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Abstract The prevalence and dynamics of circulating tumor DNA (ctDNA) in patients with breast cancer recurrence or de novo metastatic cancer were examined in a retrospective analysis of a prospective observational cohort. Twenty-three recurrent/metastatic breast cancer cases (8 locoregional, 15 distant metastasis) were enrolled, and sequential plasma samples were obtained. Anchor mutations were selected from the target sequencing of each patient’s primary and/or metastatic tumor. An in-house developed assay (UHS assay) was employed for a tumor-informed ctDNA assay during treatment and follow-up. A median of three (range 1–5) anchor mutations per case were applied for ctDNA detection. ctDNA was detected in 14 (63.6%, 14/22) cases at the time of enrollment and 18 (78.5%, 18/23) cases during follow-up. More anchor mutations and higher tumor burden were significantly related to higher ctDNA positive rates (p-value 0.036, 0.043, respectively). The mean enriched variant allele frequency (eVAF) at each time point was significantly higher for stable or progressive disease responses (ANOVA test p-value

Purpose: Germline mutations in DNA damage repair (DDR) genes such as BRCA2 have been associated with prostate cancer (PC) risk but has not been thoroughly evaluated for metastatic prostate cancer (mPC) in Asian men. This study attempts to evaluate frequency of DDR mutations in the largest cohort of Koreans. Materials and Methods: We recruited 340 patients with mPC unselected for family history of cancer and compared to 495 controls. Whole genome sequencing was applied to assess germline pathogenic/likely pathogenic variants (PV/LPVs) in 26 DDR genes and HOXB13, including 7 genes (ATM, BRCA1/2, CHEK2, BRIP1, PALB2, and NBN) associated with hereditary PC. Comparisons to published Caucasian and Japanese cohorts were performed. Results: Total of 28 PV/LPVs were identified in 30 (8.8%) patients; mutations were found in 13 genes, including BRCA2 (15 men [4.41%]), ATM (2 men [0.59%]), NBN (2 men [0.59%], and BRIP1 (2 men [0.59%]). Only one patient had HOXB13 mutation (0.29%). A lower rate of overall germline variant frequency was observed in Korean mPC compared to Caucasians (8.8% vs. 11.8%), but individual variants notably differed from Caucasian and geographically similar Japanese cohorts. PV/ LPVs in DDR genes tended to increase gradually with higher Gleason scores (GS 7, 7.1%; GS 8, 7.5%; GS 9–10, 9.9%). Conclusions: BRCA2 was the most frequently mutated gene common to different cohorts supporting its importance, but differences in variant distribution in Korean mPC underscore the need for ethnic-specific genetic models. Future ethnic-specific analyses are warranted to verify our findings.

Abstract We investigated the efficacy of intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents in branch retinal vein occlusion (BRVO). Databases, including PubMed, EMBASE, and the Cochrane Library, were searched on November 11, 2022. Studies comparing the pro-re-nata (PRN) regimen after the first treatment (PRN group) to three consecutive monthly injection regimens followed by the PRN regimen (3 + PRN group) were investigated. The primary outcomes were the change in best-corrected visual acuity (BCVA) and the change in central retinal thickness (CRT), with the secondary outcome being the injection frequency. Among 195 reports on anti-VEGF treatment, six comparative studies were included in this meta-analysis. The two groups had no statistically significant differences in terms of BCVA or CRT. However, the total number of injections during follow-up was significantly lower in the PRN group than in the 3 + PRN group (95% CI − 2.09 to − 0.83). The as-needed injection regimen is as effective as 3-monthly loading in terms of anatomical and functional improvement for BRVO, along with a lower treatment burden for patients and physicians.

AbstractPurpose We sought to evaluate the expression of matrix metalloproteinase-9 (MMP-9) in dry eyes treated with 0.05% cyclosporin A and 3.0% diquafosol tetrasodium.Methods One-hundred ninety-five eyes of 195 patients with dry eye were divided into three groups as follows: group 1, cyclosporin group (n = 69); group 2, diquafosol group (n = 59); and group 3, artificial tears eyes (n = 67). All eyes were treated and followed up for three months. Schirmer I Test, corneal staining, tear-film break-up time (TBUT), and tear-film MMP-9 content were measured at three months and compared between groups. The expression of MMP-9 was confirmed using a point-of-care test device (InflammaDry®; RPS Diagnostics, Sarasota, FL, USA) and graded as zero to four points.Results At the third month, MMP-9 expression was lower in group 1 as compared with in groups 2 and 3 (p = 0.020 and 0.006, respectively). The mean MMP-9 grade according to point-of-care testing was also lower in group 1 than in groups 2 or 3 (p = 0.002 and 0.038, respectively). MMP-9 showed a correlation with corneal staining in both groups 1 and 2 (all p

