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BACKGROUND: Phlegm is prevalent symptom in patients with chronic obstructive pulmonary disease (COPD). Few studies have investigated the effectiveness of N-acetylcysteine (NAC) nebulizer therapy in COPD patients. We evaluated the effect of nebulized NAC on the improvement of phlegm symptom in COPD patients. METHODS: This was a 12-week, prospective, single-arm, open-label, phase IV multi-center trial (NCT05102305, Registration Date: 20-October-2021). We enrolled patients aged ≥ 40 years with post bronchodilator forced expiratory volume in one second/forced vital capacity (FEV1/FVC) < 0.7 and COPD assessment test (CAT) phlegm score ≥ 2; the patients were current or ex-smoker with smoking pack-years ≥ 10. The primary endpoint was to determine the change in CAT phlegm score at 12 weeks compared to the baseline. Patients were assessed at baseline, 4, 8, and 12 weeks of treatment using the CAT score. RESULTS: In total, 100 COPD patients were enrolled from 10 hospitals. The mean age of the patients was 71.42 ± 8.20 years, with 19.78% being current-smokers and 80.22% being ex-smokers. The mean smoking pack-years was 40.32 ± 35.18. The mean FVC, FEV1, and FEV1/FVC were 3.94 L (75.44%), 2.22 L (58.50%), and 0.53, respectively. The CAT phlegm score at baseline was 3.47 ± 1.06, whereas after 12 weeks of nebulized NAC it significantly decreased to 2.62 ± 1.30 (p < 0.01). More than half (53.5%) of the patients expressed satisfaction with the effects of nebulized NAC therapy. Adverse events occurred in 8 (8.0%) patients. Notably, no serious adverse drug reactions were reported. CONCLUSION: In this study, we have established the effectiveness and safety of nebulized NAC over 12 weeks.

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The neuropathology of mood disorders, including the diagnostic transition from major depressive disorder (MDD) to bipolar disorder (BD), is poorly understood. This study investigated resting-state electroencephalography (EEG) activity in patients with MDD and those whose diagnosis changed from MDD to BD. Among sixty-eight enrolled patients with MDD, the diagnosis of 17 patients converted to BD during the study period. We applied machine learning techniques to differentiate the two groups using sensor- and source-level EEG features. At the sensor level, patients with BD showed higher theta band power at the AF3 channel and low-alpha band power at the FC5 channel compared to patients with MDD. At the source level, patients with BD showed higher theta band activity in the right anterior cingulate and low-alpha band activity in the left parahippocampal gyrus. These four EEG features were selected for discriminating between BD and MDD with the best classification performance showing an accuracy of 80.88%, a sensitivity of 76.47%, and a specificity of 82.35%. Our findings revealed distinct theta and low-alpha band activities in patients with BD and MDD. These differences could potentially serve as candidate neuromarkers for the diagnosis and diagnostic transition between the two distinct mood disorders.

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Differentiating between the diagnoses of mood disorders and other psychiatric disorders, and predicting treatment response in depression has long been a concern for clinicians. Machine learning (ML) is one part of artificial intelligence that focuses on instructing computers to mimic the cognitive abilities of the human brain through training. This study will review the research on the use of ML techniques to differentiate diagnoses and predict treatment responses in mood disorders based on electroencephalography (EEG) data. There have been several attempts to differentiate between the diagnoses of bipolar disorder and major depressive disorder , mood disorders, and other psychiatric disorders using ML techniques found on EEG markers. Previous studies have shown that accuracy varies depending on which EEG markers are used, the sample size, and the ML technique. Also, precise and improved ML approaches can be developed by adapting the various feature selection and validation methods that reflect each disease's characteristics. Although ML faces some limitations and challenges in solving for consistent and improved accuracy in the diagnosis and treatment of mood disorders, it has a great potential to understand mood disorders better and provide valuable tools to personalize both identification and treatment.

