Comprehensive genomic sequencing detects important genetic differences between right-sided and left-sided colorectal cancer

Objectives: Anti-epidermal growth factor receptor (EGFR) therapy has been found to be more effective against left-sided colorectal cancer (LCRC) than right-sided colorectal cancer (RCRC). We hypothesized that RCRC is more likely to harbor genetic alterations associated with resistance to anti-EGFR therapy and tested this using comprehensive genomic sequencing. Materials and methods: A total of 201 patients with either primary RCRC or LCRC were analyzed. We investigated tumors for genetic alterations using a 415-gene panel, which included alterations associated with resistance to anti-EGFR therapy: TK receptors (ERBB2, MET, EGFR, FGFR1, and PDGFRA), RAS pathway (KRAS, NRAS, HRAS, BRAF, and MAPK2K1), and PI3K pathway (PTEN and PIK3CA). Patients whose tumors had no alterations in these 12 genes, theoretically considered to respond to anti-EGFR therapy, were defined as all wild-type , while remaining patients were defined as mutant-type . Results: Fifty-six patients (28%) and 145 patients (72%) had RCRC and LCRC, respectively. Regarding genetic alterations associated with anti-EGFR therapy, only 6 of 56 patients (11%) with RCRC were all wild-type compared with 41 of 145 patients (28%) with LCRC (P = 0.009). Among the 49 patients who received anti-EGFR therapy, RCRC showed significantly worse progression-free survival (PFS) than LCRC (P = 0.022), and mutant-type RCRC showed significantly worse PFS compared with all wild-type LCRC (P = 0.004). Conclusions: RCRC is more likely to harbor genetic alterations associated with resistance to anti-EGFR therapy compared with LCRC. Furthermore, our data shows primary tumor sidedness is a surrogate for the non-random distribution of genetic alterations in CRC

Observation of a Highly Spin Polarized Topological Surface State in GeBi2_{2}Te4_{4}

Spin polarization of a topological surface state for GeBi$_2$Te$_4$, the newly discovered three-dimensional topological insulator, has been studied by means of the state of the art spin- and angle-resolved photoemission spectroscopy. It has been revealed that the disorder in the crystal has a minor effect on the surface state spin polarization and it exceeds 75% near the Dirac point in the bulk energy gap region ($\sim$180 meV). This new finding for GeBi$_{2}$Te$_{4}$ promises not only to realize a highly spin polarized surface isolated transport but to add new functionality to its thermoelectric and thermomagnetic properties.Comment: 5 pages, 4 figure

Comprehensive analysis of peptide-coding genes and initial characterization of an LRR-only microprotein in Marchantia polymorpha

In the past two decades, many plant peptides have been found to play crucial roles in various biological events by mediating cell-to-cell communications. However, a large number of small open reading frames (sORFs) or short genes capable of encoding peptides remain uncharacterized. In this study, we examined several candidate genes for peptides conserved between two model plants: Arabidopsis thaliana and Marchantia polymorpha. We examined their expression pattern in M. polymorpha and subcellular localization using a transient assay with Nicotiana benthamiana. We found that one candidate, MpSGF10B, was expressed in meristems, gemma cups, and male reproductive organs called antheridiophores. MpSGF10B has an N-terminal signal peptide followed by two leucine-rich repeat (LRR) domains and was secreted to the extracellular region in N. benthamiana and M. polymorpha. Compared with the wild type, two independent Mpsgf10b mutants had a slightly increased number of antheridiophores. It was revealed in gene ontology enrichment analysis that MpSGF10B was significantly co-expressed with genes related to cell cycle and development. These results suggest that MpSGF10B may be involved in the reproductive development of M. polymorpha. Our research should shed light on the unknown role of LRR-only proteins in land plants

Human and equipment resources for difficult airway management, airway education programs, and capnometry use in Japanese emergency departments: a nationwide cross-sectional study

