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Abstract Accurate segmentation of pupil light reflexes is essential for the reliable assessment of ptosis severity, a condition characterized by the drooping of the upper eyelid. This study introduces a novel encoder-decoder network specialized in reflex segmentation by focusing on addressing issues related to very small regions of interest from an architectural perspective. Specifically, the proposed network is designed to exploit low-level features effectively by integrating a multi-level skip connection and a 1 × 1 convolution-enhanced initial encoding stage. Assessed using a photograph image dataset from Chung-Ang University Hospital, which includes 87 healthy subjects, 64 with ptosis, and 257 with Graves’ orbitopathy (collected between January 2010 and February 2023), the proposed network outperforms five conventional encoder-decoders. Over 30 trials, the proposed network achieved a mean Dice coefficient of 0.767 and an Intersection over Union of 0.653, indicating a statistically significant improvement in the segmentation of reflex. Our findings show that an elaborate design based on the lowest-level skip connection and 1 × 1 convolution at initial stage enhances the segmentation of pupil light reflexes. The source code of the proposed network is available at https://github.com/tkdgur658/ReflexNet .

Abstract With the increase in the dependency on digital devices, the incidence of myopia, a precursor of various ocular diseases, has risen significantly. Because myopia and eyeball volume are related, myopia progression can be monitored through eyeball volume estimation. However, existing methods are limited because the eyeball shape is disregarded during estimation. We propose an automated eyeball volume estimation method from computed tomography images that incorporates prior knowledge of the actual eyeball shape. This study involves data preprocessing, image segmentation, and volume estimation steps, which include the truncated cone formula and integral equation. We obtained eyeball image masks using U-Net, HFCN, DeepLab v3 +, SegNet, and HardNet-MSEG. Data from 200 subjects were used for volume estimation, and manually extracted eyeball volumes were used for validation. U-Net outperformed among the segmentation models, and the proposed volume estimation method outperformed comparative methods on all evaluation metrics, with a correlation coefficient of 0.819, mean absolute error of 0.640, and mean squared error of 0.554. The proposed method surpasses existing methods, provides an accurate eyeball volume estimation for monitoring the progression of myopia, and could potentially aid in the diagnosis of ocular diseases. It could be extended to volume estimation of other ocular structures.

Abstract We aimed to evaluate the feasibility of MR elastography (MRE) using a transpelvic approach. Thirty-one patients who underwent prostate MRE and had a pathological diagnosis were included in this study. MRE was obtained using a passive driver placed at the umbilicus and iliac crests. The shear stiffness, clinical data, and conventional imaging findings of prostate cancer and benign prostatic hyperplasia (BPH) were compared. Inter-reader agreements were evaluated using the intraclass coefficient class (ICC). Prostate MRE was successfully performed for all patients (100% technical success rate). Nineteen cancer and 10 BPH lesions were visualized on MRE. The mean shear stiffness of cancer was significantly higher than that of BPH (5.99 ± 1.46 kPa vs. 4.67 ± 1.54 kPa, p = 0.045). One cancer was detected on MRE but not on conventional sequences. Six tiny cancer lesions were not visualized on MRE. The mean size of cancers that were not detected on MRE was smaller than that of cancers that were visible on MRE (0.8 ± 0.3 cm vs. 2.3 ± 1.8 cm, p = 0.001). The inter-reader agreement for interpreting MRE was excellent (ICC = 0.95). Prostate MRE with transpelvic vibration is feasible without intracavitary actuators. Transpelvic prostate MRE is reliable for detecting focal lesions, including clinically significant prostate cancer and BPH.

Abstract The purpose of this study was to assess the clinical utility and reliability of an automated eyelid measurement system utilizing neural network (NN) technology. Digital images of the eyelids were taken from a total of 300 subjects, comprising 100 patients with Graves’ orbitopathy (GO), 100 patients with ptosis, and 100 controls. An automated measurement system based on NNs was developed to measure margin–reflex distance 1 and 2 (MRD1 and MRD2), as well as the lengths of the upper and lower eyelids. The results were then compared with values measured using the manual technique. Automated measurements of MRD1, MRD2, upper eyelid length, and lower eyelid length yielded values of 3.2 ± 1.7 mm, 6.0 ± 1.4 mm, 32.9 ± 6.1 mm, and 29.0 ± 5.6 mm, respectively, showing a high level of agreement with manual measurements. To evaluate the morphometry of curved eyelids, the distance from the midpoint of the intercanthal line to the eyelid margin was measured. The minimum number of divisions for detecting eyelid abnormalities was determined to be 24 partitions (15-degree intervals). In conclusion, an automated NN-based measurement system could provide a straightforward and precise method for measuring MRD1 and MRD2, as well as detecting morphological abnormalities in the eyelids.

