ZNF212 promotes genomic integrity through direct interaction with TRAIP.

TRAIP is a key factor involved in the DNA damage response (DDR), homologous recombination (HR) and DNA interstrand crosslink (ICL) repair. However, the exact functions of TRAIP in these processes in mammalian cells are not fully understood. Here we identify the zinc finger protein 212, ZNF212, as a novel binding partner for TRAIP and find that ZNF212 colocalizes with sites of DNA damage. The recruitment of TRAIP or ZNF212 to sites of DNA damage is mutually interdependent. We show that depletion of ZNF212 causes defects in the DDR and HR-mediated repair in a manner epistatic to TRAIP. In addition, an epistatic analysis of Zfp212, the mouse homolog of human ZNF212, in mouse embryonic stem cells (mESCs), shows that it appears to act upstream of both the Neil3 and Fanconi anemia (FA) pathways of ICLs repair. We find that human ZNF212 interacted directly with NEIL3 and promotes its recruitment to ICL lesions. Collectively, our findings identify ZNF212 as a new factor involved in the DDR, HR-mediated repair and ICL repair though direct interaction with TRAIP.

Elucidation of molecular basis of osteolytic bone lesions in advanced multiple myeloma.

Osteolytic bone lesion is a major cause of lower quality of life and poor prognosis in patients with multiple myeloma (MM), but molecular pathogenesis of the osteolytic process in MM remains elusive. Fms-like tyrosine kinase 3 ligand (FLT3L) was reported to be elevated in bone marrow (BM) and blood of patients with advanced MM who often show osteolysis. Here, we investigated a functional link of FLT3L to osteolytic process in MM. We recruited 86, 306, and 52 patients with MM, acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL), respectively. FLT3L levels of patients with hematologic malignancies were measured in BM-derived plasma and found to be significantly higher in MM than in AML or ALL, which rarely show osteolysis. FLT3L levels were further elevated in MM patients with bone lesion compared with patients without bone lesion. In vitro cell-based assays showed that the administration of FLT3L to HEK293T, HeLa, and U2OS cells led to an increase in the DKK1 transcript level through STAT3 phosphorylation at tyrosine 705. WNT reporter assay showed that FLT3L treatment reduced WNT signaling and nuclear translocation of ß-catenin. These results collectively show that the FLT3L-STAT3-DKK1 pathway inhibits WNT signaling-mediated bone formation in MM, which can cause osteolytic bone lesion. Finally, transcriptomic profiles revealed that FLT3L and DKK1 were predominantly elevated in the hyperdiploidy subtype of MM. Taken together, FLT3L can serve as a promising biomarker for predicting osteolytic bone lesion and also a potential therapeutic target to prohibit the progression of the osteolytic process in MM with hyperdiploidy.

PWWP2B promotes DNA end resection and homologous recombination.

Genome instability is one of the leading causes of gastric cancers. However, the mutational landscape of driver genes in gastric cancer is poorly understood. Here, we investigate somatic mutations in 25 Korean gastric adenocarcinoma patients using whole-exome sequencing and show that PWWP2B is one of the most frequently mutated genes. PWWP2B mutation correlates with lower cancer patient survival. We find that PWWP2B has a role in DNA double-strand break repair. As a nuclear protein, PWWP2B moves to sites of DNA damage through its interaction with UHRF1. Depletion of PWWP2B enhances cellular sensitivity to ionizing radiation (IR) and impairs IR-induced foci formation of RAD51. PWWP2B interacts with MRE11 and participates in homologous recombination via promoting DNA end-resection. Taken together, our data show that PWWP2B facilitates the recruitment of DNA repair machinery to sites of DNA damage and promotes HR-mediated DNA double-strand break repair. Impaired PWWP2B function might thus cause genome instability and promote gastric cancer development.

Nutrient effects on drought responses vary across common temperate grassland species.

