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Background Treatment options for patients with melanoma brain metastasis (MBM) have changed significantly in the last decade. Few studies have evaluated changes in outcomes and factors associated with survival in MBM patients over time. The aim of this study is to evaluate changes in clinical features and overall survival (OS) for MBM patients. Methods Patients diagnosed with MBMs from 1/1/2009 to 12/31/2013 (Prior Era; PE) and 1/1/2014 to 12/31/2018 (Current Era; CE) at The University of Texas MD Anderson Cancer Center were included in this retrospective analysis. The primary outcome measure was OS. Log-rank test assessed differences between groups; multivariable analyses were performed with Cox proportional hazards models and recursive partitioning analysis (RPA). Results A total of 791 MBM patients (PE, n = 332; CE, n = 459) were included in analysis. Median OS from MBM diagnosis was 10.3 months (95% CI, 8.9–12.4) and improved in the CE vs PE (14.4 vs 10.3 months, P Conclusions OS and factors associated with OS have changed for MBM patients. This information can inform contemporary patient management and clinical investigations.

Background A recent phase III trial (NCT01372774) comparing use of stereotactic radiosurgery [SRS] versus whole-brain radiation therapy [WBRT] after surgical resection of a single brain metastasis revealed that declines in cognitive function were more common with WBRT than with SRS. A secondary endpoint in that trial, and the primary objective in this secondary analysis, was to identify baseline biomarkers associated with cognitive impairment after either form of radiotherapy for brain metastasis. Here we report our findings on APOE genotype and serum levels of associated proteins and their association with radiation-induced neurocognitive decline. Methods In this retrospective analysis of prospectively collected samples from a completed randomized clinical trial, patients provided blood samples every 3 months that were tested by genotyping and enzyme-linked immunosorbent assay, and results were analyzed in association with cognitive impairment. Results The APOE genotype was not associated with neurocognitive impairment at 3 months. However, low serum levels of ApoJ, ApoE, or ApoA protein (all P < .01) and higher amyloid beta (Aβ 1–42) levels (P = .048) at baseline indicated a greater likelihood of neurocognitive decline at 3 months after SRS, whereas lower ApoJ levels were associated with decline after WBRT (P = .014). Conclusions Patients with these pretreatment serum markers should be counseled about radiation-related neurocognitive decline.

The incidence of liver cirrhosis is increasing worldwide. Patients with cirrhosis are generally at a higher risk of harbouring hepatic and non-hepatic malignancies, including bladder cancer, likely due to the presence of related risk factors such as smoking. Cirrhosis can complicate both the operative and non-surgical management of bladder cancer. For example, cirrhotic patients undergoing abdominal surgery generally demonstrate worse postoperative outcomes, and chemotherapy in patients with cirrhosis often requires dose reduction due to its direct hepatotoxic effects and reduced hepatic clearance. Multiple other considerations in the peri-operative management for cirrhosis patients with muscle-invasive bladder cancer must be taken into account to optimize outcomes in these patients. Unfortunately, the current literature specifically related to the treatment of cirrhotic bladder cancer patients remains sparse. We aim to review the literature on treatment considerations for this patient population with respect to perioperative, surgical, and adjuvant management.

The ε4 allele of the apolipoprotein E (APOE) gene, a genetic risk factor for Alzheimer's disease, is abundantly expressed in both the brain and periphery. Here, we present evidence that peripheral apoE isoforms, separated from those in the brain by the blood-brain barrier, differentially impact Alzheimer's disease pathogenesis and cognition. To evaluate the function of peripheral apoE, we developed conditional mouse models expressing human APOE3 or APOE4 in the liver with no detectable apoE in the brain. Liver-expressed apoE4 compromised synaptic plasticity and cognition by impairing cerebrovascular functions. Plasma proteome profiling revealed apoE isoform-dependent functional pathways highlighting cell adhesion, lipoprotein metabolism and complement activation. ApoE3 plasma from young mice improved cognition and reduced vessel-associated gliosis when transfused into aged mice, whereas apoE4 compromised the beneficial effects of young plasma. A human induced pluripotent stem cell-derived endothelial cell model recapitulated the plasma apoE isoform-specific effect on endothelial integrity, further supporting a vascular-related mechanism. Upon breeding with amyloid model mice, liver-expressed apoE4 exacerbated brain amyloid pathology, whereas apoE3 reduced it. Our findings demonstrate pathogenic effects of peripheral apoE4, providing a strong rationale for targeting peripheral apoE to treat Alzheimer's disease.

Quick and reliable mass testing of infected people is an effective tool for the contingency of SARS-CoV-2. During the COVID-19 pandemic, Point-of-Care (POC) tests using Loop-Mediated Isothermal Amplification (LAMP) arose as a useful diagnostic tool. LAMP tests are a robust and fast alternative to Polymerase Chain Reaction (PCR), and their isothermal property allows easy incorporation into POC platforms. The main drawback of using colorimetric LAMP is the reported short-term stability of the pre-mixed reagents, as well as the relatively high rate of false-positive results. Also, low-magnitude amplification can produce a subtle color change, making it difficult to discern a positive reaction. This paper presents Hilab Molecular, a portable device that uses the Internet of Things and Artificial Intelligence to pre-analyze colorimetric data. In addition, we established manufacturing procedures to increase the stability of colorimetric RT-LAMP tests. We show that ready-to-use reactions can be stored for up to 120 days at −20 °C. Furthermore, we validated both the Hilab Molecular device and the Hilab RT-LAMP test for SARS-CoV-2 using 581 patient samples without any purification steps. We achieved a sensitivity of 92.93% and specificity of 99.42% (samples with CT ≤ 30) when compared to RT-qPCR.

