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To ensure high quality of food and water, the identification of traces of pathogens is mandatory. Rapid nucleic acid-based tests shorten traditional detection times while maintaining low detection limits. Challenging is the loss of nucleic acids during necessary purification processes, since elution off solid surfaces is not efficient. We therefore propose the development of a vanishing surface strategy in which cationic liposomes efficiently capture nucleic acids. A lipoplex is formed that can be easily centrifuged down and washed if needed. Adding the lipoplex to detergent solutions or nucleic acid amplification reactions dissolves the liposomes, releasing 100% of the nucleic acid into the reaction. After initial protocol optimization, it was applied to isolate DNA from Escherichia coli , Staphylococcus aureus, and adenovirus in buffer followed by qPCR detection. This enabled the detection of these pathogens down to concentrations of 1 CFU or 1 PFU/mL, respectively. Comparing it to a standard commercial DNA extraction kit, it was superior, as evidenced by lower Ct-values in the qPCR for all pathogen concentrations. Scaling up to larger volumes, samples containing bacteria were first concentrated through nitrocellulose filters (pore size = 0.45 μm). Tap water, lake water, and rinse water of fresh produce were investigated, leading to relevant limits of detection of 100 CFU in 100 mL of tap water, 1000 CFU in 100 mL of lake water, and 100 CFU in 10 g of iceberg lettuce, respectively. Since the liposome protocol is a homogeneous, simple incubation step, it is a valuable alternative to standard commercial nucleic acid extraction kits.

Purpose of Review: Isocitrate dehydrogenase (IDH) mutation is a defining molecular driver of WHO grade 2-4 astrocytomas and oligodendrogliomas. In this article, we review the recent therapeutic approaches specifically targeting IDH-mutant gliomas and summarize ongoing clinical trials in this population., Recent Findings: The IDH inhibitor vorasidenib recently demonstrated its efficacy after surgical resection in grade 2 IDH-mutated gliomas. Several studies in patients with IDH-mutant gliomas are currently exploring various strategies to target IDH mutations, including the use of small-molecule inhibitors, immunotherapies, peptide vaccines and agents targeting metabolic and epigenomic vulnerabilities., Summary: Mutant-IDH targeting holds significant promise in treating progressive or recurrent IDH-mutant gliomas. Recent results with IDH inhibitors will change practice and influence the existing guidelines in a near future., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Previous field observations from 2018 to 2019 revealed that paralytic shellfish poisoning (PSP) caused by the blooms of toxic dinoflagellate Alexandrium species occurred under low concentrations of dissolved inorganic nitrogen (DIN) and high concentrations of dissolved organic nitrogen (DON) and humic-like fluorescent dissolved organic matter (FDOM H ) in Jinhae-Masan Bay, Korea. In this study, we obtained more data for DIN, DON, FDOM H , and Alexandrium cell density from 2020 to 2023 to further validate environmental conditions for the PSP outbreak. We also measured total hydrolyzed amino acids (THAA) to determine the bioavailability of DON fueling the PSP outbreak. Over the 6-year observations, there was a consistent pattern of low DIN concentrations and high DON and FDOM H concentrations during the PSP outbreak periods. The Alexandrium cell densities, together with the PSP toxin concentrations, increased rapidly under this environmental condition. The PSP outbreak occurs when a large amount of DIN originating from the stream waters near the upstream sites is transformed into DON by biological production before entering the PSP outbreak area. The produced DON is characterized by high bioavailability based on the various AA-derived indices (enantiomeric ratio, degradation index, non-protein AA mole%, and nitrogen-normalized AA yield). In addition, the intensities of PSP outbreaks are mainly dependent on the conversion stage of DIN to DON and enhanced FDOM H . We found that the strong PSP outbreak occurred consistently under a low level of DIN (<1.0 μM) and high levels of DON (>9.0 μM) and FDOM H (>1.5 R.U.). Thus, our results suggest that the monitoring data of environmental conditions can be used to predict the PSP outbreak in the coastal oceans., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Centella asiatica , a traditional herb, is widely recognized for its pharmacologically active components, such as asiaticoside, madecassoside, asiatic acid, and madecassic acid. These components render it a highly sought-after ingredient in various industries, including cosmetics and pharmaceuticals. This study aimed to enhance the production and activity of these pharmacological constituents of C. asiatica using the plant growth-promoting rhizobacterium Priestia megaterium HyangYak-01 during its cultivation. To achieve this goal, the researchers conducted field experiments, which revealed an increase in the production of pharmacologically active compounds in C. asiatica cultivated with a P. megaterium HyangYak-01 culture solution. Additionally, quadrupole time-of-flight mass spectrometry (Q-TOF MS) confirmed that the composition ratios of the C. asiatica extract treated with the P. megaterium HyangYak-01 culture solution differed from those of the untreated control and type strain-treated groups. Skin cell experiments indicated that the C. asiatica extract treated with the P. megaterium HyangYak-01 culture solution exhibited greater skin barrier improvement and less pronounced inflammatory responses than those from plants grown without the bacterial culture solution. This study demonstrates that microbial treatment during plant cultivation can beneficially influence the production of pharmacological constituents, suggesting a valuable approach toward enhancing the therapeutic properties of plants.

Purpose: We aimed to evaluate the effect of self-training using a virtual reality head-mounted display simulator on the acquisition of surgical skills for holmium laser enucleation surgery., Methods: Thirteen medical students without surgical skills for holmium laser enucleation of the prostate were trained using multimedia to learn the technique via simulator manipulation. Thereafter, participants performed the technique on a virtual benign prostatic hyperplasia model A (test A). After a 1-week wash-out period, they underwent self-training using a simulator and performed the technique on model B (test B). Subsequently, participants were asked to respond to Training Satisfaction Questions. Video footage of hand movements and endoscope view were recorded during tests A and B for later review by 2 expert surgeons. A 20-step Assessment Checklist, 6-domain Global Rating Scale, and a Pass Rating were used to compare performance on tests A and B., Results: Thirteen participants completed both tests A and B. The 20-step Assessment Checklist and 6-domain Global Rating Scale evaluation results showed significantly improved scores in test B than in test A (P<0.05). No evaluator rated participants as passed after test A, but 11 participants (84.6%) passed after test B. Ten participants (76.9%) indicated that the simulator was helpful in acquiring surgical skills for holmium laser enucleation of the prostate., Conclusion: The virtual reality head-mounted display holmium laser enucleation of the prostate simulator was effective for surgical skill training. This simulator may help to shorten the learning curve of this technique in real clinical practice in the future.

The presented paper introduces a novel path planning algorithm designed for generating low-cost trajectories that fulfill mission requirements expressed in Linear Temporal Logic (LTL). The proposed algorithm is particularly effective in environments where cost functions encompass the entire configuration space. A core contribution of this paper is the presentation of a refined approach to sampling-based path planning algorithms that aligns with the specified mission objectives. This enhancement is achieved through a multi-layered framework approach, enabling a simplified discrete abstraction without relying on mesh decomposition. This abstraction is especially beneficial in complex or high-dimensional environments where mesh decomposition is challenging. The discrete abstraction effectively guides the sampling process, influencing the selection of vertices for extension and target points for steering in each iteration. To further improve efficiency, the algorithm incorporates a deep learning-based extension, utilizing training data to accurately model the optimal trajectory distribution between two points. The effectiveness of the proposed method is demonstrated through simulated tests, which highlight its ability to identify low-cost trajectories that meet specific mission criteria. Comparative analyses also confirm the superiority of the proposed method compared to existing methods.

