Search

Microplastics (MPs) are now a global issue due to increased plastic production and use. Recently, various studies have been performed in response to the human health risk assessment. However, these studies have focused on spherical MPs, which have smooth edges and a spherical shape and account for less than 1% of MPs in nature. Unfortunately, studies on fragment-type MPs are very limited and remain in the initial stages. In this study, we studied the effect that 16.4 µm fragment type polypropylene (PP) MPs, which have an irregular shape and sharp edges and form naturally in the environment, had on breast cancer. The detrimental effects of PPMPs on breast cancer metastasis were examined. Here, 1.6 mg/ml of PPMP, which does not induce cytotoxicity in MDA-MB-231, was used, and at this concentration, PPMP did not induce morphological changes or cellular migrating in the MDA-MB-231 and MCF-7 cells. However, PPMP incubation for 24 hours in the MDA-MB-231 cells significantly altered the level of cell cycle-related transcripts in an RNA-seq analysis. When confirmed by qRT-PCR, the gene expression of TMBIM6, AP2M1, and PTP4A2 was increased, while the transcript level of FTH1 was decreased. Further, secretion of the pro-inflammatory cytokine IL-6 from cancer cells was elevated with the incubation of PPMP for 12 hours. These results suggest that PPMP enhances metastasis-related gene expression and cytokines in breast cancer cells, exacerbating breast cancer metastasis.

The present study aimed to evaluate the performance of automated skeletal maturation assessment system for Fishman’s skeletal maturity indicators (SMI) for the use in dental fields. Skeletal maturity is particularly important in orthodontics for the determination of treatment timing and method. SMI is widely used for this purpose, as it is less time-consuming and practical in clinical use compared to other methods. Thus, the existing automated skeletal age assessment system based on Greulich and Pyle and Tanner-Whitehouse3 methods was further developed to include SMI using artificial intelligence. This hybrid SMI-modified system consists of three major steps: (1) automated detection of region of interest; (2) automated evaluation of skeletal maturity of each region; and (3) SMI stage mapping. The primary validation was carried out using a dataset of 2593 hand-wrist radiographs, and the SMI mapping algorithm was adjusted accordingly. The performance of the final system was evaluated on a test dataset of 711 hand-wrist radiographs from a different institution. The system achieved a prediction accuracy of 0.772 and mean absolute error and root mean square error of 0.27 and 0.604, respectively, indicating a clinically reliable performance. Thus, it can be used to improve clinical efficiency and reproducibility of SMI prediction.

We developed a novel prediction model for recurrence and survival in patients with localized renal cell carcinoma (RCC) after surgery and a novel statistical method of machine learning (ML) to improve accuracy in predicting outcomes using a large Asian nationwide dataset, updated KOrean Renal Cell Carcinoma (KORCC) database that covered data for a total of 10,068 patients who had received surgery for RCC. After data pre-processing, feature selection was performed with an elastic net. Nine variables for recurrence and 13 variables for survival were extracted from 206 variables. Synthetic minority oversampling technique (SMOTE) was used for the training data set to solve the imbalance problem. We applied the most of existing ML algorithms introduced so far to evaluate the performance. We also performed subgroup analysis according to the histologic type. Diagnostic performances of all prediction models achieved high accuracy (range, 0.77–0.94) and F1-score (range, 0.77–0.97) in all tested metrics. In an external validation set, high accuracy and F1-score were well maintained in both recurrence and survival. In subgroup analysis of both clear and non-clear cell type RCC group, we also found a good prediction performance.

The beginning of human immunodeficiency virus (HIV) infection treatment depends on various factors, which are significantly correlated with the initial CD4 cell number. However, a covariate correlation between these factors may not reflect the correct outcome variable. Thus, we evaluated the effects of a combination of fixed factors (reduced dimensions), which determine when to start treatment for the first time, on short-term outcome, long-term outcome, and survival, considering correlations between factors. Multiple correspondence analysis was performed on variables obtained from 925 patients who participated in a Korean HIV/acquired immunodeficiency syndrome cohort study (2006–2017). Five reduced dimension groups were derived according to clinical data, viral load, CD4 cell count at diagnosis, initial antiretroviral therapy, and others. The dimension group with high initial viral loads (55,000 copies/mL) and low CD4 cell counts (3) should start treatment promptly after diagnosis. Groups with high initial CD4 cell counts (> 350 cells/mm3) that did not require immediate treatment according to previous guidelines had a higher failure rate for long-term relative CD4 recovery. Our results highlight the importance of early diagnosis and treatment to positively influence long-term disease outcomes, even if the initial immune status is poor, given the patient’s combination of early diagnostic symptoms.

Regarding stent expansion indices, previous optical coherence tomography (OCT) studies have shown minimal stent area (MSA) to be most predictive of adverse events. We sought to evaluate the impact of various stent expansion and apposition indices by post-stent OCT on clinical outcomes and find OCT-defined optimal stent implantation criteria. A total of 1071 patients with 1123 native coronary artery lesions treated with new-generation drug-eluting stents with OCT guidance and final post-stent OCT analysis were included. Several stent expansion indices (MSA, MSA/average reference lumen area, MSA/distal reference lumen area, mean stent expansion, and stent expansion by linear model [stent volume/adaptive reference lumen volume]) were evaluated for their association with device-oriented clinical endpoints (DoCE) including cardiac death, target vessel-related myocardial infarction (MI) or stent thrombosis, and target lesion revascularization. MSA was negatively correlated with the risk of DoCE (hazard ratio [HR] 0.80 [0.68‒0.94]). However, stent expansion by linear model representing the overall volumetric stent expansion was associated with greater risk of DoCE (HR 1.02 [1.00‒1.04]). As categorical criteria, MSA 2 (HR 3.90 [1.99‒7.65]), MSA/distal reference lumen area

Previous studies on dietary iodine intake and the risk of papillary thyroid cancer (PTC) have demonstrated inconsistent results. We aimed to evaluate the association between urinary iodine concentration (UIC), a surrogate biomarker for dietary iodine intake, and the risk of thyroid cancer stratified by sex and age in an iodine-sufficient area. A hospital-based case–control study was conducted in Seoul, South Korea. A total of 492 cases of newly diagnosed PTC and 595 controls were included. Compared with the lowest quartile of creatine-adjusted UIC (ptrend = 0.01) compared with those who were ≥ 45 years old (ptrend = 0.48). For those who were

We attempted to assess the performance of an ethnic-specific polygenic risk score (PRS) designed from a Korean population to predict aggressive prostate cancer (PCa) and early-onset (age

