IL-7-primed bystander CD8 tumor-infiltrating lymphocytes optimize the antitumor efficacy of T cell engager immunotherapy.

Bispecific T cell engagers (TCEs) show promising clinical efficacy in blood tumors, but their application to solid tumors remains challenging. Here, we show that Fc-fused IL-7 (rhIL-7-hyFc) changes the intratumoral CD8 T cell landscape, enhancing the efficacy of TCE immunotherapy. rhIL-7-hyFc induces a dramatic increase in CD8 tumor-infiltrating lymphocytes (TILs) in various solid tumors, but the majority of these cells are PD-1-negative tumor non-responsive bystander T cells. However, they are non-exhausted and central memory-phenotype CD8 T cells with high T cell receptor (TCR)-recall capacity that can be triggered by tumor antigen-specific TCEs to acquire tumoricidal activity. Single-cell transcriptome analysis reveals that rhIL-7-hyFc-induced bystander CD8 TILs transform into cycling transitional T cells by TCE redirection with decreased memory markers and increased cytotoxic molecules. Notably, TCE treatment has no major effect on tumor-reactive CD8 TILs. Our results suggest that rhIL-7-hyFc treatment promotes the antitumor efficacy of TCE immunotherapy by increasing TCE-sensitive bystander CD8 TILs in solid tumors.

Prime editing: Mechanism insight and recent applications in plants.

Prime editing (PE) technology utilizes an extended prime editing guide RNA (pegRNA) to direct a fusion peptide consisting of nCas9 (H840) and reverse transcriptase (RT) to a specific location in the genome. This enables the installation of base changes at the targeted site using the extended portion of the pegRNA through RT activity. The resulting product of the RT reaction forms a 3' flap, which can be incorporated into the genomic site through a series of biochemical steps involving DNA repair and synthesis pathways. PE has demonstrated its effectiveness in achieving almost all forms of precise gene editing, such as base conversions (all types), DNA sequence insertions and deletions, chromosomal translocation and inversion and long DNA sequence insertion at safe harbour sites within the genome. In plant science, PE could serve as a groundbreaking tool for precise gene editing, allowing the creation of desired alleles to improve crop varieties. Nevertheless, its application has encountered limitations due to efficiency constraints, particularly in dicotyledonous plants. In this review, we discuss the step-by-step mechanism of PE, shedding light on the critical aspects of each step while suggesting possible solutions to enhance its efficiency. Additionally, we present an overview of recent advancements and future perspectives in PE research specifically focused on plants, examining the key technical considerations of its applications.

CRISPR-Cas9-based precise engineering of SlHyPRP1 protein towards multi-stress tolerance in tomato.

Recently, CRISPR-Cas9-based genome editing has been widely used for plant breeding. In our previous report, a tomato gene encoding hybrid proline-rich protein 1 (HyPRP1), a negative regulator of salt stress responses, has been edited using a CRISPR-Cas9 multiplexing approach that resulted in precise eliminations of its functional domains, proline-rich domain (PRD) and eight cysteine-motif (8CM). We subsequently demonstrated that eliminating the PRD domain of HyPRP1 in tomatoes conferred the highest level of salinity tolerance. In this study, we characterized the edited lines under several abiotic and biotic stresses to examine the possibility of multiple stress tolerance. Our data reveal that the 8CM removal variants of HK and the KO alleles of both HK and 15T01 cultivars exhibited moderate heat stress tolerance. Similarly, plants carrying either the domains of the PRD removal variant (PR1v1) or 8CM removal variants (PR2v2 and PR2v3) showed better germination under osmosis stress (up to 200 mM mannitol) compared to the WT control. Moreover, the PR1v1 line continuously grew after 5 days of water cutoff. When the edited lines were challenged with pathogenic bacteria of Pseudomonas syringae pv. tomato (Pto) DC3000, the growth of the bacterium was significantly reduced by 2.0- to 2.5-fold compared to that in WT plants. However, the edited alleles enhanced susceptibility against Fusarium oxysporum f. sp. lycopersici, which causes fusarium wilt. CRISPR-Cas9-based precise domain editing of the SlHyPRP1 gene generated multi-stress-tolerant alleles that could be used as genetic materials for tomato breeding.

