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Purpose: Use of cyclin-dependent kinase 4/6 inhibitors improved survival outcome of hormone receptor (HR) positive metastatic breast cancer (MBC) patients, including Asian population. However, Asian real-world data of palbociclib is limited. We analyzed the real-world clinical practice patterns and outcome in HR-positive, MBC Asian patients treated with palbociclib., Materials and Methods: Between April 2017 to November 2019, 169 HR-positive, human epidermal growth factor-2-negative MBC patients treated with letrozole or fulvestrant plus palbocilib were enrolled from eight institutions. Survival outcome (progression-free survival [PFS]), treatment response and toxicity profiles were analyzed., Results: Median age of letrozole plus palbociclib (145 patients, 85.8%) and fulvestrant plus palbociclib (24 patients, 14.2%) was 58 and 53.5 years, with median follow-up duration of 14.63 months (range 0.2 to 33.9 months). Median PFS (mPFS) of letrozole plus palbociclib and fulvestrant plus palbociclib was 25.6 (95% confidence interval [CI], 19.1 to not reached) and 6.37 months (95% CI, 5.33 to not reached), comparable to previous phase 3 trials. In letrozole plus palbociclib arm, luminal A (hazard ratio, 2.86; 95% CI, 1.20 to 6.80; p=0.017) and patients with good performance (Eastern Cooperative Oncology Group 0-1 [hazard ratio, 3.68; 95% CI, 1.70 to 7.96]) showed better mPFS. In fulvestrant plus palbociclib group, chemotherapy naïve patients showed better mPFS (hazard ratio, 12.51, 95% CI, 1.59 to 99.17; p=0.017). The most common grade 3 or 4 adverse event was neutropenia (letrozole 86.3%, fulvestrant 88.3%)., Conclusion: To our knowledge, this is the first real-world data of palbociclib reported in Asia. Palbociclib showed comparable benefit to previous phase 3 trials in Asian patients during daily clinical practice.

Background: Small-cell lung cancer (SCLC) is a highly proliferative, rapidly growing tumor with a poor prognosis, even in cases of limited disease (LD). Timely and accurate high-intensity therapy is necessary. For concurrent chemoradiotherapy (CCRT), etoposide/platinum (EP)-based regimens are recommended, although irinotecan/platinum (IP)-based regimens are also effective with radiotherapy. This large-scale, retrospective, nationwide cohort study aimed to analyze the efficacy of CCRT in patients with LD-SCLC., Methods: Population data registered between January 2008 and December 2018 was extracted from the Health Insurance Review and Assessment Service of Korea database. Survival outcomes of 4446 LD-SCLC patients who received CCRT were analyzed., Results: Patients who received EP-CCRT (n = 4187) showed better time to first subsequent therapy (TFST: 11.2 months) and overall survival (OS: 22.2 months) than those who received IP-CCRT (n = 259; TFST: 9.6 months, P = 0.0477; OS: 16.4 months, P <  0.0001). When CCRT failed, dual-agent chemotherapy (n = 925; OS: 9.1 months) provided a better survival benefit than single-agent chemotherapy (n = 815; OS: 7.5 months). IP-based chemotherapy resulted in better OS (9.6 months) than EP-based chemotherapy (7.1 months, P = 0.017) in platinum-resistant relapsed patients; the opposite was observed for platinum-sensitive relapsed patients (OS: EP, 17.2 months; IP, 6.6 months; P <  0.0001). Poisson regression analysis demonstrated that age, EP-CCRT, and hypercholesterolemia retained significant associations with OS after adjustment for all variables., Conclusion: In the Korean population, the effects of EP-CCRT on OS and TFST are significantly more favorable than those of IP-CCRT.

Systemic sclerosis (SSc) is an autoimmune disorder characterized by fibrosis of the skin and internal organs. Despite several studies on SSc treatments, effective treatments for SSc are still lacking. Since evidence suggests an association between intestinal microbiota and SSc, we focused on butyrate, which has beneficial effects in autoimmune diseases as a bacterial metabolite. Here, we investigated the therapeutic potential of sodium butyrate (SB) using a bleomycin-induced fibrosis mouse model of SSc and human dermal fibroblasts (HDFs). SB attenuated bleomycin-induced dermal and lung fibrosis in mice. SB influenced fecal microbiota composition (phyla Actinobacteria and Bacteroidetes, genera Bifidobacterium and Ruminococcus&#95;g2 ). SB controlled macrophage differentiation in mesenteric lymph nodes, spleen, and bronchoalveolar lavage cells of mice with bleomycin-induced skin fibrosis. Profibrotic and proinflammatory gene expression was suppressed by SB administration in skin. Furthermore, SB inhibited transforming growth factor β1-responsive proinflammatory expression with increased acetylation of histone 3 in HDFs. Subcutaneous SB application had antifibrogenic effects on the skin. Butyrate ameliorated skin and lung fibrosis by improving anti-inflammatory activity in a mouse model of SSc. Butyrate may exhibit indirect and direct anti-fibrogenic action on fibroblasts by regulating macrophage differentiation and inhibition of histone deacetylase 3. These findings suggest butyrate as an SSc treatment.

In recent times, two-dimensional transition-metal dichalcogenides (TMDs) have become extremely attractive and proficient electrodes for dye-sensitized solar cells (DSSCs) and water electrolysis hydrogen evolution as alternatives to the scarce metal platinum (Pt). The active TMD molybdenum selenide (MoSe 2 ) and tungsten disulfide (WS 2 ) are inspiring systems owing to their abundance of active sulfur and selenium sites, but their outputs are lacking due to their inactive basal planes and ineffective transport behavior. In this work, van der Waals interrelated MoSe 2 /WS 2 hybrid structures were constructed on conducting glass substrates by chemicophysical methodologies. For the first time, the constructed MoSe 2 /WS 2 structures were effectively used as a counter electrode for DSSCs and an active electrode for hydrogen evolution to replace the nonabundant Pt. The assembled DSSCs using the designed MoSe 2 /WS 2 heterostructure counter electrode provided a superior power-conversion efficiency of 9.92% and a photocurrent density of 23.10 mA·cm -2 , unmatchable by most of the TMD-based structures. The MoSe 2 /WS 2 heterostructure displayed excellent electrocatalytic hydrogen evolution behavior with a 75 mV overpotential to drive a 10 mA·cm -2 current density, a 60 mV·dec -1 Tafel slope, and an over 20 h durable process in an acidic medium. The results demonstrated the advantages of the MoSe 2 /WS 2 hybrid development for generating interfacial transport and active facet distribution and enriching the electrocatalytic activity for DSSCs and the water-splitting hydrogen evolution process.