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Studies exploring the neurophysiology of suicide are scarce and the neuropathology of related disorders is poorly understood. This study investigated source-level cortical functional networks using resting-state electroencephalography (EEG) in drug-naïve depressed patients with suicide attempt (SA) and suicidal ideation (SI). EEG was recorded in 55 patients with SA and in 54 patients with SI. Particularly, all patients with SA were evaluated using EEG immediately after their SA (within 7 days). Graph-theory-based source-level weighted functional networks were assessed using strength, clustering coefficient (CC), and path length (PL) in seven frequency bands. Finally, we applied machine learning to differentiate between the two groups using source-level network features. At the global level, patients with SA showed lower strength and CC and higher PL in the high alpha band than those with SI. At the nodal level, compared with patients with SI, patients with SA showed lower high alpha band nodal CCs in most brain regions. The best classification performances for SA and SI showed an accuracy of 73.39%, a sensitivity of 76.36%, and a specificity of 70.37% based on high alpha band network features. Our findings suggest that abnormal high alpha band functional network may reflect the pathophysiological characteristics of suicide and serve as a clinical biomarker for suicide.

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BACKGROUND: Poor uptake to pulmonary rehabilitation (PR) is still challenging around the world. There have been few nationwide studies investigating whether PR impacts patient outcomes in COPD. We investigated the change of annual PR implementation rate, medical costs, and COPD outcomes including exacerbation rates and mortality between 2015 and 2019. RESEARCH QUESTION: Does PR implementation improve outcomes in patients with COPD in terms of direct cost, exacerbation, and mortality? STUDY DESIGN AND METHODS: Data of patients with COPD extracted from a large Korean Health Insurance Review and Assessment service database (2015-2019) were analyzed to determine the trends of annual PR implementation rate and direct medical costs of PR. Comparison of COPD exacerbation rates between pre-PR and post-PR, and the time to first exacerbation and mortality rate according to PR implementation, were also assessed. RESULTS: Among all patients with COPD in South Korea, only 1.43% received PR. However, the annual PR implementation rate gradually increased from 0.03% to 1.4% during 4 years, especially after health insurance coverage commencement. The direct medical cost was significantly higher in the PR group than the non-PR group, but the costs in these groups showed decreasing and increasing trends, respectively. Both the incidence rate and frequency of moderate-to-severe and severe exacerbations were lower during the post-PR period compared with the pre-PR period. The time to the first moderate-to-severe and severe exacerbations was longer in the PR group than the non-PR group. Finally, PR implementation was associated with a significant decrease in mortality. INTERPRETATION: We concluded that health insurance coverage increases PR implementation rates. Moreover, PR contributes toward improving outcomes including reducing exacerbation and mortality in patients with COPD. However, despite the well-established benefits of PR, its implementation rate remains suboptimal.

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Acanthogobius lactipes is a demersal, euryhaline fish belonging to the suborder Gobiodei. This study sequenced and described the complete mitochondrial genome of A. lactipes for the first time. The circular genome of A. lactipes is 16,592 bp in length and contains 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes, and a control region. The overall A, C, G, and T contents were 27.78, 27.31, 17.52, and 27.39%, respectively. Based on the 13 protein-coding genes, the phylogenetic tree showed that A. lactipes formed a well-supported cluster with the genus Acanthogobius and rooted with other family Oxudercidae species.

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Globally, liver cancer (LC) is the sixth-most frequently occurring and the second-most fatal malignancy, responsible for 0.83 million deaths annually. Although the application of herbal drugs in cancer therapies has increased, their anti-LC activity and relevant mechanisms have not been fully studied from a systems perspective. To address these issues, we conducted a system-perspective network pharmacological investigation into the activity and mechanisms underlying the action of the herbal drug. FDY003 reduced the viability of human LC treatment. FDY003 reduced the viability of human LC cells and elevated their chemosensitivity. There were a total of 16 potential bioactive chemical components in FDY003 and they had 91 corresponding targets responsible for the pathological processes in LC. These FDY003 targets were functionally involved in regulating the survival, proliferation, apoptosis, and cell cycle of LC cells. Additionally, we found that FDY003 may target key signaling cascades connected to diverse LC pathological mechanisms, namely, PI3K-Akt, focal adhesion, IL-17, FoxO, MAPK, and TNF pathways. Overall, this study contributed to integrative mechanistic insights into the anti-LC potential of FDY003.