The association between fruit and vegetable consumption and metabolic syndrome in Korean adults: does multivitamin use matter?

OBJECTIVES: Metabolic syndrome (MetS) is closely associated with dietary intake; however, few studies have investigated whether the consumption of fruits and vegetables and multivitamin use affect MetS in the Korean population. This study aimed to examine these effects in Korean adults. METHODS: This was a cross-sectional study of 89,548 participants aged between 40 years and 69 years selected from the baseline data of the Health Examinees study conducted in Korea. Fresh vegetable and fruit consumption was assessed using a validated 106-item food frequency questionnaire. MetS and its components were defined using the National Cholesterol Education Program, Adult Treatment Panel III criteria. Multivariate logistic regression analyses were conducted to identify associations of fresh vegetable, fruit, and fresh vegetable+fruit consumption and multivitamin use with the prevalence of MetS. RESULTS: Female in the highest quartile of fresh vegetable, fruit, and fresh vegetable + fruit consumption exhibited a lower prevalence of MetS than those in the lowest quartile. An inverse association with the prevalence of MetS was observed among male with only fresh vegetable consumption. The interaction between the 3 categories and multivitamin intake on the prevalence of MetS was not significant (all pinteraction>0.05), regardless of sex. CONCLUSIONS: Multivitamin use and consumption of fresh vegetables and fruits had no significant synergistic effects. Although fresh vegetable and fruit consumption showed an inverse association with the prevalence of MetS, this relationship was not altered by multivitamin use.

Reliability and Validity of the Korean Version of Children's Depression Inventory 2 Short Version as a Screening Tool: A Comparison With the Standard 28-Item Version.

OBJECTIVE: To investigate the reliability and validity of the Korean version of Children's Depression Inventory 2 Short Version (CDI 2:S) in comparison with its full-length version (CDI 2) as a screening tool for depressive youth. METHODS: A total of 714 children from the community and 62 psychiatric patients were enrolled in this study. The Korean version of the Kiddie Schedule for Affective Disorders and Schizophrenia Present and Lifetime Version (K-SADS-PL-K) served as the reference standard for computing receiver operating characteristic (ROC) curves. To evaluate the ability of the CDI 2 and CDI 2:S to discriminate major depressive disorders, areas under the curves (AUCs) were compared. To investigate psychometric properties of the CDI 2:S, internal consistency was calculated and confirmatory factor analysis was conducted. RESULTS: For the CDI 2, the cutoff at 20 yielded the best balance between sensitivity (83%) and specificity (91%). For the CDI 2:S, the cutoff point of 10 resulted in high sensitivity (82%) and high specificity (93%). The short form was proven to be as sensitive and specific as the CDI 2. Further analyses confirmed that the CDI 2:S also had good reliability and validity. CONCLUSION: The CDI 2:S, a sensitive and brief form of the CDI 2, may serve as a better option in time-constrained psychiatric settings.

Single-strand annealing: Molecular mechanisms and potential applications in CRISPR-Cas-based precision genome editing.

