Falsiroseomonas oryziterrae sp. nov., and Falsiroseomonas oryzae sp. nov., isolated from rice paddy soil.

Three Gram-stain-negative, aerobic, non-motile and coccobacilli-shaped bacterial strains, designated as NPKOSM-4T, NPKOSM-8 and MO-31T, were isolated from rice paddy soil. They had 96.5-100 % 16S rRNA gene sequence similarity to each other, and strains NPKOSM-4T and NPKOSM-8 showed 100 % 16S rRNA gene sequence similarity, confirming that they were the same species. Comparative analysis of 16S rRNA genes with closely related type strains showed that three isolates were most closely related to Falsiroseomonas terricola EM0302T (96.1-97.8 %), Falsiroseomonas wooponensis WW53T (95.51-96.3 %) and Falsiroseomonas bella CQN31T (96.0-96.5 %), respectively. The genomes of strains NPKOSM-4T and MO-31T consisted of 4 632 875 and 6 455 771 bps, respectively, with 72.0 and 72.1 mol% G+C content. The average nucleotide identity (ANI), average amino acid identity (AAI) and digital DNA-DNA hybridization (dDDH) values between strains NPKOSM-4T and MO-31T and type strains of Falsiroseomonas species were lower than the cut-offs (≥95 % for ANI, ≥95-96 % for AAI and ≥ 70 % for dDDH) required to define a bacterial species. The major fatty acids of strains NPKOSM-4T, NPKOSM-8 and MO-31T were C18 : 1 ω7c and C18 : 1 2-OH (<10 %) and the predominant quinone was Q-10. The polar lipids of strain NPKOSM-4T were identified as diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, one unidentified aminophospholipid and three unidentified aminolipids. The polar lipid profiles of strain MO-31T contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, one unidentified aminolipid and three unidentified lipids. Based on their distinctive phenotypic, phylogenetic, and chemotaxonomic characteristics, strains NPKOSM-4T, NPKOSM-8 and MO-31T are considered to represent two novel species of the genus Falsiroseomonas, for which the names Falsiroseomonas oryziterrae sp. nov. [to accommodate strains NPKOSM-4T (= KACC 22135T=JCM 34745T), NPKOSM-8 (=KACC 22134=JCM 34746)] and Falsiroseomonas oryzae sp. nov. [to accommodate strain MO-31T (= KACC 22465T=JCM 35532T)] are proposed.

Differential response to roflumilast in patients with chronic obstructive pulmonary disease: real-world evidence.

Background: Roflumilast is effective in reducing acute exacerbation in patients with chronic obstructive pulmonary disease (COPD) at high risk of severe exacerbation. Clinical traits related to the benefits of roflumilast need to be evaluated in patients with COPD. Methods: A longitudinal observational study in patients newly diagnosed with COPD was conducted using claims data from the Health Insurance Review and Assessment Service in South Korea from 2012-2020 after a 2-year washout period. The primary outcome was to estimate the ratio of hazard ratio (RHR) of roflumilast for moderate-to-severe exacerbation in prespecified subgroups. A time-dependent Cox regression model was used to estimate the hazard ratio (HR) for moderate-to-severe exacerbations. Results: Among 823,862 patients with COPD, 0.6% used roflumilast. The adjusted HR of roflumilast for moderate-to-severe exacerbations was reduced when treated for ≥3 months (RHR =0.558). Interaction effects of the variables on the HR of roflumilast for moderate-to-severe exacerbation were identified. The adjusted HR of roflumilast for moderate-to-severe exacerbation was significantly reduced in several subgroups: older age (65 years > age ≥50 years, RHR =0.838; age ≥65 years, RHR =0.818), a higher Charlson comorbidity index (1, RHR =0.832; 2, RHR =0.798; ≥3, RHR =0.790), history of exacerbation (RHR =0.886), bronchiectasis (RHR =0.774), chronic bronchitis (RHR =0.793), inhaled therapy [mono-bronchodilator, RHR =0.824; inhaled corticosteroid (ICS)/long-acting beta-agonist (LABA), RHR =0.591; LABA/long-acting muscarinic antagonist (LAMA), RHR =0.822; ICS/LABA/LAMA, RHR =0.570], methylxanthine (RHR =0.853), and statin (RHR =0.888). Conclusions: The benefit of roflumilast in moderate-to-severe exacerbations was estimated to be greater in specific subgroups of patients with COPD. Personalised approaches to roflumilast based on clinical phenotypes would be effective for COPD.

