Drug release control and anti-inflammatory effect of biodegradable polymer surface modified by gas phase chemical functional reaction.

The plasma technique has been widely used to modify the surfaces of materials. The purpose of this study was to evaluate the probability of controlling the prednisolone delivery velocity on a polylactic acid (PLA) surface modified by plasma surface treatment. Surface modification of PLA was performed at a low-pressure radio frequency under conditions of 100 W power, 50 mTorr chamber pressure, 100-200 sccm of flow rate, and Ar, O2, and CH4gases. The plasma surface-modified PLA was characterized using scanning emission microscope, x-ray photoelectron spectroscopy (XPS), and contact angle measurements.In vitroevaluations were performed to determine cellular response, drug release behavior, and anti-inflammatory effects. The PLA surface morphology was changed to a porous structure (with a depth of approximately 100 µm) and the surface roughness was also significantly increased. The XPS results demonstrated higher oxygenized carbon contents than those in the non-treated PLA group. The prednisolone holding capacity increased and the release was relatively prolonged in the surface-modified PLA group compared to that in the non-treated PLA group. In addition, cell migration and proliferation significantly increased after PLA treatment alone. The activity of cytokines such as cyclooxygenase-2 (COX-2), tumor necrosis factor-a (TNF-α), interleukin (IL-1ß), and IL-6 were considerably reduced in the plasma-treated and prednisolone holding group. Taken together, surface-modified PLA by plasma can provide an alternative approach to conventional physicochemical approaches for sustained anti-inflammatory drug release.

North Korean defectors with PTSD and complex PTSD show alterations in default mode network resting-state functional connectivity.

BACKGROUND: North Korean defectors (NKDs) have often been exposed to traumatic events. However, there have been few studies of neural alterations in NKDs with post-traumatic stress disorder (PTSD) and complex PTSD (cPTSD). AIMS: To investigate neural alterations in NKDs with PTSD and cPTSD, with a specific focus on alterations in resting-state functional connectivity networks, including the default mode network (DMN). METHOD: Resting-state functional connectivity was assessed using brain functional magnetic resonance imaging in three groups of NKDs: without PTSD, with PTSD and with cPTSD. Statistical tests were performed, including region of interest (ROI)-to-ROI and ROI-to-voxel analysis, followed by post hoc correlation analysis. RESULTS: In the ROI-to-ROI analysis, differences in functional connectivity were found among the components of the DMN, as well as in the thalamus and the basal ganglia. Right hippocampus-left pallidum and right amygdala-left lingual gyrus connectivity differed between groups in the ROI-to-voxel analysis, as did connectivity involving the basal ganglia. The post hoc analysis revealed negative correlations between Coping and Adaptation Processing Scale (CAPS) score and left posterior cingulate cortex-right pallidum connectivity and between CAPS score and right putamen-left angular gyrus connectivity in the control group, which were not observed in other groups. CONCLUSIONS: The results suggest that there are alterations in the functional connectivity of the DMN and the limbic system in NKDs with PTSD and cPTSD, and that these alterations involve the basal ganglia. The lower correlations of CAPS score with right basal ganglia-DMN functional connectivity in patients compared with controls further implies that these connectivities are potential targets for treatment of PTSD and cPTSD.

High-response room-temperature NO2 gas sensor fabricated with thermally reduced graphene oxide-coated commercial cotton fabric.

Electronic textile-based gas sensors with a high response for NO2 gas were fabricated using reduced graphene oxide (rGO)-coated commercial cotton fabric (rGOC). Graphene oxide (GO) was coated on cotton fabric by simply dipping the cotton into a GO solution. To investigate the relationship between the degree of reduction and the sensing response, the GO-coated fabrics were thermally reduced at various temperatures (190, 200, 300, and 400 °C). The change in the amount of oxygen functional groups on the rGOCs was observed by x-ray photoelectron spectroscopy, Raman spectroscopy, and x-ray diffraction patterns. The maximum sensing response of 45.90 % at 10 ppm of NO2 gas at room temperature was exhibited by the rGOC treated at 190 °C, which was the lowest heat-treatment temperature. The high response comes from the greater amount of oxygen functional groups compared to other rGOC samples, and the tubular structure of the cotton.

A prospective, multicenter study on the clinical effectiveness of abiraterone in metastatic castration-resistant prostate cancer in Korea: Pre- vs. post-chemotherapy.

