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Site-specific integration via genome editing technologies has been implemented in Chinese hamster ovary (CHO) cells for predictable and efficient cell line development and engineering. Various strategies have been employed to enhance knock-in (KI) efficiency for precise homology-directed repair (HDR)-mediated targeted integration of transgenes in CHO cells. Given the cell cycle-dependent regulation of the DNA damage repair pathway, cell cycle synchronization to the HDR-favored S/G2 phase has been successfully utilized in mammalian cells, but the effect is limited in CHO cells. Here, we describe a cell cycle enrichment method to increase HDR-mediated KI efficiency in CHO cells. Existing G1 cell cycle synchronization methods showed transient cell cycle arrest and did not improve KI efficiency. Rather than cell cycle arrest with a high concentration of chemicals followed by a release step, cells were incubated in the presence of a lower concentration of hydroxyurea (HU) to enrich cells in the S phase. HU selection allowed for robust S phase enrichment of CHO cells by up to 70 % and maintained cell viability. This short-term selection resulted in improved KI efficiency by 1.2-1.5 fold compared with cells in the control condition. Overall, this approach serves as a simple and effective strategy for enhancement of site-specific genome engineering in CHO cells.

Processing-in-memory (PIM) comprises computational logic in the memory domain. It is the most promising solution to alleviate the memory bandwidth problem in deep neural network (DNN) processing. The hybrid memory cube (HMC), a 3D stacked memory structure, can efficiently implement the PIM architecture by maximizing the existing legacy hardware. To accelerate DNN inference, multiple HMCs can be connected, and data-independent tasks can be assigned to processing elements (PEs) within each HMC. However, owing to the packet-switched network structure, inter-HMC interconnects exhibit variable and unpredictable latencies depending on the data transmission path and link contention. A well-designed task schedule using context switching can effectively hide communication latency and improve PE utilization. Nevertheless, as the number of HMC increases, the variability of a wide range of inter-HMC communication latencies causes frequent context switching, degrading overall performance. This paper proposes a DNN task scheduling that can effectively utilize task parallelism by reducing the communication latency variance owing to HMC interconnect characteristics. Task partitions are generated to exploit parallelism while providing inter-HMC traffic within the sustainable link bandwidth. Task-to-HMC mapping is performed to hide the average communication latency of intermediate DNN processing results. A task schedule is generated using retiming to accelerate DNN inference while maximizing resource utilization. The effectiveness of the proposed method was verified through simulations using various realistic DNN applications performed on a ZSim x86-64 simulator. The simulations revealed that DNN processing with the proposed scheduling improved the DNN processing speed by reducing the processing time by 18.19% over conventional methods where each HMC operated independently.

Background This study was to assess the validity of the Korean version of the semi-structured Diagnostic Interview for Adult ADHD, third edition (DIVA-5). The secondary aim was to compare sociodemographic and psychiatric comorbidities in adult patients with and without a diagnosis of ADHD. Methods A total of 279 participants were recruited from nine psychiatric outpatient clinics in Korea. All participants were administered the Mini-International Neuropsychiatric Interview (MINI) Plus v.5.0.0, the Adult ADHD Self-Report Scale v1.1 (ASRS-v1.1) Symptom Checklist, and DIVA-5. Diagnosis concordance between two board-certified psychiatrists and DIVA-5 were analysed. Results The DIVA-5 showed a diagnostic accuracy of 92%, a sensitivity of 91.30%, and a specificity of 93.62%. Significant clinical and demographic differences between ADHD and control groups were found. Conclusion The Korean version of DIVA-5 is a reliable tool for assessing and diagnosing ADHD in adult Korean populations.

Objectives Adult attention-deficit/hyperactivity disorder (ADHD) is an important mental health problem that needs resolution, especially considering the high rates of ADHD continuation from childhood to adolescence/adulthood and the high prevalence of ADHD in adults. Adults with ADHD have lifelong negative impacts and require close monitoring with long-term follow-up. Hence, the establishment of a Korean practice parameter for adult ADHD is necessary to minimize discontinuation of treatment and enable information sharing among Korean mental health professionals. Methods The Korean practice parameter was developed using an evidence-based approach consisting of expert consensus survey coupled with literature review. Results According to the expert consensus survey, the most commonly used diagnostic methods were clinical psychiatric interview (20.66%) and self-report scales (19.25%) followed by attention (14.71%) and psychological tests (14.24%). Key evaluation instruments currently available in Korea are the World Health Organization Adult ADHD Self-Report Rating Scale, Korean Adult ADHD Rating Scale, Diagnostic Interview for ADHD in Adults, Barkley Deficits in Executive Functioning Scale for adults, Comprehensive Attention Test, Conners' Continuous Performance Test, and the subtests of Wechsler Adult Intelligence Scale, Digit Span and Letter-Number Sequencing. Although pharmacotherapy is recommended as the first-line of treatment for adult ADHD, we recommend that it be followed by a multimodal and multidisciplinary approach including psychoeducation, pharmacotherapy, cognitive behavior therapy and coaching. Conclusion The Korean practice parameter introduces not only general information for the diagnosis and treatment of adult ADHD on a global scale, but also the process of diagnosis and treatment options tailored to the Korean population.

