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Invasive cancers that arise from ductal structures can infiltrate and colonize pre-existing ducts in a process referred to as cancerization of ducts (COD). COD in cholangiocarcinoma is an under-studied process whose clinical significance remains poorly understood. Even though both cancerized ducts and biliary intraepithelial neoplasias (BilINs) show dysplastic changes, hallmarks of COD are (i) an abrupt transition from the normal/reactive epithelium to severe dysplasia and (ii) close proximity to invasive carcinoma with similar cytologic features. We investigated 113 cases of surgically resected hilar cholangiocarcinoma and identified COD in 37 cases (33%). Using immunohistochemistry, we found that COD and adjacent invasive carcinoma had a concordant pattern of p53 and SMAD4 staining in 95% (21/22) and 100% (21/21) of cases, respectively. In contrast, BilINs and cancerized ducts showed significantly lower levels of concordance in p53 and SMAD4 staining at 44% (8/18) and 47% (8/17) of cases, respectively (P = 0.0007 and 0.0001, respectively). By univariate analysis, positive lymph node metastasis (P = 0.027), positive final bile duct margin (P = 0.021), and the presence of COD (P = 0.020) were associated with decreased overall survival. We further performed multivariate analysis to demonstrate that positive lymph node metastasis (P = 0.031), positive final bile duct margin (P = 0.035), and COD (P = 0.0051) were correlated with decreased overall survival. Together, our study highlights that COD is a clinically significant process in hilar cholangiocarcinoma that can be identified using morphological criteria in conjunction with p53 and SMAD4 immunolabeling.

This work presents a highly active electrocatalyst of CO

This paper presents an analysis of antenna performance degradation due to the panel misalignment in a solid surface deployable antenna. The misalignment of the panel causes a phase error at the aperture plane due to path length differences. The radiated field is rapidly calculated using the aperture phase error method with analytic integrations in the case of uniform panel misalignment and quarter-zone uniform misalignment. The effects of the panel misalignment on the co-polarization characteristics of gain and side-lobe level (SLL) are calculated. Beam tilting is observed when the panel misalignment occurs uniformly in the half-zone of the whole panel area.

Background Individuals with an incomplete spinal cord injury (iSCI) are highly susceptible to falls during periods of walking or standing. We recently reported the findings of a novel intervention combining functional electrical stimulation with visual feedback balance training (FES + VFBT) on standing balance abilities among five individuals with motor iSCI. However, the previous publication did not report the perceived impact of the intervention on the participants’ lives. In this report, the experiences of these five individuals with incomplete spinal cord injury (iSCI) who had recently completed the four-week balance training program are described. Methods Five individuals with a motor iSCI took part in this study. Each individual was at least 12 months post-injury, capable of unassisted standing for 60 s and had a Berg Balance Scale Score Results Three themes were identified from the collected transcripts: (1) Perceived benefits across International Classification of Functioning, Disability and Health levels; (2) Change in perceived fall risk and confidence; (3) Motivation to keep going. Conclusions Participation in the FES + VFBT program resulted in perceived benefits that led to meaningful improvements in activities of daily living. Following completion of the training, individuals felt they still had the capacity to improve. Individuals felt they had increased their balance confidence, while a few participants also reported a decrease in their risk of falling. The inclusion of qualitative inquiry allows for the evaluation of the meaningfulness of an intervention and its perceived impact on the lives of the participants. Trial registration: NCT04262414 (retrospectively registered February 10, 2020)

How a single neuronal population diversifies into subtypes with distinct synaptic targets is a fundamental topic in neuroscience whose underlying mechanisms are unclear. Here, we show that the histone H3-lysine 27 demethylase Kdm6b regulates the diversification of motor neurons to distinct subtypes innervating different muscle targets during spinal cord development. In mouse embryonic motor neurons, Kdm6b promotes the medial motor column (MMC) and hypaxial motor column (HMC) fates while inhibiting the lateral motor column (LMC) and preganglionic motor column (PGC) identities. Our single-cell RNA-sequencing analyses reveal the heterogeneity of PGC, LMC, and MMC motor neurons. Further, our single-cell RNA-sequencing data, combined with mouse model studies, demonstrates that Kdm6b acquires cell fate specificity together with the transcription factor complex Isl1-Lhx3. Our study provides mechanistic insight into the gene regulatory network regulating neuronal cell-type diversification and defines a regulatory role of Kdm6b in the generation of motor neuron subtypes in the mouse spinal cord.