Drought and nutrient input are two main global change drivers that threaten ecosystem function and services. Resolving the interactive effects of human-induced stressors on individual species is necessary to improve our understanding of community and ecosystem responses. This study comparatively assessed how different nutrient conditions affect whole-plant drought responses across 13 common temperate grassland species. We conducted a fully factorial drought-fertilization experiment to examine the effect of nutrient addition [nitrogen (N), phosphorus (P), and combined NP] on species' drought survival, and on drought resistance of growth as well as drought legacy effects. Drought had an overall negative effect on survival and growth, and the adverse drought effects extended into the next growing season. Neither drought resistance nor legacy effects exhibited an overall effect of nutrients. Instead, both the size and the direction of the effects differed strongly among species and between nutrient conditions. Consistently, species performance ranking under drought changed with nitrogen availability. The idiosyncratic responses of species to drought under different nutrient conditions may underlie the seemingly contradicting effects of drought in studies on grassland composition and productivity along nutrient and land-use gradients-ranging from amplifying to dampening. Differential species' responses to combinations of nutrients and drought, as observed in our study, complicate predictions of community and ecosystem responses to climate and land-use changes. Moreover, they highlight the urgent need for an improved understanding of the mechanisms that render species more or less vulnerable to drought under different nutrients.

Hypomorphic Mutations in TONSL Cause SPONASTRIME Dysplasia.

SPONASTRIME dysplasia is a rare, recessive skeletal dysplasia characterized by short stature, facial dysmorphism, and aberrant radiographic findings of the spine and long bone metaphysis. No causative genetic alterations for SPONASTRIME dysplasia have yet been determined. Using whole-exome sequencing (WES), we identified bi-allelic TONSL mutations in 10 of 13 individuals with SPONASTRIME dysplasia. TONSL is a multi-domain scaffold protein that interacts with DNA replication and repair factors and which plays critical roles in resistance to replication stress and the maintenance of genome integrity. We show here that cellular defects in dermal fibroblasts from affected individuals are complemented by the expression of wild-type TONSL. In addition, in vitro cell-based assays and in silico analyses of TONSL structure support the pathogenicity of those TONSL variants. Intriguingly, a knock-in (KI) Tonsl mouse model leads to embryonic lethality, implying the physiological importance of TONSL. Overall, these findings indicate that genetic variants resulting in reduced function of TONSL cause SPONASTRIME dysplasia and highlight the importance of TONSL in embryonic development and postnatal growth.

Laparoscopic totally extraperitoneal ligation for pediatric inguinal hernia: a novel surgical treatment.

BACKGROUND: Laparoscopic repair is widely performed for the management of pediatric inguinal hernia (PIH), and different laparoscopic surgical methods are used. Herein, we present the application of laparoscopic totally extraperitoneal ligation (TEPL), which is a novel surgical method for PIH repair and is similar to traditional high ligation. METHODS: In this study, 103 pediatric patients underwent laparoscopic TEPL for inguinal hernia. Data including demographic characteristics, clinical presentation, time of surgery, length of hospital stay, and postoperative complications were analyzed retrospectively. RESULTS: The patient's median age at surgery was 4.3 years, and the median body weight at surgery was 18 kg. The preoperative diagnoses were as follows: n = 53, right inguinal hernia; n = 45, left inguinal hernia; and n = 5, bilateral inguinal hernia. All patients were discharged on the day of surgery. The operative times were 27.2 min for unilateral inguinal hernia and 28.8 min for bilateral inguinal hernia. All patients, except one who had scrotal bruise, did not present with postoperative complications. CONCLUSIONS: Laparoscopic TEPL, which is similar to traditional high ligation, is used for the treatment of PIH. Moreover, it is safe, beneficial, and feasible. Double ligation is performed on the extraperitoneal space, and the assessment of contralateral patent processus vaginalis is not complex. However, further studies should be conducted to assess for long-term outcomes.

Discrepancies in Educational Needs for Transition in Adolescents and Young Adults with Spina Bifida in South Korea: Use of the Borich Needs Assessment Model.

