bluuebunny/crossref_metadata_2025 huggingface dataset:
Beta-Catenin Mutation with Complex Chromosomal Changes in Desmoid Tumor of the Scalp: A Case Report
Authors: Liu Gary , Weiner Howard L. , Pederson William C. , Davies Lesley , Buchanan Edward P.
Published: November 2018

Gain-of-function mutations in the beta-catenin gene ( CTNNB1) drive genomic instability within different cancers. However, it is unclear whether alterations in beta-catenin signaling can still lead to chromosomal rearrangements in neoplasms without metastatic potential. Here, we report a unique case, whereby a desmoid tumor of the scalp contains a missense mutation in CTNNB1. This mutation is located at the T41 phosphorylation site—previously reported to be necessary for proper beta-catenin degradation. Online database analysis then revealed that our mutation is likely causative of many different cancers and also absent in the healthy public. Karyotyping of the desmoid tumor cells then showed complex chromosomal changes in 16 out of 20 cells examined. To treat this patient, we surgically removed both the neoplasm and underlying calvarium and then successfully reconstructed the skull and scalp. Taken together, our data suggest that increased beta-catenin signaling can lead to genomic instability in the absence of metastatic potential.
Investigating Intestinal Permeability of Bortezomib Using a Validated HPLC-UV Method
Authors: Mahmoudian Mohammad , Zakeri-Milani Parvin , Valizadeh Hadi
Published: November 2018

Bortezomib (BTZ), as a proteasome inhibitor, has been used for treatment of patients with relapsed/refractory multiple myeloma and mantle cell lymphoma. BTZ is available for intravenous injection or subcutaneous administration. In this study, for evaluating the potential of BTZ oral delivery, intestinal permeability of BTZ was determined using in situ single-pass intestinal perfusion (SPIP) technique and the perfused solutions were analyzed using a validated HPLC-UV method. The chromatographic separation was performed using a C18 column via isocratic mode at a flow rate of 0.5 mL/min at 270 nm. The mobile phase was a mixture of methanol/deionized water (50:50% v/v) with 0.1% glacial acetic acid. The results indicated that calibration curves were linear (r2 ˃0.99) in a concentration range of 1.65–5 µg/mL for BTZ and 8.33–25 µg/mL for phenol red. A limit of quantitation of 1.03 and 6.67 µg/mL was obtained for BTZ and phenol red, respectively. The recovery values were in the range of 96.5–105.4% for BTZ, and 88–99.2% for phenol red. The relative standard deviations (RSD) were ≤4.9% for BTZ and ≤7% for phenol red. Stability studies indicated that the working standard solution is stable over a period of 48 h at room temperature. Finally, an effective permeability (Peff) value of (3.36±0.5)×10−5 cm/sec (mean±SEM) was achieved for BTZ. Moreover, it was predicted that BTZ belongs to the biopharmaceutical class ІІІ.
Look, a human being! Anthropomorphic solipsism in postsecular thought
Authors: Vahanian Noëlle
Published: November 2018

Adding a woman’s voice to an edited volume, or a person of color on an academic panel, or an ecumenical, universalist message of welcome under a church flag—these may be well intentioned gestures of inclusion, but, even as an unintended result, minority discourses either stand on the margins, as the ‘other,’ or they morph and disappear into the dominant discourse. What is needed instead is a change of ‘being.’ Whatever we call the philosophy of religion, it owes its conception to the European Enlightenment, and the latter, its understanding of the modern subject to Christian imperialism and the colonial enterprise. How can it ever become an inclusive field? This paper reflects on the promise of inclusion of postsecular theological discourses within the Continental philosophy of religion. Can such discourses, coming on the heels of the death of God and the postmodern death of universals, overcome their patriarchal, colonial, and racist cultural archive? Such a possibility glimpses a future worth pursuing. To answer the question, this paper plays on the intersectionality of the human being as such—an imagined abstract condition of possibility of our existence—and human facticity, the embodied lived experience that is historically conditioned, culturally determined, gendered and racialized as we know it today—identities expressing or underwriting white privilege, the economic exploitation of the global south, or hegemonic Western institutions of knowledge and power. The paper analyzes key aspects of well-known postsecular theological discourses (Caputo, Vattimo, Taylor, Levinas) through the intersectional lens of feminist, race, postcolonial, and decolonial critiques (Schutte, Du Bois, Carter, Dussel, Mignolo). Error is human, but today’s sexism, racism, or economic oppression suggest it isn’t human errors we ought to correct so much as our erroneous understanding of what we call a human being. A materialist conception of being (Malabou) and a theology whose God is in and of language open the way to engage the complicity of the philosophy of religion with the dominant and hegemonic ideologies that underwrite, besides the field, today’s world order.
Novel aperiodically intermittent stability criteria for Markovian switching stochastic delayed coupled systems
Authors: Wu Yongbao , Li Qiang , Li Wenxue
Published: November 2018

