Search

We investigated exciton–phonon interactions in three types of GaAs/ Al 0.3 Ga 0.7 As quantum dots (QDs grown by droplet epitaxy. Comparative optical studies were conducted on QDs of similar species, grown under identical conditions, and on various other QD types. Multioscillator models were employed to analyze the phonon coupling channels in various QD species, with a focus on the influence of capping time on high-energy phonon channels. The findings were found to be consistent with those of previous atomic-scale structural analyses. Engineering exciton–phonon interactions offers a viable approach for implementing QD-based devices in optoelectronics, thermoelectrics, and information-processing applications. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the study was to develop a predictive model for vertebral compression fracture (VCF) prior to spinal stereotactic body radiation therapy (SBRT) using radiomics features extracted from pre-treatment planning CT images. Methods: A retrospective analysis was conducted on 85 patients (114 spinal lesions) who underwent spinal SBRT. Radiomics features were extracted from pre-treatment planning CT images and used to develop a predictive model using a classification algorithm selected from nine different machine learning algorithms. Four different models were trained, including clinical features only, clinical and radiomics features, radiomics and dosimetric features, and all features. Model performance was evaluated using accuracy, precision, recall, F1-score, and area under the curve (AUC). Results: The model that used all features (radiomics, clinical, and dosimetric) showed the highest performance with an AUC of 0.871. The radiomics and dosimetric features model had the superior performance in terms of accuracy, precision, recall, and F1-score. Conclusion: The developed predictive model based on radiomics features extracted from pre-treatment planning CT images can accurately predict the likelihood of VCF prior to spinal SBRT. This model has significant implications for treatment planning and preventive measures for patients undergoing spinal SBRT. Future research can focus on improving model performance by incorporating new data and external validation using independent data sets. [ABSTRACT FROM AUTHOR]

This study determined whether compared to conventional mechanical ventilation (MV), extracorporeal membrane oxygenation (ECMO) is associated with decreased hospital mortality or fibrotic changes in patients with COVID-19 acute respiratory distress syndrome. A cohort of 72 patients treated with ECMO and 390 with conventional MV were analyzed (February 2020–December 2021). A target trial was emulated comparing the treatment strategies of initiating ECMO vs no ECMO within 7 days of MV in patients with a PaO2/FiO2 < 80 or a PaCO2 ≥ 60 mmHg. A total of 222 patients met the eligibility criteria for the emulated trial, among whom 42 initiated ECMO. ECMO was associated with a lower risk of hospital mortality (hazard ratio [HR], 0.56; 95% confidence interval [CI] 0.36–0.96). The risk was lower in patients who were younger (age < 70 years), had less comorbidities (Charlson comorbidity index < 2), underwent prone positioning before ECMO, and had driving pressures ≥ 15 cmH2O at inclusion. Furthermore, ECMO was associated with a lower risk of fibrotic changes (HR, 0.30; 95% CI 0.11–0.70). However, the finding was limited due to relatively small number of patients and differences in observability between the ECMO and conventional MV groups. [ABSTRACT FROM AUTHOR]

Intestinal macrophages play crucial roles in both intestinal inflammation and immune homeostasis. They can adopt two distinct phenotypes, primarily determined by environmental cues. These phenotypes encompass the classically activated pro-inflammatory M1 phenotype, as well as the alternatively activated anti-inflammatory M2 phenotype. In regular conditions, intestinal macrophages serve to shield the gut from inflammatory harm. However, when a combination of genetic and environmental elements influences the polarization of these macrophages, it can result in an M1/M2 macrophage activation imbalance, subsequently leading to a loss of control over intestinal inflammation. This shift transforms normal inflammatory responses into pathological damage within the intestines. In patients with ulcerative colitis-associated colorectal cancer (UC-CRC), disorders related to intestinal inflammation are closely correlated with an imbalance in the polarization of intestinal M1/M2 macrophages. Therefore, reinstating the equilibrium in M1/M2 macrophage polarization could potentially serve as an effective approach to the prevention and treatment of UC-CRC. This paper aims to scrutinize the clinical evidence regarding Chinese medicine (CM) in the treatment of UC-CRC, the pivotal role of macrophage polarization in UC-CRC pathogenesis, and the potential mechanisms through which CM regulates macrophage polarization to address UC-CRC. Our objective is to offer fresh perspectives for clinical application, fundamental research, and pharmaceutical advancement in UC-CRC. [ABSTRACT FROM AUTHOR]

Objective: To describe the treatment patterns and survival status of advanced gastric cancer (AGC) in China in the past two decades, and objectively evaluate the impact of standardized Chinese medicine (CM) treatment on the survival of AGC patients. Methods: This multicenter registry designed and propensity score analysis study described the diagnosis characteristics, treatment-pattern development and survival status of AGC from 10 hospitals in China between January 1, 2000 and July 31, 2021. Overall survival (OS) was evaluated between non-CM cohort (standard medical treatment) and CM cohort (integrated standard CM treatment ≥3 months). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to adjust any difference in average outcomes for bias. Results: A total of 2,001 patients histologically confirmed locally advanced and/or metastasis stomach and gastroesophageal junction adenocarcinoma were enrolled. Among them, 1,607 received systemic chemotherapy, 215 (10.74%) accepted molecular targeted therapy, 44 (2.2%) received checkpoint inhibitor therapy, and 769 (38.43%) received CM. Two-drug regimen was the main choice for first-line treatment, with fluoropyrimidine plus platinum as the most common regimen (530 cases, 60.09%). While 45.71% (16 cases) of patients with HER2 amplification received trastuzumab in first-line. The application of apatinib increased (33.33%) in third-line. The application of checkpoint inhibitors has increased since 2020. COX analysis showed that Lauren mixed type (P=0.017), cycles of first-line treatment >6 (P=0.000), CM (P=0.000), palliative gastrectomy (P=0.000), trastuzumab (P=0.011), and apatinib (P=0.008) were independent prognostic factors for the OS of AGC. After PSM and IPTW, the median OS of CM cohort and non-CM cohort was 18.17 and 12.45 months, respectively (P<0.001). Conclusions: In real-world practice for AGC in China, therapy choices consisted with guidelines. Two-drug regimen was the main first-line choice. Standardized CM treatment was an independent prognostic factor and could prolong the OS of Chinese patients with AGC. (Registration No. NCT02781285) [ABSTRACT FROM AUTHOR]

