bluuebunny/crossref_metadata_2025 huggingface dataset:
111In-labeled anti-cadherin17 antibody D2101 has potential as a noninvasive imaging probe for diagnosing gastric cancer and lymph-node metastasis
Authors: Fujiwara Kentaro , Tsuji Atsushi B. , Sudo Hitomi , Sugyo Aya , Akiba Hiroki , Iwanari Hiroko , Kusano-Arai Osamu , Tsumoto Kouhei , Momose Toshimitsu , Hamakubo Takao , Higashi Tatsuya
Published: October 2019

Objective

Cadherin-17 (CDH17) is a transmembrane protein that mediates cell–cell adhesion and is frequently expressed in adenocarcinomas, including gastric cancer. CDH17 may be an effective diagnostic marker for the staging of gastric cancer. Here, we developed an 111In-labeled anti-CDH17 monoclonal antibody (Mab) as an imaging tracer and performed biodistribution and single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging studies using mice with CDH17-positive gastric cancer xenografts. CDH17 expression in gastric cancer specimens was also analyzed.

Methods

The cross-reactivity and affinity of our anti-CDH17 Mab D2101 was evaluated by surface plasmon resonance analysis and cell enzyme-linked immunosorbent assay, respectively. Biodistribution and SPECT/CT studies of 111In-labeled D2101 (111In-D2101) were performed. CDH17 expression in gastric cancer specimens was evaluated by immunohistochemistry.

Results

Surface plasmon resonance analysis revealed that D2101 specifically recognizes human CDH17, but not murine CDH17. The affinity of D2101 slightly decreased as a result of the radiolabeling procedures. The biodistribution study revealed high uptake of 111In-D2101 in tumors (maximum, 39.2 ± 9.5% ID/g at 96 h postinjection), but low uptake in normal organs, including the stomach. Temporal SPECT/CT imaging with 111In-D2101 visualized tumors with a high degree of tumor-to-nontumor contrast. Immunohistochemical analysis revealed that, compared with HER2, which is a potential marker of N-stage, CDH17 had a higher frequency of positivity in specimens of primary and metastatic gastric cancer.

Conclusion

Our 111In-anti-CDH17 Mab D2101 depicted CDH17-positive gastric cancer xenografts in vivo and has the potential to be an imaging probe for the diagnosis of primary lesions and lymph-node metastasis in gastric cancer.
Manual on the proper use of yttrium-90-labeled anti-P-cadherin antibody injection for radionuclide therapy in clinical trials
Authors: Hosono Makoto , Ikebuchi Hideharu , Kinuya Seigo , Yanagida Sachiko , Nakamura Yoshihide , Yamada Takahiro , Sakaguchi Kenta , Sugano Hiroyasu , Kojima Kiyotaka , Hatazawa Jun
Published: October 2019

We present the guideline for use of yttrium-90-labeled anti-P-cadherin antibody injection for radionuclide therapy in clinical trials on the basis of radiation safety issues in Japan. This guideline was prepared by a study supported by the Ministry of Health, Labour, and Welfare, and approved by the Japanese Society of Nuclear Medicine. Treatment using yttrium-90-labeled anti-P-cadherin antibody injection in Japan should be carried out according to this guideline. Although this guideline is applied in Japan, the issues for radiation protection shown here are considered internationally useful as well. Only the original Japanese version is the formal document.
The AUGMENT study
Authors: Dada Reyad
Published: October 2019

Follicular lymphoma is the most common form of indolent Non-Hodgkin Lymphoma and characterized by repeated relapses. Follicular lymphoma (FL) tissue was found to have association between malignant cells and benign immune cells represented in the surrounded microenvironment. Lenalidomide, an immunomodulator, is affecting this microenvironment and demonstrated relevant clinical activity in phase III trials in patients with FL lymphoma. The AUGMENT trial resulted in a better PFS with lenalidomide and rituximab than rituximab and placebo in patients with relapsed/refractory FL and marginal zone lymphoma. However, there are some concerns around the study. The following article is discussing some of these concerns.
Comparative effectiveness of busulfan/cyclophosphamide versus busulfan/fludarabine myeloablative conditioning for allogeneic hematopoietic cell transplantation in acute myeloid leukemia and myelodysplastic syndrome
Authors: Patel Sagar S. , Rybicki Lisa , Pohlman Brad , Bolwell Brian , Gerds Aaron T. , Hamilton Betty K. , Hanna Rabi , Kalaycio Matt , Majhail Navneet S. , Sobecks Ronald
Published: October 2019

Objective/Background:

Busulfan/cyclophosphamide (Bu/Cy) and busulfan/fludarabine (Bu/Flu) are both standard myeloablative conditioning (MAC) regimens for allogeneic hematopoietic cell transplantation (alloHCT). We compared the effectiveness of these regimens with a focus on quality of life (QOL).

Methods:

This was a single center, retrospective analysis of adult acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients who underwent a first T-cell replete HLA-8/8 matched related or unrelated donor alloHCT. Patients received a myeloablative regimen of either parenteral Bu/Cy or Bu/Flu. Outcomes assessed included infections, graft-versus-host-disease (GVHD), relapse, relapse mortality (RM), relapse-free survival (RFS), nonrelapse mortality (NRM), overall survival (OS), and QOL.