Atypical small acinar proliferation (ASAP) occurs in approximately 5% of prostate biopsies. Approximately 30–40% of patients with ASAP have biopsy detectable prostate cancer (PCa) within 5 years. Current guidelines recommend a repeat biopsy within 3–6 months after the initial diagnosis. The aim of the present study was to examine the association between ASAP and subsequent diagnosis of clinically significant PCa (csPCa). The need for immediate repeat biopsy was also evaluated. We identified 212 patients with an ASAP diagnosis on their first biopsy at our institution between February 2006 and March 2018. Of these patients, 102 (48.1%) had at least one follow-up biopsy. Clinicopathologic features including rates of subsequent PCa and csPCa were assessed. Thirty-five patients subsequently underwent radical prostatectomy (RP). Their pathologic results were reviewed. csPCa was defined as the presence of Gleason score (GS) ≥ 3 + 4 in ≥ 1 biopsy core. Adverse pathology (AP) was defined as high-grade (primary Gleason pattern ≥ 4) or non-organ-confined disease (pT3/N1) after RP. Of 102 patients, 87 (85.3%), 13 (12.7%), and 2 (2.0%) had one, two, and three follow-up biopsies, respectively. Median time from the initial ASAP diagnosis to the 2nd follow-up biopsy and the last follow-up biopsy were 21.9 months (range 1–129 months) and 27.7 months (range 1–129 months), respectively. Of these patients, 46 (45.1%) were subsequently diagnosed with PCa, including 20 (19.6%) with csPCa. Only 2 (2.0%) patients had GS ≥ 8 disease. Five (4.9%) patients had number of positive cores > 3. Of 35 patients who subsequently underwent RP, seven (20%) had AP after RP and 17 (48.6%) showed GS upgrading. Of these 17 patients, the vast majority (16/17, 94.1%) had GS upgrading from 3 + 3 to 3 + 4. 45.1% of patients with an initial diagnosis of ASAP who had repeat prostate biopsy were subsequently diagnosed with PCa and 19.6% were found to have csPCa. Our findings add further evidence that after a diagnosis of ASAP, a repeat biopsy is warranted and that the repeat biopsy should not be postponed.

Objectives: Childhood trauma (ChT) is a risk factor for psychosis. Negative lifestyle factors such as rumination, negative schemas, and poor diet and exercise are common in psychosis. The present study aimed to perform a network analysis of interactions between ChT and negative lifestyle in patients and controls.Methods: We used data of patients with early-stage psychosis (n = 500) and healthy controls (n = 202). Networks were constructed using 12 nodes from five scales: the Brief Core Schema Scale (BCSS), Brooding Scale (BS), Dietary Habits Questionnaire, Physical Activity Rating, and Early Trauma Inventory Self Report-Short Form (ETI). Graph metrics were calculated.Results: The nodes with the highest predictability and expected influence in both patients and controls were cognitive (Co) and emotional domains (Em) of the BS and emotional abuse (EMO) of the ETI. The EMO was a mediator in the shortest pathway connecting the ETI and negative lifestyle for both groups. The negative other (NO) and negative self (NS) of the BCSS mediated EMO to other BCSS or BS for patients and controls, respectively.Conclusion: Our findings suggest that rumination and EMO were central symptoms in both groups and that NO and NS played important mediating roles for patients and controls, respectively.Trial Registration: ClinicalTrials.gov identifier: CUH201411002

In brain magnetic resonance imaging (MRI), white matter hyperintensity (WMH) is a commonly encountered finding and is known to reflect cerebral small vessel disease. The aim of our study was to investigate the association of coronary artery calcium (CAC) with WMH and elucidate the relationship between WMH and atherosclerotic risk factors in a large-scale healthy population. This retrospective study included 1337 individuals who underwent brain MRI and CAC scoring computed tomography at healthcare centers affiliated with a tertiary hospital. Cerebral WMH was defined as Fazekas score greater than 2 on brain MRI. Intracranial artery stenosis (ICAS) was also assessed and determined to be present when stenosis was more than 50% on angiography. The associations of risk factors, CAC score, and ICAS with cerebral WMH were assessed by multivariable regression analysis. In multivariable analysis, categories of higher CAC scores showed increased associations with both periventricular and deep WMHs in a dose-dependent relationship. The presence of ICAS was also significantly related to cerebral WMH, and among the clinical variables, age and hypertension were independent risk factors. In conclusion, CAC showed a significant association with cerebral WMH in a healthy population, which might provide evidence for referring to the CAC score to identify individuals with risk of cerebral WMH.

Soil corrosion is always a critical concern to corrosion engineering because of the economic influence of soil infrastructures as has been and has recently been the focus of spent nuclear fuel canisters. Besides corrosion protection, the corrosion prediction of the canister is also important. Advanced knowledge of the corrosion rate of spent nuclear fuel canister material in a particular environment can be extremely helpful in choosing the best protection method. Applying machine learning (ML) to corrosion rate prediction solves all the challenges because of the number of variables affecting soil corrosion. In this study, several algorithms of ML, including series individual, boosting, bagging artificial neural network (ANN), series individual, boosting, bagging Chi-squared automatic interaction detection (CHAID) tree decision, linear regression (LR) and an ensemble learning (EL) merge the best option that collects from 3 algorithm methods above. From the performance of each model to find the model with the highest accuracy is the ensemble stacking method. Mean absolute error performance matrices are shown in Fig. 15. Besides applying ML, the significance of the input variables was also determined through sensitivity analysis using the feature importance criterion, and the carbon steel corrosion rate is the most sensitive to temperature and chloride.

The purpose of this study was to identify how chronic hypertension (HTN) and hypertensive retinopathy (HTNR) have different effects on retinal damage including inner retinal thinning and microvasculature impairment. The subjects were divided into three groups: controls, HTN patients without HTNR (HTN group), and patients with relieved HTNR (HTNR group). The ganglion cell-inner plexiform layer (GC-IPL) thickness, vessel density (VD), and GC-IPL/VD ratio were compared among the groups. A total of 241 eyes were enrolled; 101 in the control group, 92 in the HTN group, and 48 in the HTNR group. The mean GC-IPL thicknesses were 83.5 ± 5.7, 82.1 ± 6.2, and 75.9 ± 10.7 μm in each group, respectively (P −1 in each group, respectively (P = 0.001). The GC-IPL/VD ratio was 4.10 ± 0.33, 4.20 ± 0.40, and 3.88 ± 0.56 in each group, respectively (P P = 0.013) and systolic blood pressure (SBP) (B = −0.012, P = 0.004) were significantly associated with the GC-IPL/VD ratio. In conclusion, inner retinal reduction and retinal microvasculature impairment were observed in patients with HTN and HTNR, and the GC-IPL/VD ratio of HTNR patients was significantly lower than that of HTN patients, indicating more prominent damage to the inner retina than microvasculature in HTNR patients. Additionally, the GC-IPL/VD ratio was significantly associated with SBP in HTNR patients, so more strict BP control is required in HTNR patients.