The present study was conducted to evaluate the availability of citrus byproduct (CBP) as a vitamin C additive compared with the L-ascorbyl-polyphosphate (LAPP) for juvenile Korean rockfish Sebastes schlegelii. Four experimental diets, based on the basal diet (Con; semi-purified, crude protein 48%), were prepared by supplementing LAPP or CBP to achieve a dietary vitamin C concentration of 90 or 360 mg/kg (designated as LAPP90, LAPP360, CBP90, and CBP360, respectively). Three replicate groups of S. schlegelii (mean body weight ± standard deviation = 4.5 ± 0.0 g) were fed the experimental diets for 13 weeks. After the feeding trial, growth performance, feed utilization efficiency, and survival were significantly lower in the Con group. Liver vitamin C concentration was significantly increased (36.7–117 mg/kg) with increasing dietary LAPP levels; however, there was no significant difference in the CBP groups (14.2–14.3 mg/kg) compared with the Con group. Bone collagen concentration was significantly affected by LAPP and CBP supplementation. The LAPP and CBP groups showed significantly higher lysozyme activity and total immunoglobulin levels than the Con group. Disease resistance against Streptococcus iniaewas significantly improved in the LAPP and CBP groups (60–92% survival) than in the Con group (39% survival). These results indicate that dietary vitamin C is essential for S. schlegelii and CBP could be a LAPP substitute as a vitamin C additive. [ABSTRACT FROM AUTHOR]

To improve the interface stability between Li-rich Mn-based oxide cathodes and electrolytes, it is necessary to develop new polymer electrolytes. Here, we report an entanglement association polymer electrolyte (PVFH-PVCA) based on a poly (vinylidene fluoride-co-hexafluoropropylene) (PVFH) matrix and a copolymer stabilizer (PVCA) prepared from acrylonitrile, maleic anhydride, and vinylene carbonate. The entangled structure of the PVFH-PVCA electrolyte imparts excellent mechanical properties and eliminates the stress arising from dendrite growth during cycling and forms a stable interface layer, enabling Li//Li symmetric cells to cycle steadily for more than 4500 h at 8 mA cm−2. The PVCA acts as a stabilizer to promote the formation of an electrochemically robust cathode–electrolyte interphase. It delivers a high specific capacity and excellent cycling stability with 84.7% capacity retention after 400 cycles. Li1.2Mn0.56Ni0.16Co0.08O2/PVFH-PVCA/Li full cell achieved 125 cycles at 1 C (4.8 V cut-off) with a stable discharge capacity of ~2.5 mAh cm−2.Here, the authors report an entanglement association polymer electrolyte with a polymer matrix and copolymer stabilizer. The developed entangled structure forms a stable interface for the polymer electrolyte during charging and discharging. [ABSTRACT FROM AUTHOR]

Driver assistance systems or smart headlamp technology require accurate vehicle detection in nighttime traffic environments. This study proposes a novel nighttime vehicle detection (NVD) algorithm that can be applied to these technologies, and the algorithm was implemented using image processing. Images taken on roads at night are basically dark and lack information regarding vehicle appearance. Additionally, they contain significant noise caused by various lights and the scattering or reflection of these lights. Therefore, it is difficult to increase the performance of existing NVD methods. In addition, recent end-to-end convolutional neural network (CNN)-based object detection (OD) methods exhibit low NVD performance owing to their poor learning capability caused by lack of information and noise in the images. This study presents new methods to overcome the limitations of NVD implementation: 1) We propose a candidate search and diffusion method based on the use of experimental heuristics and hand-crafted features to utilize the characteristics related to light emitted from vehicle headlamps or taillamps. 2) We propose a CNN method that combines the approaches applied in latest CNN-based OD method with the proposed candidate search and diffusion method. To demonstrate the superiority of the proposed method, we conducted experiments and compared the proposed method to recent CNN-based OD methods. The experimental results demonstrated the higher detection performance of the proposed method compared to other methods. The code is available at https://github.com/sjg918/gj-nvd-diffusion/ [ABSTRACT FROM AUTHOR]

In the present work, attention is paid to the nonlinear vibrations and chaotic dynamic behaviors of rotating graphene platelets reinforced metal foams (GPLRMF) blades operating in a thermal environment. Considering three different distribution patterns of graphene platelets (GPL) and foams, the improved Halpin–Tsai model, mixing rules and Maxwell-Eucken model are applied to obtain the physical parameters of rotating GPLRMF plates. The motion equations of GPLRMF rotating plates are established through higher-order shear deformation theory (HSDT), in which the centrifugal force, Coriolis force and heat conduction are included. Under the cantilever and simply supported boundary conditions, the nonlinear ordinary differential equation (ODE) of the system is obtained by Galerkin method. The amplitude-frequency response, bifurcation curve, and chaotic motion of the rotating GPLRMF blades are analyzed with the aid of the methods of multi-scale and Runge–Kutta. Furthermore, comprehensive investigations into the effects of temperature, presetting angle, GPL distribution mode, foam distribution mode, volume fraction, porosity coefficient, rotational speed, damping coefficient, and excitation force on the nonlinear dynamics of rotating plates are performed through numerical analyses. [ABSTRACT FROM AUTHOR]

Frailty as a syndrome of physical decline in late life is associated with adverse health outcomes. Knee osteoarthritis (KOA) could contribute to frailty conditions. The objective of this study was to evaluate the impact of KOA on frailty risk in a Korean National Health and Nutrition Examination Survey (KNHANES) cohort. In this study (N, total = 11,910, age; 64.10 years old [63.94–64.27; mean 95% CI], sex (female, %); 6,752 (56.69)), KOA patients were defined as those with knee joint pain and grade 2 Kellgren–Lawrence (K–L) or more on plain radiographic images who were 40 years old or older in Korean population data of KNHANES. The frailty index was calculated using 46 items related to co-morbidities and laboratory parameters. The impact of KOA on frailty risk was evaluated with logistic regression analyses. The prevalence of KOA patients was 35.6% [95% CI 34.7–36.46]. In polytomous logistic regression, the relative risk ratio (RRR) of KOA was significantly increased in the pre-frail group (2.76, 95% CI 2.30–3.31) and the frail group (7.28, 95% CI 5.90–8.98). RRR of frailty was significantly increased in patients with K–L grade 3 (1.36, 95% CI 1.13–1.63) and K-L grade 4 (2.19, 95% CI 1.72–2.79). Older age, higher BMI, smoking status, alcohol intake, low-income status, higher WBC count, higher platelet count, higher serum creatinine level and low estimated GFR were significantly associated with increased frailty risk. High hemoglobin and regular walking habits were associated with decreased frailty risk in KOA patients. In this large observation population- based survey cohort, KOA is linked to an increased risk of frailty syndrome. We found a significant connection between KOA and frailty syndrome. These results show that we need to think about the overall health of people with KOA and give them special care to prevent frailty syndrome. [ABSTRACT FROM AUTHOR]