Background: Patient isolation units (PIUs) can be an effective method for effective infection control. Computational fluid dynamics (CFD) is commonly used for PIU design; however, optimizing this design requires extensive computational resources. Our study aims to provide data-driven models to determine the PIU settings, thereby promoting a more rapid design process., Method: Using CFD simulations, we evaluated various PIU parameters and room conditions to assess the impact of PIU installation on ventilation and isolation. We investigated particle dispersion from coughing subjects and airflow patterns. Machine-learning models were trained using CFD simulation data to estimate the performance and identify significant parameters., Results: Physical isolation alone was insufficient to prevent the dispersion of smaller particles. However, a properly installed fan filter unit (FFU) generally enhanced the effectiveness of physical isolation. Ventilation and isolation performance under various conditions were predicted with a mean absolute percentage error of within 13%. The position of the FFU was found to be the most important factor affecting the PIU performance., Conclusion: Data-driven modeling based on CFD simulations can expedite the PIU design process by offering predictive capabilities and clarifying important performance factors. Reducing the time required to design a PIU is critical when a rapid response is required., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor. Standard therapies, including surgical resection, chemoradiation, and tumor treating fields, have not resulted in major improvements in the survival outcomes of patients with GBM. The lack of effective strategies has led to an increasing interest in immunotherapic approaches, considering the success in other solid tumors. However, GBM is a highly immunosuppressive tumor, as documented by the presence of several mechanisms of immune escape, which may represent a reason why immunotherapy clinical trials failed in this kind of tumor. In this review, we examine the current landscape of immunotherapy strategies in GBM, focusing on the challenge of immunoresistance and potential mechanisms to overcome it. We discussed completed and ongoing clinical trials involving immune checkpoint inhibitors, oncolytic viruses, vaccines, and CAR T-cell therapies, to provide insights into the efficacy and outcomes of different immunotherapeutic interventions. We also explore the impact of radiotherapy on the immune system within the GBM microenvironment highlighting the complex interactions between radiation treatment and the immune response., (© The Author(s) 2023. Published by Oxford University Press.)

Background: The skin microbiome is essential in guarding against harmful pathogens and responding to environmental changes by generating substances useful in the cosmetic and pharmaceutical industries. Among these microorganisms, Streptococcus is a bacterial species identified in various isolation sources. In 2021, a strain of Streptococcus infantis, CX-4, was identified from facial skin and found to be linked to skin structure and elasticity. As the skin-derived strain differs from other S. infantis strains, which are usually of oral origin, it emphasizes the significance of bacterial variation by the environment., Objective: This study aims to explore the unique characteristics of the CX-4 compared to seven oral-derived Streptococcus strains based on the Whole-Genome Sequencing data, focusing on its potential role in skin health and its possible application in cosmetic strategies., Methods: The genome of the CX-4 strain was constructed using PacBio Sequencing, with the assembly performed using the SMRT protocol. Comparative whole-genome analysis was then performed with seven closely related strains, utilizing web-based tools like PATRIC, OrthoVenn3, and EggNOG-mapper, for various analyses, including protein association analysis using STRING., Results: Our analysis unveiled a substantial number of Clusters of Orthologous Groups in diverse functional categories in CX-4, among which sphingosine kinase (SphK) emerged as a unique product, exclusively present in the CX-4 strain. SphK is a critical enzyme in the sphingolipid metabolic pathway, generating sphingosine-1-phosphate. The study also brought potential associations with isoprene formation and retinoic acid synthesis, the latter being a metabolite of vitamin A, renowned for its crucial function in promoting skin cell growth, differentiation, and maintaining of skin barrier integrity. These findings collectively suggest the potential of the CX-4 strain in enhancing of skin barrier functionality., Conclusion: Our research underscores the potential of the skin-derived S. infantis CX-4 strain by revealing unique bacterial compounds and their potential roles on human skin., (© 2024. The Author(s) under exclusive licence to The Genetics Society of Korea.)

We conducted a prospective study to evaluate the efficacy of simulation-based education using a three-dimensional (3D)-printed schematic eye model in improving the retinoscopy refraction skills of medical students. A schematic eye model was printed using a fused deposition modeling-based 3D printer. Twenty medical students randomized into 3D (n = 10) and control (n = 10) groups received a 1-h lecture on the principles and methods of manifest refraction and were shown how to use the retinoscope and sciascope bars. The 3D group additionally attended a tutorial on the schematic eye. Both groups performed refractive examinations on four eyes of volunteer patients, and the results were recorded as a baseline. Instructor feedback and refraction practice was provided with the 3D group or with control group. To account for subject fatigue, patients spent no more than 8 min on the examination. After a 1-h break to allow for fatigue and familiarity, refraction tests were repeated on four randomly selected eyes of patients. Students' refraction readings were compared with the autorefractor values using a spherical equivalent value and blur strength. All participants measured the time required to complete the refraction test and reported their subjective confidence in the results of each refraction test. Refractive errors before and after training did not differ between the control and 3D groups, with a significant improvement in errors observed in both groups (p = 0.005 and 0.008, respectively). The time to complete refraction before and after training did not differ between the two groups, both of which showed a significant reduction in time (p = 0.005 and 0.028, respectively). Pre- and post-training confidence scores for the accuracy of each refraction on a 10-point Likert scale were not significantly different. However, when comparing score changes between pre- and post-training, only the control group showed a significant increase in confidence (p = 0.005). Tests for the non-inferiority of refractive errors after training indicated that the 3D group was non-inferior to the control group. In conclusion, training in retinoscopy refraction skills using a 3D-printed eye model resulted in significant improvement in accuracy and speed compared to practice with real patients. Except for better confidence in the control group, schematic eye model training was not inferior to practice with real patients., (© 2024. The Author(s).)

The intraoperative estimated blood loss (EBL), an essential parameter for perioperative management, has been evaluated by manually weighing blood in gauze and suction bottles, a process both time-consuming and labor-intensive. As the novel EBL prediction platform, we developed an automated deep learning EBL prediction model, utilizing the patch-wise crumpled state (P-W CS) of gauze images with texture analysis. The proposed algorithm was developed using animal data obtained from a porcine experiment and validated on human intraoperative data prospectively collected from 102 laparoscopic gastric cancer surgeries. The EBL prediction model involves gauze area detection and subsequent EBL regression based on the detected areas, with each stage optimized through comparative model performance evaluations. The selected gauze detection model demonstrated a sensitivity of 96.5% and a specificity of 98.0%. Based on this detection model, the performance of EBL regression stage models was compared. Comparative evaluations revealed that our P-W CS-based model outperforms others, including one reliant on convolutional neural networks and another analyzing the gauze's overall crumpled state. The P-W CS-based model achieved a mean absolute error (MAE) of 0.25 g and a mean absolute percentage error (MAPE) of 7.26% in EBL regression. Additionally, per-patient assessment yielded an MAE of 0.58 g, indicating errors < 1 g/patient. In conclusion, our algorithm provides an objective standard and streamlined approach for EBL estimation during surgery without the need for perioperative approximation and additional tasks by humans. The robust performance of the model across varied surgical conditions emphasizes its clinical potential for real-world application., (© 2024. The Author(s).)

