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Kyoung Mee Kim,1,2 Hyun Kyung Lim,1,2 Sang Hee Shim,1,2 Joohee Jung1,2 1College of Pharmacy, 2Innovative Drug Center, Duksung Women’s University, Seoul, Republic of Korea Abstract: Chrysin is a flavone that is found in several plants and in honeycomb and possesses various biological activities. However, its low solubility means it has poor bioavailability, which must be resolved to enable its pharmaceutical applications. In the present study, chrysin was incorporated into methoxy poly(ethylene glycol)-β-polycaprolactone nanoparticles (chrysin-NPs) using the oil-in-water technique in order to overcome problems associated with chrysin. The properties of chrysin-NPs were analyzed, and their anticancer effects were investigated in vitro and in vivo. Chrysin-NPs were 77 nm sized (as determined by dynamic laser light scattering) and showed a monodisperse distribution. The zeta potential of chrysin-NPs was –2.22 mV, and they were spherically shaped by cryo-transmission electron microscopy (cryo-TEM). The loading efficiency of chrysin-NPs was 46.96%. Chrysin-NPs retained the cytotoxicity of chrysin in A549 cells. The therapeutic efficacies of chrysin-NPs were compared with those of chrysin in an A549-derived xenograft mouse model. Chrysin-NPs were intravenously injected at a 10 times lower dosage than chrysin 3 times per week (q2d×3/week). However, free chrysin was orally administrated 5 times per week (q1d×5/week). Chrysin-NP-treated group showed significant tumor growth delay, which was similar to that of chrysin-treated group, despite the considerably lower total dosage. These results suggest that the injectable chrysin-NPs enhance therapeutic efficacy in vivo and offer a beneficial formulation for chemotherapy. Keywords: chrysin, nanoparticle, chemotherapeutic efficacy, non-small-cell lung cancer, in vivo model

Jong-Hyun Jeong,1 Jeong Goo Lee,2,3 Moon-Doo Kim,4 Inki Sohn,5 Se-Hoon Shim,6 Hee Ryung Wang,1 Young Sup Woo,1 Duk-In Jon,7 Jeong Seok Seo,8 Young-Chul Shin,9 Kyung Joon Min,10 Bo-Hyun Yoon,11 Won-Myong Bahk1 1Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul, 2Department of Psychiatry, Haeundae Paik Hospital, College of Medicine, Paik Institute for Clinical Research, Inje University, 3Department of Health Science and Technology, Graduate School of Inje University, Busan, 4Department of Psychiatry, Jeju National University Hospital, Jeju, 5Department of Psychiatry, Keyo Hospital, Keyo Medical Foundation, Uiwang, 6Department of Psychiatry, Soonchunhyang University Cheonan Hospital, College of Medicine, Soonchunhyang University, Cheonan, 7Department of Psychiatry, Sacred Heart Hospital, College of Medicine, Hallym University, Anyang, 8Department of Psychiatry, Konkuk University Chungju Hospital, School of Medicine, Konkuk University, Chungju, 9Department of Psychiatry, Kangbuk Samsung Hospital, School of Medicine, Sungkyunkwan University, Seoul, 10Department of Psychiatry, Chung-Ang University Hospital, College of Medicine, Chung-Ang University, Seoul, 11Department of Psychiatry, Naju National Hospital, Naju, Korea Abstract: Our goal was to compare the recommendations of the Korean Medication Algorithm Project for Bipolar Disorder 2014 (KMAP-BP 2014) with other recently published guidelines for the treatment of bipolar disorder. We reviewed a total of four recently published global treatment guidelines and compared each treatment recommendation of the KMAP-BP 2014 with those in other guidelines. For the initial treatment of mania, there were no significant differences across treatment guidelines. All recommended mood stabilizer (MS) or atypical antipsychotic (AAP) monotherapy or the combination of an MS with an AAP as a first-line treatment strategy for mania. However, the KMAP-BP 2014 did not prefer monotherapy with MS or AAP for dysphoric/psychotic mania. Aripiprazole, olanzapine, quetiapine, and risperidone were the first-line AAPs in nearly all of the phases of bipolar disorder across the guidelines. Most guidelines advocated newer AAPs as first-line treatment options in all phases, and lamotrigine in depressive and maintenance phases. Lithium and valproic acid were commonly used as MSs in all phases of bipolar disorder. As research evidence accumulated over time, recommendations of newer AAPs – such as asenapine, paliperidone, lurasidone, and long-acting injectable risperidone – became prominent. This comparison identifies that the treatment recommendations of the KMAP-BP 2014 are similar to those of other treatment guidelines and reflect current changes in prescription patterns for bipolar disorder based on accumulated research data. Further studies are needed to address several issues identified in our review. Keywords: bipolar disorder, pharmacotherapy, treatment algorithm, guideline comparison, KMAP-2014

