bluuebunny/crossref_metadata_2025 huggingface dataset:
Density Functional Theory and Single Crystal X-ray Studies on Some Bis-Chalcone Derivatives
Authors: YAKALI Gül , BİÇER Abdullah , BARUT Duygu , CİN Günseli Turgut
Published: January 2019

The three  bis-chalcone compounds, (2E,6E)-2,6-bis(3-chlorobenzylidene)cyclohexanone (1), (2E,6E)-2,6-bis(2,3-dichlorobenzylidene)cyclohexanone (2) and (2E,5E)-2,5-bis(2,6-dichloro benzylidene) cyclopentanone (3), were studied with theoretical and single-crystal X-ray diffraction (XRD) methods. The molecular geometric parameters, frontier molecular orbitals, MEP, normal mode frequencies and the corresponding vibrational assignments, gauge-including atomic orbital (GIAO) 1H-NMR, 13C-NMR chemical shift values of the bis-chalcone compounds in the ground state have been calculated using the density functional  (B3LYP) methods with 6-311G (d,p) basis set. These molecules demonstrate apparently a long and flat shape. Each molecule adopt an (E) configuration about the central olefinic bonds. The most important feature is stacking mode in the molecules. The calculated results reveal that the optimized geometries can well reproduce the crystal structure. The theoretical vibrational frequencies and 1H-NMR and 13C-NMR chemical shift values show good agreement with the experimental data.
The Influence on Response of a Combined Capacitance Sensor in Horizontal Oil–Water Two-Phase Flow
Authors: Li Lei , Kong Lingfu , Xie Beibei , Fang Xin , Kong Weihang , Liu Xingbin , Wang Yanjun , Zhao Fengda
Published: January 2019

In the process of production logging interpretation, a water cut is one of the key factors to obtain the oil phase content in the oil well. In order to measure the water cut of the horizontal oil–water two-phase flow with low yield, the response characteristics of the combined capacitance sensor (CCS) are investigated under different flow patterns. Firstly, the measuring principles of coaxial, cylindrical, and CCS are introduced in detail. Then, according to the different flow pattern conditions of the horizontal oil–water two-phase flow, the response characteristics of the CCS are simulated and analyzed using the finite element method. Additionally, compared with the other two sensors, the advantages of the CCS are verified. Finally, the temperature and pressure calibration experiments are carried out on the CCS. The horizontal oil–water two-phase flow patterns in a low yield liquid level are divided in detail with a high-speed camera. Dynamic experiments are carried out in a horizontal pipe with an inner diameter of 125 mm on the horizontal oil–water two-phase flow experimental equipment. The simulation and experimental results show that the CCS has good response characteristics under different working conditions.
A MAP Overhead Aware Two-Dimensional OFDMA Burst Construction Algorithm
Authors: Chen Lin-Kung , Jan Pi-Tzong , Chen Yen-Hung , Hung Rui-Ze , Lee Yen-Jung
Published: January 2019

Conventional orthogonal frequency division multiple access (OFDMA) burst construction methods can only support limited numbers of connections due to the map overhead and corresponding limitations in the numbers of orthogonal resources blocks, which limits the capacity of current 4G and the following 5th generation (5G) networks. This study therefore provides a novel OFDMA burst construction algorithm and enhanced burst indexing aware algorithm (EHA), which try to maximize the throughput while considering the subchannel diversity and optimizing burst indexing issues. The EHA not only allocates the subchannels with the best channel quality for each burst, but also groups the bursts to alleviate the MAP overhead. Simulation results showed that the EHA yields two times the throughput that has been achieved using previous algorithms under a heavy load. Two contributions of the EHA are: (1) the overhead of burst indexing decreases because massive numbers of connections can be accommodated by one burst; and (2) the overall throughput increases due to that one connection with large data transferring requirements can be split and distributed into several bursts and placed on the subchannels with good channel quality to adopt better modulation coding scheme (MCS), if the saved bandwidth in this burst construction is more than the increased overhead of burst indexing.
A Novel Wearable Device for Continuous Ambulatory ECG Recording: Proof of Concept and Assessment of Signal Quality
Authors: Steinberg Christian , Philippon François , Sanchez Marina , Fortier-Poisson Pascal , O’Hara Gilles , Molin Franck , Sarrazin Jean-François , Nault Isabelle , Blier Louis , Roy Karine , Plourde Benoit , Champagne Jean
Published: January 2019

Diagnosis of arrhythmic disorders is challenging because of their short-lasting, intermittent character. Conventional technologies of noninvasive ambulatory rhythm monitoring are limited by modest sensitivity. We present a novel form of wearable electrocardiogram (ECG) sensors providing an alternative tool for long-term rhythm monitoring with the potential of increased sensitivity to detect intermittent or subclinical arrhythmia. The objective was to assess the signal quality and R-R coverage of a wearable ECG sensor system compared to a standard 3-lead Holter. In this phase-1 trial, healthy individuals underwent 24-h simultaneous rhythm monitoring using the OMsignal system together with a 3-lead Holter recording. The OMsignal system consists of a garment (bra or shirt) with integrated sensors recording a single-lead ECG and an acquisition module for data storage and processing. Head-to-head signal quality was assessed regarding adequate P-QRS-T distinction and was performed by three electrophysiologists blinded to the recording technology. The accuracy of signal coverage was assessed using Bland-Altman analysis. Fifteen individuals underwent simultaneous 24-h recording. Signal quality and accuracy of the OMgaments was equivalent to Holter-monitoring (84% vs. 93% electrophysiologists rating, p = 0.06). Signal coverage of R-R intervals showed a very close overlay between the OMsignal system and Holter signals, mean difference in heart rate of 2 ± 5 bpm. The noise level of OMgarments was comparable to Holter recording. OMgarments provide high signal quality for adequate rhythm analysis, representing a promising novel technology for long-term non-invasive ECG monitoring.
Sustained Opening of the Blood-Brain Barrier with Progressive Accumulation of White Matter Hyperintensities Following Ischemic Stroke
Authors: Naqvi Imama , Hitomi Emi , Leigh Richard
Published: January 2019

