bluuebunny/crossref_metadata_2025 huggingface dataset:
Reinforcing effect of amine‐functionalized and carboxylated porous graphene on toughness, thermal stability, and electrical conductivity of epoxy‐based nanocomposites
Authors: Naderi Mehdi , Ebrahimi Farnaz , Najafi Mohammad , Naderi Hamed
Published: January 2019

Epoxy‐based nanocomposites reinforced with nonfunctionalized porous graphene (NPG), carboxylated porous graphene (CNPG), and amine‐functionalized porous graphene (ANPG) were investigated with regard to mechanical properties, thermal stability, and electrical conductivity. Nanomaterials were added to the epoxy matrix in varying contents of 0.5, 1, and 2 wt %. Generally, mechanical properties were improved as a result of introducing nanomaterials into the epoxy resin. However, the amelioration of toughness was only observed in functionalized NPGs/epoxy nanocomposites. Field emission scanning electron microscopy images showed that functionalized nanomaterials induced a rougher fracture surface compared to the neat epoxy. Dynamic mechanical analysis along with differential scanning calorimetry confirmed an increment in the glass‐transition temperature (Tg) of the reinforced nanocomposites. Also, they proved that functionalization made the epoxy network tougher and more flexible. The electrical conductivity and thermal stability of the epoxy resin were also improved when loaded with nanomaterials. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47475.
Mysticetes to MiniConference to Manuscripts: Introduction to Thematic Issue on Mysticete Anatomy
Authors: Reidenberg Joy S.
Published: January 2019

This issue of the Anatomical Record is focused on the theme of Mysticete Anatomy. There are six included articles that explore the anatomy of the nasal region (Marquez et al., 2018; Maust‐Mohl et al., 2018), larynx (Damien et al., 2018), lungs (Fetherston et al., 2018), sublingual fascia (Werth et al., 2018), and brain (Raghanti et al., 2018). These papers document anatomical features exhibited by mysticetes (baleen whales) and their related cousins (including other whales, and the semiaquatic moose and hippopotamus). This theme stems from a 2‐day MiniConference on Mysticete Anatomy, hosted at the Icahn School of Medicine at Mount Sinai in New York City on May 2016. Anatomy is explored in the contexts of function and evolution of aquatic adaptations. Anat Rec, 2019. © 2019 Wiley Periodicals, Inc. Anat Rec, 302:663–666, 2019. © 2019 Wiley Periodicals, Inc.
Automatic detection of influencers in social networks: Authority versus domain signals
Authors: Rodríguez‐Vidal Javier , Gonzalo Julio , Plaza Laura , Sánchez Henry Anaya
Published: January 2019

Given the task of finding influencers (opinion makers) for a given domain in a social network, we investigate (a) what is the relative importance of domain and authority signals, (b) what is the most effective way of combining signals (voting, classification, learning to rank, etc.) and how best to model the vocabulary signal, and (c) how large is the gap between supervised and unsupervised methods and what are the practical consequences. Our best results on the RepLab dataset (which improves the state of the art) uses language models to learn the domain‐specific vocabulary used by influencers and combines domain and authority models using a Learning to Rank algorithm. Our experiments show that (a) both authority and domain evidence can be trained from the vocabulary of influencers; (b) once the language of influencers is modeled as a likelihood signal, further supervised learning and additional network‐based signals only provide marginal improvements; and (c) the availability of training data sets is crucial to obtain competitive results in the task. Our most remarkable finding is that influencers do use a distinctive vocabulary, which is a more reliable signal than nontextual network indicators such as the number of followers, retweets, and so on.
Employee Engagement + Social Good = A Winning Combination
Authors: Allen Eleanor , Williams Jim
Published: January 2019

Water for people's employee engagement model is a win–win–win for partner companies, volunteers, and populations who benefit from water for people's efforts to address global water challenges.
Matrilin‐2 prevents the TNFα‐induced apoptosis of WB‐F344 cells via suppressing JNK pathway
Authors: Luo Junming , Peng Shaohua , Bai Wenbin , Wu Zhaoyu , Shan Zhongshu , Wu Zetao , Yuan Xin , Che Xiaoming , Duan Zhili , Peng Jinwu , Wang Yichun , Zhang Shukun
Published: January 2019