OBJECTIVE To examine the trajectory and risk factors of depression symptoms among parents from NICU admission to 30 days postdischarge. We hypothesized depression symptom scores would decrease from admission and then increase from discharge to 30 days. METHODS Prospective longitudinal cohort study of premature infants in NICU. Parents completed the validated Edinburgh Postnatal Depression Scale (EPDS) at 4 time points: NICU admission, discharge, and 14 days and 30 days postdischarge. EPDS score change across time and probability of a positive screen (EPDS ≥10) were by assessed using mixed effect regression models. RESULTS Of 431 parents enrolled (mothers, n = 230 [53%]), 33% of mothers (n = 57) and 17% of fathers (n = 21) had a positive EPDS screening. Score change was 1.9 points different between mothers and fathers (confidence interval [CI]: 1.3–2.6; P < .0001), with mothers decreasing 2.9 points (CI: 2.1–3.7; P < .0001) and fathers decreasing 1.0 points (CI: 0.1–2.0; P = .04). Over time, mothers decreased 10.96 times (CI: 2.99–38.20; P = .0003); fathers decreased at a nonsignificant rate. Admission or discharge screening improved 30-day depressive symptom prediction (AUC 0.66 baseline demographics only versus 0.84+initial [P < .0001], and versus 0.80+discharge screening [P < .001]). CONCLUSIONS Mothers and fathers experience different depressive symptom trajectories from NICU to home. Screening parents for postpartum depression during the NICU stay is likely to result in improved identification of parents at risk for postpartum depression after discharge. Focused attention on fathers appears warranted.

The timely mobilization of hematopoietic stem and progenitor cells (HSPCs) is essential for maintaining hematopoietic and tissue leukocyte homeostasis. Understanding how HSPCs migrate between bone marrow (BM) and peripheral tissues is of great significance in the clinical setting, where therapeutic strategies for modulating their migration capacity determine the clinical outcome. Here, we identify an epigenetic regulator, Phc2, as a critical modulator of HSPC trafficking. The genetic ablation of Phc2 in mice causes a severe defect in HSPC mobilization through the derepression of Vcam1 in bone marrow stromal cells (BMSCs), ultimately leading to a systemic immunodeficiency. Moreover, the pharmacological inhibition of VCAM-1 in Phc2-deficient mice reverses the symptoms. We further determine that Phc2-dependent Vcam1 repression in BMSCs is mediated by the epigenetic regulation of H3K27me3 and H2AK119ub. Together, our data demonstrate a cell-extrinsic role for Phc2 in controlling the mobilization of HSPCs by finely tuning their bone marrow niche., Mobilization of hematopoietic stem and progenitor cells (HSPCs) into the circulation is essential for maintaining homeostasis. Here, the authors show that Phc2 in bone marrow stromal cells represses the cell adhesion molecule Vcam1 and facilitates mobilization of HSPCs through regulation of epigenetic marks.

Objectives This study was conducted to re-validate the clinical efficacy of the Korean Adult Attention-Deficit/Hyperactivity Disorder (ADHD) Rating Scale (K-AARS), which is a self-report scale for ADHD in adults, and to determine the clinical utility and cut-off scores of K-AARS. Methods The participants were 135 drug naive adults with ADHD and 144 healthy controls. To diagnose ADHD based on the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, two board-certified pediatric psychiatrists interviewed the participants and completed the Mini International Neuropsychiatric Interview. K-AARS was applied to all participants. K-AARS comprises six clinical subscales, one impairment subscale, and one driving behavior subscale. The receiver operating characteristic analysis was conducted to calculate the cut-off scores of K-AARS. Results All subscale scores, including six clinical subscale, impairment subscale, and driving behavior subscale scores, were found to be significant in distinguishing adults with ADHD from healthy controls. The sensitivity and specificity of the six clinical subscales were 63.0-77.0% and 66.7-79.9%, respectively. The combined total score of the six clinical subscales, had a sensitivity of 80.0% and specificity of 79.9%. Conclusion The discriminative power of K-AARS for the diagnosis of ADHD in adults was excellent, and K-AARS and the empirical diagnosis of adults can be useful in diagnosing ADHD in adulthood.