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Pancreatic cancer (PC) is the most lethal cancer with the lowest survival rate globally. Although the prescription of herbal drugs against PC is gaining increasing attention, their polypharmacological therapeutic mechanisms are yet to be fully understood. Based on network pharmacology, we explored the anti-PC properties and system-level mechanisms of the herbal drug FDY003. FDY003 decreased the viability of human PC cells and strengthened their chemosensitivity. Network pharmacological analysis of FDY003 indicated the presence of 16 active phytochemical components and 123 PC-related pharmacological targets. Functional enrichment analysis revealed that the PC-related targets of FDY003 participate in the regulation of cell growth and proliferation, cell cycle process, cell survival, and cell death. In addition, FDY003 was shown to target diverse key pathways associated with PC pathophysiology, namely, the PIK3-Akt, MAPK, FoxO, focal adhesion, TNF, p53, HIF-1, and Ras pathways. Our network pharmacological findings advance the mechanistic understanding of the anti-PC properties of FDY003 from a system perspective.

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OBJECTIVE: This study examined the path model predicting suicide attempts (SA) by interpersonal need for suicide desire, acquired capability for suicide, the emotion dysregulation, and depression symptoms in people admitted to hospitals for medical treatment. METHODS: A total of 344 participants (200 depressed patients with attempted suicide, 144 depressed patients with suicidal ideation) were enrolled for this study. Depression, anxiety, emotion regulation, interpersonal needs, and acquired capability for suicide were evaluated. A model with pathways from emotion regulation difficulties and interpersonal needs to SA was proposed. Participants were divided into two groups according to the presence of SA or suicidal ideation. RESULTS: Acquired capability for suicide mediated the path from depression to SA. In the path model, difficulties in emotion regulation and interpersonal needs predicted depression significantly. Although depression itself was not significantly related to acquired capability for suicide, depression was significantly related to acquired capability for suicide in suicide attempter group. CONCLUSION: Interventions with two factors affecting SA will clarify the suicide risk and contribute to finding risk factors.

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OBJECTIVE: Childhood trauma is the most important environmental factor for several psychiatric disorders. Depressed patients with childhood trauma appear to have severe symptoms that frequently recur. This study investigated whether depressed patients with childhood trauma showed attenuated Nogo event-related potentials (ERPs) and source activity during response-inhibition tasks. METHODS: Forty-four patients patients with major depressive disorder (MDD) were instructed to perform a Go/Nogo task during electroencephalography. Sensors and source activities of N2 and P3 of the Nogo ERPs were analyzed. The participants' clinical symptoms were assessed using the Childhood Trauma Questionnaire (CTQ), Beck Depression Inventory, State-Trait Anxiety Inventory, Barratt Impulsivity Scale, and Affective Lability Scale. The participants were divided into two groups (low and high), based on their total CTQ scores. RESULTS: MDD subjects with high CTQ scores showed significantly decreased Nogo P3 amplitudes at the frontal, frontocentral, central, and parietal electrodes than those with low CTQ scores (all p < 0.01). In Nogo P3, the source activities of the right cuneus, right posterior cingulate cortex, right precuneus, left supramarginal gyrus, and left lingual gyrus were significantly lower in the high CTQ group than in the low one (all p < 0.01). There were significant negative correlations between the total CTQ scores and the Nogo P3 amplitudes in the frontocentral (p = 0.03) and parietal regions (p = 0.02), which showed lower source activity in the Nogo P3 condition. CONCLUSION: Depressed patients with severe childhood trauma showed different Nogo-ERP characteristics, which might reflect inhibitory failure and dysfunction in related brain regions.