The present study describes evaluation of epigenetic regulation by a small molecule as the therapeutic potential for treatment of Huntington’s disease (HD). We identified 5-allyloxy-2-(pyrrolidin-1-yl)quinoline (APQ) as a novel SETDB1/ESET inhibitor using a combined in silico and in vitro cell based screening system. APQ reduced SETDB1 activity and H3K9me3 levels in a HD cell line model. In particular, not only APQ reduced H3K9me3 levels in the striatum but it also improved motor function and neuropathological symptoms such as neuronal size and activity in HD transgenic (YAC128) mice with minimal toxicity. Using H3K9me3-ChIP and genome-wide sequencing, we also confirmed that APQ modulates H3K9me3-landscaped epigenomes in YAC128 mice. These data provide that APQ, a novel small molecule SETDB1 inhibitor, coordinates H3K9me-dependent heterochromatin remodelling and can be an epigenetic drug for treating HD, leading with hope in clinical trials of HD., Graphical Abstract

The nematic phase in iron based superconductors (IBSs) has attracted attention with a notion that it may provide important clue to the superconductivity. A series of angle-resolved photoemission spectroscopy (ARPES) studies were performed to understand the origin of the nematic phase. However, there is lack of ARPES study on LaFeAsO nematic phase. Here, we report the results of ARPES studies of the nematic phase in LaFeAsO. Degeneracy breaking between the $$d_{xz}$$ d xz and $$d_{yz}$$ d yz hole bands near the $$\Gamma$$ Γ and M point is observed in the nematic phase. Different temperature dependent band splitting behaviors are observed at the $$\Gamma$$ Γ and M points. The energy of the band splitting near the M point decreases as the temperature decreases while it has little temperature dependence near the $$\Gamma$$ Γ point. The nematic nature of the band shift near the M point is confirmed through a detwin experiment using a piezo device. Since a momentum dependent splitting behavior has been observed in other iron based superconductors, our observation confirms that the behavior is a universal one among iron based superconductors.

Obtaining spatially continuous, high resolution thermal images is crucial in order to effectively analyze heat-related phenomena in urban areas and the inherent high spatial and temporal variations. Spatiotemporal Fusion (STF) methods can be applied to enhance spatial and temporal resolutions simultaneously, but most STF approaches for the generation of Land Surface Temperature (LST) have not focused specifically on urban regions. This study therefore proposes a two-phase approach using Landsat 8 and MODIS images acquired on a study area in Beijing to first, investigate the sharpening of the fine resolution image input with urban-related spectral indices and second, to explore the potential of implementing the sharpened results into the Spatiotemporal Adaptive Data Fusion Algorithm for Temperature Mapping (SADFAT) to generate high spatiotemporal resolution LST images in urban areas. For this test, five urban indices were selected based on their correlation with brightness temperature. In the thermal sharpening phase, the Fractional Urban Cover (FUC) index was able to delineate spatial details in urban regions whilst maintaining its correlation with the original brightness temperature image. In the STF phase however, FUC sharpened results returned relatively high levels of correlation coefficient values up to 0.689, but suffered from the highest Root Mean Squared Error (RMSE) and Average Absolute Difference (AAD) values of 4.260 K and 2.928 K, respectively. In contrast, Normalized Difference Building Index (NDBI) sharpened results recorded the lowest RMSE and AAD values of 3.126 K and 2.325 K, but also the lowest CC values. However, STF results were effective in delineating fine spatial details, ultimately demonstrating the potential of using sharpened urban or built-up indices as a means to generate sharpened thermal images for urban areas, as well as for input images in the SADFAT algorithm. The results from this study can be used to further improve STF approaches for daily and spatially continuous mapping of LST in urban areas.

The spatial and angular organization of biological macromolecules is a key determinant, as well as informative readout, of their function. Correlative imaging of the dynamic spatio-angular architecture of cells and organelles is valuable, but remains challenging with current methods. Correlative imaging of spatio-angular dynamics requires fast polarization-, depth-, and wavelength-diverse measurement of intrinsic optical properties and fluorescent labels. We report a multimodal instant polarization microscope (miPolScope) that combines a broadband polarization-resolved detector, automation, and reconstruction algorithms to enable label-free imaging of phase, retardance, and orientation, multiplexed with fluorescence imaging of concentration, anisotropy, and orientation of molecules at diffraction-limited resolution and high speed. miPolScope enabled multimodal imaging of myofibril architecture and contractile activity of beating cardiomyocytes, cell and organelle architecture of live HEK293T and U2OS cells, and density and anisotropy of white and grey matter of mouse brain tissue across the visible spectrum. We anticipate these developments in joint quantitative imaging of density and anisotropy to enable new studies in tissue pathology, mechanobiology, and imaging-based screens.

