Development of underground detection system using a metal detector and aluminum tag for, Copris ochus (Coleoptera: Scarabaeidae).

Tracking of soil-dwelling insects poses greater challenges compared to aboveground-dwelling animals in terrestrial systems. A metal detector system consisting of a commercially available detector and aluminum tags was developed for detecting dung beetle, Copris ochus Motschulsky (Coleoptera: Scarabaeidae). First, detection efficacy of the system was evaluated by varying volumes of aluminum tags attached on a plastic model of the insect and also by varying angles. Then, detection efficacy was evaluated by varying depths of aluminum-tagged models under soil in 2 vegetation types. Finally, the effects of tag attachment on C. ochus adults were assessed for survivorship, burrowing depth, and horizontal movement. Generally, an increase in tag volume resulted in greater detection distance in semi-field conditions. Maximum detection distance of aluminum tag increased up to 17 cm below soil surface as the tag size (0.5 × 1.0 cm [width × length]) and thickness (16 layers) were maximized, resulting in a tag weight of 31.4 mg, comprising ca. 9% of average weight of C. ochus adult. Furthermore, the detection efficacy did not vary among angles except for 90°. In the field, metal detectors successfully detected 5 aluminum-tagged models in 20 × 10 m (W × L) arena within 10 min with detection rates ≥85% for up to depth of 10 cm and 45%-60% at depth of 20 cm. Finally, aluminum tagging did not significantly affect survivorship and behaviors of C. ochus. Our study indicates the potential of metal detector system for tracking C. ochus under soil.

Establishment of canine mammary gland tumor cell lines harboring PI3K/Akt activation as a therapeutic target.

Canine mammary gland tumors (MGT) have a poor prognosis in intact female canines, posing a clinical challenge. This study aimed to establish novel canine mammary cancer cell lines from primary tumors and characterize their cellular and molecular features to find potential therapeutic drugs. The MGT cell lines demonstrated rapid cell proliferation and colony formation in an anchorage-independent manner. Vimentin and α-SMA levels were significantly elevated in MGT cell lines compared to normal canine kidney (MDCK) cells, while CDH1 expression was either significantly lower or not detected at all, based on quantitative real-time PCR (qRT-PCR) analysis. Functional annotation and enrichment analysis revealed that epithelial-mesenchymal transition (EMT) phenotypes and tumor-associated pathways, particularly the PI3K/Akt signaling pathway, were upregulated in MGT cells. BYL719 (Alpelisib), a PI3K inhibitor, was also examined for cytotoxicity on the MGT cell lines. The results show that BYL719 can significantly inhibit the proliferation of MGT cell lines in vitro. Overall, our findings suggest that the MGT cell lines may be valuable for future studies on the development, progression, metastasis, and management of tumors.

Navigating Breast Cancer Innovation in Uganda: Within and Without the Textbook.

The Center for Bioengineering Innovation and Design (CBID) at Johns Hopkins University (JHU) has established a comprehensive approach to addressing global health challenges. Central to CBID's modality on global health is a strategy that integrates education, research, and collaboration. Through its graduate program, CBID trains the next generation of health care innovators to address the specific needs of low- and middle-income countries (LMICs). Graduate student teams at CBID begin their year with a focus on a health care thematic area associated with a target country.

History and evolution of blood pressure measurement.

Hypertension is the leading cause of morbidity and mortality worldwide. Hypertension mostly accompanies no symptoms, and therefore blood pressure (BP) measurement is the only way for early recognition and timely treatment. Methods for BP measurement have a long history of development and improvement. Invasive method via arterial cannulation was first proven possible in the 1800's. Subsequent scientific progress led to the development of the auscultatory method, also known as Korotkoff' sound, and the oscillometric method, which enabled clinically available BP measurement. However, hypertension management status is still poor. Globally, less than half of adults are aware of their hypertension diagnosis, and only one-third of them being treated are under control. Novel methods are actively investigated thanks to technological advances such as sensors and machine learning in addition to the clinical needs for easier and more convenient BP measurement. Each method adopts different technologies with its own specific advantages and disadvantages. Promises of novel methods include comprehensive information on out-of-office BP capturing dynamic short-term and long-term fluctuations. However, there are still pitfalls such as the need for regular calibration since most novel methods capture relative BP changes rather than an absolute value. In addition, there is growing concern on their accuracy and precision as conventional validation protocols are inappropriate for cuffless continuous methods. In this article, we provide a comprehensive overview of the past and present of BP measurement methods. Novel and emerging technologies are also introduced with respect to their potential applications and limitations.