Frailty of Prostate Cancer Patients Receiving Androgen Deprivation Therapy: A Scoping Review.

PURPOSE: This study aimed to explore the existing literature on frailty experienced by patients with prostate cancer (PC) receiving androgen deprivation therapy (ADT). MATERIALS AND METHODS: Database and manual searches were conducted to identify relevant studies published in English, with no limitation on the year of publication, according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines. Four databases-PubMed, Cochrane Library, EMBASE, and CINAHL-were used for database searches and reference lists, related journals, and Google Scholar were used for manual searches. RESULTS: A total of 12 studies were analyzed for this scoping review. Of these, only 2 were intervention studies, and 1 was a randomized controlled trial. Among the two intervention studies, the multidisciplinary intervention program, including psychological counseling, nutritional coaching, and supervised group physical exercise did not show significant improvement in frailty. In contrast, high-dose vitamin D supplementation significantly decreased frailty. The conceptual and operational definitions of frailty used in each study varied, and the most used one was mainly focused on physical functions. As a result of analyzing the other health-related variables associated with frailty in patients with PC receiving ADT, age, metastases, comorbidities, and incident falls were related to a high frailty level. As for the physiological index, high levels of C-reactive protein, and interleukin-6, and fibrinogen, low levels of total testosterone, lymphocyte count, and creatinine were associated with a high level of frailty. A few studies explored the relationship between psychological and cognitive variables and frailty. CONCLUSIONS: Further research related to frailty in patients with PC receiving ADT should be conducted, and effective interventions to manage frailty should be developed. Additionally, research that considers not only the physical domain of frailty but also the psychological, cognitive, and social domains needs to be conducted.

Erythrobacter oryzae sp. nov., isolated from rice paddy soil.

Two novel bacterial strains, designated as COR-2T and CR-8, were isolated from paddy soil. These isolates were aerobic, Gram-stain-negative, non-spore-forming, non-motile, rod-shaped, and formed orange-coloured colonies. Phylogenetic analysis based on 16S rRNA gene sequences showed that two strains formed a clear phylogenetic lineage with the genus Erythrobacter. Strains COR-2T and CR-8 showed 99.9 % 16S rRNA gene sequence similarity. Both strains had the highest 16S rRNA gene similarity of 99.1-99.7 % to Erythrobacter colymbi TPW-24T, Erythrobacter donghaensis SW-132T and Erythrobacter tepidarius DSM 10594T, respectively. The genome of strain COR-2T comprised 3 559 918 bp and the genomic DNA G + C content was 67.7 mol%. The average nucleotide identity and digital DNA-DNA hybridization values between strain COR-2T and its closely related species of the genus Erythrobacter were 79.3-85.5% and 24.1-29.1 %, respectively. The major respiratory quinone was Q-10, while the major fatty acids were C18 : 1 ω7c and C17 : 1 ω6c. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, two unidentified phospholipids and eight unidentified lipids. Based on phylogenetic and phenotypic considerations, the two strains [COR-2T (type strain; = KACC 22941T=JCM 35529T) and CR-8 (= KACC 22945=JCM 35530)] are considered to represent novel species of the genus Erythrobacter, for which the name Erythrobacter oryzae sp. nov. is proposed.

Empirical Characterization of False Discovery Rates of Differentially Expressed Genes and Transcriptomic Benchmark Concentrations in Zebrafish Embryos.