Elucidating the wiring diagram of the human cell is a central goal of the postgenomic era. We combined genome engineering, confocal live-cell imaging, mass spectrometry, and data science to systematically map the localization and interactions of human proteins. Our approach provides a data-driven description of the molecular and spatial networks that organize the proteome. Unsupervised clustering of these networks delineates functional communities that facilitate biological discovery. We found that remarkably precise functional information can be derived from protein localization patterns, which often contain enough information to identify molecular interactions, and that RNA binding proteins form a specific subgroup defined by unique interaction and localization properties. Paired with a fully interactive website (opencell.czbiohub.org), our work constitutes a resource for the quantitative cartography of human cellular organization.

Study question Is the prostaglandin D2 (PGD2) associated with growing follicles and ovarian reserve of poor ovarian responders? Summary answer PGD2 is correlated with ovarian stimulation activity and follicle growth. Especially, poor ovarian responders show a significant decrease in the level of follicular fluid. What is known already Prostaglandins (PGs) are involved in the female reproductive process, mainly ovulation, fertilization, and implantation. Study design, size, duration We investigated the PGD2 level in the follicular fluid of poor ovarian responders. The collection of human follicular fluid was approved by the Institutional Research and Ethical Committees of CHA University (approval number: 1044308–201611-BR–027–04) from January to December 2019. Follicular fluid was collected from patients with normal ovarian response and patients with POR. Participants/materials, setting, methods We studied whether prostaglandin has related to POR in the clinical key factor by measuring human follicular fluid. Follicular fluid was collected from patients with normal ovarian response and patients with POR. The concentration of PGD2 in follicular fluid was determined with ELISA kits following the manufacturer’s protocol. Main results and the role of chance We analyzed the level of PGD2 in the follicular fluid of patients with normal ovarian response and patients with POR using an ELISA. The PGD2 concentration was significantly lower in the follicular fluid of patients with POR than in the follicular fluid of young and old patients with normal ovarian response. Limitations, reasons for caution This study has an identification of biomarker of the clinical samples as POR criteria patients. Therefore, further investigations aimed at specific recovery of low PGD2 metabolic activity in the CCs during control ovarian stimulation. Wider implications of the findings: Until now there is no specific biomarker of POR. AMH is just an ovary reserve marker for an indication of ovary function. PGD2 is one of the metabolites in steroid metabolism in the ovary. Therefore, we can find some cure through further study for improved PGD2 production to POR patients. Trial registration number none

Study question What is primary factor of bioenergetics product activity between microtubule instability and the functional activity of mitochondria in embryo? Summary answer The actin cytoskeleton instability is presumably the primary cause for the bioenergenesis of mitochondrial function to the preimplantation embryo development. What is known already Mitochondria are cellular organelles dynamically moving and morphological changes. It provides for homeostatic energy to the cell. The dynamic property of the mitochondria is associated with the microtubule network in the cell. However, the stability of the microtubule was clearly identified for preimplantation embryo development. Study design, size, duration This study is designed to assess the ATP productivity of the mitochondria, and specifically to observe what its primary factor is in terms of providing microtubule stability in mammalian cells. Additionally, we investigated the relationship between blastocyst formation and actin cytoskeleton stabilization by EpD with 2-cell mice. Participants/materials, setting, methods We prepared the microtubule stability regulation model with the HEK293 cell line by using the microtubule stabilizer as an Epothilone D (EpD). Then we analyzed the metabolic activity of the cells through oxidative phosphorylation (OXP) ratios analysis. Also, we performed confocal live imaging to observe mitochondria morphology depending on the cells’ microtubule. Next, we treated EpD to 2-cell culture media for the analysis of blastocyst development ratios. Main results and the role of chance EpD significantly increased fusion form. Also, EpD enhance bioenergy ratios like OXP in the mitochondria and functional activity related marker, like mTOR compared with the control. These results suggest that microtubule stabilization enhances mitochondrial metabolism by increasing oxygen consumption. Also, EpD in 2-cell culture media led to a significant increase in the speed of development and 50% higher hatched out blastocyst formation ratios compared to the control group. Limitations, reasons for caution This study had limited animal experiments. For the next study, we are planning with an aim to improve the quality and development ratios of human embryos by EpD. Wider implications of the findings: Microtubule stabilizer has a possibility to recover the mitochondria’s functional activity in the preimplantation embryo development. Mitochondrial functional activity along the actin cytoskeleton may play a pivotal role in determining the embryo quality and development ratios for archive pregnancy. Trial registration number non-clinical trials