Parkinson’s disease: genetic risk factors in a Korean population A whole-genome sequencing study of Korean individuals with Parkinson’s disease (PD) has identified several new genetic risk factors, ranging from single nucleotide variations (SNVs) to larger DNA deletions. PD is the second most prevalent neurodegenerative disease globally, but most studies have focused on SNVs in European populations. Using whole-genome sequencing, Ji-Hye Oh at the University of Ulsan, Seoul, South Korea, and co-workers were able to identify genetic differences between PD patients and healthy controls, including deletions, gains, and several new SNVs. In particular, deletions of small non-coding regions that regulate gene expression may be key contributors to PD. These results provide a whole-genome perspective on genetic risk factors for PD in a Korean population, and illuminate how a whole-genome sequencing approach may be helpful in identifying genetic factors underlying other diseases.

Genome editing: Novel editors for CRISPR-Cas9 technology Tiny genome editors that can fit inside a single delivery system could potentially improve the efficiency and specificity of the editing technology known as CRISPR-Cas9. This technology is used to edit parts of the genome and shows promise for disease therapeutics. Cas9 is a bacterial enzyme that acts as molecular scissors to edit DNA and is guided to the correct DNA region by specific RNA segments (gRNAs). Yongsub Kim at the University of Ulsan in Seoul, South Korea, and co-workers used one of the smallest known Cas9 enzymes, sourced from Campylobactor jejuni, to create two ‘base editors’ (BEs), capable of specific base substitutions. Results suggest the BEs are highly efficient, covering more potential targets than previous Cas9-based BEs. One of the BEs can be packaged, alongside two gRNAs, into a single viral vector for targeted delivery.

Objective To evaluate the clinical usefulness of the Korean Developmental Screening Test (K-DST) via comparison with Korean Ages and Stages Questionnaire (K-ASQ) for the diagnosis of developmental delay in pediatric patients. Methods The K-DST and K-ASQ were used to screen pediatric patients who visited the hospital for evaluation and diagnosis of delayed development. Korean Bayley Scales of Infant Development-II (K-BSID-II) or Korean Wechsler Preschool and Primary Scale of Intelligence III (K-WPPSI-III) were used for the standardized assessment. Moreover, the final clinical diagnosis was confirmed by three expert physicians (rehabilitation doctor, psychiatrist, and neurologist). The sensitivity and specificity of each screening tool for the final diagnosis were investigated and correlated with standardized assessments. Results A total of 145 pediatric consultations were conducted, which included 123 developmental disorders (40 autism spectrum disorders, 46 global developmental delay/intellectual disability, and 37 developmental language disorders) and another 22 that were not associated with any such disorders. The sensitivity and specificity of K-DST based on the final clinical diagnosis were 82.9% and 90.9%, respectively, which were not significantly different from that of K-ASQ (83.7% and 77.3%). Both K-DST and K-ASQ showed good correlation with K-BSID-II and K-WPPSI-III. No significant difference was found between the K-DST and K-ASQ measures. Conclusion K-DST is an excellent screening tool and is expected to replace K-ASQ with high validity.

Objective To investigate the disability registration state of children with cerebral palsy (CP) in Korea. Methods Based on the National Health Information Database, the disability registration state was examined for brain lesion disability and other possible complicated disabilities accompanying brain disorder in children diagnosed with CP aged up to 5 years old who were born between 2002 and 2008. Results Of children diagnosed with CP, 73.1% were registered as having brain lesion disability for the first time before they turned 2 years old. The younger the children, the more likely they will have 1st and 2nd degree disability. However, when the age of children is increased, such likelihood is decreased. The percentage of children registered as having overlapping disabilities was 7%–20%. Conclusion It is important to establish a more accurate standard to rate disability and provide national support systems for children with CP with various severities and multiple disabilities. By reorganizing the current disability registration system for pediatric brain lesions, the system could serve as a classification standard to provide medical and social welfare services.

Objective To investigate rehabilitation treatment cost of patients with cerebral palsy (CP) according to age. Methods We analyzed the cost of rehabilitation treatment from 2007 to 2013 for patients diagnosed with CP by sourcing data from the National Health Information Database. Results While the number of recently born children requiring rehabilitation treatment has decreased, the number of patients requiring this treatment in other age groups has gradually increased. In addition, annual physical therapy, occupational therapy, hydrotherapy, and botulinum toxin injection treatment costs per person have increased. On the other hand, the number of orthopedic surgeries and selective dorsal rhizotomy performed has decreased. Conclusion This study investigated trends in the cost of treatment for patients with CP. This study can be used as a basis to provide treatment support for patients with CP.