Objective: To evaluate test-retest reliability, agreement, and convergent validity of the Lean-and-Release test for the assessment of reactive stepping among individuals with incomplete spinal cord injury or disease (iSCI/D). Design: Multi-center cross-sectional multiple test design. Setting: SCI/D rehabilitation hospital and biomechanics laboratory. Participants: Individuals with motor incomplete SCI/D (iSCI/D). Interventions: None. Outcome Measures: Twenty-six participants attended two sessions to complete the Lean-and-Release test and a battery of clinical tests. Behavioral (i.e. one-step, multi-step, loss of balance) and temporal (i.e. timing of foot off, foot contact, swing of reactive step) parameters were measured. Test-retest reliability was determined with intraclass correlation coefficients, and agreement was evaluated with Bland–Altman plots. Convergent validity was assessed through correlations with clinical tests. Results: The behavioral responses were reliable for the Lean-and-Release test (ICC = 0.76), but foot contact was the only reliable temporal parameter using data from a single site (ICC = 0.79). All variables showed agreement according to the Bland–Altman plots. The behavioral responses correlated with scores of lower extremity strength (0.54, P

Cobalt based catalysts having enhanced H

Lithium-sulfur (Li-S) batteries are one of the main challenges facing Li-ion technology because the insulating nature of sulfur and the shuttle phenomenon of dissolved lithium polysulfides (LPSs) in liquid electrolytes result in critical problems, including low Coulombic efficiency, loss of active material, and rapid capacity decay. Here, we oxidized delaminated transition metal carbides (MXenes) using CO

The liver is the most common site of metastatic disease1. Although this metastatic tropism may reflect the mechanical trapping of circulating tumour cells, liver metastasis is also dependent, at least in part, on the formation of a 'pro-metastatic' niche that supports the spread of tumour cells to the liver2,3. The mechanisms that direct the formation of this niche are poorly understood. Here we show that hepatocytes coordinate myeloid cell accumulation and fibrosis within the liver and, in doing so, increase the susceptibility of the liver to metastatic seeding and outgrowth. During early pancreatic tumorigenesis in mice, hepatocytes show activation of signal transducer and activator of transcription 3 (STAT3) signalling and increased production of serum amyloid A1 and A2 (referred to collectively as SAA). Overexpression of SAA by hepatocytes also occurs in patients with pancreatic and colorectal cancers that have metastasized to the liver, and many patients with locally advanced and metastatic disease show increases in circulating SAA. Activation of STAT3 in hepatocytes and the subsequent production of SAA depend on the release of interleukin 6 (IL-6) into the circulation by non-malignant cells. Genetic ablation or blockade of components of IL-6-STAT3-SAA signalling prevents the establishment of a pro-metastatic niche and inhibits liver metastasis. Our data identify an intercellular network underpinned by hepatocytes that forms the basis of a pro-metastatic niche in the liver, and identify new therapeutic targets.

Plantarflexors such as the soleus (SOL) and medial gastrocnemius (MG) play key roles in controlling bipedal stance; however, how the central nervous system controls the activation levels of these plantarflexors is not well understood. Here we investigated how the central nervous system controls the plantarflexors’ activation level during quiet standing in a cosine tuning manner where the maximal activation is achieved in a preferred direction (PD). Furthermore, we investigated how spinal cord injury affects these plantarflexors’ activations. Thirteen healthy adults (AB) and thirteen individuals with chronic, incomplete spinal cord injury (iSCI) performed quiet standing trials. Their body kinematics and kinetics as well as electromyography signals from the MG and SOL were recorded. In the AB group, we found that the plantarflexors followed the cosine tuning manner during quiet standing. That is, MG was most active when the ratio of plantarflexion torque to knee extension torque was ~2:-3, whereas SOL was most active when the ratio was ~2:1. This suggests that the SOL muscle, despite being a monoarticular muscle, is sensitive to both ankle plantarflexion and knee extension during quiet standing. The difference in the PDs accounts for the phasic activity of MG and for the tonic activity of SOL. Unlike the AB group, the MG’s activity was similar to the SOL’s activity in the iSCI group, and the SOL PDs were similar to those in the AB group. This result suggests that chronic iSCI affects the control strategy, i.e., cosine tuning, for MG, which may affect standing balance in individuals with iSCI. NEW & NOTEWORTHY Soleus muscle shows a tonic activity whereas medial gastrocnemius muscle shows a phasic activity during quiet standing. Cosine tuning and their preferred direction account for the different muscle activation patterns between these two muscles. In individuals with chronic incomplete spinal cord injury, the preferred direction of gastrocnemius medial head is affected, which may result in their deteriorated standing balance.