Young Sup Woo,1 Jung Goo Lee,2,3 Jong-Hyun Jeong,1 Moon-Doo Kim,4 Inki Sohn,5 Se-Hoon Shim,6 Duk-In Jon,7 Jeong Seok Seo,8 Young-Chul Shin,9 Kyung Joon Min,10 Bo-Hyun Yoon,11 Won-Myong Bahk1 1Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul, South Korea; 2Department of Psychiatry, Inje University Haeundae Paik Hospital, Busan, South Korea;3Paik Institute for Clinical Research, Inje Univeristy, Busan, South Korea; 4Department of Psychiatry, Jeju National University Hospital, Jeju, South Korea; 5Department of Psychiatry, Keyo Hospital, Keyo Medical Foundation, Uiwang, South Korea; 6Department of Psychiatry, Soonchunhyang University Cheonan Hospital, Soonchunhyang University, Cheonan, South Korea; 7Department of Psychiatry, Sacred Heart Hospital, Hallym University, Anyang, South Korea; 8Department of Psychiatry, School of Medicine, Konkuk University, Chungju, South Korea; 9Department of Psychiatry, Kangbuk Samsung Hospital, School of Medicine, Sungkyunkwan University, Seoul, South Korea; 10Department of Psychiatry, College of Medicine, Chung-Ang University, Seoul, South Korea; 11Department of Psychiatry, Naju National Hospital, Naju, South Korea Objective: To constitute the third revision of the guidelines for the treatment of bipolar disorder issued by the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP 2014). Methods: A 56-item questionnaire was used to obtain the consensus of experts regarding pharmacological treatment strategies for the various phases of bipolar disorder and for special populations. The review committee included 110 Korean psychiatrists and 38 experts for child and adolescent psychiatry. Of the committee members, 64 general psychiatrists and 23 child and adolescent psychiatrists responded to the survey. Results: The treatment of choice (TOC) for euphoric, mixed, and psychotic mania was the combination of a mood stabilizer (MS) and an atypical antipsychotic (AAP); the TOC for acute mild depression was monotherapy with MS or AAP; and the TOC for moderate or severe depression was MS plus AAP/antidepressant. The first-line maintenance treatment following mania or depression was MS monotherapy or MS plus AAP; the first-line treatment after mania was AAP monotherapy; and the first-line treatment after depression was lamotrigine (LTG) monotherapy, LTG plus MS/AAP, or MS plus AAP plus LTG. The first-line treatment strategy for mania in children and adolescents was MS plus AAP or AAP monotherapy. For geriatric bipolar patients, the TOC for mania was AAP/MS monotherapy, and the TOC for depression was AAP plus MS or AAP monotherapy. Conclusion: The expert consensus in the KMAP-BP 2014 differed from that in previous publications; most notably, the preference for AAP was increased in the treatment of acute mania, depression, and maintenance treatment. There was increased expert preference for the use of AAP and LTG. The major limitation of the present study is that it was based on the consensus of Korean experts rather than on experimental evidence. Keywords: pharmacological treatment, treatment guideline, expert consensus

To understand the effects of H2O on the mineral phases forming under the pressure-temperature conditions of the lower mantle, we have conducted laser-heated diamond-anvil cell experiments on hydrous ringwoodite (Mg2SiO4 with 1.1 wt% H2O) at pressures between 29 and 59 GPa and temperatures between 1200 and 2400 K. Our results show that hydrous ringwoodite (hRw) converts to crystalline dense hydrous silica, stishovite (Stv) or CaCl2-type SiO2 (mStv), containing 1 wt% H2O together with Brd and MgO at the pressure-temperature conditions expected for shallow lower-mantle depths between approximately 660 to 1600 km. Considering the lack of sign for melting in our experiments, our preferred interpretation of the observation is that Brd partially breaks down to dense hydrous silica and periclase (Pc), forming the phase assembly Brd + Pc + Stv. The results may provide an explanation for the enigmatic coexistence of Stv and Fp inclusions in lower-mantle diamonds.

The composition of Archean volcanic crust can be characterized by a higher Mg/Si ratio than modern mid-ocean ridge basalt (MORB), because of the higher degree melting from the warmer mantle in the Archean. Although modern MORB may become less dense than the surrounding mantle beneath the mantle transition zone (MTZ), the Mg-rich composition of Archean volcanic crust may result in the different density, and therefore different sinking behavior near the MTZ. In order to understand the compositional effect of Archean volcanic crust on the sinking behaviors and the scale of mantle mixing in the Archean, we investigated the mineralogy and density of Archean volcanic crust near the MTZ (470–910 km-depth). We conducted experiments at 19–34 GPa and 1400–2400 K using the laser-heated diamond anvil cell (LHDAC) combined with in-situ X-ray diffraction (XRD). The in-situ XRD and the chemical analysis revealed that Archean volcanic crust forms garnet and ringwoodite (84 and 16 vol%, respectively), which gradually transforms to Brg and CaPv (82 and 18 vol%, respectively) at 23–25 GPa and 1800 K. Our in-situ XRD experiments allowed us to measure the volumes of stable phases and to estimate their densities at high pressure and temperature. The results suggest that Archean volcanic crust maintains greater density than the pyrolitic mantle in the Archean regardless of temperature at 20–34 GPa (570–850 km-depth), promoting further sinking into the deeper mantle in the Archean. We also considered the density of the subducting slab in the Archean. The density model showed that the subducting slab is still denser or at least equally dense as the surrounding pyrolitic mantle in the Archean.

