejunum and showed mucosal ulceration of approximately 3.5 cm in diameter. Following resection and functional anastomosis, histology revealed a GIST with low mitotic count (

This study aims to develop highly durable, mineral carbonation-based, resource-recycling, secondary cement products based on supercritical carbon dioxide (CO2) curing as part of carbon capture utilization technology that permanently fixes captured CO2. To investigate the basic characteristics of secondary cement products containing concrete sludge waste (CSW) as the main materials after supercritical CO2 curing, the compressive strengths of the paste and mortar (fabricated by using CSW as the main binder), ordinary Portland cement, blast furnace slag powder, and fly ash as admixtures were evaluated to derive the optimal mixture for secondary products. The carbonation curing method that can promote the surface densification (intensive CaCO3 formation) of the hardened body within a short period of time using supercritical CO2 curing was defined as “Lean Carbonation”. The optimal curing conditions were derived by evaluating the compressive strength and durability improvement effects of applying Lean Carbonation to secondary product specimens. As a result of the experiment, for specimens subjected to Lean Carbonation, compressive strength increased by up to 12%, and the carbonation penetration resistance also increased by more than 50%. The optimal conditions for Lean Carbonation used to improve compressive strength and durability were found to be 35 °C, 80 bar, and 1 min.

Mycobacterium abscessus comprises rapidly growing mycobacteria, and the clinical manifestations of M. abscessus skin infection include papule, nodule, ulcer, scar and mixed form. The cutaneous infections have been reported due to minor trauma, cosmetic therapy, acupuncture and disseminated infection. A 75-year-old man presented with pruritic diffuse various sized erythematous papuloplaques and pustules on the neck and chest for 2 months. The cutaneous lesions were spread around the wound of the shaving on the neck. The histopathologic findings were consistent with abscess showing infiltrations of neutrophils and lymphocytes in the dermis and negative findings were observed on immunohistochemical stain including acid-fast bacilli stain. One month later, mycobacterial culture result showed positive findings, and the pathogen was identified by reverse-transcriptase polymerase chain reaction with hybridization. The patient was treated with combination of clarithromycin and ethambutol for 5 months and there is no evidence of recurrence after 6 months of follow-up. Herein, we report a case of M. abscessus cutaneous infection through minor trauma caused by shaving in the elderly.

Immunotherapy via interleukin-2 (IL-2) mediated activation of anti-tumor immune response is a promising approach for cancer treatment. The multi-potent cytokine, IL-2 has a central role in immune cell activation and homeostasis. Since IL-2 preferentially activates immunosuppressive T regulatory cells by IL-2Rα dependent manner, blocking IL-2:IL-2Rα interaction is a key to amplify the IL-2 activity in effector T cells toward anti-tumor response. Anti-IL-2 monoclonal antibodies are good candidates to control the IL-2:IL-2Rα interaction. In a previous study, we developed a new IL-2Rα mimetic antibody, TCB2, and showed that the human IL-2(hIL-2):TCB2 complex can stimulate T effector cells specifically and elicit potent anti-cancer immunotherapeutic effect, especially when administered in combination with immune checkpoint inhibitors. To understand the molecular mechanism, we determined the crystal structure of TCB2-Fab in a complex with hIL-2 at 2.5 Å resolution. Our structural analysis reveals that TCB2 binds to the central area of the hIL-2Rα binding region on hIL-2, and binding angle and epitope are different from previously known hIL-2Rα mimicking antibody NARA1 which recognizes the top part of hIL-2. TCB2 binding to hIL-2 also induces an allosteric effect that increases the affinity for the hetero-dimeric hIL-2 receptor, IL-2R(β + γ), on effector T cells.

BackgroundFew studies report the effects of tamoxifen intake and the occurrence of de novo fatty liver and the deterioration of existing fatty liver. The aim of this study was to investigate the effects of tamoxifen on fatty change of liver over time and also the impact of fatty liver on the prognosis of patients with breast cancer.MethodsThis was a single-center, retrospective study of patients who were diagnosed with primary breast cancer from January 2007 to July 2017. 911 consecutive patients were classified into three groups according to treatment method: tamoxifen group, aromatase inhibitor (AI) group, and control group.ResultsMedian treatment duration was 49 months (interquartile range, IQR; 32-58) and median observational period was 85 months (IQR; 50-118). Long-term use of tamoxifen significantly aggravated fatty liver status compared to AI or control groups [hazard ratio (HR): 1.598, 95% confidence interval (CI): 1.173-2.177, P = 0.003] after adjusting other factors. When analyzed separately depending on pre-existing fatty liver at baseline, tamoxifen was involved in the development of de novo fatty liver [HR: 1.519, 95% CI: 1.100-2.098, P = 0.011) and had greater effect on fatty liver worsening (HR: 2.103, 95% CI: 1.156-3.826, P = 0.015). However, the progression of fatty liver did not significantly affect the mortality of breast cancer patients.ConclusionsTamoxifen had a significant effect on the fatty liver status compared to other treatment modalities in breast cancer patients. Although fatty liver did not affect the prognosis of breast cancer, meticulous attention to cardiovascular disease or other metabolic disease should be paid when used for a long time.