Objectives: To determine whether quantitative radiomic features from cardiac CT could differentiate the left atrial appendage (LAA) thrombus from circulatory stasis in patients with valvular heart disease., Methods: Ninety-five consecutive patients with valvular heart disease and filling defects in LAA on two-phase cardiac CT from March 2016 to August 2018 were retrospectively enrolled and classified as having thrombus or stasis by transesophageal echocardiography or cardiac surgery. The ratio of Hounsfield units in the filling defects to those in the ascending aorta (AA) was calculated on early- and late-phase CT (LAA/AA E and LAA/AA L , respectively). Radiomic features were extracted from semi-automated three-dimensional segmentation of the filling defect on early-phase CT. The diagnostic ability of radiomic features for differentiating thrombus from stasis was assessed and compared to LAA/AA E and LAA/AA L by comparing the AUC of ROC curves. Diagnostic performances of CT attenuation ratios and radiomic features were validated with an independent validation set., Results: Thrombus was diagnosed in 25 cases and stasis in 70. Sixty-eight radiomic features were extracted. Values of 8 wavelet-transformed features were lower in thrombus than in stasis (p < 0.001). The AUC value of a radiomic feature, wavelet&#95;LHL, for diagnosing thrombus was 0.78, which was higher than that of LAA/AA E (AUC = 0.54, p = 0.025) and similar to that of LAA/AA L (AUC = 0.76, p = 0.773). In the validation set, the AUC of wavelet&#95;LHL was 0.71, which was higher than that of LAA/AA E (AUC = 0.57, p = 0.391) and similar to that of LAA/AA L (AUC = 0.75, p = 0.707)., Conclusions: Quantitative radiomic features from the early phase of cardiac CT may help diagnose LAA thrombus in patients with valvular heart disease., Key Points: • Wavelet-transformed grey-level non-uniformity values from radiomic analysis are significantly lower for LAA thrombus than for circulatory stasis. • Radiomic features may have an additional value for differentiating LAA thrombus from circulatory stasis when interpreting single-phase cardiac CT. • Radiomic features extracted from single-phase images may show similar diagnostic ability as conventional quantitative analysis from two-phase images.

Topologically protected chiral skyrmions are an intriguing spin texture that has attracted much attention because of fundamental research and future spintronic applications. MnSi with a non-centrosymmetric structure is a well-known material hosting a skyrmion phase. To date, the preparation of MnSi crystals has been investigated by using special instruments with an ultrahigh vacuum chamber. Here, we introduce a facile way to grow MnSi films on a sapphire substrate using a relatively low vacuum environment of conventional magnetron sputtering. Although the as-grown MnSi films have a polycrystalline nature, a stable skyrmion phase in a broad range of temperatures and magnetic fields is observed via magnetotransport properties including phenomenological scaling analysis of the Hall resistivity contribution. Our findings provide not only a general way to prepare the materials possessing skyrmion phases but also insight into further research to stimulate more degrees of freedom in our inquisitiveness.

Background: Immune checkpoint blockades (ICBs) are characterized by a durable clinical response and better tolerability in patients with a variety of advanced solid tumors. However, we not infrequently encounter patients with hyperprogressive disease (HPD) exhibiting paradoxically accelerated tumor growth with poor clinical outcomes. This study aimed to investigate implications of clinical factors and immune cell composition on different tumor responses to immunotherapy in patients with non-small cell lung cancer (NSCLC)., Methods: This study evaluated 231 NSCLC patients receiving ICBs between January 2014 and May 2018. HPD was defined as a > 2-fold tumor growth kinetics ratio during ICB therapy and time-to-treatment failure of ≤2 months. We analyzed clinical data, imaging studies, periodic serologic indexes, and immune cell compositions in tumors and stromata using multiplex immunohistochemistry., Results: Of 231 NSCLC patients, PR/CR and SD were observed in 50 (21.6%) and 79 (34.2%) patients, respectively and 26 (11.3%) patients met the criteria for HPD. Median overall survival in poor response groups (HPD and non-HPD PD) was extremely shorter than disease-controlled group (SD and PR/CR) (5.5 and 6.1 months vs. 16.2 and 18.3 months, respectively, P = 0.000). In multivariate analysis, HPD were significantly associated with heavy smoker (p = 0.0072), PD-L1 expression ≤1% (p = 0.0355), and number of metastatic site ≥3 (p = 0.0297). Among the serologic indexes including NLR, PLR, CAR, and LDH, only CAR had constantly significant correlations with HPD at the beginning of prior treatment and immunotherapy, and at the 1st tumor assessment. The number of CD4+ effector T cells and CD8+ cytotoxic T cells, and CD8+/PD-1+ tumor-infiltrating lymphocytes (TIL) tended to be smaller, especially in stromata of HPD group. More M2-type macrophages expressing CD14, CD68 and CD163 in the stromal area and markedly fewer CD56+ NK cells in the intratumoral area were observed in HPD group., Conclusions: Our study suggests that not only clinical factors including heavy smoker, very low PD-L1 expression, multiple metastasis, and CAR index, but also fewer CD8+/PD-1+ TIL and more M2 macrophages in the tumor microenvironment are significantly associated with the occurrence of HPD in the patients with advanced/metastatic NSCLC receiving immunotherapy.

Purpose: Although immune-checkpoint inhibitors (ICIs) have emerged as therapeutic options for recurrent and/or metastatic head and neck squamous cell carcinoma (R/M-HNSCC), concerns have been raised on exceptional acceleration of tumor growth during treatment with ICIs, a condition described as hyperprogressive disease (HPD). This study examined the incidence, potential predictors, and clinical impact of HPD in R/M-HNSCC., Methods: We retrospectively collected data of patients with R/M-HNSCC treated with ICIs between January 2013 and June 2018 from 11 medical centers in Korea. HPD was defined as tumor growth kinetics ratio (TGKr) > 2, which was calculated by comparing TGK on ICIs with that before treatment with ICIs., Results: Of 125 patients, 68 (54.4%) obtained progressive disease as their best responses (progressors). HPD was identified in 18 (26.5% of progressors, 14.4% of total) patients. Relatively younger age, primary tumor of oral cavity, and previous locoregional irradiation were significant predictors of HPD according to multivariable analysis (p = 0.040, 0.027, and 0.015, respectively). Compared to patients without HPD, patients with HPD had significantly shorter median progression-free survival (PFS) (1.2 vs. 3.4 months, p < 0.001) and overall survival (OS) (3.4 vs. 10.7 months, p = 0.047). However, interestingly, HPD did not significantly affect the therapeutic benefit of post-ICIs chemotherapy., Conclusions: Younger patients with oral cavity cancer or prior treatment with locoregional radiotherapy could be regarded potential risk groups for HPD in patients with R/M-HNSCC treated with ICIs. Although HPD could consistently predict poorer survival outcomes, patients who experienced HPD with ICIs should not be excluded from the subsequent salvage chemotherapy treatments.

Post-operative radiation therapy (RT) reduces loco-regional recurrence rates and mortality in most patients with non-metastatic breast cancer. The aim of this critical review is to provide an overview of the applicability of moderately hypofractionated RT for breast cancer patients, focusing on factors influencing clinical decision-making. An international group of radiation oncologists agreed to assess, integrate, and interpret the existing evidence into a practical report to guide clinicians in their daily management of breast cancer patients. We conclude that moderately hypofractionated RT to the breast, chest wall (with/without breast reconstruction), and regional lymph nodes is at least as safe and effective as conventionally fractionated regimens and could be considered as the treatment option for the vast majority of the patients.For those who are still concerned about its generalised application, we recommend participating in ongoing trials comparing moderately hypofractionated RT to conventionally fractionated RT for breast cancer patients in some clinical circumstances., (Copyright © 2020 Elsevier B.V. All rights reserved.)