BackgroundWe previously reported that microvesicles (MVs) released by human mesenchymal stem cells (MSC) were as effective as the cells themselves in both Escherichia coli lipopolysaccharide and live bacteria-induced acute lung injury (ALI) mice models. However, it remained unclear whether the biological effect of MSC MV can be applied to human ALI.MethodsIn the current study, we tested the therapeutic effects of MSC MVs in a well-established ex vivo perfused human model of bacterial pneumonia. Using human donor lungs not used for transplantation, we instilled E. coli bacteria intrabronchially and, 1 hour later, administered MSC MVs into the perfusate as therapy.ResultsAfter 6 hours, instillation of E. coli bacteria caused influx of inflammatory cells, which resulted in significant inflammation, lung protein permeability and pulmonary oedema formation. Administration of MSC MV significantly increased alveolar fluid clearance and reduced protein permeability and numerically lowered the bacterial load in the injured alveolus. The beneficial effect on bacterial killing was more pronounced with pretreatment of MSCs with a Toll-like receptor 3 agonist, polyinosinic:polycytidylic acid (Poly (I:C)), prior to the isolation of MVs. Isolated human alveolar macrophages had increased antimicrobial activity with MSC MV treatment in vitro as well. Although oxygenation and lung compliance levels were similar between injury and treatment groups, administration of MSC MVs numerically decreased median pulmonary artery pressure at 6 hours.ConclusionsIn summary, MSC MVs increased alveolar fluid clearance and reduced lung protein permeability, and pretreatment with Poly (I:C) enhanced the antimicrobial activity of MVs in an ex vivo perfused human lung with severe bacteria pneumonia.

This work addressed the gas–liquid (G/L) mass transfer limitation coming from the increasing liquid height and the circumvention of the limitation by introducing a sieve tray in a bubble column. Either monoethylene glycol (MEG) solution or n-hexane was adopted as a liquid phase and argon was used as a gas phase in the bubble column. The gas holdup and the mass transfer coefficient became lowered by the static liquid height increase due to the increase of bubble size. The loss of mass transfer was overcome by installing a sieve tray inside the column. The two sieve trays with different hole sizes were employed and both bubble diameter and standard deviation of pressure were investigated to understand the effect of the sieve tray on the mass transfer. With a smaller size hole sieve (1 mm), the mass transfer deteriorated in both liquid systems (MEG and n-hexane) due to the formation of gas cap below the sieve while with a larger hole sieve (3 mm), it was enhanced because of the reduction of bubble diameters without any gas cap formation. However, it was found that the sieve tray effect was weakened when the flow regime changes from homogeneous to heterogeneous.

STUDY DESIGN Retrospective analysis. OBJECTIVE To describe the dynamic fluctuation of truncal shift parameters during quiet standing in healthy young individuals using biomechanical analyses. SUMMARY OF BACKGROUND DATA Coronal decompensation (CD) and sagittal vertical axis (SVA) are the key radiographic parameters to assess static truncal stability, with the known cut-off value of 4 cm for SVA in determining severity of spinal deformity. These values are obtained at a specific moment during quiet standing, when the posture innately changes. Thus, unassessed truncal sway could potentially compromise the reliability of these measurements. METHODS Previously obtained biomechanical data with 11 male, healthy participants aged 16 to 29 were used to quantify the dynamic sway of standing posture. The participants were instructed to quietly stand with surface reflective markers for 130 seconds. The midpoint of bilateral acromia was used as a surrogate for C7 vertebral body. The time series of coronal and sagittal shifts of C7 to sacrum were measured as quasi-coronal decompensation (CD) and quasi-sagittal vertical axis (SVA) to simulate CD and SVA on radiographs. A force platform was also used to measure the center of pressure (COP) displacement. RESULTS The group averages of the dynamic sway range were 20.2 ± 4.1 mm (range: 15.1-28.6) in the sagittal plane (quasi-SVA) and 9.8 ± 3.2 mm (range: 5.5-15.2) in the coronal plane (quasi-CD). There were significant correlations between quasi-CD sway and medial-lateral COP velocity (Pearson r = 0.65, P = 0.03), as well as between quasi-SVA sway and COP sway area (r = 0.65, P = 0.03). CONCLUSION Given the considerable fluctuation of quasi-SVA and quasi-CD during quiet standing, the reliability of radiographic measurement using CD and SVA at a specific moment can be substantially compromised. The assessment based on the currently proposed cut-off values should be interpreted with caution, and repeat examinations are warranted. LEVEL OF EVIDENCE 4.