Abstract This study aimed to propose a neural network (NN)-based method to evaluate thyroid-associated orbitopathy (TAO) patient activity using orbital computed tomography (CT). Orbital CT scans were obtained from 144 active and 288 inactive TAO patients. These CT scans were preprocessed by selecting eleven slices from axial, coronal, and sagittal planes and segmenting the region of interest. We devised an NN employing information extracted from 13 pipelines to assess these slices and clinical patient age and sex data for TAO activity evaluation. The proposed NN’s performance in evaluating active and inactive TAO patients achieved a 0.871 area under the receiver operating curve (AUROC), 0.786 sensitivity, and 0.779 specificity values. In contrast, the comparison models CSPDenseNet and ConvNeXt were significantly inferior to the proposed model, with 0.819 (p = 0.029) and 0.774 (p = 0.04) AUROC values, respectively. Ablation studies based on the Sequential Forward Selection algorithm identified vital information for optimal performance and evidenced that NNs performed best with three to five active pipelines. This study establishes a promising TAO activity diagnosing tool with further validation.

Abstract This study aimed to evaluate the alteration of PAP compliance after nasal surgery and to determine the optimal indications of nasal surgery in obstructive sleep apnea (OSA) subjects. Among OSA subjects using PAP devices, 29 subjects who underwent septoturbinoplasty due to nasal obstruction were included and their pre- and postoperative medical and PAP records were reviewed retrospectively. Postoperative autoPAP usage data was further assessed by grouping the compliance (the percentage of days with usage ≥ 4 h) data (group 1: the good compliance group; group 2: the poor compliance group). The data showed that 56% of subjects in group 1 complained of nasal obstruction as the only barrier to using a PAP device and about 89% reported experiencing the efficacy of PAP usage. Both the mean and peak average PAP pressures were significantly reduced in group 1 following nasal surgery. Group 2 had multiple subjective problems that interfered with wearing a PAP device and reported a lack of experiencing the efficacy of PAP usage. Preoperative nasal cavity volume values were smaller and absolute blood eosinophil counts were significantly lower in group 1. The current data demonstrate that nasal surgery might increase the compliance of PAP device wear in OSA subjects who complained of only nasal obstruction as a barrier to wearing PAP and who had small nasal cavity volumes combined with allergic inflammation.

Abstract Computed tomography (CT) has been widely used to diagnose Graves’ orbitopathy, and the utility is gradually increasing. To develop a neural network (NN)-based method for diagnosis and severity assessment of Graves’ orbitopathy (GO) using orbital CT, a specific type of NN optimized for diagnosing GO was developed and trained using 288 orbital CT scans obtained from patients with mild and moderate-to-severe GO and normal controls. The developed NN was compared with three conventional NNs [GoogleNet Inception v1 (GoogLeNet), 50-layer Deep Residual Learning (ResNet-50), and 16-layer Very Deep Convolutional Network from Visual Geometry group (VGG-16)]. The diagnostic performance was also compared with that of three oculoplastic specialists. The developed NN had an area under receiver operating curve (AUC) of 0.979 for diagnosing patients with moderate-to-severe GO. Receiver operating curve (ROC) analysis yielded AUCs of 0.827 for GoogLeNet, 0.611 for ResNet-50, 0.540 for VGG-16, and 0.975 for the oculoplastic specialists for diagnosing moderate-to-severe GO. For the diagnosis of mild GO, the developed NN yielded an AUC of 0.895, which is better than the performances of the other NNs and oculoplastic specialists. This study may contribute to NN-based interpretation of orbital CTs for diagnosing various orbital diseases

Abstract Hp1404, identified from the venom of the scorpion Heterometrus petersii, displays antimicrobial activity with cytotoxicity. Several synthetic peptides were designed based on the parent peptide Hp1404 to reduce cytotoxicity and improve activity (deletion of glycine and phenylalanine, substitution with leucine and lysine). The analogue peptides generated comprised 12 amino acids and displayed amphipathic α-helical structures, with higher hydrophobic moments and net positive charge than those of the Hp1404. The analogues showed less hemolytic and toxic effects toward mammalian cells than the Hp1404, especially Hp1404-T1e, which exhibited particularly potent antibacterial and antibiofilm activities against multidrug-resistant Pseudomonas aeruginosa (MRPA) strains. The analogue peptide Hp1404-T1e was more stable against salt and trypsin than the Hp1404. Hp1404’s mechanism of action involves binding to lipopolysaccharide (LPS), thereby killing bacteria through membrane disruption. Hp1404-T1e kills bacteria more rapidly than Hp1404 and not only seems to bind more strongly to LPS but may also be able to enter bacterial cells and interact with their DNA. Additionally, Hp1404-T1e can effectively kill bacteria in vivo. The results of this study indicate that Hp1404-T1e not only displays antimicrobial activity, but is also functional in physiological conditions, confirming its potential use as an effective therapeutic agent against MRPA.