BACKGROUND: Spontaneous double-stranded DNA breaks (DSBs) frequently occur within the genome of all living organisms and must be well repaired for survival. Recently, more important roles of the DSB repair pathways that were previously thought to be minor pathways, such as single-strand annealing (SSA), have been shown. Nevertheless, the biochemical mechanisms and applications of the SSA pathway in genome editing have not been updated. PURPOSE AND SCOPE: Understanding the molecular mechanism of SSA is important to design potential applications in gene editing. This review provides insights into the recent progress of SSA studies and establishes a model for their potential applications in precision genome editing. SUMMARY AND CONCLUSION: The SSA mechanism involved in DNA DSB repair appears to be activated by a complex signaling cascade starting with broken end sensing and 5'-3' resection to reveal homologous repeats on the 3' ssDNA overhangs that flank the DSB. Annealing the repeats would help to amend the discontinuous ends and restore the intact genome, resulting in the missing of one repeat and the intervening sequence between the repeats. We proposed a model for CRISPR-Cas-based precision insertion or replacement of DNA fragments to take advantage of the characteristics. The proposed model can add a tool to extend the choice for precision gene editing. Nevertheless, the model needs to be experimentally validated and optimized with SSA-favorable conditions for practical applications.

The Obstacles and Potential Solution Clues of Prime Editing Applications in Tomato.

Precision genome editing is highly desired for crop improvement. The recently emerged CRISPR/Cas technology offers great potential applications in precision plant genome engineering. A prime editing (PE) approach combining a reverse transcriptase (RT) with a Cas9 nickase and a "priming" extended guide RNA (gRNA) has shown a high frequency for precise genome modification in mammalian cells and several plant species. Nevertheless, the applications of the PE approach in dicot plants are still limited and inefficient. We designed and tested prime editors for precision editing of a synthetic sequence in a transient assay and for desirable alleles of 10 loci in tomato by stable transformation. Our data obtained by targeted deep sequencing also revealed only low PE efficiencies in both the tobacco and tomato systems. Further assessment of the activities of the PE components uncovered that the fusion of RT to Cas9 and the structure of PE gRNAs (pegRNAs) negatively affected the cleaving activity of the Cas9 nuclease. The self-complementarity between the primer binding sequences (PBSs) and spacer sequence might pose risks to the activity of the Cas9 complex. However, modifying the pegRNA sequences by shortening or introducing mismatches to the PBSs to reduce their melting temperatures did not enhance the PE efficiency at the MADS-box protein (SlMBP21), alcobaca (SlALC), and acetolactate synthase 1 (SlALS1) loci. Our data show challenges of the PE approach in tomato, indicating that a further improvement of the PE system for successful applications is demanded, such as the use of improved expression systems for enriching active PE complexes.

Minnesota Multiphasic Personality Inventory-Adolescent-Restructured Form (MMPI-A-RF) characteristics of ADHD in a Korean psychiatric sample.

Global rates of attention-deficit/hyperactivity disorder (ADHD) have risen. In Korea, ADHD is associated with functional impairments and comorbidity with other psychological disorders. This study examined the correlates of ADHD in a psychiatric sample of Korean adolescents on the Minnesota Multiphasic Personality Inventory-Adolescent-Restructured Form (MMPI-A-RF). In a clinical sample of 247 adolescents, MMPI-A-RF scores from 46 patients diagnosed with ADHD were compared to the remainder of the clinical sample and to the Korean MMPI-A-RF norms. Results demonstrated significantly different scores for the ADHD group on scales indicating externalizing concerns and behavior dysfunction compared with the clinical group with other disorders and to a normative sample. Notable differences were also observed between clinical groups on scales reflecting interpersonal functioning. Relative risk ratio analyses demonstrated that an MMPI-A-RF T-score of 55 was generally most effective for predicting risk for an ADHD diagnosis in the clinical sample.

Effects of equine-assisted activities on attention and quality of life in children with cerebral palsy in a randomized trial: examining the comorbidity with attention-deficit/hyperactivity disorder.