PURPOSE: Transition is an important goal for ensuring that adolescents and young adults (AYAs) with spina bifida (SB) lead autonomous lives. This study aimed to identify the educational needs of AYAs with SB based on the discrepancies between perceived importance and proficiency levels during the transition process. DESIGN AND METHODS: A cross-sectional study was conducted through face-to-face and online surveys from Jan-Dec 2020 of AYAs aged 13-25 years who had previously been diagnosed with SB. The survey consisted of 37 transition-related questions, of which 11 pertained to healthcare environments and 26 pertained to transition education needs SPSS and Excel were used for statistical analysis. Transition educational needs were analyzed by the Borich Needs Assessment Model. Higher the mean weighted discrepancy scores, lower the proficiency as compared to the perceived importance, indicating that the educational needs were high. RESULTS: Overall, 108 responses were analyzed, and 56 (51.9%) AYAs were diagnosed with lipomyelomeningocele. The highest ranked educational needs were for "Health insurance system", "SB related urinary system diseases management", "SB related nervous system symptoms", and "Self-catheterization management". "The demands for 'SB related work life", "Urinary incontinence management", and "Constipation management" were significantly higher in young adults than adolescents. CONCLUSIONS: During the transition process, activities perceived as important by AYAs with SB may differ from the activities that they can actually perform proficiently. It is important to assess their needs based on these discrepancies. PRACTICE IMPLICATIONS: Transition education programs are needed that consider the individual educational needs and developmental stage-specific characteristics of AYAs with SB.

Comparative drought resistance of temperate grassland species: testing performance trade-offs and the relation to distribution.

To improve projections of consequences of increasing intensity and frequency of drought events for grasslands, we need a thorough understanding of species performance responses to drought, of performance trade-offs and how drought resistance is related to species distributions. However, comparative and quantitative assessments of whole-plant drought resistance that allow to rigorously address these aspects are lacking for temperate grassland species. We conducted a common garden experiment with 40 common temperate grassland species to compare species survival and growth under intense drought and well-irrigated conditions. Overall, survival and growth were significantly reduced under drought, with the effect varying across species. Species ranking of drought damage and survival remained consistent with progressing drought. No performance trade-offs emerged between optimal growth and drought resistance of survival ('growth-stress tolerance' trade-off hypothesis), or between growth under well-watered and dry conditions ('growth rates' trade-off hypothesis). Species local- and large-scale association with moisture (Ellenberg F value and rainfall niche) was not related to their drought resistance. Overall, our results imply that trade-offs and differences of species fundamental drought resistance are not the main drivers of hydrological niche differentiation, species coexistence and their distribution across moisture gradients. The comparative experimental assessment of species whole-plant drought responses we present provides a basis to increase our understanding of current grassland responses to variation of moisture regimes and for projecting consequences of future changes.

Two-Step Integrative Education Program and mHealth for Korean Children with Spina Bifida: A Quasi-Experimental Pre-Post Study.

PURPOSE: Self-management of the daily tasks associated with condition management is an important goal for children with spina bifida (SB)to achieve for adolescence. This study investigated the effects of a two-step self-management improvement program including an onsite, integrative education program and mHealth on children with SB based on the Individual and Family Self-Management Theory. DESIGN AND METHODS: We used a pretest-posttest, quasi-experimental design with a nonequivalent control group. Open-ended questions were administered to obtain the opinions of the participants and their parents on the intervention program. The intervention effectiveness was evaluated by repeated-measures ANOVA using factors such as school adjustment, self-management knowledge, self-efficacy, self-management behavior, and quality of life measurement in 35 children with SB aged 7-12 years and their parents from July 2018 to October 2018. RESULTS: This intervention program did not result in a significant difference in quantitative outcomes between the experimental and control groups, but qualitatively, the children participating in this study and their parents responded positively to the self-management program. CONCLUSION: The current study demonstrated the potential effectiveness of this self-management program in children with SB. PRACTICE IMPLICATIONS: When healthcare providers develop an intervention for school-going children who are the digital native generation, up-to-date technological interventions, level of motivation of children, and intervention dosage should be taken into consideration.

Regenerative Potential of Carbon Monoxide in Adult Neural Circuits of the Central Nervous System.