Abstract Pseudin-2 (Ps), isolated from the frog Pseudis paradoxa, exhibits potent antibacterial activity and cytotoxicity. To develop antimicrobial peptides with anti-inflammatory activity and low cytotoxicity, we designed Ps analogues with Lys substitutions, resulting in elevated amphipathic α-helical structure and cationicity. We further substituted Gly11 with Pro (Ps-P analogues) to increase bacterial cell selectivity. Ps analogues retained antimicrobial activity and exhibited reduced cytotoxicity, whereas Ps-P analogues exhibited lower cytotoxicity and antimicrobial activity. Tertiary structures revealed that Ps has a linear α-helix from Leu2 to Glu24, whereas Ps-P has a bend at Pro11 between two short α-helixes. Using various biophysical experiments, we found that Ps analogues produced much higher membrane depolarization than Ps-P analogues, whereas Ps-P analogues may penetrate bacterial cell membranes. Ps and its analogue Ps-K18 exhibited potent anti-inflammatory activity in LPS-stimulated RAW264.7 and mouse dendritic cells via a mechanism involving the Toll-like receptor 4 (TLR4) pathway. These activities may arise from their direct inhibition of the formation of TLR4-MD-2_LPS complex, implying that amphipathic α-helical structure with an optimum balance between enhanced cationicity and hydrophobicity may be essential for their anti-inflammatory activity. The bent structure provided by Pro substitution plays an important role in enhancing bacterial cell selectivity and cell penetration.

This study aims to figure out the worldwide prevalence of anticancer therapy-associated acute kidney injury (AKI) and tubulointerstitial nephritis (TIN) and the relative risk of each cancer drug. We conducted an analysis of VigiBase, the World Health Organization pharmacovigilance database, 1967-2023 via disproportionate Bayesian reporting method. We further categorized the anticancer drugs into four groups: cytotoxic therapy, hormone therapy, immunotherapy, and targeted therapy. Reporting odds ratio (ROR) and information component (IC) compares observed and expected values to investigate the associations of each category of anticancer drugs with AKI and TIN. We identified 32,722 and 2056 reports (male, n = 17,829 and 1,293) of anticancer therapy-associated AKI and TIN, respectively, among 4,592,036 reports of all-drug caused AKI and TIN. There has been a significant increase in reports since 2010, primarily due to increased reports of targeted therapy and immunotherapy. Immunotherapy exhibited a significant association with both AKI (ROR: 8.92; IC 0.25 : 3.06) and TIN (21.74; 4.24), followed by cytotoxic therapy (7.14; 2.68), targeted therapy (5.83; 2.40), and hormone therapy (2.59; 1.24) for AKI, and by cytotoxic therapy (2.60; 1.21) and targeted therapy (1.54; 0.61) for TIN. AKI and TIN were more prevalent among individuals under 45 years of age, with a female preponderance for AKI and males for TIN. These events were reported in close temporal relationship after initiation of the respective drug (16.53 days for AKI and 27.97 days for TIN), and exhibited a high fatality rate, with 23.6% for AKI and 16.3% for TIN. These findings underscore that kidney-related adverse drug reactions are of prognostic significance and strategies to mitigate such side effects are required to optimize anticancer therapy., (© 2024. The Author(s).)

In single-cell transcriptome analysis, numerous biomarkers related to COVID-19 severity, including cell subtypes, genes, and pathways, have been identified. Nevertheless, most studies have focused on severity groups based on clinical features, neglecting immunological heterogeneity within the same severity level. In this study, we employed sample-level clustering using cell-cell interaction scores to investigate patient heterogeneity and uncover novel subtypes. The clustering results were validated using external datasets, demonstrating superior reproducibility and purity compared to gene expression- or gene set enrichment-based clustering. Furthermore, the cell-cell interaction score-based clusters exhibited a strong correlation with the WHO ordinal severity score based on clinical characteristics. By characterizing the identified subtypes through known COVID-19 severity-associated biomarkers, we discovered a "Severe-like moderate" subtype. This subtype displayed clinical features akin to moderate cases; however, molecular features, such as gene expression and cell-cell interactions, resembled those of severe cases. Notably, all patients who progressed from moderate to severe belonged to this subtype, underscoring the significance of cell-cell interactions in COVID-19 patient heterogeneity and severity., (© 2023. The Author(s).)