This study focuses on enhancing the prediction of regulatory functional sites in DNA and RNA sequences, a crucial aspect of gene regulation. Current methods, such as motif overrepresentation and machine learning, often lack specificity. To address this issue, the study leverages evolutionary information and introduces Graphylo, a deep-learning approach for predicting transcription factor binding sites in the human genome. Graphylo combines Convolutional Neural Networks for DNA sequences with Graph Convolutional Networks on phylogenetic trees, using information from placental mammals' genomes and evolutionary history. The research demonstrates that Graphylo consistently outperforms both single-species deep learning techniques and methods that incorporate inter-species conservation scores on a wide range of datasets. It achieves this by utilizing a species-based attention model for evolutionary insights and an integrated gradient approach for nucleotide-level model interpretability. This innovative approach offers a promising avenue for improving the accuracy of regulatory site prediction in genomics., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Background: Body temperature monitoring is essential during the perioperative period. However, core body temperature measurement requires invasive device that may cause complications. This study aimed to evaluate the accuracy of non-invasive Bair Hugger™ core body temperature monitoring system (BHTMS) at the wrist compared with esophageal temperature under general anesthesia., Methods: Twenty adult patients of the American Society of Anesthesiologists physical status I or II were enrolled. BHTMS sensor was applied at wrist region. After tracheal intubation, an esophageal probe was inserted. Bair Hugger™ upper body warming blankets were used. Esophageal temperature (Teso) and BHTMS at wrist (Twrist) were recorded every 10 min., Results: Total of 257 pairs of data sets were analyzed: Teso and Twrist had no statistically significant difference (P = 0.103). Median of Teso and Twrist were 36.5°C and 36.4°C. Bland-Altman analysis showed Teso - Twrist of 0.14°C ± 1.44. Subsequently, 99 pairs of 0-40 min data set were analyzed and showed significant difference at 0 and 10 min (P < 0.001) but no significant difference at 20, 30 and 40 min. Bland- Altman plot by times showed difference (Teso - Twrist) of 1.49°C ± 2.00, 0.82°C ± 1.30, 0.29°C ± 1.32, -0.03°C ± 0.84, and -0.12°C ± 0.82 at 0, 10, 20, 30 and 40 min respectively., Conclusions: BHTMS at wrist area under the upper body warming blanket is a potential alternative other than esophageal temperature for monitoring body temperature after 30 min of anesthesia induction.

Background: The skin microbiome, a diverse community of microorganisms, plays a crucial role in maintaining skin health. Among these microorganisms, the gram-positive bacterium Micrococcus luteus exhibits potential for promoting skin health. This study focuses on postbiotics derived from M. luteus YM-4, a strain isolated from human skin., Objective: Our objective is to explore the beneficial effects of YM-4 culture filtrate on dermatological health, including enhancing barrier function, modulating immune response, and aiding recovery from environmental damage., Methods: The effects of the YM-4 culture filtrate were tested on human keratinocytes and fibroblasts under various conditions using real-time PCR for gene expression analysis and fibroblast migration assays. A dehydration-simulated model was employed to prepare RNA-Seq samples from HaCaT cells treated with the YM-4 culture filtrate. Differentially expressed genes were identified and functionally classified through k-means clustering, gene ontology terms enrichment analyses, and protein-protein interactions mapping., Results: The YM-4 culture filtrate enhanced the expression of genes involved in skin hydration, hyaluronic acid synthesis, barrier function, and cell proliferation. It also reduced inflammation markers in keratinocytes and fibroblasts under stress conditions. It mitigated UVB-induced collagen degradation while promoted collagen synthesis, suggesting anti-aging properties, and accelerated wound healing processes by promoting cell proliferation and migration. RNA sequencing analysis revealed that the YM-4 culture filtrate could reverse dehydration-induced transcriptional changes towards a state similar to untreated cells., Conclusion: M. luteus YM-4 culture filtrate exhibits significant therapeutic potential for dermatological applications., (© 2023. The Author(s) under exclusive licence to The Genetics Society of Korea.)

Introduction: This study aims to evaluate cognitive load (CL), emotional levels (EL), and stress levels (SL) of students when using a wearable manikin vs. a standard manikin for tracheostomy suctioning (TS)., Methods: This study was approved by the Institutional Review Board. Subjects were recruited by email. Subjects completed a baseline demographics questionnaire, then they were randomized into two groups: wearable manikin group (WMG) or standard manikin group (SMG). For the WMG, an actor simulated a patient by wearing the device. In phase I, both groups were educated on how to perform TS by video and offered hands-on practice. Then I put through a tracheostomy suctioning clinical simulation and completed a post sim-survey. In phase II, the same survey was repeated after encountering a real patient as part of their clinical rotation., Results: A total of 30 subjects with a mean age 26.0 ± 5.5 years participated. 20 (66.7%) were respiratory care students and 10 (33.3%) were nursing students. In the WMG, the median stress level dropped significantly post phase II compared to post phase I [2(1,4) vs.3(1,5), p  = 0.04]. There were no significant changes in median CL, confidence, and satisfaction levels between post phase II and post phase I ( p  > 0.05). In the SMG, the satisfaction level increased significantly post phase II compared to post phase I [5(4,5) vs.4(2,5), p  = 0.004], but there were no significant changes in CL, SL, and confidence levels between post phase I and phase II. There was no significant difference in mean EL scores over time and these changes did not differ by group. Subjects in the WMG showed a higher mean competency score than those in the SMG (85.5 ± 13.6 vs. 78.5 ± 20.8, p  = 0.14, Cohen's d  = 0.4), yet not significant., Conclusion: Our results showed that the WMG is beneficial in helping bridge the gap of learning TS from the sim setting to the real-world clinical setting. More studies with higher sample size and use of other CL scales that assesses the different types of CL are needed to validate our findings., Competing Interests: The wearable manikin were provided by Avkin® (https://wwww.avkin.com) to the study investigators. Avkin® did not participate in any part of the study. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lumowa, Lui, Daher, Baek, Tan and Alismail.)

In the wake of increasingly frequent bushfires emerging as a threat to wildlife worldwide, koalas have notably been the most rescued species in Australia. However, our understanding of burns and their severity in koalas is limited; hence, this study investigated the histopathological features and depth of burns in koala skin, as well as the presence of smoke-induced respiratory tract damage. In four bushfire-affected koalas that had been euthanised on welfare grounds, skin burns in various body regions were scored based on clinical appearance as superficial, partial thickness, or full thickness. Histological sections of affected regions of skin were assessed as Grades I-IV and showed that furred regions on the ear margins and dorsum were histologically more severe, at Grade III, compared with the clinical score. There was a similar finding for footpad burns, which were the most common body region affected. In the respiratory tract, pulmonary oedema and congestion were evident in all koalas. Overall, the results highlight that cutaneous burn lesions on furred and palmar/plantar surfaces can have higher severity based on the burn depth than is clinically apparent. Therefore, there is a need to consider this when developing treatment plans and establishing prognosis for burnt koalas at triage, as well as that a high likelihood of pulmonary oedema exists.