Predicting disease recurrence in limited disease small cell lung cancer using cell-free DNA-based mutation and fragmentome analyses.

Background: Limited disease (LD) small cell lung cancer (SCLC) treated with definitive concurrent chemoradiotherapy (CCRT) potentially experience disease recurrence. We investigated the feasibility of circulating-tumor DNA (ctDNA)-based genomic and fragmentome analyses to assess the risk of recurrence. Methods: Targeted sequencing was conducted using pre-treatment and on-treatment blood samples from definitive CCRT-treated patients with LD-SCLC (n=50). Based on 12-month recurrence-free survival (RFS), patients were categorized into persistent-response (PeR, n=29) and non-PeR (n=21) groups. Fragmentome analysis was conducted using ctDNA fragments of different lengths: P1 (100-155 bp) and P2 (160-180 bp). Results: Patients with TP53 (n=15) and RB1 (n=11) mutation in on-treatment samples demonstrated significantly shorter RFS than patients with wild-type (WT) (P=0.05, P=0.0014, respectively). Fragmentome analysis of all available on-treatment samples (n=26) revealed that the non-PeR group (n=10) had a significantly higher P1 range (P=0.003) and lower P2 range (P=0.002). The areas under the curves for P1, P2, and the fragmentation ratio (P1/P2) in distinguishing the PeR and non-PeR were 0.850, 0.725, and 0.900, respectively. Using optimal cut-off, longer RFSs were found with the low-fragmentation-ratio group than with the high-fragmentation-ratio group (not reached vs. 7.6 months, P=0.002). Patients with both WT RB1 and a low-fragmentation-ratio (n=10) showed better outcomes than patients with both mutated RB1 and a high-fragmentation-ratio (n=10; hazard ratio, 7.55; 95% confidence interval: 2.14-26.6; P=0.002). Conclusions: RB1 mutations and high fragmentation ratios correlated with early disease recurrence. Analyzing ctDNA could help in predicting early treatment failure and making clinical decisions for high-risk patients.

Analytical and Clinical Validation of a Highly Sensitive NGS-Based ctDNA Assay with Real-World Concordance in Non-Small Cell Lung Cancer.

PURPOSE: There have been needs to improve the sensitivity of liquid biopsy. This report aims to report the analytical and clinical validation of a next-generation sequencing (NGS)-based circulating tumor DNA (ctDNA) assay. MATERIALS AND METHODS: Analytical validation was conducted in vitro by evaluating the limit of detection (LOD), precision, and specificity for various genomic aberrations. The real-world performance in non-small cell lung cancer (NSCLC) was assessed by comparing the results of AlphaLiquid100 to the tissue-based results. RESULTS: The LODs with 30 ng input DNA were 0.11%, 0.11%, 0.06%, 0.21%, and 2.13 copies for detecting single nucleotide variants, insertions, deletions, fusions, and copy number alterations (CNA), respectively. Quantitatively, single nucleotide variants/insertions and deletions, fusions, and CNAs showed a good correlation (R2=0.91, 0.40, and 0.65; y=0.95, 1.06, and 1.19) to the manufacturer's values, and per-base specificities for all types of variants were near 100%. In real-world NSCLC (n=122), key actionable mutations in NSCLC were detected in 60.7% (74/122) with the ctDNA assay. Comparative analysis against the NGS-based tissue results for all key mutations showed positive percent agreement (PPA) of 85.3%. For individual genes, the PPA was as high as 95.7% for epidermal growth factor receptor (EGFR) mutations and 83.3% for ALK translocations. AlphaLiquid100 detected drug-sensitive EGFR mutation at a variant allele frequency as low as 0.02% and also identified an EGFR mutation in a case where tissue sample missed. Blood samples collected post-targeted therapies revealed additional acquired mutations. CONCLUSION: The AlphaLiquid100 ctDNA assay demonstrates robust analytical validity, offering clinically important information for NSCLC patients.