Oval cells, a kind of hepatic progenitor cell quiescent at normal condition, activates to proliferate and differentiate into hepatocytes under severe and long‐term liver injury, which usually raises severe inflammation. However, how oval cell survives in the inflammatory milieu interne is still unclear. Tumor necrosis factor α (TNFα), mimicking inflammatory hepatic milieu interne, was used to treat oval cell line, WB‐F344, to test the protective function of matrilin‐2. In this study, our data suggested that matrilin‐2 prevented TNFα‐induced apoptosis in WB‐F344 cells via inhibiting ASK1/MKK7/JNK pathway. In conclusion, we determined that matrilin‐2 plays the key role in maintaining the survival of oval cell and guarantees its proliferation under various injury factors.
Systematic review of the use of big data to improve surgery in low- and middle-income countries
Authors: Knight S R , Ots R , Maimbo M , Drake T M , Fairfield C J , Harrison E M
Published: January 2019

Background

Technological advances have led to the generation of large amounts of data, both in surgical research and practice. Despite this, it is unclear how much originates in low- and middle-income countries (LMICs) and what barriers exist to the use of such data in improving surgical care. The aim of this review was to capture the extent and impact of programmes that use large volumes of patient data on surgical care in LMICs.

Methods

A PRISMA-compliant systematic literature review of PubMed, Embase and Google Scholar was performed in August 2018. Prospective studies collecting large volumes of patient-level data within LMIC settings were included and evaluated qualitatively.

Results

A total of 68 studies were included from 71 LMICs, involving 708 032 patients. The number of patients in included studies varied widely (from 335 to 428 346), with 25 reporting data on 3000 or more LMIC patients. Patient inclusion in large-data studies in LMICs has increased dramatically since 2015. Studies predominantly involved Brazil, China, India and Thailand, with low patient numbers from Africa and Latin America. Outcomes after surgery were commonly the focus (33 studies); very few large studies looked at access to surgical care or patient expenditure. The use of large data sets specifically to improve surgical outcomes in LMICs is currently limited.

Conclusion

Large volumes of data are becoming more common and provide a strong foundation for continuing investigation. Future studies should address questions more specific to surgery.
Evaluation of a surgical training programme for clinical officers in Malawi
Authors: Gajewski J , Borgstein E , Bijlmakers L , Mwapasa G , Aljohani Z , Pittalis C , McCauley T , Brugha R
Published: January 2019

Background

Shortages of specialist surgeons in African countries mean that the needs of rural populations go unmet. Task-shifting from surgical specialists to other cadres of clinicians occurs in some countries, but without widespread acceptance. Clinical Officer Surgical Training in Africa (COST-Africa) developed and implemented BSc surgical training for clinical officers in Malawi.

Methods

Trainees participated in the COST-Africa BSc training programme between 2013 and 2016. This prospective study done in 16 hospitals compared crude numbers of selected numbers of major surgical procedures between intervention and control sites before and after the intervention. Volume and outcomes of surgery were compared within intervention hospitals between the COST-Africa trainees and other surgically active cadres.

Results

Seventeen trainees participated in the COST-Africa BSc training. The volume of surgical procedures undertaken at intervention hospitals almost doubled between 2013 and 2015 (+74 per cent), and there was a slight reduction in the number of procedures done in the control hospitals (–4 per cent) (P = 0·059). In the intervention hospitals, general surgery procedures were more often undertaken by COST-Africa trainees (61·2 per cent) than other clinical officers (31·3 per cent) and medical doctors (7·4 per cent). There was no significant difference in postoperative wound infection rates for hernia procedures at intervention hospitals between trainees and medical doctors (P = 0·065).