PURPOSE: The proper treatment sequence for administering abiraterone acetate plus prednisolone (AAP) and chemotherapeutic agents has not yet been elucidated for metastatic castration-resistant prostate cancer (mCRPC). Hence, this study evaluated the effectiveness and safety of AAP in pre- and post-chemotherapy settings using real-world data. MATERIALS AND METHODS: This prospective, multicenter, open-label, observational study included 506 patients with mCRPC. Patients were classified according to the timing of chemotherapy into pre- and post-chemotherapy groups. The effectiveness and safety of AAP were compared between the groups; the prostate-specific antigen (PSA) response, PSA progression-free survival, and radiologic progression-free survival were assessed; and adverse drug reactions were recorded. RESULTS: Among the included patients, 319 and 187 belonged to the pre- and post-chemotherapy groups, respectively. Risk classification was similar between the two groups. The PSA response was 61.8% in the pre-chemotherapy group and 39.0% in the post-chemotherapy group (p<0.001). The median time to PSA progression (5.00 vs. 2.93 mo, p=0.001) and radiologic progression-free survival (11.84 vs. 9.17 mo, p=0.002) were significantly longer in the pre-chemotherapy group. Chemotherapy status was associated with PSA (hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.09-1.77) and radiologic progression (HR 1.66, 95% CI 1.18-2.33) during AAP treatment. Adverse drug reactions were reported at similar frequencies in both groups. CONCLUSIONS: In this postmarketing surveillance, AAP benefited patients with mCRPC, especially in settings before chemotherapy was administered, resulting in a high PSA response and longer PSA and radiologic progression-free survival with tolerable adverse drug reactions.

Corrigendum: Correction of the Figure. Trends of stratified prostate cancer risk in a single Korean province from 2003 to 2021: A multicenter study conducted using regional training hospital data.

This corrects the article on p. 140 in vol. 64, PMID: 36882172.

Early Detection of Secondary Bladder Urothelial Carcinoma and Disseminated Bone Metastases with Normal Prostate-Specific Antigen Level after Pelvic Salvage Radiotherapy in Prostate Cancer.

This report describes the case of a 65-year-old man who presented with gross hematuria and a history of pelvic salvage radiotherapy for prostate cancer. Cystoscopy and transurethral resection of the bladder revealed urothelial carcinoma. Subsequently, disseminated bone metastases were detected with normal prostate-specific antigen (PSA) levels, and palliative radiotherapy and systemic chemotherapy were administered. Because gross hematuria can appear in both acute/chronic cystitis and bladder cancer in patients who have undergone pelvic radiotherapy for prostate cancer, close follow-up along with a detailed evaluation is needed. In addition, because prostate cancer disease progression with normal PSA levels may be associated with specific pathological findings, a detailed evaluation of symptoms and a careful review of pathologic reports are important.

Antidepressant-induced mania in panic disorder: a single-case study of clinical and functional connectivity characteristics.

Background: Mental health issues, including panic disorder (PD), are prevalent and often co-occur with anxiety and bipolar disorders. While panic disorder is characterized by unexpected panic attacks, and its treatment often involves antidepressants, there is a 20-40% risk of inducing mania (antidepressant-induced mania) during treatment, making it crucial to understand mania risk factors. However, research on clinical and neurological characteristics of patients with anxiety disorders who develop mania is limited. Methods: In this single case study, we conducted a larger prospective study on panic disorder, comparing baseline data between one patient who developed mania (PD-manic) and others who did not (PD-NM group). We enrolled 27 patients with panic disorder and 30 healthy controls (HCs) and examined alterations in amygdala-based brain connectivity using a seed-based whole-brain approach. We also performed exploratory comparisons with healthy controls using ROI-to-ROI analyses and conducted statistical inferences at a threshold of cluster-level family-wise error-corrected p < 0.05, with the cluster-forming threshold at the voxel level of uncorrected p < 0.001. Results: The patient with PD-mania showed lower connectivity in brain regions related to the default mode network (left precuneous cortex, maximum z-value within the cluster = -6.99) and frontoparietal network (right middle frontal gyrus, maximum z-value within the cluster = -7.38; two regions in left supramarginal gyrus, maximum z-value within the cluster = -5.02 and -5.86), and higher in brain regions associated with visual processing network (right lingual gyrus, maximum z-value within the cluster = 7.86; right lateral occipital cortex, maximum z-value within the cluster = 8.09; right medial temporal gyrus, maximum z-value within the cluster = 8.16) in the patient with PD-mania compared to the PD-NM group. One significantly identified cluster, the left medial temporal gyrus (maximum z-value within the cluster = 5.82), presented higher resting-state functional connectivity with the right amygdala. Additionally, ROI-to-ROI analysis revealed that significant clusters between PD-manic and PD-NM groups differed from HCs in the PD-manic group but not in the PD-NM group. Conclusion: Here, we demonstrate altered amygdala-DMN and amygdala-FPN connectivity in the PD-manic patient, as reported in bipolar disorder (hypo) manic episodes. Our study suggests that amygdala-based resting-state functional connectivity could serve as a potential biomarker for antidepressant-induced mania in panic disorder patients. Our findings provide an advance in understanding the neurological basis of antidepressant-induced mania, but further research with larger cohorts and more cases is necessary for a broader perspective on this issue.