Cancer signature ensemble integrating cfDNA methylation, copy number, and fragmentation facilitates multi-cancer early detection.

Cell-free DNA (cfDNA) sequencing has demonstrated great potential for early cancer detection. However, most large-scale studies have focused only on either targeted methylation sites or whole-genome sequencing, limiting comprehensive analysis that integrates both epigenetic and genetic signatures. In this study, we present a platform that enables simultaneous analysis of whole-genome methylation, copy number, and fragmentomic patterns of cfDNA in a single assay. Using a total of 950 plasma (361 healthy and 589 cancer) and 240 tissue samples, we demonstrate that a multifeature cancer signature ensemble (CSE) classifier integrating all features outperforms single-feature classifiers. At 95.2% specificity, the cancer detection sensitivity with methylation, copy number, and fragmentomic models was 77.2%, 61.4%, and 60.5%, respectively, but sensitivity was significantly increased to 88.9% with the CSE classifier (p value < 0.0001). For tissue of origin, the CSE classifier enhanced the accuracy beyond the methylation classifier, from 74.3% to 76.4%. Overall, this work proves the utility of a signature ensemble integrating epigenetic and genetic information for accurate cancer detection.

Diagnostic performance of respirators for collection and detection of SARS-CoV-2.

Respirators, called as face mask, have been used to protect the wearer from the outside harmful air environment and prevent any virus from being released to neighbors from potentially infected exhaled breath. The antiviral effectiveness of respirators has not only been researched scientifically, but has also become a global issue due to society's obligation to wear respirators. In this paper, we report the results of a study on the collection and detection of viruses contained in exhaled breath using respirators. The inner electrostatic filter was carefully selected for virus collection because it does not come in direct contact with either human skin or the external environment. In the study of a healthy control group, it was confirmed that a large amount of DNA and biomolecules such as exosomes were collected from the respirator exposed to exhalation, and the amount of collection increased in proportion to the wearing time. We conducted experiments using a total of 72 paired samples with nasopharyngeal swabs and respirator samples. Out of these samples, fifty tested positive for SARS-CoV-2 and twenty-two tested negative. The PCR results of the NPS and respirator samples showed a high level of agreement, with a positive percent agreement of ≥ 90% and a negative percent agreement of ≥ 99%. Furthermore, there was a notable level of concordance between RCA-flow tests and PCR when examining the respirator samples. These results suggest that this is a non-invasive, quick and easy method of collecting samples from subjects using a respirator, which can significantly reduce the hassle of waiting at airports or public places and concerns about cross-contamination. Furthermore, we expect miniaturized technologies to integrate PCR detection into respirators in the near future.

Practical Utility of Liquid Biopsies for Evaluating Genomic Alterations in Castration-Resistant Prostate Cancer.

Traditional tissue-based assessments of genomic alterations in castration-resistant prostate cancer (CRPC) can be challenging. To evaluate the real-world clinical utility of liquid biopsies for the evaluation of genomic alterations in CRPC, we preemptively collected available plasma samples and archival tissue samples from patients that were being treated for clinically confirmed CRPC. The cell-free DNA (cfDNA) and tumor tissue DNA were analyzed using the AlphaLiquid®100-HRR panel. Plasma samples from a total of 87 patients were included in this study. Somatic mutations from cfDNA were detected in 78 (89.7%) patients, regardless of the presence of overt metastasis or concomitant treatment given at the time of plasma sample collection. Twenty-three patients were found to have known deleterious somatic or germline mutations in HRR genes from their cfDNA. Archival tissue samples from 33 (37.9%) patients were available for comparative analysis. Tissue sequencing was able to yield an NGS result in only 51.5% of the tissue samples. The general sensitivity of cfDNA for detecting somatic mutations in tissues was 71.8%, but important somatic/germline mutations in HRR genes were found to have a higher concordance (100%). Liquid biopsies can be a reasonable substitute for tissue biopsies in CRPC patients when evaluating genomic alterations.