Purpose: Recently, reduced-dose whole-brain radiotherapy (WBRT) has been used to treat primary central nervous system lymphoma (PCNSL). However, whether reduced-dose WBRT is also an acceptable option for curative or salvage purposes has not yet been reported. We analyzed the clinical outcomes of patients with PCNSL who received radiotherapy for curative or salvage purposes and compared the clinical outcomes according to the WBRT dose. Methods: A total of 66 patients were divided into two groups: those treated with 30 Gy (2 Gy per fraction) or less WBRT (low-dose WBRT, n = 34) and those treated with more than 30 Gy WBRT (high-dose WBRT, n = 32). The median WBRT dose was 25.2 and 49.6 Gy in low-dose and high-dose WBRT groups, respectively. The median total radiotherapy dose, including the boost dose, was 50 Gy (range, 36.0-55.8 Gy). Results: The 3-year overall survival and progression-free survival were 77.8% and 29.8%, respectively. Intracranial relapse occurred in 31 patients (47.0%) at a median of 27 months after RT. Overall survival and progression-free survival did not differ between the two groups. The 3-year intracranial disease control rate did not differ between the two groups (35.2% vs. 41.6%, p = 0.300). Grade 3 or higher neurological toxicities were observed in six patients, of whom five were in the high-dose WBRT group. Conclusion: Reduced-dose WBRT in curative and salvage treatments for PCNSL had no significant negative effect on the intracranial disease control rate or survival. Therefore, without impaired efficacy, use of reduced-dose WBRT appears promising for reduction of neurotoxicity. [ABSTRACT FROM AUTHOR]

Quaternary amino acids are one of the essential building blocks and precursors of medicinally important compounds. Various synthetic strategies towards their synthesis have been reported. On the other hand, developing core-structure-oriented cross-dehydrogenative coupling (CDC) reactions, is a largely unsolved problem. Herein, we describe a copper-catalyzed regiodivergent electrochemical CDC reaction of Schiff bases and commercially available hydroquinones to obtain three classes of chiral quaternary amino acid derivatives for the efficient assembly of complex scaffolds with excellent stereocontrol. The electrochemical anodic oxidation process with slow releasing of quinones serves as an internal syringe pump and provides high levels of reaction efficiency and enantiomeric control. The utility of this strategy is highlighted through the synthetic utility in the asymmetric total synthesis of (-)-fumimycin. Quaternary amino acids are important building blocks and precursors of medicinal compounds. Here, the authors describe a copper-catalyzed regiodivergent electrochemical core structure-oriented crossdehydrogenative coupling reaction of Schiff bases and commercially available hydroquinones to obtain three classes of chiral quaternary amino acid derivatives [ABSTRACT FROM AUTHOR]

Background: Restoration of HBV-specific T cell immunity is a promising approach for the functional cure of chronic Hepatitis B (CHB), necessitating the development of valid assays to boost and monitor HBV-specific T cell responses in patients with CHB. Methods: We analyzed hepatitis B virus (HBV) core- and envelope (env)-specific T cell responses using in vitro expanded peripheral blood mononuclear cells (PBMCs) from patients with CHB exhibiting different immunological phases, including immune tolerance (IT), immune activation (IA), inactive carrier (IC), and HBeAg-negative hepatitis (ENEG). Additionally, we evaluated the effects of metabolic interventions, including mitochondria-targeted antioxidants (MTA), polyphenolic compounds, and ACAT inhibitors (iACAT), on HBV-specific T-cell functionality. Results: We found that HBV core- and env-specific T cell responses were finely coordinated and more profound in IC and ENEG than in the IT and IA stages. HBV env-specific T cells were more dysfunctional but prone to respond to metabolic interventions using MTA, iACAT, and polyphenolic compounds than HBV core-specific T-cells. The responsiveness of HBV env-specific T cells to metabolic interventions can be predicted by the eosinophil (EO) count and the coefficient of variation of red blood cell distribution width (RDW-CV). Conclusion: These findings may provide valuable information for metabolically invigorating HBV-specific T-cells to treat CHB. [ABSTRACT FROM AUTHOR]

CD8 + T cells are essential for long-lasting HIV-1 control and have been harnessed to develop therapeutic and preventive approaches for people living with HIV-1 (PLWH). HIV-1 infection induces marked metabolic alterations. However, it is unclear whether these changes affect the anti-HIV function of CD8 + T cells. Here, we show that PLWH exhibit higher levels of plasma glutamate than healthy controls. In PLWH, glutamate levels positively correlate with HIV-1 reservoir and negatively correlate with the anti-HIV function of CD8 + T cells. Single-cell metabolic modeling reveals glutamate metabolism is surprisingly robust in virtual memory CD8 + T cells (TVM). We further confirmed that glutamate inhibits TVM cells function via the mTORC1 pathway in vitro. Our findings reveal an association between metabolic plasticity and CD8 + T cell-mediated HIV control, suggesting that glutamate metabolism can be exploited as a therapeutic target for the reversion of anti-HIV CD8 + T cell function in PLWH. Analysis of plasma metabolites in virologically suppressed individuals infected with HIV-1 and controls, reveals an association between metabolic plasticity and CD8 + T cell-mediated HIV infection control. [ABSTRACT FROM AUTHOR]

Convolutional neural networks (CNNs) have been successful for tasks such as object detection; however, they involve time-consuming processes. Therefore, there are difficulties in applying these CNNs to autonomous driving. Moreover, most autonomous driving technologies require both object detection and distance prediction. However, CNNs that predict distance involve more time-consuming processes than object detection models. In addition, the applications for autonomous driving require object detection and distance prediction accuracy. This paper proposes an end-to-end trainable CNN that can meet these requirements. The proposed CNN accurately implements object detection and distance prediction in real time using stereo images. We demonstrate the superiority of the proposed CNN using stereo images from the KITTI 3D object detection dataset. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) spheroid culture has applications in many fields as spheroids closely recapitulate physiological conditions. However, spheroid culture and maintenance are time-consuming and unsuitable for urgent situations; therefore, appropriate cryopreservation methods for spheroids are required for their use in an on-demand and ready-to-use manner. We hypothesized that the feasibility of a ready-to-use system relies on diffusion of the preservation solution within spheroids; we thus evaluated the effects of spheroid-forming parameters, such as cell number and culture period, on spheroid viability and functionality. Long-term spheroid culture for seven days interfered with penetration of the cryopreservation solution as it caused cell condensation and extracellular matrix (ECM) secretion, as well as low viability and migratory activity upon replating after storage. However, ready-to-use spheroids, which were cultured for one day and then cryopreserved, showed viability and migration similar to those of non-cryopreserved spheroids, confirming that a short incubation period was suitable for this system. The chondrocyte-based ready-to-use spheroid system designed in this study can be easily applied to regenerative medicine applications that require a large number of cells in the future and can provide information for applying the ready-to-use spheroid system to various cell types. [ABSTRACT FROM AUTHOR]