SAMHD1-induced endosomal FAK signaling promotes human renal clear cell carcinoma metastasis by activating Rac1-mediated lamellipodia protrusion.

Human sterile α motif and HD domain-containing protein 1 (SAMHD1) has deoxyribonucleoside triphosphohydrolase (dNTPase) activity that allows it to defend against human immunodeficiency virus type I (HIV-1) infections and regulate the cell cycle. Although SAMHD1 mutations have been identified in various cancer types, their role in cancer is unclear. Here, we aimed to investigate the oncogenic role of SAMHD1 in human clear cell renal cell carcinoma (ccRCC), particularly as a core molecule promoting cancer cell migration. We found that SAMHD1 participated in endocytosis and lamellipodia formation. Mechanistically, SAMHD1 contributed to the formation of the endosomal complex by binding to cortactin. Thereafter, SAMHD1-stimulated endosomal focal adhesion kinase (FAK) signaling activated Rac1, which promoted lamellipodia formation on the plasma membrane and enhanced the motility of ccRCC cells. Finally, we observed a strong correlation between SAMHD1 expression and the activation of FAK and cortactin in tumor tissues obtained from patients with ccRCC. In brief, these findings reveal that SAMHD1 is an oncogene that plays a pivotal role in ccRCC cell migration through the endosomal FAK-Rac1 signaling pathway.

Trends of stratified prostate cancer risk in a single Korean province from 2003 to 2021: A multicenter study conducted using regional training hospital data.

PURPOSE: To identify changes in prostate cancer (PCa) risk-stratification during the last two decades in Korea, where the social perception of PCa was limited due to a relatively low incidence but has recently been triggered by the rapidly increasing incidence of benign prostate hyperplasia. MATERIALS AND METHODS: Retrospective data of patients who had received a diagnosis of PCa in a single Korean province (Daegu-Gyeongsangbuk) at all seven training hospitals in the years 2003, 2007, 2011, 2015, 2019, and 2021 were subjected to analysis. Changes in PCa risk-stratification were investigated with respect to serum prostate-specific antigen (PSA), Gleason score (GS), and clinical stage. RESULTS: Of the 3,393 study subjects that received a diagnosis of PCa, 64.1% had high-risk disease, 23.0% intermediate, and 12.9% low-risk disease. The proportion diagnosed with high-risk disease was 54.8% in 2003, 30.6% in 2019, but then increased to 35.1% in 2021. The proportion of patients with high PSA (>20 ng/mL) steadily decreased from 59.4% in 2003 to 29.6% in 2021, whereas the proportion with a high GS (>8) increased from 32.8% in 2011 to 34.0% in 2021, and the proportion with advanced stage disease (over cT2c) increased from 26.5% in 2011 to 37.1% in 2021. CONCLUSIONS: In this retrospective study, conducted in a single Korean province, high-risk PCa accounted for the largest proportion of newly registered Korean PCa patients during the last two decades and increased in the early 2020s. This outcome supports the adoption of nationwide PSA screening, regardless of current Western guidelines.

Current treatment patterns within 1 year after prostate cancer diagnosis in Korean patients over 75 years old: a retrospective multicenter study.

