This study introduces the prostate cancer linear energy transfer sensitivity index (PCLSI) as a novel method to predict relative biological effectiveness (RBE) in prostate cancer using linear energy transfer (LET) in proton therapy based on screening for DNA repair mutations.

Five prostate cancer cell lines with DNA repair mutations known to cause sensitivity to LET and DNA repair inhibitors were examined using published data. Relative Du145 LET sensitivity data were leveraged to deduce the LET equivalent of olaparib doses. The PCLSI model was built using three of the prostate cancer cell lines (LNCaP, 22Rv1 and Du145) with DNA mutation frequency from patient cohorts. The PCLSI model was compared against two established RBE models, McNamara and McMahon, for LET-optimized prostate cancer treatment plans.

The PCLSI model relies on the presence of eight DNA repair mutations: AR, ATM, BRCA1, BRCA2, CDH1, ETV1, PTEN and TP53, which are most likely to predict increased LET sensitivity and RBE in proton therapy. In the LET-optimized plan, the PCLSI model indicates that prostate cancer cells with these DNA repair mutations are more sensitive to increased LET than the McNamara and McMahon RBE models, with expected RBE increases ranging from 11%–33% at 2keV/µm.

The PCLSI model predicts increasing RBE as a function of LET in the presence of certain genetic mutations. The integration of LET-optimized proton therapy and genetic mutation profiling could be a significant step toward the use of individualized medicine to improve outcomes using RBE escalation without the potential toxicity of physical dose escalation.

Transcranial direct current stimulation (tDCS) is a promising treatment for major depressive disorder (MDD). This study evaluated its antidepressant and cognitive effects as a safe, effective, home-based therapy for MDD.

This double-blind, sham-controlled, randomized trial divided participants into low-intensity (1 mA, n = 47), high-intensity (2 mA, n = 49), and sham (n = 45) groups, receiving 42 daily tDCS sessions, including weekends and holidays, targeting the dorsolateral prefrontal cortex for 30 minutes. Assessments were conducted at baseline and weeks 2, 4, and 6. The primary outcome was cognitive improvement assessed by changes in total accuracy on the 2-back test from baseline to week 6. Secondary outcomes included changes in depressive symptoms (HAM-D), anxiety (HAM-A), and quality of life (QLES). Adverse events were monitored. This trial was registered with ClinicalTrials.gov (NCT04709952).

In the tDCS study, of 141 participants (102 [72.3%] women; mean age 35.7 years, standard deviation 12.7), 95 completed the trial. Mean changes in the total accuracy scores from baseline to week 6 were compared across the three groups using an F-test. Linear mixed-effects models examined the interaction of group and time. Results showed no significant differences among groups in cognitive or depressive outcomes at week 6. Active groups experienced more mild adverse events compared to sham but had similar rates of severe adverse events and dropout.

Home-based tDCS for MDD demonstrated no evidence of effectiveness but was safe and well-tolerated. Further research is needed to address the technical limitations, evaluate broader cognitive functions, and extend durations to evaluate its therapeutic potential.

In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.

A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.

We performed 1,351 transfusions in 16 months. The transparency of the digital inventory at each site was critical to facilitate qualification, randomization, and overnight shipments of blood group-compatible plasma for transfusions into trial participants. While inventory challenges were heightened with COVID-19 convalescent plasma, the cloud-based system, and the flexible approach of the plasma coordination center staff across the blood bank network enabled decentralized procurement and distribution of investigational products to maintain inventory thresholds and overcome local supply chain restraints at the sites.

The rapid creation of a plasma coordination center for outpatient transfusions is infrequent in the academic setting. Distributing more than 3,100 plasma units to blood banks charged with managing investigational inventory across the U.S. in a decentralized manner posed operational and regulatory challenges while providing opportunities for the plasma coordination center to contribute to research of global importance. This program can serve as a template in subsequent public health emergencies.

High-quality evidence is lacking for the impact on healthcare utilisation of short-stay alternatives to psychiatric inpatient services for people experiencing acute and/or complex mental health crises (known in England as psychiatric decision units [PDUs]). We assessed the extent to which changes in psychiatric hospital and emergency department (ED) activity were explained by implementation of PDUs in England using a quasi-experimental approach.