The lower mantle is believed to contain much less hydrogen (or H2O) because of the low storage capacity of the dominant mineral phases, such as bridgmanite and ferropericlase. However, possible hydrogen storage in the third most abundant mineral in the region, CaSiO3 perovskite (Ca-Pv), is not well unknown. We have synthesized Ca-Pv from different starting materials with varying H2O contents at 19–120 GPa and 1400–2200 K in laser-heated diamond-anvil cell. While cubic perovskite structure is stable at the mantle-related pressures-temperatures (P−T) in anhydrous systems, we found non-cubic diffraction peak splitting in Ca-Pv even at high temperatures when it is synthesized from hydrous starting materials. In-situ high-pressure infrared spectroscopy showed OH vibration possibly from Ca-Pv. The unit-cell volume of hydrothermally synthesized Ca-Pv is systematically smaller than that of anhydrous Ca-Pv at high pressures. These observations suggest possible H2O storage in Ca-Pv at mantle-related P−T conditions. We also found the formation of separate δ–AlOOH and Ca-Pv phases from Al-bearing CaSiO3 glass starting materials in an H2O medium at 60 GPa and 1400 K. Ca-Pv still showed non-cubic peak splitting at high temperatures in this experiment. Therefore, it is possible that hydrous phases may coexist together with hydrous Ca-Pv in the lower mantle.

In this paper, we introduce a new class of completely generalized strongly nonlinear implicit quasivariational inclusions and prove its equivalence with a class of fixed point problems by using some properties of maximal monotone mappings. We also prove the existence of solutions for the completely generalized strongly nonlinear implicit quasivariational inclusions and the convergence of iterative sequences generated by the perturbed algorithms with errors.

Soldiers from the Republic of Korea and the United States conduct armistice military operations at Twin Bridges Training Area (TBTA) located near the demilitarized zone (DMZ) and are exposed to zoonotic disease pathogens that small mammals and their potentially disease-carrying ectoparasites transmit. TBTA is a 36 km2 rural training site with small villages and various forms of agriculture along its boundary. At TBTA, rodents, insectivores, and their ectoparasites are commonly found in association with unmanaged habitats of various densities of tall grasses, herbaceous plants, shrubs, briars, and crawling vegetation. Rodents and insectivores were collected during the winter (November-December 2005 and December 2006) and early spring (March 2007), and serologically tested for the presence of scrub typhus, murine typhus, and leptospirosis antibodies. Of the six species of small mammals collected, Apodemus agrarius, the common striped field mouse and known reservoir of scrub typhus, was the most frequently collected (96.1%), followed by Crocidura lasiura (2.5%), Micromys minutus (0.5%), Myodes regulus (0.5%), Mus musculus (0.3%), and Rattus rattus (0.1%). A. agrarius (56.1%), M. musculus (66.7%), M. minutus (25%), and R. rattus (100%) were positive for scrub typhus antibodies. Only A. agrarius (14.7%) and C. lasiura (4.5%) were positive for murine typhus antibodies, whereas only A. agrarius (1.5%) was seropositive for leptospirosis. Seroprevalence rates of scrub typhus and murine typhus based on weight and sex of A. agrarius are presented. [ABSTRACT FROM AUTHOR]