Reconfigurable metasurfaces (RMSs) that enable the switching function of absorption and polarization conversion have attracted increasing attention. However, the design of RMSs to achieve wideband and high efficiency for both absorption and polarization conversion functions simultaneously remains a great challenge. Here, we propose the design of a RMS structure with a high-efficiency cross-polarization conversion and nearly perfect absorption. The reconfiguration between different functions of polarization conversion and absorption is obtained based on the reversible insulator-to-metal phase transition of Vanadium dioxide (VO$$_{2}$$ 2 ). When the VO$$_{2}$$ 2 is in insulator state, the RMS realizes the cross-polarization conversion function in the wideband of 1.04–3.75 THz with a relative bandwidth up to 113 $$\%$$ % due to the multi-resonant modes of electric and magnetic resonances. Meanwhile, the nearly-perfect absorption is achieved in the range of 1.36–3.38 THz with the corresponding relative bandwidth up to 85 $$\%$$ % for the VO$$_{2}$$ 2 in metallic state. Specially, the wideband and high-efficiency performance of these functionalities is maintained for a wide angle incidence. The capability of bi-functional switch and integration with polarization conversion and absorption in a single metasurface structure endowed with both wideband and high-efficiency characteristics for a wide incident angle is very promising for emerging RMS devices in the terahertz region.

Non-syndromic inherited defects of tooth dentin are caused by two classes of dominant negative/gain-of-function mutations in dentin sialophosphoprotein (DSPP): 5′ mutations affecting an N-terminal targeting sequence and 3′ mutations that shift translation into the − 1 reading frame. DSPP defects cause an overlapping spectrum of phenotypes classified as dentin dysplasia type II and dentinogenesis imperfecta types II and III. Using CRISPR/Cas9, we generated a Dspp−1fs mouse model by introducing a FLAG-tag followed by a single nucleotide deletion that translated 493 extraneous amino acids before termination. Developing incisors and/or molars from this mouse and a DsppP19L mouse were characterized by morphological assessment, bSEM, nanohardness testing, histological analysis, in situ hybridization and immunohistochemistry. DsppP19L dentin contained dentinal tubules but grew slowly and was softer and less mineralized than the wild-type. DsppP19L incisor enamel was softer than normal, while molar enamel showed reduced rod/interrod definition. Dspp−1fs dentin formation was analogous to reparative dentin: it lacked dentinal tubules, contained cellular debris, and was significantly softer and thinner than Dspp+/+ and DsppP19L dentin. The Dspp−1fs incisor enamel appeared normal and was comparable to the wild-type in hardness. We conclude that 5′ and 3′ Dspp mutations cause dental malformations through different pathological mechanisms and can be regarded as distinct disorders.

Purpose: Craniopharyngiomas are rare epithelial tumors derived from pituitary gland embryonic tissue. This epithelial tumor can be categorized as an adamantinomatous craniopharyngioma (ACP) or papillary craniopharyngioma (PCP) subtype with histopathological and genetic differences. Genomic and transcriptomic profiles of craniopharyngiomas have been investigated; however, the proteomic profile has yet to be elucidated and added to these profiles. Recent improvements in high-throughput quantitative proteomic approaches have introduced new opportunities for a better understanding of these diseases and the efficient discovery of biomarkers. We aimed to confirm subtype-associated proteomic changes between ACP and PCP specimens.Methods: We performed a system-level proteomic study using an integrated approach that combines mass spectrometry-based quantitative proteomic, statistical, and bioinformatics analyses.Results: The bioinformatics analysis showed that differentially expressed proteins between ACP and PCP were significantly involved in mitochondrial organization, fatty acid metabolic processes, exocytosis, the inflammatory response, the cell cycle, RNA splicing, cell migration, and neuron development. Furthermore, using network analysis, we identified hub proteins that were positively correlated with ACP and PCP phenotypes.Conclusions: Our findings improve our understanding of the pathogenesis of craniopharyngiomas and provide novel insights that may ultimately translate to the development of craniopharyngioma subtype-specific therapeutics.

For pheochromocytoma and sympathetic paraganglioma (PPGL), surgery can be used as a curative treatment; however, the life-threatening risk of perioperative hemodynamic instability (HI) presents challenges. This study aimed to analyze the incidence and predictive factors of perioperative HI. The electronic medical records of 114 consecutive patients who underwent surgery for PPGLs at our institution were retrospectively reviewed. HI was defined as one or more episodes of systolic blood pressure > 200 mmHg or mean blood pressure

Copeptin levels reflect arginine vasopressin (AVP) release from the hypothalamus. Pituitary surgery often impairs AVP release and results in central diabetes insipidus (CDI). Here, we aimed to investigate how serum copeptin level changes 3 months after pituitary surgery and whether it has a diagnostic value for postoperative permanent CDI. Consecutive patients who underwent endoscopic transsphenoidal surgery at a single tertiary hospital were recruited. Serum copeptin levels were measured preoperatively and 3 months postoperatively. Among 88 patients, transient and permanent CDI occurred in 17 (19.3%) and 23 (26.1%), respectively. Three-month postoperative copeptin levels significantly declined from preoperative levels in permanent CDI group (P P = 0.002, − 27.2%). Three months postoperative copeptin level

Polypharmacy and its rising global prevalence is a growing public health burden. Using a large representative nationwide Korean cohort (N = 761,145), we conducted a retrospective cross-sectional study aiming to identify subpopulations of patients with polypharmacy and characterize their unique patterns through cluster analysis. Patients aged ≥ 30 years who were prescribed at least one medication between 2014 and 2018 were included in our study. Six clusters were identified: cluster 1 mostly included patients who were hospitalized for a long time (4.3 ± 5.3 days); cluster 2 consisted of patients with disabilities (100.0%) and had the highest mean number of prescription drugs (7.7 ± 2.8 medications); cluster 3 was a group of low-income patients (99.9%); cluster 4 was a group of high-income patients (80.2%) who frequently (46.4 ± 25.9 days) visited hospitals/clinics (7.3 ± 2.7 places); cluster 5 was mostly elderly (74.9 ± 9.8 years) females (80.3%); and cluster 6 comprised mostly middle-aged (56.4 ± 1.5 years) males (88.6%) (all P P

Nanomaterials have gained enormous interest in improving the performance of energy harvest systems, biomedical devices, and high-strength composites. Many studies were performed fabricating more elaborate and heterogeneous nanostructures then the structures were characterized using TEM tomographic images, upgrading the fabrication technique. Despite the effort, intricate fabrication process, agglomeration characteristic, and non-uniform output were still limited to presenting the 3D panoramic views straightforwardly. Here we suggested in situ synthesis method to prepare complex and hierarchically-assembled nanostructures that consisted of ZnS nanowire core and nanoparticles under Ag2S catalyst. We demonstrated that the vaporized Zn and S were solidified in different shapes of nanostructures with the temperatures solely. To our knowledge, this is the first demonstration of synthesizing heterogeneous nanostructures, consisting of a nanowire from the vapor–liquid–solid and then nanoparticles from the vapor–solid grown mechanism by in situ temperature control. The obtained hierarchically-assembled ZnS nanostructures were characterized by various TEM technologies, verifying the crystal growth mechanism. Lastly, electron tomography and 3D printing enabled the nanoscale structures to visualize with centimeter scales. The 3D printing from randomly fabricated nanomaterials is rarely performed to date. The collaborating work could offer a better opportunity to fabricate advanced and sophisticated nanostructures.