Background: We aimed to evaluate the current status of first-line treatment options for prostate cancer in patients aged ≥75 years in Korea. Materials and methods: The study included 873 patients diagnosed with biopsy-proven prostate cancer at 5 institutions in Korea from January 2009 to December 2018. Inclusion criteria were aged ≥75 years at diagnosis, prostate biopsy with ≥12 cores, and follow-up period ≥1 year. Clinical data were retrospectively collected from electronic medical records. Results: Primary treatment for prostate cancer in patients aged ≥75 years included androgen deprivation therapy (ADT) (n = 614), radical prostatectomy (RP) (n = 114), and radiation therapy (n = 62). Among patients with RP, nine patients received ADT before RP. The RP group was younger with better Eastern Cooperative Oncology Group Performance Status (ECOG PS), lower initial prostate-specific antigen (PSA), Gleason score (GS), max percent positive cores, less positive cores, and less advanced clinical Tumor Node Metastasis (TNM) stage compared with the ADT group. Multivariate analysis showed that age, ECOG PS, and PSA were independent prognostic factors for RP. When the ADT group was classified by therapeutic regimens, the most common therapeutic regimen was maximal androgen blockade (MAB) (n = 571), and leuprolide + bicalutamide (n = 330) was the most common MAB regimen. Multivariate analysis for secondary treatment showed that age, ECOG PS, GS, and clinical N1 or M1 stage were independent predictive factors. Enzalutamide was the most preferred treatment for tertiary treatment. Conclusion: In patients with prostate cancer aged ≥75 years, the most common treatment option was MAB, and the leuprolide + bicalutamide was the most common MAB regimen. Age, ECOG PS, and PSA are the useful indicators of surgical treatment, which increased during the study period. Younger patients with high GS and advanced clinical stage were more likely to undergo secondary treatment.

DMP1 and IFITM5 Regulate Osteogenic Differentiation of MC3T3-E1 on PEO-Treated Ti-6Al-4V-Ca2+/Pi surface.

Despite numerous studies on various surface modifications on titanium and its alloys, it remains unclear what kind of titanium-based surface modifications are capable of controlling cell activity. This study aimed to understand the mechanism at the cellular and molecular levels and investigate the in vitro response of osteoblastic MC3T3-E1 cultured on the Ti-6Al-4V surface modified by plasma electrolytic oxidation (PEO) treatment. A Ti-6Al-4V surface was prepared by PEO at 180, 280, and 380 V for 3 or 10 min in an electrolyte containing Ca2+/Pi ions. Our results showed that PEO-treated Ti-6Al-4V-Ca2+/Pi surfaces enhanced the cell attachment and differentiation of MC3T3-E1 compared to the untreated Ti-6Al-4V control but did not affect cytotoxicity as shown by cell proliferation and cell death. Interestingly, on the Ti-6Al-4V-Ca2+/Pi surface treated by PEO at 280 V for 3 or 10 min, MC3T3-E1 showed a higher initial adhesion and mineralization. In addition, the alkaline phosphatase (ALP) activity significantly increased in MC3T3-E1 on the PEO-treated Ti-6Al-4V-Ca2+/Pi (280 V for 3 or 10 min). In RNA-seq analysis, the expression of dentin matrix protein 1 (DMP1), sortilin 1 (Sort1), signal-induced proliferation-associated 1 like 2 (SIPA1L2), and interferon-induced transmembrane protein 5 (IFITM5) was induced during the osteogenic differentiation of MC3T3-E1 on the PEO-treated Ti-6Al-4V-Ca2+/Pi. DMP1 and IFITM5 silencing decreased the expression of bone differentiation-related mRNAs and proteins and ALP activity in MC3T3-E1. These results suggest that the PEO-treated Ti-6Al-4V-Ca2+/Pi surface induces osteoblast differentiation by regulating the expression of DMP1 and IFITM5. Therefore, surface microstructure modification through PEO coatings with Ca2+/Pi ions could be used as a valuable method to improve biocompatibility properties of titanium alloys.

Feasibility of the virtual reality-based assessments in patients with panic disorder.