High-throughput transcriptomics (HTTr) is increasingly applied to zebrafish embryos to survey the toxicological effects of environmental chemicals. Before the adoption of this approach in regulatory testing, it is essential to characterize background noise in order to guide experimental designs. We thus empirically quantified the HTTr false discovery rate (FDR) across different embryo pool sizes, sample sizes, and concentration groups for toxicology studies. We exposed zebrafish embryos to 0.1% dimethyl sulfoxide (DMSO) for 5 days. Pools of 1, 5, 10, and 20 embryos were created (n = 24 samples for each pool size). Samples were sequenced on the TempO-Seq platform and then randomly assigned to mock treatment groups before differentially expressed gene (DEG), pathway, and benchmark concentration (BMC) analyses. Given that all samples were treated with DMSO, any significant DEGs, pathways, or BMCs are false positives. As expected, we found decreasing FDRs for DEG and pathway analyses with increasing pool and sample sizes. Similarly, FDRs for BMC analyses decreased with increasing pool size and concentration groups, with more stringent BMC premodel filtering reducing BMC FDRs. Our study provides foundational data for determining appropriate experiment designs for regulatory toxicity testing with HTTr in zebrafish embryos.

Menstrual and psychosocial characteristics associated with high-risk of premenstrual dysphoric disorder among university students: a cross-sectional study.

Up to 92 percent of Chinese women of reproductive age have pre-menstrual syndrome (PMS). The severe form of PMS (i.e. pre-menstrual dysphoric disorder [PMDD]) negatively affects women's everyday functioning and reproductive health. This study examined the relationships between menstrual, psychosocial characteristics and the risk of PMDD among young Chinese women. A cross-sectional online survey was conducted among Chinese university students in Hong Kong. Logistic regression was used to compute adjusted odds ratio (aOR) for the association of high-risk PMDD with menstrual and psychosocial characteristics. A total of 541 Chinese university students were recruited. Approximately 53 percent of female students were at high risk of developing PMDD. The high-risk PMDD group was significantly associated with a heavy volume of menstrual flow (aOR = 2.17, 95 percent CI 1.06-4.45), irregular menstrual cycle (1.72, 1.17-2.52), high dysmenorrhea (2.80, 1.95-4.04) and older ages of menarche (0.67, 0.45-0.98) in the menstrual characteristics. In the psychosocial characteristics, high-risk PMDD was significantly associated with symptoms of anxiety (2.19, 1.48-3.32) and depression (2.22, 1.48-3.32), high loneliness (1.94, 1.34-2.79) and low resilience (2.21, 1.52-3.23) levels. Additionally, resilience had a potential moderating effect on the associations between the high risk of PMDD and anxiety, depression and loneliness. The development and delivery of interventions that can enhance resilience and manage psychological distress would be beneficial for young Chinese women's reproductive health.

FGFR inhibition augments anti-PD-1 efficacy in murine FGFR3-mutant bladder cancer by abrogating immunosuppression.

The combination of targeted therapy with immune checkpoint inhibition (ICI) is an area of intense interest. We studied the interaction of fibroblast growth factor receptor (FGFR) inhibition with ICI in urothelial carcinoma (UC) of the bladder, in which FGFR3 is altered in 50% of cases. Using an FGFR3-driven, Trp53-mutant genetically engineered murine model (UPFL), we demonstrate that UPFL tumors recapitulate the histology and molecular subtype of their FGFR3-altered human counterparts. Additionally, UPFL1 allografts exhibit hyperprogression to ICI associated with an expansion of T regulatory cells (Tregs). Erdafitinib blocked Treg proliferation in vitro, while in vivo ICI-induced Treg expansion was fully abrogated by FGFR inhibition. Combined erdafitinib and ICI resulted in high therapeutic efficacy. In aggregate, our work establishes that, in mice, co-alteration of FGFR3 and Trp53 results in high-grade, non-muscle-invasive UC and presents a previously underappreciated role for FGFR inhibition in blocking ICI-induced Treg expansion.

Persistent Organic Pollutants released from decomposed adipose tissue affect mitochondrial enzyme function in the brain and eyes other than the liver.