Selonsertib is a first-in-class apoptosis signal-regulating kinase 1 (ASK1) inhibitor in clinical trials for treating NASH and diabetic kidney disease due to its anti-inflammatory and anti-fibrotic activities. In the present study, we investigated the anti-neuroinflammatory effects and brain pharmacokinetic properties of selonsertib. It inhibited inflammatory cytokines and NO production by suppressing phosphorylated ASK1 in the LPS-stimulated microglial cell line, BV2 cells. Consistent with the in vitro results, selonsertib attenuated plasma and brain TNF-α levels in the LPS-induced murine neuroinflammation model. In vitro and in vivo pharmacokinetic studies of selonsertib were conducted in support of central nervous system (CNS) drug discovery. In both Caco-2 and MDR-MDCK cells, selonsertib exhibited a high efflux ratio, showing that it is a P-gp substrate. Selonsertib was rapidly and effectively absorbed into the systemic circulation after oral treatment, with a Tmax of 0.5 h and oral bioavailability of 74%. In comparison with high systemic exposure with Cmax of 16.2 µg/ml and AUC of 64 µg·h/mL following oral dosing of 10 mg/kg, the brain disposition of selonsertib was limited, with Cmax of 0.08 µg/g and Kp value of 0.004. This study demonstrates that selonsertib can be a therapeutic agent for neuroinflammatory diseases. [ABSTRACT FROM AUTHOR]

Background and aims: Natural killer (NK) cells are critical innate effectors that respond to viral infections and contribute to immunopathology. Here, we aimed to investigate the role of NK cells in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) and elucidate the underlying mechanism by examining their phenotypic and functional profiles. Methods: We included patients with HBV-ACLF (n = 37) and chronic hepatitis B (n = 19), and healthy controls (n = 13) in our study. We examined the phenotype and function of different subsets of peripheral NK cells using flow cytometry and RNA-sequencing analysis, and screened liver NK cells using immunohistochemistry. We detected inflammatory cytokines using a Luminex assay. In addition, we analyzed the relationships between these parameters and disease severity. Results: Peripheral NK cells were decreased and characterized by high expression of caspase-3, Ki67, CXCR3, NKG2D, NKp46, CD107a, and GM-CSF, and typified by higher cell migration and immune response by RNA-sequencing analysis in patients with HBV-ACLF than in those with chronic hepatitis B. Accumulations of CXCL-10 and NK cells were found in the liver, and excessive production of CXCL-10 in the peripheral blood contributed to the apoptosis of NK cells in vitro. The decrease in NK cells was associated with the level of HBV DNA and disease severity and had good prognostic performance in predicting the outcome of patients with HBV-ACLF through AUROC analysis. Conclusion: NK cells were significantly decreased and showed dysfunction of phenotypic and functional profiles across distinct subsets in the peripheral blood of patients with ACLF. Crosstalk between CXCL-10 and NK cells may mediate the unbalanced distribution of NK cells. Understanding the dysfunction and decrease in NK cells may provide new insights into ACLF pathogenesis. [ABSTRACT FROM AUTHOR]

To obtain a comprehensive scenario of T cell profiles and synergistic immune responses, we performed single-cell RNA sequencing (scRNA-seq) on the peripheral T cells of 14 individuals with chronic human immunodeficiency virus 1 (HIV-1) infection, including nine treatment-naive (TP) and eight antiretroviral therapy (ART) participants (of whom three were paired with TP cases), and compared the results with four healthy donors (HD). Through analyzing the transcriptional profiles of CD4+ and CD8+ T cells, coupled with assembled T cell receptor sequences, we observed the significant loss of naive T cells, prolonged inflammation, and increased response to interferon-α in TP individuals, which could be partially restored by ART. Interestingly, we revealed that CD4+ and CD8+ Effector-GNLY clusters were expanded in TP cases, and persistently increased in ART individuals where they were typically correlated with poor immune restoration. This transcriptional dataset enables a deeper understanding of the pathogenesis of HIV-1 infection and is also a rich resource for developing novel immune targeted therapeutic strategies. [ABSTRACT FROM AUTHOR]

The use of fossil fuels by anthropogenic activities causes ocean acidification and warming, and these changes in the marine environment can negatively affect the metabolism, growth, and survival of fish. In the present study, we evaluated the ability of olive flounder Paralichthys olivaceus to cope with future marine environmental changes by investigating the oxidative stress (cortisol, HSP70), antioxidant enzyme (superoxide dismutase; SOD, catalase; CAT) activity, and apoptosis (caspase-3) after exposure to control conditions (20 °C and pH 8.1), warming (30 °C) and acidification (pH 7.5) conditions, and a combined environment (30 °C and pH 7.5) for 28 days. Under warming conditions, increased oxidative stress, activity of antioxidant enzymes, and apoptosis were observed. Acidifying conditions showed negative effects at the beginning of exposure, but these effects were offset over time. Even in a combined environment of acidification and warming, negative effects were seen only at the beginning of exposure and were not sustained. In conclusion, the effects of acidification on oxidative stress, antioxidant response, and apoptosis in P. olivaceus did not exceed the effects of warming. These results suggest that P. olivaceus can cope with the predicted future acidifying environment. [ABSTRACT FROM AUTHOR]

Background and aims: Hepatitis E virus-related acute liver failure (HEV-ALF) rapidly worsens and has a high mortality. However, no simple and specific parameters for predicting short-term mortality are available. Methods: A derivation cohort including 97 patients with HEV-ALF and another validation cohort were enrolled. Laboratory and clinical parameters were recorded. Platelet count, model for end-stage liver disease (MELD), and King's College criteria (KCC) were separately used for predicting mortality, and the levels of cytokines associated with systemic inflammation, platelet production, and platelet activation were measured. Results: Platelet counts were significantly lower in patients with HEV-ALF, and nonsurvivors had lower platelet counts than survivors (p < 0.001). Platelet count was an independent risk factor for predicting 28- and 90-day mortality in patients with HEV-ALF. The AUROC of the baseline platelet count (cutoff, 131 × 109/L) for 28- and 90-day mortality was 0.786 and 0.764, respectively, which was superior to KCC score (p < 0.05) and comparable to MELD score. Furthermore, the platelet counts at 3 and 7 days after ALF diagnosis had similar predictive power for 28- and 90-day mortality. The value of platelet count was also confirmed in the validation cohort. Moreover, platelet-associated cytokines, including thrombopoietin, platelet factor 4, and P-selectin, were increased in patients with HEV-ALF. Conclusions: Decreased platelet count is a simple and reliable indicator for predicting 28- and 90-day mortality in patients with HEV-ALF. Overactivation of platelets is an important risk for platelet counts decrease, and treatment aiming at platelet count recovery may be considered. [ABSTRACT FROM AUTHOR]