Introduction: Recurrences and diagnostic instability of panic disorder (PD) are common and have a negative effect on its long-term course. Developing a novel assessment tool for anxiety that can be used in a multimodal approach may improve these problems in panic disorder patients. This study assessed the feasibility of virtual reality-based assessment in panic disorder (VRA-PD). Methods: Twenty-five patients with PD (ANX group) and 28 healthy adults (CON group) participated in the study. VRA-PD consisted of four modules based on the key components of cognitive behavior therapy for an anxiety disorder: "Baseline evaluation module" (M0), "Daily environment exposure module" (M1), "Relaxation module" (M2), and "Interoceptive exposure module" (M3). Multiple evaluations, including self-rating anxiety scores (AS) and physiological responses [heart rate variability (HRV) index], were performed in three steps at M1, M2, and M3, and once at M0. Comparisons between patients with PD and healthy controls, factor analysis of variables in VRA-PD, changes in responses within modules, and correlation analysis between variables in VRA-PD and anxiety symptoms assessed by psychological scales were performed. Results: All participants completed the VRA-PD without discontinuation. The ANX group reported significantly higher AS for all steps and a smaller HRV index in M1 (steps 1 and 2) and M2 (step 1). Repeated-measures analysis of covariance (ANCOVA) revealed significant interaction effects for AS in M1 (F = 4.09, p = 0.02) and M2 (F = 4.20, p = 0.02), and HRV index in M2 (F = 16.22, p < 0.001) and M3 (F = 21.22, p = 0.02). The HRV index only indicated a good model fit for the three-factor model, reflecting the construct of the VRA-PD. Both AS and HRV indexes were significantly correlated with anxiety and depression symptoms. Discussion: The current study provides preliminary evidence that the VRA-PD could be a valid anxiety behavior assessment tool.

Lead-Free Piezoelectric Acceleration Sensor Built Using a (K,Na)NbO3 Bulk Ceramic Modified by Bi-Based Perovskites.

Piezoelectric accelerometers using a lead-free (K,Na)NbO3 (KNN) piezoceramic modified by a mixture of two Bi-based perovskites, Bi(Na,K,Li)ZrO3 (BNKLZ) and BiScO3 (BS), were designed, fabricated and characterized. Ring-shaped ceramics were prepared using a conventional solid-state reaction method for integration into a compression-mode accelerometer. A beneficial rhombohedral-tetragonal (R-T) phase boundary structure, especially enriched with T phase, was produced by modifying intrinsic phase transition temperatures, yielding a large piezoelectric charge coefficient d33 (310 pC/N) and a high Curie temperature Tc (331 °C). Using finite element analyses with metamodeling techniques, four optimum accelerometer designs were obtained with high magnitudes of charge sensitivity Sq and resonant frequency fr, as evidenced by two key performance indicators having a trade-off relation. Finally, accelerometer sensor prototypes based on the proposed designs were fabricated using the KNN-BNKLZ-BS ceramic rings, which exhibited high levels of Sq (55.1 to 223.8 pC/g) and mounted fr (14.1 to 28.4 kHz). Perfect charge-to-acceleration linearity as well as broad flat frequency ranges were achieved with excellent reliability. These outstanding sensing performances confirm the potential application of the modified-KNN ceramic in piezoelectric sensors.

Robotic-assisted simple prostatectomy versus holmium laser enucleation of the prostate for large benign prostatic hyperplasia: A single-center preliminary study in Korea.

Background: Holmium laser enucleation of the prostate (HoLEP) and robotic-assisted simple prostatectomy (RASP) are the two most important therapeutic modalities for large benign prostatic hyperplasia. However, there are currently no studies comparing these two treatments in a Korean setting. In this study, the authors seek to compare the safety and efficacy associated with these procedures. Methods: The authors retrospectively analyzed 59 male patients who underwent HoLEP (n = 26) or RASP (n = 33) at single center. The following preoperative data were compared: age, the International Prostatic Symptom Score (IPSS), transrectal ultrasonography, uroflowmetry, and hemoglobin. Intraoperative data included operation time and specimen weight. Postoperative data included change in IPSS, uroflowmetry, and hemoglobin. Length of stay, catheterization time, and complications were also reviewed. Results: No significant differences between the two groups were found in terms of age, total prostate, and transitional volume. Postoperatively, both groups showed similar improvement in the maximum flow rate, post-void residual urine, IPSS, and quality of life. Intraoperatively, there were no differences regarding operation time and resected prostate volume. Catheter removal time and length of stay were significantly shorter in the HoLEP group than the RASP group. In addition, postoperative hemoglobin changes were significantly lower in the HoLEP group. However, incontinence rates at 1 month and 2 months postoperative in the RASP group were lower than the HoLEP group. Conclusions: Both HoLEP and RASP can produce excellent postoperative outcomes. However, catheter removal time, length of stay, and hemoglobin changes were more favorable in the HoLEP group. On the other hand, postoperative incontinence was more favorable in the RASP group. These factors must be heavily considered when deciding surgical the method for large benign prostatic hyperplasia.