Study question Lovastatin enhanced E2 productive ratios in the cumulus cells through promoted expression of Low-density lipoprotein receptor (LDLR). Summary answer Lovastatin up-regulated gene expression of LDLR in the CCs. And the high expression of LDLR promoted E2 productive ratios from CCs. What is known already We already reported that the up-regulation of LDLR correlated with clinical pregnancy. Therefore, we found lovastatin as an up-regulator of LDLR expression of clinical pregnancy. Study design, size, duration This is an expended study of LDLR to enhance steroidogenesis regarding the effect of lovastatin in the CCs. The collection of human cumulus cells was approved by the Institutional Research and Ethical Committees of CHA University (approval number: 1044308–201611-BR–027–04) from January to December 2019. The CCs were collected from 12 patients with normal ovarian response after oocyte denudation for ICSI. Participants/materials, setting, methods We studied whether lovastatin has up-regulated LDLR expression in human CCs. Cumulus cells were collected from patients with young (∼ 36) and old aged patients (37 ∼). After culturing human CCs, they were treated lovastatin for one day. The concentration of E2 in culture medium was measured using Chemiluminescence immunoassay. The mRNA isolated from CCs was analyzed gene expression level through real time-PCR. Main results and the role of chance The concentration of E2 was significantly increased in the culture medium treated with lovastatin. The CCs treated with lovastatin increased the expression of LDLR and StAR which are components of the steroidogenesis pathway. Limitations, reasons for caution We have found that the role of lovastatin promotes the E2 production by increasing the ldlr gene of CCs. Therefore, further investigations aimed at lovastatin effect on human oocytes embryo whether enhanced quality of oocytes or not. Wider implications of the findings: Previous data show that high activation of LDLR and StAR was associated with embryo quality and clinical pregnancy in infertile women. Our data suggest that lovastatin is stimulated LDLR expression to enhanced pregnancy ratios of IVF patients. Trial registration number none

Background Deaths in gluteal autografting occur due to gluteal vein injuries, but data are lacking on the precise location and caliber of these veins. Objectives The authors sought to present the first in vivo study of gluteal vein anatomy utilizing magnetic resonance imaging. Methods Magnetic resonance imaging venography of 16 volunteer hemi-sections was conducted in the supine, prone, prone with a bump (jack-knife), and left and right decubitus positions in 1 session after a single contrast administration. Caliber and course of the superior and inferior gluteal veins (SGV/IGV) were analyzed vs bony landmarks and position changes. Results The SGV has a very short submuscular course before splitting into 2 smaller branches superolaterally. The IGV runs immediately deep to the gluteus maximus in the center of the buttock as a single large trunk, on average 56 mm deep (mean 27 mm of muscle belly and 30 mm subcutaneous fat). No intramuscular or subcutaneous branches greater than 2 mm were found. In the prone position, the IGV and SGV have an average caliber of 5.96 mm and 5.63 mm. Vessel caliber decreased by 21% and 27%, respectively, in the jack-knife position and by 14% and 15% in lateral decubitus. Conclusions The SGV and IGV are immediately deep to gluteus maximus approximately 6 cm deep with a caliber on the order of 6 mm in the prone position. The distribution of these vessels suggests there is no “safe zone” in the intramuscular or submuscular planes. The jackknife or lateral decubitus positions can decrease vein caliber by up to 27%, possibly reducing the risk of injury due to either traction or direct cannula impact.

Omental infarction, a rare cause of acute abdominal pain, is usually difficult to diagnose before surgery. Several studies have shown that CT is useful in diagnosing an omental infarction. We report the first case of an omental infarction secondary to rib cage anomaly associated with achondroplasia. Preoperative CT revealed a fatty mass in the anterior perihepatic space and anterior flaring of the ribs. The patient, a 41-year-old man, was diagnosed with omental infarction in the anterior perihepatic space and treated with intravenous painkillers. After discharge, because of recurrent abdominal pain, he was readmitted and successfully underwent laparoscopic partial omentectomy. The mass was confirmed to be an infarcted omentum with fat necrosis and hemorrhage. Thus, omental infarction should be considered as a differential diagnosis for acute abdominal pain, especially in patients with achondroplasia. Contrast-enhanced abdominal CT can help in correctly diagnosing a suspected omental infarction.

To achieve a high concentration of dopants over 1 × 1020 cm-3 on germanium (Ge), co-doping with phosphorus (P) and antimony (Sb) by plasma assisted atomic layer deposition (PALD) and a subsequent annealing process [rapid thermal annealing process (RTP) or flash lamp annealing process (FLP)] are proposed and investigated. We found that the PALD stacked co-doping (POx /SiOy and Sb2O5 ) films were uniformly deposited. Using the conventional RTP method led to a low doping concentration (19 cm-3 ). However, FLP with a Xenon (Xe) lamp (lamp duration: 3 ms; energy density: 56 J/cm2 ) raised the surface temperature to nearly 800 °C. Furthermore, high concentrations of both P and Sb (>1 × 1020 cm-3 ) were achieved at the surface. Our findings suggest that the FLP with high energy in a short amount of time (~3 ms) can create the peak power effect and the co-doping effect. The evidence shows that these effects contribute to enhancing n-type doping levels in the Ge structure.

A major rate-limiting step in developing more effective immunotherapies for GBM is our inadequate understanding of the cellular complexity and the molecular heterogeneity of immune infiltrates in gliomas. Here, we report an integrated analysis of 201,986 human glioma, immune, and other stromal cells at the single cell level. In doing so, we discover extensive spatial and molecular heterogeneity in immune infiltrates. We identify molecular signatures for nine distinct myeloid cell subtypes, of which five are independent prognostic indicators of glioma patient survival. Furthermore, we identify S100A4 as a regulator of immune suppressive T and myeloid cells in GBM and demonstrate that deleting S100a4 in non-cancer cells is sufficient to reprogram the immune landscape and significantly improve survival. This study provides insights into spatial, molecular, and functional heterogeneity of glioma and glioma-associated immune cells and demonstrates the utility of this dataset for discovering therapeutic targets for this poorly immunogenic cancer.