Conclusion

The COST-Africa study demonstrated that in-service training of practising clinical officers can improve the surgical productivity of district-level hospitals.
Optimization and scale up of itaconic acid production from potato starch waste in stirred tank bioreactor
Authors: Bafana Richa , Sivanesan Saravanadevi , Pandey R. A.
Published: January 2019

Present study used Aspergillus terreus strain C1 isolated from mangrove soil for itaconic acid (IA) production from potato starch waste. Fermentation parameters were optimized by classical one factor approach and statistical experimental designs, such as Plackett‐Burman and response surface designs. Anionic deionization of potato waste was found to be a very effective, economic, and easy way of improving IA production. The increase in IA production by deionization was found to correlate with removal of phosphate. In our knowledge, this is the first report on application of deionization of potato waste to enhance IA production. Other parameters like inoculum development conditions, pH, presence of peptone and certain salts in the medium also significantly affected IA production. IA production by strain C1 increased 143‐fold during optimization when compared with the starting condition. The optimized IA level (35.75 g/L) was very close to the maximum production predicted by RSM (38.88 g/L). Bench scale production of IA was further optimized in 3‐L stirred tank reactor by varying parameters like agitation and aeration rate. The maximum IA production of 29.69 g/L was obtained under the agitation speed of 200 rpm and aeration rate of 0.25 vvm. To the best of our knowledge, it is the first report on IA production from potato starch waste at bioreactor level. © 2019 American Institute of Chemical Engineers Biotechnol. Prog., 35: e2774, 2019.
Improving marking efficiency for longer programming solutions based on a semi‐automated assessment approach
Authors: Buyrukoglu Selim , Batmaz Firat , Lock Russell
Published: January 2019

In recent years, many students in higher education have begun to learn programming languages. In doing so they will complete a variety of programming tasks of varying degrees of complexity. The students need to get consistent and personalized feedback to develop their programming skills. Human markers can provide personalized feedback using traditional manual approaches to assessment, but they may provide inconsistent feedback (especially for long programming solutions) since marking the programming solutions of multiple students can represent a significant workload for them. While full‐automated assessment systems are the best to provide consistent feedback, they may not provide sufficiently personalized feedback for novice programmers. This study develops a novel semi‐automated assessment approach in order to improve efficiency of human marker in the marking process and increase consistency of feedback (for both short and long programming solutions). It advocates the reuse of human marker's comments for similar code snippets, defined as segmented marking in this study. New full and partial marking models are developed based on segmented marking and they are tested by expert markers. The findings show that the two models are similar in efficiency, but that a partial marking approach potentially offers an improved efficiency for longer programming solutions. Such a finding has significant potential to reduce time spent on marking throughout the sector, which would have significant impact on both resourcing and timeliness of feedback.
Exosome proteomic analyses identify inflammatory phenotype and novel biomarkers in African American prostate cancer patients
Authors: Panigrahi Gati K. , Praharaj Prakash P. , Kittaka Hiroki , Mridha Asit R. , Black Olen M. , Singh Rakesh , Mercer Roger , van Bokhoven Adrie , Torkko Kathleen C. , Agarwal Chapla , Agarwal Rajesh , Abd Elmageed Zakaria Y. , Yadav Hariom , Mishra Santosh K. , Deep Gagan
Published: January 2019

African American men face a stark prostate cancer (PCa)‐related health disparity, with the highest incidence and mortality rates compared to other races. Additional and innovative measures are warranted to reduce this health disparity. Here, we focused on the identification of a novel serum exosome‐based “protein signature” for potential use in the early detection and better prognosis of PCa in African American men. Nanoparticle tracking analyses showed that compared to healthy individuals, exosome concentration (number/ml) was increased by ~3.2‐fold (P ˂ 0.05) in the sera of African American men with PCa. Mass spectrometry‐based proteomic analysis of serum exosomes identified seven unique and fifty‐five overlapping proteins (up‐ or downregulated) in African Americans with PCa compared to healthy African Americans. Furthermore, ingenuity pathway analyses identified the inflammatory acute‐phase response signaling as the top pathway associated with proteins loaded in exosomes from African American PCa patients. Interestingly, African American PCa E006AA‐hT cells secreted exosomes strongly induced a proinflammatory M2‐phenotype in macrophages and showed calcium response on sensory neurons, suggesting a neuroinflammatory response. Additionally, proteomic analyses showed that the protein Isoform 2 of Filamin A has higher loading (2.6‐fold) in exosomes from African Americans with PCa, but a lesser loading (0.6‐fold) was observed in exosomes from Caucasian men with PCa compared to race‐matched healthy individuals. Interestingly, TCGA and Taylor's dataset as well as IHC analyses of PCa tissue showed a lower Filamin A expression in tissues of PCa patients compared with normal subjects. Overall, these results support the usefulness of serum exosomes to noninvasively detect inflammatory phenotype and to discover novel biomarkers associated with PCa in African American men.
The interactional workings of laughter in group supervision for psychotherapeutic counsellors
Authors: Hutchby Ian , Dart Alison
Published: January 2019

Background

This article examines the uses of laughter in group supervision meetings for psychotherapeutic counsellors.