Migration of methane-rich fluids at submarine cold seeps drives intense microbial activity and precipitation of authigenic carbonates. In this study, we analyzed microbially derived authigenic carbonate samples recently recovered from active gas hydrate mounds on the southwestern slope of the Chukchi Borderlands (CB), western Arctic Ocean. Our main aim was to characterize the distribution patterns of trace elements in carbonate-hosted lipid fractions to assess metalloenzyme requirements of microbes involved in anaerobic oxidation of methane (AOM). We measured stable isotopes, trace elements, lipid biomarkers, and genomic DNA, and results indicate the dominance of AOM-related lipid biomarkers in studied carbonate samples, as well as a predominant occurrence of the anaerobic methanotrophic archaea (ANME)-1. We also report evidence for significant preferential enrichments of various trace elements (Li, Ni, Co, Cu, Zn, and Mo) in the total lipid fractions of CB carbonates, relative to elemental compositions determined for corresponding carbonate fractions, which differ from those previously reported for other seep sites. We hypothesize that trace element enrichments in carbonate-hosted lipid fractions could vary depending on the type of AOM microbial assemblage. Additional work is required to further investigate the mechanisms of lipid-bound trace elements in cold seep carbonates as potential metalloenzymes in AOM.

To investigate the impact of the combination of type 2 diabetes (DM) and high myopia on inner retinal layer thickness of the macular area. The patients were divided into four groups: control (group 1), patients with DM without high myopia (group 2), patients with high myopia without DM (group 3), and patients with DM and high myopia (group 4). Ganglion cell complex (GCC) thickness was compared among the groups. Linear regression analysis was performed to identify factors associated with GCC thickness. A total of 194 eyes were enrolled: 59 in group 1, 52 in group 2, 49 in group 3, and 34 in group 4. The average parafovea GCC thicknesses were 113.9 ± 10.4, 112.4 ± 11.2, 112.2 ± 7.8, and 102.6 ± 15.1 μm (P

Interspecific hybridization occurs among birds, and closely related sister taxa tend to hybridize at a high rate. Genomic hybridization markers are useful for understanding the patterns and processes of hybridization and for conserving endangered species in captivity and the wild. In this study, we developed genomic hybridization markers for the F1 progeny of the sister taxa feral pigeons (Columba livia var. domestica) and endangered hill pigeons (Columba rupestris) (family Columbidae). Using whole-genome re-sequencing data, we performed genome-wide analysis for insertion/deletion (InDel) polymorphisms and validated using primers. We conducted polymerase chain reaction (PCR) and agarose gel electrophoresis to identify species-specific InDels. We produced eight F1 hybrids of hill and feral pigeons, and their samples were tested by re-performing analyses and sequencing using 11 species-specific InDel polymorphisms. Eight InDel markers simultaneously amplified two DNA fragments from all F1 hybrids, and there was no abnormality in the sequencing results. The application of genomic tools to detect hybrids can play a crucial role in the assessment of hybridization frequency in the wild. Moreover, systematic captive propagation efforts with hybrids can help control the population decline of hill pigeons.

Background Extracorporeal membrane oxygenation (ECMO) provides hemodynamic and oxygenation support to critically ill patients. Due to multiple catheter cannulations, patients on ECMO are vulnerable to bloodstream infections (BSIs). We aimed to investigate the incidence, clinical characteristics, risk factors, and microorganisms associated with BSIs during ECMO. MethodsThis single-center retrospective cohort study was conducted between January 2015 and May 2021. Patients aged 18 years or older with an ECMO duration of >48 hours for cardiogenic or respiratory support were included in the study. Patients who developed bacteremia or candidemia from 12 h after ECMO cannulation to 7 days after de-cannulation were included. The clinical factors between non-BSI and BSI were compared, along with an analysis of the risk factors associated with BSI during ECMO. Results A total of 480 patients underwent ECMO for cardiogenic shock (n=267, 55.6%) or respiratory failure (n=213, 44.4%) during the study period. The incidence was 20.0 episodes per 1,000 ECMO-days. Approximately 20.2% (97/480) and 5.4% (26/480) of the patients developed bacteremia and candidemia, respectively. The median numbers of days of BSI development were 8.00 days for bacteremia and 11.0 days for candidemia. The most common pathogens were methicillin-resistant coagulase-negative staphylococci (n=24), followed by vancomycin-resistant Enterococcus (n=21). Multivariable logistic analysis demonstrated that hemodialysis (odds ratio [OR]=2.647, p ConclusionBSI is a common complication of patients receiving ECMO support and is associated with poor clinical outcomes. Determining the type of frequently isolated organisms and the median onset time of BSI would help in the selection of appropriate prophylactic antibiotics or antifungal agents.

Phase diagrams of ternary π-bonded polymer (PTB7-Th) solutions were constructed as a function of molecular weight, temperature, and electron acceptor species (ITIC, PC61BM and PC71BM). For this purpose, the Flory–Huggins lattice theory was employed with a constant χ interaction parameter, describing a binodal, spinodal, tie line, and critical point. Then, the morphologies of the blends composed of highly disordered PTB7-Th and crystallizable ITIC were investigated by atomic force microscopy. Subsequently, the surface polarities of the PTB7-Th:ITIC thin films were examined by water contact-angle goniometer, exhibiting a transition at the composition of ~ 60 ± 10 wt.% ITIC. Furthermore, X-ray diffraction indicated the presence of ITIC’s crystallites at ≥ 70 wt.% ITIC. Hence, the PTB7-Th:ITIC system was observed to undergo a phase transition at ~ 60–70 wt.% ITIC.

We investigated the impact of pre-percutaneous coronary intervention (pre-PCI) thrombolysis in myocardial infarction (TIMI) flow grade (pre-TIMI) on 3-month (3-mo) and 12-mo of dual antiplatelet therapy (DAPT) in patients with acute myocardial infarction (AMI). This was a post hoc analysis of the TICO trial. A total of 2083 patients with AMI (pre-TIMI 0/1: n = 1143; pre-TIMI 2/3: n = 940) were evaluated. The primary outcome was the occurrence of net adverse clinical events (NACE), defined as a composite of TIMI major bleeding and major adverse cardiac and cerebrovascular events (MACCE) within 12-mo following PCI. The secondary outcomes were the occurrence of the individual components of TIMI bleedings and MACCE. In the pre-TIMI 0/1 group, the primary and second outcomes were not significantly different between the 3-mo and 12-mo DAPT groups. However, in the pre-TIMI 2/3 group, the occurrences of TIMI minor (adjusted hazard ratio [aHR]: 0.294; p = 0.016) and major or minor bleeding (aHR: 0.483; p = 0.014) on intention-to-treat analysis were significantly higher in the 12-mo than in the 3-mo DAPT group. The occurrence of MACCE was similar between the two groups. A higher bleeding tendency in 12-mo DAPT compared with 3-mo DAPT was more obvious in the pre-TIMI 2/3 group than in the pre-TIMI 0/1 group.Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02494895.