A non-motile, novel actinobacterial strain, Kera-3 T , which is a gram-positive, aerobic, rod-shaped bacterium, was isolated from human keratinocytes on 1/10 diluted R2A agar. Whole-cell hydrolysis of amino acids revealed the presence of meso-DAP, alanine, and glutamic acid. The predominant menaquinone was MK-9 (H8), whereas the primary fatty acids were C 16:0 and C 18:1 ω9c. The major phospholipids included diphosphatidylglycerol and aminophospholipids, along with an unidentified phosphoglycolipid and an aminophosphoglycolipid. The G+C content of the genomic DNA was 73.2%, based on the complete genome sequence. Phylogenetic analyses of the 16S rRNA gene sequence and phylogenomic analysis of 91 core genes showed that strain Kera-3 T formed a new lineage in the family Iamiaceae, with the closest neighbour Rhabdothermincola sediminis SYSU G02662 T having 91.19% 16S rRNA gene sequence identity. A comparative genomic study of the predicted general metabolism and carbohydrate-active enzymes supported the phylogenetic and phylogenomic data. Based on the analysis of physiological, biochemical, and genomic characteristics, strain Kera-3 T can be distinguished from known genera in the family Iamiaceae and represents a novel genus and species. Therefore, the name Dermatobacter hominis gen. nov., sp. nov. was proposed, with the type strain Kera-3 T (= KACC 22415 T  = LMG 32493 T )., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Microcystis aeruginosa (M. aeruginosa) cause the eutrophication of lakes and rivers. To effectively control the overgrowth of M. aeruginosa, a suitable measurement method should be required in the aquatic fields. To address this, we developed a field-ready cyanobacterial pretreatment device and an electrochemical clustered regularly interspaced short palindromic repeats (EC-CRISPR) biosensor. The cyanobacterial pretreatment device consists of a syringe, glass bead, and graphene oxide (GO) bead. Then, the M. aeruginosa dissolved in the freshwater sample was added to fabricated filter. After filtration, the purified gene was loaded onto a CRISPR-based electrochemical biosensor chip to detect M. aeruginosa gene fragments. The biosensor was composed of CRISPR/Cpf1 protein conjugated with MXene on an Au microgap electrode (AuMGE) integrated into a printed circuit board (PCB). This AuMGE/PCB system maximizes the signal-to-noise ratio, which controls the working and counter electrode areas requiring only 3 μL samples to obtain high reliability. Using the extracted M. aeruginosa gene with a pre-treatment filter, the CRISPR biosensor showed a limit of detection of 0.089 pg/μl in fresh water. Moreover, selectivity test and matrix condition test carried out using the EC-CRISPR biosensor. These handheld pre-treatment kit and biosensors can enable field-ready detection of CyanoHABs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Dengue fever is an infectious disease caused by the dengue virus (DENV) and is transmitted by mosquitoes in tropical and subtropical regions. The early detection method at a low cost is essential. To address this, we synthesized the isolated DENV aptamer for fabricating a rapid electrochemical biosensor on a Au interdigitated microgap electrode (AuIMGE). The DENV aptamers were generated using the SELEX (systemic evolution of ligands by exponential enrichment) method for binding to DENV surface envelope proteins. To reduce the manufacturing cost, unnecessary nucleotide sequences were excluded from the isolation process of the DENV aptamer. To reduce the detection time, the alternating current electrothermal flow (ACEF) technique was applied to the fabricated biosensor, which can shorten the detection time to 10 min. The performance of the biosensor was evaluated using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). In the diluted DENV protein solution, the linear range of the concentrations was from 1 pM to 1 μM and the LOD was 76.7 fM. Moreover, the proposed biosensor detected DENV in a diluted spiked sample at a linear range of 10 -6 to 10 6 TCID 50 /mL, while the detection performance was proven with an LOD of 1.74 × 10 -7 TCID 50/ mL along with high selectivity.

Left ventricular ejection fraction (EF) is a predictor of mortality and guides clinical decisions. Although transthoracic echocardiography (TTE) is commonly used for measuring EF, it has limitations, such as subjectivity and requires expert personnel. Advancements in biosensor technology and artificial intelligence are allowing systems capable of determining left ventricular function and providing automated measurement of EF. In this study, we tested new wearable automated real-time biosensors (Cardiac Performance System [CPS]) that compute EF using waveform machine learning on cardiac acoustic signals. The primary aim was to compare the accuracy of CPS EF with TTE EF. Adult patients presenting to cardiology, presurgical, and diagnostic radiology clinical settings in an academic center were enrolled. TTE examination was performed by a sonographer, followed immediately by a 3-minute recording of acoustic signals from CPS biosensors placed on the chest by nonexpert personnel. TTE EF was calculated offline using the Simpson biplane method. A total of 81 patients (aged 19 to 88 years, 27 women, 20% to 80% EF) were included. Deming regression and Bland-Altman analysis were performed to assess the accuracy of CPS EF against TTE EF. Both Deming regression (slope 0.9981; intercept 0.03415%) and Bland-Altman analysis (bias -0.0247%; limits of agreement [-11.65, 11.60]%) demonstrated equivalency between CPS EF and TTE EF. The receiver operating characteristic for measuring sensitivity and specificity of CPS in identifying subjects with abnormal EF showed an area under the curve value of 0.974 for identifying EF <35% and 0.916 for detecting EF <50% CPS EF intraoperator and interoperator assessments demonstrated low variability. In conclusion, this technology measuring cardiac function from noninvasive biosensors and machine learning on acoustic signals provides an accurate EF measurement that is automated, real-time, and acquired rapidly by personnel with minimal training., Competing Interests: Declaration of Competing Interest Profs. Mahajan and Kaiser report a relation with Sensydia that includes: board membership, consulting or advisory, equity or stocks, and nonfinancial support. Prof. Kaiser, Dr. Borgstrom, and Prof. Mahajan have patent number US20190059748A1 issued to University of California. Profs. Mahajan and Kaiser are inventors of the acoustic waveform machine learning technology employed in the Cardiac Performance System and serve as co-founders of Sensydia. They contributed to the scientific discussions and design of the study but did not participate in patient recruitment and data collection or computation of ejection fraction by echocardiography or Cardiac Performance System. They reviewed the data and were involved in preparation of the manuscript. Dr. Howard-Quijano was the principal investigator for the study and oversaw every aspect of the investigation., (Copyright © 2023 Elsevier Inc. All rights reserved.)

A retinal prosthesis is a device that can provide artificial vision to people who have lost their sight from certain retinal disorder. Because the device needs to be inserted into the body, high flexibility and reliability is required. Recently, devices using thermoplastic polymers such as LCP and COC as substrates have been studied. Being a highly functional integrated device, retinal prosthesis poses many design challenges. Among them, the stimulation chip embedding can be a particularly important task. Although it is common to use a wire bonding method for chip embedding, there are several limitations that are difficult to apply to implantable device. In this investigation, a novel approach is developed for high spaceefficient electrical connections and perform reliable encapsulation of integrated circuits to replace wire bonding. Since designing and manufacturing the stimulator chip used in retinal prosthesis requires non-negligible cost, a silicon die with the identical shape was selected as a substitute for testing purposes.

Centella asiatica is a traditional herbaceous plant with numerous beneficial effects, widely known for its medicinal and cosmetic applications. Maximizing its growth can lead to beneficial effects, by focusing on the use of its active compounds. The use of plant growth-promoting rhizobacteria (PGPR) is known to be an alternative to chemical fertilizers. In this study, we used the PGPR Priestia megaterium HY-01 to increase the yield of C. asiatica . In vitro assays showed that HY-01 exhibited plant growth-promoting activities (IAA production, denitrification, phosphate solubilization, and urease activity). Genomic analyses also showed that the strain has plant growth-promoting-related genes that corroborate with the different PGP activities found in the assays. This strain was subsequently used in field experiments to test its effectiveness on the growth of C. asiatica . After four months of application, leaf and root samples were collected to measure the plant growth rate. Moreover, we checked the rhizosphere microbiome between the treated and non-treated plots. Our results suggest that treatment with Hyang-yak-01 not only improved the growth of C. asiatica (leaf length, leaf weight, leaf width, root length, root width, and chlorophyll content) but also influenced the rhizosphere microbiome. Biodiversity was higher in the treated group, and the bacterial composition was also different from the control group.

Knots are the weakest link in surgical sutures, serving as mechanical ligatures between filaments. Exceeding their safe operational limits can cause fatal complications. The empirical nature of present guidelines calls for a predictive understanding of the mechanisms underlying knot strength. We identify the primary ingredients dictating the mechanics of surgical sliding knots, highlighting the previously overlooked but critical effect of plasticity and its interplay with friction. The characterization of surgeon-tied knots reveals the relevant ranges of tightness and geometric features. Using model experiments coupled with finite element simulations, we uncover a robust master curve for the target knot strength versus the tying pre-tension, number of throws, and frictional properties. These findings could find applications in the training of surgeons and robotic-assisted surgical devices.