Regeneration of adult neural circuits after an injury is limited in the central nervous system (CNS). Heme oxygenase (HO) is an enzyme that produces HO metabolites, such as carbon monoxide (CO), biliverdin and iron by heme degradation. CO may act as a biological signal transduction effector in CNS regeneration by stimulating neuronal intrinsic and extrinsic mechanisms as well as mitochondrial biogenesis. CO may give directions by which the injured neurovascular system switches into regeneration mode by stimulating endogenous neural stem cells and endothelial cells to produce neurons and vessels capable of replacing injured neurons and vessels in the CNS. The present review discusses the regenerative potential of CO in acute and chronic neuroinflammatory diseases of the CNS, such as stroke, traumatic brain injury, multiple sclerosis and Alzheimer's disease and the role of signaling pathways and neurotrophic factors. CO-mediated facilitation of cellular communications may boost regeneration, consequently forming functional adult neural circuits in CNS injury.

Factors affecting home-based disaster preparedness among school-aged children's parents: A cross-sectional study.

This study aimed to identify the factors affecting home-based disaster preparedness among Korean parents of school-aged children, based on an ecological model. A descriptive study was conducted involving 233 parents with school-aged children, using an online survey questionnaire. Parents' home-based disaster preparedness scores were classified into four groups: not prepared (36.5%), minimally prepared (38.2%), better prepared (17.6%), and most prepared (7.7%). Home-based disaster preparedness predictors corresponded to occupation and disaster-related knowledge in Model I, parents who had received disaster education in Model II, and age and participation in disaster education for parents and children together in Model III. The findings indicate that home-based disaster preparedness in Korea is inadequate. Therefore, it is necessary to develop and provide disaster-related education programs that consider each population group's needs and disaster preparedness level. Additionally, it is important to form networks for sharing the latest disaster-related information both inside and outside the family to maintain and manage disaster preparedness at home.

Bladder and Bowel Dysfunction in Korean Children with Down Syndrome and Parental Quality of Life.

PURPOSE: Children with Down syndrome (DS) are more likely to experience bladder bowel dysfunction (BBD) than typically developing children, which could in turn have a serious effect on children with DS and on their parents and other family members. This study aimed to explore the prevalence of BBD in Korean children with DS and its effect on parental quality of life (QOL). DESIGN AND METHODS: To assess BBD and parental QOL, we used self-administered questionnaires (Dysfunctional Voiding Symptom Score [DVSS], Rome IV criteria, and World Health Organization Quality of Life scale [WHOQOL-BREF]) for parents of children with DS. We collected data from 86 parents between September and October 2017 through an online community website. RESULTS: DVSS was elevated in 26.7% of the children with DS. Specifically, 14% had daytime urinary incontinence, and 33.7% had functional constipation. Moreover, 18.6% of children had BBD according to the DVSS and Rome IV criteria. The sensitivity and specificity of DVSS to functional constipation was 55.17% and 87.72%, respectively. The BBD score and total parental QOL score were statistically correlated (r = 0.291, p = 0.007). CONCLUSIONS: Although children with DS are a high-risk group for BBD, their BBD symptoms are often overlooked because of their intellectual disability. Consequently, this could negatively affect children's and family's health and QOL in the long term. PRACTICE IMPLICATIONS: Health-care providers should reconsider a routine check-up of BBD in children with DS. If a child has BBD, health-care providers should consult a urologist to determine the appropriate diagnosis and intervention.

A 2-Step Integrative Education Program and mHealth for Self-Management in Korean Children with Spina Bifida: Feasibility Study.

PURPOSE: The aim of this study was to develop and test the feasibility of a 2-step self-management program, including onsite integrative education and a mobile health (mHealth) intervention, for children with spina bifida (SB). DESIGN AND METHODS: This feasibility study used a quasi-experimental single group pre-and post-test design. The onsite integrative education and the mHealth program, "Glowing Stars™," were developed and then tested for content validity by a panel of experts. The feasibility and user satisfaction were evaluated using factors such as school adjustment, self-management knowledge, self-efficacy, self-management behavior, and quality of life measurement by children aged 10 to 12 years with SB and their parents, from March 2018 to April 2018. RESULTS: A total of five children with SB completed this intervention. All children perceived that this program was usable and feasible to maintain self-management behavior. A statistically significant difference was observed in the children's self-management behavior domain between the first and second post-test (p = .043). CONCLUSION: This innovative 2-step self-management intervention program complements existing single interventions and confirms the possibility of mHealth technology as an intervention for children with SB. PRACTICE IMPLICATIONS: In pediatric nursing, this innovative intervention could be adapted for children with chronic conditions, with a positive effect on self-management.