Background: Although two recent phase III randomized controlled trials showed survival benefits of undergoing secondary cytoreductive surgery for an initial relapse of ovarian cancer, patients who received a poly-ADP ribose polymerase inhibitor (PARPi) as the first-line maintenance treatment, which is currently the standard treatment for advanced ovarian cancer, were not included in those trials. Therefore, determining an optimal treatment strategy, including secondary cytoreductive surgery, in patients whose cancer progresses even with PARPi treatment, is needed., Primary Objective: To determine whether secondary cytoreductive surgery is beneficial in patients who have progressed on PARPi maintenance treatment., Study Hypothesis: Secondary cytoreductive surgery followed by chemotherapy is superior to chemotherapy alone for patients who have progressed on PARPi maintenance treatment., Trial Design: The SOCCER-P study is a multicenter randomized phase II clinical trial. Patients who meet the eligibility criteria will be randomized to either undergo secondary cytoreductive surgery and subsequent platinum-based chemotherapy plus or minus bevacizumab, or to receive platinum-based chemotherapy plus or minus bevacizumab alone. Patients randomly allocated to the surgery group will undergo secondary cytoreductive surgery followed by six cycles of a physician's choice of platinum-based chemotherapy once they have recovered from surgery., Major Inclusion/exclusion Criteria: The major inclusion criteria are as follows: first recurrence of disease with treatment-free interval from last platinum dose (TFIp) ≥6 months and progression during PARPi maintenance or treatment-free interval from last PARPi therapy (TFI PARPi ) <3 months. The major exclusion criteria are as follows: >1 line of prior chemotherapy, TFIp <6 months, and radiological signs suggesting metastases not accessible to surgical removal (complete resection is deemed not possible)., Primary Endpoint: Progression-free survival., Sample Size: 124 patients., Estimated Dates for Completing Accrual and Presenting Results: Accrual completion approximately the end of 2026 and the results are expected after 2 years of follow-up in 2029., Trial Registration: NCT05704621., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Objective: To evaluate whether intraoperative rupture affects oncological outcomes in patients with early-stage epithelial ovarian cancer (EOC)., Methods: A multicenter retrospective study was conducted on patients with early-stage EOC based on surgical and final pathological reports between 2007 and 2021. Oncologic outcomes were compared between the unruptured group (International Federation of Gynaecology and Obstetrics [FIGO] stage IA/IB) and ruptured group (FIGO stage IC1). The primary endpoint was progression-free survival (PFS). Propensity score matching (PSM) was performed to adjust for the imbalance in prognostic factors between the groups., Results: Overall, 197 (58.3 %) patients comprised the unruptured group (FIGO stage IA/IB), and 141 (41.7 %) were in the intraoperatively ruptured group (FIGO stage IC1). No significant difference in the 5-year PFS was observed between the two groups before PSM (92.65 % vs. 92.80 %, P = 0.93). After PSM, the 5-year PFS showed a noticeable decrease in the ruptured group compared to the unruptured group, although this difference showed borderline statistical significance (96.90 % vs. 89.82 %, P = 0.061). This trend was particularly discernible in cases with aggressive tumor characteristics; intraoperative rupture remained an independent prognostic factor for shorter PFS in patients with high-grade histology (adjusted hazard ratio = 14.4, 95 % confidence interval = 2.8-74.1)., Conclusions: Although not statistically significant, intraoperative rupture may negatively affect PFS in these patients after PSM. Therefore, rupture during surgery should be avoided as it can cause upstaging and unnecessary chemotherapy., (Copyright © 2024. Published by Elsevier Ltd.)

Mycotoxin-contaminated feed or food can affect physiological responses and cause illnesses in humans and animals. In this study, we evaluated the effects of deoxynivalenol (DON) toxicity on the growth performance, blood biochemistry, histology, microbiome, and metabolism of rats fed with different toxin concentrations. After 1 week of acclimatization, seven-week-old male rats received 0.9% saline as a control, 0.02 mg/kg DON as T1, and 0.2 mg/kg DON as T2 via oral gavage for 4 weeks. The final body weight of the T2 group was significantly lower than that of the control and T1; however, the average daily gain, feed intake, and feed conversion ratio did not differ. Fibrosis and apoptosis were observed in various tissues as DON concentration increased. Creatinine and alkaline phosphatase levels were significantly lower in the DON-treated group than in the control. Firmicutes and Desulfobacterota phyla dominated the cecum, whereas those in the feces were Proteobacteria and Bacteroidetes. Metabolomic profiling showed phenylalanine, tyrosine, and tryptophan biosynthesis as the most prominent pathways. Overall, our results suggest that low-dose and short-term DON exposure can trigger several adverse effects in rats. Dietary toxicants in rats may explain the physiological effects associated with the metabolism commonly reported in animals.

Aim: This study examined the efficacy of AST-001 for the core symptoms of autism spectrum disorder (ASD) in children., Methods: This phase 2 clinical trial consisted of a 12-week placebo-controlled main study, a 12-week extension, and a 12-week follow-up in children aged 2 to 11 years with ASD. The participants were randomized in a 1:1:1 ratio to a high-dose, low-dose, or placebo-to-high-dose control group during the main study. The placebo-to-high-dose control group received placebo during the main study and high-dose AST-001 during the extension. The a priori primary outcome was the mean change in the Adaptive Behavior Composite (ABC) score of the Korean Vineland Adaptive Behavior Scales II (K-VABS-II) from baseline to week 12., Results: Among 151 enrolled participants, 144 completed the main study, 140 completed the extension, and 135 completed the follow-up. The mean K-VABS-II ABC score at the 12th week compared with baseline was significantly increased in the high-dose group (P = 0.042) compared with the placebo-to-high-dose control group. The mean CGI-S scores were significantly decreased at the 12th week in the high-dose (P = 0.046) and low-dose (P = 0.017) groups compared with the placebo-to-high-dose control group. During the extension, the K-VABS-II ABC and CGI-S scores of the placebo-to-high-dose control group changed rapidly after administration of high-dose AST-001 and caught up with those of the high-dose group at the 24th week. AST-001 was well tolerated with no safety concern. The most common adverse drug reaction was diarrhea., Conclusions: Our results provide preliminary evidence for the efficacy of AST-001 for the core symptoms of ASD., (© 2024 The Author(s). Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