Results:

From 2008 to 2017, 126 AML and 84 MDS adult patients age ≥18 years were identified meeting inclusion criteria. In terms of QOL, there were no significant differences between Bu/Cy and Bu/Flu cohorts in the Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale (FACT-BMT) scores or mucositis severity for either AML or MDS patients. Amongst AML patients, those receiving Bu/Flu had more rapid neutrophil and platelet recovery and a shorter length of hospital stay (LOS); there were no differences in the other posttransplant outcomes. Similarly, amongst MDS patients, those receiving Bu/Flu had more rapid platelet recovery and a shorter LOS as well as more CMV infections, but less NRM and no differences in other outcomes.

Conclusion:

We confirmed that myeloablative Bu/Flu conditioning has comparable clinical and QOL outcomes to Bu/Cy.
Can Reconnection be Triggered as a Solar Wind Directional Discontinuity Crosses the Bow Shock? A Case of Asymmetric Reconnection
Authors: Hamrin M. , Gunell H. , Goncharov O. , De Spiegeleer A. , Fuselier S. , Mukherjee J. , Vaivads A. , Pitkänen T. , Torbert R. B. , Giles B.
Published: October 2019

Here we present some unique observations of reconnection at a quasi‐perpendicular bow shock as an interplanetary directional discontinuity (DD) is crossing it simultaneously with the Magnetospheric Multiscale (MMS) mission. There are no burst data, but available data show indications of ongoing reconnection at the shock southward of MMS: a bifurcated current sheet with signatures of Hall magnetic and electric fields, normal magnetic fields indicating a magnetic connection between the two reconnecting regions, field‐aligned currents and electric fields, E·J>0 indicating a conversion of magnetic to kinetic energy, and subspin resolution ion energy‐time spectrograms indicating ions being accelerated away from the X‐line. The DD is also observed by four upstream spacecraft (ACE, WIND, Geotail, and ARTEMIS P1) and one downstream in the magnetosheath (Cluster 4), but none of them resolve signatures of ongoing reconnection. We therefore suggest that reconnection was temporarily triggered as the DD was compressed by the shock. Reconnection at the bow shock is inevitably asymmetric with both the density and magnetic field strength being higher on one side of the X‐line (magnetosheath side) than on the other side where the plasma flow also is supersonic (solar wind side). This is different from the asymmetry exhibited at the more commonly studied case of asymmetric reconnection at the magnetopause. Asymmetric reconnection of the bow shock type has never been studied before, and the data discussed here present some first indications of the properties of the reconnection region for this type of reconnection.
Introduction of Water‐Vapor Broadening Parameters and Their Temperature‐Dependent Exponents Into the HITRAN Database: Part I—CO2, N2O, CO, CH4, O2, NH3, and H2S
Authors: Tan Y. , Kochanov R. V. , Rothman L. S. , Gordon I. E.
Published: October 2019

The amount of water vapor in the terrestrial atmosphere is highly variable both spatially and temporally. In the tropics it sometimes constitutes 4–5% of the atmosphere. At the same time collisional broadening of spectral lines by water vapor is much larger than that by nitrogen and oxygen. Therefore, in order to accurately characterize and model spectra of the atmospheres with significant amounts of water vapor, the line‐shape parameters for spectral lines broadened by water vapor are required. In this work, the pressure‐broadening parameters (and their temperature‐dependent exponents) due to the pressure of water vapor for spectral lines of CO2, N2O, CO, CH4, O2, NH3, and H2S from both experimental and theoretical studies were collected and carefully reviewed. A set of semiempirical models based on these collected data was proposed and then used to estimate water broadening and its temperature dependence for all transitions of selected molecules in the HITRAN2016 database.
The Orinoco Low‐Level Jet: An Investigation of Its Characteristics and Evolution Using the WRF Model
Authors: Jiménez‐Sánchez Giovanni , Markowski Paul M. , Jewtoukoff Valerian , Young George S. , Stensrud David J.
Published: October 2019

The structure and evolution of the low‐level jet over the Orinoco River basin is characterized using finer horizontal, vertical, and temporal resolution than possible in previous studies via dynamical downscaling. The investigation relies on a 5‐month‐long simulation (November 2013 to March 2014) performed with the Weather Research and Forecasting model, with initial and boundary conditions provided by the Global Forecast System analysis. Dynamical downscaling is demonstrated to be an effective method to better resolve the horizontal and vertical characteristics of the Orinoco low‐level jet (OLLJ), improving not only the representation of small‐scale jet streaks within the broader region of low‐level wind enhancement but also its diurnal and austral‐summer evolution. The OLLJ is found to be a single stream tube over Colombia and Venezuela with wind speeds greater than 8 m/s and four distinctive cores varying in height under the influence of sloping terrain. The OLLJ has its maximum monthly mean wind speed (13 m/s) and largest spatial extent (2,100 km × 400 km) in January. The maximum mean wind speeds (13–17 m/s) in the diurnal cycle occur in the early morning, whereas wind speeds are a minimum (8–9 m/s) in the late afternoon when a deep, convective boundary layer is present. The intraseasonal variability of the wind speed and potential temperature only presents significant periodicity in the diurnal and semidiurnal scales, with no other meaningful cycles evident during the austral summer.
Mountain‐Block Recharge: A Review of Current Understanding
Authors: Markovich Katherine H. , Manning Andrew H. , Condon Laura E. , McIntosh Jennifer C.
Published: October 2019