Hypoxic tissue conditions occur during a number of inflammatory diseases and are associated with the breakdown of barriers and induction of proinflammatory responses. At the same time, hypoxia is also known to induce several adaptive and tissue-protective pathways that dampen inflammation and protect tissue integrity. Hypoxia-inducible factors (HIFs) that are stabilized during inflammatory or hypoxic conditions are at the center of mediating these responses. In the past decade, several genes regulating extracellular adenosine metabolism and signaling have been identified as being direct targets of HIFs. Here, we discuss the relationship between inflammation, hypoxia, and adenosine and that HIF-driven adenosine metabolism and signaling is essential in providing tissue protection during inflammatory conditions, including myocardial injury, inflammatory bowel disease, and acute lung injury. We also discuss how the hypoxia-adenosine link can be targeted therapeutically in patients as a future treatment approach for inflammatory diseases.

Inflammation mediated by activation of JAK/STAT signaling is a major cause of chemotherapy resistance in cancer. We studied the impact of selectively blocking the IL6 receptor (IL6R) as a strategy to inhibit IL6-induced STAT activation and to overcome chemoresistance in pancreatic ductal adenocarcinoma (PDAC). To do this, STAT activation was investigated in tumors arising spontaneously in LSL-KrasG12D/+;LSL-Trp53R172H/+;Pdx-1Cre (KPC) mice. Plasma from patients with PDAC was assessed for its ability to activate STAT3/SOCS3 in human monocytes using immunofluorescence microscopy and quantitative gene expression assays. KPC mice and syngeneic mice (wild type and IL6−/−) implanted with KPC-derived cell lines were treated with an IL6R-blocking antibody (anti-IL6R). The impact of treatment on tumor growth in KPC mice and mice with KPC-derived tumor implants was monitored using ultrasonography and calipers, respectively. Tumors were analyzed by IHC to detect changes in STAT activation, tumor viability, and proliferation. We found that STAT3 was the most activated STAT protein in PDAC tumors from KPC mice. Plasma from patients with advanced PDAC stimulated STAT3/SOCS3 activation in human monocytes. In mice, anti-IL6R antibodies targeted Ly6Chi monocytes, inhibited STAT3 activation in tumor cells, and decreased tumor cell proliferation in vivo. IL6R blockade in combination with chemotherapy induced tumor cell apoptosis, tumor regressions, and improved overall survival. Overall, we show that IL6 signaling drives STAT3 activation in tumor cells and mediates chemoresistance in PDAC. Thus, disrupting IL6 signaling using anti-IL6R antibodies holds promise for improving chemotherapy efficacy in PDAC. Mol Cancer Ther; 16(9); 1898–908. ©2017 AACR.

In situ transesterification (direct conversion) of microalgal cells is a promising method to produce biodiesel from microalgae because it integrates the oil extraction and conversion process in one step. Not only biodiesel but also a few biochemicals can be produced through this process because both lipids and carbohydrates are converted under acidic conditions. Levulinic acid ester (levulinate) is one of the byproducts of in situ transesterification, which can be used as an additive in fuels or fragrances. This study investigated the effect of cell composition and reactive variables on the productivity of levulinic acid ester. The cell compositions of microalgal strains were compared between Nannochloropsis and Chlorella , and more levulinate was produced from carbohydrate-rich Chlorella cells. Both reaction temperature and acid concentration highly affected the levulinate yield, whereas the type of alcohols did not have much influence on the yield. Consequently, more than 40 mol% glucose inside the cell was converted to levulinate with a 15 v% sulfuric acid concentration at 130 °C.