This paper concerns pth moment exponential stability of stochastic coupled systems with multiple time-varying delays, and Markovian switching topologies via intermittent control. Compared with previous research results, the mathematical model of this kind of stochastic coupled systems with multiple time-varying delays and Markovian switching topologies is studied for the first time. The intermittent control designed in this paper is aperiodical, which is more general in practice. Moreover, the restriction between control width and time delays is removed. By constructing a new differential inequality on delayed dynamical systems with Markovian switching topologies and combining the graph-theoretic approach with M-matrix theory, two sufficient criteria are derived to guarantee pth moment exponential stability of systems. Moreover, the exponential convergence rate has a close relationship with the maximum ratio of the rest width to the aperiodical time span (the sum of the control width and the rest width). Finally, we employ the theoretical results to study the exponential stability of stochastic coupled oscillators with multiple time-varying delays and Markovian switching topologies. Meanwhile, a numerical example is presented to illustrate the effectiveness and feasibility of the proposed results.
A simple atomic force microscope-based method for quantifying wear of sliding probes
Authors: Flater Erin E. , Barnes Jared D. , Hitz Graff Jesse A. , Weaver Jayse M. , Ansari Naveed , Poda Aimee R. , Robert Ashurst W. , Khanal Subarna R. , Jacobs Tevis D. B.
Published: November 2018

Sliding wear is particularly problematic for micro- and nano-scale devices and applications, and is often studied at the small scale to develop practical and fundamental insights. While many methods exist to measure and quantify the wear of a sliding atomic force microscope (AFM) probe, many of these rely on specialized equipment and/or assumptions from continuum mechanics. Here we present a methodology that enables simple, purely AFM-based measurement of wear, in cases where the AFM probe wears to a flat plateau. The rate of volume removal is recast into a form that depends primarily on the time-varying contact area. This contact area is determined using images of sharp spikes, which are analyzed with a simple thresholding technique, rather than requiring sophisticated computer algorithms or continuum mechanics assumptions. This approach enables the rapid determination of volume lost, rate of material removal, normal stress, and interfacial shear stress at various points throughout the wear experiment. The method is demonstrated using silicon probes sliding on an aluminum oxide substrate. As a validation for the present method, direct imaging in the transmission electron microscope is used to verify the method’s parameters and results. Overall, it is envisioned that this purely AFM-based methodology will enable higher-throughput wear experiments and direct hypothesis-based investigation into the science of wear and its dependence on different variables.
Increased yield of MoS2 monolayer exfoliation through the bimetallic corrosion of aluminum
Authors: Dinc Fatih , Ertop Ozan , Sonmez Bedri Gurkan , Zhao Peida , Raegen Adam N. , Forrest James A. , Mutlu Senol
Published: November 2018

In this paper, we propose a corrosion assisted exfoliation method as an improvement to the traditional tape exfoliation to obtain transition-metal dichalcogenide monolayers. Our method primarily relies on the electrochemical potential difference between transition metals and aluminum. The assistance of bubbles resulting from the bimetallic corrosion increases the yield of the exfoliation process for monolayers by 30-fold while boosting the probability of obtaining isolated monolayers. We use Raman measurements and a statistical comparison of the improved method with tape exfoliation to lay the evidence for our findings.
A new class of Euler equation on the dual of the N = 1 extended Neveu-Schwarz algebra
Authors: Ge Yanyan , Zuo Dafeng
Published: November 2018

Let G be the N = 1 extended Neveu-Schwarz algebra and Greg* its regular dual. In this paper, we will study a super-Euler system with seven parameters (s1, s2, c1, …, c5) associated with Greg*. We will show that the super-Euler system is (1) local bi-superbihamiltonian if s1=14c1 and s2=12c2; (2) supersymmetric if s1 = c1 and s2 = c2; (3) local bi-superbihamiltonian and supersymmetric if s1 = c1 = 0 and s2 = c2 = 0. By choosing different parameters, we could obtain several supersymmetric or bi-superhamiltonian generalizations of some well-known integrable systems including the Ito equation, the 2-component Camassa-Holm equation, the 2-component Hunter-Saxton equation, and, especially, the Whitham-Broer-Kaup dispersive water-wave system.
Numerical parameter optimizations of the Ignition and Growth model for a HMX plastic bonded explosive
Authors: Gambino James R. , Tarver Craig M. , Springer H. Keo
Published: November 2018

We present a novel method for optimizing parameters of the Ignition and Growth (I&G) reactive flow model for high explosives. The I&G model predicts the shock initiation response of explosives subjected to dynamic loading. However, calibrating the model is a time-consuming process because it has several parameters, typically requires multiple data sets, and there are no direct correlations between parameters and data. In this study, we couple a scalable optimization algorithm to simulations of shock initiation experiments in the multi-physics code ALE3D. We develop four I&G model parameter sets for the HMX (1,3,5,7-tetranitro-1,3,5,7-tetrazocane)-based explosive LX-07 [90 wt. % HMX, 10 wt. % Viton A] based on minimizing the difference between calculations and measurements at the embedded pressure gauges in 1D gun shock experiments. Our study shows that a cost function based on both shock time of arrival and pressure pulse shape demonstrates the best agreement with experimental data.
Generation of micro-arc discharge plasma in highly pressurized seawater
Authors: Gamaleev Vladislav , Furuta Hiroshi , Hatta Akimitsu
Published: November 2018

Micro-arc discharge plasma was generated in highly conductive seawater at high pressures up to 19 MPa. Using a microscaled rod-to-rod electrode system, a micro-arc discharge was ignited reproducibly using voltages below 850 V. Even at high pressure, the current and voltage characteristics showed the same scheme of micro-arc discharges as those at atmospheric pressure. The energy consumption for the preheating phase, in which bubbles were generated by joule heating and micro-arc discharges were consequently ignited in the bubbles, gradually increased from 5 to 36 mJ with an increase in pressure from 0.1 to 19 MPa. The micro-arc discharge plasma at high pressure exhibited high-luminance photo-emissions with distinctive spectra consisting of an intense flat continuum band and extremely broadened peaks.
Preferential water condensation on superhydrophobic nano-cones array
Authors: Jin Yong , Qamar Adnan , Shi Yusuf , Wang Peng
Published: November 2018