Persistent organic pollutants (POPs) are toxic chemicals that can accumulate in the human body, and particularly in adipose tissue. POPs can induce metabolic diseases via mitochondrial dysfunction and can also cause cancer, obesity, and cardiovascular and neurodegenerative diseases. Although the effects of POPs were studied by evaluating mitochondrial function, which is fundamental in investigating the etiologies of various metabolic diseases, the physiological impact of POPs released by the decomposition of fat in adipose tissue is barely understood. Therefore, to investigate the mitochondrial dysfunction caused by POPs released from adipose tissue to other organs, zebrafish were exposed to POPs and placed into four groups: control (C), obesity control (OC), obesity control with POPs (OP), and POP exposure with obesity and caloric restriction (OPR). Next, the activities of the mitochondrial respiratory complexes and the levels of ATP production, reactive oxygen species/reactive nitrogen species (ROS/RNS), and antioxidants, such as glutathione and superoxide dismutase, were measured in the brain, eyes, and liver, as these are the major organs most susceptible to metabolic diseases. POPs released from adipose tissue showed a stronger effect than the direct effects of obesity and POPs on mitochondrial enzyme activity in the brain and eye. Released POPs increased mitochondrial complex I activity and decreased mitochondrial complex II activity compared with normal, obesity, and POP-treated conditions in the brain and eyes. However, the mitochondrial complexes' activities in the liver were affected more by obesity and POPs. In the liver, the mitochondrial enzyme activities of the OPR group seemed to recover to the control level, but it was slightly lowered in the OC and OP groups. Independently, the ROS/RNS and antioxidant levels were not affected by obesity, POPs, or the released POPs in the brain, eye, and liver. The results indicate that POPs stored in adipose tissue and released during fat decomposition did not affect oxidative stress but could affect mitochondrial respiratory enzymes in organ dependent manner. This study is meaningful in that it provides experimental evidence that stored POPs affect specific organs for prolonged periods and can be linked to various diseases in advance.

Immune Activation Modulation via Magnetically Localized Bacteria Based Micro/Bio Robot (BBMBR).

Understanding tumor's microenvironment is one of the key factors in the cancer therapy. Especially, from the perspective of immunotherapy, immune desert or cold tumor is referred as significantly downregulated T cell in-filtration due to lack of immune surveillance in the tumor microenvironment. There are many studies are dedicated to convert cold tumor to hot tumor for enhancing the efficacy of immunotherapy. In this study, we suggested selective immune activation system through the spatiotemporal control of the bacteria as an immune boosting agent. To this end, we have developed bacteria-based micro/bio robot system (BBMBR) by attaching bacteria with magnetic nanoparticles (MNP) so that the localization can be controlled through the magnetic field. The biomanufacturing results showed that BBMBR includes 6.6 ± 1.54 MNP attached and the presence ratio of bacteria-MNP out of total bacteria population reached 75.2 ± 3.37%. Spatial controllability experiments have shown that rotational and translation localization has been controlled as intended. The function of the immune modulation system through BBMBR was confirmed through experiments that magnetically driven BBMBR localization induced localized immune activation. M1-phenotype differentiation of macrophage cells were quantified CD80 staining, and overall immune response level was evaluated through IL-6 measurements. As the distance from the activation point increased, the population of M1 differentiated macrophages decreased, and when the movement of BBMBR was magnetically restricted, overall immune activation was found to be regulated downward. Proposed BBMBR and immune modulation framework could introduce a powerful new paradigm in cancer treatment by improving the localization controllability of immune-boosting agent and the spatial immune activation strategies.

Long Term Effects of a Social Capital-Based Exercise Adherence Intervention for Breast Cancer Survivors With Moderate Fatigue: A Randomized Controlled Trial.