Mountain‐block recharge (MBR) is the subsurface inflow of groundwater to lowland aquifers from adjacent mountains. MBR can be a major component of recharge but remains difficult to characterize and quantify due to limited hydrogeologic, climatic, and other data in the mountain block and at the mountain front. The number of MBR‐related studies has increased dramatically in the 15 years since the last review of the topic was conducted by Wilson and Guan (2004), generating important advancements. We review this recent body of literature, summarize current understanding of factors controlling MBR, and provide recommendations for future research priorities. Prior to 2004, most MBR studies were performed in the southwestern United States. Since then, numerous studies have detected and quantified MBR in basins around the world, typically estimating MBR to be 5–50% of basin‐fill aquifer recharge. Theoretical studies using generic numerical modeling domains have revealed fundamental hydrogeologic and topographic controls on the amount of MBR and where it originates within the mountain block. Several mountain‐focused hydrogeologic studies have confirmed the widespread existence of mountain bedrock aquifers hosting considerable groundwater flow and, in some cases, identified the occurrence of interbasin flow leaving headwater catchments in the subsurface—both of which are required for MBR to occur. Future MBR research should focus on the collection of high‐priority data (e.g., subsurface data near the mountain front and within the mountain block) and the development of sophisticated coupled models calibrated to multiple data types to best constrain MBR and predict how it may change in response to climate warming.
Physical layer security in cooperative amplify‐and‐forward relay networks over mixed Nakagami‐m and double Nakagami‐m fading channels: performance evaluation and optimisation
Authors: Pandey Anshul , Yadav Suneel
Published: October 2019

The authors investigate the secrecy performance of a cooperative relaying network, wherein a fixed source communicates with a fixed destination via an amplify‐and‐forward mobile relay in the presence of a passive mobile eavesdropper. They assume that the source‐to‐relay channel and relay‐to‐destination channel experience Nakagami‐m fading, whereas relay‐to‐eavesdropper link follows double Nakagami‐m fading. Under such a mixed fading environment, they derive the novel tight closed‐form expressions for the secrecy outage probability (SOP), probability of non‐zero secrecy capacity, and intercept probability of the considered system. They also deduce the asymptotic secrecy outage and intercept probability expressions in the high signal‐to‐noise ratio regime to highlight the impact of fading parameters and channel conditions on the secrecy diversity order. It is shown that the system can achieve secrecy diversity order of min() in terms of SOP, and in terms of intercept probability, where and represent the fading severity parameters between source and relay and between relay and destination, respectively. They also formulate and investigate analytically two optimisation problems, namely, optimal relay location with fixed power allocation and optimal power allocation with fixed relay location, to minimise the system SOP. They verify analytical findings via numerical and simulation results.
Optimal resource utilisation algorithm for visible light communication‐based vehicular ad‐hoc networks
Authors: Msongaleli Dawson Ladislaus , Kucuk Kerem
Published: October 2019

With the advent of visible light communication (VLC) and vehicular ad‐hoc networks (VANETs), the realisation of the intelligent transportation system (ITS) is becoming a reality. In high‐mobility networks such as VANETs packet transmission failure may occur frequently if network lifetime, connectivity, and load balancing are not considered during next‐hop link selection. Optimal resource utilisation can address the network lifetime, network connectivity, and network load balancing problems in ITS. This study investigates the problem of optimal resource allocation for VLC‐based VANETs. The authors present a multi‐objective integer linear programming (ILP) model that optimises resource utilisation in VLC‐based VANETs, wherein the objectives are maximising network lifetime, load balancing, and network connectivity. Illustrative numerical results demonstrate that their solution achieves promising results, however, for high vehicle density, the problem is intractable. Therefore, they proposed a heuristic algorithm that addresses the problem when vehicle density is high in a network. They demonstrate the benefits of the proposed algorithm by comparing their solution against optimal resource utilisation unaware strategy, wherein resources are assigned randomly without considering resource optimisation. Their experimental study shows that both the ILP model and the heuristic algorithm increase network performance in terms of maximising network lifetime, connectivity, and load balancing.
Examining regional mobility patterns of public transit and automobile users based on the smart card and mobile Internet data: a case study of Chengdu, China
Authors: Chen Xi , Wang Yinhai , Tang Jinjun , Dai Zhuang , Ma Xiaolei
Published: October 2019

Understanding human travel patterns with relation to land uses and other land characteristics is a crucial topic in urban studies and offers guidance to better design, plan and manage diverse transportation systems and infrastructures. However, previous studies on such patterns still have some limitations. First, current studies mainly focus on mobility pattern analysis on stop and route levels. Rare studies have investigated user mobility on region levels to exhibit a macroscopic perspective on human activities. Second, the works usually examine one specific transportation mode and fail to compare regional mobility among multiple modes. This study proposes a comprehensive methodology framework to uncover regional travel patterns and regularities. Regional travel patterns are analysed using the non‐negative matrix factorisation method. The travel regularity is examined using the Lempel–Ziv algorithm. A case study of Chengdu, China, is conducted to validate the proposed framework. Results can support several applications that are beneficial for urban transportation planning.
Z-Isomers of lycopene exhibit greater liver accumulation than the all-E-isomer in mice
Authors: Honda Masaki , Nakayama Yuki , Nishikawa Sho , Tsuda Takanori
Published: October 2019

The effect of oral administration of all-E-isomer-rich and Z-isomer-rich lycopene on liver accumulation in mice was investigated. When a diet rich in the Z-isomers was administered for 4 weeks, the total lycopene concentration in the liver was more than 3 times higher than that of all-E-isomer administration. This result clearly indicates that lycopene Z-isomers show greater bioavailability and/or liver accumulation than the all-E-isomer in mice.
Association between student characteristics and rankings when applying for a residency in health-system pharmacy administration
Authors: Morbitzer Kathryn A , Eckel Stephen F
Published: October 2019

Purpose

Results of a study to identify characteristics associated with pharmacy residency applicant success in obtaining an invitation to interview and a top candidate ranking are reported. Subsequent development and initial validation of a predictive model based on those characteristics are described.