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. The clinical relevance of 11 urinary exosomal microRNAs (miRNAs) was evaluated in patients with IgAN. From January 2009 to November 2018, IgAN (n = 93), disease control (n = 11), and normal control (n = 19) groups were enrolled. We evaluated the expression levels of urinary exosomal miRNAs at the baseline and their relationship with clinical and pathologic features. This study aimed to discriminate statistically powerful urinary exosomal miRNAs for the prognosis of IgAN. Urinary miRNA levels of miR-16-5p, miR-29a-3p, miR-124-3p, miR-126-3p, miR-199a-3p, miR-199b-5p, and miR-335-3p showed significant correlation with both estimated glomerular filtration rate (eGFR) and urine protein-to-creatinine ratio (uPCR). In univariate regression analysis, age, body mass index, hypertension, eGFR, uPCR, Oxford classification E, and three miRNAs (miR-16-5p, miR-199a-3p, and miR-335-3p) were associated with disease progression in patients with IgAN. The area under the curve (AUC) of miR-199a-3p was high enough (0.749) without any other clinical or pathologic factors, considering that the AUC of the International IgAN Risk Prediction Tool was 0.853. Urinary exosomal miRNAs may serve as alternative prognostic biomarkers of IgAN with further research., (© 2023. Springer Nature Limited.)

Polycystic ovary syndrome (PCOS) is a highly complex reproductive metabolic disorder and women with PCOS have high prevalence of non-alcoholic fatty liver disease (NAFLD). Despite both hyperandrogenism and insulin resistance are common pathophysiologies in NAFLD and PCOS, this association is still controversial. Therefore, the aim of this study is to evaluate the relationship between hyperandrogenism and NAFLD in females diagnosed with PCOS. We recruited 667 women diagnosed with PCOS and 289 women with regular menstrual cycles as control. The PCOS diagnosis was made using National Institute of Child Health and Human Disease criteria. Total and free testosterone levels (TT and TF, respectively), and free androgen index (FAI) were used as measures of hyperandrogenism. Fatty liver index and liver fat score (FLI and LFS, respectively), and hepatic steatosis index (HSI) were used to assess NAFLD. The prevalence of NAFLD in PCOS women evaluated by LFS, FLI, and HIS were 19.9, 10.3, and 32.2%, respectively. In the control group, the incidence was 2.1, 0.7, and 4.2%, respectively. Both FT and FAI levels showed significant association with increased NAFLD-related indices, after adjusting for insulin resistance and other factors (LFS (OR 3.18 (95% CI 1.53-6.63) in FT; 1.12 (1.04-1.22) in FAI), FLI (OR 2.68 (95% CI 1.43-5.03) in FT; 1.13 (1.06-1.20) in FAI), and HSI (OR 3.29 (95% CI 2.08-5.21) in FT; 1.5 (1.09-1.21) in FAI). TT did not exhibit association with any NAFLD index. In women with PCOS, significantly higher rate of NAFLD was observed compared to the control women. The FT and FAI were independently associated with NAFLD in women with PCOS. The findings suggest the possibility of hyperandrogenism contributing to the progression and/or development of NAFLD in PCOS., (© 2023. Springer Nature Limited.)

This work investigates the function of the oxygen partial pressure in photo-induced current measurement of extended defect properties related to the distribution and quantity of defect states in electronic structures. The Fermi level was adjusted by applying a negative gate bias in the TFT structure, and the measurable range of activation energy was extended to < 2.0 eV. Calculations based on density functional theory are used to investigate the changes in defect characteristics and the role of defects at shallow and deep levels as a function of oxygen partial pressure. Device characteristics, such as mobility and threshold voltage shift under a negative gate bias, showed a linear correlation with the ratio of shallow level to deep level defect density. Shallow level and deep level defects are organically related, and both defects must be considered when understanding device characteristics., (© 2023. Springer Nature Limited.)

The foodborne bacterium Staphylococcus equorum strain KS1030 harbours plasmid pSELNU1, which encodes a lincomycin resistance gene. pSELNU1 undergoes horizontal transfer between bacterial strains, thus spreading antibiotic resistance. However, the genes required for horizontal plasmid transfer are not encoded in pSELNU1. Interestingly, a relaxase gene, a type of gene related to horizontal plasmid transfer, is encoded in another plasmid of S. equorum KS1030, pKS1030-3. The complete genome of pKS1030-3 is 13,583 bp long and encodes genes for plasmid replication, biofilm formation (the ica operon), and horizontal gene transfer. The replication system of pKS1030-3 possesses the replication protein-encoding gene repB, a double-stranded origin of replication, and two single-stranded origins of replication. The ica operon, relaxase gene, and a mobilization protein-encoding gene were detected in pKS1030-3 strain-specifically. When expressed in S. aureus RN4220, the ica operon and relaxase operon of pKS1030-3 conferred biofilm formation ability and horizontal gene transfer ability, respectively. The results of our analyses show that the horizontal transfer of pSELNU1 of S. equorum strain KS1030 depends on the relaxase encoded by pKS1030-3, which is therefore trans-acting. Genes encoded in pKS1030-3 contribute to important strain-specific properties of S. equorum KS1030. These results could contribute to preventing the horizontal transfer of antibiotic resistance genes in food., (© 2023. The Author(s).)