Congenital hyperinsulinism (CHI) is a rare genetic condition characterized by uncontrolled insulin secretion, resulting in hypoglycemia. Although glucagon has lately been regarded as a therapeutic option for CHI, its use is severely hampered by its poor solubility and stability at physiological pH, as well as its short duration of action. To address these constraints, we developed HM15136, a novel long-acting glucagon analog composed of a glucagon analog conjugated to the Fc fragment of human immunoglobulin G4 via a polyethylene glycol linker. In this study, we established that HM15136 was more soluble than natural glucagon (≥ 150 mg/mL vs 0.03 mg/mL). Next, we confirmed that HM15136 activated glucagon receptor in vitro and induced glycogenolysis and gluconeogenesis in rat primary hepatocytes. Pharmacokinetics (PK)/Pharmacodynamics (PD) analysis of HM15136 shows that HM15136 has a markedly longer half-life (36 h vs.

Human ACP4 (OMIM*606362) encodes a transmembrane protein that belongs to histidine acid phosphatase (ACP) family. Recessive mutations in ACP4 cause non-syndromic hypoplastic amelogenesis imperfecta (AI1J, OMIM#617297). While ACP activity has long been detected in developing teeth, its functions during tooth development and the pathogenesis of ACP4-associated AI remain largely unknown. Here, we characterized 2 AI1J families and identified a novel ACP4 disease-causing mutation: c.774_775del, p.Gly260Aspfs*29. To investigate the role of ACP4 during amelogenesis, we generated and characterized Acp4

The aim of this study was to evaluate the intra- and inter-observer reliability of maxillary digital dental model integration into cone-beam computed tomography (CBCT) scans to reconstruct three-dimensional (3D) skeletodental models for orthognathic patients. This retrospective study consisted of CBCT and digital maxillary dentition images of 20 Class III orthognathic patients. After two repeated fusions of digital cast images with reconstructed CBCT images by a digital engineer and an orthodontist respectively, the 3D coordinate values of the canines, first molars, and central incisors were evaluated. The intra- and inter-observer reliability of 3D positions of maxillary teeth were compared using intraclass correlation coefficients (ICCs). Intra-observer reliability of x-, y-, and z-coordinate values of maxillary teeth showed significant and excellent agreement in an engineer (0.946 ≤ ICC ≤ 1.000) and an orthodontist (0.876 ≤ ICC ≤ 1.000). The inter-observer reliability of the y- and z-coordinates of each tooth was significantly excellent or good, but that of the x-coordinates showed insignificantly poor to moderate agreement. This study showed that the integration of maxillary digital models into CBCT scans was clinically reliable. However, considering the low inter-observer reliability on the x-coordinates of dentition, clinical experience and repeated learning are needed for accurate application of digital skeletodental model in orthognathic patients.

In the hemodynamic study, computational fluid dynamics (CFD) analysis has shown that high wall shear stress (WSS) is an important parameter in cerebral aneurysm formation. However, CFD analysis is not more realistic than fluid–structure interaction (FSI) analysis given its lack of considering the involvement of vascular structures. To investigate the relationship between the hemodynamic parameters and the aneurysm formation, the locations of high WSS and high strain were extracted from the CFD and FSI analyses, respectively. Then the distances between the aneurysm formation site and the locations of high WSS or high strain were calculated. A total of 37 intracranial paraclinoid aneurysms were enrolled for quantitative comparison. Additionally, the dura mater was modeled to facilitate realistic results in FSI analysis. The average distance from the location of the aneurysm formation site to the high strain (1.74 mm $$\pm $$ ± 1.04 mm) was smaller than the average distance to the high WSS (3.33 mm $$\pm $$ ± 1.18 mm). The presence of dura mater also influenced the findings in the aneurysm formation site. High strain extracted by FSI analysis is an important hemodynamic factor related to the formation of cerebral aneurysms. Strain parameter could help to predict the formation of aneurysms and elucidate the appropriate treatment.

The rDNA clusters and flanking sequences on human chromosomes 13, 14, 15, 21 and 22 represent large gaps in the current genomic assembly. The organization and the degree of divergence of the human rDNA units within an individual nucleolar organizer region (NOR) are only partially known. To address this lacuna, we previously applied transformation-associated recombination (TAR) cloning to isolate individual rDNA units from chromosome 21. That approach revealed an unexpectedly high level of heterogeneity in human rDNA, raising the possibility of corresponding variations in ribosome dynamics. We have now applied the same strategy to analyze an entire rDNA array end-to-end from a copy of chromosome 22. Sequencing of TAR isolates provided the entire NOR sequence, including proximal and distal junctions that may be involved in nucleolar function. Comparison of the newly sequenced rDNAs to reference sequence for chromosomes 22 and 21 revealed variants that are shared in human rDNA in individuals from different ethnic groups, many of them at high frequency. Analysis infers comparable intra- and inter-individual divergence of rDNA units on the same and different chromosomes, supporting the concerted evolution of rDNA units. The results provide a route to investigate further the role of rDNA variation in nucleolar formation and in the empirical associations of nucleoli with pathology.

Understanding the mechanisms underlying the metabolically unhealthy normal weight (MUHNW) and metabolically healthy obese (MHO) phenotypes is important for developing strategies to prevent cardiometabolic diseases. Here, we conducted genome-wide association studies (GWASs) to identify the MUHNW and MHO genetic indices. The study dataset comprised genome-wide single-nucleotide polymorphism genotypes and epidemiological data from 49,915 subjects categorised into four phenotypes—metabolically healthy normal weight (MHNW), MUHNW, MHO, and metabolically unhealthy obese (MUHO). We conducted two GWASs using logistic regression analyses and adjustments for confounding variables (model 1: MHNW versus MUHNW and model 2: MHO versus MUHO). GCKR, ABCB11, CDKAL1, LPL, CDKN2B, NT5C2, APOA5, CETP, and APOC1 were associated with metabolically unhealthy phenotypes among normal weight individuals (model 1). LPL, APOA5, and CETP were associated with metabolically unhealthy phenotypes among obese individuals (model 2). The genes common to both models are related to lipid metabolism (LPL, APOA5, and CETP), and those associated with model 1 are related to insulin or glucose metabolism (GCKR, CDKAL1, and CDKN2B). This study reveals the genetic architecture of the MUHNW and MHO phenotypes in a Korean population-based cohort. These findings could help identify individuals at a high metabolic risk in normal weight and obese populations and provide potential novel targets for the management of metabolically unhealthy phenotypes.

Cholinesterase (ChE) and monoamine oxidase (MAO) inhibitors have been attracted as candidate treatments for Alzheimer's disease (AD). Fifteen khellactone-type coumarins from the roots of Peucedanum japonicum Thunberg were tested for acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and MAO inhibitory activities. Compound 3′-angeloyl-4′-(2-methylbutyryl)khellactone (PJ13) most potently inhibited AChE (IC50 = 9.28 µM), followed by 3′-isovaleryl-4′-(2-methylbutyroyl)khellactone (PJ15) (IC50 = 10.0 μM). Compound senecioyl-4′-angeloyl-khellactone (PJ5) most potently inhibited BChE (IC50 = 7.22 μM) and had the highest selectivity index (> 5.54), followed by 3′-senecioyl-4′-(2-methylbutyryl)khellactone (PJ10) and 3′,4′-disenecioylkhellactone (PJ4) (IC50 = 10.2 and 10.7 μM, respectively). Compounds PJ13, PJ15, and PJ5 showed reversible and mixed-types of inhibition with Ki values of 5.98, 10.4 (for AChE), and 4.16 µM (for BChE), respectively. However, all 15 compounds weakly inhibited MAO-A and MAO-B. Molecular docking simulation revealed that PJ13 had a higher binding affinity (− 9.3 kcal/mol) with AChE than PJ15 (− 7.8 kcal/mol) or PJ5 (− 5.4 kcal/mol), due to the formation of a hydrogen bond with Tyr121 (distance: 2.52 Å). On the other hand, the binding affinity of PJ5 (− 10.0 kcal/mol) with BChE was higher than for PJ13 (− 7.7 kcal/mol) or PJ15 (− 8.1 kcal/mol), due to the formation of a hydrogen bond with Ser198 (distance: 2.05 Å). These results suggest that PJ13 and PJ5 are potential reversible selective inhibitors of AChE and BChE, respectively, for the treatment of AD.