OBJECTIVES: This study reports on the long-term effects of the Better Life After Cancer: Energy, Strength, and Support (BLESS) program, a 12-week social capital-based exercise adherence program for breast cancer survivors (BCS), implemented using a randomized controlled trial design. The study investigated outcomes related to cancer-related fatigue (CRF), quality of life (QOL), physical activity, depression, anxiety, sleep quality, and social capital. METHODS: Participants who had moderate or greater CRF were randomly assigned to the intervention (n = 24), consisting of supervised and home-based exercise, or the control (n = 26), who received exercise leaflets. Generalized estimating equations models were fitted for the outcome variables. The assessment points were baseline (M1), immediately after completing the intervention at 12 weeks (M2), 1 month (M3), and 6 months post-intervention (M4). RESULTS: A significant reduction in the total CRF score was found for both groups. We observed a significant time by group effect at M2, indicating a reduction of behavioral/severity CRF scores and a higher increase of physical activity. Also, there was an increase in the QOL score of both groups at M2, M3, and M4, compared to M1. Both groups had reduced anxiety at M3 and M4 compared to M1. The time by group effect for depression, sleep quality and social capital was not statistically significant. CONCLUSION: This 12-week exercise adherence program improved behavioral/severity CRF and physical activity post-intervention. Both the experimental group and control group showed significant improvements in CRF, QOL, and anxiety domains compared to the baseline, which extended to 6 months post-intervention. TRIAL REGISTRATION: Korean Clinical Research Information Service (KCT0005763).

Abdominal aortic calcification in patients newly diagnosed with essential thrombocythemia.

Background: Although atherosclerosis is likely to be involved in the development of arterial thrombotic events in patients with essential thrombocythemia (ET), abdominal aortic calcification (AAC) has rarely been investigated. We evaluated the prevalence and clinical relevance of AAC at the time of ET diagnosis. Methods: This retrospective study included patients newly diagnosed with ET who underwent abdominal computed tomography (CT) at the time of diagnosis between January 2002 and December 2021 at Chungnam National University Hospital, Daejeon, Korea. CT images were reviewed and an aortic calcification score was assigned. Results: Of the 94 patients (median age, 62 yr; range, 18‒90 yr), AAC was detected in 62 (66.0%). AAC was most commonly mild (33.0%), followed by moderate (22.7%) and severe (5.3%). Old age [odds ratio (OR), 34.37; 95% confidence interval (CI), 12.32‒95.91; P＜0.001] was an independent risk factor for AAC. The patients with AAC had a higher WBC count (11.8±4.7 vs. 9.7±2.9×109/L, P=0.017), higher neutrophil-to-lymphocyte ratio (4.3±2.7 vs. 3.1±1.5, P=0.039), and higher JAK2V617F positivity (81.5% vs. 58.8%, P=0.020) compared to those without AAC. AAC was an independent risk factor for arterial thrombotic vascular events that occurred before or at diagnosis of ET (OR, 4.12; 95% CI, 1.11‒15.85; P=0.034). Conclusion: AAC is common in patients with ET and is associated with arterial thrombotic events.

Oryzibacter oryziterrae gen. nov., sp. nov., isolated from rice paddy soil.

A novel Gram-stain-negative, aerobic, motile and pleomorphic rod-shaped bacterial strain, designated COJ-58T, was isolated from rice paddy soil. Strain COJ-58T grew optimally at 20-30 °C, at pH 5.0-8.0 and with 0-1.0 % (w/v) NaCl. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain COJ-58T forms a distinct lineage within the family Pleomorphomonadaceae, with highest similarity to Pleomorphomonas carboxyditropha SVCO-16T (95.9 %), Pleomorphomonas koreensis Y9T (95.8 %), Pleomorphomonas oryzae F-7T (95.7 %) and Pleomorphomonas diazotrophica R5-392T (95.6 %), respectively. The average nucleotide identity, digital DNA-DNA hybridization, average amino acid identity and percentage of conserved proteins values between the genomes of strain COJ-58T and its closely related taxa are ≤77.2 %, ≤21.6 %, ≤68.3 % and ≤61.3 %, respectively. The genome size of strain COJ-58T is 4.9 Mb and the genomic DNA G + C content is 63.7 mol%. The major fatty acids are C18 : 1 ω7c, C16 : 0 and summed feature 2 (C14 : 0 3-OH and/or iso-C16 : 1 I). The differential phenotypic and genotypic characteristics of strain COJ-58T indicate that it represents a novel genus and species, for which the name Oryzibacter oryziterrae gen. nov., sp. nov. is proposed, with strain COJ-58T (=KACC 22108T=JCM 34744T) as the type strain.