Condensed water droplet jumping on superhydrophobic surfaces has been a hot research topic during the last decade for various applications including enhancing condensation, antifogging, self-cleaning, electrostatic energy harvesting, and anti-icing/frosting surfaces. In the present work, a superhydrophobic nano-cone array is prepared by simple chemical bath reaction followed by silane modification. The tip of an individual nano-cone is only around 10 nm. The nano-cone array is also characterized by cavities among cones with varying sizes due to the imperfect alignment of individual nano-cones to the substrate. We demonstrate theoretically and experimentally that water condensation preferentially occurs within larger cavities among hydrophobized nano-cone arrays. After extrusion from cavities, droplets form a partial Cassie state which is a prerequisite of coalescence induced jumping. Moreover, growth rates of droplets extruded from larger cavities are larger than those from smaller cavities. Droplet jumping is observed at the very first coalescence and after multiple coalescence events under a microscope. The jumping droplet size is at tens of microns, demonstrating that droplets can be efficiently removed from the nano-cone array. In general, it is indicated that condensation can be controlled by purposely designing nano-scale structures, which would provide valuable suggestion for applications involving water condensation.
Evaluation of the readout electronics based on the center of gravity method for position sensitive radiation detection
Authors: Yu L. , Cao P. , Li J. W. , Zhang Y. , Yang B. , An Q.
Published: November 2018

In the application of position sensitive radiation detection, the center of gravity method is often used to obtain better spatial resolution. In order to obtain the resolution degradation caused by the readout electronics, an evaluation method is put forward in this paper. The principle of the method is to simulate the signal distribution on sense wires of the MWPC (Multiwire Proportional Chamber) detector. The evaluation software quantizes the simulated data and drives the digital to analog converter to generate test signals. The readout electronics is evaluated with these stimulus signals according to the readout scale. An evaluation board based on this method is implemented. Tests are carried out in the laboratory to evaluate a readout circuit for the MWPC detector. The position resolution contributed by the electronics is better than 15 μm when the swtiching frenquency of the switch array is 12.5 MHz. The test results proved that the evaluation method is correct and practical. It can greatly simplify the evaluation of the readout electronics.
Stability of E-H type regular shock refraction
Authors: Hu Dian , Sheng Wancheng
Published: November 2018

A regular refraction wave structure may appear when a shock coming from infinity hits an interface between two different media. In such a case, the interface will be deflected, the incident shock will refract, and some reflected wave arises. If the incoming flow and the incident shock are specifically presented, then the refraction shock can be transonic and the reflection wave can be a rarefaction wave. For such a wave pattern, we show that it is conditionally and locally stable provided that a pressure condition, which is determined by the incoming flow, is presented in downstream behind the refraction shock.
Refining evERdock: Improved selection of good protein-protein complex models achieved by MD optimization and use of multiple conformations
Authors: Shinobu Ai , Takemura Kazuhiro , Matubayasi Nobuyuki , Kitao Akio
Published: November 2018

A method for evaluating binding free energy differences of protein-protein complex structures generated by protein docking was recently developed by some of us. The method, termed evERdock, combined short (2 ns) molecular dynamics (MD) simulations in explicit water and solution theory in the energy representation (ER) and succeeded in selecting the near-native complex structures from a set of decoys. In the current work, we performed longer (up to 100 ns) MD simulations before employing ER analysis in order to further refine the structures of the decoy set with improved binding free energies. Moreover, we estimated the binding free energies for each complex structure based on an average value from five individual MD snapshots. After MD simulations, all decoys exhibit a decrease in binding free energy, suggesting that proper equilibration in explicit solvent resulted in more favourably bound complexes. During the MD simulations, non-native structures tend to become unstable and in some cases dissociate, while near-native structures maintain a stable interface. The energies after the MD simulations show an improved correlation between similarity criteria (such as interface root-mean-square distance) to the native (crystal) structure and the binding free energy. In addition, calculated binding free energies show sensitivity to the number of contacts, which was demonstrated to reflect the relative stability of structures at earlier stages of the MD simulation. We therefore conclude that the additional equilibration step along with the use of multiple conformations can make the evERdock scheme more versatile under low computational cost.
Non-destructive position measurement of coasting beam using Schottky signals
Authors: Singh R. , Forck P. , Kowina P. , Reiter A.
Published: November 2018

The beam position appears in the transverse Schottky signal spectra of coasting beams at revolution frequency and its harmonics. In this contribution, we utilize this signal for beam position monitoring using regular shoe-box monitors at heavy ion synchrotron GSI SIS-18. Position resolution below 1 mm at 1 kHz rate for 10 mA current was obtained. These results demonstrate the feasibility of non-destructive position monitoring of unbunched beams in synchrotrons and storage rings using capacitive pick-up data with appropriate signal processing.
Response of lentil to high temperature under variable water supply and carbon dioxide enrichment
Authors: Delahunty Audrey , Nuttall James , Nicolas Marc , Brand Jason
Published: November 2018