BACKGROUND: Attention problems and decreased quality of life are frequently accompanied in Cerebral Palsy (CP), which can negatively affect rehabilitation of physical disability. However, the majority of affected children remain untreated in the aspects of attention or psychosocial factors. Equine-Assisted Activities and Therapies (EAAT) use horse as a therapeutic modality including grooming as well as mounted riding activities in which patients exercise and experience mounted stimulation. It is known to help improve attention in children with ADHD, so that it can be an exercise therapy that is expected to improvement of attention as well as rehabilitating effects in CP patients. EAA may be a promising strategy to address the unmet need for CP patients. This study aims to investigate the efficacy of EAA for children with CP, those with both CP and ADHD and confirm the comorbidity between CP and ADHD. METHODS: Forty-six children with cerebral palsy participated in this study. For the exercise group, they participated in a 40-min session twice a week for a 16-week period, while the control group engaged in daily life without any special treatments. Each children individually were assessed on attention and psychological wellbeing at baseline and post-treatment. Comorbidity were identified based on the Diagnostic and Statistical Manual of Mental Disorder 5th edition (DSM-5) and confirmed by Korean Kiddie-Schedule for Affective Disorders and Schizophrenia Present and Lifetime Version (K-SADS-PL). RESULTS: Perseveration rated using the Conner's Performance Test (CPT) showed a significant decrease only in the exercise group (p < .024). However, no significant improvement in children's quality of life was observed after EAA program compared with control group. Among the total participants, fifteen children (31.91%) were diagnosed with ADHD. When conducting an additional analysis with the subsample of CP patients diagnosed with ADHD, the d', commission error and perseveration showed a significant decrease only in the exercise group. Children with CP and ADHD reported an improvement in quality of life both in exercise and control group, but only in the exercise group social functioning exhibited a significant difference. CONCLUSION: The positive effects of the EAA on attention and quality of life were confirmed. Children with CP in the exercise group were more capable to sustain their attention longer. Those with CP and ADHD showed an increase in attention and perceived to have better social skills after receiving 16 weeks of EAA compared to those in the control group. Considering high comorbidity of CP and ADHD, it seems that the EAA program could be the better alternative treatment for CP with attentional problem. The results of this study will contribute to growing evidence for the efficacy of EAA in children especially with CP and ADHD. TRIAL REGISTRATION: This trial was registered on ClinicalTrials.gov ( NCT03870893 ). Registered 26 July 2017.

B7-H3×4-1BB bispecific antibody augments antitumor immunity by enhancing terminally differentiated CD8+ tumor-infiltrating lymphocytes.

Cancer immunotherapy with 4-1BB agonists has limited further clinical development because of dose-limiting toxicity. Here, we developed a bispecific antibody (bsAb; B7-H3×4-1BB), targeting human B7-H3 (hB7-H3) and mouse or human 4-1BB, to restrict the 4-1BB stimulation in tumors. B7-H3×m4-1BB elicited a 4-1BB-dependent antitumor response in hB7-H3-overexpressing tumor models without systemic toxicity. BsAb primarily targets CD8 T cells in the tumor and increases their proliferation and cytokine production. Among the CD8 T cell population in the tumor, 4-1BB is solely expressed on PD-1+Tim-3+ "terminally differentiated" subset, and bsAb potentiates these cells for eliminating the tumor. Furthermore, the combination of bsAb and PD-1 blockade synergistically inhibits tumor growth accompanied by further increasing terminally differentiated CD8 T cells. B7-H3×h4-1BB also shows antitumor activity in h4-1BB-expressing mice. Our data suggest that B7-H3×4-1BB is an effective and safe therapeutic agent against B7-H3-positive cancers as monotherapy and combination therapy with PD-1 blockade.

Niche-specific MHC II and PD-L1 regulate CD4+CD8αα+ intraepithelial lymphocyte differentiation.

Conventional CD4+ T cells are differentiated into CD4+CD8αα+ intraepithelial lymphocytes (IELs) in the intestine; however, the roles of intestinal epithelial cells (IECs) are poorly understood. Here, we showed that IECs expressed MHC class II (MHC II) and programmed death-ligand 1 (PD-L1) induced by the microbiota and IFN-γ in the distal part of the small intestine, where CD4+ T cells were transformed into CD4+CD8αα+ IELs. Therefore, IEC-specific deletion of MHC II and PD-L1 hindered the development of CD4+CD8αα+ IELs. Intracellularly, PD-1 signals supported the acquisition of CD8αα by down-regulating the CD4-lineage transcription factor, T helper-inducing POZ/Krüppel-like factor (ThPOK), via the Src homology 2 domain-containing tyrosine phosphatase (SHP) pathway. Our results demonstrate that noncanonical antigen presentation with cosignals from IECs constitutes niche adaptation signals to develop tissue-resident CD4+CD8αα+ IELs.