We prepared bulk samples of supercooled liquid water under pressure by isochoric heating of high-density amorphous ice to temperatures of 205 ± 10 kelvin, using an infrared femtosecond laser. Because the sample density is preserved during the ultrafast heating, we could estimate an initial internal pressure of 2.5 to 3.5 kilobar in the high-density liquid phase. After heating, the sample expanded rapidly, and we captured the resulting decompression process with femtosecond x-ray laser pulses at different pump-probe delay times. A discontinuous structural change occurred in which low-density liquid domains appeared and grew on time scales between 20 nanoseconds to 3 microseconds, whereas crystallization occurs on time scales of 3 to 50 microseconds. The dynamics of the two processes being separated by more than one order of magnitude provides support for a liquid-liquid transition in bulk supercooled water., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Plasticizers are added to diverse consumer products including children's products. Owing to their potential for endocrine disruption, the use of phthalate plasticizers is restricted in many children's products. In this study, exposure to five phthalate esters (dibutylphthalate, di(2-ethylhexyl) phthalate (DEHP), diethyl phthalate, di-isobutyl phthalate, and diisononyl phthalate (DINP)) and an alternative (di-ethylhexyl adipate) was assessed by the use of children's products based on chemical analysis of 3345 products purchased during 2017 and 2019 in Korea. Plasticizers were found above the detection limits in 387 products, and DEHP and DINP were the two most predominantly detected plasticizers. Deterministic and probabilistic estimation of the margin of exposure at a screening level revealed that the use of children's products might be an important risk factor. However, it is also highly likely that the exposure could be overestimated, because the migration rate was estimated based solely on the content of plasticizers in children's products. Chemical migration is a key process determining the absorption of plasticizers from products; thus, further refinements in experimental determination or model estimation of the migration rate are required.

Human exposure to microplastics contained in food has become a significant concern owing to the increasing accumulation of microplastics in the environment. In this paper, we summarize the presence of microplastics in food and the analytical methods used for isolation and identification of microplastics. Although a large number of studies on seafood such as fish and shellfish exist, estimating the overall human exposure to microplastics via food consumption is difficult owing to the lack of studies on other food items. Analytical methods still need to be optimized for appropriate recovery of microplastics in various food matrices, rendering a quantitative comparison of different studies challenging. In addition, microplastics could be added or removed from ingredients during processing or cooking. Thus, research on processed food is crucial to estimate the contribution of food to overall human microplastic consumption and to mitigate this exposure in the future.

Tungsten sulfide (WS 2 ) and tungsten carbide (W 2 C) are materialized as the auspicious candidates for various electrochemical applications, owing to their plentiful active edge sites and better conductivity. In this work, the integration of W 2 C and WS 2 was performed by using a simple chemical reaction to form W 2 C/WS 2 hybrid as a proficient electrode for hydrogen evolution and supercapacitors. For the first time, a W 2 C/WS 2 hybrid was engaged as a supercapacitor electrode and explored an incredible specific capacitance of ~1018 F g -1 at 1 A g -1 with the outstanding robustness. Furthermore, the constructed symmetric supercapacitor using W 2 C/WS 2 possessed an energy density of 45.5 Wh kg -1 at 0.5 kW kg -1 power density. For hydrogen evolution, the W 2 C/WS 2 hybrid produced the low overpotentials of 133 and 105 mV at 10 mA cm -2 with the small Tafel slopes of 70 and 84 mV dec -1 in acidic and alkaline media, respectively, proving their outstanding interfaced electrocatalytic characteristics. The engineered W 2 C/WS 2 -based electrode offered the high-performance for electrochemical energy applications.

Many properties of layered materials change as they are thinned from their bulk forms down to single layers, with examples including indirect-to-direct band gap transition in 2H semiconducting transition metal dichalcogenides as well as thickness-dependent changes in the valence band structure in post-transition-metal monochalcogenides and black phosphorus. Here, we use angle-resolved photoemission spectroscopy to study the electronic band structure of monolayer ReSe 2 , a semiconductor with a distorted 1T structure and in-plane anisotropy. By changing the polarization of incoming photons, we demonstrate that for ReSe 2 , in contrast to the 2H materials, the out-of-plane transition metal d z 2 and chalcogen p z orbitals do not contribute significantly to the top of the valence band, which explains the reported weak changes in the electronic structure of this compound as a function of layer number. We estimate a band gap of 1.7 eV in pristine ReSe 2 using scanning tunneling spectroscopy and explore the implications on the gap following surface doping with potassium. A lower bound of 1.4 eV is estimated for the gap in the fully doped case, suggesting that doping-dependent many-body effects significantly affect the electronic properties of ReSe 2 . Our results, supported by density functional theory calculations, provide insight into the mechanisms behind polarization-dependent optical properties of rhenium dichalcogenides and highlight their place among two-dimensional crystals.

The evolution of next-generation sequencing technology has resulted in a generation of large amounts of cancer genomic data. Therefore, increasingly complex techniques are required to appropriately analyze this data in order to determine its clinical relevance. In this study, we applied a neural network-based technique to analyze data from The Cancer Genome Atlas and extract useful microRNA (miRNA) features for predicting the prognosis of patients with lung adenocarcinomas (LUAD). Using the Cascaded Wx platform, we identified and ranked miRNAs that affected LUAD patient survival and selected the two top-ranked miRNAs (miR-374a and miR-374b) for measurement of their expression levels in patient tumor tissues and in lung cancer cells exhibiting an altered epithelial-to-mesenchymal transition (EMT) status. Analysis of miRNA expression from tumor samples revealed that high miR-374a/b expression was associated with poor patient survival rates. In lung cancer cells, the EMT signal induced miR-374a/b expression, which, in turn, promoted EMT and invasiveness. These findings demonstrated that this approach enabled effective identification and validation of prognostic miRNA markers in LUAD, suggesting its potential efficacy for clinical use.

Iron is one of the most studied chemical elements due to its sociotechnological and planetary importance; hence, understanding its structural transition dynamics is of vital interest. By combining a short pulse optical laser and an ultrashort free electron laser pulse, we have observed the subnanosecond structural dynamics of iron from high-quality x-ray diffraction data measured at 50-ps intervals up to 2500 ps. We unequivocally identify a three-wave structure during the initial compression and a two-wave structure during the decaying shock, involving all of the known structural types of iron (α-, γ-, and ε-phase). In the final stage, negative lattice pressures are generated by the propagation of rarefaction waves, leading to the formation of expanded phases and the recovery of γ-phase. Our observations demonstrate the unique capability of measuring the atomistic evolution during the entire lattice compression and release processes at unprecedented time and strain rate., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Nearly three million people in the USA suffer traumatic brain injury (TBI) yearly; however, there are no pre- or post-TBI treatment options available. KCNQ2-5 voltage-gated K + channels underlie the neuronal "M current", which plays a dominant role in the regulation of neuronal excitability. Our strategy towards prevention of TBI-induced brain damage is predicated on the suggested hyper-excitability of neurons induced by TBIs, and the decrease in neuronal excitation upon pharmacological augmentation of M/KCNQ K + currents. Seizures are very common after a TBI, making further seizures and development of epilepsy disease more likely. Our hypothesis is that TBI-induced hyperexcitability and ischemia/hypoxia lead to metabolic stress, cell death and a maladaptive inflammatory response that causes further downstream morbidity. Using the mouse controlled closed-cortical impact blunt TBI model, we found that systemic administration of the prototype M-channel "opener", retigabine (RTG), 30 min after TBI, reduces the post-TBI cascade of events, including spontaneous seizures, enhanced susceptibility to chemo-convulsants, metabolic stress, inflammatory responses, blood-brain barrier breakdown, and cell death. This work suggests that acutely reducing neuronal excitability and energy demand via M-current enhancement may be a novel model of therapeutic intervention against post-TBI brain damage and dysfunction.