Author(s): Crawford, Emily D; Acosta, Irene; Ahyong, Vida; Anderson, Erika C; Arevalo, Shaun; Asarnow, Daniel; Axelrod, Shannon; Ayscue, Patrick; Azimi, Camillia S; Azumaya, Caleigh M; Bachl, Stefanie; Bachmutsky, Iris; Bhaduri, Aparna; Brown, Jeremy Bancroft; Batson, Joshua; Behnert, Astrid; Boileau, Ryan M; Bollam, Saumya R; Bonny, Alain R; Booth, David; Borja, Michael Jerico B; Brown, David; Buie, Bryan; Burnett, Cassandra E; Byrnes, Lauren E; Cabral, Katelyn A; Cabrera, Joana P; Caldera, Saharai; Canales, Gabriela; Castaneda, Gloria R; Chan, Agnes Protacio; Chang, Christopher R; Charles-Orszag, Arthur; Cheung, Carly; Chio, Unseng; Chow, Eric D; Citron, Y Rose; Cohen, Allison; Cohn, Lillian B; Chiu, Charles; Cole, Mitchel A; Conrad, Daniel N; Constantino, Angela; Cote, Andrew; Crayton-Hall, Tre'Jon; Darmanis, Spyros; Detweiler, Angela M; Dial, Rebekah L; Dong, Shen; Duarte, Elias M; Dynerman, David; Egger, Rebecca; Fanton, Alison; Frumm, Stacey M; Fu, Becky Xu Hua; Garcia, Valentina E; Garcia, Julie; Gladkova, Christina; Goldman, Miriam; Gomez-Sjoberg, Rafael; Gordon, M Grace; Grove, James CR; Gupta, Shweta; Haddjeri-Hopkins, Alexis; Hadley, Pierce; Haliburton, John; Hao, Samantha L; Hartoularos, George; Herrera, Nadia; Hilberg, Melissa; Ho, Kit Ying E; Hoppe, Nicholas; Hosseinzadeh, Shayan; Howard, Conor J; Hussmann, Jeffrey A; Hwang, Elizabeth; Ingebrigtsen, Danielle; Jackson, Julia R; Jowhar, Ziad M; Kain, Danielle; Kim, James YS; Kistler, Amy; Kreutzfeld, Oriana; Kulsuptrakul, Jessie; Kung, Andrew F

Introduction The coronavirus disease 2019 (COVID-19) pandemic has been unprecedented in recent history. The rapid global spread has demonstrated how the emergence of a novel pathogen necessitates new information to advise both healthcare systems and policy-makers. The directives for the management of COVID-19 have been limited to infection control measures and treatment of patients, which has left physicians and researchers alone to navigate the massive amount of research being published while searching for evidence-based strategies to care for patients. To tackle this barrier, we launched CovidReview.ca, an open-access, continually updated, online platform that screens available COVID-19 research to determine higher quality publications. This paper uses data from this review process to explore the activity and trends of COVID-19 research worldwide over time, while specifically looking at the types of studies being published. Materials and Methods The literature search was conducted on PubMed. Search terms included “COVID-19”, “severe acute respiratory syndrome coronavirus 2”, “coronavirus 19”, “SARS-COV-2”, and “2019-nCoV”. All articles captured by this strategy were reviewed by a minimum of two reviewers and categorized by type of research, relevant medical specialties, and type of publication. Criteria were developed to allow for inclusion or exclusion to the website. Due to the volume of research, only a level 1 (title and abstract) screen was performed. Results The time period for the analysis was January 17, 2020, to May 10, 2020. The total number of papers captured by the search criteria was 10,685, of which 2,742 were included on the website and 7,943 were excluded. The greatest increase in the types of studies over the 16 weeks was narrative review/expert opinion papers followed by case series/reports. Meta-analyses, systematic reviews, and randomized controlled trials remained the least published types of studies. Conclusions The surge of research that accompanied the COVID-19 pandemic is unparalleled in recent years. From our analysis, it is clear that case reports and narrative reviews were the most widely published, particularly in the earlier days of this pandemic. Continued research that falls higher on the evidence pyramid and is more applicable to clinical settings is warranted.

The nematic phase in iron based superconductors (IBSs) has attracted attention with a notion that it may provide important clue to the superconductivity. A series of angle-resolved photoemission spectroscopy (ARPES) studies were performed to understand the origin of the nematic phase. However, there is lack of ARPES study on LaFeAsO nematic phase. Here, we report the results of ARPES studies of the nematic phase in LaFeAsO. Degeneracy breaking between the \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$d_{xz}$$\end{document}dxz and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$d_{yz}$$\end{document}dyz hole bands near the \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\Gamma$$\end{document}Γ and M point is observed in the nematic phase. Different temperature dependent band splitting behaviors are observed at the \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\Gamma$$\end{document}Γ and M points. The energy of the band splitting near the M point decreases as the temperature decreases while it has little temperature dependence near the \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\Gamma$$\end{document}Γ point. The nematic nature of the band shift near the M point is confirmed through a detwin experiment using a piezo device. Since a momentum dependent splitting behavior has been observed in other iron based superconductors, our observation confirms that the behavior is a universal one among iron based superconductors.