Objective: To report a patient in whom an acute ischemic stroke precipitated chronic blood-brain barrier (BBB) disruption and expansion of vascular white matter hyperintensities (WMH) into regions of normal appearing white matter (NAWM) during the following year. Background: WMH are a common finding in patients with vascular risk factors such as a history of stroke. The pathophysiology of WMH is not fully understood; however, there is growing evidence to suggest that the development of WMH may be preceded by the BBB disruption in the NAWM. Methods: We studied a patient enrolled in the National Institutes of Health Natural History of Stroke Study who was scanned with magnetic resonance imaging (MRI) after presenting to the emergency room with an acute stroke. After a treatment with IV tPA, she underwent further MRI scanning at 2 h, 24 h, 5 days, 30 days, 90 days, 6 months, and 1-year post stroke. BBB permeability images were generated from the perfusion weighted imaging (PWI) source images. MRIs from each time point were co-registered to track changes in BBB disruption and WMH over time. Results: An 84-year-old woman presented after acute onset right hemiparesis, right-sided numbness and aphasia with an initial NIHSS of 13. MRI showed diffusion restriction in the left frontal lobe and decreased blood flow on perfusion imaging. Fluid attenuated inversion recovery (FLAIR) imaging showed bilateral confluent WMH involving the deep white matter and periventricular regions. She was treated with IV tPA without complication and her NIHSS improved initially to 3 and ultimately to 0. Permeability maps identified multiple regions of chronic BBB disruption remote from the acute stroke, predominantly spanning the junction of WMH and NAWM. The severity of BBB disruption was greatest at 24 h after the stroke but persisted on subsequent MRI scans. Progression of WMH into NAWM over the year of observation was detected bilaterally but was most dramatic in the regions adjacent to the initial stroke. Conclusions: WMH-associated BBB disruption may be exacerbated by an acute stroke, even in the contralateral hemisphere, and can persist for months after the initial event. Transformation of NAWM to WMH may be evident in areas of BBB disruption within a year after the stroke. Further studies are needed to investigate the relationship between chronic BBB disruption and progressive WMH in patients with a history of cerebrovascular disease and the potential for acute stroke to trigger or exacerbate the process leading to the development of WMH.
The Influence of Geo-Hazard Effects on the Physical Vulnerability Assessment of the Built Heritage: An Application in a District of Naples
Authors: Chieffo Nicola , Formisano Antonio
Published: January 2019

The proposed study aims at analysing a sub-urban sector in the historic centre of Qualiano, located in the province of Naples (Italy), in order to assess the seismic vulnerability of the main typology classes (masonry and reinforced concrete) in the study area and the consequent expected damage scenarios. The typological and structural characterisation of the investigated area is done through the CARTIS form developed by the PLINIVS research centre together with the Italian Civil Protection Department. Subsequently, the vulnerability simulation analysis is carried out by means of a quick methodology integrated into a GIS tool in order to identify the structural units (S.U.) most susceptible at damage under seismic events. Furthermore, in order to take into account the possible damage scenarios, a parametric analysis is performed using a seismic attenuation law in order to obtain the maximization of the expected urban losses. Finally, the site and topographical local conditions, which negatively influence the severity of the seismic damage on the structures, have been taken into account in order to more correctly foresee the expected damage of the inspected sub-urban sector to be used for appropriate seismic risk mitigation plans.
Prognostic Role of High-Grade Tumor Budding in Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-Analysis with a Focus on Epithelial to Mesenchymal Transition
Authors: Lawlor Rita T. , Veronese Nicola , Nottegar Alessia , Malleo Giuseppe , Smith Lee , Demurtas Jacopo , Cheng Liang , Wood Laura D. , Silvestris Nicola , Salvia Roberto , Scarpa Aldo , Luchini Claudio
Published: January 2019

This study aims at clarifying the prognostic role of high-grade tumor budding (TB) in pancreatic ductal adenocarcinoma (PDAC) with the first systematic review and meta-analysis on this topic. Furthermore, we analyzed with a systematic review the relationship between TB and a recently suggested TB-associated mechanism: the epithelial to mesenchymal transition (EMT). Analyzing a total of 613 patients, 251 of them (40.9%) with high grade-TB, we found an increased risk of all-cause mortality (RR, 1.46; 95% CI, 1.13–1.88, p = 0.004; HR, 2.65; 95% CI, 1.79–3.91; p < 0.0001) and of recurrence (RR, 1.61; 95% CI, 1.05–2.47, p = 0.03) for PDAC patients with high-grade TB. Moreover, we found that EMT is a central process in determining the presence of TB in PDAC. Thanks to this meta-analysis, we demonstrate the potential clinical significance of high-grade TB for prognostic stratification of PDAC. TB also shows a clear association with the process of EMT. Based on the results of the present study, TB should be conveyed in pathology reports and taken into account by future oncologic staging systems.
Expression of Proteolytic Enzymes by Small Cell Lung Cancer Circulating Tumor Cell Lines
Authors: Rath Barbara , Klameth Lukas , Plangger Adelina , Hochmair Maximilian , Ulsperger Ernst , Huk Ihor , Zeillinger Robert , Hamilton Gerhard
Published: January 2019