Aims

Focusing on its production in the course of talk‐in‐interaction, we explore how laughter is used systematically to complete a range of group‐specific actions.

Method

A set of group supervision sessions were drawn from a large corpus of recorded, naturally occurring counselling and group supervision meetings. Data were transcribed and analysed using the methods of Conversation Analysis.

Results

More than simply a response to humour, laughter in group supervision is shown to be a complex phenomenon used to perform a range of actions. Three types of use are identified: laughter in re‐assigning “problems” to other parties; laughter in doing “being‐in‐charge” of the supervision discourse; and laughter in the negotiation of ethically or relationally “tricky business.”

Conclusion

The practical significance of our analysis is to raise awareness, for supervisors and counsellors, of how laughter can play a key role in the discursive organisation of relations between supervisors, supervisees and the practical work of counselling.
Keep your eye on…
Authors: Knopf Alison
Published: January 2019

High out‐of‐pocket costs for some families for ASD services

The role of genetics in emotional deficits associated with irritability

The importance of social interaction in sports clubs
Rh/Ce0.25Zr0.75O2 Catalyst for Steam Reforming of Propane at Low Temperature
Authors: Yu Lin , Sato Katsutoshi , Nagaoka Katsutoshi
Published: January 2019

Solid oxide fuel cells (SOFCs) show high energy‐conversion efficiency and thus emit less CO2 than conventional combustion engines. Although SOFCs can directly convert hydrocarbons such as liquefied petroleum gas, these fuels readily induce coking on the electrodes of fuel cell stacks. To avoid coking, hydrocarbons can be subjected to a preliminary endothermic steam‐reforming step at a relatively low temperature using waste heat from the stack. Herein, we report that a Rh/Ce0.25Zr0.75O2 catalyst exhibited higher propane‐steam‐reforming activity than other Rh/Ce1−xZrxO2 catalysts and Rh/γ‐Al2O3. Catalyst characterization revealed that Rh/Ce0.25Zr0.75O2 had excellent redox property and high H2O‐adsorption activity, which contributed to the activation of steam and thus enhanced the propane‐steam‐reforming activity of this catalyst.
Catalysts Encapsulated in Biopolymer Hydrogels for Chemoenzymatic One‐Pot Processes in Aqueous Media
Authors: Pauly Jan , Gröger Harald , Patel Anant V.
Published: January 2019

Combining bio‐ and chemocatalysts for chemoenzymatic reaction sequences is of high interest to organic chemistry. In this study, we combined a ring‐closing metathesis reaction conducted by a Grubbs’ catalyst and a subsequent enzymatic ester hydrolysis reaction conducted by pig liver esterase within a two‐step one‐pot process. We addressed sustainability by encapsulating both catalysts in biopolymer‐based hydrogels derived from renewable resources to allow straightforward recycling and using aqueous media for the reactions. When we investigated the approaches of either conducting the reaction sequence in the same solvent for both reactions or using different preferred solvents for each reaction, the enzyme activity turned out to be enhanced when encapsulating the enzyme, thus shielding it from the Grubbs’ catalyst. In terms of recycling, the encapsulated catalysts demonstrated promising performance with >80 % conversion for seven runs.
Photoluminescence of Seven‐Coordinate Zirconium and Hafnium Complexes with 2,2′‐Pyridylpyrrolide Ligands
Authors: Zhang Yu , Akhmedov Novruz G. , Petersen Jeffrey L. , Milsmann Carsten
Published: January 2019