Dynamic scripting languages are becoming more and more widely adopted not only for fast prototyping but also for developing production-grade applications. They provide high-productivity programming environments featuring high levels of abstraction with powerful built-in functions, automatic memory management, object-oriented programming paradigm and dynamic typing. However, their flexible, dynamic type systems easily become the source of inefficiency in terms of instruction count, memory footprint, and energy consumption. This overhead makes it challenging to deploy these high-productivity programming technologies on emerging single-board computers for IoT applications. Addressing this challenge, this paper introduces Typed Architectures, a high-efficiency, low-cost execution substrate for dynamic scripting languages, where each data variable retains high-level type information at an ISA level. Typed Architectures calculate and check the dynamic type of each variable implicitly in hardware, rather than explicitly in software, hence significantly reducing instruction count for dynamic type checking. Besides, Typed Architectures introduce polymorphic instructions (e.g., xadd), which are bound to the correct native instruction at runtime within the pipeline (e.g., add or fadd) to efficiently implement polymorphic operators. Finally, Typed Architectures provide hardware support for flexible yet efficient type tag extraction and insertion, capturing common data layout patterns of tag-value pairs. Our evaluation using a fully synthesizable RISC-V RTL design on FPGA shows that Typed Architectures achieve geomean speedups of 11.2% and 9.9% with maximum speedups of 32.6% and 43.5% for two production-grade scripting engines for JavaScript and Lua, respectively. Moreover, Typed Architectures improve the energy-delay product (EDP) by 19.3% for JavaScript and 16.5% for Lua with an area overhead of 1.6% at a 40nm technology node.

NUMA (non-uniform memory access) servers are commonly used in high-performance computing and datacenters. Within each server, a processor-interconnect (e.g., Intel QPI, AMD HyperTransport) is used to communicate between the different sockets or nodes. In this work, we explore the impact of the processor-interconnect on overall performance -- in particular, the performance un- fairness caused by processor-interconnect arbitration. It is well known that locally-fair arbitration does not guarantee globally-fair bandwidth sharing as closer nodes receive more bandwidth in a multi-hop network. However, this work demonstrates that the opposite can occur in a commodity NUMA server where remote nodes receive higher bandwidth (and perform better). We analyze this problem and iden- tify that this occurs because of external concentration used in router micro-architectures for processor-interconnects without globally-aware arbitration. While accessing remote memory can occur in any NUMA system, performance un- fairness (or performance variation) is more critical in cloud computing and virtual machines with shared resources. We demonstrate how this unfairness creates significant performance variation when a workload is executed on the Xen virtualization platform. We then provide analysis using synthetic workloads to better understand the source of unfair- ness and eliminate the impact of other shared resources, including the shared last-level cache and main memory. To provide fairness, we propose a novel, history-based arbitration that tracks the history of arbitration grants made in the previous history window. A weighted arbitration is done based on the history to provide global fairness. Through simulations, we show our proposed history-based arbitration can provide global fairness and minimize the processor- interconnect performance unfairness at low cost.

The liver is the most frequent site of metastatic spread in malignancies that arise from the digestive system, including pancreatic ductal adenocarcinoma (PDAC). Metastasis to the liver is a major cause of morbidity and mortality in cancer patients, yet mechanisms that govern this process remain poorly understood. Until recently, liver tropism of metastasis was believed to be driven by mechanical factors that direct the passive flow of circulating cancer cells to the liver. However, emerging evidence now shows that liver metastasis is a dynamic process that is, at least in part, dependent on the formation of a "pro-metastatic niche". Key features of this niche are myeloid cells and fibrosis that support cancer cell colonization and growth. Inflammatory responses that are mounted early during primary tumor development are critical for the recruitment of myeloid cells and the deposition of extracellular matrix (ECM) proteins within the liver. Intriguingly, the inflammatory processes that direct the formation of a pro-metastatic niche share remarkable resemblance to mechanisms of liver injury and regeneration, suggesting that cancer co-opts physiological liver functions to support metastasis. Therefore, therapeutic strategies that target key elements of liver inflammation that form the basis of a pro-metastatic niche may lead to effective treatments for metastatic cancer.

