Gene-gene interaction analysis for age at onset of bipolar disorder in a Korean population.

BACKGROUND: Multiple genes might interact to determine the age at onset of bipolar disorder. We investigated gene-gene interactions related to age at onset of bipolar disorder in the Korean population, using genome-wide association study (GWAS) data. METHODS: The study population consisted of 303 patients with bipolar disorder. First, the top 1000 significant single-nucleotide polymorphisms (SNPs) associated with age at onset of bipolar disorder were selected through single SNP analysis by simple linear regression. Subsequently, the QMDR method was used to find gene-gene interactions. RESULTS: The best 10 SNPs from simple regression were located in chromosome 1, 2, 3, 10, 11, 14, 19, and 21. Only five SNPs were found in several genes, such as FOXN3, KIAA1217, OPCML, CAMSAP2, and PTPRS. On QMDR analyses, five pairs of SNPs showed significant interactions with a CVC exceeding 1/5 in a two-locus model. The best interaction was found for the pair of rs60830549 and rs12952733 (CVC = 1/5, P < 1E-07). In three-locus models, four combinations of SNPs showed significant associations with age at onset, with a CVC of >1/5. The best three-locus combination was rs60830549, rs12952733, and rs12952733 (CVC = 2/5, P < 1E-6). The SNPs showing significant interactions were located in the KIAA1217, RBFOX3, SDK2, CYP19A1, NTM, SMYD3, and RBFOX1 genes. CONCLUSIONS: Our analysis confirmed genetic interactions influencing the age of onset for bipolar disorder and identified several potential candidate genes. Further exploration of the functions of these promising genes, which may have multiple roles within the neuronal network, is necessary.

Radiation Oncologists' Perspectives on Oligometastatic Prostate Cancer: A Survey from Korean Oligometastasis Working Group.

BACKGROUND: Interest in the oligometastatic prostate cancer (OMPC) is increasing, and various clinical studies have reported the benefits of metastasis-directed radiation therapy (MDRT) in OMPC. However, the recognition regarding the adopted definitions, methodologies of assessment, and therapeutic approaches is diverse among radiation oncologists. This study aims to evaluate the level of agreement for issues in OMPC among radiation oncologists. METHODS: We generated 15 key questions (KQs) for OMPC relevant to definition, diagnosis, local therapies, and endpoints. Additionally, three clinical scenarios representing synchronous metastatic prostate cancer (mPC) (case 1), metachronous mPC with visceral metastasis (case 2), and metachronous mPC with castration-resistance and history of polymetastasis (case 3) were developed. The 15 KQs were adapted according to each scenario and transformed into 23 questions with 6-9 per scenario. The survey was distributed to 80 radiation oncologists throughout the Republic of Korea. Answer options with 0.0-29.9%, 30-49.9%, 50-69.9%, 70-79.9%, 80-89.9%, and 90-100% agreements were considered as no, minimal, weak, moderate, strong, and near perfect agreement, respectively. RESULTS: Forty-five candidates voluntarily participated in this study. Among 23 questions, near perfect (n = 4), strong (n = 3), or moderate (n = 2) agreements were shown in nine. For the case recognized as OMPC with agreements of 93% (case 1), near perfect agreements on the application of definitive radiation therapy (RT) for whole metastatic lesions were achieved. While ≥70% agreements regarding optimal dose-fractionation for metastasis-directed RT (MDRT) has not been achieved, stereotactic body RT (SBRT) is favored by clinicians with higher clinical volume. CONCLUSION: For the case recognized as OMPC, near perfect agreement for the application of definitive RT for whole metastatic lesions was reached. SBRT was more favored as a MDRT by clinicians with a higher clinical volume.

Distributable, metabolic PET reporting of tuberculosis.