Small cell lung cancer (SCLC) is an aggressive type of lung cancer which disseminates vigorously and has a dismal prognosis. Metastasis of SCLC is linked to an extremely high number of circulating tumor cells (CTCs), which form chemoresistant spheroids, termed tumorospheres. Intravasation and extravasation during tumor spread requires the activity of a number of proteases to disintegrate the stroma and vascular tissue. Generation of several permanent SCLC CTC lines allowed us to screen for the expression of 35 proteases using Western blot arrays. Cell culture supernatants of two CTC lines, namely BHGc7 and 10, were analyzed for secreted proteases, including matrix metalloproteinases (MMPs), ADAM/TS, cathepsins, kallikreins, and others, and compared to proteases expressed by SCLC cell lines (GLC14, GLC16, NCI-H526 and SCLC26A). In contrast to NCI-H526 and SCLC26A, MMP-9 was highly expressed in the two CTC lines and in GLC16 derived of a relapse. Furthermore, cathepsins (S, V, X/Z/P, A and D) were highly expressed in the CTC lines, whereas ADAM/TS and kallikreins were not detectable. In conclusion, SCLC CTCs express MMP-9 and a range of cathepsins for proteolysis and, aside from tissue degradation, these enzymes are involved in cell signaling, survival, and the chemoresistance of tumor cells.
Vonoprazan-Based Third-Line Therapy Has a Higher Eradication Rate against Sitafloxacin-Resistant Helicobacter pylori
Authors: Saito Yoshimasa , Konno Kaho , Sato Moeka , Nakano Masaru , Kato Yukako , Saito Hidetsugu , Serizawa Hiroshi
Published: January 2019

Eradication of Helicobacter pylori (H. pylori) is an effective strategy for preventing various gastrointestinal diseases such as gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. However, the eradication success rate is decreasing because of a recent increase in drug-resistant strains of H. pylori. Here, we evaluated the success rate of eradication therapy with vonoprazan (VPZ), a new potassium-competitive acid blocker, against drug-resistant H. pylori. In total, 793 patients who received H. pylori eradication therapy were investigated retrospectively. All underwent esomeprazole (EPZ)-based triple therapy (n = 386) or VPZ-based triple therapy (n = 407) for first-, second- and third-line H. pylori eradication for 7 days. The overall success rates of first- and third-line H. pylori eradication were significantly higher for VPZ-based triple therapy (88.4% and 93.0%, respectively, per protocol (PP)) than for EPZ-based triple therapy (69.5% and 56.5%, respectively, PP). Moreover, the success rates of first- and third-line eradication of clarithromycin (CLR)- and sitafloxacin (STFX)-resistant H. pylori were significantly higher for VPZ-based triple therapy (72.0% and 91.7%, PP) than for EPZ-based triple therapy (38.5% and 20.0%, PP). In addition, patient age did not affect the eradication rate of VPZ-based first-line therapy, whereas the success rate of EPZ-based therapy was lower in patients under 65 years of age. Our results clearly demonstrated that VPZ-based therapy achieved a higher eradication rate even against CLR- and STFX-resistant H. pylori, and that patient age did not affect the eradication rate of VPZ-based therapy. These findings suggest that dual therapy using VPZ and amoxicillin may be sufficient for standard H. pylori eradication, and may thus also be beneficial for avoiding antibiotic misuse.
A Barter Economy in Tumors: Exchanging Metabolites through Gap Junctions
Authors: Swietach Pawel , Monterisi Stefania
Published: January 2019

To produce physiological functions, many tissues require their cells to be connected by gap junctions. Such diffusive coupling is important in establishing a cytoplasmic syncytium through which cells can exchange signals, substrates and metabolites. Often the benefits of connectivity become apparent solely at the multicellular level, leading to the notion that cells work for a common good rather than exclusively in their self-interest. In some tumors, gap junctional connectivity between cancer cells is reduced or absent, but there are notable cases where it persists or re-emerges in late-stage disease. Diffusive coupling will blur certain phenotypic differences between cells, which may seem to go against the establishment of population heterogeneity, a central pillar of cancer that stems from genetic instability. Here, building on our previous measurements of gap junctional coupling between cancer cells, we use a computational model to simulate the role of connexin-assembled channels in exchanging lactate and bicarbonate ions down their diffusion gradients. Based on the results of these simulations, we propose that an overriding benefit of gap junctional connectivity may relate to lactate/bicarbonate exchange, which would support an elevated metabolic rate in hypoxic tumors. In this example of barter, hypoxic cancer cells provide normoxic neighbors with lactate for mitochondrial oxidation; in exchange, bicarbonate ions, which are more plentiful in normoxic cells, are supplied to hypoxic neighbors to neutralize the H+ ions co-produced glycolytically. Both cells benefit, and so does the tumor.
Oral Administration of Fermented Papaya (FPP®) Controls the Growth of a Murine Melanoma through the In Vivo Induction of a Natural Antioxidant Response
Authors: Logozzi Mariantonia , Mizzoni Davide , Di Raimo Rossella , Macchia Daniele , Spada Massimo , Fais Stefano
Published: January 2019