Research questions in the human sciences often seek to answer if and when a process changes across time. In functional MRI studies, for instance, researchers may seek to assess the onset of a shift in brain state. For daily diary studies, the researcher may seek to identify when a person's psychological process shifts following treatment. The timing and presence of such a change may be meaningful in terms of understanding state changes. Currently, dynamic processes are typically quantified as static networks where edges indicate temporal relations among nodes, which may be variables reflecting emotions, behaviors, or brain activity. Here we describe three methods for detecting changes in such correlation networks from a data-driven perspective. Networks here are quantified using the lag-0 pair-wise correlation (or covariance) estimates as the representation of the dynamic relations among variables. We present three methods for change point detection: dynamic connectivity regression, max-type method, and a PCA-based method. The change point detection methods each include different ways to test if two given correlation network patterns from different segments in time are significantly different. These tests can also be used outside of the change point detection approaches to test any two given blocks of data. We compare the three methods for change point detection as well as the complementary significance testing approaches on simulated and empirical functional connectivity fMRI data examples., (© 2023. The Author(s) under exclusive licence to The Psychometric Society.)

Microglia are specialized brain-resident macrophages that play crucial roles in brain development, homeostasis, and disease. However, until now, the ability to model interactions between the human brain environment and microglia has been severely limited. To overcome these limitations, we developed an in vivo xenotransplantation approach that allows us to study functionally mature human microglia (hMGs) that operate within a physiologically relevant, vascularized immunocompetent human brain organoid (iHBO) model. Our data show that organoid-resident hMGs gain human-specific transcriptomic signatures that closely resemble their in vivo counterparts. In vivo two-photon imaging reveals that hMGs actively engage in surveilling the human brain environment, react to local injuries, and respond to systemic inflammatory cues. Finally, we demonstrate that the transplanted iHBOs developed here offer the unprecedented opportunity to study functional human microglia phenotypes in health and disease and provide experimental evidence for a brain-environment-induced immune response in a patient-specific model of autism with macrocephaly., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Microelectrode-based cell chip studies for cellular responses often require improved adhesion and growth conditions for efficient cellular diagnosis and high throughput screening in drug discovery. Cell-chip studies are often performed on gold electrodes due to their biocompatibility, and stability, but the electrode-electrolyte interfacial capacitance is the main drawback to the overall sensitivity of the detection system. Thus, here, we developed reduced graphene oxide-polyaniline-modified gold microelectrodes for real-time impedance-based monitoring of human gastric adenocarcinoma cancer (MKN-1) cells. The impedance characterization on modified electrodes showed 28-fold enhanced conductivity than the bare electrodes, and the spectra were modeled with proper equivalent circuits to extrapolate the values of circuit elements. The impedance of both time-and frequency-dependent measurements of cell-covered modified electrodes with equivalent model circuits was analyzed to achieve cellular behavior, such as adhesion, spreading, proliferation, and influence of anti-cancer agents. The normalized impedance at 41.5 kHz (|Z| norm 41 kHz ) was selected to monitor the cell growth analysis, which was found linear with the proliferation of adherent cells along with the influence of the anticancer drug agent on the MKN-1 cells. The synergistic effects and biocompatible nature of PANI-RGO modifications improved the overall sensitivity for the cell-growth studies of MKN-1 cells., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

In this study, the optimum mixing ratio for backfill was determined by analyzing the mechanical properties and microstructure of controlled low-strength material (CLSM)-the backfill material for road excavation and restoration-using the total amount of stone sludge generated during aggregate production, including analysis of the flow and material separation resistance by compounding factors. A small-scale field evaluation was conducted using the derived optimal mixing ratio. A comprehensive analysis of the mechanical properties was based on the relevant standards and specifications, and a microstructure analysis indicated that the optimal mixing ratio of CLSM containing stone sludge was 350% W/B. A field applicability evaluation indicated that the flow was 230 mm, and the initial and re-excavation properties were 0.75 and 1.15 MPa, respectively, which met ASTM standards. Monitoring for approximately 5 months revealed that there was no ground subsidence caused by traffic, and it was confirmed that re-excavation with equipment was possible. After re-excavation, the filling properties of CLSM using stone sludge and the pipe periphery were checked, and it was found that no significant filling and pipe damage had occurred.

Background: Menopausal hormone therapy (MHT) has been associated with a decreased risk of gastric cancer (GC) and colorectal cancer (CRC); however, few studies have been conducted in diverse ethnic groups, particularly in the Asian population. Therefore, the current study evaluated if MHT is inversely associated with GC and CRC in East Asia using a representative population-based study in Korea., Methods: This retrospective cohort study was conducted using the National Health Insurance Service-National Sample Cohort 2.0 in South Korea from 2002 to 2015. A total of 196,095 women aged ≥40 years were included in the study. The numbers of participants who did and did not use MHT were 19,063 (9.7 %) and 177,032 (90.3 %), respectively. Hazard ratios (HRs) and the corresponding 95 % confidence intervals (CIs) were estimated using a time-dependent Cox proportional hazards model. Age was considered as a time scale, and other confounding factors, including income levels based on insurance premiums, region of residence, and comorbidities, were included in the multivariable-adjusted model., Results: The total number of incident cases of GC and CRC were 1339 (0.68 %) and 1428 (0.73 %), respectively. We observed an inverse association of the use of estrogen replacement therapy (ERT; estrogen-containing therapy regardless of other regimen types) with GC [HR (95 % CI):0.68 (0.51-0.90)], CRC [0.57 (0.42-0.78)] and gastrointestinal cancer [GI, 0.63 (0.51-0.77)]. In the analyses by CRC subsite, the risks of both colon and rectal cancers were associated with ERT. In addition, both estrogen and combined estrogen and progestogen regimens were significantly associated with CRC and GI cancer., Conclusion: ERT was associated with a decreased risk of GC and CRC. Our findings support the protective effect of estrogen against GC and CRC in Korean women., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The high-dimensional encoding of single photons can offer various possibilities for enhancing quantum information processing. This work experimentally demonstrates the quantum interference of an engineered multidimensional quantum state through the space-division multiplexing of a heralded single-photon state with a spatial light modulator (SLM) and spatial-mode mixing of a single photon through a long multimode fiber (MMF). In our experiment, the heralded single photon generated from a warm 87 Rb atomic ensemble was bright, robust, and long-coherent. The multidimensional spatial quantum state of the long-coherent single photon was transported through a 4-m-long MMF and arbitrarily controlled using the SLM. We observed the quantum interference of a single-photon multidimensional spatial quantum state with a visibility of >95%. These results may have potential applications in quantum information processing, for example, in photonic variational quantum eigensolve with high-dimensional single photons and realizing high information capacity per photon for quantum communication.

Background: Medication nonadherence among older patients with cancer can have profound health consequences. This study examines the association between prescription drug coverage satisfaction and medication nonadherence among Medicare beneficiaries with cancer., Methods: We analyzed the 2017 Medicare Current Beneficiary Survey Public Use File of beneficiaries aged ≥65 years with reported non-skin cancer (n = 806). Beneficiaries were considered to have medication nonadherence if they reported: skipping doses, taking smaller doses than prescribed, or delaying or not filling a prescription because of cost. A survey-weighted logistic model, adjusted for covariates, was conducted to examine the association between prescription drug coverage satisfaction and medication nonadherence., Results: Of study beneficiaries with cancer, 14.7% reported medication nonadherence. Higher proportions of beneficiaries with medication nonadherence were dissatisfied with the amount paid for medications (33.2% vs. 11.0%, p < 0.001) and the medications included on formulary (29.5% vs 5.2%, p < 0.001). In the adjusted analysis, the risk for medication nonadherence was higher among those who were dissatisfied with the amount paid for medications (OR = 2.22; p = 0.050) and the medications included on formulary (OR = 5.03; p = 0.005)., Conclusions: Strategic mitigation of these barriers is essential to improving health outcomes in this at-risk population.