Continued scaling of electronic devices shows the need to incorporate high mobility alternatives to silicon, the cornerstone of the semiconductor industry, into modern field effect transistor (FET) devices. Germanium is well-poised to serve as the channel material in FET devices as it boasts an electron and hole mobility more than twice and four times that of Si, respectively. However, its unstable native oxide makes its passivation a crucial step toward its potential integration into future FETs. The International Roadmap for Devices and Systems (IRDS) predicts continued aggressive scaling not only of the device size but also of the pitch in nanowire arrays. The development of a vapor-phase chemical passivation technique will be required to prevent the collapse of these structures that can occur because of the surface tension and capillary forces that are experienced when tight-pitched nanowire arrays are processed via liquid-phase chemistry. Reported here is a vapor-phase process using hexanethiol for the passivation of planar Ge(100) substrates. Results benchmarking it against its well-established liquid-phase equivalent are also presented. X-ray photoelectron spectroscopy was used to monitor the effectiveness of the developed vapor-phase protocol, where the presence of oxide was monitored at 0, 24, and 168 h. Water contact angle measurements compliment these results by demonstrating an increase in hydrophobicity of the passivated substrates. Atomic force microscopy monitored the surface topology before and after processing to ensure the process does not cause roughening of the surface, which is critical to demonstrate suitability for nanostructures. It is shown that the 200 min vapor-phase passivation procedure generates stable, passivated surfaces with less roughness than the liquid-phase counterpart., Raw data from publication: ACS Appl. Mater. Inter. 2020, 12 (26), 29899-29907.

Background:. Implant malposition is one of the most common causes for revision after prosthetic breast reconstruction. There is a paucity of research on the incidence, etiology and risk factors for implant malposition in this setting. Methods:. Retrospective review of a single surgeon’s prosthetic breast reconstructions was performed. Variables collected included age, BMI, radiation, chemotherapy, implant characteristics and malposition location (inferior or lateral). Binary logistic regression identified risk factors for malposition. Chi-square test assessed malposition rate as a function of implant volume to BMI subgroups. Results:. Of 836 breasts, 82 (9.8%) exhibited implant malposition. Risk factors for any malposition were older age (OR 1.05, 95% CI 1.02-1.07), BMI

Background: The purpose of this study was to clarify the anatomy of the superior hypogastric plexus, which would contribute to advancement of nerve-sparing paraaortic lymphadenectomy. Materials and methods: Eighteen cadavers were dissected and morphometrically analysed based on photographic images. Anatomical landmarks such as aortic bifurcation, transitional points of abdominal aorta to bilateral common iliac arteries, and cross point of the right ureter and pelvic brim, and cross point of sigmoid mesentery and pelvic brim were selected as reference points. Results: The left lowest lumbar splanchnic nerve was located more laterally to transitional point of abdominal aorta to in 11/18 specimens, whereas the right lowest lumbar splanchnic nerve passed onto the right transitional point in only one specimen. The lowest lumbar splanchnic nerves or the superior hypogastric plexus covered the aortic bifurcation in 11/18 specimens. The superior hypogastric plexus was separate from the cross point of right ureter and pelvic brim as well as cross point of sigmoid mesentery and pelvic brim. Conclusions: The superior hypogastric plexus is at risk of injury during paraaortic lymphadenectomy because of its topography. Preservation of the superior hypogastric plexus regarding its anatomic basis during paraaortic lymphadenectomy is required.

Background Tumor necrosis factor (TNF) antagonists are recommended for patients with ulcerative colitis (UC) for the effectiveness in inducing and maintaining clinical remission. We investigated the altered fecal metabolites and lipids by anti-TNF treatment and prediction model of remission in patients with UC. Methods A prospective, observational multicenter study was conducted at 17 academic hospitals in Korea. Fecal samples were collected from adult patients with moderately to severely active UC (n=116) before and after 8 and 56 weeks of adalimumab treatment and from healthy controls (HC, n=37). Clinical remission was assessed using Mayo score. Metabolome and lipidome analyses were performed using gas chromatography-, and nano electro spray ionization-mass spectrometry, respectively. Prediction models of remission were developed using baseline fecal samples by Fourier transform-infrared (FT-IR) spectroscopy combined with machine learning algorithms. Results Fecal metabolites and lipids in UC were different from HC at baseline and were changed similarly to HC during treatment. Fecal metabolites and lipids in remitters (RM) after treatment were more grouped and clustered with those of HC compared with non-remitters (NRM). In RM, 2-aminobutyric acid, galactose and dodecanoate levels which were previously decreased at baseline compared to HC increased to the levels of HC, whereas benzoate, stigmasterol, 3-hydroxybutyrate, diacylglycerol and triacylglycerol levels which were previously increased at baseline compared to HC decreased to the levels of HC after 56 weeks of treatment. The best model predicting short-term remission was developed by applying logistic regression (LR) and radial basis functions (rbf) support vector machine (SVM) with an accuracy of 0.99 (95% confidence interval [CI], 0.98–1.01). For long-term remission, the best prediction model was developed by rbf-SVM revealing 0.99 [CI 0.98–1.01]. LR and K-nearest neighbors also showed excellent performance for prediction of long-term remission (accuracy of 0.96 [CI 0.90–1.02] and 0.96 [CI 0.92–1.00], respectively. Conclusion Fecal characteristics in UC were changed after anti-TNF treatment and became similar to those of HC. Potential therapeutic target compounds were suggested to develop novel therapeutic strategies for UC. Novel remission prediction models by FT-IR spectroscopy were also established.