A Water-Resistant, Self-Healing Encapsulation Layer for a Stable, Implantable Wireless Antenna.

Polymers for implantable devices are desirable for biomedical engineering applications. This study introduces a water-resistant, self-healing fluoroelastomer (SHFE) as an encapsulation material for antennas. The SHFE exhibits a tissue-like modulus (approximately 0.4 MPa), stretchability (at least 450%, even after self-healing in an underwater environment), self-healability, and water resistance (WVTR result: 17.8610 g m-2 day-1). Further, the SHFE is self-healing in underwater environments via dipole-dipole interactions, such that devices can be protected from the penetration of biofluids and withstand external damage. With the combination of the SHFE and antennas designed to operate inside the body, we fabricated implantable, wireless antennas that can transmit information from inside the body to a reader coil that is outside. For antennas designed considering the dielectric constant, the uniformity of the encapsulation layer is crucial. A uniform and homogeneous interface is formed by simply overlapping two films. This study demonstrated the possibility of wireless communication in vivo through experiments on rodents for 4 weeks, maintaining the maximum communication distance (15 mm) without chemical or physical deformation in the SHFE layer. This study illustrates the applicability of fluoroelastomers in vivo and is expected to contribute to realizing the stable operation of high-performance implantable devices.

Association between successful weaning from nasogastric tube feeding and thoracic muscle mass in patients with aspiration pneumonia.

Nasogastric tube feeding is often used to provide optimal nutrition and hydration in patients with aspiration pneumonia. However, evidence regarding radiologic indicators for successful nasogastric tube weaning is lacking. We investigated whether thoracic skeletal muscle assessment can be useful for predicting successful weaning from nasogastric tube feeding in patients with aspiration pneumonia. This longitudinal, observational study included subjects with aspiration pneumonia who underwent a videofluoroscopic swallowing study (VFSS) and chest computed tomography (CT) in Boramae Medical Center, from January 2012 to December 2019. We estimated the area under the receiver operating characteristics curve (AUC) to evaluate the predictive performance of skeletal muscle and visceral fat parameters and VFSS results for successful weaning from nasogastric tube feeding. A board-certified radiologist measured muscle and fat areas. Muscle and fat volumes were segmented and measured using an externally validated convolutional neural network model. Among the 146 included patients, nasogastric tube feeding was successfully transitioned to oral feeding in 46.6%. After adjusting for covariables related to successful weaning, skeletal muscle areas, indices, and volume indices were positively associated with successful nasogastric tube weaning. Although VFSS results and skeletal muscle parameters alone showed suboptimal performance for predicting successful weaning, a prediction model combining skeletal muscle index at the T4 level and VFSS results improved the prediction performance to an acceptable level (AUC ≥ 0.7). Skeletal muscle index measured at the T4 level may be a useful supplementary indicator for predicting successful weaning from nasogastric tube feeding in patients with aspiration pneumonia.

Microbiota dysbiosis associated with type 2 diabetes-like effects caused by chronic exposure to a mixture of chlorinated persistent organic pollutants in zebrafish.