In vitro-in vivo correlation (IVIVC) analysis reveals a relationship between in vitro release and in vivo pharmacokinetic response of the drug of interest. Sandostatin LAR Depot (SLD) for endocrine tumors and acromegaly is a sustained-release formulation of octreotide, a cyclic oligomer of 8 amino acids, which prolongs therapeutic efficacy and enhances medication compliance of octreotide. Since the efficacy of SLD is dependent on the pharmacokinetic characteristics of octreotide released from a biodegradable matrix polymer, poly(lactide-co-glycolide)-glucose, of SLD, the IVIVC of SLD is critical for predicting an in vivo behavior of the octreotide. In this study, in vitro release of octreotide from SLD was investigated using the release test media each containing 0.02% or 0.5% surfactant and having different pH values of 7.4 and 5.5. In vivo pharmacokinetic profiles of SLD were determined by LC–MS/MS analysis of the systemic blood concentration of octreotide after the SLD injection to rodents. In IVIVC analysis, the Weibull model was adopted as a drug release model for biodegradable microsphere formulation. The IVIVC analyses revealed the in vitro release test condition of SLD with the highest IVIV correlation coefficient. By applying the in vitro release data to the model derived from the IVIVC analysis, pharmacokinetic parameters of SLD could be predicted with the prediction error of ± 10 ~ 15%. IVIVC analysis and pharmacokinetic prediction model of SLD in our study can be an efficient tool for the development of long-acting pharmaceutical dosage forms. [ABSTRACT FROM AUTHOR]

The electrospray process has been extensively applied in various fields, including energy, display, sensor, and biomedical engineering owing to its ability to generate of functional micro/nanoparticles. Although the mode of the electrospray process has a significant impact on the quality of micro/nano particles, observing and discriminating the mode of electrospray during the process has not received adequate attention. This study develops a simple automated method to discriminate the mode of the electrospray process based on the current signal using a deep convolutional neural network (CNN) and class activation map (CAM). The solution flow rate and applied voltage are selected as experimental variables, and the electrospray process is classified into three modes: dripping, pulsating, and cone-jet. The current signal through the collector is measured to detect the deposition of electrospray droplets on the collector. The 1D CNN model is trained using frequency data converted from the current data. The model exhibits excellent performance with an accuracy of 96.30%. Adoption of the CAM configuration enables the model to provide a discriminative cue for each mode and elucidate the decision-making process of the CNN model. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is an aggressive malignant tumor of the digestive system, with high morbidity rates. We previously demonstrated that miR-17-5p can modify tumorigenesis in GC. In addition, other studies have shown that circRNAs can regulate GC progression by sponging various miRNAs. However, the association between circRNAs and miR-17-5p in GC has not yet been explored. Hence, this study aimed to explore the possible interactions between various circRNAs and miR-17-5p using a dual-luciferase assay. CCK-8 was used to determine cell viability, and a Transwell assay was used to measure cell invasion and migration. Gene expression was assessed using quantitative reverse transcription PCR (RT-qPCR), and exosomes were identified using transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Annexin V/PI staining was also used to detect cell apoptosis. These investigations collectively revealed that miR-17-5p is a target of the circRNA hsa_circ_0017252 and hsa_circ_0017252 is significantly downregulated in GC tissues. In addition, the overexpression of hsa_circ_0017252 inhibited GC cell migration by sponging of miR-17-5p, and GC cell-secreted exosomal hsa_circ_0017252 effectively inhibited macrophage M2-like polarization, which in turn suppressed GC cell invasion. Notably, exosomes containing hsa_circ_0017252 also suppressed GC tumor growth in vivo. Thus, our data suggest that the overexpression of hsa_circ_0017252 suppresses GC malignancy by sponging miR-17-5p. In addition, exosomal hsa_circ_0017252 excreted from GC cells attenuated GC progression by suppressing macrophage M2-like polarization. These findings improve our basic understanding of GC and open a novel avenue for developing more effective GC treatments. [ABSTRACT FROM AUTHOR]

This letter to the editor describes a case of Guillain-Barré syndrome (GBS) with blurry vision as the initial symptom. The patient, a 38-year-old man, presented with visual blurring, difficulty breathing, and slurred speech. The neurological examination showed mydriasis and nonreactive pupils, dysarthria, bilateral facial paralysis, and areflexia. The patient was diagnosed with GBS and received plasma exchange treatment, which resulted in improvement. The authors discuss the atypical characteristics of this case and the possible underlying mechanism. They emphasize the importance of accurate diagnosis and early treatment for GBS. [Extracted from the article]

Accurate prediction of the enemy's combat missions in combat deductions is helpful to improve the quality of command decision. Intelligent combat mission prediction method is a technical means to adapt to the fast-paced complex modern war, and is an important part of intelligent command decision technology. In this paper, based on the solution of the problems of combat mission prediction, it is modeled as a multi-instance learning (MIL) problem according to the characteristics of the problem. To effectively integrate expert knowledge and combat deduction data, a MIL model called multi-instance genetic fuzzy system (MIGFS) is designed and implemented based on the genetic fuzzy systems (GFSs). The model is composed of multiple genetic sub-fuzzy systems (sub-FSs). By means of multi-tasking genetic fuzzy systems (MTGFSs) algorithm, multiple sub-FSs have been trained separately to solve the problem of excessive time consuming and high cost because of synchronously training too many sub-FSs. Furthermore, to complete the integration of instance prediction to bag prediction, the weighted average is used instead of the traditional max function, and the mutation problem of taking the max function is solved by learning the weight parameters of the sub-FSs. A more continuous and smooth result integration method is implemented, and the prediction accuracy is improved. Finally, a demonstrative experimental case of wargaming has been taken to illustrate that MIGFS can successfully apply MIL to combat deductions with a small amount of data, and effectively solve the problems of combat mission prediction, which demonstrates the feasibility and practicability of the proposed MIGFS model. This method can well model the problems of combat mission prediction into MIL problems, and solve the problems well, which is a good start. [ABSTRACT FROM AUTHOR]