Little is known about the prevalence of chronic kidney disease (CKD) during the coronavirus disease 2019 (COVID-19) pandemic. We aimed to investigate the long-term trends in CKD prevalence from South Korea including the early pandemic. We used data from 108,152 Korean adults from 2007 to 2020 obtained from a representative longitudinal serial study. We defined CKD as a condition when the participant's estimated glomerular filtration rate was < 60 mL/min/1.73 m 2 , or one-time spot proteinuria was ≥ 1 +, and then examined the overall trends in the prevalence of CKD. Among the included adults (n = 80,010), the overall national prevalence of CKD was 6.2%. The trend slope gradually increased from 2007 to 2019, however, there was a sudden decrease in 2020 (2007-2010, 5.1% [95% confidence interval (CI) 4.7-5.5]; 2017-2019, 7.1% [95% CI 6.6-7.6]; pandemic period, 6.5% [95% CI 5.7-7.3]; and β diff , - 0.19; 95% CI - 0.24 to - 0.13). The prevalence of CKD among younger adults and those with poor medical utilization significantly decreased during the early pandemic. This study was the first large-scale study to investigate the longitudinal prevalence of CKD from 2007 to 2020. Further research is needed to fully understand the exact causes for this decline and to identify healthcare policy strategies for preventing and managing CKD., (© 2023. The Author(s).)

Following the recent terrorist attacks using Novichok agents and the subsequent decomposition operations, understanding the chemical structures of nerve agents has become important. To mitigate the ever-evolving threat of new variants, the Organization for the Prohibition of Chemical Weapons has updated the list of Schedule 1 substances defined by the Chemical Weapons Convention. However, owing to the several possible structures for each listed substance, obtaining an exhaustive dataset is almost impossible. Therefore, we propose a nuclear magnetic resonance-based prediction method for 1 H and 13 C NMR chemical shifts of Novichok agents based on conformational and density functional study calculations. Four organophosphorus compounds and five G- and V-type nerve agents were used to evaluate the accuracy of the proposed procedure. Moreover, 1 H and 13 C NMR prediction results for an additional 83 Novichok candidates were compiled as a database to aid future research and identification. Further, this is the first study to successfully predict the NMR chemical shifts of Novichok agents, with an exceptional agreement between predicted and experimental data. The conclusions enable the prediction of all possible structures of Novichok agents and can serve as a firm foundation for preparation against future terrorist attacks using new variants of nerve agents., (© 2022. The Author(s).)

The resistive switching behavior of the solution processed SiO x device was investigated by inserting TiO 2 nanoparticles (NPs). Compared to the pristine SiO x device, the TiO 2 NPs inserted SiO x (SiO x @TiO 2 NPs) device achieves outstanding switching characteristics, namely a higher ratio of SET/RESET, lower operating voltages, improved cycle-to-cycle variability, faster switching speed, and multiple-RESET states. Density functional theory calculation (DFT) and circuit breaker simulation (CB) were used to detail the origin of the outstanding switching characteristic of the SiO x @TiO 2 NPs. The improvement in resistive switching is mainly based on the difference in formation/rupture of the conductive path in the SiO 2 and SiO 2 @TiO 2 NPs devices. In particular, the reduction of resistance and lower switching voltage of TiO 2 NPs control the formation and rupture of the conductive path to achieve more abrupt switching between SET/RESET with higher on/off ratio. This method of combined DFT calculation and CB offers a promising approach for high-performance non-volatile memory applications., (© 2022. The Author(s).)