We conducted an interrupted time series (ITS) analysis of weekly aggregated data pre- and post-PDU implementation in one rural and two urban sites using segmented regression, adjusting for temporal and seasonal trends. Primary outcomes were changes in the number of voluntary inpatient admissions to (acute) adult psychiatric wards and number of ED adult mental health-related attendances in the 24 months post-PDU implementation compared to that in the 24 months pre-PDU implementation.

The two PDUs (one urban and one rural) with longer (average) stays and high staff-to-patient ratios observed post-PDU decreases in the pattern of weekly voluntary psychiatric admissions relative to pre-PDU trend (Rural: −0.45%/week, 95% confidence interval [CI] = −0.78%, −0.12%; Urban: −0.49%/week, 95% CI = −0.73%, −0.25%); PDU implementation in each was associated with an estimated 35–38% reduction in total voluntary admissions in the post-PDU period. The (urban) PDU with the highest throughput, lowest staff-to-patient ratio and shortest average stay observed a 20% (−20.4%, CI = −29.7%, −10.0%) level reduction in mental health-related ED attendances post-PDU, although there was little impact on long-term trend. Pooled analyses across sites indicated a significant reduction in the number of voluntary admissions following PDU implementation (−16.6%, 95% CI = −23.9%, −8.5%) but no significant (long-term) trend change (−0.20%/week, 95% CI = −0.74%, 0.34%) and no short- (−2.8%, 95% CI = −19.3%, 17.0%) or long-term (0.08%/week, 95% CI = −0.13, 0.28%) effects on mental health-related ED attendances. Findings were largely unchanged in secondary (ITS) analyses that considered the introduction of other service initiatives in the study period.

The introduction of PDUs was associated with an immediate reduction of voluntary psychiatric inpatient admissions. The extent to which PDUs change long-term trends of voluntary psychiatric admissions or impact on psychiatric presentations at ED may be linked to their configuration. PDUs with a large capacity, short length of stay and low staff-to-patient ratio can positively impact ED mental health presentations, while PDUs with longer length of stay and higher staff-to-patient ratios have potential to reduce voluntary psychiatric admissions over an extended period. Taken as a whole, our analyses suggest that when establishing a PDU, consideration of the primary crisis-care need that underlies the creation of the unit is key.

Three-dimensional chromatin interactions regulate gene expressions. The significance of de novo mutations (DNMs) in chromatin interactions remains poorly understood for autism spectrum disorder (ASD).

To investigate the genomic architecture of ASD in terms of non-coding de novo mutations and 3-dimensional chromatin interactions

We generated 813 whole-genome sequences from 242 Korean simplex families to detect DNMs, and identified target genes which were putatively affected by non-coding DNMs in chromatin interactions.

Non-coding DNMs in chromatin interactions were significantly involved in transcriptional dysregulations related to ASD risk. Correspondingly, target genes showed spatiotemporal expressions relevant to ASD in developing brains and enrichment in biological pathways implicated in ASD, such as histone modification. Regarding clinical features of ASD, non-coding DNMs in chromatin interactions particularly contributed to low intelligence quotient levels in ASD probands. We further validated our findings using two replication cohorts, Simons Simplex Collection (SSC) and MSSNG, and showed the consistent enrichment of non-coding DNM-disrupted chromatin interactions in ASD probands. Generating human induced pluripotent stem cells in two ASD families, we were able to demonstrate that non-coding DNMs in chromatin interactions alter the expression of target genes at the stage of early neural development.

Taken together, our findings indicate that non-coding DNMs in ASD probands lead to early neurodevelopmental disruption implicated in ASD risk via chromatin interactions.

None Declared

This study investigated the prevalence and comorbidities of attention deficit hyperactivity disorder (ADHD) among adults and children/adolescents in Korea.

This study used data from the Korea Health Insurance Review and Assessment Service collected from 2008 to 2018. Study participants comprised patients with at least one diagnosis of ADHD (International Statistical Classification of Diseases and Related Health Provisions, 10th revision code F90.0). Prevalence rates and psychiatric comorbidities were also analyzed.