Methods

Bivariable analyses were performed for planned stratifications of applicants to a health-system pharmacy administration residency program according to whether they were offered an on-site interview or were among the 8 top candidates by final candidate ranking. A Random Forest algorithm was created to identify predictors of the likelihood of an applicant being offered an on-site interview.

Results

Applicants who were offered interviews had a higher median pharmacy school grade point average (GPA) than those not invited to interview: 3.63 (interquartile range [IQR], 3.46–3.79) versus 3.35 (IQR, 3.2–3.49); p < 0.001. Invited applicants also received more scholarships during pharmacy school (median, 2 [IQR, 1–3) versus 1 [IQR, 0–2]; p = 0.002). Applicants with prior work experience as a hospital pharmacy intern were also more likely than those without such experience to be offered an interview (70.0% versus 37.8% were invited, p = 0.001), as were applicants who presented a poster at a national meeting during pharmacy school (80% versus 60%, p = 0.02) or who served in a national pharmacy organization leadership position (41.4% versus 20%, p = 0.03). Pharmacy school GPA was associated with final candidate ranking; top-ranked candidates had a significantly higher median GPA than lower-ranked applicants (3.68 [IQR, 3.51–3.8] versus 3.48 [IQR, 3.23–3.7]; p = 0.003).

Conclusion

Objective criteria within the realms of academic performance and prior work experience may be used to streamline the applicant screening process when determining candidates to invite for an on-site interview. Pharmacy school GPA was the only characteristic found to be associated with applicant final ranking.
Inpatient pain management in sickle cell disease
Authors: Zassman Stefanie M , Zamora Francis J , Roberts John D
Published: October 2019

Purpose

A novel strategy for management of acute pain associated with sickle cell disease (SCD), referred to as the oral tier approach, is described.

SCD is an inherited blood disorder characterized by episodic acute pain known as vaso-occlusive crisis (VOC), which is the most common reason for emergency department visits and hospital admissions in patients with SCD; these patients are often treated with parenteral opioids on admission and then transitioned to oral opioids prior to discharge. In this report, experience with use of the oral tier approach in 3 patients with SCD hospitalized for management of VOC is reported. As per usual practice, acute pain was initially managed with parenteral opioids via patient-controlled analgesia (PCA). Once pain control was established, an oral tier was added. The oral tier consisted of 3 orders. The first order was for an oral opioid, to be administered every 3 hours on a scheduled basis; however, the patient could refuse 1 or more of these scheduled doses. Two additional orders specified that the patients could receive additional oral opioids in incremental doses for moderate (grade 4–7) or severe (grade 8–10) pain if appropriate. To facilitate transition to an oral regimen with which the patients might be discharged, they were encouraged to use oral opioids in preference to parenteral opioids. Opioid usage and average daily pain scores for the 3 patients are reported.

Conclusion

Healthcare providers can use the oral tier approach to facilitate rapid inpatient conversion from i.v. PCA to oral opioids while providing adequate pain control in patients with SCD who develop VOC.
The Use of An EHR Patient Portal (Mychart-Epic) in Patients With Inflammatory Bowel Disease
Authors: Reich Jason , Canakis Andrew , Shankar Divya , Harrington Jill , Apte Manisha , Weinberg Janice , Jones Eric , Noronha Ansu , Wasan Sharmeel K , Farraye Francis A
Published: October 2019

Introduction

Inflammatory bowel disease (IBD) has a significant effect on patients’ overall quality of life (QoL). We hypothesized that an Electronic Health Record (EHR) patient portal (EPIC’s Mychart) can be utilized to improve QoL in IBD patients and increase vaccine uptake.

Methods

Patients were randomized to receive specific disease (INT) information and to a control arm (CTRL) that received periodic non-IBD related messages. Disease severity was assessed using the Harvey-Bradshaw index, and Simple Clinical Colitis Activity index. QoL was measured using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ). Secondary outcome measures included overall satisfaction with the portal and influenza and pneumococcal vaccine uptake.

Results

One hundred twenty-seven patients were randomized: At baseline the CTRL group had a statistically significant higher QoL (Median SIBDQ 53.7) compared with the INT group (median SIBDQ 49.3), P = 0.04. At 6 months, the INT group had a trend towards a significantly greater increase in QoL (median SIBDQ 58) when compared with the CTRL group (median SIBDQ 57.5), P = 0.06. At 6 months more frequent portal use showed a significantly lower median SIBDQ (median 53) compared with patients with less frequent portal use (median 59), P = 0.038. At 6 months 88% of patients felt that the MyChart portal was useful with respect to IBD management. Patients had high rates of portal utilization with one-third of patients logging on weekly, and one-third logging on monthly. With respect to vaccine uptake, both influenza and pneumococcal pneumonia had higher rates of vaccine uptake.