DNA visualization has advanced across multiple microscopy platforms, albeit with limited progress in the identification of novel staining agents for electron microscopy (EM), notwithstanding its ability to furnish a broad magnification range and high-resolution details for observing DNA molecules. Herein, a non-toxic, universal, and simple method is proposed that uses gold nanoparticle-tagged peptides to stain all types of naturally occurring DNA molecules, enabling their visualization under EM. This method enhances the current DNA visualization capabilities, allowing for sequence-specific, genomic-scale, and multi-conformational visualization. Importantly, an artificial intelligence (AI)-enabled pipeline for identifying DNA molecules imaged under EM is presented, followed by classification based on their size, shape, or conformation, and finally, extraction of their significant dimensional features, which to the best of authors' knowledge, has not been reported yet. This pipeline strongly improved the accuracy of obtaining crucial information such as the number and mean length of DNA molecules in a given EM image for linear DNA (salmon sperm DNA) and the circumferential length and diameter for circular DNA (M13 phage DNA), owing to its image segmentation capability. Furthermore, it remained robust to several variations in the raw EM images arising from handling during the DNA staining stage., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

Molten silicates at depth are crucial for planetary evolution, yet their local structure and physical properties under extreme conditions remain elusive due to experimental challenges. In this study, we utilize in situ X-ray diffraction (XRD) at the Matter in Extreme Conditions (MEC) end-station of the Linear Coherent Linac Source (LCLS) at SLAC National Accelerator Laboratory to investigate liquid silicates. Using an ultrabright X-ray source and a high-power optical laser, we probed the local atomic arrangement of shock-compressed liquid (Mg,Fe)SiO 3 with varying Fe content, at pressures from 81(9) to 385(40) GPa. We compared these findings to ab initio molecular dynamics simulations under similar conditions. Results indicate continuous densification of the O-O and Mg-Si networks beyond Earth's interior pressure range, potentially altering melt properties at extreme conditions. This could have significant implications for early planetary evolution, leading to notable differences in differentiation processes between smaller rocky planets, such as Earth and Venus, and super-Earths, which are exoplanets with masses nearly three times that of Earth., (© 2024. The Author(s).)

Objective: Suicide is a significant public health issue, with South Korea having the highest suicide rate among Organisation for Economic Cooperation and Development countries. This study aimed to develop clinical guidelines for suicide prevention in psychiatric patients in Korea using the ADAPTE methodology., Methods: The development process involved a comprehensive review of literature, expert consultations, and consensus-building using the Nominal Group Technique and Delphi method. The guidelines focus on evidence-based psychiatric treatments, including both pharmacological and non-pharmacological approaches, tailored to the Korean context. Key findings underscoring the need for standardized treatment protocols for patients with major psychiatric disorders, including bipolar disorder, major depressive disorder, and schizophrenia., Results: The guidelines incorporate treatments like lithium, clozapine, atypical antipsychotics, electroconvulsive therapy, and cognitive behavioral therapy, which have shown effectiveness in suicide prevention. Applicability and acceptability within Korea's healthcare system were addressed, ensuring feasibility given the country's medical insurance coverage and accessibility. The guidelines were validated through expert reviews and Delphi rounds, achieving consensus on the final recommendations., Conclusion: The developed guidelines provide a structured, evidence-based approach to reducing suicide rates among psychiatric patients in Korea. Future research will focus on expanding these guidelines to include screening protocols for high-risk groups.

Objective: To evaluate whether treatment with erythropoiesis-stimulating agents (ESAs) for chemotherapy-induced anemia affects progression-free survival (PFS) in patients receiving front-line chemotherapy following surgery for ovarian cancer (OC)., Methods: We retrospectively reviewed all consecutive patients who received front-line chemotherapy after surgery between 2013 and 2019 at six institutions. The patients were divided according to the use of ESAs during front-line chemotherapy. The primary endpoint was PFS. The secondary endpoint was the occurrence of thromboembolism. Propensity score matching (PSM) analysis was used to compare survival between matched cohorts., Results: Overall, 2147 patients (433 receiving ESA and 1714 for no-ESA) were identified, with a median follow-up of 44.0 months. The ESA group showed a significantly higher proportion of stage III/IV disease (81.8% vs 61.1%; P < 0.001) and postoperative gross residual disease (32.3% vs 21.2%; P < 0.001) than the no-ESA group. In the multivariable Cox regression analysis, the use of ESAs did not affect PFS (adjusted hazard ratio, 1.03; 95% confidence interval [CI]: 0.89-1.20; P = 0.661). The incidence of thromboembolism was 10.2% in the ESA group and 4.6% in the no-ESA group (adjusted odds ratio, 6.58; 95% CI: 3.26-13.28; P < 0.001). When comparing the well-matched cohorts after PSM, PFS did not differ between the ESA (median PFS 23.5 months) and no-ESA groups (median PFS 22.2 months) (P = 0.540, log-rank test)., Conclusions: The use of ESAs during front-line chemotherapy did not negatively affect PFS in patients with OC after surgery but increased the risk of thromboembolism., (© 2024 International Federation of Gynecology and Obstetrics.)