Luminescent seven‐coordinated zirconium and hafnium complexes bearing three mono‐anionic 2,2′‐pyridylpyrrolide ligands and one chloride were synthesized. Solid‐state structures and the dynamic behaviors in solution were probed by X‐ray crystallography and variable temperature 1H NMR experiments, respectively. Absorption spectroscopy and time‐dependent density functional theory (TD‐DFT) calculations supported a hybrid of ligand‐to‐metal charge transfer (LMCT)/ligand‐to‐ligand charge transfer (LLCT) for the visible light absorption band. The complexes (MePMPMe)3MCl (M=Zr, Hf, MePMPMe=3,5‐dimethyl‐2‐(2‐pyridyl)pyrrolide) are emissive in solution at room temperature upon irradiation with visible light due to a combination of phosphorescence and fluorescence characterized by excited state lifetimes in the μs and low to sub‐ns timescale, respectively. Electrochemical experiments revealed that the zirconium complex possesses a reversible redox event under highly reducing condition (−2.29 V vs. Fc+/0).
Azaindolo[3,2,1‐jk]carbazoles: New Building Blocks for Functional Organic Materials
Authors: Kader Thomas , Stöger Berthold , Fröhlich Johannes , Kautny Paul
Published: January 2019

The preparation and characterization of 12 azaindolo[3,2,1‐jk]carbazoles is presented. Ring‐closing C−H activation allowed for the convenient preparation of six singly and six doubly nitrogen‐substituted indolo[3,2,1‐jk]carbazole derivatives in which ten of the materials have not been described in the literature before. The detailed photophysical and electrochemical characterization of the developed materials revealed a significant impact of the incorporation of pyridine‐like nitrogen into the fully planar indolo[3,2,1‐jk]carbazole backbone. Furthermore, the nitrogen position decisively impacted intermolecular hydrogen bonding and thus the solid‐state alignment. Ultimately, the versatility of the azaindolo[3,2,1‐jk]carbazoles scaffold makes this class of materials an attractive new building block for the design of functional organic materials.
Synthesis of Functional Monosilanes by Disilane Cleavage with Phosphonium Chlorides
Authors: Santowski Tobias , Sturm Alexander G. , Lewis Kenrick M. , Felder Thorsten , Holthausen Max C. , Auner Norbert
Published: January 2019

The Müller–Rochow direct process (DP) for the large‐scale production of methylchlorosilanes MenSiCl4−n (n=1–3) generates a disilane residue (MenSi2Cl6−n, n=1–6, DPR) in thousands of tons annually. This report is on methylchlorodisilane cleavage reactions with use of phosphonium chlorides as the cleavage catalysts and reaction partners to preferably obtain bifunctional monosilanes MexSiHyClz (x=2, y=z=1; x,y=1, z=2; x=z=1, y=2). Product formation is controlled by the reaction temperature, the amount of phosphonium chloride employed, the choice of substituents at the phosphorus atom, and optionally by the presence of hydrogen chloride, dissolved in ethers, in the reaction mixture. Replacement of chloro by hydrido substituents at the disilane backbone strongly increases the overall efficiency of disilane cleavage, which allows nearly quantitative silane monomer formation under comparably moderate conditions. This efficient workup of the DPR thus not only increases the economic value of the DP, but also minimizes environmental pollution.
Hierarchical Porous N‐Doped Carbon Nanosheets Obtained by Organic–Inorganic Bipolymeric Engineering for Improved Lithium–Sulfur Batteries
Authors: Fan Xiaojing , Tan Furui , Meng Fancheng , Liu Jiehua
Published: January 2019

A new route for obtaining N‐doped carbon nanosheets through an in situ solid‐state thermal organic–inorganic polymerization and carbonization method, with glucose and melamine as precursors, due to different temperature intervals for glucose or melamine polymerization, is reported. At a current rate of 0.2 C, as a cathode for a lithium–sulfur cell, the N‐doped carbon nanosheet/sulfur hybrid delivers a high capacity of 1313 and 722 mA h g−1 in the 1st and 200th cycles, respectively; these values are over 40 % higher than that of cells with glucose‐derived carbon nanosheets.
A Unified Mechanism to Account for Manganese‐ or Ruthenium‐Catalyzed Nitrile α‐Olefinations by Primary or Secondary Alcohols: A DFT Mechanistic Study
Authors: Lu Yu , Zhao Ruihua , Guo Jiandong , Liu Zheyuan , Menberu Wasihun , Wang Zhi‐Xiang
Published: January 2019