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Precision medicine has been considered a promising approach to diagnosis, treatment, and various interventions, considering the individual clinical and biological characteristics. Recent advances in biomarker development hold promise for guiding a new era of precision medicine style trials for psychiatric illnesses, including psychosis. Electroencephalography (EEG) can directly measure the full spatiotemporal dynamics of neural activation associated with a wide variety of cognitive processes. This manuscript reviews three aspects: prediction of diagnosis, prognostic aspects of disease progression and outcome, and prediction of treatment response that might be helpful in understanding the current status of electrophysiological biomarkers in precision medicine for patients with psychosis. Although previous EEG analysis could not be a powerful method for the diagnosis of psychiatric illness, recent methodological advances have shown the possibility of classifying and detecting mental illness. Some event-related potentials, such as mismatch negativity, have been associated with neurocognition, functioning, and illness progression in schizophrenia. Resting state studies, sophisticated ERP measures, and machine-learning approaches could make technical progress and provide important knowledge regarding neurophysiology, disease progression, and treatment response in patients with schizophrenia. Identifying potential biomarkers for the diagnosis and treatment response in schizophrenia is the first step towards precision medicine.

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Highly pathogenic avian influenza virus (HPAIv) H5N6 has destructive consequences on the global poultry production system. Recently, a growing number of layer farms have been heavily damaged from the HPAIv epidemic due to the increased virulence of the virus and the intensification of the production system. Therefore, stakeholders should implement effective preventive practices at the farm level that are aligned with contingency measures at the national level to minimize poultry losses. However, numerous biosecurity protocols for layer farm workers to follow have been developed, impeding efficient prevention and control. Furthermore, the effectiveness of biosecurity practices varies with the geographical condition and inter-farm contact structures. Hence, the objective of our study was to examine the preventive effect of five biosecurity actions commonly practiced at layer farms in the Republic of Korea against HPAIv H5N6: (i) fence installation around a farm, ii) rodent control inside a farm; iii) disinfection booth for visitors for disinfection protocols, iv) an anterior room in the sheds before entering the bird area and v) boots changes when moving between sheds in the same farm. We conducted a case-control study on 114 layer case farms and 129 layer control farms during the 2016-17 HPAI epidemic. The odds ratios for five on-farm biosecurity practices implemented in those study groups were estimated as a preventive effect on the HPAI infection with covariates, including seven geographical conditions and three network metrics using Bayesian hierarchical logistic regression and geographical location weighted logistic regression. The results showed that the use of a disinfection booth for personnel reduced the odds of HPAIv H5N6 infection (adjusted odds ratio [AOR] = 0.002, 95 % credible interval [CrI] = 0.00007 - 0.025) with relatively small spatial variation (minimum AOR - maximum AOR: 0.084-0.263). Changing boots between sheds on the same farm reduced the odds of HPAIv H5N6 infection (AOR = 0.160, 95 % CrI = 0.024-0.852) with relatively wide spatial variation (minimum AOR - maximum AOR = 0.270-0.688). Therefore, enhanced personnel biosecurity protocols at the farm of entry for layer farms is recommended to effectively prevent and respond to HPAIv H5N6 infection under different local condition. Our study provides an important message for layer farmers to effectively implement on-farm biosecurity actions against HPAIv H5N6 infection at their farms by setting priorities based on their spatial condition and network position.

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Loudness dependence of auditory evoked potentials (LDAEP) has been proposed as a biological marker of central serotonergic activity related to suicides. This study's objective was to analyze the difference in LDAEP between depressed patients with suicide attempts (SA) and suicidal ideation (SI). It included 130 participants (45 depressed patients with SA, 49 depressed patients with SI, and 36 healthy controls) aged > 18 years who exhibited LDAEP during electroencephalography. Psychological characteristics and event-related potentials of the three groups were compared. There was no significant difference in LDAEP between major depressive disorder (MDD) patients with SA and SI (p = 0.59). MDD patients with SI, who attempted suicide had significantly lower LDAEP than healthy controls (p = 0.01 and p = 0.01, respectively). However, the significance disappeared when psychological characteristics were controlled. Our results suggest that LDAEP might not be possible biomarkers for suicidal behaviors in patients with MDD. Further studies to assess the biological basis of suicide and identify the underlying dimensions that mediate the relationship between the biological basis and suicidal behaviors will be needed.