Alteration of resting-state functional connectivity network properties in patients with social anxiety disorder after virtual reality-based self-training.

Social anxiety disorder (SAD) is a mental disorder characterized by excessive anxiety in social situations. This study aimed to examine the alteration of resting-state functional connectivity in SAD patients related to the virtual reality-based self-training (VRS) which enables exposure to social situations in a controlled environment. Fifty-two SAD patients were randomly assigned to the experimental group who received the VRS, or the control group who did not. Self-report questionnaires and resting-state functional magnetic resonance imaging (fMRI) were performed to assess clinical symptoms and analyze the resting-state network properties, respectively. Significant decrease in social anxiety and an increase in self-esteem was found in the experimental group. From the resting-state fMRI analysis, alteration of local network properties in the left dorsolateral prefrontal gyrus (-10.0%, p = 0.025), left inferior frontal gyrus (-32.3%, p = 0.044), left insula (-17.2%, p = 0.046), left Heschl's gyrus (-21.2%, p = 0.011), bilateral inferior temporal gyrus (right: +122.6%, p = 0.045; left:-46.7%, p = 0.015), and right calcarine sulcus (+17.0%, p = 0.010) were found in the experimental group. Average shortest path length (+8.3%, p = 0.008) and network efficiency (-7.6%, p = 0.011) are found to be altered from the global network property analysis. In addition, the experimental group displayed more positive and more negative changes in the correlation trend of average shortest path length (p = 0.004) and global network efficiency (p = 0.014) with the severity of social anxiety, respectively. These results suggest potential effectiveness of the VRS, which is possibly related to the change of aberrant processing and control of visual and auditory linguistic stimuli and the adaptive change in rumination pattern.

Validation of MRI-Based Models to Predict MGMT Promoter Methylation in Gliomas: BraTS 2021 Radiogenomics Challenge.

O6-methylguanine-DNA methyl transferase (MGMT) methylation prediction models were developed using only small datasets without proper external validation and achieved good diagnostic performance, which seems to indicate a promising future for radiogenomics. However, the diagnostic performance was not reproducible for numerous research teams when using a larger dataset in the RSNA-MICCAI Brain Tumor Radiogenomic Classification 2021 challenge. To our knowledge, there has been no study regarding the external validation of MGMT prediction models using large-scale multicenter datasets. We tested recent CNN architectures via extensive experiments to investigate whether MGMT methylation in gliomas can be predicted using MR images. Specifically, prediction models were developed and validated with different training datasets: (1) the merged (SNUH + BraTS) (n = 985); (2) SNUH (n = 400); and (3) BraTS datasets (n = 585). A total of 420 training and validation experiments were performed on combinations of datasets, convolutional neural network (CNN) architectures, MRI sequences, and random seed numbers. The first-place solution of the RSNA-MICCAI radiogenomic challenge was also validated using the external test set (SNUH). For model evaluation, the area under the receiver operating characteristic curve (AUROC), accuracy, precision, and recall were obtained. With unexpected negative results, 80.2% (337/420) and 60.0% (252/420) of the 420 developed models showed no significant difference with a chance level of 50% in terms of test accuracy and test AUROC, respectively. The test AUROC and accuracy of the first-place solution of the BraTS 2021 challenge were 56.2% and 54.8%, respectively, as validated on the SNUH dataset. In conclusion, MGMT methylation status of gliomas may not be predictable with preoperative MR images even using deep learning.

Nanophotosensitizers Composed of Phenyl Boronic Acid Pinacol Ester-Conjugated Chitosan Oligosaccharide via Thioketal Linker for Reactive Oxygen Species-Sensitive Delivery of Chlorin e6 against Oral Cancer Cells.