Background: Although human and equipment resources, proper training, and the verification of endotracheal intubation are vital elements of difficult airway management (DAM), their availability in Japanese emergency departments (EDs) has not been determined. How ED type and patient volume affect DAM preparation is also unclear. We conducted the present survey to address this knowledge gaps. Methods: This nationwide cross-sectional study was conducted from April to September 2016. All EDs received a mailed questionnaire regarding their DAM resources, airway training methods, and capnometry use for tube placement. Outcome measures were the availability of: (1) 24-h in-house back-up; (2) key DAM resources, including a supraglottic airway device (SGA), a dedicated DAM cart, surgical airway devices, and neuromuscular blocking agents; (3) anesthesiology rotation as part of an airway training program; and (4) the routine use of capnometry to verify tube placement. EDs were classified as academic, tertiary, high-volume (upper quartile of annual ambulance visits), and urban. Results: Of the 530 EDs, 324 (61.1%) returned completed questionnaires. The availability of in-house back-up coverage, surgical airway devices, and neuromuscular blocking agents was 69.4, 95.7, and 68.5%, respectively. SGAs and dedicated DAM carts were present in 51.5 and 49.7% of the EDs. The rates of routine capnometry use (47.8%) and the availability of an anesthesiology rotation (38.6%) were low. The availability of 24-h back-up coverage was significantly higher in academic EDs and tertiary EDs in both the crude and adjusted analysis. Similarly, neuromuscular blocking agents were more likely to be present in academic EDs, high-volume EDs, and tertiary EDs; and the rate of routine use of capnometry was significantly higher in tertiary EDs in both the crude and adjusted analysis. Conclusions: In Japanese EDs, the rates of both the availability of SGAs and DAM carts and the use of routine capnometry to confirm tube placement were approximately 50%. These data demonstrate the lack of standard operating procedures for rescue ventilation and post-intubation care. Academic, tertiary, and high-volume EDs were likely to be well prepared for DAM

Are prehospital airway management resources compatible with difficult airway algorithms? A nationwide cross-sectional study of helicopter emergency medical services in Japan

PURPOSE: Immediate access to the equipment required for difficult airway management (DAM) is vital. However, in Japan, data are scarce regarding the availability of DAM resources in prehospital settings. The purpose of this study was to determine whether Japanese helicopter emergency medical services (HEMS) are adequately equipped to comply with the DAM algorithms of Japanese and American professional anesthesiology societies. METHODS: This nationwide cross-sectional study was conducted in May 2015. Base hospitals of HEMS were mailed a questionnaire about their airway management equipment and back-up personnel. Outcome measures were (1) call for help, (2) supraglottic airway device (SGA) insertion, (3) verification of tube placement using capnometry, and (4) the establishment of surgical airways, all of which have been endorsed in various airway management guidelines. The criteria defining feasibility were the availability of (1) more than one physician, (2) SGA, (3) capnometry, and (4) a surgical airway device in the prehospital setting. RESULTS: Of the 45 HEMS base hospitals questioned, 42 (93.3 %) returned completed questionnaires. A surgical airway was practicable by all HEMS. However, in the prehospital setting, back-up assistance was available in 14.3 %, SGA in 16.7 %, and capnometry in 66.7 %. No HEMS was capable of all four steps. CONCLUSION: In Japan, compliance with standard airway management algorithms in prehospital settings remains difficult because of the limited availability of alternative ventilation equipment and back-up personnel. Prehospital health care providers need to consider the risks and benefits of performing endotracheal intubation in environments not conducive to the success of this procedure

Difficult airway management resources and capnography use in Japanese intensive care units: a nationwide cross-sectional study