Mixtures of chlorinated persistent organic pollutants (C-POPs-Mix) are chemically related risk factors for type 2 diabetes mellitus (T2DM); however, the effects of chronic exposure to C-POPs-Mix on microbial dysbiosis remain poorly understood. Herein, male and female zebrafish were exposed to C-POPs-Mix at a 1:1 ratio of five organochlorine pesticides and Aroclor 1254 at concentrations of 0.02, 0.1, and 0.5 µg/L for 12 weeks. We measured T2DM indicators in blood and profiled microbial abundance and richness in the gut as well as transcriptomic and metabolomic alterations in the liver. Exposure to C-POPs-Mix significantly increased blood glucose levels while decreasing the abundance and alpha diversity of microbial communities only in females at concentrations of 0.02 and 0.1 µg/L. The majorly identified microbial contributors to microbial dysbiosis were Bosea minatitlanensis, Rhizobium tibeticum, Bifidobacterium catenulatum, Bifidobacterium adolescentis, and Collinsella aerofaciens. PICRUSt results suggested that altered pathways were associated with glucose and lipid production and inflammation, which are linked to changes in the transcriptome and metabolome of the zebrafish liver. Metagenomics outcomes revealed close relationships between intestinal and liver disruptions to T2DM-related molecular pathways. Thus, microbial dysbiosis in T2DM-triggered zebrafish occurred as a result of chronic exposure to C-POPs-Mix, indicating strong host-microbiome interactions.

Immune response enhancement with GLS-5310 DNA primary vaccine against SARS-CoV-2 followed by administration of an mRNA vaccine heterologous boost.

Heterologous boost regimens are being increasingly considered against SARS-CoV-2. We report results for the 32 of 45 participants in the Phase 1 CoV2-001 clinical trial (Kim et al., Int J Iinfect Dis 2023, 128:112-120) who elected to receive an EUA-approved SARS-CoV-2 mRNA vaccine 6 to 8 months following a two-dose primary vaccination with the GLS-5310 bi-cistronic DNA vaccine given intradermally and followed by application of suction using the GeneDerm device. Receipt of EUA-approved mRNA vaccines after GLS-5310 vaccination was well-tolerated, with no reported adverse events. Immune responses were enhanced such that binding antibody titers, neutralizing antibody titers, and T-cell responses increased 1,187-fold, 110-fold, and 2.9-fold, respectively. This paper is the first description of the immune responses following heterologous vaccination with a DNA primary series and mRNA boost.

Integrative multi-omics reveals analogous developmental neurotoxicity mechanisms between perfluorobutanesulfonic acid and perfluorooctanesulfonic acid in zebrafish.

The molecular mechanism of perfluorobutanesulfonic acid (PFBS), an alternative to legacy perfluorooctanesulfonic acid (PFOS), is not fully understood yet. Therefore, we conducted a developmental toxicity evaluation on zebrafish embryos exposed to PFBS and PFOS and assessed neurobehavioral changes at concentrations below each point of departure (POD) determined by embryonic mortality. Using transcriptomics, proteomics, and metabolomics, biomolecular perturbations in response to PFBS were profiled and then integrated for comparison with those for PFOS. Although PFBS (7525.47 µM POD) was approximately 700 times less toxic than PFOS (11.42 µM POD), altered neurobehavior patterns and affected kinds of endogenous neurochemicals were similar between PFBS and PFOS at the corresponding POD-based concentrations. Multi-omics analysis revealed that the PFBS neurotoxicity mechanism was associated with oxidative stress, lipid metabolism, and glycolysis/glucogenesis. The commonalities in developmental neurotoxicity-related mechanisms between PFBS and PFOS interconnected by knowledge-based integration of multi-omics included the calcium signaling pathway, lipid homeostasis, and primary bile acid biosynthesis. Despite being less toxic than PFOS, PFBS exhibited similar dysregulated molecular mechanisms, suggesting that chain length differences do not affect the intrinsic toxicity mechanism. Overall, carefully managing potential toxicity of PFBS can secure its status as an alternative to PFOS.

DNA Vaccines for Epidemic Preparedness: SARS-CoV-2 and Beyond.

We highlight the significant progress in developing DNA vaccines during the SARS-CoV-2 pandemic. Specifically, we provide a comprehensive review of the DNA vaccines that have progressed to Phase 2 testing or beyond, including those that have received authorization for use. DNA vaccines have significant advantages with regard to the rapidity of production, thermostability, safety profile, and cellular immune responses. Based on user needs and cost, we compare the three devices used in the SARS-CoV-2 clinical trials. Of the three devices, the GeneDerm suction device offers numerous benefits, particularly for international vaccination campaigns. As such, DNA vaccines represent a promising option for future pandemics.