Conclusions

Patients showed a trend towards improved QoL after receiving disease-specific information through our EHR portal. A significant increase in vaccine uptake was also seen. Frequent automated messages sent via an EHR portal can improve patient’s overall QoL. Larger studies will be needed to determine if automated portal reminders have a significant association with improved QoL, and furthermore to determine if there is any impact on disease activity.
European Heart Rhythm Association (EHRA) international consensus document on how to prevent, diagnose, and treat cardiac implantable electronic device infections—endorsed by the Heart Rhythm Society (HRS), the Asia Pacific Heart Rhythm Society (APHRS), the Latin American Heart Rhythm Society (LAHRS), International Society for Cardiovascular Infectious Diseases (ISCVID) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS)
Authors: Blomström-Lundqvist Carina , Traykov Vassil , Erba Paola Anna , Burri Haran , Nielsen Jens Cosedis , Bongiorni Maria Grazia , Poole Jeanne , Boriani Giuseppe , Costa Roberto , Deharo Jean-Claude , Epstein Laurence M , Saghy Laszlo , Snygg-Martin Ulrika , Starck Christoph , Tascini Carlo , Strathmore Neil ,   ESC Scientific Document Group, Kalarus Zbigniew , Boveda Serge , Dagres Nikolaos , Rinaldi Christopher A , Biffi Mauro , Gellér LászlóA , Sokal Adam , Birgersdotter-Green Ulrika , Lever Nigel , Tajstra Mateusz , Kutarski Andrzej , Rodríguez Diego A , Hasse Barbara , Zinkernagel Annelies , Mangoni EmanueleDurante
Published: October 2019

Pacemakers, implantable cardiac defibrillators, and cardiac resynchronization therapy devices are potentially life-saving treatments for a number of cardiac conditions, but are not without risk. Most concerning is the risk of a cardiac implantable electronic device (CIED) infection, which is associated with significant morbidity, increased hospitalizations, reduced survival, and increased healthcare costs. Recommended preventive strategies such as administration of intravenous antibiotics before implantation are well recognized. Uncertainties have remained about the role of various preventive, diagnostic, and treatment measures such as skin antiseptics, pocket antibiotic solutions, anti-bacterial envelopes, prolonged antibiotics post-implantation, and others. Guidance on whether to use novel device alternatives expected to be less prone to infections and novel oral anticoagulants is also limited, as are definitions on minimum quality requirements for centres and operators and volumes. Moreover, an international consensus document on management of CIED infections is lacking. The recognition of these issues, the dissemination of results from important randomized trials focusing on prevention of CIED infections, and observed divergences in managing device-related infections as found in an European Heart Rhythm Association worldwide survey, provided a strong incentive for a 2019 International State-of-the-art Consensus document on risk assessment, prevention, diagnosis, and treatment of CIED infections.
The nonsmooth landscape of phase retrieval
Authors: Davis Damek , Drusvyatskiy Dmitriy , Paquette Courtney
Published: October 2019

We consider a popular nonsmooth formulation of the real phase retrieval problem. We show that under standard statistical assumptions a simple subgradient method converges linearly when initialized within a constant relative distance of an optimal solution. Seeking to understand the distribution of the stationary points of the problem, we complete the paper by proving that as the number of Gaussian measurements increases, the stationary points converge to a codimension two set, at a controlled rate. Experiments on image recovery problems illustrate the developed algorithm and theory.
The orientation of planes of dwarf galaxies in the quasi-linear Universe
Authors: Libeskind Noam I , Carlesi Edoardo , Müller Oliver , Pawlowski Marcel S , Hoffman Yehuda , Pomarède Daniel , Courtois Helene M , Tully R , Gottlöber Stefan , Steinmetz Matthias , Sorce Jenny , Knebe Alexander
Published: October 2019

To date at least 10 highly flattened planes of dwarf galaxies are claimed to have been discovered in the Local Universe. The origin of these planes of galaxies remains unknown. One suggestion is that they are related to the large-scale structure of the cosmic web. A recent study found that the normal of a number of these dwarf galaxy planes is very closely aligned with the eigenvector of the shear tensor corresponding to the direction of greatest collapse obtained by reconstructing the full velocity field in the linear regime. Here we extend that work by both considering an additional 5 planes beyond the five examined previously and examining the alignment with respect to the quasi-linear field, a more sophisticated reconstruction, which is a better approximation on smaller (quasi-linear) scales. Our analysis recovers the previous result while not finding a significantly tight alignment with the additional five planes. However, the additional five plane normals also do not appear to be randomly oriented. We conclude that this could be due either to the normals of the new planes being poorly defined and described; the quasi-linear field at those locations being poorly constrained; or different formation mechanisms for the orientation of planes of dwarf galaxies.
Size and density sorting of dust grains in SPH simulations of protoplanetary discs – II. Fragmentation
Authors: Pignatale F C , Gonzalez J-F , Bourdon Bernard , Fitoussi Caroline
Published: October 2019

Grain growth and fragmentation are important processes in building up large dust aggregates in protoplanetary discs. Using a 3D two-phase (gas–dust) sph code, we investigate the combined effects of growth and fragmentation of a multiphase dust with different fragmentation thresholds in a time-evolving disc. We find that our fiducial disc, initially in a fragmentation regime, moves towards a pure-growth regime in a few thousands years. Time-scales change as a function of the disc and dust properties. When fragmentation is efficient, it produces, in different zones of the disc, Fe/Si and rock/ice ratios different from those predicted when only pure growth is considered. Chemical fractionation and the depletion/enrichment in iron observed in some chondrites can be linked to the size–density sorting and fragmentation properties of precursor dusty grains. We suggest that aggregation of chondritic components could have occurred where/when fragmentation was not efficient if their aerodynamical sorting has to be preserved. Chondritic components would allow aerodynamical sorting in a fragmentation regime only if they have similar fragmentation properties. We find that, in the inner disc, and for the same interval of time, fragmenting dust can grow larger when compared to the size of grains predicted by pure growth. This counter-intuitive behaviour is due to the large amount of dust that piles up in a fragmenting zone followed by the rapid growth that occurs when this zone transitions to a pure growth regime. As an important consequence, dust can overcome the radial-drift barrier within a few thousands years.
An unusually large gaseous transit in a debris disc
Authors: Iglesias Daniela P , Olofsson Johan , Bayo Amelia , Zieba Sebastian , Montesinos Matías , Smoker Jonathan , Kennedy Grant M , Godoy Nicolás , Pantoja Blake , Talens Geert Jan , Wahhaj Zahed , Zamora Catalina
Published: October 2019