Major non-legume crops can form beneficial associations with nitrogen-fixing bacteria like Azospirillum brasilense. Our current understanding of the molecular aspects and signaling that occur between important crops like rice and these nitrogen-fixing bacteria is limited. In this study, we used an experimental system where the bacteria could colonize the plant roots and promote plant growth in wild type rice and symbiotic mutants (dmi3 and pollux) in rice. Our data suggest that plant growth promotion and root penetration is not dependent on these genes. We then used this colonization model to identify regulation of gene expression at two different time points during this interaction: at 1day post inoculation (dpi), we identified 1622 differentially expressed genes (DEGs) in rice roots, and at 14dpi, we identified 1995 DEGs. We performed a comprehensive data mining to classify the DEGs into the categories of transcription factors (TFs), protein kinases (PKs), and transporters (TRs). Several of these DEGs encode proteins that are involved in the flavonoid biosynthetic pathway, defense, and hormone signaling pathways. We identified genes that are involved in nitrate and sugar transport and are also implicated to play a role in other plant-microbe interactions. Overall, findings from this study will serve as an excellent resource to characterize the host genetic pathway controlling the interactions between non-legumes and beneficial bacteria which can have long-term implications towards sustainably improving agriculture.

As the first step to discover protein disease biomarkers from saliva, global analyses of the saliva proteome have been carried out since the early 2000s, and more than 3,000 proteins have been identified in human saliva. Recently, ethnic differences in the human plasma proteome have been reported, but such corresponding studies on human saliva in this aspect have not been previously reported. Thus, here, in order to determine ethnic differences in the human saliva proteome, a Korean whole saliva (WS) proteome catalogue indexing 480 proteins was built and characterized through nLC-Q-IMS-TOF analyses of WS samples collected from eleven healthy South Korean male adult volunteers for the first time. Identification of 226 distinct Korean WS proteins, not observed in the integrated human saliva protein dataset, and significant gene ontology distribution differences in the Korean WS proteome compared to the integrated human saliva proteome strongly support ethnic differences in the human saliva proteome. Additionally, the potential value of ethnicity-specific human saliva proteins as biomarkers for diseases highly prevalent in that ethnic group was confirmed by finding 35 distinct Korean WS proteins likely to be associated with the top 10 deadliest diseases in South Korea. Finally, the present Korean WS protein list can serve as the first level reference for future proteomic studies including disease biomarker studies on Korean saliva.

BACKGROUND AND OBJECTIVE: Menopause is the cessation of ovarian activity and anxiety is one of its symptoms. Many studies show that anxiety is due to decreased estrogen levels after menopause. Since phytoestrogens are plant sterols that are similar to estrogen in structure and function, so the present study was done to evaluate the effect of vitex agnus castus, which has high levels of phytoestrogen on anxiety in ovariectomized rats and compare its effect with estrogen and tamoxifen.METHODS: In this experimental study thirty-five female Wistar rats (150 to 200g) were divided into five groups as following: control group, Vitex agnus castus at the dose of 80 mg/kg, Vitex agnus castus at the dose of 8 mg/kg, Estradiol valerat at the dose of 40µg/kg, and the combination of tamoxifen (100 mg/kg) and herbal extract (80mg/kg). All animals were ovariectomized by cauterizing ovaries through bilateral incisions under anesthesia. After two months, anxiety-related indices (% OAE) and (% OAT) was determined using elevated plus-maze test of anxiety for 5 minutes.FINDINGS: Compared to the control group (21.67%±3.47%), Vitex agnus castus extract at the dose of 8 mg/kg (36%±7.34%) or 80 mg/kg (48.61%±1.25) (p

Skin aging is a multisystem degenerative process caused by several factors, such as, UV irradiation, stress, and smoke. Furthermore, wrinkle formation is a striking feature of photoaging and is associated with oxidative stress and inflammatory response. In the present study, we investigated whether caffeic acid, S-allyl cysteine, and uracil, which were isolated from garlic, modulate UVB-induced wrinkle formation and effect the expression of matrix-metalloproteinase (MMP) and NF-κB signaling. The results obtained showed that all three compounds significantly inhibited the degradation of type І procollagen and the expressions of MMPs in vivo and attenuated the histological collagen fiber disorder and oxidative stress in vivo. Furthermore, caffeic acid and S-allyl cysteine were found to decrease oxidative stress and inflammation by modulating the activities of NF-κB and AP-1, and uracil exhibited an indirect anti-oxidant effect by suppressing cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expressions levels and downregulating transcriptional factors. These results suggest that the anti-wrinkle effects of caffeic acid, S-allyl cysteine, and uracil are due to anti-oxidant and/or anti-inflammatory effects. Summarizing, caffeic acid, S-allyl cysteine, and uracil inhibited UVB-induced wrinkle formation by modulating MMP via NF-κB signaling.