PURPOSE: The availability of difficult airway management (DAM) resources and the extent of capnometry use in Japanese intensive care units (ICUs) remained unclear. The purpose of this study was to clarify whether: (1) DAM resources were adequate, and (2) capnometry was routinely applied in Japanese ICUs. METHODS: This nationwide cross-sectional study was conducted from September 2015 to February 2016. All ICUs received a mailed questionnaire about their DAM resources and use of capnometry. Outcome measures were availability of: (1) 24-h in-house backup coverage; (2) a supraglottic airway device (SGA); (3) a dedicated DAM cart; and (4) surgical airway devices, and (5) routine use of capnometry to verify tube placement and for continuous monitoring of ventilator-dependent patients. The association between these outcomes and ICU type (academic, high-volume, closed, surgical) was also analyzed. RESULTS: Of the 289 ICUs, 196 (67.8 %) returned completed questionnaires. In-house backup coverage and surgical airway devices were highly available (89.3 and 95.9 %), but SGAs and dedicated DAM carts were not (60.2 and 60.7 %). The routine use of capnometry to confirm tube placement was reported by 55.6 % of the ICUs and was highest in closed ICUs (67.2 %, p = 0.03). The rate of continuous capnography monitoring was also 55.6 % and was highest in academic ICUs (64.5 %, p = 0.04). CONCLUSION: In Japanese ICUs, SGAs and dedicated DAM carts were less available, and capnometry was not universally applied either to confirm tube placement, or for continuous monitoring of ventilated patients. Our study revealed areas in need of improvement

Novel insights into the intraepithelial spread of extrahepatic cholangiocarcinoma: clinicopathological study of 382 cases on extrahepatic cholangiocarcinoma

BackgroundExtrahepatic cholangiocarcinoma (eCCA) is a rare and aggressive disease and consisted of conventional eCCA and intraductal papillary neoplasm of the bile duct (IPNB). Intraepithelial spread (IES) of cancer cells beyond the invasive area is often observed in IPNBs; however, the prevalence of IES remains to be examined in conventional eCCAs. Here, we evaluated the clinicopathological features of eCCAs according to tumor location, with a focus on the presence of IES. The IES extension was also compared among biliary tract cancers (BTCs).MethodsWe examined the prevalence and clinicopathological significance of IES in eCCAs (n=382) and the IES extension of BTCs, including gallbladder (n=172), cystic duct (n=20), and ampullary cancers (n=102).ResultsAmong the invasive eCCAs, IPNB had a higher rate of IES (89.2%) than conventional eCCAs (57.0%). Among conventional eCCAs, distal eCCAs (75.4%) had a significantly higher prevalence of IES than perihilar eCCAs (41.3%). The presence of IES was associated with a significantly higher survival rate in patients with distal eCCAs (P=0.030). Extension of the IES into the cystic duct (CyD) in distal eCCAs that cancer cells reached the junction of the CyD was a favorable prognostic factor (P<0.001). The association of survival with IES, either on the extrahepatic bile duct or on the CyD, differed depending on the tumor location and type of eCCA. The extension properties of IES were also dependent on different types of tumors among BTCs; usually, the IES incidence became higher than 50% in the tissues that the tumor developed, whereas IES extension to other tissues decreased the incidence.ConclusionThus, eCCAs have different clinicopathological characteristics depending on the tumor location and type

Another century of gods ? A re-evaluation of Seleukid ruler cult.

This paper argues that numismatic representations portraying living Seleukid kings as divine can be found before the reign of Antiochos III on royal coinage. Furthermore, the numismatic evidence does not support a claim that Antiochos III presented his own divinity on coinage in a way that is significantly different from that of his predecessors. Instead it was not until the reign of Antiochos IV that the living king was unequivocally portrayed as divine through the legend on his coinage. The numismatic evidence therefore differs from the epigraphic evidence as it is only under Antiochos III that there is inscriptional evidence for the recognition of a deified living Seleukid king in a non-civic context. This paper argues that the coinage re-examined here provides evidence for the royal presentation of the kings’ divinity in a non-civic context. In doing so, this paper opens the possibility of re-assessing when a Seleukid royal cult developed