Abstract Background Cutaneous bacterial pathogens including Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Propionibacterium acnes are often involved in acne vulgaris. The currently available therapeutic option for these skin pathogens is an antibiotic treatment, resulting in the emergence of antibiotic-resistant bacteria. The objective of this study was to discover an alternative antibacterial agent with lower side effect from marine algae. Results The ethanolic extract of edible brown algae Ishige okamurae exhibits potent antibacterial activity against cutaneous bacterial pathogens. Among the ethanol soluble fractions, the n-hexane (Hexane)-soluble fraction exhibited the strongest antibacterial activity against the pathogens with MIC values ranging 64 to 512 μg/mL and with minimum bactericidal concentration values ranging 256 to 2048 μg/mL. Furthermore, the combination with Hexane fraction and antibiotics (ceftazidime, ciprofloxacin, and meropenem) exhibited synergistic effect. Conclusion This study revealed that the I. okamurae extract exhibited a synergistic antibacterial effect against acne-related cutaneous bacterial pathogens acquired antibiotic resistant. Thus, the results of the present study suggested that the edible seaweed extract will be a promising antibacterial therapeutic agent against antibiotic-human skin pathogens and its infections.

Background : Due to its anatomical location, the external ear is easily exposed and damaged due to trauma, weathering, and inflammation. Therefore, depending on the patient’s age, different cutaneous diseases can occur. In addition, because of its small percentage of the overall body area, patients and doctors may miss observing dermatologic diseases of the ear. The purpose of this study was to provide information on the most common dermatologic diseases according to the location on the external ear. Methods : This retrospective study was conducted on patients who visited the Department of Dermatology of Chosun University Hospital in the past 7 years. Results : We included 269 patients and categorized their ear lesions according to 8 anatomical locations and 5 types of dermatologic diseases. In older patients over 60 years of age, the most common site of dermatologic disease was the postauricular region (33.9%), followed by the antihelix (19.4%), and earlobe (12.9%). The most common dermatologic disease was benign tumor (53.2%), followed by malignant and premalignant tumors (32.3% and 9.7%, respectively). Conclusion : The proportion of older adults with premalignant and malignant diseases was relatively high and these were most commonly observed in the antihelix and postauricular area. Therefore, it is important to aware the need for the examination, diagnosis, and treatment of disease in the antihelix and postauricular area.

Protopanaxadiol (PPD), an aglycon found in several dammarene-type ginsenosides, has high potency as a pharmaceutical. Nevertheless, application of these ginsenosides has been limited because of the high production cost due to the rare content of PPD in Panax ginseng and a long cultivation time (4–6 years). For the biological mass production of the PPD, de novo biosynthetic pathways for PPD were introduced in Saccharomyces cerevisiae and the metabolic flux toward the target molecule was restructured to avoid competition for carbon sources between native metabolic pathways and de novo biosynthetic pathways producing PPD in S. cerevisiae. Here, we report a CRISPRi (clustered regularly interspaced short palindromic repeats interference)-based customized metabolic flux system which downregulates the lanosterol (a competing metabolite of dammarenediol-II (DD-II)) synthase in S. cerevisiae. With the CRISPRi-mediated suppression of lanosterol synthase and diversion of lanosterol to DD-II and PPD in S. cerevisiae, we increased PPD production 14.4-fold in shake-flask fermentation and 5.7-fold in a long-term batch-fed fermentation.

The Archimedes screw turbine (AST) is the most sustainable mini-hydropower extraction method that offers number of economic, social, and environmental advantages. Nowadays, many researchers are interested in AST development as it is considered a new technology. Currently, a lot of researchers are conducting experimental testing of the screws, comparing their reliability with computational fluid dynamic (CFD) analyses. Almost all of them are lab-scale testing models that claiming an average 80% efficiency for low pitch angles. In the case of a real site with a small inclination angle, the length of the screw is large enough to cause severe problems, specially related to bending of the screw. Therefore, this research was conducted to analyze the CFD flow field in a real site-scale AST with the maximum possible inclination of 45 degrees. In addition, the design was done without the upper and lower reservoir as it was conceived as a run-of-river flow system. The simulated real scale AST result showed a maximum efficiency of around 82% for a 5.2 m hydraulic head and 0.232 m3/s discharge. Many researchers claim above 80% efficiency for low inclination angle ASTs with reservoirs. This CFD study indicates that even higher inclination angle ASTs can achieve 80% efficiency in run-of-river; real-scale applications.