The International Telecommunications Union Radiocommunication Sector (ITU‐R) Study Group 3 identified the need for a number of radio channel models in anticipation of the World Radiocommunications Conference in 2019 when the frequency allocation for 5G will be discussed. In response to the call for propagation path loss models, members of the study group carried out measurements in the frequency bands between 0.8 GHz up to 73 GHz in urban low rise and urban high rise as well as suburban environments. The data were subsequently merged to generate site general path loss models. The paper presents an overview of the radio channel measurements, the measured environments, the data analysis and the approach for the derivation of the path loss model adopted in Recommendation ITU‐R P.1411‐10.

Background During myocardial ischemia, hypoxia-inducible factors are stabilized and provide protection from ischemia and reperfusion injury. Recent studies show that myocyte-specific hypoxia-inducible factor 2A promotes myocardial ischemia tolerance through induction of epidermal growth factor, amphiregulin. Here, the authors hypothesized that hypoxia-inducible factor 2A may enhance epidermal growth factor receptor 1 (ERBB1) expression in the myocardium that could interface between growth factors and its effect on providing tolerance to ischemia and reperfusion injury. Methods Human myocardial tissues were obtained from ischemic heart disease patients and normal control patients to compare ERBB1 expression. Myocyte-specific Hif2a or ErbB1 knockout mice were generated to observe the effect of Hif2a knockdown in regulating ERBB1 expression and to examine the role of ERBB1 during myocardial ischemia and reperfusion injury. Results Initial studies of myocardial tissues from patients with ischemic heart disease showed increased ERBB1 protein (1.12 ± 0.24 vs. 13.01 ± 2.20, P < 0.001). In contrast, ERBB1 transcript was unchanged. Studies using short hairpin RNA repression of Hif2A or Hif2aloxP/loxP Myosin Cre+ mice directly implicated hypoxia-inducible factor 2A in ERBB1 protein induction during hypoxia or after myocardial ischemia, respectively. Repression of RNA-binding protein 4 abolished hypoxia-inducible factor 2A–dependent induction of ERBB1 protein. Moreover, ErbB1loxP/loxP Myosin Cre+ mice experienced larger infarct sizes (22.46 ± 4.06 vs. 46.14 ± 1.81, P < 0.001) and could not be rescued via amphiregulin treatment. Conclusions These findings suggest that hypoxia-inducible factor 2A promotes transcription-independent induction of ERBB1 protein and implicates epidermal growth factor signaling in protection from myocardial ischemia and reperfusion injury. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Two substrate integrated waveguide (SIW)-based antennas for the application of software-defined radar are proposed and investigated herein. It is usually well known that SIWs are easily integrated, lightweight, have low insertion loss, and low interference levels compared to conventional microstrip structures. The primary function of the proposed antennas is to transmit continuous waves for indoor motion detection, with the lowest amount of loss and an appropriate amount of gain. Moreover, the results of this study show that the size of the antenna can be reduced significantly (i.e., by about 40%) by applying a meander line structure. The operating frequencies of the proposed antennas are both within the industrial, scientific, and medical band (i.e., 2.4–2.4835 GHz). Measured results of return loss are -16 dB and -20 dB at 2.435 GHz and 2.43 GHz, respectively, and the measured gain is 8.2 dBi and 5.5 dBi, respectively. Antenna design and verification are undertaken through commercially available full electromagnetic software.

// Muhammad Shahid 1, * , Kyoung Min Cho 2, * , Minh Nam Nguyen 3 , Tae Gyu Choi 3 , Yong Hwa Jo 3 , Saurav Nath Aryal 1 , Ji Youn Yoo 1 , Hyeong Rok Yun 1 , Jae Woong Lee 1 , Young Gyu Eun 4 , Ju-Seog Lee 5 , Insug Kang 1, 3 , Joohun Ha 1, 3 , Hwi-Joong Yoon 2 , Si-Young Kim 2 , Sung Soo Kim 1, 3 1 Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, Republic of Korea 2 Department of Internal Medicine, Graduate School, Kyung Hee University, Seoul, Republic of Korea 3 Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea 4 Department of Otolaryngology-Head and Neck Surgery, Kyung Hee University Medical Center, Seoul, Republic of Korea 5 Department of Systems Biology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA * These authors contributed equally to this work Correspondence to: Sung Soo Kim, email: sgskim@khu.ac.kr Keywords: glioma, gene expression profile, prognosis, chemosensitivity Received: March 03, 2016 Accepted: May 20, 2016 Published: June 13, 2016 ABSTRACT Gliomas are the most common and aggressive primary tumors in adults. The current approaches, such as histological classification and molecular genetics, have limitation in prediction of individual therapeutic outcomes due to heterogeneity within the tumor groups. Recent studies have proposed several gene signatures to predict glioma’s prognosis. However, most of the gene expression profiling studies have been performed on relatively small number of patients and combined probes from diverse microarray chips. Here, we identified prognostic 89 common genes from diverse microarray chips. The 89-gene signature classified patients into good and bad prognostic groups which differed in the overall survival significantly, reflecting the biological characteristics and heterogeneity. The robustness and accuracy of the gene signature as an independent prognostic factor was validated in three microarray and one RNA-seq data sets independently. By incorporating into histological classification and molecular marker, the 89-gene signature could further stratify patients with 1p/19q co-deletion and IDH1 mutation. Additionally, subset analyses suggested that the 89-gene signature could predict patients who would benefit from adjuvant chemotherapy. Conclusively, we propose that the 89-gene signature would have an independent and accurate prognostic value for clinical use. This study also offers opportunities for novel targeted treatment of individual patients.