We present the detection of an unusually large transient gas absorption in several ionized species in the debris disc star HD 37306 using high-resolution optical spectra. We have been analysing a large sample of debris discs searching for circumstellar gas absorptions aiming to determine the frequency of gas in debris discs. HD 37306 stood out showing remarkably broad absorptions superimposed on to several photospheric Ca ii, Fe ii, and Ti ii lines. The observed absorptions, unlike typical exocometary transits, lasted for at least eight days. Here, we analyse simultaneous spectroscopic and photometric data of the event and evaluate different scenarios that might explain the observed features. We conclude that the most likely scenario might be an exocometary break-up releasing a significant amount of gas close to the star, producing an occulting ‘ring’/‘torus’ shape.
The chaotic wind of WR 40 as probed by BRITE
Authors: Ramiaramanantsoa Tahina , Ignace Richard , Moffat Anthony F J , St-Louis Nicole , Shkolnik Evgenya L , Popowicz Adam , Kuschnig Rainer , Pigulski Andrzej , Wade Gregg A , Handler Gerald , Pablo Herbert , Zwintz Konstanze
Published: October 2019

Among Wolf–Rayet stars, those of subtype WN8 are the intrinsically most variable. We have explored the long-term photometric variability of the brightest known WN8 star, WR 40, through four contiguous months of time-resolved, single-passband optical photometry with the BRIght Target Explorer nanosatellite mission. The Fourier transform of the observed light curve reveals that the strong light variability exhibited by WR 40 is dominated by many randomly triggered, transient, low-frequency signals. We establish a model in which the whole wind consists of stochastic clumps following an outflow visibility promptly rising to peak brightness upon clump emergence from the optically thick pseudo-photosphere in the wind, followed by a gradual decay according to the right-half of a Gaussian. Free electrons in each clump scatter continuum light from the star. We explore a scenario where the clump size follows a power-law distribution, and another one with an ensemble of clumps of constant size. Both scenarios yield simulated light curves morphologically resembling the observed light curve remarkably well, indicating that one cannot uniquely constrain the details of clump size distribution with only a photometric light curve. Nevertheless, independent evidence favours a negative-index power law, as seen in many other astrophysical turbulent media.
Combined epigenetic signature and gene copy number variations in IDH-mutant glioblastomas showed varied risk stratification
Authors: Keung Ng Ho , Li Kay Ka-Wai , Malta Tathiane M , Shi Zhi-feng , Noushmehr Houtan
Published: October 2019

The number of IDH-mutant glioblastoma examined in the literature and TCGA is few. We used Infinium MethylationEPIC BeadChip array to classify 64 IDH-mutant-GBM into methylation groups. Gene copy number variations were determined from methylation. 53.1%, 35.9%, and 10.9% of tumors belonged to G-CIMP-high, G-CIMP-low and codel groups respectively. G-CIMP-low group of IDH-mutant glioblastoma was associated with worse survival as compared to G-CIMP-high (p=0.005) and Codel groups (p=0.009). CDKN2A deletion (24/64; 37.5%) was the most common gene copy number variation, and was significantly associated with GCIMP-low subgroup (p=0.001). Amplification of MET was identified in 3/64 (9.4%), CCND2 11/64 (17.2%), PDGFRA 9/64 (14.1%), CDK4 8/64 (12.5%) and EGFR 8/64 cases (12.5%). Both CDKN2A deletion (p=0.008) and MET amplification (p<0.001) were associated with poor survival. Combined methylation signature and gene copy number variations separated IDH-mutant glioblastoma into Group 1 (codeleted), Group 2 (GCIMP-high without CDKN2A deletion), Group 3 (GCIMP-high with CDKN2A deletion), Group 4 (GCIMP-low without CDKN2A and MET alterations), and Group 5 (GCIMP-low with CDKN2A and/or MET alterations). Group 1 had a favorable overall survival with a median survival of 1240 days. Groups 2, 3, and 4 exhibited an intermediate outcome with a median survival of 536, 619, and 655 days respectively. Group 5 exhibited a poor outcome with a median survival of 255 days. Groups based on combined methylation signature and CDKN2A/MET status are an independent prognostic factor. Conclusion: IDH mutant glioblastomas should be stratified for risk with combined epigenetic signature and CDKN2A/MET status and some cases have unfavorable outcomes.
Utilising functional imaging to predict survival in paediatric brain tumours.
Authors: Grist James , Withey Stephanie , MacPherson Lesley , Oates Adam , Stephen Powell Mr , Novak Jan , Abernethy Laurence , Pizer Barry , Grundy Richard , Bailey Simon , Mitra Dipayan , Arvantis Theodoros , Auer Dorothee , Avula Shivaram , Peet Andrew
Published: October 2019

Introduction

Brain tumours are a common cause of death in the paediatric population. We have previously shown that MR imaging and spectroscopy can be used to non-invasively differentiate between tumour types. Here, we demonstrate that functional imaging can be highly predictive of survival and grade in a paediatric cohort.

Methods

Perfusion (PWI) and diffusion weighted imaging (DWI) were performed in a multi-site (Birmingham Children’s Hospital, Royal Victoria Infirmary, Alder Hey, Nottingham) cohort ([grade, 5-year survival alive:dead number] = [I,15:1],[II, 5:1],[III,2:3],[IV,8:11]). ROIs were drawn on T2 imaging and functional imaging features (mean, standard deviation, skewness, and kurtosis) were derived. Supervised machine learning was used to predict 5-year survival and tumour grade from features. ANOVA and post-hoc tests were used to assess differences in features between grade and 5-year survival status.