Objectives No randomized controlled trials have evaluated the comparative outcomes of cefazolin versus nafcillin for methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia. Methods A prospective observational cohort study including all S. aureus bacteraemia was conducted at 10 hospitals. Patients (≥15 years) with MSSA bacteraemia who received cefazolin or nafcillin as definitive antibiotics were included. The rates of treatment failure (premature discontinuation of antibiotics because of adverse effects, switching of antibiotics because of clinical failure, all-cause mortality within 1 month, or recurrence) were compared between the cefazolin and nafcillin groups. Propensity score matching analyses were performed to balance the factors influencing the selection of antibiotics. Results Among the 242 included cases, the bones and joints (36.8%) were the most common sites of infection and 60.7% of the patients had sepsis. The overall treatment failure rate was 43.8% (106/242). All-cause mortality within 1 month was 6.2% (15/242). After propensity score matching, the treatment failure rate of cefazolin was lower than that of nafcillin (30.4% (24/79) vs. 49.4% (39/79), p 0.015) because of a higher rate of discontinuation caused by adverse events. When the data were limited to patients with sepsis, the treatment failure rates of both groups were not significantly different. Approximately 22% (24/110) of MSSA isolates exhibited a cefazolin-inoculum effect (CIE) that had significant impact on the failure rate and mortality of the cefazolin group. Conclusions Cefazolin might be recommended as an adequate and better-tolerated treatment for MSSA bacteraemia in the absence of CIE.

While haemodynamic variability interferes with the assumption of constant flow underlying thermodilution cardiac output calculation, variability in (peripheral) arterial vascular physiology may affect pulse contour cardiac output methods. We compared non-invasive finger arterial pressure-derived continuous cardiac output measurements (Nexfin® ) with cardiac output measured using thermodilution during cardiothoracic surgery and determined the impact of cardiovascular variability on either method. We compared cardiac output derived from non-invasive finger arterial pressure with cardiac output measured by thermodilution at four grades (A-D) of cardiovascular variability. We defined Grade A data as heart rate and mean arterial pressure variability < 5% and the absence of arrhythmias (implying stable flow) and Physiocal® interval (as measure of variability in finger arterial physiology) > 30 beats. Grade B included all levels of heart rate/mean arterial pressure variability and arrhythmias (Physiocal < 30 excluded). Grade C included all Physiocal intervals (heart rate/mean arterial pressure variability > 5% and arrhythmias excluded). Grade D included all data. Comparison results were quantified as percentage errors. We analysed measurements in 27 patients undergoing coronary artery bypass surgery. Before extracorporeal circulation, the percentage error was 23% (n = 14 patients) in grade A, 28% (n = 20) in grade B, 32% (n = 22) in grade C and 37% (n = 26) in grade D, with a significant increase in variance (p = 0.035). Bias did not differ between grades. After extracorporeal circulation (n = 27), percentage errors became larger, but were not different between grades. Variability during cardiothoracic surgery affected the comparison between thermodilution and non-invasive finger arterial pressure-derived cardiac output. When the main sources of variability were included, percentage errors were large. Future cardiac output methodology comparison studies should report haemodynamic variability.

Background We investigated the real-life effectiveness and safety of vedolizumab maintenance treatment among Korean patients with Crohn’s disease (CD) or ulcerative colitis (UC) who previously failed anti-tumour necrosis factor (anti-TNF) therapy. Methods Adult patients with CD or UC who have previously failed anti-TNF therapy and received vedolizumab were prospectively enrolled from 16 hospitals in Korea. The primary outcome was clinical remission at week 54. Clinical remission was defined as a Crohn’s disease activity index (CDAI) Results Between August 2017 to July 2020, a total of 165 patients (81 with CD and 84 with UC) received vedolizumab therapy, of whom 154 patients (93.3%) (75 with CD and 79 with UC) received vedolizumab maintenance therapy (Table 1). Clinical remission and response rates at week 54 were 22.2% and 24.1% among patients with CD and 41.4% and 45.7% among patients with UC, respectively (Figure 1A and 1B). Among 70 patients with UC with baseline Mayo endoscopic subscore ≥2, endoscopic remission (Mayo endoscopic subscore ≤1) at week 54 was observed in 19 patients (27.1%). Out of 50 patients with CD with ulcers in baseline endoscopy, 2 patients (4%) showed a disappearance of ulcers at week 54 (Figure 1C). In the multivariable analysis, age at baseline (adjusted odds ration [aOR] 1.065, 95% confidence interval [CI] 1.003–1.131, P=0.041) and Mayo endoscopic subscore at baseline (aOR 0.141, 95% CI 0.026–0.746, P=0.021) were significantly associated with clinical remission at week 54 among patients with UC (Table 2). No factors were found to be associated with clinical remission at week 54 among patients with CD. Among patients who experienced one or more adverse events (n=134, 81.2%), serious adverse events occurred in 82 patients (49.7%) (Table 3). Disease exacerbation was the most common adverse events (n=89, 53.9%). Conclusion The real-life effectiveness of vedolizumab maintenance treatment for Korean patients with UC who failed anti-TNF therapy was generally similar with the outcomes reported from the previous Western studies. A substantial proportion of patients with CD experienced a loss of response during the first year of treatment. Less severe disease at baseline was associated with clinical remission at 1 year of vedolizumab therapy among patients with UC.