Lentil (Lens culinaris Medik.) production in arable, Mediterranean-type climates is limited by heat waves and unreliable rainfall. Under climate change scenarios, increased atmospheric carbon dioxide (CO2) concentration will increase plant growth; however, the net effect of increasing occurrence and intensity of heat waves and drought is unclear. This study tested the response of combined acute high temperature (>32°C) at the early pod-filling stage and (i) crop-available soil water, and (ii) elevated CO2 on three lentil genotypes in two experiments. The three lentil genotypes selected were commercial cultivar PBA Bolt and two landraces sourced from the Australian Grains Genebank, AGG 71457 and AGG 73838. High soil-water availability (0.42 Mg m–3) throughout the growing season increased yield by 28% compared with low soil-water availability (0.35 Mg m–3). Across contrasting water treatments, there was no difference in patterns of crop response to high temperature during the early pod-filling phase (5 days at 42°C daytime, 25°C night), where yields were reduced by 45%. A significant interaction between high temperature response and genotype was observed, where reduction in grain number was higher for AGG 73838 (0.20% per degree-hour >32°C) than for AGG 71457 (0.07% per degree-hour >32°C) or PBA Bolt (0.10% per degree-hour >32°C). For heat and CO2 effects, there was no significant interaction between high temperature (3 days at 38°C daytime, ambient night temperature) and CO2 treatment on yield components. There was, however, an overall trend of increased biomass, grain number and yield due to elevated CO2. Although non-limiting soil water did not reduce the impact of high temperature in this study, the range in response across genotypes to high temperature supports opportunity for increased adaptation of lentil toward increasing yield stability under effects of climate change.
Potential shift from a carbon sink to a source in Amazonian peatlands under a changing climate
Authors: Wang Sirui , Zhuang Qianlai , Lähteenoja Outi , Draper Frederick C. , Cadillo-Quiroz Hinsby
Published: November 2018

Significance

We use a process-based biogeochemistry model to quantify the carbon accumulation for peatland ecosystems in the Pastaza-Marañon foreland basin in the Peruvian Amazon from 12,000 y before present to AD 2100. We find that warming accelerates peat carbon loss, while increasing precipitation slightly enhances peat carbon accumulation at millennial time scales. With these impacts, our simulations suggest that the basin might lose up to 0.4 Pg⋅C by AD 2100, with the largest loss from palm swamp. If this loss rate is true for all Amazonia peatlands, we project that these carbon-dense peatlands may switch from a current carbon sink into a future source in this century.
Biological sex affects vaccine efficacy and protection against influenza in mice
Authors: Fink Ashley L. , Engle Kyrra , Ursin Rebecca L. , Tang Wan-Yee , Klein Sabra L.
Published: November 2018

Significance

Biological sex is typically not considered in the evaluation of vaccine responses and protection against infection. We show that female mice mount greater humoral and cell-mediated immune responses to influenza infection and vaccination than males. Females can rely solely on antibody for protection following vaccination, which is associated with greater expression of toll-like receptor 7 (
Tlr7
) caused by epigenetic mechanisms in B cells from females. Deletion of
Tlr7
reduces sex differences in vaccine-induced antibody responses and protection. The increased expression of
Tlr7
in B cells contributes to greater antibody production in females than males, which has a functional advantage for vaccine efficacy.
Detecting and explaining why aquifers occasionally become degraded near hydraulically fractured shale gas wells
Authors: Woda Josh , Wen Tao , Oakley David , Yoxtheimer David , Engelder Terry , Castro M. Clara , Brantley Susan L.
Published: November 2018

Significance

Development of shale gas has changed the economics of global energy. However, methane sometimes escapes from shale gas wells into aquifers and the atmosphere. Although many researchers investigate leakage of this greenhouse gas, detection can be difficult where natural sources of methane are present. Here, methane was studied in water near gas wells previously cited for well integrity issues. We identify chemical clues that can distinguish methane migration related to shale gas development from methane that was preexisting. We also document a geological setting—the upper part of a large geological fold at shallow depth—that may be prone to methane migration. Knowledge gained from this study may lessen the chances for fugitive methane emissions into aquifers in the future.
ALS mutations of FUS suppress protein translation and disrupt the regulation of nonsense-mediated decay
Authors: Kamelgarn Marisa , Chen Jing , Kuang Lisha , Jin Huan , Kasarskis Edward J. , Zhu Haining
Published: November 2018

Significance

Mutations in
fused in sarcoma
(
FUS
) contribute to a subset of familial amyotrophic lateral sclerosis (ALS). ALS-linked mutations cause a liquid–liquid phase separation of FUS protein, induce cytoplasmic inclusions in cells, and interfere with RNA metabolism pathways. Our proteomic analysis shows that proteins sequestered into inclusions are enriched in translation and RNA quality surveillance pathways. This study demonstrates that ALS mutations in FUS indeed suppress protein translation and affect the mRNA nonsense-mediated decay (NMD) pathway. NMD-promoting factors UPF1 and UPF3b increased, whereas the negative regulator UPF3a decreased in the cells of patients with ALS. The disruption in NMD regulation and suppression of protein biosynthesis likely contribute to neurodegeneration in ALS.
Interlinked regulatory loops of ABA catabolism and biosynthesis coordinate fruit growth and ripening in woodland strawberry
Authors: Liao Xiong , Li Mengsi , Liu Bin , Yan Miaoling , Yu Xiaomin , Zi Hailing , Liu Renyi , Yamamuro Chizuko
Published: November 2018