Tuberculosis remains a large global disease burden for which treatment regimens are protracted and monitoring of disease activity difficult. Existing detection methods rely almost exclusively on bacterial culture from sputum which limits sampling to organisms on the pulmonary surface. Advances in monitoring tuberculous lesions have utilized the common glucoside [18F]FDG, yet lack specificity to the causative pathogen Mycobacterium tuberculosis (Mtb) and so do not directly correlate with pathogen viability. Here we show that a close mimic that is also positron-emitting of the non-mammalian Mtb disaccharide trehalose - 2-[18F]fluoro-2-deoxytrehalose ([18F]FDT) - is a mechanism-based reporter of Mycobacteria-selective enzyme activity in vivo. Use of [18F]FDT in the imaging of Mtb in diverse models of disease, including non-human primates, successfully co-opts Mtb-mediated processing of trehalose to allow the specific imaging of TB-associated lesions and to monitor the effects of treatment. A pyrogen-free, direct enzyme-catalyzed process for its radiochemical synthesis allows the ready production of [18F]FDT from the most globally-abundant organic 18F-containing molecule, [18F]FDG. The full, pre-clinical validation of both production method and [18F]FDT now creates a new, bacterium-selective candidate for clinical evaluation. We anticipate that this distributable technology to generate clinical-grade [18F]FDT directly from the widely-available clinical reagent [18F]FDG, without need for either custom-made radioisotope generation or specialist chemical methods and/or facilities, could now usher in global, democratized access to a TB-specific PET tracer.

Replication Stress in Activated Human NK Cells Induces Sensitivity to Apoptosis.

NK cells are innate immune effectors that kill virally infected or malignant cells. NK cell deficiency (NKD) occurs when NK cell development or function is impaired and variants in MCM4, GINS1, MCM10, and GINS4 result in NKD. Although NK cells are strongly impacted by mutational deficiencies in helicase proteins, the mechanisms underlying this specific susceptibility are poorly understood. In this study, we induced replication stress in activated NK cells or T cells by chemical and genetic methods. We found that the CD56bright subset of NK cells accumulates more DNA damage and replication stress during activation than do CD56dim NK cells or T cells. Aphidicolin treatment increases apoptosis of CD56bright NK cells through increased pan-caspase expression and decreases perforin expression in surviving cells. These findings show that sensitivity to replication stress affects NK cell survival and function and contributes to NKD.

Freezing-enhanced degradation of azo dyes in the chloride-peroxymonosulfate system.

In this study, we investigated the freezing-induced acceleration of dye bleaching by chloride-activated peroxymonosulfate (PMS). It has been observed that the oxidation of chloride by PMS generates a free chlorine species, such as hypochlorous acid (HOCl), under mild acidic and circumneutral pH condition. This process is the major reason for the enhanced oxidation capacity for electron-rich organic compounds (e.g., phenol) in the chloride-PMS system. However, we demonstrated that the chloride-PMS system clearly reduced the total organic carbon concentration (TOC), whereas the HOCl system did not lead to decrease in TOC. Overall, the chemical reaction is negligible in an aqueous condition if the concentrations of reagents are low, and freezing the solution accelerates the degradation of dye pollutants remarkably. Most notably, the pseudo-first order kinetic rate constant for acid orange 7 (AO7) degradation is approximately 0.252 h-1 with 0.5 mM PMS, 1 mM NaCl, initial pH 3, and a freezing temperature of -20 °C. AO7 degradation is not observed when the solution is not frozen. According to a confocal Raman-microscope analysis and an experiment that used an extremely high dose of reactants, the freeze concentration effect is the main reason for the acceleration phenomenon. Because the freezing phenomenon is spontaneous at high latitudes and at mid-latitudes in winter, and the chloride is ubiquitous elsewhere, the frozen chloride-PMS system has potential as a method for energy-free and eco-friendly technology for the degradation of organic pollutants in cold environments.

Integrated proteomic and genomic analysis to identify predictive biomarkers for valproate response in bipolar disorder: a 6-month follow-up study.