Objectives: Awareness of attention-deficit/hyperactivity disorder (ADHD) in adults has significantly increased; however, clinical data specific to the Korean population are insufficient. Clinical experience of ADHD may differ based on whether psychiatrists have received pediatric psychiatry-specific training. In order to prepare a practice parameter for adult ADHD patients in Korea, we examined questionnaire data to observe how pediatric psychiatry training could affect clinical practice for adults with ADHD. Methods: A questionnaire about the diagnosis and treatment process was distributed to both general psychiatrists (GPsy) and child and adolescent psychiatrists (CAP) at the summer and winter workshop meetings of Korean Academy of Child and Adolescent Psychiatry. Results: In total, 142 psychiatrists participated in the survey (86 GPsy, 56 CAP). GPsy and CAP preferred pharmacotherapy (GPsy 82.40%, CAP 64.30%) as the primary treatment option and answered that the clinical psychiatric interview is the most necessary step in diagnostic assessment (GPsy 22.16%, CAP 19.00%). The GPsy responded with an optimal and average treatment duration that was shorter than that reported by CAP. Conclusion: Identification of the initial presenting symptom as the correct diagnosis and the optimal duration of pharmacotherapy differed between GPsy and CAP in practice, whereas concepts in diagnosis and treatment of ADHD in adults were similar for both groups. These results suggest the urgent need for the Continuing Medical Education program for psychiatrists treating adults with ADHD.

Purpose Gambling disorder is a psychiatric condition characterized by persistent and recurrent maladaptive gambling. In the present study, we evaluated the characteristics of resting-state electroencephalogram (EEG) recordings in patients with gambling disorder. In addition, we explored the association between the EEG characteristics of the patients and the stages of change in a transtheoretical model. Methods All participants were men who visited a gambling disorder clinic in Seoul, Korea. At the assessment, questionnaires, including the Readiness to Change Questionnaire (RCQ), were administered and resting-state EEGs were carried out. Participants were grouped based on Ward's method for cluster analysis. Independent sample t-tests were used to evaluate group differences. To assess the relationship between the clinical data and the EEG recordings, we used Pearson's partial correlation analysis. Results Overall, 63 male participants were enrolled. Cluster analysis of the alpha activity revealed two clusters. No significant differences were observed in the demographic or clinical data between the two groups except for the Beck Depression Inventory (BDI). We found that the precontemplation score of the RCQ was positively correlated with the z-score of the relative alpha power in almost all cortical regions. Conclusion This study suggests that EEG parameters, particularly alpha activity, could inform us about the subtypes or stages of change in gambling disorder. Alpha power is the predominant EEG rhythm in a relaxed, alert person; thus, alpha power serves as an index of relaxation. We expect that the level of alpha activity could be utilized as an additional parameter to help clinicians assess and treat patients with gambling disorder.

Objective: There is an updated conceptualization of whole-lifespan attention-deficit hyperactivity disorder (ADHD), promoted by awareness of probable persistence of impairment into adulthood. We investigated cognition trajectories from adolescence to mid-adulthood in ADHD. Method: Data of 240 patients with ADHD and 244 healthy controls (HCs) were obtained; clinical symptoms and neuropsychological functions were assessed using the various tests. Results: Compared to HCs, patients with ADHD except 35 to 44 age interval showed lower full scale intelligence quotient. They showed decreased verbal comprehensive scores except in the 35 to 44 age interval and working memory scores in all intervals. In the Comprehensive Attention Test, patients with ADHD showed increased working memory error frequencies except in the 15 to 17 age interval and divided attention omission error in all intervals. Conclusion: Adults with ADHD showed deficits not in simple attention but in complex attention, including divided attention and working memory.

Numerous engineering efforts have been made in Chinese hamster ovary (CHO) cells for high level production of therapeutic proteins. However, the dynamic regulation of transgene expression is limited in current systems. Here, we investigated the effective regulation of transgene expression in CHO cells via targeted integration-based endogenous gene tagging with engineering target genes. Targeted integration of EGFP-human Bcl-2 into the p21 locus effectively reduced the apoptosis, compared with random populations in which Bcl-2 expression was driven by cytomegalovirus (CMV) promoter. Endogenous p21 and EGFP-human Bcl-2 displayed similar expression dynamics in batch cultures, and the antiapoptotic effect altered the expression pattern of endogenous p21 showing the mutual influences between expression of p21 and Bcl-2. We further demonstrated the inducible transgene expression by adding low concentrations of hydroxyurea. The present engineering strategy will provide a valuable CHO cell engineering tool that can be used to control dynamic transgene expression in accordance with cellular states.