Fundamental studies of chemical reactions often consider the molecular dynamics along a reaction coordinate using a calculated or suggested potential energy surface 1-5 . But fully mapping such dynamics experimentally, by following all nuclear motions in a time-resolved manner-that is, the motions of wavepackets-is challenging and has not yet been realized even for the simple stereotypical bimolecular reaction 6-8 : A-B + C → A + B-C. Here we track the trajectories of these vibrational wavepackets during photoinduced bond formation of the gold trimer complex [Au(CN) 2 - ] 3 in an aqueous monomer solution, using femtosecond X-ray liquidography 9-12 with X-ray free-electron lasers 13,14 . In the complex, which forms when three monomers A, B and C cluster together through non-covalent interactions 15,16 , the distance between A and B is shorter than that between B and C. Tracking the wavepacket in three-dimensional nuclear coordinates reveals that within the first 60 femtoseconds after photoexcitation, a covalent bond forms between A and B to give A-B + C. The second covalent bond, between B and C, subsequently forms within 360 femtoseconds to give a linear and covalently bonded trimer complex A-B-C. The trimer exhibits harmonic vibrations that we map and unambiguously assign to specific normal modes using only the experimental data. In principle, more intense X-rays could visualize the motion not only of highly scattering atoms such as gold but also of lighter atoms such as carbon and nitrogen, which will open the door to the direct tracking of the atomic motions involved in many chemical reactions.

To investigate the prognostic value of DGM-CM6 (Distant Genetic Model-Clinical variable Model 6) for endocrine-responsive breast cancer (ERBC) patients, we analyzed 752 operable breast cancer patients treated in a Taiwan cancer center from 2005 to 2014. Among them, 490 ERBC patients (identified by the PAM50 or immunohistochemistry method) were classified by DGM-CM6 into low- and high-risk groups (cutoff <33 and ≥33, respectively). Significant differences were observed between the DGM-CM6 low- and high-risk groups for 10-year distant recurrence-free survival (DRFS) in both lymph node (LN)- ( P < 0.05) and LN+ patients ( P < 0.05). Multivariate analysis confirmed the independent strength of DGM-CM6 for the prediction of high- vs. low- risk groups for DRFS ( P < 0.0001, HR: 6.76, 95% CI, 1.8-25.42) and overall survival ( P = 0.01, HR: 6.06, 95% CI:1.55-23.47), respectively. In summary, DGM-CM6 may be used to classify low- and high-risk groups for 10-year distant recurrence in both LN- and LN+ ERBC patients in the Asian population. A large scale clinical trial is warranted., (Copyright © 2020 Lei, Wang, Mo, Cheng and Zhou.)

In this work, we demonstrate a highly enhanced electrocatalytic activity of vanadium-doped CoP (V-CoP), directly grafted on a vertical graphene/carbon cloth electrode (VG/CC) by a facile electrochemical deposition method. Impressively, V-CoP/VG/CC exhibited a superior catalytic activity toward the hydrogen evolution reaction (HER) in alkaline solution. Compared to CoP/VG/CC, V-doping decreased the overpotential for HER at 10 mA cm -2 by more than half to 40 mV. The new catalyst even outperformed Pt/C beyond 150 mA cm -2 . The overpotential for OER at 50 mA cm -2 was merely 314 mV, more than 100 mV lower than that of IrO 2 . Moreover, our novel catalyst worked as an excellent bifunctional catalyst with a low cell voltage of 1.69 V to achieve a current density of 50 mA cm -2 . Detailed characterizations revealed that the V-doping in CoP resulted in improved electrical conductivity and increased active sites. Our findings highlight the significant advantage of V doping on the catalytic activities of CoP, already boosted by VG. Furthermore, concurrent doping with the electrodeposition of catalyst offers a new approach for practical water electrolysis., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Whey, a by-product of cheese making, is a collection of several milk proteins and has functional and nutritional values. Whey protein concentrate (WPC) exhibits various functional effects by glycation. Studies to find sugar-binding sites in a protein having a functional effect are reported. However, it is rarely clear whether it confirms that glycated single protein exhibits the same effect of protein cluster. This study confirmed which protein sites are responsible for the effect of glycated WPC (G-WPC). β-Lactoglobulin (LG) was the major protein of G-WPC and glycated with lactose. The glycated LG increased the nitric oxide and cytokine secretion similar to G-WPC and peptide sequences of active compound was confirmed using the high molecular weight band of G-WPC. The K151 and K157 residues of LG were modified by glycation with sugar in common with G-WPC. These residues of glycated LG potentially contribute to the immune-modulation effect of G-WPC., Competing Interests: Conflict of interestThe authors declare no conflict of interest., (© The Korean Society of Food Science and Technology 2020.)

This study aimed to validate the long-term prognostic value of a new clinical-genomic model, Distant Genetic Model-Clinical Variable Model 6 (DGM-CM6), developed in Asia as a prognostic panel for all subtypes of breast cancer. We included 752 operable stage I-III breast cancer patients representing all subtypes treated from 2005 to 2014 as the validation cohort. The median follow-up was 95.8 months. The low- and high-risk patients classified by DGM-CM6 (RI-DR) had significant differences in 10-year distant recurrence-free interval (DRFI) (94.1% vs. 85.0%, P < 0.0001) and relapse-free survival (RFS) (90.0% vs. 80.5%, P = 0.0003). External validation using EMTAB-365 dataset showed similar observation (P < 0.0001). DGM-CM6 was an independent prognostic factor by multivariate analysis with hazard ratios of 3.1 (1.6-6.0) for RFS (P = 0.0009) and 3.8 (1.6-9.0) for DRFI (P = 0.0028). Comparing the C-index of DGM-CM6 and PAM50-ROR scores, the former performed better than the latter in predicting long-term DRFI and RFS, especially in N0, ER/PR-positive, and HER2-negative patients.

Superconductivity near room temperature in the sulfur-hydrogen system arises from a sequence of reactions at high pressures, with X-ray diffraction experiments playing a central role in understanding these chemical-structural transformations and the corresponding S:H stoichiometry. Here we document X-ray irradiation acting as both a probe and as a driver of chemical reaction in this dense hydride system. We observe a reaction between molecular hydrogen (H 2 ) and elemental sulfur (S 8 ) under high pressure, induced directly by X-ray illumination, at photon energies of 12 keV using a free electron laser. The rapid synthesis of hydrogen sulfide (H 2 S) at 0.3 GPa was confirmed by optical observations, spectroscopic measurements, and microstructural changes detected by X-ray diffraction. These results document X-ray induced chemical synthesis of superconductor-forming dense hydrides, revealing an alternative production strategy and confirming the disruptive nature of X-ray exposure in studies on high-pressure hydrogen chalcogenides, from water to high-temperature superconductors.