Background We aimed to compare trough infliximab levels and the development of anti-drug antibody (ADA) for 1 year between Crohn’s disease (CD) and ulcerative colitis (UC) patients who were biologic-naïve and to evaluate their impact on clinical outcomes. Methods This was a prospective, multi-center, observational study. Biologic-naïve patients with moderate to severe CD and UC who started CT-P13 therapy were eligible for the study. The trough drug and ADA levels were measured serially for 1-year after CT-P13 initiation. Clinical outcomes were assessed with intention-to-treat purpose. Results 267 patients who received CT-P13 treatment were enrolled in the study (CD 168, UC 99). The rates of clinical remission (72% vs. 32.3%, p Conclusion CD shows favorable pharmacokinetics of infliximab including high trough drug and low ADA level compared with UC which might be related with better clinical outcomes for 1-year of infliximab.

Mitochondrial dysfunction is associated with neuronal damage in Huntington's disease (HD), but the precise mechanism of mitochondria-dependent pathogenesis is not understood yet. Herein, we found that colocalization of XIAP and p53 was prominent in the cytosolic compartments of normal subjects but reduced in HD patients and HD transgenic animal models. Overexpression of mutant Huntingtin (mHTT) reduced XIAP levels and elevated mitochondrial localization of p53 in striatal cells in vitro and in vivo. Interestingly, XIAP interacted directly with the C-terminal domain of p53 and decreased its stability via autophagy. Overexpression of XIAP prevented mitochondrially targeted-p53 (Mito-p53)-induced mitochondrial oxidative stress and striatal cell death, whereas, knockdown of XIAP exacerbated Mito-p53-induced neuronal damage in vitro. In vivo transduction of AAV-shRNA XIAP in the dorsal striatum induced rapid onset of disease and reduced the lifespan of HD transgenic (N171-82Q) mice compared to WT littermate mice. XIAP dysfunction led to ultrastructural changes of the mitochondrial cristae and nucleus morphology in striatal cells. Knockdown of XIAP exacerbated neuropathology and motor dysfunctions in N171-82Q mice. In contrast, XIAP overexpression improved neuropathology and motor behaviors in both AAV-mHTT-transduced mice and N171-82Q mice. Our data provides a molecular and pathological mechanism that deregulation of XIAP triggers mitochondria dysfunction and other neuropathological processes via the neurotoxic effect of p53 in HD. Together, the XIAP-p53 pathway is a novel pathological marker and can be a therapeutic target for improving the symptoms in HD.

In this study, we investigated an energy harvesting effect of tensile stress using piezoelectric polymers and flexible electrodes. A chemical-vapor-deposition grown graphene film was transferred onto both sides of the PVDF and P(VDF-TrFE) films simultaneously by means of a conventional wet chemical method. Output voltage induced by sound waves was measured and analyzed when a mechanical tension was applied to the device. Another energy harvester was made with a metallic electrode, where Al and Ag were deposited by using an electron-beam evaporator. When acoustic vibrations (105 dB) were applied to the graphene/PVDF/graphene device, an induced voltage of 7.6 Vpp was measured with a tensile stress of 1.75 MPa, and this was increased up to 9.1 Vpp with a stress of 2.18 MPa for the metal/P(VDF-TrFE)/metal device. The 9 metal/PVDF/metal layers were stacked as an energy harvester, and tension was applied by using springs. Also, we fabricated a full-wave rectifying circuit to store the electrical energy in a 100 μF capacitor, and external vibration generated the electrical charges. As a result, the stored voltage at the capacitor, obtained from the harvester via a bridge diode rectifier, was saturated to ~7.04 V after 180 s charging time.

Omental torsion and infarction are rare causes of acute abdominal pain, and it is often difficult to diagnose these conditions preoperatively. There are several reports showing that computed tomography is useful to diagnose these conditions. Here, we report a case of a 59-year-old man with omental infarction due to secondary omental torsion associated with an untreated inguinal hernia. Preoperative computed tomography showed a fatty mass in the right lower quadrant and a right inguinal hernia containing torsion of the greater omentum. He underwent laparoscopic partial omentectomy and herniorrhaphy, and the postoperative course was uneventful.

Development of tungsten brazing technology for the upgraded Korea superconducting tokamak advanced research divertor was launched in early 2013. ITER grade tungsten block was brazed on the CuCrZr alloy in vacuum at 980 °C for 30 min using silver free brazing alloy. An OFHC-copper was used as an interlayer between tungsten and the CuCuZr. The brazing alloy is a 0.05 mm thickness of plate of which component is a Ni–Cu–Mn. It is found that the optimal loading on mock-up is about 20 kPa. Ultrasonic test and shear strength test were carried out to check the strength between tungsten and substrate material. And the joint conditions were analyzed by scanning electron microscopy. Tungsten-brazed mock-ups with a cooling tube were tested at the electron beam facility, Korea heat load test facility-electron beam in Korea Atomic Energy Research Institute. The high heat flux test was performed for tungsten-brazed mock-ups under heat flux of about 5 MW/ $\text{m}^{2}$ with more than 2000 cycles. All the tungsten-brazed mock-ups met the requirements and there was no delamination or failure at the bonding joints.