Prolonged oxidative stress may play a key role in tumor development. Antioxidant molecules are contained in many foods and seem to have a potential role in future anti-tumor strategies. Among the natural antioxidants the beneficial effect of Fermented Papaya (FPP®) is well known. The aim of this study was to investigate the effects of orally administered FPP® in either the prevention or treatment of a murine model of melanoma. The tumor growth was analyzed together with the blood levels of both oxidants (ROS) and anti-oxidants (SOD-1 and GSH). The results showed that FPP® controlled tumor growth, reducing the tumor mass of about three to seven times vs. untreated mice. The most significant effect was obtained with sublingual administration of FPP® close to the inoculation of melanoma. At the time of the sacrifice none of mice treated with FPP® had metastases and the subcutaneous tumors were significantly smaller and amelanotic, compared to untreated mice. Moreover, the FPP® anti-tumor effect was consistent with the decrease of total ROS levels and the increase in the blood levels of GSH and SOD-1. This study shows that a potent anti-oxidant treatment through FPP® may contribute to both preventing and inhibiting tumors growth.
Combination of Different Fecal Immunochemical Tests in Colorectal Cancer Screening: Any Gain in Diagnostic Performance?
Authors: Gies Anton , Cuk Katarina , Schrotz-King Petra , Brenner Hermann
Published: January 2019

A variety of fecal immunochemical tests (FITs) are used for colorectal cancer screening. FIT performance could be improved further. It is unclear, whether the combination of different FITs with different analytical characteristics (such as, different antibodies for the detection of fecal hemoglobin) can yield a better diagnostic performance. Fecal samples were obtained from 2042 participants of screening colonoscopy. All participants with advanced neoplasm (AN, colorectal cancer (n = 16) or advanced adenoma (n = 200)) and 300 randomly selected participants without AN were included. Nine quantitative FITs were evaluated simultaneously. Sensitivity and specificity was calculated for single tests (n = 9) and for their pairwise test combinations (n = 36) (requiring either both FITs (P++) or at least one FIT (P+) to be positive for defining a positive test result). Mean age of the participants (n = 516) was 63 (range: 50–79) years and 56% were men. At cutoffs yielding a specificity of 96.7% for single FITs, the median gain in specificity by P++ combination was +1.0%, whereas the median loss in sensitivity for AN was −4.2%. For P+ combination the median gain in sensitivity for AN was +2.8%, at a prize of median loss of −1.0% of specificity. Combinations of different FITs do not yield any relevant gain in diagnostic performance.
Location-Dependent Patient Outcome and Recurrence Patterns in IDH1-Wildtype Glioblastoma
Authors: Jungk Christine , Warta Rolf , Mock Andreas , Friauf Sara , Hug Bettina , Capper David , Abdollahi Amir , Debus Jürgen , Bendszus Martin , von Deimling Andreas , Unterberg Andreas , Herold-Mende Christel
Published: January 2019

Recent studies suggest that glioblastomas (GBMs) contacting the subventricular zone (SVZ) as the main adult neurogenic niche confer a dismal prognosis but disregard the unique molecular and prognostic phenotype associated with isocitrate dehydrogenase 1 (IDH1) mutations. We therefore examined location-dependent prognostic factors, growth, and recurrence patterns in a consecutive cohort of 285 IDH1-wildtype GBMs. Based on pre-operative contrast-enhanced MRI, patients were allotted to four location-dependent groups with (SVZ+; groups I, II) and without (SVZ−; groups III, IV) SVZ involvement or with (cortex+; groups I, III) and without (cortex−; groups II, IV) cortical involvement and compared for demographic, treatment, imaging, and survival data at first diagnosis and recurrence. SVZ involvement was associated with lower Karnofsky performance score (p < 0.001), lower frequency of complete resections at first diagnosis (p < 0.0001), and lower non-surgical treatment intensity at recurrence (p < 0.001). Multivariate survival analysis employing a Cox proportional hazards model identified SVZ involvement as an independent prognosticator of inferior overall survival (p < 0.001) and survival after relapse (p = 0.041). In contrast, multifocal growth at first diagnosis (p = 0.031) and recurrence (p < 0.001), as well as distant recurrences (p < 0.0001), was more frequent in cortex+ GBMs. These findings offer the prospect for location-tailored prognostication and treatment based on factors assessable on pre-operative MRI.
PKA at a Cross-Road of Signaling Pathways Involved in the Regulation of Glioblastoma Migration and Invasion by the Neuropeptides VIP and PACAP
Authors: Bensalma Souheyla , Turpault Soumaya , Balandre Annie-Claire , De Boisvilliers Madryssa , Gaillard Afsaneh , Chadéneau Corinne , Muller Jean-Marc
Published: January 2019