The skin tissue of the scalp is unique from other skin tissues because it coexists with hair, and many differences in microbial composition have been confirmed. In scalp tissues, hair loss occurs due to a combination of internal and external factors, and several studies are being conducted to counteract this. However, not many studies have addressed hair loss from the perspective of the microbiome. In this study, subjects with hair loss and those with normal scalps were set as experimental and control groups, respectively. In the experimental group, hair loss had progressed, and there was a large difference in microbiome composition compared to the group with normal scalps. In particular, differences in Accumulibacter , Staphylococcus , and Corynebacterium were found. From Staphylococcus epidermidis Cicaria, two active components were isolated as a result of repeated column chromatography. Spectroscopic data led to the determination of chemical structures for adenosine and biotin. Fractions were obtained, and ex vivo tests were conducted using hair follicles derived from human scalp tissue. When the microbiome adenosine-treated group was compared to the control group, hair follicle length was increased, and hair root diameter was maintained during the experimental periods. In addition, the Cicaria culture medium and the microbial adenosine- and biotin-treated groups maintained the anagen phase, reducing progression to the catagen phase in the hair growth cycle. In conclusion, it was confirmed that the Cicaria culture medium and the microbial adenosine and biotin derived from the culture were effective in inhibiting hair loss.

Genotyping of single nucleotide variants (SNVs) has enabled the assessment of disease-related risk factors and significantly improved the potency of diagnosis and prognosis. Meanwhile, genotyping of SNVs is challenging due to the high sequence similarity between wild-type (WT) and SNV. To increase the discrimination between WT and SNV, probes are modified with nucleic acid analogues such as locked nucleic acid (LNA), or deliberate mismatches are introduced to the probe sequence. However, nucleic acid analogues have limitation in high cost and complexity in their synthesis. And a generalized methodology has not been proposed for determining the position and type of deliberate mismatches at the designated experimental conditions to the best of our knowledge. Herein, we propose a reliable workflow for designing mismatch-introduced probes (MIPs) based on nucleic acid thermodynamic analysis and rejection sampling. The theoretical hybridization state of MIP was calculated using nucleic acid thermodynamics, and the detectability was estimated by rejection sampling that simulates the errors from experimental environments. We fabricated MIPs for SNVs in epidermal growth factor receptor, and experimentally demonstrated optimized detectability. The detectability increased up to 7.19-fold depending on the position and type of mismatch; moreover, the optimized MIP showed higher detectability than the LNA probe. This indicates that the workflow can be broadly applied to the optimization of probe sequence for the detection of various disease-related SNVs., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Cyclic Olefin Copolymer is emerging as a packaging material for implantable electrodes due to its physical properties such as low water absorption rate and low water vapor permeability. The electrode-tissue interface is often regarded as a major focus of implantable electrodes, but its packaging should also be considered thoroughly since it directly contacts the adjoining body cells. Therefore, eliminating any sharp boundaries or edges around the package would be beneficial to minimize potential inflammatory responses caused by physical/mechanical stresses. To smooth both inner/outer edges of a cyclic olefin copolymer packaging, an optimal UV laser condition was investigated by varying its marking speed and iterations. Clinical relevance - This establishes a method that can selectively smooth the edges around a cyclic olefin copolymer pack-aged implantable electrodes for reduced mechanical mismatch after insertion.

Recent studies have revealed that the composition of human gut microbiota varies according to region, race, age, diet, living environment, and sampling and DNA extraction method. The purpose of this study was to broaden our understanding of the intestinal microbial composition of Koreans by conducting a 16S rRNA amplicon sequencing on 78 Korean samples composed of adults, children, normal and obese groups. We compared the microbiome composition and diversity of these groups at different levels including the phylum and genus level using two different stool DNA extraction kits of QIAamp® PowerFecal® DNA Kit (Qiagen, Hilden, Germany) and CT Max Fecal DNA Kit (Ct bio, Korea). We found that Ct bio (Ct) kit recovered higher DNA yields and OTUs than QIAamp® PowerFecal® DNA Kit (Qia). The Ct kit, which adopted more rigorous bead beating method, detected the most Gram-positive (G+) bacteria, Firmicutes, at the Phylum level, whereas the Qia kit, which used a less rigorous cell lysis method, found the most Gram-negative (G-) bacteria, Bacteroidetes. The Firmicutes-to-Bacteroidetes (F/B) ratio showed no significant difference between the obese and the normal groups of same kit; however, they were significantly different with two different kits. There was a difference in the intestinal flora between healthy Korean adults and children. The taxa that differed significantly between the adults and children were Bacteroides, Bifidobacterium, Prevotella, and Subdoligranulum. There was no significant difference in the intestinal flora between the normal weight group and the obese group in adults and children, respectively. This is probably because the difference in body mass index (BMI) between the sample groups collected in this study is statistically significant, but it is not large enough to show a clear difference in the flora. Therefore, these results should be interpreted with caution while considering the BMI values and Korean obesity criterion together., Competing Interests: The authors have declared that no competing interests exist.

Norovirus is one of the most common causes of gastroenteritis, a disease characterized by diarrhea, vomiting, and stomach pain. A rapid on-site identification of the virus from fecal samples of patients is a prerequisite for accurate medical management. Here, we demonstrate a rapid nucleic acid-based detection platform as an on-site biosensing tool that can concentrate viruses from fecal samples. Moreover, it can perform RNA extraction and identification, and signal amplification using G-quadruplex and hemin containing DNA probes (G-DNA probes) and graphene oxide (GO)-coated microbeads. Briefly, murine noroviruses are lysed without chemicals on the surface of the GO microbeads. Subsequently, the target RNA is hybridized with G-DNA probes, and the resultant RNA/G-DNA probe complex is separated from unbound G-DNA probes using GO beads and is mixed with the detection buffer (ABTS/H 2 O 2 ). Presence of murine noroviruses causes a colorimetric change of the buffer from colorless to green. Thus, we integrated all processes required to detect murine noroviruses in stool samples in a simple foldable microfluidic chip. Moreover, it can detect 10 1  pfu of the virus in 30 min in a fecal sample., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Considering the worldwide health crisis associated with highly contagious severe respiratory disease of COVID-19 outbreak, the development of multiplexed, simple and rapid diagnostic platforms to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is in high demand. Here, a nucleic acid amplification-free electrochemical biosensor based on four-way junction (4-WJ) hybridization is presented for the detection of SARS-CoV-2. To form a 4-WJ structure, a Universal DNA-Hairpin (UDH) probe is hybridized with two adaptor strands and a SARS-CoV-2 RNA target. One of the adaptor strands is functionalized with a redox mediator that can be detected using an electrochemical biosensor. The biosensor could simultaneously detect 5.0 and 6.8 ag/μL of S and Orf1ab genes, respectively, within 1 h. The biosensor was evaluated with 21 clinical samples (16 positive and 5 negative). The results revealed a satisfactory agreement with qRT-PCR. In conclusion, this biosensor has the potential to be used as an on-site, real-time diagnostic test for COVID-19., (Copyright © 2021 Elsevier B.V. All rights reserved.)