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Herbal medicines have drawn considerable attention with regard to their potential applications in breast cancer (BC) treatment, a frequently diagnosed malignant disease, considering their anticancer efficacy with relatively less adverse effects. However, their mechanisms of systemic action have not been understood comprehensively. Based on network pharmacology approaches, we attempted to unveil the mechanisms of FDY003, an herbal drug comprised of Lonicera japonica Thunberg, Artemisia capillaris Thunberg, and Cordyceps militaris, against BC at a systemic level. We found that FDY003 exhibited pharmacological effects on human BC cells. Subsequently, detailed data regarding the biochemical components contained in FDY003 were obtained from comprehensive herbal medicine-related databases, including TCMSP and CancerHSP. By evaluating their pharmacokinetic properties, 18 chemical compounds in FDY003 were shown to be potentially active constituents interacting with 140 BC-associated therapeutic targets to produce the pharmacological activity. Gene ontology enrichment analysis using g:Profiler indicated that the FDY003 targets were involved in the modulation of cellular processes, involving the cell proliferation, cell cycle process, and cell apoptosis. Based on a KEGG pathway enrichment analysis, we further revealed that a variety of oncogenic pathways that play key roles in the pathology of BC were significantly enriched with the therapeutic targets of FDY003; these included PI3K-Akt, MAPK, focal adhesion, FoxO, TNF, and estrogen signaling pathways. Here, we present a network-perspective of the molecular mechanisms via which herbal drugs treat BC.

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With growing evidence on the therapeutic efficacy and safety of herbal drugs, there has been a substantial increase in their application in the lung cancer treatment. Meanwhile, their action mechanisms at the system level have not been comprehensively uncovered. To this end, we employed a network pharmacology methodology to elucidate the systematic action mechanisms of FDY2004, an anticancer herbal drug composed of Moutan Radicis Cortex, Persicae Semen, and Rhei Radix et Rhizoma, in lung cancer treatment. By evaluating the pharmacokinetic properties of the chemical compounds present in FDY2004 using herbal medicine-associated databases, we identified its 29 active chemical components interacting with 141 lung cancer-associated therapeutic targets in humans. The functional enrichment analysis of the lung cancer-related targets of FDY2004 revealed the enriched Gene Ontology terms, involving the regulation of cell proliferation and growth, cell survival and death, and oxidative stress responses. Moreover, we identified key FDY2004-targeted oncogenic and tumor-suppressive pathways associated with lung cancer, including the phosphatidylinositol 3-kinase-Akt, mitogen-activated protein kinase, tumor necrosis factor, Ras, focal adhesion, and hypoxia-inducible factor-1 signaling pathways. Overall, our study provides novel evidence and basis for research on the comprehensive anticancer mechanisms of herbal medicines in lung cancer treatment.

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Herbal drugs have drawn substantial interest as effective analgesic agents; however, their therapeutic mechanisms remain to be fully understood. To address this question, we performed a network pharmacology study to explore the system-level mechanisms that underlie the analgesic activity of Jakyak-Gamcho decoction (JGd; Shaoyao-Gancao-Tang in Chinese and Shakuyaku-Kanzo-To in Japanese), an herbal prescription consisting of Paeonia lactiflora Pallas and Glycyrrhiza uralensis Fischer. Based on comprehensive information regarding the pharmacological and chemical properties of the herbal constituents of JGd, we identified 57 active chemical compounds and their 70 pain-associated targets. The JGd targets were determined to be involved in the regulation of diverse biological activities as follows: calcium- and cytokine-mediated signalings, calcium ion concentration and homeostasis, cellular behaviors of muscle and neuronal cells, inflammatory response, and response to chemical, cytokine, drug, and oxidative stress. The targets were further enriched in various pain-associated signalings, including the PI3K-Akt, estrogen, ErbB, neurotrophin, neuroactive ligand-receptor interaction, HIF-1, serotonergic synapse, JAK-STAT, and cAMP pathways. Thus, these data provide a systematic basis to understand the molecular mechanisms underlying the analgesic activity of herbal drugs.