RNA-Seq for Gene Expression Profiling of Human Necrotizing Enterocolitis: a Pilot Study.

Necrotizing enterocolitis (NEC) characterized by inflammatory intestinal necrosis is a major cause of mortality and morbidity in newborns. Deep RNA sequencing (RNA-Seq) has recently emerged as a powerful technology enabling better quantification of gene expression than microarrays with a lower background signal. A total of 10 transcriptomes from 5 pairs of NEC lesions and adjacent normal tissues obtained from preterm infants with NEC were analyzed. As a result, a total of 65 genes (57 down-regulated and 8 up-regulated) revealed significantly different expression levels in the NEC lesion compared to the adjacent normal region, based on a significance at fold change ≥ 1.5 and P ≤ 0.05. The most significant gene, DPF3 (P < 0.001), has recently been reported to have differential expressions in colon segments. Our gene ontology analysis between NEC lesion and adjacent normal tissues showed that down-regulated genes were included in nervous system development with the most significance (P = 9.3 × 10⁻7; P(corr) = 0.0003). In further pathway analysis using Pathway Express based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, genes involved in thyroid cancer and axon guidance were predicted to be associated with different expression (P(corr) = 0.008 and 0.020, respectively). Although further replications using a larger sample size and functional evaluations are needed, our results suggest that altered gene expression and the genes' involved functional pathways and categories may provide insight into NEC development and aid in future research.

A normalization method for combination of laboratory test results from different electronic healthcare databases in a distributed research network.

PURPOSE: Distributed research networks (DRNs) afford statistical power by integrating observational data from multiple partners for retrospective studies. However, laboratory test results across care sites are derived using different assays from varying patient populations, making it difficult to simply combine data for analysis. Additionally, existing normalization methods are not suitable for retrospective studies. We normalized laboratory results from different data sources by adjusting for heterogeneous clinico-epidemiologic characteristics of the data and called this the subgroup-adjusted normalization (SAN) method. METHODS: Subgroup-adjusted normalization renders the means and standard deviations of distributions identical under population structure-adjusted conditions. To evaluate its performance, we compared SAN with existing methods for simulated and real datasets consisting of blood urea nitrogen, serum creatinine, hematocrit, hemoglobin, serum potassium, and total bilirubin. Various clinico-epidemiologic characteristics can be applied together in SAN. For simplicity of comparison, age and gender were used to adjust population heterogeneity in this study. RESULTS: In simulations, SAN had the lowest standardized difference in means (SDM) and Kolmogorov-Smirnov values for all tests (p < 0.05). In a real dataset, SAN had the lowest SDM and Kolmogorov-Smirnov values for blood urea nitrogen, hematocrit, hemoglobin, and serum potassium, and the lowest SDM for serum creatinine (p < 0.05). CONCLUSION: Subgroup-adjusted normalization performed better than normalization using other methods. The SAN method is applicable in a DRN environment and should facilitate analysis of data integrated across DRN partners for retrospective observational studies.

Effect of mechanically deboned chicken meat hydrolysates on the physicochemical properties of imitation fish paste.

This study investigated on the effects of adding mechanically deboned chicken meat (MDCM) hydrolysates on the quality properties of imitation fish paste (IFP) during storage. IFP was prepared from Alaska Pollack, spent laying hens surimi and protein hydrolysates which were enzymatically extracted from MDCM. The study was designed as a 3×4 factorial design with three MDCM hydrolysate content groups (0%, 0.4%, and 0.8%) and four storage times (0, 2, 4, and 6 weeks). Addition of MDCM hydrolysates increased crude fat content but lowered water content (p<0.05). The breaking force of IFP, an indicator of gel formation, increased in treated groups compared to control (p<0.05). Angiotensin I-converting enzyme (ACE) activity was inhibited and free radical scavenging activity increased with increasing MDCM hydrolysate content (p<0.05). In conclusion, the addition of MDCM to IFP improves gel characteristics. Additionally, protein hydrolysates from MDCM serve as a potential source of ACE inhibiting peptides.