Uterine fibroid and benign thyroid disease are both common diseases in women. This study aimed to evaluate whether these diseases are related. We established the uterine fibroid group according to diagnosis and surgery codes using the Korea National Health Insurance data from 2009 to 2020. All women from 20 to 50 years old who underwent uterine myomectomy from 2009 to 2020 were identified. We selected the control group by performing a 1:1 propensity score matching on age at 5-year intervals, socioeconomic status (SES), region, Charlson comorbidity index (CCI), menopause, and year among women who visited a medical institution for a health check-up. Thyroid disease cases were selected using the thyroid disease diagnosis code and thyroid-associated laboratory tests. A total of 181,419 patients were included in the uterine fibroid and control groups. The median age of each group was 40 (range, 35 ~ 44) and 40 (range, 35 ~ 45) years old, respectively. Benign thyroid disease affected 1162 (0.6%) in the uterine fibroid group and 1137 (0.6%) in the control group. Among the benign thyroid diseases, hypothyroidism was the most common in both groups, followed by a nontoxic single thyroid nodule. The uterine fibroid group had a higher risk of thyroid goiter (hazard ratio (HR) 1.169, 95% confidence interval (CI) 1.022–1.338), nontoxic single thyroid nodule (HR 1.268, 95% CI 1.182–1.361), and total thyroid disease (HR 1.078, 95% CI 1.036–1.121) in stratified Cox regression analysis adjusted for age, SES, region, CCI, parity, menopause, hypertension, diabetes, dyslipidemia, systemic lupus erythematosus, irritable bowel syndrome, Crohn’s disease, and endometriosis than the control group. The results suggest that women with uterine fibroids have an increased risk of thyroid goiters and thyroid nodules. Although the mechanism is not well known, estrogen and iodide might be a link between uterine fibroids and thyroid goiters and nodules. Future studies that prospectively follow women with uterine fibroids across a lifetime are needed.

To facilitate rapid determination of cellular viability caused by the inhibitory effect of drugs, numerical deep learning algorithms was used for unlabeled cell culture images captured by a light microscope as input. In this study, A549, HEK293, and NCI-H1975 cells were cultured, each of which have different molecular shapes and levels of drug responsiveness to doxorubicin (DOX). The microscopic images of these cells following exposure to various concentrations of DOX were trained with the measured value of cell viability using a colorimetric cell proliferation assay. Convolutional neural network (CNN) models for the study cells were constructed using augmented image data; the predicted cell viability using CNN models was compared to the cell viability measured by colorimetric assay. The linear relationship coefficient (r2) between measured and predicted cell viability was determined as 0.94–0.95 for the three cell types. In addition, the measured and predicted IC50 values were not statistically different. When drug responsiveness was estimated using allogenic models that were trained with a different cell type, the correlation coefficient decreased to 0.004085–0.8643. Our models could be applied to label-free cells to conduct rapid and large-scale tests while minimizing cost and labor, such as high-throughput screening for drug responsiveness.

Anti-dementia medications are widely prescribed to patients with Alzheimer’s dementia (AD) in South Korea. This study investigated the pattern of medical management in newly diagnosed patients with AD using a standardized data format—the Observational Medical Outcome Partnership Common Data Model from five hospitals. We examined the anti-dementia treatment patterns from datasets that comprise > 5 million patients during 2009–2019. The medication utility information was analyzed with respect to treatment trends and persistence across 11 years. Among the 8653 patients with newly diagnosed AD, donepezil was the most commonly prescribed anti-dementia medication (4218; 48.75%), followed by memantine (1565; 18.09%), rivastigmine (1777; 8.98%), and galantamine (494; 5.71%). The rising prescription trend during observation period was found only with donepezil. The treatment pathways for the three cholinesterase inhibitors combined with N-methyl-d-aspartate receptor antagonist were different according to the drugs (19.6%; donepezil; 28.1%; rivastigmine, and 17.2%; galantamine). A 12-month persistence analysis showed values of approximately 50% for donepezil and memantine and approximately 40% for rivastigmine and galantamine. There were differences in the prescribing pattern and persistence among anti-dementia medications from database using the Observational Medical Outcome Partnership Common Data Model on the Federated E-health Big Data for Evidence Renovation Network platform in Korea.

Spectral-domain optical coherence tomography (SD-OCT) must accurately identify and measure the peripapillary retinal nerve fiber layer (pRNFL) thickness to improve the repeatability and reproducibility, and reduce measurement errors. Because Weiss ring can be located in front of the optic disc, we hypothesized that it may affect pRNFL thickness measurements obtained using SD-OCT. We retrospectively reviewed the medical records of patients with (group W) and without (group N) Weiss ring, observed on OCT fundus image and an RNFL map devised using SD-OCT. Optic disc cube scans (200 × 200) were obtained to measure pRNFL thicknesses (superior, temporal, inferior, nasal, and average) at two consecutive visits. Pearson's correlation coefficient (r), intraclass correlation coefficient (ICC), and coefficient of variation (CV) were calculated. The r and ICC values for the pRNFL thickness measurements at the two visits were lower for group W compared to group N, but statistical significance was reached only for inferior pRNFL thickness. In addition, CV values were greater for group W compared to group N, but the differences were significant only for inferior and average pRNFL thickness measurements (p p = 0.004, respectively). Weiss ring located near the optic disc can affect pRNFL thickness measurements and repeatability thereof, especially the inferior quadrant and average values. Therefore, it is important to identify the presence of Weiss ring when analyzing pRNFL thickness values.

While boron neutron capture therapy (BNCT) depends primarily on the short flight range of the alpha particles emitted by the boron neutron capture reaction, gadolinium neutron capture therapy (GdNCT) mainly relies on gamma rays and Auger electrons released by the gadolinium neutron capture reaction. BNCT and GdNCT can be complementary in tumor therapy. Here, we studied the combined effects of BNCT and GdNCT when boron and gadolinium compounds were co-injected, followed by thermal neutron irradiation, and compared these effects with those of the single therapies. In cytotoxicity studies, some additive effects (32‒43%) were observed when CT26 cells were treated with both boron- and gadolinium-encapsulated PEGylated liposomes (B- and Gd-liposomes) compared to the single treatments. The tumor-suppressive effect was greater when BNCT was followed by GdNCT at an interval of 10 days rather than vice versa. However, tumor suppression with co-injection of B- and Gd-liposomes into tumor-bearing mice followed by neutron beam irradiation was comparable to that observed with Gd-liposome-only treatment but lower than B-liposome-only injection. No additive effect was observed with the combination of BNCT and GdNCT, which could be due to the shielding effect of gadolinium against thermal neutrons because of its overwhelmingly large thermal neutron cross section.