Gold particles have been widely used in the treatment of prostate cancer due to their unique optical properties, such as their light-heat conversion in response to near-infrared radiation. Due to well-defined synthesis mechanisms and simple manufacturing methods, gold particles have been fabricated in various sizes and shapes. However, the low photothermal transduction efficiency in their present form is a major obstacle to practical and therapeutic uses of these particles. In the current work, we present a silica-coated gold nanoparticle cluster to address the therapeutic limit of single gold nanoparticles (AuNPs) and use its photothermal effect for treatment against PC-3, a typical prostate cancer. Due to its specific nanostructure, this gold nanocluster showed three times higher photothermal transduction efficiency than free single AuNPs. Moreover, while free single particles easily clump and lose optical properties, this silica-coated cluster form remained stable for a longer time in a given medium. In photothermal tests under near-infrared radiation, the excellent therapeutic efficacy of gold nanoclusters, referred to as AuNC@SiO 2 , was observed in a preclinical sample. Only the samples with both injected nanoclusters followed by photothermal treatment showed completely degraded tumors after 15 days. Due to the unique intrinsic biocompatibility and higher therapeutic effect of these silica-coated gold nanoclusters, they may contribute to enhancement of therapeutic efficacy against prostate cancer.

Accurate prediction of non-small cell lung cancer (NSCLC) prognosis after surgery remains challenging. The Cox proportional hazard (PH) model is widely used, however, there are some limitations associated with it. In this study, we developed novel neural network models called binned time survival analysis (DeepBTS) models using 30 clinico-pathological features of surgically resected NSCLC patients (training cohort, n = 1,022; external validation cohort, n = 298). We employed the root-mean-square error (in the supervised learning model, s- DeepBTS) or negative log-likelihood (in the semi-unsupervised learning model, su-DeepBTS) as the loss function. The su-DeepBTS algorithm achieved better performance (C-index = 0.7306; AUC = 0.7677) than the other models (Cox PH: C-index = 0.7048 and AUC = 0.7390; s-DeepBTS: C-index = 0.7126 and AUC = 0.7420). The top 14 features were selected using su-DeepBTS model as a selector and could distinguish the low- and high-risk groups in the training cohort (p = 1.86 × 10 -11 ) and validation cohort (p = 1.04 × 10 -10 ). When trained with the optimal feature set for each model, the su-DeepBTS model could predict the prognoses of NSCLC better than the traditional model, especially in stage I patients. Follow-up studies using combined radiological, pathological imaging, and genomic data to enhance the performance of our model are ongoing.

Melting is a fundamental process of matter that is still not fully understood at the microscopic level. Here, we use time-resolved x-ray diffraction to examine the ultrafast melting of polycrystalline gold thin films using an optical laser pump followed by a delayed hard x-ray probe pulse. We observe the formation of an intermediate new diffraction peak, which we attribute to material trapped between the solid and melted states, that forms 50 ps after laser excitation and persists beyond 500 ps. The peak width grows rapidly for 50 ps and then narrows distinctly at longer time scales. We attribute this to a melting band originating from the grain boundaries and propagating into the grains. Our observation of this intermediate state has implications for the use of ultrafast lasers for ablation during pulsed laser deposition., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).)

Repetitive blast traumatic brain injury (TBI) affects numerous soldiers on the battlefield. Mild TBI has been shown to have long-lasting effects with repeated injury. We have investigated effects on neuronal excitability after repetitive, mild TBI in a mouse model of blast-induced brain injury. We exposed mice to mild blast trauma of an average peak overpressure of 14.6 psi, repeated across three consecutive days. While a single exposure did not reveal trauma as indicated by the glial fibrillary acidic protein indicator, three repetitive blasts did show significant increases. As well, mice had an increased indicator of inflammation (Iba-1) and increased tau, tau phosphorylation, and altered cytokine levels in the spleen. Video-electroencephalographic monitoring 48 h after the final blast exposure demonstrated seizures in 50% (12/24) of the mice, most of which were non-convulsive seizures. Long-term monitoring revealed that spontaneous seizures developed in at least 46% (6/13) of the mice. Patch clamp recording of dentate gyrus hippocampus neurons 48 h post-blast TBI demonstrated a shortened latency to the first spike and hyperpolarization of action potential threshold. We also found that evoked excitatory postsynaptic current amplitudes were significantly increased. These findings indicate that mild, repetitive blast exposures cause increases in neuronal excitability and seizures and eventual epilepsy development in some animals. The non-convulsive nature of the seizures suggests that subclinical seizures may occur in individuals experiencing even mild blast events, if repeated.

Owing to its precise manipulation in nanoscale, DNA as a genetic code becomes a promising and generic material in lots of nanotechnological outstanding exploitations. The nanoscale assembly of nucleic acids in aqueous solution has showed very remarkable capability that is not achievable from any other material resources. In the meantime, their striking role played by effective intracellular interactions have been identified, making these more attractive for a variety of biological applications. Lately, a number of interesting attempts have been made to augment their marvelous diagnostic and therapeutic capabilities, as being integrated with inorganic compounds involving gold, iron oxide, quantum dot, upconversion, etc. It was profoundly studied how structural DNA-inorganic hybrid materials have complemented with each other in a synergistic way for better-graded biological performances. Such hybrid materials consisting of both structural DNAs and inorganics are gradually receiving much attention as a practical and future-oriented material substitute. However, any special review articles highlighting the significant and innovative materials have yet to be published. At the first time, we here demonstrate novel hybrid complexes made of structural DNAs and inorganics for some practical applications.

The purpose of this study was to describe and compare the duration of Staphylococcus aureus bacteremia (SAB) according to methicillin resistance and the primary foci of infection. We also aimed to newly define persistent SAB considering these results. Nonduplicated episodes of SAB in patients aged ≥15 years from 14 hospitals in the Republic of Korea were analyzed between January 2009 and February 2018. The duration of SAB was defined as the number of days from the time of administration of an antibiotic to which the isolate was susceptible after the onset of SAB to the last day of a positive blood culture for S. aureus SAB durations were described and compared based on methicillin resistance and the primary foci of infection. Cases in the top quartile for the duration of bacteremia in the respective clinical context were classified as newly defined persistent SAB, and its association with in-hospital mortality was evaluated. A total of 1,917 cases were analyzed. The duration of SAB was longer in patients with methicillin-resistant SAB (MRSAB; n  = 995) than in patients with methicillin-susceptible SAB (MSSAB; n  = 922) (median duration, 1 day [interquartile range, 1 to 3 days] for MSSAB and 1 day [interquartile range, 0 to 5 days] for MRSAB; P <  0.001). The duration of bacteremia was longer in patients with endocarditis and bone and joint, endovascular, and surgical site infections and was shorter in patients with skin and soft tissue infections. Newly defined persistent SAB was independently associated with in-hospital mortality (adjusted odds ratio, 1.97; 95% confidence interval, 1.54 to 2.53; P <  0.001). The durations of SAB were dependent on methicillin resistance and the primary foci of infection, and considering these contexts, persistent SAB was significantly associated with in-hospital mortality., (Copyright © 2019 American Society for Microbiology.)