Costoclavicular brachial plexus block is emerging as a promising infraclavicular approach performed just below the clavicle. However, there are relatively little data regarding the hemidiaphragmatic paralysis (HDP) compared to the commonly performed supraclavicular block. We hypothesized that the incidence of HDP in costoclavicular block is lower than supraclavicular block like classical infraclavicular approach. Eighty patients were randomly assigned to ultrasound-guided supraclavicular (group S) or costoclavicular (group C) block with 25 mL of local anesthetics (1:1 mixture of 1% lidocaine and 0.75% ropivacaine). The primary outcome was the incidence of HDP, defined as less than 20% of fractional change in the diaphragm thickness on ultrasound M-mode. Also, pulmonary function test and chest radiograph were assessed before and after the surgery. The incidence of HDP was 4/35 (11.4%) in the group C and 19/40 (47.5%) in the group S (risk difference, - 36%; 95% CI - 54 to - 17%; P = 0.002). The mean (SD) change of DTF values were 30.3% (44.0) and 56.9% (39.3) in the group C and S, respectively (difference in means, - 26.6%; 95% CI - 45.8 to - 7.4%; P = 0.007). The pulmonary function was more preserved in group C than in group S. The determined diagnostic cut off value of the diaphragm elevation on chest radiograph was 29 mm. Despite the very contiguous location of the two approaches around the clavicle, costoclavicular block can significantly reduce the risk of HDP compared with supraclavicular block., (© 2021. The Author(s).)

Several drug candidates have been proposed and tested as the latest clinical treatment for coronavirus pneumonia (COVID-19). Chloroquine, hydroxychloroquine, ritonavir/lopinavir, and favipiravir are under trials for the treatment of this disease. The hyperpolarization technique has the ability to further provide a better understanding of the roles of these drugs at the molecular scale and in different applications in the field of nuclear magnetic resonance/magnetic resonance imaging. This technique may provide new opportunities in diagnosis and research of COVID-19. Signal amplification by reversible exchange-based hyperpolarization studies on large-sized drug candidates were carried out. We observed hyperpolarized proton signals from whole structures, due to the unprecedented long-distance polarization transfer by para-hydrogen. We also found that the optimal magnetic field for the maximum polarization transfer yield was dependent on the molecular structure. We can expect further research on the hyperpolarization of other important large molecules, isotope labeling, as well as polarization transfer on nuclei with a long spin relaxation time. A clinical perspective of these features on drug molecules can broaden the application of hyperpolarization techniques for therapeutic studies.

Breast cancer (BC) in patients with germline mutations of BRCA1/BRCA2 are associated with benefit from drugs targeting DNA damage response (DDR), but they account for only 5-7% of overall breast cancer. To define the characteristics of these tumors and also to identify tumors without BRCA mutation but with homologous recombination deficiency (HRD) is clinically relevant. To define characteristic features of HRD tumors and analyze the correlations between BRCA1/BRCA2 and BC subtypes, we analyzed 981 breast tumors from the TCGA database using the signature analyzer. The BRCA signature was strongly associated with the HRD score top 10% (score ≥ 57) population. This population showed a high level of mutations in DDR genes, including BRCA1/BRCA2. HRD tumors were associated with high expression levels of BARD1 and BRIP1. Besides, BRCA1/2 mutations were dominantly observed in basal and luminal subtypes, respectively. A comparison of HRD features in BC revealed that BRCA1 exerts a stronger influence inducing HRD features than BRCA2 does. It reveals genetic differences between BRCA1 and BRCA2 and provides a basis for the identification of HRD and other BRCA-associated tumors.

Polycystic ovary syndrome (PCOS) is a highly complex disorder influenced by genetic and environmental factors. Previous genome-wide association studies (GWAS) on Han Chinese, Korean, and European populations identified multiple PCOS-susceptible loci; however, only a few studies reported the association of susceptibility genes with disease phenotypic traits. This cross-sectional study aimed to investigate the association between PCOS susceptibility genes from GWAS and disease-related clinical features. A total of 1,810 reproductive-aged women were recruited, including 927 control women and 883 women with PCOS, diagnosed based on the European Society for Human Reproduction and Embryology criteria. Genomic DNA was extracted and genotyped, and a Bonferroni test was performed to determine the association between 12 independent SNPs and the clinical features of PCOS. In women with PCOS, rs11031006, nearest to FSHB, was significantly associated with free testosterone (P = 1.94 × 10 -3 ) and luteinizing hormone (P = 1.96 × 10 -3 ) levels. The menstruation number per year, ovarian follicular number, ovarian volume, and insulin sensitivity index were not associated with any SNP. In the control group, no SNPs were associated with any PCOS traits. Collectively, our results suggest that FSHB may play an important role in the development and progression of PCOS.

The signal amplification by reversible exchange (SABRE) technique is a very promising method for increasing magnetic resonance (MR) signals. SABRE can play a particularly large role in studies with a low or ultralow magnetic field because they suffer from a low signal-to-noise ratio. In this work, we conducted real-time superconducting quantum interference device (SQUID)-based nuclear magnetic resonance (NMR)/magnetic resonance imaging (MRI) studies in a microtesla-range magnetic field using the SABRE technique after designing a bubble-separated phantom. A maximum enhancement of 2658 for 1 H was obtained for pyridine in the SABRE-NMR experiment. A clear SABRE-enhanced MR image of the bubble-separated phantom, in which the para-hydrogen gas was bubbling at only the margin, was successfully obtained at 34.3 μT. The results show that SABRE can be successfully incorporated into an ultralow-field MRI system, which enables new SQUID-based MRI applications. SABRE can shorten the MRI operation time by more than 6 orders of magnitude and establish a firm basis for future low-field MRI applications.