Glioblastoma (GBM) remains an incurable disease, mainly due to the high migration and invasion potency of GBM cells inside the brain. PI3K/Akt, Sonic Hedgehog (SHH), and PKA pathways play major regulatory roles in the progression of GBM. The vasoactive intestinal peptide (VIP) family of neuropeptides and their receptors, referred in this article as the “VIP-receptor system”, has been reported to regulate proliferation, differentiation, and migration in a number of tumor cell types and more particularly in GBM cells. These neuropeptides are potent activators of the cAMP/PKA pathway. The present study aimed to investigate the cross-talks between the above cited signaling cascades. Regulation by VIP-related neuropeptides of GBM migration and invasion was evaluated ex vivo in rat brain slices explanted in culture. Effects of different combinations of VIP-related neuropeptides and of pharmacological and siRNA inhibitors of PKA, Akt, and of the SHH/GLI1 pathways were tested on GBM migration rat C6 and human U87 GBM cell lines using the wound-healing technique. Quantification of nuclear GLI1, phospho-Akt, and phospho-PTEN was assessed by western-immunoblotting. The VIP-receptor system agonists VIP and PACAP-38 significantly reduced C6 cells invasion in the rat brain parenchyma ex vivo, and C6 and U87 migration in vitro. A VIP-receptor system antagonist, VIP10-28 increased C6 cell invasion in the rat brain parenchyma ex vivo, and C6 and migration in vitro. These effects on cell migration were abolished by selective inhibitors of the PI3K/Akt and of the SHH pathways. Furthermore, VIP and PACAP-38 reduced the expression of nuclear GLI1 while VIP10-28 increased this expression. Selective inhibitors of Akt and PKA abolished VIP, PACAP-38, and VIP10-28 effects on nuclear GLI1 expression in C6 cells. PACAP-38 induced a time-dependent inhibition of phospho-Akt expression and an increased phosphorylation of PTEN in C6 cells. All together, these data indicate that triggering the VIP-receptor system reduces migration and invasion in GBM cells through a PKA-dependent blockade of the PI3K/Akt and of the SHH/GLI1 pathways. Therefore, the VIP-receptor system displays anti-oncogenic properties in GBM cells and PKA is a central core in this process.
Detection of TP53 Mutations in Tissue or Liquid Rebiopsies at Progression Identifies ALK+ Lung Cancer Patients with Poor Survival
Authors: Christopoulos Petros , Dietz Steffen , Kirchner Martina , Volckmar Anna-Lena , Endris Volker , Neumann Olaf , Ogrodnik Simon , Heussel Claus-Peter , Herth Felix J. , Eichhorn Martin , Meister Michael , Budczies Jan , Allgäuer Michael , Leichsenring Jonas , Zemojtel Tomasz , Bischoff Helge , Schirmacher Peter , Thomas Michael , Sültmann Holger , Stenzinger Albrecht
Published: January 2019

Anaplastic lymphoma kinase (ALK) sequencing can identify resistance mechanisms and guide next-line therapy in ALK+ non-small-cell lung cancer (NSCLC), but the clinical significance of other rebiopsy findings remains unclear. We analysed all stage-IV ALK+ NSCLC patients with longitudinally assessable TP53 status treated in our institutions (n = 62). Patients with TP53 mutations at baseline (TP53mutbas, n = 23) had worse overall survival (OS) than patients with initially wild-type tumours (TP53wtbas, n = 39, 44 vs. 62 months in median, p = 0.018). Within the generally favourable TP53wtbas group, detection of TP53 mutations at progression defined a “converted” subgroup (TP53mutconv, n = 9) with inferior OS, similar to that of TP53mutbas and shorter than that of patients remaining TP53 wild-type (TP53wtprogr, 45 vs. 94 months, p = 0.043). Progression-free survival (PFS) under treatment with tyrosine kinase inhibitors (TKI) for TP53mutconv was comparable to that of TP53mutbas and also shorter than that of TP53wtprogr cases (5 and 8 vs. 13 months, p = 0.0039). Fewer TP53wtprogr than TP53mutbas or TP53mutconv cases presented with metastatic disease at diagnosis (67% vs. 91% or 100%, p < 0.05). Thus, acquisition of TP53 mutations at progression is associated with more aggressive disease, shorter TKI responses and inferior OS in ALK+ NSCLC, comparable to primary TP53 mutated cases.
Prognostic Biomarkers in Pancreatic Cancer: Avoiding Errata When Using the TCGA Dataset
Authors: Nicolle Remy , Raffenne Jerome , Paradis Valerie , Couvelard Anne , de Reynies Aurelien , Blum Yuna , Cros Jerome
Published: January 2019

Data from the Cancer Genome Atlas (TCGA) are now easily accessible through web-based platforms with tools to assess the prognostic value of molecular alterations. Pancreatic tumors have heterogeneous biology and aggressiveness ranging from the deadly adenocarcinoma (PDAC) to the better prognosis, neuroendocrine tumors. We assessed the availability of the pancreatic cancer TCGA data (TCGA_PAAD) from several repositories and investigated the nature of each sample and how non-PDAC samples impact prognostic biomarker studies. While the clinical and genomic data (n = 185) were fairly consistent across all repositories, RNAseq profiles varied from 176 to 185. As a result, 35 RNAseq profiles (18.9%) corresponded to a normal, inflamed pancreas or non-PDAC neoplasms. This information was difficult to obtain. By considering gene expression data as continuous values, the expression of the 5312 and 4221 genes were significantly associated with the progression-free and overall survival respectively. Considering the cohort was not curated, only 4 and 14, respectively, had prognostic value in the PDAC-only cohort. Similarly, mutations in key genes or well-described miRNA lost their prognostic significance in the PDAC-only cohort. Therefore, we propose a web-based application to assess biomarkers in the curated TCGA_PAAD dataset. In conclusion, TCGA_PAAD curation is critical to avoid important biological and clinical biases from non-PDAC samples.
Functional Characterization of Ubiquitin-Like Core Autophagy Protein ATG12 in Dictyostelium discoideum
Authors: Fischer Sarah , Rijal Ramesh , Frommolt Peter , Wagle Prerana , Konertz Roman , Faix Jan , Meßling Susanne , Eichinger Ludwig
Published: January 2019