Significance

Using strawberry fruit as a model system, we uncover the mechanistic interactions between auxin, gibberellic acid (GA), and abscisic acid (ABA) that regulate the entire process of fruit development. Interlinked regulatory loops control ABA levels during fruit development. During the early stages, auxin/GA turns on a feedback loop to activate the removal of ABA viaFveCYP707A4a-dependent catabolism needed for fruit growth. Down-regulation of auxin/GA results in the suppression of the feedback loop and the activation of the ABA biosynthesis-dependent feedforward loop, leading to a steep ABA accumulation for fruit ripening. The interlinked regulatory loops provide a conceptual framework that underlies the connection between the regulation of fruit growth and that of ripening as well as a molecular basis for manipulation of fruit sizes and ripening times.
Artemisinin resistance phenotypes and K13 inheritance in a
Plasmodium falciparum
cross and
Aotus
model
Authors: Sá Juliana M. , Kaslow Sarah R. , Krause Michael A. , Melendez-Muniz Viviana A. , Salzman Rebecca E. , Kite Whitney A. , Zhang Min , Moraes Barros Roberto R. , Mu Jianbing , Han Paul K. , Mershon J. Patrick , Figan Christine E. , Caleon Ramoncito L. , Rahman Rifat S. , Gibson Tyler J. , Amaratunga Chanaki , Nishiguchi Erika P. , Breglio Kimberly F. , Engels Theresa M. , Velmurugan Soundarapandian , Ricklefs Stacy , Straimer Judith , Gnädig Nina F. , Deng Bingbing , Liu Anna , Diouf Ababacar , Miura Kazutoyo , Tullo Gregory S. , Eastman Richard T. , Chakravarty Sumana , James Eric R. , Udenze Kenneth , Li Suzanne , Sturdevant Daniel E. , Gwadz Robert W. , Porcella Stephen F. , Long Carole A. , Fidock David A. , Thomas Marvin L. , Fay Michael P. , Sim B. Kim Lee , Hoffman Stephen L. , Adams John H. , Fairhurst Rick M. , Su Xin-zhuan , Wellems Thomas E.
Published: November 2018

Significance

Artemisinin-based combination therapies (ACTs) are first-line antimalarial therapies used worldwide. The artemisinin drug (ART) component clears the bulk of infection rapidly, but small numbers of persistent parasites must be removed by the partner drug. Longer parasite clearance
t
1/2
values have been associated with a Kelch-propeller mutation (K13 C580Y), raising concerns of increased ART resistance. We investigated effects of C580Y by using a
Plasmodium falciparum
cross and a monkey malaria model. Following three standard doses of ART, infections with or without the C580Y mutation cleared to microscopically undetectable levels, as in humans; however, frequent recrudescences occurred with both types of infection. These results emphasize the importance of effective partner drugs to kill the parasites that persist through the ART component of ACT.
Dynamic effects of enforcement on cooperation
Authors: Galbiati Roberto , Henry Emeric , Jacquemet Nicolas
Published: November 2018

Significance

This paper shows experimentally how past fines on noncooperation can affect cooperative behavior even when they are no longer in force. Our experiment allows us to separate different forces: a direct effect of past fines on individual preferences and an indirect effect driven by a response to others’ cooperation. We show that this second mechanism is prominent and creates a snowball effect of cooperation.
ERVmap analysis reveals genome-wide transcription of human endogenous retroviruses
Authors: Tokuyama Maria , Kong Yong , Song Eric , Jayewickreme Teshika , Kang Insoo , Iwasaki Akiko
Published: November 2018

Endogenous retroviruses (ERVs) are integrated retroviral elements that make up 8% of the human genome. However, the impact of ERVs on human health and disease is not well understood. While select ERVs have been implicated in diseases, including autoimmune disease and cancer, the lack of tools to analyze genome-wide, locus-specific expression of proviral autonomous ERVs has hampered the progress in the field. Here we describe a method called ERVmap, consisting of an annotated database of 3,220 human proviral ERVs and a pipeline that allows for locus-specific genome-wide identification of proviral ERVs that are transcribed based on RNA-sequencing data, and provide examples of the utility of this tool. Using ERVmap, we revealed cell-type–specific ERV expression patterns in commonly used cell lines as well as in primary cells. We identified 124 unique ERV loci that are significantly elevated in the peripheral blood mononuclear cells of patients with systemic lupus erythematosus that represent an IFN-independent signature. Finally, we identified additional tumor-associated ERVs that correlate with cytolytic activity represented by granzyme and perforin expression in breast cancer tissue samples. The open-source code of ERVmap and the accompanied web tool are made publicly available to quantify proviral ERVs in RNA-sequencing data with ease. Use of ERVmap across a range of diseases and experimental conditions has the potential to uncover novel disease-associated antigens and effectors involved in human health that is currently missed by focusing on protein-coding sequences.
Loss of protein synthesis quality control in host-restricted organisms
Authors: Melnikov Sergey V. , van den Elzen Antonia , Stevens David L. , Thoreen Carson C. , Söll Dieter
Published: November 2018

Significance

This case study reveals that parasitic and symbiotic lifestyles affect the structure of essential molecular machineries of a living cell. We provide evidence that intracellular parasitism and endosymbiosis cause degeneration of the editing domains in aminoacyl-tRNA synthetases, a defect that is known to cause inaccurate translation of the genetic code. This finding suggests that most intracellular pathogens, including causative agents of human disease, have an unanticipated proteome diversity caused by inaccurate translation of the genetic code. Our finding may change current approaches to the study of proteomes of intracellular parasites, parasite–host interactions, and parasites’ sensitivity to drugs, which cause errors in transcription, translation, and protein folding.
Discovery of Kaposi’s sarcoma herpesvirus-encoded circular RNAs and a human antiviral circular RNA
Authors: Tagawa Takanobu , Gao Shaojian , Koparde Vishal N. , Gonzalez Mileidy , Spouge John L. , Serquiña Anna P. , Lurain Kathryn , Ramaswami Ramya , Uldrick Thomas S. , Yarchoan Robert , Ziegelbauer Joseph M.
Published: November 2018