BACKGROUND: Several genetic studies have been undertaken to elucidate the intricate interplay between genetics and drug responses in bipolar disorder (BD). However, there has been notably limited research on biomarkers specifically linked to valproate, with only a few studies investigating integrated proteomic and genomic factors in response to valproate treatment. Therefore, this study aimed to identify biological markers for the therapeutic response to valproate treatment in BD. Patients with BD in remission were assessed only at baseline, whereas those experiencing acute mood episodes were evaluated at three points (baseline, 8 ± 2 weeks, and 6 ± 1 months). The response to valproate treatment was measured using the Alda scale, with individuals scoring an Alda A score ≥ 5 categorized into the acute-valproate responder (acute-VPAR) group. We analyzed 158 peptides (92 proteins) from peripheral blood samples using multiple reaction monitoring mass spectrometry, and proteomic result-guided candidate gene association analyses, with 1,627 single nucleotide variants (SNVs), were performed using the Korean chip. RESULTS: The markers of 37 peptides (27 protein) showed temporal upregulation, indicating possible association with response to valproate treatment. A total of 58 SNVs in 22 genes and 37 SNVs in 16 genes showed nominally significant associations with the Alda A continuous score and the acute-VPAR group, respectively. No SNVs reached the genome-wide significance threshold; however, three SNVs (rs115788299, rs11563197, and rs117669164) in the secreted phosphoprotein 2 gene reached a gene-based false discovery rate-corrected significance threshold with response to valproate treatment. Significant markers were associated with the pathophysiological processes of bipolar disorders, including the immune response, acute phase reaction, and coagulation cascade. These results suggest that valproate effectively suppresses mechanisms associated with disease progression. CONCLUSIONS: The markers identified in this study could be valuable indicators of the underlying mechanisms associated with response to valproate treatment.

Social signals predict contemporary art prices better than visual features, particularly in emerging markets.

What determines the price of an artwork? This article leverages a comprehensive and novel dataset on art auctions of contemporary artists to examine the impact of social and visual features on the valuation of artworks across global markets. Our findings indicate that social signals allow us to predict the price of artwork exceptionally well, even approaching the professionals' prediction accuracy, while the visual features play a marginal role. This pattern is especially pronounced in emerging markets, supporting the idea that social signals become more critical when it is more difficult to assess the quality. These results strongly support that the value of artwork is largely shaped by social factors, particularly in emerging markets where a stronger preference for "buying an artist" than "buying an artwork." Additionally, our study shows that it is possible to boost experts' performance, highlighting the potential benefits of human-machine models in uncertain or rapidly changing markets, where expert knowledge is limited.

Adjuvant Pembrolizumab in Patients with Stage IIIA/N2 Non-Small Cell Lung Cancer Completely Resected after Neoadjuvant Concurrent Chemoradiation: A Prospective, Open-Label, Single-Arm, Phase 2 Trial.

Purpose: Optimal treatment for stage IIIA/N2 non-small cell lung cancer (NSCLC) is controversial. We aimed to assess the efficacy and safety of adjuvant pembrolizumab for stage IIIA/N2 NSCLC completely resected after neoadjuvant concurrent chemoradiation therapy (CCRT). Materials and Methods: In this open-label, single-center, single-arm phase 2 trial, patients with stage IIIA/N2 NSCLC received adjuvant pembrolizumab for up to two years after complete resection following neoadjuvant CCRT. The primary endpoint was disease-free survival (DFS). Secondary endpoints included overall survival (OS) and safety. As an exploratory biomarker analysis, we evaluated the proliferative response of blood CD39+PD-1+CD8+ T cells using fold changes in the percentage of proliferating Ki-67+ cells from days 1 to 7 of cycle 1 (Ki-67D7/D1). Results: Between October 2017 and October 2018, 37 patients were enrolled. Twelve (32%) and three (8%) patients harbored EGFR and ALK alterations, respectively. Of 34 patients with programmed cell death ligand 1 assessment, 21 (62%), 9 (26%), and 4 (12%) had a tumor proportion score of <1%, 1-50%, and ≥50%, respectively. The median follow-up was 71 months. The median DFS was 22.4 months in the overall population, with a five-year DFS rate of 29%. The OS rate was 86% at two years and 76% at five years. Patients with tumor recurrence within six months had a significantly lower Ki-67D7/D1 among CD39+PD-1+CD8+ T cells than those without (p=0.036). No new safety signals were identified. Conclusion: Adjuvant pembrolizumab may offer durable disease control in a subset of stage IIIA/N2 NSCLC patients after neoadjuvant CCRT and surgery.

Unveiling the Potential of Ultrasonic-Assisted Ethanol Extract from Sargassum horneri in Inhibiting Tyrosinase Activity and Melanin Production in B16F10 Murine Melanocytes.