Polymorphic genes with immune functions, namely those of the human leukocyte antigen (HLA) system, have been implicated in sarcoidosis pathogenesis. As HLA polymorphisms in sarcoidosis have not been yet investigated in the Korean population, we used next-generation sequencing (NGS), allowing detailed characterization of HLA alleles to investigate the role of HLA variation in Korean sarcoidosis patients. We enrolled 103 patients diagnosed by the ATS/ERS/WASOG guidelines at Asan Medical Centre, Seoul, Korea. Among those, genotyping of 7 HLA loci (HLA-A, -B, -C, -DQA1, -DQB1, -DRB1, -DPB1) was performed using Omixon Holotype™ kit and HLATwin software™. HLA allele frequencies were compared with frequency data on healthy Koreans from the allelic frequency databases, and 4-digit characteristics of HLA genotyping were used. Associations were assessed by two-tailed Fischer's exact test with correction for multiple comparisons. Variants previously associated with sarcoidosis risk (HLA-C*03:04, HLA-DRB1*12:01, HLA-DRB1*14:54) and a known protective variant HLA-DPB1*04:01, were associated with sarcoidosis in Koreans. Further, we suggest new HLA variants associated with sarcoidosis risk (e.g., HLA-DQA1*05:08) and novel protective variants HLA-DQB1*03:02 and HLA-DQA1*01:02 in Koreans. This first study of HLA variation in Korean patients with sarcoidosis by precise genotyping methodology reports data that could serve future meta-analyses on HLA variation's role in sarcoidosis. [ABSTRACT FROM AUTHOR]

We present one of the simplest nanoscale systems for a high-performance refractive index (RI) sensor. We investigate analytically and numerically the transmission response of the system, which consists of the rectangular nanocavity coupled to metal–insulator–metal (MIM) nanowaveguide according to its structural parameter and resonance mode of the cavity. From the theoretical results, we find that a square cavity is able to support a hybrid resonant mode of two resonance modes with the opposite symmetry to each other. By comparison with single modes, the hybrid mode enables us to obtain ultra-low transmission response with high quality factor through the system at the resonance and it gives us possibility for realization of RI sensor with both high sensitivity and figure of merit (FoM) based on the system. And the simulation results confirm the theoretical analysis. This nanoscale sensor has a sensitivity as high as 1400nm/RIU and a FoM as large as 3000. The suggested sensor can be widely used as a high-sensitive, highly integrated sensor. [ABSTRACT FROM AUTHOR]

Background: The left-sided and right-sided colon cancer (LCCs and RCCs, respectively) have unique molecular features and clinical heterogeneity. This study aimed to identify the characteristics of immune cell infiltration (ICI) subtypes for evaluating prognosis and therapeutic benefits. Methods: The independent gene datasets, corresponding somatic mutation and clinical information were collected from The Cancer Genome Atlas and Gene Expression Omnibus. The ICI contents were evaluated by "ESTIMATE" and "CIBERSORT." We performed two computational algorithms to identify the ICI landscape related to prognosis and found the unique infiltration characteristics. Next, principal component analysis was conducted to construct ICI score based on three ICI patterns. We analyzed the correlation between ICI score and tumor mutation burden (TMB), and stratified patients into prognostic-related high- and low- ICI score groups (HSG and LSG, respectively). The role of ICI scores in the prediction of therapeutic benefits was investigated by "pRRophetic" and verified by Immunophenoscores (IPS) (TCIA database) and an independent immunotherapy cohort (IMvigor210). The key genes were preliminary screened by weighted gene co-expression network analysis based on ICI scores. And they were further identified at various levels, including single cell, protein and immunotherapy response. The predictive ability of ICI score for prognosis was also verified in IMvigor210 cohort. Results: The ICI features with a better prognosis were marked by high plasma cells, dendritic cells and mast cells, low memory CD4+ T cells, M0 macrophages, M1 macrophages, as well as M2 macrophages. A high ICI score was characterized by an increased TMB and genomic instability related signaling pathways. The prognosis, sensitivities of targeted inhibitors and immunotherapy, IPS and expression of immune checkpoints were significantly different in HSG and LSG. The genes identified by ICI scores and various levels included CA2 and TSPAN1. Conclusion: The identification of ICI subtypes and ICI scores will help gain insights into the heterogeneity in LCC and RCC, and identify patients probably benefiting from treatments. ICI scores and the key genes could serve as an effective biomarker to predict prognosis and the sensitivity of immunotherapy. [ABSTRACT FROM AUTHOR]

The revised definition of acute exacerbation (AE) in idiopathic pulmonary fibrosis (IPF) was proposed in 2016, but changes in the incidence and impact on prognosis of the re-defined AE compared to those of the previous definition remain unclear. Clinical data of 445 patients with IPF (biopsy proven cases: 165) were retrospectively reviewed. The median follow-up period was 36.8 months and 17.5% (n = 78) experienced AE more than once. The 1- and 3-year incidence rates of AE were 6.7% and 16.6%, respectively, and idiopathic AE accounted for 82.1% of AE. Older age, lower diffusing capacity of the lung for carbon monoxide and 10% relative decline in forced vital capacity for 6 months were independently associated with AE. The in-hospital mortality rate following AE was 29.5%. In the multivariable analysis, AE was independently associated with poor prognosis in patients with IPF. Compared to the old definition, the revised definition relatively increased the incidence of AE by 20.4% and decreased the in-hospital mortality by 10.1%. Our results suggest that the revised definition affects approximately 20% increase in the incidences and 10% reduction in the in-hospital mortality of AE defined by the past definition. [ABSTRACT FROM AUTHOR]

Background: Comprehensive management of type 2 diabetes mellitus (T2DM) patients has a low control rate, and there is a lack of prospective studies involving clinical pharmacists in outpatient management of patients with T2DM. This study was designed to investigate the effectiveness of pharmacists participating in the comprehensive management of T2DM patients in the form of building doctor-pharmacist joint pharmacy clinic in the National Metabolic Management Center (MMC). Methods: A total of 204 patients with type 2 diabetes mellitus were enrolled and randomly divided into control group and intervention group. During the 3-month study period, both groups received standardized MMC diagnosis and treatment, and clinical pharmacists provided pharmaceutical care for the intervention group. Observation indicators include drug compliance, fasting blood glucose (FPG), glycosylated hemoglobin (HbA1c), blood pressure, blood lipid, and other comprehensive management indicators. Results: The baseline characteristics of the two groups were similar, and there was no significant difference (p > 0.05). After 3 months of follow-up, drug compliance, HbA1c, FPG, low-density cholesterol (LDL-c), and diastolic blood pressure in the intervention group were more significantly improved compared with those in the control group (p < 0.05). There was no significant difference in the incidence of adverse events between the two groups (p = 0.825). Conclusion: Clinical pharmacist can improve the comprehensive management of diabetes mellitus by building doctor-pharmacist joint pharmacy clinic for outpatients. [ABSTRACT FROM AUTHOR]