Stretchable materials are essential for next generation wearable and stretchable electronic devices. Intrinsically stretchable and highly conductive polymers (termed ISHCP) are designed with semi interpenetrating polymer networks (semi-IPN) that enable polymers to be simultaneously applied to transparent electrodes and electrochromic materials. Through a facile method of acid-catalyzed polymer condensation reaction, optimized ISHCP films show the highest electrical conductivity, 1406 S/cm, at a 20% stretched state. Without the blending of any other elastomeric matrix, ISHCP maintains its initial electrical properties under a cyclic stretch-release of over 50% strain. A fully stretchable electrochromic device based on ISHCP is fabricated and shows a performance of 47.7% ∆T and high coloration efficiency of 434.1 cm2/C at 590 nm. The device remains at 45.2% ∆T after 50% strain stretching. A simple patterned electrolyte layer on a stretchable electrochromic device is also realized. The fabricated device, consisting of all-plastic, can be applied by a solution process for large scale production. The ISHCP reveals its potential application in stretchable electrochromic devices and satisfies the requirements for next-generation stretchable electronics.

Preeclampsia is one of the most serious complications of pregnancy, affecting 5–10% of parturients worldwide. Recent studies have suggested that autophagy is involved in trophoblast invasion and may be associated with defective placentation underlying preeclampsia. We thus aimed to understand the mechanistic link between autophagy and trophoblast invasion. Using the two most commonly used trophoblast cell lines, JEG-3 and HTR-8/SVneo, we inhibited autophagy by ATG5 and beclin-1 shRNA. Conversion of LC3-II was evaluated in ATG5 and beclin-1 knock-down cells in the presence of the lysosomal protease inhibitors E-64d and pepstatin A, to detect the efficiency of autophagy inhibition. Upon autophagy inhibition, we measured cell invasion, activity of NF-κB and related signaling pathways, MMP-2, MMP-9, sFlt-1, and TNF-α levels. Autophagy inhibition increased the invasiveness of these trophoblastic cell lines and increased Akt and NF-κB activity as well as p65 expression. Of note, an NF-κB inhibitor significantly attenuated the trophoblast invasion induced by autophagy inhibition. Autophagy inhibition was also associated with increased MMP-2 and MMP-9 levels and decreased the production of sFlt-1 and TNF-α. Collectively, our results indicate that autophagy regulates trophoblast invasiveness in which the NF-κB pathway and MMP-2, MMP-9, sFlt-1 and TNF-α levels are affected.

In this study, four plastomes of Hymenophyllum, distributed in the Korean peninsula, were newly sequenced and phylogenomic analysis was conducted to reveal (1) the evolutionary history of plastomes of early-diverging fern species at the species level, (2) the importance of mobile open reading frames in the genus, and (3) plastome sequence divergence providing support for H. coreanum to be recognized as an independent species distinct from H. polyanthos. In addition, 1C-values of H. polyanthos and H. coreanum were measured to compare the genome size of both species and to confirm the diversification between them. The rrn16-trnV intergenic regions in the genus varied in length caused by Mobile Open Reading Frames in Fern Organelles (MORFFO). We investigated enlarged noncoding regions containing MORFFO throughout the fern plastomes and found that they were strongly associated with tRNA genes or palindromic elements. Sequence identity between plastomes of H. polyanthos and H. coreanum is quite low at 93.35% in the whole sequence and 98.13% even if the variation in trnV-rrn16 intergenic spacer was ignored. In addition, different genome sizes were found for these species based on the 1C-value. Consequently, there is no reason to consider them as a conspecies.

Although sleep disturbances are highly prevalent in adolescents, neuroimaging evidence on the effects of sleep disturbances on their developing brains remains limited. Therefore, we explored gray matter volumes (GMVs) at the whole-brain level and investigated their relationship to sleep disturbances in a sample of Korean adolescents in the general population. We recruited participants from one middle school and high school. All participants and their legal guardians gave informed consent before participating in our study. We used component 5 of the Pittsburgh Sleep Quality Index to measure sleep disturbances and conducted a voxel-based morphometry-DARTEL procedure to measure GMVs. We performed partial correlation analyses to examine whether the GMVs were associated with sleep disturbances. A total of 56 adolescents participated in this study. Our results revealed that GMVs in multiple global regions were negatively correlated with sleep disturbances. Moreover, most of these identified regions belong to large-scale brain networks categorized by functional neuroimaging studies. We found an association between regional GMVs in multiple global regions involved in large-scale networks and the severity of sleep disturbances in the adolescent population. Based on this evidence and previous neuroimaging evidence, we suggest that structural alterations in the networks may be linked to sleep disturbances.

The CCAAT sequence is a ubiquitous cis-element of eukaryotic promoters, and genes containing CCAAT sequences have been shown to be activated by the CCAAT-binding transcription factor complex in several eukaryotic model organisms. In general, CCAAT-binding transcription factors form heterodimers or heterotrimeric complexes that bind to CCAAT sequences within the promoters of target genes and regulate various cellular processes. To date, except Hap complex, CCAAT-binding complex has been rarely reported in fungi. In this study, we characterized two CCAAT-binding transcription factors (Fct1 and Fct2) in the plant pathogenic fungus Fusarium graminearum. Previously, FCT1 and FCT2 were shown to be related to DNA damage response among eight CCAAT-binding transcription factors in F. graminearum. We demonstrate that the nuclear CCAAT-binding complex of F. graminearum has important functions in various fungal developmental processes, not just DNA damage response but virulence and mycotoxin production. Moreover, the results of biochemical and genetic analyses revealed that Fct1 and Fct2 may form a complex and play distinct roles among the eight CCAAT-binding transcription factors encoded by F. graminearum. To the best of our knowledge, the results of this study represent a substantial advancement in our understanding of the molecular mechanisms underlying the functions of CCAAT-binding factors in eukaryotes.

Although human induced pluripotent stem cell (hiPSC) lines are karyotypically normal, they retain the potential for mutation in the genome. Accordingly, intensive and relevant quality controls for clinical-grade hiPSCs remain imperative. As a conceptual approach, we performed RNA-seq-based broad-range genetic quality tests on GMP-compliant human leucocyte antigen (HLA)-homozygous hiPSCs and their derivatives under postdistribution conditions to investigate whether sequencing data could provide a basis for future quality control. We found differences in the degree of single-nucleotide polymorphism (SNP) occurring in cells cultured at three collaborating institutes. However, the cells cultured at each centre showed similar trends, in which more SNPs occurred in late-passage hiPSCs than in early-passage hiPSCs after differentiation. In eSNP karyotyping analysis, none of the predicted copy number variations (CNVs) were identified, which confirmed the results of SNP chip-based CNV analysis. HLA genotyping analysis revealed that each cell line was homozygous for HLA-A, HLA-B, and DRB1 and heterozygous for HLA-DPB type. Gene expression profiling showed a similar differentiation ability of early- and late-passage hiPSCs into cardiomyocyte-like, hepatic-like, and neuronal cell types. However, time-course analysis identified five clusters showing different patterns of gene expression, which were mainly related to the immune response. In conclusion, RNA-seq analysis appears to offer an informative genetic quality testing approach for such cell types and allows the early screening of candidate hiPSC seed stocks for clinical use by facilitating safety and potential risk evaluation.