Accurate Detection of Urothelial Bladder Cancer Using Targeted Deep Sequencing of Urine DNA.

Patients with hematuria are commonly given an invasive cystoscopy test to detect bladder cancer (BC). To avoid the risks associated with cystoscopy, several urine-based methods for BC detection have been developed, the most prominent of which is the deep sequencing of urine DNA. However, the current methods for urine-based BC detection have significant levels of false-positive signals. In this study, we report on uAL100, a method to precisely detect BC tumor DNA in the urine without tumor samples. Using urine samples from 43 patients with BC and 21 healthy donors, uAL100 detected BC with 83.7% sensitivity and 100% specificity. The mutations identified in the urine DNA by uAL100 for BC detection were highly associated with BC tumorigenesis and progression. We suggest that uAL100 has improved accuracy compared to other urine-based methods for early BC detection and can reduce unnecessary cystoscopy tests for patients with hematuria.

Personalised circulating tumour DNA assay with large-scale mutation coverage for sensitive minimal residual disease detection in colorectal cancer.

BACKGROUND: Postoperative minimal residual disease (MRD) detection using circulating-tumour DNA (ctDNA) requires a highly sensitive analysis platform. We have developed a tumour-informed, hybrid-capture ctDNA sequencing MRD assay. METHODS: Personalised target-capture panels for ctDNA detection were designed using individual variants identified in tumour whole-exome sequencing of each patient. MRD status was determined using ultra-high-depth sequencing data of plasma cell-free DNA. The MRD positivity and its association with clinical outcome were analysed in Stage II or III colorectal cancer (CRC). RESULTS: In 98 CRC patients, personalised panels for ctDNA sequencing were built from tumour data, including a median of 185 variants per patient. In silico simulation showed that increasing the number of target variants increases MRD detection sensitivity in low fractions (<0.01%). At postoperative 3-week, 21.4% of patients were positive for MRD by ctDNA. Postoperative positive MRD was strongly associated with poor disease-free survival (DFS) (adjusted hazard ratio 8.40, 95% confidence interval 3.49-20.2). Patients with a negative conversion of MRD after adjuvant therapy showed significantly better DFS (P < 0.001). CONCLUSION: Tumour-informed, hybrid-capture-based ctDNA assay monitoring a large number of patient-specific mutations is a sensitive strategy for MRD detection to predict recurrence in CRC.

A Novel Screening, Brief Intervention, and Referral to Treatment (SBIRT) Based Model for Mental Health in Occupational Health Implemented on Smartphone and Web-Based Platforms: Development Study With Results From an Epidemiologic Survey.

BACKGROUND: While the importance of mental health is well-recognized in the field of occupational health, implementation of effective strategies in the workplace has been limited by gaps in infrastructure, program comprehensiveness, coverage, and adherence. The authors developed a Screening, Brief Intervention, and Referral to Treatment (SBIRT) model based occupational mental health intervention, and implemented in a web-based format with a smartphone application. METHODS: The SBIRT-based intervention was developed by a multidisciplinary team, including occupational health physicians, nurses, psychiatrists, and software developers. The following mental health areas were included, based on outcomes of an epidemiological survey conducted: insomnia, depression, anxiety, problematic alcohol use, and suicidal risk. The viability of the two-step evaluation process utilizing a combination of the brief version and the full-length version of the questionnaire was examined using responses from the survey. The intervention was adjusted according to the survey results and expert opinions. RESULTS: The epidemiological survey included 346 employees who completed the long-form version of mental health scales. These data were the used to confirm the diagnostic value of using a combination of short-form and long-form version of the scales for screening in the SBIRT model. The model uses a smartphone application for screening, provision of psychoeducation, and for surveillance. The universal methods of the model ensure it can be implemented by all occupational managers, regardless of their specialization in mental health. In addition to the two-step screening procedure to identify employees at-risk for mental health problems, the model includes a stepped care approach, based on risk stratification, to promote mental health education, management, and follow-up for continuous care. CONCLUSION: The SBIRT model-based intervention provides an easy-to-implement approach for the management of mental health in the workplace. Further studies are required to examine the effectiveness and feasibility of the model.