Interstitial lung disease associated with primary Sjögren's syndrome (SJS-ILD) has a variable clinical course. We aimed to investigate the role of blood biomarkers in predicting prognosis for SJS-ILD. Clinical data of 46 SJS-ILD patients were retrospectively reviewed. Plasma biomarker levels, including Krebs von den Lungen-6 (KL-6), CC chemokine ligand 18 (CCL18), chitinase-3-like-1 (YKL-40), interleukin-4 receptor alpha (IL-4Ra), and matrix metalloproteinase-7 (MMP-7) were measured using the multiplex Luminex assays (R&D Systems, Minneapolis, USA). The median follow-up period was 69.0 months. The mean age of the patients was 59.4 years; 17.4% were men. The KL-6 level was significantly higher in non-survivors (n = 12; 119.6 vs. 59.5 pg/mL, P = 0.037) than survivors (n = 34), while the levels of the other biomarkers did not differ. Receiver operating characteristic analysis indicated that KL-6 shows the best performance for predicting survival (area under the curve = 0.705, P = 0.037; best cut-off value = 53.5 pg/mL). Multivariable Cox analysis that was adjusted by age and diffusing capacity for carbon monoxide suggested a high KL-6 level (> 53.5 pg/mL) as an independent prognostic factor for survival (hazard ratio = 5.939, 95% confidence interval 1.312–26.881, P = 0.021). Our results suggest that blood KL-6 might be a useful in predicting the prognosis for patients with SJS-ILD. [ABSTRACT FROM AUTHOR]

Acute exacerbation (AE) significantly affects the prognosis of patients with interstitial lung disease (ILD). This study aimed to investigate the best prognostic biomarker for patients with AE-ILD. Clinical data obtained during hospitalization were retrospectively analyzed for 96 patients with AE-ILD at three tertiary hospitals. The mean age of all subjects was 70.1 years; the percentage of males was 66.7%. Idiopathic pulmonary fibrosis accounted for 60.4% of the cases. During follow-up (median: 88 days), in-hospital mortality was 24%. Non-survivors had higher lactate dehydrogenase and C-reactive protein (CRP) levels, lower ratio of partial pressure of oxygen to the fraction of inspiratory oxygen (P/F ratio), and higher relative change in Krebs von den Lungen-6 (KL-6) levels over 1 week after hospitalization than survivors. In multivariable analysis adjusted by age, the 1-week change in KL-6—along with baseline P/F ratio and CRP levels—was an independent prognostic factor for in-hospital mortality (odds ratio 1.094, P = 0.025). Patients with remarkable increase in KL-6 (≥ 10%) showed significantly worse survival (in-hospital mortality: 63.2 vs. 6.1%) than those without. In addition to baseline CRP and P/F ratio, the relative changes in KL-6 over 1 week after hospitalization might be useful for predicting in-hospital mortality in patients with AE-ILD. [ABSTRACT FROM AUTHOR]

Despite that asymmetric stereodivergent synthesis has experienced great success to provide unusual processes for the creation of chirality complexity, concepts appliable to asymmetric stereodivergent catalysis are still limited. The dependence on the unusual capacity of each catalyst to precisely control the reactive site planar in the region poses unparalleled constraints on this field. Here, we first demonstrate that the chiral Cu-allenylidene species can participate in the stereodivergent propargylic alkylation of enals, in concert with chiral N-heterocyclic carbenes (NHCs). Thus, all four stereoisomers were obtained with excellent enantioselectivity and diastereoselectivity (up to >99% e.e. and >95:5 d.r.) from the same starting materials by simply altering chiral Cu-Pybox complex and NHC combinations. The rich chemistry workable in the products enables the structurally diverse synthesis of chiral functional molecules and holds great potential in alkaloid synthesis, as showcased by the preparation of the key building block to access (-)-perophoramidine. The ability to construct multiple stereocenters in a modular fashion is an important goal of synthetic organic chemistry. Here the authors present a method to construct oxindoles in four stereoisomers with high enantioselectivity and diastereoselectivity from the same starting materials by using cooperative copper- and organocatalysis. [ABSTRACT FROM AUTHOR]

Most marine mollusks exhibit osmoregulatory mechanisms to cope with hypo- or hyperosmotic stress. In the present study, we elucidated the effects of exposure to hyposmotic and hyperosmotic stress on bay scallop Argopecten irradians. The Na+, K+, and Cl− ions of bay scallop hemolymph traversed in a similar direction as that of surrounding salinity. Moreover, the gill Na+/K+-ATPase was affected by changes in salinity. We further evaluated the heat shock protein (HSP)70 mRNA expression in the digestive diverticula and glucose levels in the hemolymph of bay scallops. Sudden changes in salinity were found to affect the HSP70 mRNA expression and glucose levels. In 55% salt water (SW) at 48–72 h, HSP70 mRNA expression and glucose levels were reduced compared to the control. HSP70 mRNA was present in the cells of digestive diverticula tissue at higher levels in 120% SW at 72 h than in the control. A TUNEL assay revealed that salinity changes increased cell apoptosis. Thus, exposure to 55% SW or more for more than 24 h may threaten the survival of marine mollusks. [ABSTRACT FROM AUTHOR]

Purpose: The standard treatment of stage II–III rectal cancer is preoperative chemoradiotherapy (CRT), followed by total mesorectal excision (TME). However, the rate of metastasis is still high following this treatment. Therefore, several adjuvant chemotherapy studies have been conducted on reducing subsequent metastases and increasing survival, although there are still no definite conclusions. Methods: We searched for published prospective randomized controlled trials comparing adjuvant chemotherapy regimens following standard preoperative CRT and curative surgery in stage II–III rectal cancer. We systematically searched Medline, Embase, and the Cochrane Library for relevant trials done from January 2004 to January 2021. Review Manager (RevMan, version 5.3) was used to analyze the data. Results: We initially searched 1955 studies. We screened and carefully selected four randomized controlled trials with 2897 patients. Compared to the 5-FU-based regimen group, the oxaliplatin-added regimen group attained a higher 3-year locoregional control rate (relative risk [RR] of 0.64, 95% confidence interval [CI], 0.48–0.86; p = 0.003) and 3-year distant metastasis control rate (RR of 0.82, 95% CI, 0.71–0.95; p = 0.007). The oxaliplatin-added regimen group had significantly increased 3-year disease-free survival with a hazard ratio (HR) of 0.85 (95% CI: 0.74–0.97, p = 0.020), but not overall survival (p = 0.740). Grade 3 or higher acute toxicity rates did not differ between the two groups (p = 0.190). Conclusion: The addition of oxaliplatin to adjuvant therapy for stage II–III rectal cancer following preoperative CRT and TME may increase disease-free survival without significant increases in toxicity, but not overall survival. [ABSTRACT FROM AUTHOR]