We identified 878,996 patients diagnosed with ADHD between 2008 and 2018. The overall prevalence rate of diagnosed ADHD increased steeply from 127.1/100,000 in 2008 to 192.9/100,000 in 2018; it increased 1.47 times in children/adolescents (≤ 18 years) and 10.1 times in adults (> 18 years) during this period. Among children/adolescent and adult ADHD patients, 61.84% (95% confidence interval [95% CI] 61.74−61.93) and 78.72% (95% CI 78.53−78.91) had at least one psychiatric comorbidity, respectively.

Our results showed that the prevalence rate of diagnosed ADHD has increased in Korea; however, it is lower than the global average. Further studies are required to identify and treat vulnerable populations appropriately.

None Declared

Nurses are at an increased risk for work-related stress resulting in post-traumatic stress disorder (PTSD). They are susceptible due to frequent exposure to traumatic situations providing care for patients.

The purpose of this systematic review is to comprehensively review the content and characteristics of intervention programs for reducing the post-traumatic stress of nurses or nursing students, providing a basis for developing a standardized protocol for programs to promote the integrated health of nurses and protect them from stress events in clinical environments.

This is a systematic review. Participants (P) targeted nurses or nursing students; Intervention (I) included intervention programs for reducing post-traumatic stress; Comparison (C) was control groups provided with usual or no interventions ; and Outcomes (O) referred to changes in physical or emotional reactions toward post-traumatic stress. Two researchers searched four databases including PubMed, CINAHL, PsycINFO, and EMBASE with keywords such as “nurse,” “post-trumatic stress disorder,” “program,” and “intervention”. A total of 7,523 studies were searched and 10 studies were included for final analysis (Image 1). The Risk of Bias2 (Image 2) and the Risk of Bias for Non-randomized Study I (Image 3) were used to evaluate the quality the included studies.

The number of studies is increasing, with four studies published before 2020, and six studies published since, of which three in 2022. Definitions of trauma situations to which nurses are exposed included diverse elements such as patient death, workplace violence, the COVID-19 pandemic, and complex trauma experiences due to working environments. Most studies have provided multiple intervention sessions, which is appropriate considering the characteristics of PTSD. Most studies examined the secondary effects on mental health such as anxiety, depression, and burnout caused by stress rather than evaluating stress itself. The quality of the study was generally highly biased. The risk of bias increased for the two randomized controlled trials in terms of measurement outcomes and outcome description. The other eight non-randomized studies all included a self-reporting questionnaire of participants, leading to a risk of bias in terms of measurement outcomes.

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Studies have been conducted to confirm the effectiveness of interventions given heightened concerns about PTSD in nurses. However, the concept of the trauma experienced by nurses was not integrally defined, and information on interventions was often limited. Efforts are required to improve the quality of research in terms of experimental study design.

None Declared

Bladder cancer, which is primarily a non-muscle invasive bladder cancer (NMIBC), is prevalent worldwide and its incidence is increasing. NMIBC shows a high recurrence rate of 50-70%, and in 25% of cases, progresses to muscle-invasive disease (Saginala K et al. Med Sci 2020; 15) (Fernandez-Gomez, J et al. J Urol 2009; 182(5) 2195-2203). Frequent recurrence and consecutive medical interventions in patients with NMIBC lead to psychological problems such as anxiety, fear of recurrence, depression, and stress, resulting in reduced quality of life (Chung et al. Support Care Cancer 2019; 27(10), 3877-3885). It is expected that the increased accessibility and convenience of mobile health (mHealth) will be effective in providing a mobile-based psychological intervention program to promote the mental health of patients with NMIBC.

This study aims to develop a mobile-based mental health improvement program for NMIBC patients, design a protocol for evaluating feasibility, and provide preliminary evidence of the efficacy of the developed program.

The program content was developed based on the results of a needs assessment conducted among patients with NMIBC through a cross-sectional study. The draft program was prepared by referring to the guidelines of the National Comprehensive Cancer Network and publications of the International Continence Society. Based on the developed draft, two professors of nursing, a professor of counseling psychology, a registered nurse, and a counseling practitioner verified the validity of the content before finalizing the program. The final version of the developed program consisted of one session on NMIBC knowledge and symptom management and five sessions on mental health improvement. Researchers sent an online link to the YouTube video comprising lecture materials and voice recordings of health professionals weekly using a mobile messenger (Kakao Talk) (Image 1). The topics of each session were as follows: Session 1 (Understanding of bladder cancer and treatment), Session 2 (Understanding and respecting myself), Session 3 (Maintaining reasonable thoughts and positive emotions), Session 4 (Benefits of positive emotions and healthy communication), Session 5 (Living in a healthy way through stress management), and Session 6 (Finding happiness and meanings in daily life).