Autophagy is a highly conserved intracellular degradative pathway that is crucial for cellular homeostasis. During autophagy, the core autophagy protein ATG12 plays, together with ATG5 and ATG16, an essential role in the expansion of the autophagosomal membrane. In this study we analyzed gene replacement mutants of atg12 in Dictyostelium discoideum AX2 wild-type and ATG16‾ cells. RNAseq analysis revealed a strong enrichment of, firstly, autophagy genes among the up-regulated genes and, secondly, genes implicated in cell motility and phagocytosis among the down-regulated genes in the generated ATG12‾, ATG16‾ and ATG12‾/16‾ cells. The mutant strains showed similar defects in fruiting body formation, autolysosome maturation, and cellular viability, implying that ATG12 and ATG16 act as a functional unit in canonical autophagy. In contrast, ablation of ATG16 or of ATG12 and ATG16 resulted in slightly more severe defects in axenic growth, macropinocytosis, and protein homeostasis than ablation of only ATG12, suggesting that ATG16 fulfils an additional function in these processes. Phagocytosis of yeast, spore viability, and maximal cell density were much more affected in ATG12‾/16‾ cells, indicating that both proteins also have cellular functions independent of each other. In summary, we show that ATG12 and ATG16 fulfil autophagy-independent functions in addition to their role in canonical autophagy.
Telomere Biology and Human Phenotype
Authors: Turner Kara , Vasu Vimal , Griffin Darren
Published: January 2019

Telomeres are nucleoprotein structures that cap the end of each chromosome arm and function to maintain genome stability. The length of telomeres is known to shorten with each cell division and it is well-established that telomere attrition is related to replicative capacity in vitro. Moreover, telomere loss is also correlated with the process of aging in vivo. In this review, we discuss the mechanisms that lead to telomere shortening and summarise telomere homeostasis in humans throughout a lifetime. In addition, we discuss the available evidence that shows that telomere shortening is related to human aging and the onset of age-related disease.
Application of Prostate Cancer Models for Preclinical Study: Advantages and Limitations of Cell Lines, Patient-Derived Xenografts, and Three-Dimensional Culture of Patient-Derived Cells
Authors: Namekawa Takeshi , Ikeda Kazuhiro , Horie-Inoue Kuniko , Inoue Satoshi
Published: January 2019

Various preclinical models have been developed to clarify the pathophysiology of prostate cancer (PCa). Traditional PCa cell lines from clinical metastatic lesions, as exemplified by DU-145, PC-3, and LNCaP cells, are useful tools to define mechanisms underlying tumorigenesis and drug resistance. Cell line-based experiments, however, have limitations for preclinical studies because those cells are basically adapted to 2-dimensional monolayer culture conditions, in which the majority of primary PCa cells cannot survive. Recent tissue engineering enables generation of PCa patient-derived xenografts (PDXs) from both primary and metastatic lesions. Compared with fresh PCa tissue transplantation in athymic mice, co-injection of PCa tissues with extracellular matrix in highly immunodeficient mice has remarkably improved the success rate of PDX generation. PDX models have advantages to appropriately recapitulate the molecular diversity, cellular heterogeneity, and histology of original patient tumors. In contrast to PDX models, patient-derived organoid and spheroid PCa models in 3-dimensional culture are more feasible tools for in vitro studies for retaining the characteristics of patient tumors. In this article, we review PCa preclinical model cell lines and their sublines, PDXs, and patient-derived organoid and spheroid models. These PCa models will be applied to the development of new strategies for cancer precision medicine.
The Effects of Chlorinated Drinking Water on the Assembly of the Intestinal Microbiome
Authors: Martino David
Published: January 2019

This concept paper discusses the potential impact of chlorinated public drinking water on the assembly of the intestinal microbiome in infancy. The addition of chlorine or hypochlorite to metropolitan drinking water is routinely used worldwide as a sanitizer because of its potent anti-microbial properties. It is one of the most effective means of delivering safe drinkable water because it produces a residual disinfectant that persists within the distribution system. Levels of chlorine used to treat metropolitan water are considered safe for the individual, based on toxicity studies. However, to our knowledge there have been no studies examining whether levels of persistent chlorine exposure from tap water are also safe for the ecosystem of microorganisms that colonize the gastrointestinal tract. Given the importance of the microbiome in health, persistent exposure to low levels of chlorine may be a hitherto unrecognized risk factor for gut dysbiosis, which has now been linked to virtually every chronic non-communicable disease of the modern era. Although effects may be subtle, young children and infants are more susceptible to ecological disturbance, given that the microbiome is highly influenced by environmental factors during this period. Here I outline considerations for the safety of water disinfectants not just in terms of toxicity to the host, but also for the ecosystem of microorganisms that inhabit us. Research in this is likely to bear fruitful information that could either bring attention to this issue, potentially driving new innovations in public water management; or could help confirm the safety profile of chlorine levels in public drinking water.
Geographical Analysis of the Distribution of Publications Describing Spatial Associations among Outdoor Environmental Variables and Really Small Newborns in the USA and Canada
Authors: Nielsen Charlene C. , Amrhein Carl G. , Osornio-Vargas Alvaro R.
Published: January 2019