Acceptorless dehydrogenative coupling (ADC) reactions generally involve a nucleophile (e.g., amine) as a coupling partner. Intriguingly, it has been reported that nitriles could also act as nucleophiles in ADC reactions, achieving the α‐olefination of nitriles with primary or secondary alcohols by employing a manganese or ruthenium pincer complex as the catalyst, respectively. Although different mechanisms have been postulated for the two catalytic systems, the results of our DFT mechanistic study, reported herein, have allowed us to propose a unified mechanism to account for both nitrile α‐olefinations. The reactions take place in four stages, namely alcohol dehydrogenation, nitrile activation to generate a nucleophilic metal species, coupling of an aldehyde or ketone with the metal species to form a C−C bond and to transfer a nitrile (Cα−)H atom to the carbonyl group, and dehydration by transferring the protonic (N−)H to the hydroxy group. A notable feature of the coupling stage is the activation of water or alcohol to give an intermediate featuring an OH−‐ or OR−‐like group that activates a nitrile Cα−H bond. Moreover, the mechanism can even be applied to the base (KOtBu, modeled by the (KOtBu)4 cluster)‐catalyzed Knoevenagel condensation of nitriles with ketones, which further indicates the generality of the mechanism and the resemblance of the metal pincer complexes to the (KOtBu)4 base. We expect these in‐depth mechanistic insights and the finding of the resemblance of the metal pincer complexes to the (KOtBu)4 cluster could assist the development of new ADC reactions.
„Brot aus Luft“ und andere chemische Beiträge zur Welternährung
Authors: Fischer Pauline J. , Kühn Fritz E.
Published: January 2019

Seit der Etablierung und Verbreitung der Mineralstofftheorie durch Justus von Liebig ist es gelungen, durch gezielten Einsatz von vor allem mineralischen Düngern die Ernteerträge erheblich zu steigern und so Nahrung für die wachsende Weltbevölkerung bereitzustellen. Bei der Versorgung der Pflanzen spielt Stickstoff, welcher der wichtigste Pflanzennährstoff nach den gut verfügbaren Nährstoffen C, H und O ist, eine entscheidende Rolle. Durch die großtechnische Stickstofffixierung im Haber‐Bosch‐Prozess gelang der Durchbruch zur Produktion diverser mineralischer N‐Dünger. Des Weiteren sind die Nährstoffe P, K, Ca, Mg und einige Spurenelemente wie Fe und Mn essentiell für das Pflanzenwachstum und den Ertrag. Neben der Düngung mit den richtigen Nährstoffen sind auch der pH‐Wert des Bodens und die Bodenstruktur entscheidend für ein gutes Pflanzenwachstum. Aufgrund der unerwünschten Folgen für Umwelt und Ernteprodukte bei unsachgerechter und vor allem übertrieben starker Düngung ist die Vermittlung von Grundkenntnissen über die Auswirkung und den sinnvollen Einsatz von Düngemitteln von großer und wachsender Bedeutung.
Cocaine addicted to cytoskeletal change and a fibrosis high
Authors: Verma Avnish , Bennett Jason , Örme Ayşe Merve , Polycarpou Elena , Rooney Brian
Published: January 2019

Cocaine is one of the most widely abused illicit drugs due to its euphoric and addictive properties. Cocaine‐mediated cognitive impairments are the result of dynamic cytoskeletal rearrangements involved in mediating structural and behavioural plasticity. Cytoskeletal changes initiated following cocaine abuse are regulated by the Rho family of GTPases with significant downstream activity in key actin binding proteins. Moreover, signalling via the endoplasmic reticulum chaperone protein, sigma‐1 receptor has highlighted the possibility of cocaine regulated pathology in other organ systems. However, the question of whether upstream stimulation of such a high affinity binding receptor is directly involved in cocaine‐mediated cytoskeletal changes at present remains unknown. In this review, we describe the functional role of key cytoskeletal regulators in response to cocaine‐induced signalling cues. In addition, we ascertain the extent of whether global cytoskeletal modulators involved in cocaine‐induced neurological stimulation can be used as a platform for future studies into elucidating its fibrotic potential within the hepatic microenvironment. A focus on aspects still poorly understood relating to the nonneuronal pathological impact of cocaine is discussed in the sphere of hepatic dysregulation. Lastly, we suggest that cocaine may mediate its pathological capacity via the sigma1 receptor in regulating hepatoxicity, hepatic stellate cells activity, cytoskeletal dynamics, and the transcriptional regulation of key hepato‐fibrogenic modulators.
Advancements in the Development of non‐BET Bromodomain Chemical Probes
Authors: Clegg Michael A. , Tomkinson Nicholas C. O. , Prinjha Rab K. , Humphreys Philip G.
Published: January 2019