Polymorphisms allowing multiple structural phases are among the most fascinating properties of transition metal dichalcogenides (TMDs). Herein, the polymorphic 1T' phase and its lattice dynamics for bilayer VSe 2 grown on epitaxial bilayer graphene are investigated via low temperature scanning tunneling microscopy (STM). The 1T' structure, mostly observed in group-6 TMDs, is unexpected in VSe 2 , which is a group-5 TMD. Emergence of the 1T' structure in bilayer VSe 2 suggests the important roles of interface and layer configurations, providing new possibilities regarding the polymorphism of TMDs. Detailed topographical analysis elucidates the microscopic nature of the 1T' structure, confirming that Se-like and V-like surfaces can be resolved depending on the polarity of the sample bias. In addition, bilayer VSe 2 can transit from a static state of the 1T' phase to a dynamic state consisting of lattice vibrations, triggered by tunneling current from the STM tip. Topography also shows hysteretic behavior during the static-dynamic transition, which is attributed to latent energy existing between the two states. The observed lattice dynamics involve vibrational motion of the Se atoms and the middle V atoms. Our observations will provide important information to establish in-depth understanding of the microscopic nature of 1T' structures and the polymorphism of two-dimensional TMDs.

Purpose: There is no useful model for predicting the risk of recurrence in node-positive patients regardless of breast cancer subtype. We developed and validated 2 clinical-genomic models (recurrence index [RI]-local recurrence [LR]) and RI-distant recurrence (RI-DR) for stratifying these patients into low- and high-risk groups., Methods and Materials: The 4 data sets were (1) training group (n = 112); (2) testing group (n = 46); (3) validation group (n = 388); and (4) E-MTAB-365 data set (n = 426). Patients who had undergone mastectomy or breast-conserving surgery and mRNA microarray analysis of their primary tumor tissue and had a pathologic stage of I to III were enrolled in the training, testing, and validation groups. Using preset cut-offs obtained from the training group, the models were tested and validated in the 3 other independent groups., Results: In the validation data set, the RI-LR distinguished between low- and high-risk groups according to 10-year LR-free interval (100% vs 93.0%, P = .015) and relapse-free survival (RFS; 85.0% vs 76.9%, P = .032). The RI-DR distinguished the low-risk group from the high-risk group according to RFS (85.7% vs 77.4%, P = .025). RI-DR and RI-LR scores were independent prognostic factors in N1-N2 patients (hazard ratio [HR], 3.3; 95% confidence interval, 1.1-10.2; and HR, 2.7; 95% confidence interval, 1.1-6.7, respectively) by multivariate analysis. The RI-DR and RI-LR genetic models were tested similarly using the E-MTAB data set with HRs of 2.5 (P = .0048) and 2.7 (P = .0285), respectively, in node-positive patients., Conclusions: Both RI-DR and RI-LR can partition N1-N2 patients into low- and high-risk groups for RFS; however, the latter is superior for predicting locoregional recurrence., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The synthesis of low cost, high efficacy, and durable hydrogen evolution electrocatalysts from the non-noble metal group is a major challenge. Herein, we establish a simple and inexpensive chemical reduction method for producing molybdenum carbide (Mo 2 C) and tungsten carbide (W 2 C) nanoparticles that are efficient electrocatalysts in alkali and acid electrolytes for hydrogen evolution reactions (HER). Mo 2 C exhibits outstanding electrocatalytic behavior with an overpotential of -134 mV in acid medium and of -116 mV in alkaline medium, while W 2 C nanoparticles require an overpotential of -173 mV in acidic medium and -130 mV in alkaline medium to attain a current density of 10 mA cm -2 . The observed results prove the capability of high- and low-pH active electrocatalysts of Mo 2 C and W 2 C nanoparticles to be efficient systems for hydrogen production through HER water electrolysis., (Copyright © 2019 Hussain, Vikraman, Feroze, Song, An, Kim, Chun and Jung.)

Much research has been done on reliable and low-cost electrocatalysts for hydrogen generation by water splitting. In this study, we synthesized thin films of silver selenide (Ag 2 Se) using a simple thermal evaporation route and demonstrated their electrocatalytic hydrogen evolution reaction (HER) activity. The Ag 2 Se catalysts show improved electrochemical surface area and good HER electrocatalytic behavior (367 mV overpotential @ 10 mA·cm -2 , exchange current density: ~1.02 × 10 -3 mA·cm -2 , and Tafel slope: 53 mV·dec -1 ) in an acidic medium). The reliability was checked in 0.5 M sulfuric acid over 20 h. Our first-principles calculations show the optimal energy of hydrogen adsorption, which is consistent with experimental results. The works could be further extended for finding a new catalyst by associating the selenide, sulfide or telluride-based materials without complex catalyst synthesis procedures.

Purpose: Physician Orders for Life-Sustaining Treatment (POLST) form is a legal document for terminally ill patients to make medical decisions with physicians near the end-of-life. A multicenter prospective study was conducted to evaluate the feasibility of POLST administration in actual oncological practice., Materials and Methods: Patients with terminal cancer, age ≥ 20 years, and capable of communicating were eligible. The primary endpoint was the completion rate of POLST. Data about physicians' or patients' barriers were also collected., Results: From June to December 2017, 336 patients from seven hospitals were eligible. Median patient age was 66 years (range, 20 to 94 years); 52.7% were male; and 60.4% had poor performance status. Primary cancer sites were hepato-pancreato-biliary (26.2%), lung (23.2%), and gastrointestinal (19.9%). Expected survival duration was 10.6±7.3 weeks, with 41.2% receiving hospice care, 37.9% showing progression after cancer treatment, and the remaining patients were under active treatment (15.8%) or initially diagnosed with terminal cancer (5.1%). POLST forms were introduced to 60.1% of patients, and 31.3% signed the form. Physicians' barriers were reluctance of family (49.7%), lack of rapport (44.8%), patients' denial of prognosis (34.3%), lack of time (22.7%), guilty feelings (21.5%), and uncertainty about either prognosis (21.0%) or the right time to discuss POLST (16.6%). The patients' barriers were the lack of knowledge/understanding of POLST (65.1%), emotional discomfort (63.5%), difficulty in decision-making (66.7%), or denial of prognosis (14.3%)., Conclusion: One-third of patients completed POLST forms, and various barriers were identified. To overcome such barriers, social engagement, education, and systematic support might be necessary.

The microRNA-200 (miR-200) family plays a major role in specifying epithelial phenotype by preventing expression of the transcription repressors ZEB1 and ZEB2, which are well-known regulators of the epithelial-to-mesenchymal transition (EMT) in epithelial tumors including oral squamous cell carcinoma (OSCC). Here, we elucidated whether miR-200 family members control RNA-binding protein quaking (QKI), a newly identified tumor suppressor that is regulated during EMT. We predicted that miR-200a and miR-200b could recognize QKI 3'-UTR by analyzing TargetScan and The Cancer Genome Atlas head and neck squamous cell carcinoma (HNSCC) dataset. Forced expression of miR-200b/a/429 inhibited expression of ZEB1/2 and decreased cell migration in OSCC cell lines CAL27 and HSC3. QKI expression was also suppressed by miR-200 overexpression, and the 3'-UTR of QKI mRNA was directly targeted by miR-200 in luciferase reporter assays. Interestingly, shRNA-mediated knockdown of QKI led to pronounced EMT and protumor effects in both in vitro and in vivo studies of OSCC. Furthermore, high expression of QKI protein is associated with favorable prognosis in surgically resected HNSCC and lung adenocarcinoma. In conclusion, QKI increases during EMT and is targeted by miR-200; while, it suppresses EMT and tumorigenesis. We suggest that QKI and miR-200 form a negative feedback loop to maintain homeostatic responses to EMT-inducing signals., (© 2019 UICC.)