Multi-level cell (MLC) phase-change memory (PCM) is an attractive solution for next-generation memory that is composed of resistance-based nonvolatile devices. MLC PCM is superior to dynamic random-access memory (DRAM) with regard to scalability and leakage power. Therefore, various studies have focused on the feasibility of MLC PCM-based main memory. The key challenges in replacing DRAM with MLC PCM are low reliability, limited lifetime, and long write latency, which are predominantly affected by the most error-vulnerable data pattern. Based on the physical characteristics of the PCM, where the reliability depends on the data pattern, a tri-level-cell (3LC) PCM has significantly higher performance and lifetime than a four-level-cell (4LC) PCM. However, a storage density is limited by binary-to-ternary data mapping. This paper introduces error-vulnerable pattern-aware binary-to-ternary data mapping utilizing 3LC PCM without an error-correction code (ECC) to enhance the storage density. To mitigate the storage density loss caused by the 3LC PCM, a two-way encoding is applied. The performance degradation is minimized through parallel encoding. The experimental results demonstrate that the proposed method improves the storage density by 17.9%. Additionally, the lifetime and performance are enhanced by 36.1% and 38.8%, respectively, compared with those of a 4LC PCM with an ECC.

Cap1 2′-O-ribose methyltransferase (CMTR1) modifies RNA transcripts containing the 7-methylguanosine cap via 2′-O-ribose methylation of the first transcribed nucleotide, yielding cap1 structures. However, the role of CMTR1 in small RNA-mediated gene silencing remains unknown. Here, we identified and characterized a Drosophila CMTR1 gene (dCMTR1) mutation. We found that the catalytic activity of dCMTR1 was involved in the biogenesis of small interfering RNAs (siRNAs) but not microRNAs. Additionally, dCMTR1 interacted with R2D2, a key component for the assembly of the RNA-induced silencing complex (RISC) containing Argonaute 2 (Ago2). Consistent with this finding, loss of dCMTR1 function impaired RISC assembly by inhibiting the unwinding of Ago2-bound siRNA duplexes, thus preventing the retention of the guide strand. Moreover, dCMTR1 is unlikely to modify siRNAs during RISC assembly. Collectively, our data indicate that dCMTR1 is a positive regulator of the small RNA pathway associated with Ago2 with roles in both siRNA biogenesis and RISC assembly.

Background So far, studies on workplace mental health have only focused on work-related environmental risk factors, disregarding both protective and individual factors of employees. Therefore, we aimed to identify character strengths that act as protective factors against depressive moods and suicidality in Korean employees. Methods In total, 84 male and 151 female employees (aged 19–50 years) reported their sociodemographic characteristics; depressive symptoms, as measured by the Beck Depression Inventory-II; suicidality, as measured by the Korean version of the MINI International Neuropsychiatric Interview suicidality module; and character strengths, as measured by the 24 Character Strength Alphas on the Values in Action Survey-72. We conducted a hierarchical logistic regression, in which depressive mood and suicidality served as the categorical outcome variables. Results In females, scores on the “curiosity” (B = 1.107, Wald = 10.207, odds ratio = 3.026, p = .001) and “love” (B = .862, Wald = 5.767, odds ratio = 2.367, p = .016) sub scales of the 24 Character Strength Alphas on the Values in Action Survey-72 were statistically significant predictors of having depressive mood. Additionally, females’ scores on “judgment” (B = − 1.405, Wald = 5.663, odds ratio = .245, p = .017) and “kindness” (B = − 1.456, Wald = 6.486, odds ratio = .233, p = .011) were protective factors against suicidality. In males, the “love” (B = 1.746, Wald = 4.279, odds ratio = 5.729, p = .039) score was a predictor of having depressive mood, while “teamwork” (B = − 2.204, Wald = 4.666, odds ratio = .110, p = .031) and “creativity” (B = − 1.384, Wald = 4.202, odds ratio = .251, p = .040) scores were protective factors against having depressive mood and suicidality, respectively. Conclusions We suggest that focusing on “judgement” and “kindness” in female employees, and “teamwork” and “creativity” in male employees, and engaging in activities that use these strengths at the workplace can be protective factors against depression and suicidality. Future research should focus on developing interventions to promote these character strengths among employees at the workplace.