The bromodomain and extra terminal (BET) family of bromodomain‐containing proteins (BCPs) have been the subject of extensive research over the past decade, resulting in a plethora of high‐quality chemical probes for their tandem bromodomains. In turn, these chemical probes have helped reveal the profound biological role of the BET bromodomains and their role in disease, ultimately leading to a number of molecules in active clinical development. However, the BET subfamily represents just 8/61 of the known human bromodomains, and attention has now expanded to the biological role of the remaining 53 non‐BET bromodomains. Rapid growth of this research area has been accompanied by a greater understanding of the requirements for an effective bromodomain chemical probe and has led to a number of new non‐BET bromodomain chemical probes being developed. Advances since December 2015 are discussed, highlighting the strengths/caveats of each molecule, and the value they add toward validating the non‐BET bromodomains as tractable therapeutic targets.
Beyond chemotherapy: Emerging biomarkers and therapies as small cell lung cancer enters the immune checkpoint era
Authors: Della Corte Carminia M. , Gay Carl M. , Byers Lauren A.
Published: January 2019

For decades, clinicians have witnessed no therapeutic advances for small cell lung cancer, including no US Food and Drug Administration‐approved targeted therapies; recently, immune‐checkpoint blockade has emerged as a promising new option for the treatment of patients with relapsed small cell lung cancer (including recent US Food and Drug Administration approval of nivolumab in the third‐line setting) and soon may represent the frontline standard of care in combination with chemotherapy. However, there is a need to uncover biomarkers to guide patient selection and develop novel approaches to enhance response to immunotherapies.
Impact of conditioning intensity on outcomes of haploidentical stem cell transplantation for patients with acute myeloid leukemia 45 years of age and over
Authors: Santoro Nicole , Labopin Myriam , Ciceri Fabio , Van Lint Maria Teresa , Nasso Daniela , Blaise Didier , Arcese William , Tischer Johanna , Bruno Benedetto , Ehninger Gerhard , Koc Yener , Santarone Stella , Huang Xiao‐Jun , Savani Bipin N. , Mohty Mohamad , Ruggeri Annalisa , Nagler Arnon
Published: January 2019

Background

T cell–replete haploidentical stem cell transplantation (haplo‐SCT) is a valid therapeutic option for adult patients with high‐risk acute myeloid leukemia (AML) lacking an HLA‐matched sibling or unrelated donor.

Method

We retrospectively analyzed the outcomes of 912 AML patients ≥45 years of age who had undergone haplo‐SCT with either myeloablative conditioning (MAC; n = 373) or reduced intensity conditioning (RIC; n = 539) regimens.

Results

The median follow‐up was 31.1 and 25.7 months for MAC and RIC, respectively. The incidence of relapse and nonrelapse mortality (NRM) were 25.1% versus 28.7% and 31.0% versus 30.3% for MAC and RIC, respectively; 2‐year leukemia‐free survival (LFS) was 43.9% for MAC versus 41.0% for RIC. In multivariate analysis, the use of MAC versus RIC was not associated with a difference in the outcomes. Results were confirmed in the propensity score–weighted analysis. Disease status and performance status at transplantation were associated with outcomes. Notably, the use of posttransplantation cyclophosphamide was associated with reduced acute graft‐versus‐host disease (aGVHD) stage III‐IV, and NRM and increased overall survival, LFS, and GVHD‐free, relapse‐free survival. The use of mobilized peripheral blood stem cells was associated with an increased risk of stage II‐IV aGVHD.