Newborns defined as being of “low birth weight” (LBW) or “small for gestational age” (SGA) are global health issues of concern because they are vulnerable to mortality and morbidity. Prenatal exposures may contribute to LBW/SGA. In this review, we searched peer-reviewed scientific literature to determine what location-based hazards have been linked with LBW/SGA in the industrialized nations of Canada and the USA. After selecting studies based on inclusion/exclusion criteria, we entered relevant details in to an evidence table. We classified and summarized 159 articles based on type of environment (built = 108, natural = 10, and social = 41) and general category of environmental variables studied (e.g., air pollution, chemical, water contamination, waste site, agriculture, vegetation, race, SES, etc.). We linked the geographic study areas by province/state to political boundaries in a GIS to map the distributions and frequencies of the studies. We compared them to maps of LBW percentages and ubiquitous environmental hazards, including land use, industrial activity and air pollution. More studies had been completed in USA states than Canadian provinces, but the number has been increasing in both countries from 1992 to 2018. Our geographic inquiry demonstrated a novel, spatially-focused review framework to promote understanding of the human ‘habitat’ of shared environmental exposures that have been associated with LBW/SGA.
Children Are Born to Dance! Pediatric Medical Dance/Movement Therapy: The View from Integrative Pediatric Oncology
Authors: Tortora Suzi
Published: January 2019

Children freely expressing themselves through spontaneous dance is a natural part of childhood. The healing powers of dance are universal in all cultures across history. Dance/movement therapy (DMT) in pediatric oncology is little known and underutilized. This article discusses DMT, specifically focusing on pediatric oncology. It defines and clarifies the difference between medical DMT as a psychotherapeutic modality aimed at addressing the patient’s psychosocial needs, and dance and therapeutic dance used recreationally to engage patients during their hospital visits. A literature review of DMT with medically ill children in the United States and worldwide is provided. It culminates with a focus on advancements in the field, discussing the future of pediatric medical DMT. Grounded in a biopsychosocial perspective, the intrinsically nonverbal and embodied nature of pediatric medical DMT is uniquely positioned to be a strong component of integrative oncology services. The use of DMT to synthesize potentially traumatic aspects of the medical experience is proposed. It ends with a call for research posing the question: Can pediatric medical DMT support the patient to express feelings while in cancer treatment within the context of a psychotherapeutic milieu, enabling the patient to create an embodied coherent narrative that fosters expressivity and empowerment?
Co-Association Matrix-Based Multi-Layer Fusion for Community Detection in Attributed Networks
Authors: Luo Sheng , Zhang Zhifei , Zhang Yuanjian , Ma Shuwen
Published: January 2019

Community detection is a challenging task in attributed networks, due to the data inconsistency between network topological structure and node attributes. The problem of how to effectively and robustly fuse multi-source heterogeneous data plays an important role in community detection algorithms. Although some algorithms taking both topological structure and node attributes into account have been proposed in recent years, the fusion strategy is simple and usually adopts the linear combination method. As a consequence of this, the detected community structure is vulnerable to small variations of the input data. In order to overcome this challenge, we develop a novel two-layer representation to capture the latent knowledge from both topological structure and node attributes in attributed networks. Then, we propose a weighted co-association matrix-based fusion algorithm (WCMFA) to detect the inherent community structure in attributed networks by using multi-layer fusion strategies. It extends the community detection method from a single-view to a multi-view style, which is consistent with the thinking model of human beings. Experiments show that our method is superior to the state-of-the-art community detection algorithms for attributed networks.
A Coupled, Semi-Numerical Model for Thermal Analysis of Medium Frequency Transformer
Authors: Tian Haonan , Wei Zhongbao , Vaisambhayana Sriram , Thevar Madasamy , Tripathi Anshuman , Kjær Philip
Published: January 2019

Medium-frequency (MF) transformer has gained much popularity in power conversion systems. Temperature control is a paramount concern, as the unexpected high temperature declines the safety and life expectancy of transformer. The scrutiny of losses and thermal-fluid behavior are thereby critical for the design of MF transformers. This paper proposes a coupled, semi-numerical model for electromagnetic and thermal-fluid analysis of MF oil natural air natural (ONAN) transformer. An analytical model that is based on spatial distribution of flux density and AC factor is exploited to calculate the system losses, while the thermal-hydraulic behavior is modelled numerically leveraging the computational fluid dynamics (CFD) method. A close-loop iterative framework is formulated by coupling the analytical model-based electromagnetic analysis and CFD-based thermal-fluid analysis to address the temperature dependence. Experiments are performed on two transformer prototypes with different conductor types and physical geometries for validation purpose. Results suggest that the proposed model can accurately model the AC effects, losses, and the temperature rises at different system components. The proposed model is computationally more efficient than the full numerical method but it reserves accurate thermal-hydraulic characterization, thus it is promising for engineering utilization.
Landscape-Scale Mixtures of Tree Species are More Effective than Stand-Scale Mixtures for Biodiversity of Vascular Plants, Bryophytes and Lichens
Authors: Heinrichs Steffi , Ammer Christian , Mund Martina , Boch Steffen , Budde Sabine , Fischer Markus , Müller Jörg , Schöning Ingo , Schulze Ernst-Detlef , Schmidt Wolfgang , Weckesser Martin , Schall Peter
Published: January 2019