Noncoding RNAs have substantial effects in host–virus interactions. Circular RNAs (circRNAs) are novel single-stranded noncoding RNAs which can decoy other RNAs or RNA-binding proteins to inhibit their functions. The role of circRNAs is largely unknown in the context of Kaposi’s sarcoma herpesvirus (KSHV). We hypothesized that circRNAs influence viral infection by inhibiting host and/or viral factors. Transcriptome analysis of KSHV-infected primary endothelial cells and a B cell line identified human circRNAs that are differentially regulated upon infection. We confirmed the expression changes with divergent PCR primers and RNase R treatment of specific circRNAs. Ectopic expression of hsa_circ_0001400, a circRNA induced by infection, suppressed expression of key viral latent gene
LANA
and lytic gene
RTA
in KSHV de novo infections. Since human herpesviruses express noncoding RNAs like microRNAs, we searched for viral circRNAs encoded in the KSHV genome. We performed circRNA-Seq analysis with RNase R-treated, circRNA-enriched RNA from KSHV-infected cells. We identified multiple circRNAs encoded by the KSHV genome that are expressed in KSHV-infected endothelial cells and primary effusion lymphoma (PEL) cells. The KSHV circRNAs are located within ORFs of viral lytic genes, are up-regulated upon the induction of the lytic cycle, and alter cell growth. Viral circRNAs were also detected in lymph nodes from patients of KSHV-driven diseases such as PEL, Kaposi’s sarcoma, and multicentric Castleman’s disease. We revealed new host–virus interactions of circRNAs: human antiviral circRNAs are activated in response to KSHV infection, and viral circRNA expression is induced in the lytic phase of infection.
Links Between Behavior Change Techniques and Mechanisms of Action: An Expert Consensus Study
Authors: Connell Lauren E , Carey Rachel N , de Bruin Marijn , Rothman Alexander J , Johnston Marie , Kelly Michael P , Michie Susan
Published: November 2018

Background

Understanding the mechanisms through which behavior change techniques (BCTs) can modify behavior is important for the development and evaluation of effective behavioral interventions. To advance the field, we require a shared knowledge of the mechanisms of action (MoAs) through which BCTs may operate when influencing behavior.

Purpose

To elicit expert consensus on links between BCTs and MoAs.

Methods

In a modified Nominal Group Technique study, 105 international behavior change experts rated, discussed, and rerated links between 61 frequently used BCTs and 26 MoAs. The criterion for consensus was that at least 80 per cent of experts reached agreement about a link. Heat maps were used to present the data relating to all possible links.

Results

Of 1,586 possible links (61 BCTs × 26 MoAs), 51 of 61 (83.6 per cent) BCTs had a definite link to one or more MoAs (mean [SD] = 1.44 [0.96], range = 1–4), and 20 of 26 (76.9 per cent) MoAs had a definite link to one or more BCTs (mean [SD] = 3.27 [2.91], range = 9). Ninety (5.7 per cent) were identified as “definite” links, 464 (29.2 per cent) as “definitely not” links, and 1,032 (65.1 per cent) as “possible” or “unsure” links. No “definite” links were identified for 10 BCTs (e.g., “Action Planning” and “Behavioural Substitution”) and for six MoAs (e.g., “Needs” and “Optimism”).

Conclusions

The matrix of links between BCTs and MoAs provides a basis for those developing and synthesizing behavioral interventions. These links also provide a framework for specifying empirical tests in future studies.
Incest Survivors
Authors: Valandra  , McIntyre Jeni
Published: November 2018

Incest is recognized as a societal taboo in many cultures. Despite customs, laws, and moral edicts that forbid sex between familial adults and children or minors and adults, incest continues to occur. Although incidence rates have generally declined over the last three decades, incest is still a prevalent problem in society. The primary focus of this article is incest between adults and children, between siblings, and between children in the United States. The article provides content on the complex interplay of individual, family, and cultural structures that shape survivors’ lives using an ecological, person-in-environment perspective and an examination of the clinical and empirical forces that drive assessment, evaluation, and treatment approaches in support of culturally informed trauma recovery and healing.
Multilingualism and Mobility as Collateral Results of Hegemonic Language Policy
Authors: Albury Nathan John
Published: November 2018

This article shows, with Malaysia as a case study, that an ethnonationalist language policy need not have disempowering consequences for minorities. Malaysia politicizes ethnic difference between Malaysians of Malay, Chinese, and Indian descent. Ethnic Malays enjoy economic concessions unavailable to others, law defines Malaysia as Islamic and speaking Bahasa, and Malay ethnonationalism constructs Chinese– and Indian–Malaysians as perpetual visitors. Nonetheless, Bahasa has only added to the multilingual repertoires of non-Malays, rather than replaced it. This article analyses survey data about the multilingual practices of Malaysian youth and their folk linguistic talk about what guides their multilingualism. By drawing on critical language policy, it appears that policy may be so ethnonationalist that it has caused disassociation, especially amongst Indian–Malaysians, and sustained multilingualism. The Chinese–Malaysian experience, however, is better explained by a posthumanist perspective whereby language choices appear guided by material and immaterial resources within the Chinese–Malaysian community, rather than by matters of power or politics. In any case, the relative greater multilingualism of Chinese– and Indian–Malaysians was perceived as empowering non-Malay mobility despite ethnonationalist policy.
The Microbiome Modeling Toolbox: from microbial interactions to personalized microbial communities
Authors: Baldini Federico , Heinken Almut , Heirendt Laurent , Magnusdottir Stefania , Fleming Ronan M T , Thiele Ines
Published: November 2018

Motivation

The application of constraint-based modeling to functionally analyze metagenomic data has been limited so far, partially due to the absence of suitable toolboxes.