Cancer immunotherapy with T-cell targeting cytokines: IL-2 and IL-7.

Clinical trials have demonstrated that an increased number of effector cells, especially tumor-specific T cells, is positively linked with patients' prognosis. Although the discovery of checkpoint inhibitors (CPIs) has led to encouraging progress in cancer immunotherapy, the lack of either T cells or targets for CPIs is a limitation for patients with poor prognosis. Since interleukin (IL)-2 and IL-7 are cytokines that target many aspects of T-cell responses, they have been used to treat cancers. In this review, we focus on the basic biology of how these cytokines regulate T-cell response and on the clinical trials using the cytokines against cancer. Further, we introduce several recent studies that aim to improve cytokines' biological activities and find the strategy for combination with other therapeutics. [BMB Reports 2021; 54(1): 21-30].

Evaluating the Measurement Invariance of MMPI-2-RF Restructured Clinical Scale 4 (Antisocial Behavior) between American and Korean Clinical Samples: Exploring Cultural and Translation Issues Affecting Item Responding.

Establishing the cross-cultural measurement invariance of psychometric scales is considered an essential step before scale means are compared across cultures. Although the MMPI instruments have been extensively researched, few studies have examined the measurement equivalence of MMPI scales in cross-cultural research. This study examined the measurement invariance of MMPI-2-RF Restructured Clinical Scale 4 (RC4; Antisocial Behavior) using multi-group confirmatory factor analysis with American and Korean clinical samples by (a) comparing a rationally-derived four-factor model (School Problems, Substance Abuse, Family Problems, and Violation of Social Norms) with a one-factor model, and (b) examining the measurement invariance of the RC4 four-factor model. After adjusting for age and gender, partial scalar invariance was achieved, and six non-invariant items were identified, most of which centered around substance abuse. Results support the generalizability of the four factors across cultures; however, special attention is needed when using substance abuse items with Korean clinical populations. Plausible sources of item non-invariance were explored in the context of translation challenges and observed patterns of relationship with external measures.

CRISPR/Cas9-based precise excision of SlHyPRP1 domain(s) to obtain salt stress-tolerant tomato.

KEY MESSAGE: CRISPR/Cas9-based multiplexed editing of SlHyPRP1 resulted in precise deletions of its functional motif(s), thereby resulting in salt stress-tolerant events in cultivated tomato. Crop genetic improvement to address environmental stresses for sustainable food production has been in high demand, especially given the current situation of global climate changes and reduction of the global food production rate/population rate. Recently, the emerging clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas)-based targeted mutagenesis has provided a revolutionary approach to crop improvement. The major application of CRISPR/Cas in plant genome editing has been the generation of indel mutations via error-prone nonhomologous end joining (NHEJ) repair of DNA DSBs. In this study, we examined the power of the CRISPR/Cas9-based novel approach in the precise manipulation of protein domains of tomato hybrid proline-rich protein 1 (HyPRP1), which is a negative regulator of salt stress responses. We revealed that the precise elimination of SlHyPRP1 negative-response domain(s) led to high salinity tolerance at the germination and vegetative stages in our experimental conditions. CRISPR/Cas9-based domain editing may be an efficient tool to engineer multidomain proteins of important food crops to cope with global climate changes for sustainable agriculture and future food security.

CRISPR/Cas-based precision genome editing via microhomology-mediated end joining.