Chlorin E6 (Ce6)-incorporated nanophotosensitizers were fabricated for application in photodynamic therapy (PDT) of oral cancer cells. For this purpose, chitosan oligosaccharide (COS) was conjugated with hydrophobic and reactive oxygen species (ROS)-sensitive moieties, such as phenyl boronic acid pinacol ester (PBAP) via a thioketal linker (COSthPBAP). ThdCOOH was conjugated with PBAP to produce ThdCOOH-PBAP conjugates and then attached to amine groups of COS to produce a COSthPBAP copolymer. Ce6-incorporated nanophotosensitizers using the COSthPBAP copolymer were fabricated through the nanoprecipitation and dialysis methods. The Ce6-incorporated COSthPBAP nanophotosensitizers had a small diameter of less than 200 nm with a mono-modal distribution pattern. However, it became a multimodal and/or irregular distribution pattern when H2O2 was added. In a morphological observation using TEM, the nanophotosensitizers were disintegrated by the addition of H2O2, indicating that the COSthPBAP nanophotosensitizers had ROS sensitivity. In addition, the Ce6 release rate from the COSthPBAP nanophotosensitizers accelerated in the presence of H2O2. The SO generation was also higher in the nanophotosensitizers than in the free Ce6. Furthermore, the COSthPBAP nanophotosensitizers showed a higher intracellular Ce6 uptake ratio and ROS generation in all types of oral cancer cells. They efficiently inhibited the viability of oral cancer cells under light irradiation, but they did not significantly affect the viability of either normal cells or cancer cells in the absence of light irradiation. The COSthPBAP nanophotosensitizers showed a tumor-specific delivery capacity and fluorescence imaging of KB tumors in an in vivo animal tumor imaging study. We suggest that COSthPBAP nanophotosensitizers are promising candidates for the imaging and treatment of oral cancers.

Should Contemporary Western Guidelines Based on Studies Conducted in the 2000s Be Adopted for the Prostate-Specific Antigen Screening Policy for Asian Men in the 2020s?

Though prostate cancer (PCa) is the second most common cancer world widely, there exist substantial differences exist between Asia and the west. Genetic susceptibility and lifestyle may contribute to disproportionately lower incidences and mortalities of PCa in Asian countries, but the differences in diagnostic practices are also likely to contribute, and a large part of them may be explained by the lesser chance of prostate-specific antigen (PSA) testing. In the US, about half of men aged over 50 years had been exposed to the screening test in the early 2000s. The shifts in the risk stratification from the high-risk dominant disease in the late 1980s to the low-risk dominant disease in the early 2000s led to criticism regarding the unconditional nature of PSA-based screening. Based on the conflicting outcomes from the randomized clinical trials which investigated the benefit of PSA testing, US Preventive Study Task Force recommended ceasing mass screening in 2012. Accordingly, guidelines begin to emphasize shared decision-making on the PSA testing narrowing their scopes to men aged 55 to 69 years since 2013. Though most Asian countries have not begun to recognize PCa as a major agenda item until the 2010s, a clear trend of expanding incidence of it implies that the time to come to reconsider PSA testing as a higher priority in the public health sphere in the 2020s. Concerns regarding over-diagnosis and over-treatment of insignificant diseases are imperative. However, the distinctive epidemiologic characteristics of PCa in Asia areas, such as low exposure to the repetitive PSA testing, the recent increase in its incidence driven by the elderly and super-elderly, and racial differences should be considered when it comes to the establishment of screening policy utilizing PSA test.

Predicting social anxiety in young adults with machine learning of resting-state brain functional radiomic features.

Social anxiety is a symptom widely prevalent among young adults, and when present in excess, can lead to maladaptive patterns of social behavior. Recent approaches that incorporate brain functional radiomic features and machine learning have shown potential for predicting certain phenotypes or disorders from functional magnetic resonance images. In this study, we aimed to predict the level of social anxiety in young adult participants by training machine learning models with resting-state brain functional radiomic features including the regional homogeneity, fractional amplitude of low-frequency fluctuation, fractional resting-state physiological fluctuation amplitude, and degree centrality. Among the machine learning models, the XGBoost model achieved the best performance with balanced accuracy of 77.7% and F1 score of 0.815. Analysis of input feature importance demonstrated that the orbitofrontal cortex and the degree centrality were most relevant to predicting the level of social anxiety among the input brain regions and the input type of radiomic features, respectively. These results suggest potential validity for predicting social anxiety with machine learning of the resting-state brain functional radiomic features and provide further understanding of the neural basis of the symptom.