Diabetes is expected to accelerate age-related ganglion cell–inner plexiform layer (GC-IPL) loss, but there is limited information on the rate of reduction in GC-IPL thicknesses. We aimed to evaluate the reduction rate of GC-IPL thickness in diabetic patients, and to compare the rates between patients without and with diabetic retinopathy (DR). We included 112 eyes of 112 patients with diabetes [49 eyes without DR (no-DR group) and 63 eyes with mild to moderate non-proliferative DR (NPDR group)] and 63 eyes of 63 normal controls (control group) in this study. Macular GC-IPL thickness in all participants was measured for 3 years at 1-year intervals. The reduction rates of GC-IPL thickness were determined by linear mixed models and compared among the three groups. The estimated reduction rates of the average GC-IPL thickness in the no-DR (−0.627 μm/year) and NPDR (−0.987 μm/year) groups were 2.26-fold (p = 0.010) and 3.56-fold (p = 0.001) faster, respectively, than the control group (−0.277 μm/year). Age, duration of diabetes, and baseline average GC-IPL thickness were associated with longitudinal changes in average GC-IPL thickness. The GC-IPL reduction rate was significantly faster in diabetic patients, with and without DR. Physicians should therefore be aware that GC-IPL damage continues even if there is no DR.

To evaluate changes in peripapillary microvascular parameters in diabetes mellitus (DM) patients using optical coherence tomography angiography (OCTA). Seventy-one diabetic patients (40 in the no diabetic retinopathy [DR] group and 31 in the non-proliferative DR [NPDR] group) and 50 control subjects. OCTA (Zeiss HD-OCT 5000 with AngioPlex) 6 × 6 mm scans centered on the optic disc were analyzed. Peripapillary vessel density (VD), perfusion density (PD) in superficial capillary plexus (SCP) were automatically calculated. The average macular ganglion cell-inner plexiform layer (mGC-IPL) and peripapillary retinal nerve fiber layer (pRNFL) thicknesses of the no DR and NPDR groups were significantly thinner than those of the control group. The no DR and NPDR groups showed lower peripapillary VD and PD in SCP compared with the control group. Using univariate regression analyses, the average mGC-IPL thickness, the pRNFL thickness, the no DR group and NPDR group were significant factors that affected the peripapillary VD and PD in SCP. Multivariate regression analyses showed that the grade of DR was a significant factor affecting the peripapillary VD and PD in SCP. OCTA revealed that peripapillary microvascular parameters in the no DR and NPDR groups were lower than those of normal controls. The peripapillary VD and PD in SCP were correlated with the mGC-IPL thickness, the pRNFL thickness, and the no DR and NPDR groups. Changes in peripapillary OCTA parameters may help with understanding the pathophysiology of DM and evaluating a potentially valuable biomarker for patients with subclinical DR.

This study aimed to evaluate the most common primary metastatic location of acral malignant melanoma and to evaluate the usefulness of preoperative ultrasound for sentinel lymph node metastasis. Ninety-eight Korean acral malignant melanoma patients were enrolled. Acral malignant melanoma was present in 76 lower limbs and in 22 upper limbs. The most common origin location was the sole (33.7%). The most common location of primary metastasis was loco-regional recurrence (22/34, 64.7%). The sensitivity, specificity, positive predictive value, and negative predictive value of preoperative sentinel lymph node ultrasound was 29.1%, 94.6%, 63.6%, and 80.5%, respectively. We postulate the unusefulness of preoperative ultrasound for sentinel lymph node metastasis in acral malignant melanoma.

Various factors can affect repeatability of optical coherence tomography angiography (OCTA) measurements, and they have not been studied sufficiently. We aimed to investigate the factors associated with the repeatability of automated superficial retinal vessel density (VD) and foveal avascular zone (FAZ) metrics acquired from OCTA. A total of 141 normal eyes from 141 healthy subjects were included, and two consecutive macular 6 × 6-mm angiography scans were performed. VD, perfusion density (PD), and FAZ of the superficial capillary plexus were calculated automatically. Reproducibility was assessed based on intraclass correlations (ICCs) and coefficients of variation (CVs). VD (ICC: 0.824, CV: 3.898) and PD (ICC: 0.845, CV: 4.042) over the entire 6-mm scan area showed better repeatability than VD (ICC: 0.752, CV: 17.470) and PD (ICC: 0.752, CV: 18.552) in the 1-mm scan, and with respect to the obtained FAZ metrics (ICC 10.0%). Regression analyses showed that two factors, signal strength (p = 0.004) and average VD over the total 6-mm scan area (p

Three-dimensional visualization of cellular and subcellular-structures in histological-tissues is essential for understanding the complexities of biological-phenomena, especially with regards structural and spatial relationships and pathologlical-diagnosis. Recent advancements in tissue-clearing technology, such as Magnified Analysis of Proteome (MAP), have significantly improved our ability to study biological-structures in three-dimensional space; however, their wide applicability to a variety of tissues is limited by long incubation-times and a need for advanced imaging-systems that are not readily available in most-laboratories. Here, we present optimized MAP-based method for paper-thin samples, Paper-MAP, which allow for rapid clearing and subsequent imaging of three-dimensional sections derived from various tissues using conventional confocal-microscopy. Paper-MAP successfully clear tissues within 1-day, compared to the original-MAP, without significant differences in achieved optical-transparency. As a proof-of-concept, we investigated the vasculature and neuronal-networks of a variety of human and rodent tissues processed via Paper-MAP, in both healthy and diseased contexts, including Alzheimer’s disease and glioma.

This is a prospective observational study to establish the short- and long-term repeatability of measurements of peripapillary optical coherence tomography angiography (OCTA) parameters in healthy eyes and identify factors affecting long-term repeatability. We enrolled 84 healthy eyes. Participants with a history of any ophthalmic disease (except high myopia) or intraocular surgery were excluded from the study. An experienced examiner performed OCTA using disc-centered 6 × 6 mm scans. All examinations were conducted twice at 5-min intervals at the initial visit and repeated at least 6 months later. For short-term repeatability, the coefficient of variation (CV) was 2.94–4.22% and the intraclass correlation coefficient (ICC) was 0.840–0.934. For long-term repeatability, the CV was 2.73–3.84% and the ICC was 0.737–0.934. Multivariate analyses showed that the axial length (AL) (B = 0.970; p = 0.002) and mean signal strength (SS) (B = − 2.028; p