The protocol for evaluating the feasibility of the developed program is outlined in Image 2.

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The feasibility of the mental health improvement program for patients with NMIBC based on mobile messenger (KakaoTalk) will be evaluated through the developed protocol. Moreover, by introducing a program that reflects the feasibility of test results into practice, the results of this study can contribute to improving the quality of life of patients with NMIBC.

None Declared

Lamina-specific alterations of inhibitory circuitries have been considered the crucial pathogenesis of perceptual, cognitive and behavioral symptoms presented in schizophrenia and mood disorders. Especially, with emerging evidences indicating the close lamina-specific relationship between synaptic defects and γ-Aminobutyric acid (GABA)-related gene dysfunctions, it has been suggested the mRNA dysregulations of Tyrosine kinase B (TrkB) and Glutamate decarboxylase 67 (GAD67) could particularly be implicated in middle and deep layers of neocortex of patients with major psychiatric disorders.

Giving inquiries of whether defects of these mRNA levels in Orbitofrontal cortex (OFC) would be involved as lamina-specific patterns in individuals with schizophrenia and mood disorders.

We examined mRNA levels of BDNF, TrkB and GAD67 in each OFC layer I through VI. We analyzed data from postmortem brain tissue of the Stanley Neuropathology Consortium Integrative Database (SNCID). SNCID consists of 15 subjects in each of four groups (schizophrenia, bipolar disorder, major depression without psychotic features, and unaffected controls). All groups were matched for age, sex, race, brain pH and post-mortem interval.

We found TrkB mRNA levels to be significantly reduced in layer VI in both groups with schizophrenia (25.8%) and bipolar disorder (35.7%) compared with controls. GAD67 mRNA levels were also significantly reduced in layer III and IV in patients with schizophrenia (23.4% and 22.7%, respectively) and bipolar disorder (31.2% and 24.9%, respectively) compared with controls. Individuals with major depression showed only trends toward decreased mRNA levels of GAD67 in layer III and IV and of TrkB in layer VI compared with controls. TrkB mRNA levels in layer VI were significantly correlated with GAD67 mRNA levels in layer III (ρ=0.581, p=0.037) and IV (ρ=0.857, p<0.001) in subjects with bipolar disorder, but not in those with schizophrenia. When analyzed with partial correlation controlling the effects of pH and PMI, significance of correlation remained only between GAD67 mRNA in layer IV and TrkB mRNA in layer VI in individuals with bipolar disorder (ρ=0.768, p=0.006).

The resulting lamina-specific decreases in inhibitory tone across layers of OFC may contribute to the unrestrained irritability and violent behaviors in common shared by both patients with schizophrenia and bipolar disorder. Nonetheless, our findings indicate the obvious correlations between lamina-specifically altered TrkB and GAD67 mRNA levels in OFC might be a candidate for endophenotype of bipolar disorder.

None Declared

Obsessive-compulsive disorder (OCD) and schizophrenia are often reported as co-morbid conditions. However, the evidence of an association between OCD and the risk of schizophrenia is limited. This study investigated the risk of schizophrenia in patients newly diagnosed with OCD using a nationally representative sample cohort in South Korea.

Data were obtained from the 2002–2013 Korean National Health Insurance Service-National Sample Cohort of the National Health Insurance Service. Using propensity score matching, 2509 patients with OCD and a control group of 7527 patients were included in the analysis. Chi-squared tests were used to investigate and compare the general characteristics of the study population. The risk of schizophrenia was analysed using the Cox proportional hazard model.

The incidence rate was 45.79/10 000 person-year for patients with OCD and 4.19/10 000 person-year for patients without OCD. Patients with OCD had a higher risk of schizophrenia compared to the control group after adjusting for covariates (hazard ratio = 10.46, 95% confidence interval = 6.07–18.00).

This study identified an association between the diagnosis of OCD and the risk of schizophrenia in a South Korean national representative cohort. Further research using a prospective design to clarify the causality of OCD in schizophrenia in a controlled environment should be conducted to validate these findings.