Results

5-year survival was predicted with 89%, 85%, and 87% accuracy with all imaging, perfusion, or diffusion features, respectively.

A significant difference in perfusion was found between surviving and diseased participants (1.71 ± 0.82 vs 2.62 ± 1 mL/100g/min, respectively, p < 0.05). A significant difference in ADC (mm2 s-1) between tumour grades was found (1 vs 4 (1533 ± 458 vs 857 ± 239), 4 vs 3 (857 ± 239 vs 1197 ± 137), 4 vs 2 (857 ± 239 vs 1440 ± 557), corrected p < 0.05).

Conclusion

We have shown that perfusion and diffusion imaging features can be used to non-invasively assess tumour grade and estimate 5-year survival status in a cohort of paediatric brain tumours.
Multiparametric 18F-Choline PET/MR in childhood and teenage-young adult gliomas: assessment of suspected disease progression
Authors: Ferrazzoli Valentina , Shankar Ananth , V Cockle Julia , Tang Christine , Bomanji Francesco Fraioli Jamshed , Hyare Harpreet
Published: October 2019

Aim

Evaluation of post-treatment glioma burden remains a significant challenge in childhood, Teenage and Young Adults (TYA). Although amino acid PET impacts on glioma imaging, 18fluoro-Choline Positron Emission Tomography (ChoPET) is more widely available. The aim was to evaluate the utility of ChoPET/MRI for suspected disease progression in childhood and TYA gliomas.

Methods

27 consecutive patients with suspected glioma disease progression were evaluated with ChoPET/MR and 59 scans included. Relative cerebral blood volume (rCBV), ADC and SUVmax in enhancing (enh), non-enhancing (ne) tumour volumes and normal appearing white matter (wm) were calculated (rCBVenh, rCBVne, rCBVwm, ADCenh, ADCne, ADCwm, SUVenh, SUVne, SUVwm). Blinded nuclear medicine and neuroradiologist scored the images on tumour probability (1:unlikely-5:definitely). Receiver Operating Characteristic (ROC) analysis considering as gold standard histopathology or clinical follow-up was performed.

Results

Combined ChoPET/MR accuracy was 100% for residual tumour, conventional MR accuracy was 96.3% (91.7% <14years, 100% ≥15years) and ChoPET accuracy was 73.1% (66.7% <14years, 80.0% ≥15 years). Lack ack of agreement in 9/27 with ChoPET superior to MR in 1 case. Tumour component analysis demonstrated significantly higher SUVenh and SUVne than SUVwm (SUVenh: p<0.001,SUVne: p=0.003) equivalent to ADC (ADCenh, ADCnenh: p<0.001) and rCBV (rCBVenh, rCBVnenh: p<0,001).

Conclusions

Combined ChoPET/MR has 100% accuracy in TYA gliomas with suspected disease progression. ChoPET is able to detect enhancing and non-enhancing tumour but it is more reliable for evaluating enhancing disease >15 years. In selected cases where MRI is equivocal, a quantitative multi-modality ChoPET/MR better defines both enhancing and non-enhancing tumour for improved assessment of childhood and TYA gliomas.
Predicting meningioma recurrence using spectrochemical analysis of tissues and subsequent predictive computational algorithms
Authors: Lilo Taha , Morais Camilo , Ashton Kate , Pardilho Ana , Dawson Timothy , Gurusinghe Nihal , Davis Charles , Martin Frank
Published: October 2019

Introduction

Meningioma recurrence remains a clinical dilemma. This has a significant clinical and huge financial implication. Hence, the search for predictors for meningioma recurrence has become an increasingly urgent research topic in recent years.

Objective

Using spectrochemical analytical methods such as attenuated total reflection Fourier-transform infrared (ATR-FTIR) and Raman spectroscopy, our primary objective is to compare the spectral fingerprint signature of WHO grade I meningioma vs. WHO grade I meningioma that recurred. Secondary objectives compare WHO grade I meningioma vs. WHO grade II meningioma and WHO grade II meningioma vs. WHO grade I meningioma recurrence.

Materials and Methods

Our selection criteria included convexity meningioma only restricted to Simpson grade I & II only and WHO grade I & grade II only with a minimum 5 years follow up. We obtained tissue from tumour blocks retrieved from the tissue bank. These were sectioned onto slides and de-waxed prior to ATR-FTIR or Raman spectrochemical analysis. Derived spectral datasets were then explored for discriminating features using computational algorithms in the IRootLab toolbox within MATLAB; this allowed for classification and feature extraction.

Results

After analysing the data using various classification algorithms with cross-validation to avoid over-fitting of the spectral data, we can readily and blindly segregate those meningioma samples that recurred from those that did not recur in the follow-up timeframe. The forward feature extraction classification algorithms generated results that exhibited excellent sensitivity and specificity, especially with spectra obtained following ATR-FTIR spectroscopy. Our secondary objectives remain to be fully developed.
Characterisation of the invasive tumour niche using astrocyte-glioblastoma organoids and decellularised human brain
Authors: Diksin Mohammed , Rowlinson Jonathan , Kondrashov Alexandar , Denning Chris , Hughes Jamie , Constantin-Teodo Tim , Cui Wei , Gell Chris , Onion David , Croxall Nicola , Smith Stuart , Rahman Ruman
Published: October 2019

Glioblastoma therapeutic challenges are in considerable part due to myriad survival adaptations and mechanisms, which allow malignant cells to repurpose signalling pathways within discreet microenvironments. These Darwinian adaptations facilitate invasion into brain parenchyma and perivascular space or promote evasion from repressive factors that represent anti-cancer defence mechanisms.