Tree species diversity can positively affect the multifunctionality of forests. This is why conifer monocultures of Scots pine and Norway spruce, widely promoted in Central Europe since the 18th and 19th century, are currently converted into mixed stands with naturally dominant European beech. Biodiversity is expected to benefit from these mixtures compared to pure conifer stands due to increased abiotic and biotic resource heterogeneity. Evidence for this assumption is, however, largely lacking. Here, we investigated the diversity of vascular plants, bryophytes and lichens at the plot (alpha diversity) and at the landscape (gamma diversity) level in pure and mixed stands of European beech and conifer species (Scots pine, Norway spruce, Douglas fir) in four regions in Germany. We aimed to identify compositions of pure and mixed stands in a hypothetical forest landscape that can optimize gamma diversity of vascular plants, bryophytes and lichens within regions. Results show that gamma diversity of the investigated groups is highest when a landscape comprises different pure stands rather than tree species mixtures at the stand scale. Species mainly associated with conifers rely on light regimes that are only provided in pure conifer forests, whereas mixtures of beech and conifers are more similar to beech stands. Combining pure beech and pure conifer stands at the landscape scale can increase landscape level biodiversity and conserve species assemblages of both stand types, while landscapes solely composed of stand scale tree species mixtures could lead to a biodiversity reduction of a combination of investigated groups of 7 up to 20%.
Effect of Herbaceous Layer Interference on the Post-Fire Regeneration of a Serotinous Pine (Pinus pinaster Aiton) across Two Seedling Ages
Authors: Castro Jorge , Leverkus Alexandro B.
Published: January 2019

Herbaceous vegetation is a major source of interference with the regeneration of woody species. This is particularly the case after forest fires, as a dense herbaceous layer usually regenerates naturally. Although the competitive effect of the herbaceous vegetation upon tree seedlings has been widely studied, there are still gaps in knowledge for management related to the effect of tree seedling age and size on the outcome of the interaction. In this study, we seek to determine the response of maritime pine (Pinus pinaster Aiton) seedlings to herbaceous competition at two different seedling ages. For that, two treatments of herbaceous competition were implemented, namely unweeded (no action around pine seedlings) and weeded (herbaceous cover removed around pine seedlings). Treatments were conducted twice (2 and 4 years after the fire), and we monitored seedling survival and growth at the end of each growing season. The treatments were implemented across three adjacent landscape units that differed in the management of burned wood and that are representative of common post-fire scenarios: no intervention, salvage logging, and an intermediate degree of intervention. Weeding increased seedling survival from 44.7% to 67.8% when seedlings were 2 years old, but had no effect for four-year-old seedlings, which showed 99% survival. Seedling growth also increased in the weeding treatment, but only slightly. Moreover, growth (and survival for two-year-old seedlings) was strongly correlated with initial seedling size, particularly in the case of two-year-old seedlings. Initial pine seedling height was strongly and positively correlated with the height of the herbaceous layer, supporting the existence of microsite features that promote plant growth above competitive effects. The results support that management actions conducive to foster post-fire pine forest restoration in this Mediterranean ecosystem should reduce herbaceous competition at early stages after fire (second or third year) and focus on larger seedlings.
Abiotic and Biotic Disturbances Affecting Forest Health in Poland over the Past 30 Years: Impacts of Climate and Forest Management
Authors: Sierota Zbigniew , Grodzki Wojciech , Szczepkowski Andrzej
Published: January 2019

The current nature of forest management in Poland reflects its history and more than 100 years of economic activity affecting forests since independence in 1918. Before that time, different forest management models were used, related to the nature of the Prussian economy in the north of the country, the Russian economy in the central-eastern part, and the Austrian economy in south-eastern Poland. The consequence of these management models, as well as the differing climate zones in which they were used, resulted in varied forest health. Since the end of World War II, forest coverage within Poland‘s new borders has increased from 20.8% to currently 29.6%, mainly as a result of afforestation of wastelands and former agricultural lands. This paper describes changes in the health of forests and their biological diversity in Poland in the context of weather extremes, species composition, forest management, the forest industry, and damage from insects and pathogenic fungi over the last 30 years.
Effect of Yeast Extract on Seedling Growth Promotion and Soil Improvement in Afforestation in a Semiarid Chestnut Soil Area
Authors: Xi Qin , Lai Wenhao , Cui Youyuan , Wu Hailong , Zhao Tingning
Published: January 2019

Yeast extract, which is environmentally friendly, nutritious, and convenient to use, has advantages over common plant growth regulators and soil conditioners. It is worth verifying the effect of the application of yeast extract to afforestation in a semiarid chestnut soil area. This study was conducted through a wild field afforestation experiment in Inner Mongolia, northern China. We designed an orthogonal experiment of 25 treatments with 30 repetitions on Pinus sylvestris(Pinus sylvestris var. mongolica Litv.) sand Armeniaca sibirica（Armeniaca sibirica (L.) Lam）. Three factors with different levels were considered: application to rhizosphere soil with the amounts of 0 g, 10 g, 20 g, 30 g, and 40 g; foliar spraying with concentrations of 0%, 0.5%, 1%, 1.5%, and 2%; and spraying at three moments. The results showed that yeast extract could enhance the seedlings of Pinus sylvestris and Armeniaca sibirica. When applying 40 g of yeast extract, the survival rates and root parameters were significantly boosted. Foliar spraying plays an important role in promoting the growth of seedlings. It was most effective for the two species to be sprayed with a concentration of 2% after leafing of the seedlings. The data also revealed that the application of yeast extract improved the properties of the rhizosphere soil. The porosities and moisture contents were increased, and the bulk densities were reduced. Forty grams (40 g) was the best amount to apply, especially for the soil at 20–40 cm where the seedling roots are mainly located. The chemical properties were also improved, as there was a significant increase in the conductivities, organic matter, nitrogen, and phosphorus as well as a slight reduction in the calcium carbonate content and pH. Therefore, yeast extract has a beneficial effect on both seedling growth promotion and soil improvement. It is considered to be an environmentally efficient method for afforestation and ecological remediation in semiarid chestnut soil areas.