BACKGROUNDS: Melanogenesis, regulated by genetic, hormonal, and environmental factors, occurs in melanocytes in the basal layer of the epidermis. Dysregulation of this process can lead to various skin disorders, such as hyperpigmentation and hypopigmentation. Therefore, the present study investigated the effect of ultrasonic-assisted ethanol extract (SHUE) from Sargassum horneri (S. horneri), brown seaweed against melanogenesis in α-melanocyte-stimulating hormone (MSH)-stimulated B16F10 murine melanocytes. METHODS: Firstly, yield and proximate compositional analysis of the samples were conducted. The effect of SHUE on cell viability has been evaluated by using 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. After that, the melanin content and cellular tyrosinase activity in α-MSH-stimulated B16F10 murine melanocytes were examined. Western blot analysis was carried out to investigate the protein expression levels of microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 (TRP1), and tyrosinase-related protein-2 (TRP2). In addition, the effect of extracellular signal-regulated kinase (ERK) on the melanogenesis process was assessed via Western blotting. RESULTS: As per the analysis, SHUE contained the highest average yield on a dry basis at 28.70 ± 3.21%. The findings showed that SHUE reduced the melanin content and cellular tyrosinase activity in α-MSH-stimulated B16F10 murine melanocytes. Additionally, the expression levels of MITF, TRP1, and TRP2 protein were significantly downregulated by SHUE treatment in α-MSH-stimulated B16F10 murine melanocytes. Moreover, SHUE upregulated the phosphorylation of ERK and AKT in α-MSH-stimulated B16F10 murine melanocytes. In addition, experiments conducted using the ERK inhibitor (PD98059) revealed that the activity of SHUE depends on the ERK signaling cascade. CONCLUSION: These results suggest that SHUE has an anti-melanogenic effect and can be used as a material in the formulation of cosmetics related to whitening and lightening.

The characteristics and clinical outcomes of a pluripotent high-risk group with the potential to develop a diverse range of psychiatric disorders.

BACKGROUND: Recent studies have indicated that clinical high risk for psychosis (CHR-P) is highly specific for psychotic disorders other than pluripotential to various serious mental illnesses. However, not all CHR-P develop psychotic disorder only, and psychosis can occur in non-psychotic disorders as well. Our prospective cohort study aims to investigate the characteristics and clinical outcomes of a pluripotent high-risk group with the potential to develop a diverse range of psychiatric disorders. METHODS: The SPRIM study is a prospective naturalistic cohort program that focuses on the early detection of those at risk of developing serious mental illness, including psychosis (CHR-P), bipolar (CHR-B), and depressive disorder (CHR-D), as well as undifferentiated risk participants (UCHR). Our study has a longitudinal design with a baseline assessment and eight follow-up evaluations at 6, 12, 18, 24, 30, 36, 42, and 48 months to determine whether participants have transitioned to psychosis or mood disorders. RESULTS: The SPRIM sample consisted of 90 CHR participants. The total cumulative incidence rate of transition was 53.3% (95% CI 32.5-77.2). CHR-P, CHR-B, CHR-D, and UCHR had cumulative incidence rates of 13.7% (95% CI 3.4-46.4), 52.4% (95% CI 28.1-81.1), 66.7% (95% CI 24.6-98.6) and 54.3% (95% CI 20.5-93.1), respectively. The cumulative incidence of psychosis, bipolar, and depressive disorder among all participants was 3.3% (95% CI 0.8-11.5), 45.7% (95% CI 24.4-73.6), and 11.2% (95% CI 3.1-36.2), respectively. CONCLUSIONS: Our study suggests that the concept of pluripotent high-risk for a diverse range of psychiatric disorders is an integrative approach to examining transdiagnostic interactions between illnesses with a high transition rate and minimizing stigma.

Mtb-Selective 5-Aminomethyl Oxazolidinone Prodrugs: Robust Potency and Potential Liabilities.