Maillard reaction products formed from whey protein isolate (WPI) and sugar have been shown to have an anti-inflammatory effect in vitro. Here, we incubated WPI and galactose (GWA) in an aqueous solution at 65°C for 24 h to produce a glycated conjugate, which was then fermented using Lactobacillus gasseri 4M13 to obtain the fermented product (F-GWA). We demonstrated that F-GWA had an anti-inflammatory effect on lipopolysaccharide (LPS)-stimulated RAW264.7 cells. It reduced both LPS-stimulated nitric oxide production and LPS-stimulated increases in the gene expression levels of tumor necrosis factor-α and cyclooxygenase-2 in a dose-dependent manner. Furthermore, F-GWA inhibited the LPS-induced phosphorylation of extracellular signal-regulated kinase and c-Jun N-terminal kinase, members of the mitogen-activated protein kinase family. The glycation process was evaluated by measuring fluorescence intensity and the furosine concentration during the Maillard reaction to form GWA. The protein modifications of WPI were analyzed using MALDI-TOF tandem mass spectrometry. We found that the combination of the Maillard reaction and L. gasseri 4M13 fermentation increased the prebiotic properties of GWA as well as organic acid production, compared with the nonreacted WPI and galactose., (Copyright © 2019 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Background: This study aimed to develop a prognostic model to predict the breast cancer-specific survival and overall survival for breast cancer patients in Asia and to demonstrate a significant difference in clinical outcomes between Asian and non-Asian patients., Methods: We developed our prognostic models by applying a multivariate Cox proportional hazards model to Taiwan Cancer Registry (TCR) data. A data-splitting strategy was used for internal validation, and a multivariable fractional polynomial approach was adopted for prognostic continuous variables. Subjects who were Asian, black, or white in the US-based Surveillance, Epidemiology, and End Results (SEER) database were analyzed for external validation. Model discrimination and calibration were evaluated in both internal and external datasets., Results: In the internal validation, both training data and testing data calibrated well and generated good area under the ROC curves (AUC; 0.865 in training data and 0.846 in testing data). In the external validation, although the AUC values were larger than 0.85 in all populations, a lack of model calibration in non-Asian groups revealed that racial differences had a significant impact on the prediction of breast cancer mortality. For the calibration of breast cancer-specific mortality, P values < 0.001 at 1 year and 0.018 at 4 years in whites, and P values ≤ 0.001 at 1 and 2 years and 0.032 at 3 years in blacks, indicated that there were significant differences (P value < 0.05) between the predicted mortality and the observed mortality. Our model generally underestimated the mortality of the black population. In the white population, our model underestimated mortality at 1 year and overestimated it at 4 years. And in the Asian population, all P values > 0.05, indicating predicted mortality and actual mortality at 1 to 4 years were consistent., Conclusions: We developed and validated a pioneering prognostic model that especially benefits breast cancer patients in Asia. This study can serve as an important reference for breast cancer prediction in the future.

Background: Ureaplasma spp. is a known risk factor for bronchopulmonary dysplasia (BPD). However, little is known about the effect of different degrees of maternal Ureaplasma colonization and their adverse outcomes. Hence, the aim of this study was to determine the effects of different degrees of maternal Ureaplasma colonization on BPD., Methods: A retrospective cohort study of preterm infants delivered at <32 weeks' gestational age (GA) was performed. The infants were divided according to maternal Ureaplasma status as follows: high-colonization (≥10 4  CCU/ml, UUH), low-colonization (<10 4  CCU/ml, UUL), and noncolonization (controls). Subgroup analysis according to neonatal respiratory Ureaplasma (n-UU) was also performed to evaluate vertical transmission., Results: In total, 245 infants were included in this study (UUH = 105, UUL = 47, controls = 93). The rates of preterm labor and histological chorioamnionitis were significantly different. The rate of BPD was significantly high in UUH (P = 0.044). The transmission rate of n-UU colonization was 36% in UUH and 32% in UUL (P = 0.609). The rate of BPD was 78% in n-UU (+) of UUH but 43% in n-UU (-) of UUL (P = 0.027)., Conclusions: High-degree colonization of maternal Ureaplasma was associated with preterm labor, histological chorioamnionitis, and neonatal BPD. The incidence of BPD was significantly higher in Ureaplasma-colonized infants born to women with high-degree colonization., (Copyright © 2018. Published by Elsevier B.V.)

Background: The biological function of protein arginine methyltransferase 3 (PRMT3) is not well known because very few physiological substrates of this methyltransferase have been identified to date., Methods: The clinical significance of PRMT3 in pancreatic cancer was studied by database analysis. The PRMT3 protein level of human pancreatic tumors was detected by immunoblotting and immunohistochemical staining. PRMT3-associated proteins and the methylation sites on the proteins were investigated using mass spectrometry. Seahorse Bioscience analyzed the metabolic reprogramming. Combination index analysis and xenograft animal model were conducted to explore the effects of combination of inhibitors of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and oxidative phosphorylation on tumor growth., Results: We found that the expression of PRMT3 is upregulated in pancreatic cancer, and its expression is associated with poor survival. We identified GAPDH as a PRMT3-binding protein and demonstrated that GAPDH is methylated at R248 by PRMT3 in vivo. The methylation of GAPDH by PRMT3 enhanced its catalytic activity while the mutation of R248 abolished the effect. In cells, PRMT3 overexpression triggered metabolic reprogramming and enhanced glycolysis and mitochondrial respiration simultaneously in a GAPDH-dependent manner. PRMT3-overexpressing cancer cells were addicted to GAPDH-mediated metabolism and sensitive to the inhibition of GAPDH and mitochondrial respiration. The combination of inhibitors of GAPDH and oxidative phosphorylation induced a synergistic inhibition on cellular growth in vitro and in vivo., Conclusion: Our results suggest that PRMT3 mediates metabolic reprogramming and cellular proliferation through methylating R248 of GAPDH, and double blockade of GAPDH and mitochondrial respiration could be a novel strategy for the treatment of PRMT3-overexpressing pancreatic cancer.

Artificial neural network-based analysis has recently been used to predict clinical outcomes in patients with solid cancers, including lung cancer. However, the majority of algorithms were not originally developed to identify genes associated with patients' prognoses. To address this issue, we developed a novel prognosis-related feature selection framework called Cascaded Wx (CWx). The CWx framework ranks features according to the survival of a given cohort by training neural networks with three different high- and low-risk groups in a cascaded fashion. We showed that this approach accurately identified features that best identify the patients' prognoses, compared to other feature selection algorithms, including the Cox proportional hazards and Coxnet models, when applied to The Cancer Genome Atlas lung adenocarcinoma (LUAD) transcriptome data. The prognostic potential of the top 100 genes identified by CWx outperformed or was comparable to those identified by the other methods as assessed by the concordance index ( c -index). In addition, the top 100 genes identified by CWx were found to be associated with the Wnt signaling pathway, providing biologically relevant evidence for the value of these genes in predicting the prognosis of patients with LUAD. Further analyses of other cancer types showed that the genes identified by CWx had the highest prognostic values according to the c -index. Collectively, the CWx framework will potentially be of great use to prognosis-related biomarker discoveries in a variety of diseases.