This study aimed to characterise the distribution of choroidal thickness (CT) in diabetic retinopathy eyes, inside and outside of the vascular arcade, as well as at the fovea, using spectral-domain optical coherence tomography (OCT). Forty-nine healthy eyes, 80 diabetic retinopathy (DR) eyes (59 non-proliferative diabetic retinopathy (NPDR) eyes and 21 proliferative diabetic retinopathy (PDR) eyes) were examined with OCT to obtain nine horizontal lines (far superotemporal, near superotemporal, central, near inferotemporal, far inferotemporal, far superonasal, near superonasal, near inferonasal, far inferonasal) inside and outside of the vascular arcade. Nine points were chosen in 0.5-mm intervals to calculate CT, which was measured at 81 points in each patient. In the DR group, CT decreased significantly, compared with the control group, in all nine horizontal lines except central and near inferotemporal (-29.74 to -36.97 μm, p < 0.05 for all). In the PDR group, CT decreased compared with the NPDR group, in all nine horizontal lines (-6.18 μm to -34.58 μm), but this difference was not significant. In DR eyes, an overall significant reduction of CT was observed inside and outside of the vascular arcade; CT showed a non-significant decrease in PDR eyes, compared with NPDR eyes.

Protein tyrosine kinase (PTK) activity has been implicated in pro-inflammatory gene expression following tumor necrosis factor-α (TNF-α) or interkeukin-1β (IL-1β) stimulation. However, the identity of responsible PTK(s) in cytokine signaling have not been elucidated. To evaluate which PTK is critical to promote the cytokine-induced inflammatory cell adhesion molecule (CAM) expression including VCAM-1, ICAM-1, and E-selectin in human aortic endothelial cells (HAoECs), we have tested pharmacological inhibitors of major PTKs: Src and the focal adhesion kinase (FAK) family kinases - FAK and proline-rich tyrosine kinase (Pyk2). We found that a dual inhibitor of FAK/Pyk2 (PF-271) most effectively reduced all three CAMs upon TNF-α or IL-1β stimulation compared to FAK or Src specific inhibitors (PF-228 or Dasatinib), which inhibited only VCAM-1 expression. In vitro inflammation assays showed PF-271 reduced monocyte attachment and transmigration on HAoECs. Furthermore, FAK/Pyk2 activity was not limited to CAM expression but was also required for expression of various pro-inflammatory molecules including MCP-1 and IP-10. Both TNF-α and IL-1β signaling requires FAK/Pyk2 activity to activate ERK and JNK MAPKs leading to inflammatory gene expression. Knockdown of either FAK or Pyk2 reduced TNF-α-stimulated ERK and JNK activation and CAM expression, suggesting that activation of ERK or JNK is specific through FAK and Pyk2. Finally, FAK/Pyk2 activity is required for VCAM-1 expression and macrophage recruitment to the vessel wall in a carotid ligation model in ApoE-/- mice. Our findings define critical roles of FAK/Pyk2 in mediating inflammatory cytokine signaling and implicate FAK/Pyk2 inhibitors as potential therapeutic agents to treat vascular inflammatory disease such as atherosclerosis.

We investigate minimal control power (MCP) for controlled dense coding defined by the channel capacity. We obtain MCPs for extended three-qubit Greenberger-Horne-Zeilinger (GHZ) states and generalized three-qubit W states. Among those GHZ states, the standard GHZ state is found to maximize the MCP and so does the standard W state among the W-type states. We find the lower and upper bounds of the MCP and show for pure states that the lower bound, zero, is achieved if and only if the three-qubit state is biseparable or fully separable. The upper bound is achieved only for the standard GHZ state. Since the MCP is nonzero only when three-qubit entanglement exists, this quantity may be a good candidate to measure the degree of genuine tripartite entanglement.

We investigated changes in the crystal structure of GeTe during its phase transition. Using density functional theory (DFT) calculations, four possible crystal structures were identified: R3m, P1, Cm, and Fm3m. Among these, P1 and Cm were examined here for the first time. By calculating the internal energy of the crystal volume change, we verified that P1, R3m, and Cm can coexist in crystalline GeTe. The X-ray diffraction spectra of annealed and laser-irradiated GeTe films revealed coexisting P1 or R3m and Cm. In addition, we confirmed that Cm transforms into P1 or R3m after laser irradiation. The presence of these new structures was revealed in the crystal Raman spectra. Many of the Raman peaks in the crystalized GeTe could be explained by the coexistence of various structures. By calculating the band gaps of these structures, we also found that a structural transformation induces a change in the crystal resistance, owing to differences in the band gaps of individual structures. The generation of new crystal structures suggests a facile phase change and instability during the structural transformation.