Results

To address this gap, we created a comprehensive toolbox to model (i) microbe–microbe and host–microbe metabolic interactions, and (ii) microbial communities using microbial genome-scale metabolic reconstructions and metagenomic data. The Microbiome Modeling Toolbox extends the functionality of the constraint-based reconstruction and analysis toolbox.

Availability and implementation

The Microbiome Modeling Toolbox and the tutorials at https://git.io/microbiomeModelingToolbox.
Long-Term Risk of Skin Cancer Among Childhood Cancer Survivors: A DCOG-LATER Cohort Study
Authors: Teepen Jop C , Kok Judith L , Kremer Leontien C , Tissing Wim J E , van den Heuvel-Eibrink Marry M , Loonen Jacqueline J , Bresters Dorine , van der Pal Helena J , Versluys Birgitta , van Dulmen-den Broeder Eline , Nijsten Tamar , Hauptmann Michael , Hollema Nynke , Dolsma Wil V , van Leeuwen Flora E , Ronckers Cécile M ,   DCOG-LATER Study Group
Published: November 2018

Background

Skin cancer is common after radiotherapy among childhood cancer survivors (CCSs). We studied risks and risk factors for subsequent skin cancers, with emphasis on radiation dose, exposed skin surface area, and chemotherapeutic agents.

Methods

The DCOG-LATER cohort study includes 5-year Dutch CCSs diagnosed 1963–2001. Subsequent skin cancers were identified from record linkages with the Netherlands Cancer Registry and Dutch Pathology Registry. Incidence rates were compared with general population rates. Multivariable Cox regression models were used, applying a novel method of case-control sampling enabling use of tumor location in cohort analyses. All statistical tests were two-sided.

Results

Among 5843 CCSs, 259 developed 1061 basal cell carcinomas (BCCs) (standardized incidence ratio [SIR] = 29.8, 95% confidence interval [CI] = 26.3 to 33.6; excess absolute risk per 10 000 person-years (EAR) = 24.6), 20 had melanoma (SIR = 2.3, 95% CI = 1.4 to 3.5; EAR = 1.1), and 10 had squamous cell carcinoma (SIR = 7.5, 95% CI = 3.6 to 13.8; EAR = 0.8). Cumulative incidence of BCC 40 years after childhood cancer was 19.1% (95% CI = 16.6 to 21.8%) after radiotherapy vs 0.6% expected based on general population rates. After a first BCC, 46.7% had more BCCs later. BCC risk was associated with any radiotherapy to the skin compartment of interest (hazard ratio [HR] = 14.32, 95% CI = 10.10 to 20.29) and with estimated percentage in-field skin surface area (26–75%: HR = 1.99, 95% CI = 1.24 to 3.20; 76–100%: HR = 2.16, 95% CI = 1.33 to 3.53, vs 1–25% exposed; Ptrend among exposed = .002), but not with prescribed radiation dose and likelihood of sun-exposed skin-area. Of all chemotherapy groups examined, only vinca alkaloids increased BCC risk (HR = 1.54, 95% CI = 1.04 to 2.27).

Conclusion

CCSs have a strongly, 30-fold increased BCC risk. BCC risk appears to increase with increasing skin surface area exposed. This knowledge underscores the need for awareness by survivors and their health care providers.
Low-intensity shockwave therapy in the treatment of diabetic nephropathy: a prospective Phase 1 study
Authors: Skov-Jeppesen Sune Moeller , Yderstraede Knud Bonnet , Bistrup Claus , Jensen Boyle L , Marcussen Niels , Hanna Milad , Lund Lars
Published: November 2018

Background

Low-intensity shockwave therapy (LI-SWT) is suggested as a therapy for promoting tissue regeneration. In pigs, it was recently found that LI-SWT improved renal function after ischaemic injury. Our objectives were to study glomerular filtration rate (GFR) and albuminuria in diabetic nephropathy (DN) after treatment with LI-SWT. The present pilot study reports on the clinical safety of LI-SWT in DN.

Methods

A total of 14 patients with diabetes mellitus and Stage 3 chronic kidney disease were recruited for this prospective, one-arm Phase 1 study. The patients were treated with six sessions of LI-SWT during a 3-week period. At each session, 3000 shockwaves were applied to each kidney with 0.265 mJ/mm2, extended focal size and 4 Hz. Follow-up visits were performed at 1, 3 and 6 months.

Results

In general, the treatment was well tolerated. Transient macroscopic haematuria was observed in three patients immediately after LI-SWT. The majority of patients experienced lower back tenderness lasting up to 2 days after treatment. There was no need for analgesic treatment. LI-SWT showed no negative effect on GFR and albuminuria. At baseline, median (interquartile range) GFR was 33.5 mL/min/1.73 m2 (27.8–43.8) compared with 36.0 mL/min/1.73 m2 (27.5–52.0) at 6 months follow-up. In parallel, median albuminuria was 256 mg/24 h (79–619) at baseline and tended to decrease to 137 mg/24 h (41–404) 6 months after LI-SWT. There was no statistical difference between baseline and follow-up results.