Hwa-Byung is characterized by feelings of anger or resent about unreasonable social violence and trauma. Although Prevalence of Hwa-Byung is high in middle-aged, recently Hwa-Byung is occurred in young people. And it is suggested that young Hwa-Byung patients will show different patterns from middle-aged.

The purpose of present study was to qualitatively analyze young Hwa-Byung patients’ experiences of symptoms and psychological characteristics related to antecedent events of Hwa-Byung.

10 women aged 20s were Interviewed using semi-structured questionnaires to in-depth study on their experiences related to Hwa-Byung. The interview data were analyzed using phenomenological approach in order to understand the essence of experiences. In particular, it was analyzed through five steps according to Giorgi (1985). First, by repeatedly reading the material, recurring themes were identified. Second, the meaning units were divided to capture important parts of participants’ statements. Third, similar meaning units were grouped together. Fourth, the determined meaning units were described in psychological term. Finally, research data were integrated and presented according to the described meaning units. Reliability between coders was higher than the minimum reliability coefficient.

In symptoms, two themes and seven sub-themes were emerged. In psychological characteristics, three components and five sub-themes were derived. In particular, the antecedent events of young Hwa-Byung patients were related to vertical social relationships, suggesting that Hwa-Byung need to be understood under social context which make them angry.

Present study revealed the social context of Hwa-Byung by discussing the differences between young and middle-aged patients, and furthermore, differences between Hwa-Byung and depression, PTSD patients.

No significant relationships.

Hwa-Byung is a cultural-related mental syndrome that reflects the cultural characteristics of Korean in DSM-IV. This syndrome is caused by anger or resentment towards unreasonable social violence and trauma.

The purpose of this study is to revise and validate the ’Hwa-Byung scale’, which can be used to diagnose Hwa-Byung and evaluate the severity of its symptoms.

To begin with, the factors of the Hwa-Byung scale were set based on the previous studies. Additionally, the respective subfactors were generated by the semi-structured interviews with these patients. Based on these factors and previous studies, a 142-item pool was developed and verified by six Oriental Neuropsychiatrists. A pilot study was conducted on 50 patients with Hwa-Byung and the main study for the validation was conducted on 200 Hwa-Byung patients. Item analysis, internal consistency, and exploratory/confirmatory factor analysis were performed. Lastly, this study analyzed the ROC curve to present the diagnostic cut-off score of the scale.

As a result of analyzing the content validity of the item pool, we constructed a preliminary scale. We excluded the inadequate questions from the pilot study results. In the main study, The Hwa-Byung scale showed high internal consistency and its items were suitable for the factor structure. Finally, we suggest an optimal cut-off score of the symptoms sub-scale for screening Hwa-Byung.

Overall, the results of this study indicated the reliability and validity of the Hwa-Byung Scale. Based on these results, we discussed several values and limitations of this study and provided suggestions for further research.

No significant relationships.

Hwa-Byung is a mental syndrome classified as a “cultural-related syndrome” which reflects the cultural characteristics of Korea in DSM-IV. Hwa-Byung is caused by anger, which is characterized by feelings of anger or resent about unreasonable social violence and trauma. Kwon et al (2008) had developed self-report measure to assess severity of Hwa-Byung but it has several limitations to use in current clinical settings. Therefore, we investigated opinions of experts who have professionality in giving treatment of Hwa-Byung patients in the clinical settings.

The present study aimed to reach consent of oriental neuropsychiatrists’ opinions about the direction of revision of the Hwa-Byung scale.

The Delphi method is a survey method that induces people to freely present their opinions without face-to-face processes and reaches consent through continuous feedback of survey results while ensuring anonymity. The Consensus Panel consists of 16 experts who are Oriental neuropsychiatrists and have experience in diagnosing patients with Hwa-Byung. A total of four surveys were conducted as consensus was reached on the fourth round. Each questionnaire was distributed by mail to a panel of experts and was asked to submit a response after receiving the questionnaire.

The results of the study are as follows. First, common factors for Hwa-Byung include anger, resent/blame, modify memory bias and attention bias for anger events. Second, characteristics of young Hwa-Byung patients include stress caused by social factors and excessive immersion in certain things such as drinking or smoking.

Therefore, when revising the Hwa-Byung scale, it would be necessary to include these factors.

No significant relationships.