Mutational evolution after chemotherapy-progression in metastatic colorectal cancer revealed by circulating tumor DNA analysis.

Emerging new mutations after treatment can provide clues to acquired resistant mechanisms. Circulating tumor DNA (ctDNA) sequencing has enabled noninvasive repeated tumor mutational profiling. We aimed to investigate newly emerging mutations in ctDNA after disease progression in metastatic colorectal cancer (mCRC). Blood samples were prospectively collected from mCRC patients receiving palliative chemotherapy before treatment and at radiological evaluations. ctDNA from pretreatment and progressive disease (PD) samples were sequenced with a next-generation sequencing panel targeting 106 genes. A total of 712 samples from 326 patients were analyzed, and 381 pretreatment and PD pairs (163 first-line, 85 second-line and 133 later-line [≥third-line]) were compared. New mutations in PD samples (mean 2.75 mutations/sample) were observed in 49.6% (189/381) of treatments. ctDNA samples from later-line had more baseline mutations (P = .002) and were more likely to have new PD mutations (adjusted odds ratio [OR] 2.27, 95% confidence interval [CI]: 1.40-3.69) compared to first-line. RAS/BRAF wild-type tumors were more likely to develop PD mutations (adjusted OR 1.87, 95% CI: 1.22-2.87), independent of cetuximab treatment. The majority of new PD mutations (68.5%) were minor clones, suggesting an increasing clonal heterogeneity after treatment. Pathways involved by PD mutations differed by the treatment received: MAPK cascade (Gene Ontology [GO]: 0000165) in cetuximab and regulation of kinase activity (GO: 0043549) in regorafenib. The number of mutations revealed by ctDNA sequencing increased during disease progression in mCRC. Clonal heterogeneity increased after chemotherapy progression, and pathways involved were affected by chemotherapy regimens.

Twenty-Five Year Trend Change in the Etiology of Pediatric Invasive Bacterial Infections in Korea, 1996-2020.

BACKGROUND: The coronavirus disease-2019 (COVID-19) pandemic has contributed to the change in the epidemiology of many infectious diseases. This study aimed to establish the pre-pandemic epidemiology of pediatric invasive bacterial infection (IBI). METHODS: A retrospective multicenter-based surveillance for pediatric IBIs has been maintained from 1996 to 2020 in Korea. IBIs caused by eight bacteria (Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pyogenes, Listeria monocytogenes, and Salmonella species) in immunocompetent children > 3 months of age were collected at 29 centers. The annual trend in the proportion of IBIs by each pathogen was analyzed. RESULTS: A total of 2,195 episodes were identified during the 25-year period between 1996 and 2020. S. pneumoniae (42.4%), S. aureus (22.1%), and Salmonella species (21.0%) were common in children 3 to 59 months of age. In children ≥ 5 years of age, S. aureus (58.1%), followed by Salmonella species (14.8%) and S. pneumoniae (12.2%) were common. Excluding the year 2020, there was a trend toward a decrease in the relative proportions of S. pneumoniae (rs = -0.430, P = 0.036), H. influenzae (rs = -0.922, P < 0.001), while trend toward an increase in the relative proportion of S. aureus (rs = 0.850, P < 0.001), S. agalactiae (rs = 0.615, P = 0.001), and S. pyogenes (rs = 0.554, P = 0.005). CONCLUSION: In the proportion of IBIs over a 24-year period between 1996 and 2019, we observed a decreasing trend for S. pneumoniae and H. influenzae and an increasing trend for S. aureus, S. agalactiae, and S. pyogenes in children > 3 months of age. These findings can be used as the baseline data to navigate the trend in the epidemiology of pediatric IBI in the post COVID-19 era.