Objective: This study aimed to assess the recurrence risk factors in patients with early-stage endometrioid endometrial cancer (EC) who achieved a complete response (CR) through fertility-sparing hormonal treatment (FST)., Methods: We retrospectively analyzed patients who received FST for presumed stage IA and grade 1 endometrioid EC at two institutions. Medroxyprogesterone (MPA)- and levonorgestrel-releasing intrauterine devices (LNG-IUD) were used concurrently. Maintenance therapy involved maintaining the LNG-IUDs in situ for those who did not attempt to conceive immediately after achieving CR. Cox regression analysis was used to identify clinicopathological variables for recurrence-free survival (RFS) following CR., Results: Among 178 patients with endometrioid EC who received FST, 142 (79.8 %) achieved CR. The median time to achieve CR and the median FST duration were 10 months (range 1-34) and 14 months (range 3-49), respectively. During the median follow-up period of 44 months (range 6-143), 59.9 % (85/142) of patients had recurrence, with a median RFS of 14 months (range 1-123) after CR. In multivariable analysis, age > 35-years (hazard ratio (HR) 1.892, 95 % confidence interval (CI) 1.224-2.923; P < 0.05) and pregnancy after the first CR (HR 0.203, 95 % CI 0.093-0.444; P < 0.05) were significantly associated with RFS., Conclusions: Older age and non-pregnancy status may be risk factors for recurrence after CR. Therefore, patients with these conditions should undergo stringent follow-up, including imaging and histological examinations, to detect recurrence after CR., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: This report describes the oncologic outcomes for patients with advanced ovarian cancer who had bowel surgery performed by gynecologic oncologists (GOs) and compares the outcomes with those for bowel surgery performed by general surgeons (GSs) during maximal cytoreductive surgery., Methods: Patients from six academic institutions who had FIGO stage III or IV ovarian cancer and underwent any bowel surgeries during maximal cytoreductive surgery were eligible for the study. The patients were divided into two groups according to whether bowel surgery was performed by a GO or a GS. In both groups, the GOs were mainly involved in extra bowel debulking procedures. Perioperative and survival outcomes were compared between the two groups., Results: The 761 patients in this study included 113 patients who underwent bowel surgery by a GO and 648 who had bowel surgery by a GS. No discernible differences were observed in age, American Society of Anesthesiology (ASA) score, FIGO stage, histologic type, timing of cytoreductive surgery (primary or interval debulking surgery), or complications between the two groups. The GO group exhibited a shorter operation time than the GS group. Kaplan-Meier analysis showed no survival differences between the two groups. In the Cox analysis, non-serous cell types and gross residual diseases were associated with adverse effects on overall survival. However, performance of bowel surgery by a GO did not have an impact on survival., Conclusion: Performance of bowel surgery by a GO during maximal cytoreductive surgery is both feasible and safe. These results should be reflected in the training system for GOs regarding bowel surgery, and further research is needed to confirm that GOs can play a more leading role in performing extra-uterine procedures., (© 2024. Society of Surgical Oncology.)

Peppers (Piper nigrum L.) are distinguished by their pungent flavor and aroma. Piperine is a major acid-amide alkaloid with a piperidine ring that gives pepper its flavor and scent. In plant metabolomics research, the accessibility of the chemical standards is critical for scientific credibility. We isolated and identified 10 novel dimers of acid amide alkaloids (9-15 and 20-22), along with 12 known monomers (1-6) and dimers (7, 8, 16-19) from black pepper. Subsequently, we found the distribution of monomers and dimers of acid amide alkaloids in black and white peppers by twenty-two acid amide alkaloids which we obtained using the molecular networking technique and multivariate analysis to reveal the molecular relationships between the acid amide alkaloids in black and white peppers. Our research delved into the chemical diversity of acid amide alkaloids in black and white peppers, which could help inform future culinary and potential medicinal utilization of pepper., Competing Interests: Declaration of competing interest Heejung Yang, Sang Hee Shim reports financial support was provided by Cooperative Research Program for Agriculture Science and Technology Development, Rural Development Administration, Republic of Korea. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Five new lipopeptaibols ( 1 - 5 ) and eight new 19-residue peptaibols ( 8 - 15 ) along with two known lipopeptaibols, lipovelutibols C ( 6 ) and D ( 7 ) were isolated from Trichoderma strigosum . The planar structures of the newly discovered peptaibols ( 1 - 5 , 8 - 15 ) were elucidated using 1D and 2D NMR, and UPLC-MS/MS data. The absolute configurations for new peptaibols ( 1 - 5 , 8 - 15 ) were elucidated using the advanced Marfey's method and GITC (2,3,4,6-tetra- O -acetyl-β-d-glucopyranosyl isothiocyanate) derivatization. Through analysis of CD spectra, these peptabols were found to have right-handed helical conformations. While most of the new compounds were significantly more active than the positive control, 9 , 10 , 12 , and 15 containing Ser and Leu at positions 10 and 11, respectively, were the most cytotoxic against MDA-MB-231, SNU449, SKOV3, DU145, and HCT116 cancer cell lines, and the 19-residue peptaibols were generally more potent than lipopeptaibols.