Linezolid is a drug with proven human antitubercular activity whose use is limited to highly drug-resistant patients because of its toxicity. This toxicity is related to its mechanism of action─linezolid inhibits protein synthesis in both bacteria and eukaryotic mitochondria. A highly selective and potent series of oxazolidinones, bearing a 5-aminomethyl moiety (in place of the typical 5-acetamidomethyl moiety of linezolid), was identified. Linezolid-resistant mutants were cross-resistant to these molecules but not vice versa. Resistance to the 5-aminomethyl molecules mapped to an N-acetyl transferase (Rv0133) and these mutants remained fully linezolid susceptible. Purified Rv0133 was shown to catalyze the transformation of the 5-aminomethyl oxazolidinones to their corresponding N-acetylated metabolites, and this transformation was also observed in live cells of Mycobacterium tuberculosis. Mammalian mitochondria, which lack an appropriate N-acetyltransferase to activate these prodrugs, were not susceptible to inhibition with the 5-aminomethyl analogues. Several compounds that were more potent than linezolid were taken into C3HeB/FeJ mice and were shown to be highly efficacious, and one of these (9) was additionally taken into marmosets and found to be highly active. Penetration of these 5-aminomethyl oxazolidinone prodrugs into caseum was excellent. Unfortunately, these compounds were rapidly converted into the corresponding 5-alcohols by mammalian metabolism which retained antimycobacterial activity but resulted in substantial mitotoxicity.

Risk factors of reattempt among suicide attempters in South Korea: A nationwide retrospective cohort study.

This study aimed to identify underlying demographic and clinical characteristics among individuals who had previously attempted suicide, utilizing the comprehensive Health Insurance Review and Assessment Service (HIRA) database. Data of patients aged 18 and above who had attempted suicide between January 1 and December 31, 2014, recorded in HIRA, were extracted. The index date was identified when a suicide attempt was made within the year 2014. The medical history of the three years before the index date and seven years of follow-up data after the index date were analyzed. Kaplan-Meier estimate was used to infer reattempt of the suicide attempters, and Cox-proportional hazard analysis was used to investigate risk factors associated with suicide reattempts. A total of 17,026 suicide attempters were identified, of which 1,853 (10.9%) reattempted suicide; 4,925 (28.9%) patients had been diagnosed with depressive disorder. Of the reattempters, 391 (21.1%) demonstrated a history of suicide attempts in the three years before the index date, and the mean number of prior attempts was higher compared to that of the non-reattempters (1.7 vs.1.3, p-value < 0.01). Prior psychiatric medication, polypharmacy, and an increase in the number of psychotropics were associated with suicide reattempt in overall suicide attempters. (Hazard ratio (HR) = 3.20, 95% confidence interval [CI] = 2.56-4.00; HR = 2.42, 95% CI = 1.87-3.14; HR = 19.66, 95% CI = 15.22-25.39 respectively). The risk of reattempt decreased in individuals receiving antidepressant prescriptions compared to those unmedicated, showing a reduction of 78% when prescribed by non-psychiatrists and 89% when prescribed by psychiatrists. Similar risk factors for suicide reattempts were observed in the depressive disorder subgroup, but the median time to reattempt was shorter (556.5 days) for this group compared to that for the overall attempters (578 days). Various risk factors including demographics, clinical characteristics, and medications should be considered to prevent suicide reattempts among suicide attempters, and patients with depressive disorder should be monitored more closely.

Emergence of simple and complex contagion dynamics from weighted belief networks.

Social contagion is a ubiquitous and fundamental process that drives individual and social changes. Although social contagion arises as a result of cognitive processes and biases, the integration of cognitive mechanisms with the theory of social contagion remains an open challenge. In particular, studies on social phenomena usually assume contagion dynamics to be either simple or complex, rather than allowing it to emerge from cognitive mechanisms, despite empirical evidence indicating that a social system can exhibit a spectrum of contagion dynamics-from simple to complex-simultaneously. Here, we propose a model of interacting beliefs, from which both simple and complex contagion dynamics can organically arise. Our model also elucidates how a fundamental mechanism of complex contagion-resistance-can come about from cognitive mechanisms.

Photodegradation of bisphenol A in water and ice: identification of products using three photosensitizers.

Bisphenol A (BPA) is a widespread organic micro-pollutant, found in most environments, including alpine and Arctic regions, and several matrices such as waters and aerosols. Polar regions are characterized by periods of intense irradiation with no sunset due to the continuous sunlight, while alpine areas, despite following the day-night cycle of mid-latitudes, also undergo strong irradiation. For such conditions, it is possible that a fraction of the BPA present in snow may degrade through direct photolysis, producing other unknown species with different environmental mobility and possible ecotoxic effects. Furthermore, the snowpack is rich in species (known as photosensitizers) that facilitate indirect photodegradation processes through reactions involving hydroxyl radicals  · OH , singlet oxygen (1O2), excited triplet states of the organic fraction (3CDOM*), and nitrite/nitrate. In this study, we investigated both direct and indirect photodegradation of BPA in the presence of specific photosensitizers producing  · OH , 1O2, 3CDOM*, and NO2- to specifically explore the products of the reaction. The study was conducted in both liquid water and ice, under light and dark conditions. Results, obtained by HPLC-HRMS, revealed that the matrix in which the reaction takes place, in addition to the photosensitizer used, may influence the degradation by-products. This allows for the possibility of distinguishing the reaction environment based on the identified product.