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OBJECTIVE: The objective of the present study was to explore causal pathways to understand how second traumatic experiences could affect the development of emotional exhaustion and psychiatric problems. METHODS: A total of 582 workers who had jobs vulnerable to secondary traumatic experiences were enrolled for this study. Emotional exhaustion, secondary trauma, resilience, perceived stress, depression, anxiety, and sleep problems were evaluated. A model with pathways from secondary traumatic experience score to depression and anxiety was proposed. The participants were divided into three groups according to the resilience: the low, middle and high resilience group. RESULTS: Resilience was a meaningful moderator between secondary traumatic experiences and psychiatric problems. In the path model, the secondary trauma and perceived stress directly and indirectly predicted perceived stress, emotional exhaustion, depression, anxiety, and sleep problems in all three groups. Direct effects of perceived stress on depression and anxiety were the largest in the low resilience group. However, direct effects of secondary trauma on perceived stress and emotional exhaustion were the largest in the high resilience group. CONCLUSION: Understanding the needs of focusing for distinct psychological factors offers a valuable direction for the development of intervention programs to prevent emotional exhaustion among workers with secondary traumatic experiences.

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BACKGROUND/AIM: Accumulating evidence has shown therapeutic effects of herbals on breast cancer, a commonly diagnosed malignancy in women worldwide. However, their underlying mechanisms remain unclear. We aimed to explore the mode of action of a recently developed herbal combination at system-level. MATERIALS AND METHODS: We employed network pharmacological approaches to study the mechanism of a combination of three herbals, Astragalus membranaceus, Angelica gigas and Trichosanthes kirilowii by investigating active compounds and performing functional enrichment analysis for the interacting targets. RESULTS: For in silico pharmacokinetic evaluation, ten active ingredients interacted with fifty-six breast cancer-associated therapeutic targets. Functional enrichment analysis revealed that TNF, estrogen, PI3K-Akt and MAPK signaling pathways were involved in tumorigenesis and development of breast cancer. The pharmacological mechanisms might be associated with cellular effects on proliferation, cell cycle process and apoptosis. CONCLUSION: The present study provides novel insights into the system-level pharmacological mechanisms underlying a herbal combination used for breast cancer therapies.

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Backgrounds/Aims: Distinguishing gastric ectopic pancreas (GEP) from malignant tumors is relatively difficult. This study evaluated the endosonography findings of pathologically proven GEP. Methods: Thirty-one patients diagnosed with GEP based on a histopathological analysis from January 2004 to July 2018 were enrolled in this study. All patients underwent EUS and an endoscopic resection. Results: Seventeen patients were female, and the median age was 41.1 years (range, 14-74). The lesions were localized most commonly in the antrum. The mean size of the GEP was 10.6 mm (range, 7-15). Superficial type lesions, lesions with heterogeneous echogenicity, mixed pattern lesions, and lesions with indistinct borders were commonly observed on EUS. Calcification, anechoic duct-like structures, and thickening of the muscularis propria were observed in some patients. Endoscopic mucosal resection (41.9%) and endoscopic submucosal dissection (58.1%) were performed. The mean procedure time was 22.5 minutes. Complete resection was achieved for 71% of patients. No statistically significant results between the endosonography findings and complete resection rates were obtained. The mean follow-up esophagogastroduodenoscopy duration was 4.5 months. None of the patients presented with residual lesions on subsequent endoscopy. Conclusions: EUS can help identify the features of GEP. Careful observations of the EUS findings can avoid unnecessary removal of GEP.

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