Covering: up to December 2023Decalin-containing tetramic acid derivatives, especially 3-decalinoyltetramic acids (3-DTAs), are commonly found as fungal secondary metabolites. Numerous biological activities of this class of compounds, such as antibiotic, antiviral, antifungal, antiplasmodial, and antiprotozoal properties, have been the subject of ongoing research. For this reason, these molecules have attracted a lot of interest from the scientific community and various efforts including semi-synthesis, co-culturing with bacteria and biosynthetic gene sequencing have been made to obtain more derivatives. In this review, 3-DTAs are classified into four major groups based on the absolute configuration of the bicyclic decalin ring. Their biosynthetic pathways, various biological activities, and structure-activity relationship are then introduced.

Background: Despite a plethora of research on the topic, there is still no solid evidence that pharmacological treatment actually reduces the risk of suicide in patients with mental illness. In this study, we aimed to assess the effect of psychotropic medications on suicidal ideation in patients with major depressive disorder (MDD) and bipolar disorder (BPD) in two age groups: less than 25 years and 25 years and older., Methods: We analyzed 312 patients with mood disorders with current suicidal thoughts or recent suicide attempts. We followed the participants from baseline for 6 months and assessed changes in suicidal ideation with Columbia-Suicide Severity Rating Scale (C-SSRS). The effect of psychotropic drug administration on suicidal ideation over time was analyzed using a linear mixed model., Results: In patients aged 25 years and older with mood disorders, suicidal ideation was more severe when using psychotropic drugs than when not using them. However, suicidal ideation decreased rapidly over time. The time-dependent reduction in suicidal ideation was accelerated when using antidepressants and sedatives/hypnotics in adult MDD, and when using mood stabilizers in adult BPD. However, this effect was not observed in participants aged less than 25 years., Conclusion: Adequate psychotropic medication may reduce suicidal ideation in patients with mood disorders aged 25 years and older. Additional research on psychotropic drugs is needed to effectively reduce the risk of suicide among children and adolescents with mood disorders., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Despite previous efforts to build statistical models for predicting the risk of suicidal behavior using machine-learning analysis, a high-accuracy model can lead to overfitting. Furthermore, internal validation cannot completely address this problem. In this study, we created models for predicting the occurrence of suicide attempts among Koreans at high risk of suicide, and we verified these models in an independent cohort. We performed logistic and penalized regression for suicide attempts within 6 months among suicidal ideators and attempters in The Korean Cohort for the Model Predicting a Suicide and Suicide-related Behavior (K-COMPASS). We then validated the models in a test cohort. Our findings indicated that several factors significantly predicted suicide attempts in the models, including young age, suicidal ideation, previous suicidal attempts, anxiety, alcohol abuse, stress, and impulsivity. The area under the curve and positive predictive values were 0.941 and 0.484 after variable selection and 0.751 and 0.084 in the test cohort. The corresponding values for the penalized regression model were 0.943 and 0.524 in the original training cohort and 0.794 and 0.115 in the test cohort. The prediction model constructed through a prospective cohort study of the suicide high-risk group showed satisfactory accuracy even in the test cohort. The accuracy with penalized regression was greater than that with the "classical" logistic model., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Plant growth must be regulated throughout the plant life cycle. The myeloblastosis (MYB) transcription factor (TF) family is one of the largest TF families and is involved in metabolism, lignin biosynthesis, and developmental processes. Here, we showed that OsMYB14, a rice R2R3-MYB TF, was expressed in leaves and roots, especially in rice culm and panicles, and that it localized to the nucleus. Overexpression of OsMYB14 (OsMYB14-ox) in rice resulted in a 30% reduction in plant height compared to that of the wild type (WT), while the height of the osmyb14-knockout (osmyb14-ko) mutant generated using the CRISPR/Cas9 system was not significantly different. Microscopic observations of the first internode revealed that the cell size did not differ significantly among the lines. RNA sequencing analysis revealed that genes associated with plant development, regulation, lipid metabolism, carbohydrate metabolism, and gibberellin (GA) and auxin metabolic processes were downregulated in the OsMYB14-ox line. Hormone quantitation revealed that inactive GA19 accumulated in OsMYB14-ox but not in the WT or knockout plants, suggesting that GA20 generation was repressed. Indole-3-acetic acid (IAA) and IAA-aspartate accumulated in OsMYB14-ox and osmyb14-ko, respectively. Indeed, real-time PCR analysis revealed that the expression of OsGA20ox1, encoding GA20 oxidase 1, and OsGH3-2, encoding IAA-amido synthetase, was downregulated in OsMYB14-ox and upregulated in osmyb14-ko. A protein-binding microarray revealed the presence of a consensus DNA-binding sequence, the ACCTACC-like motif, in the promoters of the OsGA20ox1 and GA20ox2 genes. These results suggest that OsMYB14 may act as a negative regulator of biological processes affecting plant height in rice by regulating GA biosynthesis and auxin metabolism., Competing Interests: Declaration of Competing Interests The authors declare that they have no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Robotic single-site plus one-port myomectomy (RSOM) was designed to reduce the number of incision sites for greater cosmetic satisfaction of patients while retaining the benefits of conventional robotic multi-site myomectomy (CRM). Robotic single-site plus two-port myomectomy (RSTM) eliminated one port relative to conventional CRM, and RSOM achieved the same advantage with respect to RSTM. This study aimed to compare RSOM with RSTM in terms of their respective methodologies and surgical outcomes., Materials and Methods: The medical records of 230 patients who had undergone RSOM and 146 patients who had undergone RSTM were reviewed. The groups' surgical outcomes were compared using propensity score matching (PSM) analysis., Results: In the total data, RSOM had a shorter operative time (135.1±57.4 min vs. 149.9±46.2 min, p =0.009) and a shorter hospital stay (5.2±0.5 days vs. 5.4±0.7 days, p =0.033) relative to RSTM. The PSM analysis showed that there were no statistically significant intergroup differences in the patients' baseline characteristics. Regarding the surgical outcomes, the RSOM group showed shorter operative time (129.2±49.3 min vs. 148.7±46.3 min, p =0.001) compared to the RSTM group., Conclusion: Compared with RSTM, RSOM was associated with shorter operative time. Additionally, more detailed comparative and prospective studies are needed to evaluate RSOM relative to RSTM., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2024.)