It is challenging to employ nucleic acid-based diagnostics for the in situ detection of Clostridium difficile from complex fecal samples because essential sample preparation and amplification procedures require various experimental resources. In this study, a simple and effective on-site nucleic acid-based detection system was used to detect C. difficile in stool samples. Two columns containing different microbeads, namely, glass and functionalized graphene oxide-coated microbeads, were designed to remove relatively large impurities by filtration and concentrate bacteria, including C. difficile, from stool samples by adsorption. The bacterial nucleic acids were effectively extracted using a small bead beater. The effectiveness of enzyme inhibitors remaining in the sample was efficiently reduced by the direct buffer developed in this study. This sample preparation kit consisting of two simple columns showed better performance in real-time polymerase chain reaction (PCR) and equivalent performance in loop-mediated isothermal amplification (LAMP) than other sample preparation kits, despite 90% simplification of the process. The amplification-ready samples were introduced into two microtubes containing LAMP pre-mixtures (one each for E. coli as an external positive control and C. difficile) by a simple sample loader, which was operated using a syringe. LAMP, which indicates amplification based on color change, was performed at 65 °C in a small water bath. The limit of detection (L.O.D) and analytical sensitivity/specificity of our simple and effective kit were compared with those of a commercial kit. C. difficile in stool samples could be detected within 1 h with 10 3 cfu/10 mg using LAMP combined simple on-site detection kit., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Skin is an essential outer barrier and supports the growth of commensal microorganisms that protects a host from the offense of foreign toxic organisms. With the rapid development of next-generation sequencing (NGS)-based applications, skin microbiome research for facial health care has reached industry growth, such as therapy and cosmetic product development. Despite the acceleration of skin microbiome research, experimental standardization protocol has not yet been established in the facial site and method of sampling., Objective: Thus, we aimed to investigate the differences in microbial composition at each facial site (cheek, mouth, forehead, and entire face) using comprehensive microbiome analysis., Methods: Twelve specimens from three men (four specimens per one person) were collected. The hypervariable regions (V3-V4) of the bacterial 16S rRNA gene were targeted for 16S amplicon library construction and classification of bacterial taxonomy. Skin microbial composition for all specimens was investigated, and the differences site-by-site in skin microbial composition were analyzed and evaluated by the various statistical tests., Results: We were able to validate the independent correlation between the skin microbiome composition and the facial sites. The cheek site showed the highest alpha-diversity in richness and evenness scores compared to the forehead and mouth. The cheek and mouth sites showed a positive correlation (R 2 value > 0.93) with the entire face, while the forehead sites were negatively correlated (R 2 value < 0.2). Given the relative abundance based on statistical correlation analysis, we estimated that the cheek site could be considered an optimal topical site to replace the entire face., Conclusion: Our study suggests that skin microbiome profiling of four facial sites confirms that the cheek shows the most similar skin flora with the entire face. This study would be informative for preventing bias caused by sampling methods before researching and understanding skin cosmetics development or skin diseases., (© 2021. The Genetics Society of Korea.)

Micro-lens array, an artificial compound eye vision system, provides a wide field of view and multi-perspective view. However, it has not been adopted as a computer vision application due to its limited visible range and high optical interference. In this research, a novel fabrication method for the flexible polydimethylsiloxane micro-lens array with a polytetrafluoroethylene light screen-aperture integrated layer was established by the simple protrusion method. The integrated layer provided longer visible range by one meter while maintaining the wide field-of-view of 100 °. The resulting images were used for obtaining depth information of a target as an example and for analyzing the rectangular and hexagonal arrangements of the micro-lenses for the future applications. With the improved visual range, wide field-of-view and flexibility, the fabricated micro-lens array can be applied to the small and curved CMOS image sensors in the future.

Micro-lens array is a great example of bio-mimetic technology which was inspired by compound eyes found in insects and is used in lasers, optical communication, and 3D imaging. In this study, a micro-lens array was fabricated from cyclic olefin copolymer using a cost-effective method: compression molding and thermal reflow. Also, a light screen was installed between lenses to reduce the optical interference for clearer individual images. Cyclic olefin copolymer-based micro-lens array showed good optical results under a standard optical microscope. By placing the fabricated micro-lens array directly on an image sensor, it was observed that the light screen shows significant improvement in image quality. Also, the point spread function was analyzed to confirm the optical performance and the effectiveness of the micro-lens array with the light screen installed.

It is highly important to sensitively measure the abundance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on various surfaces. Here, we present a nucleic acid-based detection method consisting of a new sample preparation protocol that isolates only viruses, not the free RNA fragments already present on the surfaces of indoor human-inhabited environments, using a graphene oxide-coated microbead filter. Wet wipes (100 cm 2 ), not cotton swabs, were used to collect viruses from environmental surfaces with large areas, and viruses were concentrated and separated with a graphene oxide-coated microbead filter. Viral RNA from virus was recovered 88.10 ± 8.03% from the surface and free RNA fragment was removed by 99.75 ± 0.19% from the final eluted solution. When we tested the developed method under laboratory conditions, a 10-fold higher viral detection sensitivity (Detection limit: 1 pfu/100 cm 2 ) than the current commercial protocol was observed. Using our new sample preparation protocol, we also confirmed that the virus was effectively removed from surfaces after chemical disinfection; we were unable to measure the disinfection efficiency using the current commercial protocol because it cannot distinguish between viral RNA and free RNA fragments. Finally, we investigated the presence of SARS-CoV-2 and bacteria in 12 individual negative pressure wards in which patients with SARS-CoV-2 infection had been hospitalized. Bacteria (based on 16 S DNA) were found in all samples collected from patient rooms; however, SARS-CoV-2 was mainly detected in rooms shared by two patients., (© 2021. The Author(s).)

Triaxial weaving is a handicraft technique that has long been used to create curved structures using initially straight and flat ribbons. Weavers typically introduce discrete topological defects to produce nonzero Gaussian curvature, albeit with faceted surfaces. We demonstrate that, by tuning the in-plane curvature of the ribbons, the integrated Gaussian curvature of the weave can be varied continuously, which is not feasible using traditional techniques. Further, we reveal that the shape of the physical unit cells is dictated solely by the in-plane geometry of the ribbons, not elasticity. Finally, we leverage the geometry-driven nature of triaxial weaving to design a set of ribbon profiles to weave smooth spherical, ellipsoidal, and toroidal structures.

Many studies on anti-bacterial/antiviral surfaces have been conducted to prevent epidemic spread worldwide. Several nanoparticles such as those composed of silver and copper are known to have antiviral properties. In this study, we developed copper oxide (CuO) nanoparticle-incorporated nanofibers to inactivate or remove viruses. The CuO nanoparticle-incorporated nanofiber was fabricated with a hydrophobic polymer-polyvinylpyrrolidone (PVP)-using electrospinning, and CuO nanoparticles were exposed from the PVP polymer surface by etching the nanofiber with oxygen plasma. The fabrication conditions of electrospinning and oxygen plasma etching were investigated by scanning electron microscopy (SEM), and field emission transmission electron microscopy (FETEM)/ energy dispersive spectrometry (EDS). H1N1 virus was utilized as the target sample and quantified by RT-qPCR. The antiviral efficacy of CuO nanoparticle-incorporated nanofibers was compared against bare CuO nanoparticles. Overall, 70% of the viruses were inactivated after CuO nanoparticle-incorporated nanofibers were incubated with 10² pfu/mL of H1N1 virus solution for 4 h. This indicates that the developed CuO nanoparticle-incorporated nanofibers have noticeable antiviral efficacy. As the developed CuO nanoparticle-incorporated nanofibers exerted promising antiviral effects against H1N1 virus, it is expected to benefit global health by preventing epidemic spread.

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.