RNA biomarkers have been recently reported to be associated tightly with the diagnosis and prognosis of many diseases. Particularly, cancers considered to be a serious threat to primates are known to be vastly dominated by genetic networks where RNA plays a key role. RNAs are thus recognized as a major target group that can be used for numerous cancer treatments and it is still required to identify and enumerate them in an effective manner. Here, a new topological transformation-based nanobarcoding technique (TNT) is first reported using fluorescence-DNA barcodes engaged with graphene oxide (GO x ) for effectively discriminating short RNAs such as miRNAs and their single nucleotide polyporphisms in tissue and plasma. Through topological transformation into 3D DNA-RNA polygonal structures, various kinds of microRNAs have been read at the same time and analyzed quantitatively. Also, it positively discerned epidermal growth factor receptor (EGFR) mutations known as single base variations of typical lung cancer specific RNAs. A single variant of 0.785% in target EGFR mutations is explicitly detected. It is speculated that the TNT may be a versatile method for polymerase chain reaction (PCR)-free practical diagnosis of several clinical genetic deviations such as significant biotic RNA and genic fragments and would be a promising alternative to conventional PCR terrains., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A wake monochromator based on a large-area diamond single crystal for hard X-ray self-seeding has been successfully installed and commissioned in the hard X-ray free-electron laser (FEL) at the Pohang Accelerator Laboratory with international collaboration. For this commissioning, the self-seeding was demonstrated with a low bunch charge (40 pC) and the nominal bunch charge (180 pC) of self-amplified spontaneous emission (SASE) operation. The FEL pulse lengths were estimated as 7 fs and 29.5 fs, respectively. In both cases, the average spectral brightness increased by more than three times compared with the SASE mode. The self-seeding experiment was demonstrated for the first time using a crystal with a thickness of 30 µm, and a narrow bandwidth of 0.22 eV (full width at half-maximum) was obtained at 8.3 keV, which confirmed the functionality of a crystal with such a small thickness. In the nominal bunch-charge self-seeding experiment, the histogram of the intensity integrated over a 1 eV bandwidth showed a well defined Gaussian profile, which is evidence of the saturated FEL and a minimal electron-energy jitter (∼1.2 × 10 -4 ) effect. The corresponding low photon-energy jitter (∼2.4 × 10 -4 ) of the SASE FEL pulse, which is two times lower than the Pierce parameter, enabled the seeding power to be maximized by maintaining the spectral overlap between SASE FEL gain and the monochromator.

Background: Atrophic acne facial scars still pose a treatment challenge. Needle-free high-pressure pneumatic injection has recently been introduced; however, few studies exist regarding its effectiveness., Objective: To evaluate the efficacy and safety of pneumatic injection for treating atrophic acne scars using a 3-dimensional optical profiling system., Methods and Materials: A pneumatic injection device with a 0.2-mm nozzle diameter, 50% pressure power, and 85-μL injection volume was used. The degree of depression was examined and analyzed using a 3-dimensional optical profiling system and clinical photographs. The patients also evaluated any side effects. Each subject underwent a single treatment session and was followed up after 1 and 2 months., Results: A total of 13 atrophic acne scars from 10 Korean men and women aged 20 to 29 (mean age 25.8 ± 2.4) years were studied. The mean scar volume values were 0.964, 0.741, and 0.566 mm, respectively, at baseline, 1 month, and 2 months after the injection. Scar volumes after 2 months were significantly different compared with baseline volumes. However, there was no significant difference between the baseline and 1-month volumes., Conclusion: Treatment with pneumatic injection is safe and effective in reducing atrophic acne facial scars; it results in quantitative improvement in scar volumes.

Perfluorinated compounds (PFCs) are widely distributed in nature and have many applications due to their unique chemical and physicochemical properties. While, PFCs are present in soil, water, and air, their pathway for entry into the human body is circumstantially via contaminated food. The demand for seafood has been increasing. In this study, we investigated via LC-MS/MS, the content of 19 different types of PFCs in 302 samples belonging to five different categories of the typical South Korean seafood. The highest levels of PFOA, PFTrDA, PFOS, and PFPeA were found in dried seafood, canned and salted seafood, processed fish food, and seasoned laver, respectively. The levels of PFOA and PFOS were compared on the basis of various criteria including the nomenclature, biological classification, and habitat of the source of seafood. High levels of PFOA and PFOS were detected in anchovy, sea squirt, and mackerel based on the nomenclature of raw seafood, in crustaceans based on the biological classification, and in demersal organisms based on the habitat. The human intake values of PFOA and PFOS from the processed marine products in South Korea were lower than the tolerable daily intake, indicating that the consumption of these processed seafood poses no immediate harm., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Needle-free pneumatic injections have been recently introduced to the field of dermatology to inject such substances as hyaluronic acid. However, data on the influence of various pneumatic injection parameters on collagen synthesis are lacking., Objective: Compare the effect of diameter, pressure, and volume of a pneumatic injection jet on collagen synthesis and fluid dispersion pattern using a rat model. Investigate if the total work force of the injection jet is useful in predicting the degree of collagen synthesis., Materials and Methods: We injected fluid with 1 mg/ml of hyaluronic concentration to adult rats. Different injection pressures and volumes were tested using devices with nozzles of different diameters. Collagen synthesis areas were then measured, and statistical analyses were performed., Results: The area of collagen fibers increased for up to two months. The injection pressure and volume did not correlate with the degree of collagen synthesis. The nozzle diameter showed a significant after two and four weeks of injection. The total work force correlated with collagen synthesis 2, 4, and 8 weeks post-injection. (P = 0.043, 0.027, and 0.000, respectively)., Conclusion: Collagen formation is more prominent 2 months post-hyaluronic acid injection than after 1 month when using a needle-free pneumatic injection device. The total work force, which is affected by both the nozzle diameter and injection pressure, can be helpful in predicting the degree of collagen synthesis. Lasers Surg. Med. 51:278-285, 2019. © 2019 Wiley Periodicals, Inc., (© 2019 Wiley Periodicals, Inc.)

Pax6 transcription factor is a key player in several aspects of brain development and function. Autism spectrum disorder (ASD) is a neurodevelopmental disorder in which several loci and/or genes have been suggested as causative candidate factors. Based on data obtained from meta-analyses of the transcriptome and ChIP analyses, we hypothesized that the neurodevelopmental gene PAX6 regulates and/or binds to a large number of genes (including many ASD-related ones) that modulate the fate of neural stem/progenitor cells and functions of neuronal cells, subsequently affecting animal behavior. Network analyses of PAX6/ASD-related molecules revealed significant clusters of molecular interactions involving regulation of cell-cell adhesion, ion transport, and transcriptional regulation. We discuss a novel function of Pax6 as a chromatin modulator that alters the chromatin status of ASD genes, thereby inducing diverse phenotypes of ASD and related neurodevelopmental diseases., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Two-dimensional (2D) transition metal dichalcogenides with van der Waals gaps have attracted much attention due to their peculiarly distinctive physical properties from their bulk counterparts. Among them, vanadium diselenide (VSe2) has been considered to be a promising candidate for future spintronic devices, as room temperature ferromagnetism was reported recently. However, detailed crystallography and properties of VSe2 nanosheets have been less explored. Here, we report the atomistic real-space observation of the van der Waals layered structure of VSe2 for the first time. Furthermore, simply by controlling the carrier gas flow rate, a morphological variation of the surface area and thickness of VSe2 nanosheets was observed. The room temperature ferromagnetic feature of single VSe2 nanosheets was also revealed by magnetic force microscopy measurements. Our findings will play a significant role in the research of intrinsic 2D ferromagnetic materials.