Objective: This study aimed to evaluate the therapeutic role of lymphadenectomy in patients surgically treated for clinically early-stage epithelial ovarian cancer (EOC)., Methods: This retrospective, multicenter study included patients with clinically early-stage EOC based on preoperative abdominal-pelvic computed tomography or magnetic resonance imaging findings between 2007 and 2021. Oncologic outcomes and perioperative complications were compared between the lymphadenectomy and non-lymphadenectomy groups. Independent prognostic factors were determined using Cox regression analysis. Disease-free survival (DFS) was the primary outcome. Overall survival (OS) and perioperative outcomes were the secondary outcomes., Results: In total, 586 patients (lymphadenectomy group, n=453 [77.3%]; non-lymphadenectomy groups, n=133 [22.7%]) were eligible. After surgical staging, upstaging was identified based on the presence of lymph node metastasis in 14 (3.1%) of 453 patients. No significant difference was found in the 5-year DFS (88.9% vs. 83.4%, p=0.203) and 5-year OS (97.2% vs. 97.7%, p=0.895) between the two groups. Using multivariable analysis, lymphadenectomy was not significantly associated with DFS or OS. However, using subgroup analysis, the lymphadenectomy group with serous histology had higher 5-year DFS rates than did the non-lymphadenectomy group (86.5% vs. 74.4%, p=0.048; adjusted hazard ratio=0.281; 95% confidence interval=0.107-0.735; p=0.010). The lymphadenectomy group had longer operating time (p<0.001), higher estimated blood loss (p<0.001), and higher perioperative complication rate (p=0.004) than did the non-lymphadenectomy group., Conclusion: In patients with clinically early-stage EOC with serous histology, lymphadenectomy was associated with survival benefits. Considering its potential harm, lymphadenectomy should be performed according to histologic subtype and subsequent chemotherapy in patients with clinically early-stage EOC., Trial Registration: Clinical Research Information Service Identifier: KCT0007309., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Epstein-Barr virus (EBV), the first virus found to induce cancer in humans, has been frequently detected in various types of B cell lymphomas. During its latent phase, EBV expresses a limited set of proteins crucial for its persistence. Induction of the lytic phase of EBV has shown promise in the treatment of EBV-associated malignancies. The present study assessed the ability of phomaherbarine A, a novel compound derived from the endophytic fungus Phoma herbarum DBE-M1, to stimulate lytic replication of EBV in B95-8 cells. Phomaherbarine A was found to efficiently initiate the expression of both early and late EBV lytic genes in B95-8 cells, with this initiation being further heightened by the addition of phorbol myristate acetate and sodium butyrate. Moreover, phomaherbarine A demonstrated notable cytotoxicity against the EBV-associated B cell lymphoma cell lines B95-8 and Raji. Mechanistically, phomaherbarine A induces apoptosis in these cells through the activation of caspase-3/7. When combined with ganciclovir, phomaherbarine A does not interfere with the reduction of viral replication by ganciclovir and sustains its apoptosis induction. In conclusion, these findings indicate that phomaherbarine A may be a promising candidate for therapeutic intervention in patients with EBV-associated B cell lymphomas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)