EBS-seq: enrichment-based method for accurate analysis of 5-hydroxymethylcytosine at single-base resolution.

BACKGROUND: A growing body of research has emphasized 5-hydroxymethylcytosine (5hmC) as an important epigenetic mark. High-resolution methods to detect 5hmC require high sequencing depth and are therefore expensive. Many studies have used enrichment-based methods to detect 5hmC; however, conventional enrichment-based methods have limited resolution. To overcome these limitations, we developed EBS-seq, a cost-efficient method for 5hmC detection with single-base resolution that combines the advantages of high-resolution methods and enrichment-based methods. RESULTS: EBS-seq uses selective labeling of 5hmC, deamination of cytosine and 5-methylcytosine, pull-down of labeled 5hmC, and C-to-T conversion during DNA amplification. Using this method, we profiled 5hmC in HEK293T cells and two colorectal cancer samples. Compared with conventional enrichment-based 5hmC detection, EBS-seq improved 5hmC signals by localizing them at single-base resolution. Furthermore, EBS-seq was able to determine 5hmC levels in CpG-dense regions where distortion of signals can occur, such as CpG islands and CpG shores. Comparing EBS-seq and conventional high-resolution 5hmC detection by ACE-seq, we showed that EBS-seq is more effective at finding 5hmC sites. Using EBS-seq, we found strong associations between gene expression and gene-body 5hmC content in both HEK293T cells and colorectal cancer samples. CONCLUSIONS: EBS-seq is a reliable and cost-efficient method for 5hmC detection because it simultaneously enriches 5hmC-containing DNA fragments and localizes 5hmC signals at single-base resolution. This method is a promising choice for 5hmC detection in challenging clinical samples with low 5hmC levels, such as cancer tissues.

Circulating Tumor DNA Dynamics and Treatment Outcome of Regorafenib in Metastatic Colorectal Cancer.

PURPOSE: Circulating tumor DNA (ctDNA) is emerging as a valuable non-invasive tool to identify tumor heterogeneity and tumor burden. This study investigated ctDNA dynamics in metastatic colorectal cancer patients treated with regorafenib. Materials and Methods: In this prospective biomarker study, plasma cell-free DNA (cfDNA) samples obtained at baseline, at the first response evaluation after 2 cycles of treatment, and at the time of progressive disease were sequenced using a targeted next-generation sequencing platform which included 106 genes. RESULTS: A total of 285 blood samples from 110 patients were analyzed. Higher baseline cfDNA concentration was associated with worse progression-free survival (PFS) and overall survival (OS). After 2 cycles of treatment, variant allele frequency (VAF) in the majority of ctDNA mutations decreased with a mean relative change of -31.6%. Decreases in the VAF of TP53, APC, TCF7L2, and ROS1 after 2 cycles of regorafenib were associated with longer PFS. We used the sum of VAF at each time point as a surrogate for the overall ctDNA burden. A reduction in sum (VAF) of ≥ 50% after 2 cycles was associated with longer PFS (6.1 vs. 2.7 months, p=0.002), OS (11.3 vs. 5.9 months, p=0.001), and higher disease control rate (86.3% vs. 51.1%, p < 0.001). VAF of the majority of the ctDNA mutations increased at the time of disease progression, and VAF of BRAF increased markedly. CONCLUSION: Reduction in ctDNA burden as estimated by sum (VAF) could be used to predict treatment outcome of regorafenib.

Efficacy of Olaparib in Treatment-Refractory, Metastatic Breast Cancer with Uncommon Somatic BRCA Mutations Detected in Circulating Tumor DNA.