Conclusions

LI-SWT is a safe treatment for DN. Inclusion of more patients is needed to determine whether LI-SWT can improve renal functional outcomes.
Evaluation of a Systems-Based Tobacco Cessation Program Using Bedside Volunteers
Authors: Taylor Denise S , Medaglio Dominique , Jurkovitz Claudine T , Patterson Freda , Zhang Zugui , Gbadebo Adebayo , Bradley Elisabeth , Wessells Rose , Goldenberg Edward
Published: November 2018

Introduction

Hospitalization and post-discharge provide an opportune time for tobacco cessation. This study tested the feasibility, uptake, and cessation outcomes of a hospital-based tobacco cessation program, delivered by volunteers to the bedside with post-discharge referral to Quitline services. Patient characteristics associated with Quitline uptake and cessation were assessed.

Methods

Between February and November 2016, trained hospital volunteers approached inpatient tobacco users on six pilot units. Volunteers shared a cessation brochure and used the ASK-ADVISE-CONNECT model to connect ready to quit patients to the Delaware Quitline via fax-referral. Volunteers administered a follow-up survey to all admitted tobacco users via telephone or email at 3-months post-discharge.

Results

Of the 743 admitted tobacco users, 531 (72%) were visited by a volunteer, and 97% (531/547) of those approached, accepted the visit. Over one-third (201/531; 38%) were ready to quit and fax-referred to the Quitline, and 36% of those referred accepted Quitline services. At 3 months post-discharge, 37% (135/368) reported not using tobacco in the last 30 days; intent-to-treat cessation rate was 18% (135/743). In a multivariable regression model of Quitline fax-referral completion, receiving nicotine replacement therapy (NRT) during hospitalization was the strongest predictor (odds ratios [OR] = 1.97; 95% confidence interval [CI] = 1.34 to 2.90). In a model of 3-month cessation, receiving Quitline services (OR = 3.21, 95% CI = 1.35 to 7.68) and having coronary artery disease (OR = 2.28; 95% CI = 1.11 to 4.68) were associated with tobacco cessation, but a volunteer visit was not.

Conclusions

An “opt-out” tobacco cessation service using trained volunteers is feasible for connecting patients to Quitline services.

Implications

This study demonstrates the feasibility of a systems-based approach to link inpatients to evidence-based treatment for tobacco use. This model used trained bedside volunteers to connect inpatients to a state-funded Quitline after discharge that offers free cessation treatment of telephone coaching and cessation medications. Receiving NRT during hospitalization positively impacted Quitline referral, and engagement with Quitline resources was critical to tobacco abstinence post-discharge. Future work is needed to evaluate the cost-effectiveness and sustainability of this volunteer model.
Epidemiology of Bloodstream Infections Caused by Escherichia coli and Klebsiella pneumoniae That Are Piperacillin-Tazobactam-Nonsusceptible but Ceftriaxone-Susceptible
Authors: Baker Thomas M , Rogers Wesley , Chavda Kalyan D , Westblade Lars F , Jenkins Stephen G , Nicolau David P , Kreiswirth Barry N , Calfee David P , Satlin Michael J
Published: November 2018

Background

Piperacillin-tazobactam-nonsusceptible (TZP-NS) Enterobacteriaceae are typically also resistant to ceftriaxone. We recently encountered bacteremias due to Escherichia coli (Ec) and Klebsiella pneumoniae (Kp) that were TZP-NS but ceftriaxone-susceptible (CRO-S).

Methods

We reviewed all Ec and Kp bacteremias from 2011 to 2015 at our center and assessed the prevalence, antimicrobial susceptibilities, genetic profiles, patient characteristics, treatments, and outcomes of TZP-NS/CRO-S infections. We identified risk factors for TZP-NS/CRO-S infections compared with Ec and Kp bacteremias that were TZP-S and CRO-S (Control Group 1) and compared outcomes of patients with TZP-NS/CRO-S bacteremias, Control Group 1, and patients bacteremic with extended-spectrum β-lactamase (ESBL)–producing Ec and Kp.

Results

There were 1857 Ec and Kp bacteremia episodes, of which 78 (4.2%) were TZP-NS/CRO-S (Ec: 50/1227 [4.1%]; Kp: 28/630 [4.4%]). All TZP-NS/CRO-S isolates were also ampicillin-sulbactam-NS. Of 32 TZP-NS/CRO-S isolates that were sequenced, 28 (88%) harbored blaTEM-1 or blaSHV-1, none had an ESBL or AmpC β-lactamase gene, and many sequence types were represented. Independent risk factors for TZP-NS/CRO-S bacteremia were exposure to β-lactam/β-lactamase inhibitors (BL/BLIs; adjusted odds ratio [aOR], 5.5; P < .001) and cephalosporins (aOR, 3.0; P = .04). Thirty-day mortality after TZP-NS/CRO-S bacteremia was 25%, which was similar to control groups and was similar in patients treated empirically with BL/BLIs compared with those treated with cephalosporins or carbapenems. Targeted therapy with cephalosporins did not yield a higher 30-day mortality rate than carbapenem therapy.

Conclusions

TZP-NS/CRO-S Ec and Kp are emerging causes of bacteremia, and further research is needed to better understand the epidemiology, resistance mechanisms, and clinical impact of these strains.