Potassium copper hexacyanoferrate (KCuHCF)-incorporated magnetic chitosan beads (HMC) were synthesized for both selective Cs

Study objective To investigate the impact of utilizing a multimodal analgesia protocol to allow the implementation of Enhanced Recovery after Cardiac Surgery (ERACS) in patients requiring cardio-pulmonary bypass. Design Retrospective analysis of patients treated with the proposed ERACS bundle in comparison to matched controls. Setting Single-center study. Patients A total of 50 patients undergoing elective cardiac surgery limited to on pump coronary artery bypass graft. Measurements Perioperative outcomes of 25 patients that underwent ERACS protocol and 25 controls were measured. In-operating room (OR) extubation, total intubation time, total intra-OP fentanyl given, total post-OP morphine equivalent given, intensive care unit (ICU) length of stay (LOS), hospital LOS and post-OP complications were examined. Main results The ERACS group and control group were equivalent with regards to age, gender, comorbidities, ASA classification and type of surgery. Mean cardiac bypass time and mean aortic clamp time were similar. Extubation in the OR was achieved for 12 patients in the ERACS group compared to 1 in the control group. Post-operative opioid consumption was lower in ERACS group (27.3 vs. 51.7 morphine equivalents, p = 0.006). Although ICU LOS and hospital LOS were shorter in the ERACS group, this did not reach significance. Conclusions The ERACS group showed a significant decrease in opioid use and increased incidence of successful in OR extubation.

Background & Aims Immunotherapies that induce T-cell responses have shown efficacy against some solid malignancies in patients and mice, but these have little effect on pancreatic ductal adenocarcinoma (PDAC). We investigated whether the ability of PDAC to evade T-cell responses induced by immunotherapies results from the low level of immunogenicity of tumor cells, the tumor's immunosuppressive mechanisms, or both. Methods Kras G12D/+ ;Trp53 R172H/+ ;Pdx-1-Cre (KPC) mice, which develop spontaneous PDAC, or their littermates (controls) were given subcutaneous injections of a syngeneic KPC-derived PDAC cell line. Mice were then given gemcitabine and an agonist of CD40 to induce tumor-specific immunity mediated by T cells. Some mice were also given clodronate-encapsulated liposomes to deplete macrophages. Tumor growth was monitored. Tumor and spleen tissues were collected and analyzed by histology, flow cytometry, and immunohistochemistry. Results Gemcitabine in combination with a CD40 agonist induced T-cell−dependent regression of subcutaneous PDAC in KPC and control mice. In KPC mice given gemcitabine and a CD40 agonist, CD4 + and CD8 + T cells infiltrated subcutaneous tumors, but only CD4 + T cells infiltrated spontaneous pancreatic tumors (not CD8 + T cells). In mice depleted of Ly6C low F4/80 + extratumoral macrophages, the combination of gemcitabine and a CD40 agonist stimulated infiltration of spontaneous tumors by CD8 + T cells and induced tumor regression, mediated by CD8 + T cells. Conclusions Ly6C low F4/80 + macrophages that reside outside of the tumor microenvironment regulate infiltration of T cells into PDAC and establish a site of immune privilege. Strategies to reverse the immune privilege of PDAC, which is regulated by extratumoral macrophages, might increase the efficacy of T-cell immunotherapy for patients with PDAC.