Poly(ADP-ribose) polymerase inhibitors have been shown dramatic responses in patients with BRCAness. However, clinical studies have been limited to breast cancer patients with germline mutations. Here, we describe a patient with metastatic breast cancer who had a rare BRCA1 somatic mutation (BRCA1 c.4336G>T (p.E1446*)) detected by cell-free DNA analysis after failing standard therapies. This tier III variant of unknown significance was predicted to be a pathogenic variant in our assessment, leading us to consider off-label treatment with olaparib. The patient responded well to olaparib for several months, with a decrease in allele frequency of this BRCA1 somatic mutation in cell-free DNA. Olaparib resistance subsequently developed with an increase in the allele frequency and new BRCA1 reversion mutations. To our knowledge, this is the first report confirming BRCA1 c.4336G>T (p.E1446*) as a mutation sensitive to olaparib in breast cancer and describing the dynamic changes in the associated mutations using liquid biopsy.

Ferroelectric Domain Wall Engineering Enables Thermal Modulation in PMN-PT Single Crystals.

Acting like thermal resistances, ferroelectric domain walls can be manipulated to realize dynamic modulation of thermal conductivity (k), which is essential for developing novel phononic circuits. Despite the interest, little attention has been paid to achieving room-temperature thermal modulation in bulk materials due to challenges in obtaining a high thermal conductivity switching ratio (khigh /klow ), particularly in commercially viable materials. Here, room-temperature thermal modulation in 2.5 mm-thick Pb(Mg1/3 Nb2/3 )O3 -xPbTiO3 (PMN-xPT) single crystals is demonstrated. With the use of advanced poling conditions, assisted by the systematic study on composition and orientation dependence of PMN-xPT, a range of thermal conductivity switching ratios with a maximum of ≈1.27 is observed. Simultaneous measurements of piezoelectric coefficient (d33 ) to characterize the poling state, domain wall density using polarized light microscopy (PLM), and birefringence change using quantitative PLM reveal that compared to the unpoled state, the domain wall density at intermediate poling states (0< d33

The Prevalence of Symptomatic Congenital Cytomegalovirus Disease in Korea; A 15-Year Multicenter Study and Analysis of Big Data From National Health Insurance System.

The birth prevalence of symptomatic congenital cytomegalovirus (cCMV) disease among live birth in Korea from a multicenter study was 0.06% during 2001-2015 with increasing frequency. The administrative prevalence of cCMV infection by big-data analysis from the national health insurance system was 0.01% and the average healthcare cost was US$2010 per person.

Upconverting nanoparticle-containing erythrocyte-sized hemoglobin microgels that generate heat, oxygen and reactive oxygen species for suppressing hypoxic tumors.

Inspired by erythrocytes that contain oxygen-carrying hemoglobin (Hb) and that exhibit photo-driven activity, we introduce homogenous-sized erythrocyte-like Hb microgel (µGel) systems (5-6 µm) that can (i) emit heat, (ii) supply oxygen, and (iii) generate reactive oxygen species (ROS; 1O2) in response to near-infrared (NIR) laser irradiation. Hb µGels consist of Hb, bovine serum albumin (BSA), chlorin e6 (Ce6) and erbium@lutetium upconverting nanoparticles (UCNPs; ∼35 nm) that effectively convert 808 nm NIR light to 660 nm visible light. These Hb µGels are capable of releasing oxygen to help generate sufficient reactive oxygen species (1O2) from UCNPs/Ce6 under severely hypoxic condition upon NIR stimulation for efficient photodynamic activity. Moreover, the Hb µGels emit heat and increase surface temperature due to NIR light absorption by heme (iron protoporphyrin IX) and display photothermal activity. By changing the Hb/UCNP/Ce6 ratio and controlling the amount of NIR laser irradiation, it is possible to formulate bespoke Hb µGels with either photothermal or photodynamic activity or both in the context of combined therapeutic effect. These Hb µGels effectively suppress highly hypoxic 4T1 cell spheroid growth and xenograft mice tumors in vivo.