Single-crystal Bi2Te3 nanowires (NWs) and nanoribbons (NRs) were synthesized by a vapor-liquid-solid (VLS) method from Bi2Te3 powder. To investigate the thermal properties of the Bi2Te3 nanostructure, a nondestructive technique based on temperature dependent Raman mapping was carried out. The Raman peaks were red shifted with increasing temperature. In addition, the fraction of the laser power absorbed inside the Bi2Te3 nanostructures was estimated by optical simulation and used to calculate the thermal conductivity value (κ). The thermal conductivity value obtained for the Bi2Te3 NW and NR was 1.47 Wm(-1)K(-1) and 1.81 Wm(-1)K(-1) at 300 K, respectively. The electrical conductivity of the Bi2Te3 nanostructure was also measured. In particular, an excellent electrical conductivity value of 1.22 * 10(3 )Ω(-1) cm(-1) was obtained for the Bi2Te3 NW at 300 K. This result can be attributed to topological insulator surface states. As a result of our study, the figure of merit (ZT) for the Bi2Te3 NW and NR can be significantly improved.

Mammalian T-type Ca(2+) channels are encoded by three separate genes (Cav3.1, 3.2, 3.3). These channels are reported to be sleep stabilizers important in the generation of the delta rhythms of deep sleep, but controversy remains. The identification of precise physiological functions for the T-type channels has been hindered, at least in part, by the potential for compensation between the products of these three genes and a lack of specific pharmacological inhibitors. Invertebrates have only one T-type channel gene, but its functions are even less well-studied. We cloned Ca-α1T, the only Cav3 channel gene in Drosophila melanogaster, expressed it in Xenopus oocytes and HEK-293 cells, and confirmed it passes typical T-type currents. Voltage-clamp analysis revealed the biophysical properties of Ca-α1T show mixed similarity, sometimes falling closer to Cav3.1, sometimes to Cav3.2, and sometimes to Cav3.3. We found Ca-α1T is broadly expressed across the adult fly brain in a pattern vaguely reminiscent of mammalian T-type channels. In addition, flies lacking Ca-α1T show an abnormal increase in sleep duration most pronounced during subjective day under continuous dark conditions despite normal oscillations of the circadian clock. Thus, our study suggests invertebrate T-type Ca(2+) channels promote wakefulness rather than stabilizing sleep.

While the objective of conventional quantum key distribution (QKD) is to secretly generate and share the classical bits concealed in the form of maximally mixed quantum states, that of private quantum channel (PQC) is to secretly transmit individual quantum states concealed in the form of maximally mixed states using shared one-time pad and it is called Gaussian private quantum channel (GPQC) when the scheme is in the regime of continuous variables. We propose a GPQC enhanced with squeezed coherent states (GPQCwSC), which is a generalization of GPQC with coherent states only (GPQCo) [Phys. Rev. A 72, 042313 (2005)]. We show that GPQCwSC beats the GPQCo for the upper bound on accessible information. As a subsidiary example, it is shown that the squeezed states take an advantage over the coherent states against a beam splitting attack in a continuous variable QKD. It is also shown that a squeezing operation can be approximated as a superposition of two different displacement operations in the small squeezing regime.

Circadian clocks orchestrate essential physiology in response to various cues, yet their mechanistic and functional plasticity remains unclear. Here, we investigated Clock(Δ19/+) heterozygous (Clk/+) mice, known to display lengthened periodicity and dampened amplitude, as a model of partially perturbed clocks. Interestingly, Clk/+ mice exhibited improved glycemic control and resistance to circadian period lengthening under high-fat diet (HFD). Furthermore, BMAL1 protein levels in Clk/+ mouse liver were upregulated compared with wild-type (WT) mice under HFD. Pharmacological and molecular studies showed that BMAL1 turnover entailed proteasomal and autophagic activities, and CLOCKΔ19 attenuated both processes. Consistent with an important role of BMAL1 in glycemic control, enhanced activation of insulin signaling was observed in Clk/+ mice relative to WT in HFD. Finally, transcriptome analysis revealed reprogramming of clock-controlled metabolic genes in Clk/+ mice. Our results demonstrate a novel role of autophagy in circadian regulation and reveal an unforeseen plasticity of circadian and metabolic networks.