Networks of flexible filaments often involve regions of tight contact. Predictively understanding the equilibrium configurations of these systems is challenging due to intricate couplings between topology, geometry, large nonlinear deformations, and friction. Here, we perform an in-depth study of a simple, yet canonical, problem that captures the essence of contact between filaments. In the orthogonal clasp, two filaments are brought into contact, with each centerline lying in one of a pair of orthogonal planes. Our data from X-ray tomography (μCT) and mechanical testing experiments are in excellent agreement with finite element method (FEM) simulations. Despite the apparent simplicity of the physical system, the data exhibit strikingly unintuitive behavior, even when the contact is frictionless. Specifically, we observe a curvilinear diamond-shaped ridge in the contact-pressure field between the two filaments, sometimes with an inner gap. When a relative displacement is imposed between the filaments, friction is activated, and a highly asymmetric pressure field develops. These findings contrast to the classic capstan analysis of a single filament wrapped around a rigid body. Both the μCT and FEM data indicate that the cross-sections of the filaments can deform significantly. Nonetheless, an idealized geometrical theory assuming undeformable tube cross-sections and neglecting elasticity rationalizes our observations qualitatively and highlights the central role of the small, but nonzero, tube radius of the filaments. We believe that our orthogonal clasp analysis provides a building block for future modeling efforts in frictional contact mechanics of more complex filamentary structures., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Far-infrared rays (FIR) are known to have various effects on atoms and molecular structures within cells owing to their radiation and vibration frequencies. The present study examined the effects of FIR on gene expression related to glucose transport through microarray analysis in rat skeletal muscle cells, as well as on mitochondrial biogenesis, at high and low glucose conditions. FIR were emitted from a bio-active material coated fabric (BMCF). L6 cells were treated with 30% BMCF for 24 h in medium containing 25 or 5.5 mM glucose, and changes in the expression of glucose transporter genes were determined. The expression of GLUT3 (Slc2a3) increased 2.0-fold (p < 0.05) under 5.5 mM glucose and 30% BMCF. In addition, mitochondrial oxygen consumption and membrane potential (ΔΨ m ) increased 1.5- and 3.4-fold (p < 0.05 and p < 0.001), respectively, but no significant change in expression of Pgc-1a , a regulator of mitochondrial biogenesis, was observed in 24 h. To analyze the relationship between GLUT3 expression and mitochondrial biogenesis under FIR, GLUT3 was down-modulated by siRNA for 72 h. As a result, the ΔΨ m of the GLUT3 siRNA-treated cells increased 3.0-fold (p < 0.001), whereas that of the control group increased 4.6-fold (p < 0.001). Moreover, Pgc-1a expression increased upon 30% BMCF treatment for 72 h; an effect that was more pronounced in the presence of GLUT3 . These results suggest that FIR may hold therapeutic potential for improving glucose metabolism and mitochondrial function in metabolic diseases associated with insufficient glucose supply, such as type 2 diabetes.

Background: Healthcare-associated pneumonia (HCAP) is a heterogeneous disease. We redefined nursing-home- and hospital-associated infections (NHAI) group by revising existing HCAP risk factors. The NHAI group comprised nursing home residents with a poor functional status, or recent (past 90 days) hospitalization or recent (past 180 days) antibiotic therapy. Our aim was to determine whether respiratory microbiota profiles are related to newly defined NHAI group in critically ill patients on mechanical ventilation., Methods: The 180 endotracheal aspirates (ETAs) from 60 mechanically ventilated ICU patients (NHAI group, n = 24; non-NHAI group, n = 36) were prospectively collected on days 1, 3 and 7 in a university hospital. The bacterial community profiles of the ETAs were explored by 16S rRNA gene sequencing. A phylogenetic-tree-based microbiome association test (TMAT), generalized linear mixed models (GLMMs), the Wilcoxon test and the reference frame method were used to analyze the association between microbiome abundance and disease phenotype., Results: The relative abundance of the genus Corynebacterium was significantly higher in the pneumonia than in the non-pneumonia group. The microbiome analysis revealed significantly lower α-diversity in the NHAI group than in the non-NHAI group. In the analysis of β-diversity, the structure of the microbiome also differed significantly between the two groups (weighted UniFrac distance, Adonis, p < 0.001). The abundance of Corynebacterium was significantly higher, and the relative abundances of Granulicatella, Staphylococcus, Streptococcus and Veillonella were significantly lower, in the NHAI group than in the non-NHAI group., Conclusions: The microbiota signature of the ETAs distinguished between patients with and without risk factors for NHAI. The lung microbiome may serve as a therapeutic target for NHAI group.

Purpose: The aim of this study was to investigate gender-related differences in the sagittal curvature of the distal femoral condyle in the Korean osteoarthritic population METHODS: The sagittal curvatures of the distal femoral condyle of 1979 Korean patients (1680 female and 299 male) were evaluated using magnetic resonance imaging (MRI). MRI scans were obtained before total knee arthroplasty (TKA) in consecutive patients with end-stage osteoarthritis. The sagittal curvature of the distal medial and lateral femoral condyles was characterized with respect to the anterior, distal, and posterior circles. The diameter of each circle was measured. This study included 1873 varus and 106 valgus knees., Results: The anterior, distal, and posterior diameters were significantly greater in the male patients than in the female patients (P < 0.05). In the male patients, the lateral diameter was significantly greater than the medial diameter in the anterior and posterior circles (P < 0.05). However, in the female patients, the lateral diameter was significantly greater only in the anterior circle. In both genders, the medial diameter was significantly greater than the lateral diameter of the distal circle (P < 0.05). For both the varus and valgus knees, the lateral diameter was greater than the medial diameter in the anterior circle., Conclusions: It has been concluded that the sagittal curvature of the femoral condyles in females is significantly different to their male counterparts. This study provides a reliable evaluation of the sagittal curvature of the femoral condyle in the Korean population. These gender-related differences in the sagittal curvature of the femoral condyle may require further investigation to determine surgical implications such as in TKA, and the existence of gender-related dimorphism in specific knee injuries and pathologies, such as ligament injuries and tibiofemoral problems., Level of Evidence: III.

A systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies was conducted to assess the association between menopausal hormone therapy and cardiovascular disease. The PubMed and EMBASE databases were searched for articles published from 2000 to 2019, using review methods based on a previous Cochrane review. Quality assessment of RCTs and observational studies was conducted using the Jadad scale and the Newcastle-Ottawa Scale, respectively. A total of 26 RCTs and 47 observational studies were identified. The study populations in the RCTs were older and had more underlying diseases than those in the observational studies. Increased risks of venous thromboembolism [summary estimate (SE), 95% confidence interval (CI): RCTs, 1.70, 1.33-2.16; observational studies, 1.32, 1.13-1.54] were consistently identified in both study types, whereas an increased risk of stroke in RCTs (SE: 1.14, 95% CI: 1.04-1.25) and a decreased risk of myocardial infarction in observational studies (SE: 0.79, 95% CI: 0.75-0.84) were observed. Differential clinical effects depending on timing of initiation, underlying disease, regimen type, and route of administration were identified through subgroup analyses. These findings suggest that underlying disease and timing of initiation should be carefully considered before starting therapy in postmenopausal women.

Heat sinks that dissipate heat effectively play a significant role in devices with high-precision temperature control, such as thermal cyclers for polymerase chain reaction (PCR). This study was carried out to develop a heat sink with a high thermal conductivity to dissipate heat effectively. To increase the surface area of the heat sink, zinc oxide (ZnO) nanostructures were fabricated on an aluminum plate. ZnO nanostructures were fabricated by hydrothermal method and confirmed by scanning electron microscopy and X-ray diffraction. With the increase in the concentration of the precursors, the length of the nanorods increased, and with longer reaction time, nanostructures connected with higher stability and larger surface area. Thermal conductivity is increased by ZnO nanostructures and is affected by the concentration of precursors and the reaction time. Thermal conductivity of an optimal ZnO-coated Al plate is 2 times higher than that of a bare one. This technology can be applied to portable PCR devices to reduce weight, size, and power consumption.