A Review of Plasma-Synthesized and Plasma Surface-Modified Piezoelectric Polymer Films for Nanogenerators and Sensors.

In this review, we introduce recently developed plasma-based approaches for depositing and treating piezoelectric nanoparticles (NPs) and piezoelectric polymer films for nanogenerator (NG) and sensor applications. We also present the properties and an overview of recently synthesized or modified piezoelectric materials on piezoelectric polymers to highlight the existing challenges and future directions of plasma methods under vacuum, low pressure, and ambient air conditions. The various plasma processes involved in piezoelectric NGs and sensors, including plasma-based vapor deposition, dielectric barrier discharge, and surface modification, are introduced and summarized for controlling various surface properties (etching, roughening, crosslinking, functionalization, and crystallinity).

Successful outcome with oral sirolimus treatment for complicated lymphatic malformations: a retrospective multicenter cohort study.

Purpose: Sirolimus has emerged as a safe and effective treatment for complicated lymphatic malformations (LMs). We aim to prove the effectiveness and safety of sirolimus as a therapeutic option for patients with complicated LMs. Methods: Fifty-eight patients with complicated LMs treated with sirolimus for at least 6 months at multicenter between July 2018 and January 2023 were enrolled. All patients were administered oral sirolimus starting at 0.8 mg/m2 every 12 hours, with target serum concentration levels of 8-15 ng/mL. Evaluation for clinical symptoms and LMs volume on MRI were reviewed to assess treatment response and toxicities. Evaluation of disease response was divided into 3 values: complete response, partial response (significant, moderate, and modest), and progressive disease. Results: The median age at the initiation of sirolimus treatment was 6.0 years (range, 1 month-26.7 years). The median duration of treatment was 2.0 years (range, 6 months-4.4 years). The most common lesions were head and neck (25 of 58, 43.1%). Forty-six patients (79.3%) demonstrated a reduction in LMs volume on MRI or improvement of clinical symptoms including 2 complete responses. The young age group and the patients who underwent few prior therapies showed better responses. None of the patients had toxicities attributable to sirolimus with a Common Terminology Criteria for Adverse Events grade of ≥3. Conclusion: Oral sirolimus treatment brought a successful outcome without severe adverse effects. It could be the first-line therapy, especially for the young age group of complicated LMs, and an additional option for refractory lesions that did not respond to conventional treatment.

Water use by a warm-temperate deciduous forest under the influence of the Asian monsoon: contributions of the overstory and understory to forest water use.

The warm temperate deciduous forests in Asia have a relatively dense understory, hence, it is imperative that we understand the dynamics of transpiration in both the overstory (E O) and understory (E U) of forest stands under the influence of the Asian monsoon in order to improve the accuracy of forest water use budgeting and to identify key factors controlling forest water use under climate change. In this study, E O and E U of a temperate deciduous forest stand located in South Korea were measured during the growing season of 2008 using sap flow methods. The objectives of this study were (1) to quantify the total transpiration of the forest stand, i.e., overstory and understory, (2) to determine their relative contribution to ecosystem evapotranspiration (E eco), and (3) to identify factors controlling the transpiration of each layer. E O and E U were 174 and 22 mm, respectively. Total transpiration accounted for 55 % of the total E eco, revealing the importance of unaccounted contributions to E eco (i.e., soil evaporation and wet canopy evaporation). During the monsoon period, there was a strong reduction in the total transpiration, likely because of reductions in photosynthetic active radiation, vapor pressure deficit and plant area index. The ratio of E U to E O declined during the same period, indicating an effect of monsoon on the partitioning of E eco in its two components. The seasonal pattern of E O was synchronized with the overstory canopy development, which equally had a strong regulatory influence on E U.