We hypothesised that pre-clinical modelling of glioma invasion by recapitulating early events occurring immediately after surgery at the glioblastoma invasive margin, could reveal the cross-talk between malignant cells and the surrounding healthy astrocytes, which facilitates tumour recurrence.

We first generated transgenic H1-derived neural stem cells using CRISPR/Cas9-mediated knock-in of the YFP reporter gene under the control of the GFAP promoter. Reproducible ultrahigh-throughput AggreWells™ (19,200 micro-wells per 24-well plate) were used to create astrocyte-glioblastoma organoids, which we term ‘Gliomasphere Matrices’. YFP-labelled astrocytes were co-cultured with 10 treatment-naïve patient-derived cell lines isolated from the 5-aminolevulinic (5ALA)-determined glioblastoma invasive margin. Co-cultures were seeded upon on a sequentially constructed, time-of-flight secondary ion mass spectrometry (ToF-SIMS)-characterised 3D scaffold, composed of decellularised human brain extract with defined PEGDA hydrogel.

YFP-astrocytes were purified from each of the 10 Gliomasphere Matrices using fluorescence-activated cell sorting (FACS) after 6- and 10-days co-culture. RNAseq profiling to address both putative astrocytic reprogramming by invasive glioblastoma cells and gene expression changes intrinsic to tumour cells will be discussed in relation to RNAseq data from patient-derived 5ALA FACS-purified glioblastoma invasive margin tissue.

This novel multi-faceted model offers a unique opportunity to recapitulate early molecular cross-talk which facilitates glioblastoma recurrence and may be utilised for high-throughput drug screening.
CRISPR/Cas9 gene editing of brain cancer stem cells using lipid-based nano-delivery
Authors: Rouatbi Nadia , Mun Lim Yau , Grant Vivien , Miguel Costa Pedro , Pollard Steven M , Wang Julie Tzu-Wen , Al-Jamal Khuloud T
Published: October 2019

Despite advances in cancer therapy glioblastoma (GBM) remains one of the deadliest brain tumours. Effective therapy is restricted by the presence of multiple resistance mechanisms. Physical barriers such as the blood-brain barrier limit the brain delivery of therapeutic compounds. In addition, the presence of a subset of GBM-stem-like cells (GSCs), characterized by radio/chemoresistance, and the intratumor heterogeneity impede standard therapies from being effective. New therapeutic approaches are urgently needed. Given its high specificity, CRISPR/Cas9-mediated genome editing provides new prospects for novel therapeutic targets. While promising, in vivo application of CRISPR/Cas9 is currently hampered by poor pharmacokinetics and limited ability to cross biological membranes.

The present research is designed to utilise stable nucleic acid lipid nanoparticles (SNALPs) for in vivo delivery of CRISPR/Cas9 to GSC by disrupting the epidermal growth factor receptor variant III (EGFRvIII), a GBM associated mutation, responsible for tumour cell proliferation, angiogenesis and invasion. Near Infrared fluorescence labelling and live optical imaging confirmed SNALPs uptake in GSC tumours implanted intracranially in mice after intravenous injection. Higher uptake of SNALPs in tumourous tissues compared to healthy brain tissues was further confirmed by ex vivo imaging and flow cytometry. EGFRvIII-specific sgRNA has been designed and validated in GSCs using commercial transfection regents. Studies are underway to load CRISPR/Cas9 mRNA/gRNA into SNALPs to test their in vitro gene editing efficacy. Successful in vivo delivery of CRISPR/Cas9 will represent a promising approach for identifying GBM therapeutic targets in vivo which in the long-run can be applied for GBM treatment.
Low grade glioma patients: how does this patient group perceive their quality of life prior to surgical or oncological interventions?
Authors: Robinson Charlotte , Pedro Lavrador Jose , Gullan Richard , Brazil Lucy , Swampillai Angela , Al’Salihi Omar , Bhangoo Ranj , Vergani Francesco , Hurwitz Vicky , La Jess , Mullens Laura , Ford Liz , Mcewan Maria , Ashkan Keyoumars
Published: October 2019

Introduction

Literature analysing how patients with a provisional low-grade glioma perceive their own quality of life prior to any surgical or oncological intervention is scarce. This patient group are often highly functioning individuals, able to lead ordinary lives which stresses that their management must be carefully considered in a holistic sense. Low grade gliomas represent 5 % of brain tumours and they are typically of a younger cohort who will be less equipped to manage the uncertainties a diagnosis like this brings.

Methods

Prospective single centre cohort study over 14 months where 56 patients completed the EORTC QLQ – BN 20 and 30 prior to initial consultation in the dedicated low grade glioma clinic.

Results

54% of patients did not feel ‘limited in doing work or other daily activities’ but of those who were affected to some degree, 21% of women felt ‘very much affected’ compared to 3% of men. 78% of patients expressed to a degree some ‘uncertainty about the future’ and this was shown to be a common theme among all age groups which reflects the huge burden of anxiety this patient group faces regardless of age.

Conclusion

Data demonstrated a variety of quality of life scores that are not particular to a certain age group/gender which reinforces the importance of individual assessment as assumptions of patients in a particular category cannot be made. By assessing quality of life, clinical management is improved as a more in-depth assessment is facilitated on an individual basis and patient experience is enhanced.