Gene editing and/or allele introgression with absolute precision and control appear to be the ultimate goals of genetic engineering. Precision genome editing in plants has been developed through various approaches, including oligonucleotide-directed mutagenesis (ODM), base editing, prime editing and especially homologous recombination (HR)-based gene targeting. With the advent of CRISPR/Cas for the targeted generation of DNA breaks (single-stranded breaks (SSBs) or double-stranded breaks (DSBs)), a substantial advancement in HR-mediated precise editing frequencies has been achieved. Nonetheless, further research needs to be performed for commercially viable applications of precise genome editing; hence, an alternative innovative method for genome editing may be required. Within this scope, we summarize recent progress regarding precision genome editing mediated by microhomology-mediated end joining (MMEJ) and discuss their potential applications in crop improvement.

Hybrid Fc-fused interleukin-7 induces an inflamed tumor microenvironment and improves the efficacy of cancer immunotherapy.

OBJECTIVES: Emerging oncotherapeutic strategies require the induction of an immunostimulatory tumor microenvironment (TME) containing numerous tumor-reactive CD8+ T cells. Interleukin-7 (IL-7), a T-cell homeostatic cytokine, induces an antitumor response; however, the detailed mechanisms underlying the contributions of the IL-7 to TME remain unclear. Here, we aimed to investigate the mechanism underlying the induction of antitumor response by hybrid Fc-fused long-acting recombinant human IL-7 (rhIL-7-hyFc) through regulation of both adaptive and innate immune cells in the TME. METHODS: We evaluated rhIL-7-hyFc-mediated antitumor responses in murine syngeneic tumor models. We analysed the cellular and molecular features of tumor-infiltrating lymphocytes (TILs) and changes in the TME after rhIL-7-hyFc treatment. Furthermore, we evaluated the antitumor efficacy of rhIL-7-hyFc combined with chemotherapy and checkpoint inhibitors (CPIs). RESULTS: Systemic delivery of rhIL-7-hyFc induced significant therapeutic benefits by expanding CD8+ T cells with enhanced tumor tropism. In tumors, rhIL-7-hyFc increased both tumor-reactive and bystander CD8+ TILs, all of which displayed enhanced effector functions but less exhausted phenotypes. Moreover, rhIL-7-hyFc suppressed the generation of immunosuppressive myeloid cells in the bone marrow of tumor-bearing mice, resulting in the immunostimulatory TME. Combination therapy with chemotherapy and CPIs, rhIL-7-hyFc elicited a strong antitumor response and even under a T lymphopenic condition by restoring CD8+ T cells. When combined with chemotherapy and CPIs, rhIL-7-hyFc administration enhanced antitumor response under intact andlymphopenic conditions by restoring CD8+ T cells. CONCLUSION: Taken together, these data demonstrate that rhIL-7-hyFc induces antitumor responses by generating T-cell-inflamed TME and provide a preclinical proof of concept of immunotherapy with rhIL-7-hyFc to enhance therapeutic responses in the clinic.

Development and validation study of Game Overuse Screening Questionnaire.

The aim of this study was to develop a screening questionnaire to distinguish high-risk individuals associated with game overuse from casual internet users. Reliability, validity, and diagnostic ability were evaluated for the newly developed Game Overuse Screening Questionnaire (GOS-Q). Preliminary items were assessed by 50 addiction experts online and 30 questions were selected. A total of 158 subjects recruited from six community centers for internet addiction participated in this study. Finally, 150 people were used in the analysis after excluding eight non-respondents. GOS-Q, Young's internet addiction scale, and Korean scale for internet addiction were used to assess concurrent validity. Internal consistency and item-total correlations were favorable (α= 0.96, r= 0.47-0.82). Test-retest reliability was moderate in size (r= 0.74). GOS-Q showed superior concurrent validity, and the highest correlation with Y-Scale (r= 0.77). The construct validity was marginally supported by a six-factor model using exploratory factor analysis. The area under the Receiver Operating Characteristic curve was 0.945. The high-risk addiction group was effectively characterized by a cut-off point of 38.5, with a sensitivity of 0.87 and a specificity of 0.88. Overall, the current study supports the use of GOS-Q as a reliable screening tool in a variety of settings.