Despite encouraging preclinical data, therapies to reduce ARDS mortality remains a globally unmet need, including during the COVID-19 pandemic. We previously identified extracellular nicotinamide phosphoribosyltransferase (eNAMPT) as a novel damage-associated molecular pattern protein (DAMP) via TLR4 ligation which regulates inflammatory cascade activation. eNAMPT is tightly linked to human ARDS by biomarker and genotyping studies in ARDS subjects. We now hypothesize that an eNAMPT-neutralizing mAb will significantly reduce the severity of ARDS lung inflammatory lung injury in diverse preclinical rat and porcine models. Sprague Dawley rats received eNAMPT mAb intravenously following exposure to intratracheal lipopolysaccharide (LPS) or to a traumatic blast (125 kPa) but prior to initiation of ventilator-induced lung injury (VILI) (4 h). Yucatan minipigs received intravenous eNAMPT mAb 2 h after initiation of septic shock and VILI (12 h). Each rat/porcine ARDS/VILI model was strongly associated with evidence of severe inflammatory lung injury with NFkB pathway activation and marked dysregulation of the Akt/mTORC2 signaling pathway. eNAMPT neutralization dramatically reduced inflammatory indices and the severity of lung injury in each rat/porcine ARDS/VILI model (~ 50% reduction) including reduction in serum lactate, and plasma levels of eNAMPT, IL-6, TNFα and Ang-2. The eNAMPT mAb further rectified NFkB pathway activation and preserved the Akt/mTORC2 signaling pathway. These results strongly support targeting the eNAMPT/TLR4 inflammatory pathway as a potential ARDS strategy to reduce inflammatory lung injury and ARDS mortality. [ABSTRACT FROM AUTHOR]

Asian sand dust (ASD), which mainly originates in China and Mongolia in the spring and blows into Korea, can exacerbate respiratory and immunological diseases. This study aims to observe effects of co-exposure to ASD on ovalbumin (OVA)-induced asthmatic lung inflammation and of treatment with a phosphodiesterase 7 (PDE7) inhibitor in a mouse model. The challenge with OVA increased airway hyperresponsiveness (AHR) and inflammatory cell infiltration into the lung tissue. Interleukin (IL)-13, tumor necrosis factor-alpha, monocyte-protein-1, mucin, and antigen-specific IgE and IgG1 production increased in mouse serum. The co-exposure of ASD significantly exacerbated these effects in this asthma model. Notably, the administration of a PDE7 inhibitor, BRL-50481 (BRL), significantly reduced AHR, infiltration of inflammatory cells into the lungs, and the levels of type 2 T helper cell-related cytokines, antigen-specific immunoglobulins, and mucin. Thus, the administration of BRL ameliorated OVA-induced allergic asthmatic responses exacerbated by co-exposure to ASD. This study suggests that PDE7 inhibition can be a therapeutic strategy for inflammatory lung diseases and asthma via the regulation of T lymphocytes and reduction of IL-13, and, consequently, mucin production. [ABSTRACT FROM AUTHOR]

Neuroendocrine (NE) prostate cancer (NEPC) is a lethal subtype of castration-resistant prostate cancer (PCa) arising either de novo or from transdifferentiated prostate adenocarcinoma following androgen deprivation therapy (ADT). Extensive computational analysis has identified a high degree of association between the long noncoding RNA (lncRNA) H19 and NEPC, with the longest isoform highly expressed in NEPC. H19 regulates PCa lineage plasticity by driving a bidirectional cell identity of NE phenotype (H19 overexpression) or luminal phenotype (H19 knockdown). It contributes to treatment resistance, with the knockdown of H19 re-sensitizing PCa to ADT. It is also essential for the proliferation and invasion of NEPC. H19 levels are negatively regulated by androgen signaling via androgen receptor (AR). When androgen is absent SOX2 levels increase, driving H19 transcription and facilitating transdifferentiation. H19 facilitates the PRC2 complex in regulating methylation changes at H3K27me3/H3K4me3 histone sites of AR-driven and NEPC-related genes. Additionally, this lncRNA induces alterations in genome-wide DNA methylation on CpG sites, further regulating genes associated with the NEPC phenotype. Our clinical data identify H19 as a candidate diagnostic marker and predictive marker of NEPC with elevated H19 levels associated with an increased probability of biochemical recurrence and metastatic disease in patients receiving ADT. Here we report H19 as an early upstream regulator of cell fate, plasticity, and treatment resistance in NEPC that can reverse/transform cells to a treatable form of PCa once therapeutically deactivated. Elevated expression of long noncoding RNA H19 is seen in clinical samples of neuroendocrine prostate cancer (PCa). Here the authors show H19 promotes plasticity from luminal to neuroendocrine by epigenetic reprogramming. [ABSTRACT FROM AUTHOR]

Sarcoidosis is a systemic granulomatous disorder of unknown cause involving multiple organs. Its clinical presentation and prognosis vary among races. We identified the clinical characteristics and outcomes of Korean patients with sarcoidosis. Clinical data of 367 Korean patients with biopsy-proven sarcoidosis diagnosed in 2001–2017 were retrospectively analyzed. Treatment responses included improvement, stability, or progression based on changes in pulmonary sarcoidosis on chest images. The mean age was 47.4 years, and 67.3% of patients were women. The median follow-up period was 80 months. The highest prevalence was observed in individuals aged 50–59 years (30–39 years in men, 50–59 years in women), and the number of diagnoses showed an increasing trend. Lung involvement was the most common (93.5%), followed by the skin, eyes, and extrathoracic lymph nodes. Among patients with lung involvement and a follow-up period of ≥ 3 months, 66.8%, 31.0%, and 2.2% showed improvement, stability, and progression, respectively. Eleven patients (2.9%) died, and the 5-year survival rate was 99%. The number of diagnosed cases showed an increasing trend, and the mean age at diagnosis was increased compared with that in previous reports. Organ involvement was similar to that of Westerners, although the prognosis appeared better. [ABSTRACT FROM AUTHOR]