Microbial Profiles in Oral Lichen Planus: Comparisons with Healthy Controls and Erosive vs. Non-Erosive Subtypes.

Recent studies have begun exploring the potential involvement of microbiota in the pathogenesis of oral lichen planus (OLP), yet comprehensive investigations remain limited. Hence, this study aimed to compare the microbial profiles in saliva samples obtained from patients with OLP against those from healthy controls (HC), along with a comparison between erosive (E) and non-erosive (NE) OLP patients. Saliva samples were collected from 60 OLP patients (E: n = 25, NE: n = 35) and 30 HC individuals. Analysis revealed no significant differences in alpha diversity, as assessed by the Chao1 and Shannon index, across the three groups. However, Bray-Curtis distance analysis indicated a significant disparity in microbiome composition distribution between HC and E-OLP, as well as HC and NE-OLP groups. The six most abundant phyla observed across the groups were Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, Fusobacteria, and Saccharibacteria (TM7). Notably, OLP groups exhibited a higher prevalence of Bacteroidetes. Prevotella emerged as the predominant genus in the OLP groups, while Capnocytophaga showed a relatively higher prevalence in E-OLP compared to NE-OLP. This study's findings indicate a notable difference in microbiota composition between HC and patients with OLP. Additionally, differences in the microbiome were identified between the E-OLP and NE-OLP groups. The increase in the proportion of certain bacterial species in the oral microbiome suggests that they may exacerbate the inflammatory response and act as antigens for OLP.

Comparison of radiotherapy techniques in patients with thymic epithelial tumor who underwent postoperative radiotherapy.

PURPOSE: This retrospective study aimed to compare clinical outcomes and dosimetric parameters between radiation therapy (RT) techniques in patients with thymic epithelial tumor (TET). MATERIALS AND METHODS: From January 2016 to December 2020, 101 patients with TET received adjuvant RT (median, 52.8 Gy; range, 48.4 to 66.0). Three different RT techniques were compared: three-dimensional conformal RT (3D-CRT; n = 59, 58.4%), intensity-modulated RT (IMRT; n = 23, 22.8%), and proton beam therapy (PBT; n = 19, 18.8%). RESULTS: The median age of the patients and the follow-up period were 55 years (range, 28 to 79) and 43.4 months (range, 7.7 to 77.2). Patients in the PBT group were of the youngest age (mean age, 45.4 years), while those in IMRT group had the largest clinical target volume (mean volume, 149.6 mL). Patients in the PBT group had a lower mean lung dose (4.4 Gy vs. 7.6 Gy vs. 10.9 Gy, respectively; p < 0.001), lower mean heart dose (5.4 Gy vs. 10.0 Gy vs. 13.1 Gy, respectively; p = 0.003), and lower mean esophageal dose than patients in the 3D-CRT and IMRT groups (6.3 Gy vs. 9.8 Gy vs. 13.5 Gy, respectively; p = 0.011). Twenty patients (19.8%) showed disease recurrence, and seven patients (6.9%) died. The differences in the survival rates between RT groups were not statistically significant. CONCLUSION: In patients with TET who underwent adjuvant RT, PBT resulted in a lower dose of exposure to adjacent organs at risk. Survival outcomes for patients in PBT group were not significantly different from those in other groups.

Clinical Outcomes in Adenoid Cystic Carcinoma of the Nasal Cavity and Paranasal Sinus: A Comparative Analysis of Treatment Modalities.