Highly efficient homology-directed repair using CRISPR/Cpf1-geminiviral replicon in tomato.

Genome editing via the homology-directed repair (HDR) pathway in somatic plant cells is very inefficient compared with error-prone repair by nonhomologous end joining (NHEJ). Here, we increased HDR-based genome editing efficiency approximately threefold compared with a Cas9-based single-replicon system via the use of de novo multi-replicon systems equipped with CRISPR/LbCpf1 in tomato and obtained replicon-free but stable HDR alleles. The efficiency of CRISPR/LbCpf1-based HDR was significantly modulated by physical culture conditions such as temperature and light. Ten days of incubation at 31 °C under a light/dark cycle after Agrobacterium-mediated transformation resulted in the best performance among the tested conditions. Furthermore, we developed our single-replicon system into a multi-replicon system that effectively increased HDR efficiency. Although this approach is still challenging, we showed the feasibility of HDR-based genome editing of a salt-tolerant SlHKT1;2 allele without genomic integration of antibiotic markers or any phenotypic selection. Self-pollinated offspring plants carrying the HKT1;2 HDR allele showed stable inheritance and germination tolerance in the presence of 100 mm NaCl. Our work may pave the way for transgene-free editing of alleles of interest in asexually and sexually reproducing plants.

Challenges and Perspectives in Homology-Directed Gene Targeting in Monocot Plants.

Continuing crop domestication/redomestication and modification is a key determinant of the adaptation and fulfillment of the food requirements of an exploding global population under increasingly challenging conditions such as climate change and the reduction in arable lands. Monocotyledonous crops are not only responsible for approximately 70% of total global crop production, indicating their important roles in human life, but also the first crops to be challenged with the abovementioned hurdles; hence, monocot crops should be the first to be engineered and/or de novo domesticated/redomesticated. A long time has passed since the first green revolution; the world is again facing the challenge of feeding a predicted 9.7 billion people in 2050, since the decline in world hunger was reversed in 2015. One of the major lessons learned from the first green revolution is the importance of novel and advanced trait-carrying crop varieties that are ideally adapted to new agricultural practices. New plant breeding techniques (NPBTs), such as genome editing, could help us succeed in this mission to create novel and advanced crops. Considering the importance of NPBTs in crop genetic improvement, we attempt to summarize and discuss the latest progress with major approaches, such as site-directed mutagenesis using molecular scissors, base editors and especially homology-directed gene targeting (HGT), a very challenging but potentially highly precise genome modification approach in plants. We therefore suggest potential approaches for the improvement of practical HGT, focusing on monocots, and discuss a potential approach for the regulation of genome-edited products.

A comparative evaluation of Korean MMPI-A and MMPI-A-RF Substance Abuse Scales.

OBJECTIVE: The purpose of the present study was to compare psychometric properties of the Substance Abuse (SUB) Scale on the Korean Minnesota Multiphasic Personality Inventory-Adolescent-Restructured Form (MMPI-A-RF) with those on the Korean MMPI-A (the Alcohol/Drug Problem Acknowledgment Scale [ACK]), the Alcohol/Drug Problem Proneness Scale [PRO], and the MacAndrew Alcoholism Scale-Revised Scale [MAC-R]). METHOD: Participants consisted of 237 Korean adolescent psychiatric patients whose scores on these measures were compared in terms of internal consistency and predictive validity. RESULTS: Scores on SUB exhibited superior internal consistency to that of the MMPI-A substance abuse scales. Further, scores on SUB predicted substance abuse more accurately than did the optimal combination of scores on the MMPI-A substance abuse scales. CONCLUSION: Results provide strong support for the use of the Korean MMPI-A-RF SUB scale when assessing substance abuse in Korean youth.