A Study on 'Insul (An Art of Benevolence)': Formation of Korean Medical Ethics in Modern Korea.

"Medicine is an art of benevolence [Kr. 인술 Insul, Ch. Renshu]." This slogan is widely accepted in East Asia, and at least in South Korea, it is generally regarded as an innate medical ethic. However, the original meaning of 'In' (Ch. Ren), which means 'benevolence,' 'humanity,' or simply 'love for one another,' is a Confucian virtue emphasized by Mencius. It is unclear when this Confucian term became the representative medical ethic in South Korea. The term "medical ethic" was not coined until the 19th century in the West (Robert Baker and Laurence B. McCullough, eds. 2009). We often use the terms 'Insul,' 'affection,' 'Hippocratic Oath,' and other related concepts interchangeably, but these words come from different times and have different ideological implications (Shin 2000). This paper examines how 'Insul' has been recreated under the tensions between Western and Eastern Medicine in modern Korea. The arrival of Western medicine caused an existential crisis in traditional Korean medicine. The status of TKM doctors was demoted by the 'Uisaeng Regulation' in 1913 by the JGGK, which aimed to establish a unicameral medical system based on Western medicine. In response, the scientification of Eastern medicine became an inevitable task, and Eastern medicine had to maintain its identity while also modernizing itself to avoid being absorbed into Western medicine. Until the late Joseon period, 'Insul' was rarely used in medicine but rather for political practices. Medical practice was a peripheral way of conducting Ren, the Confucian benevolence. However, TKM rediscovered the concept during the modern era. With the Convention of Korean Uisaeng in October 1915, the TKM community actively used 'Insul' as their identity. At this convention, Governor General Terauchi Mastake used the term to mean traditional medicine and implied that without scientification, 'Insul' would be disused. This address was immediately and widely quoted in TKM journals. TKM doctors and adherents interpreted his address to mean that if they could achieve scientification of TKM, their medical ideal (Insul) would be used in the future. Soon, a number of articles on 'Insul' as a medical ethic were published in newspapers and journals. From the mid-1920s, regardless of whether the doctors practiced East or West medicine, people started to claim that only those who pursued 'Insul' were true medical personnel, and they used this as a criterion for evaluating medical doctors. The people's demand for 'Insul' influenced medicine in general, and Western doctors also linked their medical practices to 'Insul.' This is an interesting example of the localization of Western medicine in Korea. Through the rivalry relationship or interaction between East and West medicine that took place in modern Korea, 'Insul' gradually became a representative term of Korean medical ethics since the mid-1920s. The process took place gradually over a decade, and it has now become firmly established throughout medicine in Korea.

Battery-Free, Wireless, Cuff-Type, Multimodal Physical Sensor for Continuous Temperature and Strain Monitoring of Nerve.

Peripheral nerve injuries cause various disabilities related to loss of motor and sensory functions. The treatment of these injuries typically requires surgical operations for improving functional recovery of the nerve. However, capabilities for continuous nerve monitoring remain a challenge. Herein, a battery-free, wireless, cuff-type, implantable, multimodal physical sensing platform for continuous in vivo monitoring of temperature and strain from the injured nerve is introduced. The thin, soft temperature, and strain sensors wrapped around the nerve exhibit good sensitivity, excellent stability, high linearity, and minimum hysteresis in relevant ranges. In particular, the strain sensor integrated with circuits for temperature compensation provides reliable, accurate strain monitoring with negligible temperature dependence. The system enables power harvesting and data communication to wireless, multiple implanted devices wrapped around the nerve. Experimental evaluations, verified by numerical simulations, with animal tests, demonstrate the feasibility and stability of the sensor system, which has great potential for continuous in vivo nerve monitoring from an early stage to complete regeneration.