This study aimed to present the treatment patterns and outcomes for adenoid cystic carcinoma (ACC) arising in the nasal cavity and paranasal sinus. Sixty-one sinonasal ACC patients were retrospectively reviewed: 31 (50.8%) underwent surgery followed by postoperative radiation therapy (S+PORT), and 30 (49.2%) received definitive radiation therapy (D(C)RT). T4 disease was significantly more frequent in the D(C)RT group (25.8% vs. 80.0%, p < 0.001), where all T4b disease patients underwent D(C)RT. The 5-year local failure-free survival (LFFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival were 61.8% versus 37.8% (p = 0.003), 64.8% versus 38.1% (p = 0.036), 52.6% versus 19.3% (p = 0.010), and 93.2% versus 73.4% (p = 0.001) in the S+PORT and D(C)RT groups, respectively. The absolute differences in 5-year rates of LFFS, DMFS, and PFS between the two groups were smaller in the T3-4 subgroup. The univariate analysis showed that T4b disease, neurologic symptoms, longest diameter of tumor, radiological evidence of nerve involvement, and undergoing D(C)RT were associated with worse clinical outcomes, but the significance disappeared in the multivariate analysis, except for in the case of radiological evidence of nerve involvement. In conclusion, most patients with extensive disease underwent upfront D(C)RT and generally exhibited inferior clinical outcomes when compared to those with less extensive disease and who underwent S+PORT.

Structural and functional characterization of sulfurtransferase from Frondihabitans sp. PAMC28461.

Sulfurtransferases transfer of sulfur atoms from thiols to acceptors like cyanide. They are categorized as thiosulfate sulfurtransferases (TSTs) and 3-mercaptopyruvate sulfurtransferases (MSTs). TSTs transfer sulfur from thiosulfate to cyanide, producing thiocyanate. MSTs transfer sulfur from 3-mercaptopyruvate to cyanide, yielding pyruvate and thiocyanate. The present study aimed to isolate and characterize the sulfurtransferase FrST from Frondihabitans sp. PAMC28461 using biochemical and structural analyses. FrST exists as a dimer and can be classified as a TST rather than an MST according to sequence-based clustering and enzyme activity. Furthermore, the discovery of activity over a wide temperature range and the broad substrate specificity exhibited by FrST suggest promising prospects for its utilization in industrial applications, such as the detoxification of cyanide.

Serum lipids as predictive markers for death by suicide.

Serum lipid levels have been associated with an increased risk of suicidal behaviors. This retrospective cohort study aimed to investigate the association between serum lipid levels and death by suicide among suicide attempters according to sex. Suicide attempters visiting emergency departments between 2007 and 2011 were followed up until the date of all-cause death or December 31, 2012. Sex-stratified Cox proportional hazards regression and competing risk models were constructed to obtain the hazard ratios (HR) of serum lipid measures and suicide. For each significant lipid variable in the final models, Kaplan-Meier survival analysis and cumulative incidence function (CIF) were employed to compare the time to suicide between the high- and low-lipid groups based on the best cutoff point from the receiver operating characteristic curve. In 408 female attempters (65.8 %), the HR in the Cox regression model and subdistribution HR in the competing risk model for increased total cholesterol (TC) were 0.968 and 0.970, respectively. In the Kaplan-Meier survival analysis and CIF, increased death by suicide was demonstrated in the low-TC group (< 165 mg/dL). Lower serum TC levels among female suicide attempters may predict suicide. More careful monitoring is warranted in women with lower TC levels who recently attempted suicide.

Identifying predictive factors for mood recurrence in early-onset major mood disorders: A 4-year, multicenter, prospective cohort study.

We investigate the predictive factors of the mood recurrence in patients with early-onset major mood disorders from a prospective observational cohort study from July 2015 to December 2019. A total of 495 patients were classified into three groups according to recurrence during the cohort observation period: recurrence group with (hypo)manic or mixed features (MMR), recurrence group with only depressive features (ODR), and no recurrence group (NR). As a result, the baseline diagnosis of bipolar disorder type 1 (BDI) and bipolar disorder type 2 (BDII), along with a familial history of BD, are strong predictors of the MMR. The discrepancies in wake-up times between weekdays and weekends, along with disrupted circadian rhythms, are identified as a notable predictor of ODR. Our findings confirm that we need to be aware of different predictors for each form of mood recurrences in patients with early-onset mood disorders. In clinical practice, we expect that information obtained from the initial assessment of patients with mood disorders, such as mood disorder type, family history of BD, regularity of wake-up time, and disruption of circadian rhythms, can help predict the risk of recurrence for each patient, allowing for early detection and timely intervention.