Conclusion

No differences were found between MAC and RIC regimens for haplo‐SCT in adults with AML who were ≥45 years of age. The type of GVHD prophylaxis, disease status, and performance status were the major predictors of transplantation outcome. These results may serve as the background for randomized study comparing RIC versus MAC for haplo‐SCT in adults with AML.
Circulating tumor DNA alterations in patients with metastatic castration‐resistant prostate cancer
Authors: Sonpavde Guru , Agarwal Neeraj , Pond Gregory Russell , Nagy Rebecca J. , Nussenzveig Roberto H. , Hahn Andrew W. , Sartor Oliver , Gourdin Theodore Stewart , Nandagopal Lakshminarayanan , Ledet Elisa M. , Naik Gurudatta , Armstrong Andrew J. , Wang Jue , Bilen Mehmet Asim , Gupta Shilpa , Grivas Petros , Pal Sumanta K. , Lanman Richard B. , Talasaz AmirAli , Lilly Michael B.
Published: January 2019

Background

Because cell‐free DNA (cfDNA) analysis facilitates the noninvasive genomic profiling of metastatic castration‐resistant prostate cancer (mCRPC), the authors evaluated the association between cfDNA alterations and outcomes and evolution with therapy.

Methods

Patients with mCRPC underwent cfDNA genomic profiling using Guardant360, which examines major cancer‐associated genes. Clinical factors, therapy information, failure‐free survival, and overall survival (OS) were obtained for select patients. The association between genomic alterations and outcomes was investigated.

Results

Of 514 men with mCRPC, 482 (94%) had ≥1 circulating tumor DNA (ctDNA) alteration. The most common recurrent somatic mutations were in TP53 (36%), androgen receptor (AR) (22%), adenomatous polyposis coli (APC) (10%), neurofibromin 1 (NF1) (9%), epidermal growth factor receptor (EGFR), catenin beta‐1 (CTNNB1), and AT‐rich interactive domain‐containing protein 1A (ARID1A) (6% each); and BRCA1, BRCA2, and phosphatidylinositol‐4,5‐bisphosphate 3‐kinase catalytic subunit alpha (PIK3CA) (5% each) The most common genes with increased copy numbers were AR (30%), MYC (20%), and BRAF (18%). Clinical outcomes were available for 163 patients, 46 of whom (28.8%) were untreated for mCRPC. A higher number of ctDNA alterations, AR alterations, and amplifications of MYC and BRAF were associated with worse failure‐free survival and/or OS. On multivariable analysis, MYC amplification remained significantly associated with OS. Prior therapy and serial profiling demonstrated the evolution of alterations in AR and other genes.

Conclusions

ctDNA frequently was detected in this large cohort of “real‐world” patients with mCRPC, and the alterations appeared to be similar to previously reported tumor tissue alterations. A higher number of alterations, and AR and MYC alterations, appear to compromise clinical outcomes, suggesting a role for immune checkpoint inhibitors and novel AR and BET inhibitors in selected patients.
Survey on DDoS defense mechanisms
Authors: Fenil E. , Mohan Kumar P.
Published: January 2019

It is a prominent attack used by the attackers to cripple an online service. The method of implementation can either be from a single source or a list of common users (zombie army) who are modulated from the command centers. Hence, in the latter case, they are called denial‐of‐service attacks. A substantial amount of distributed users has malware software that turns all these systems into bots without the user's consent. This aspect adds more to the complexity of detecting the attacker who is well masqueraded. These serve as a severe problem for Internet services and the network. It is mandatory to distinguish between a legitimate and a malicious user. There are many defense mechanisms that combat these types of attacks. This presentation mainly highlights the details of denial‐of‐service attacks and their various mechanisms and types and compares studies on different mechanisms that have been proposed. Finally, this gives an insight into future prospects in the research field for secured Internet services.
PreDiKT‐OnOff: A complex adaptive approach to study the impact of digital social networks on Pakistani students' personal and social life
Authors: uz Zaman S. Khaliq , Khan Iftikhar Ahmed , Hussain Syed Sajid , Iqbal Tassawar , Shuja Juanid , Ahmed Syed Faraz , Jararweh Yaser , Ko Kwangman
Published: January 2019

The growing popularity of Digital Social Networks (DSNs) among young students demands an introspection of its impact across different dimensions, such as students' academic performance and daily life. The results of the existing literature on the issue vary across societies due to differences in cultural and religious values. This research aims to examine the social network usage among students to analyze their bonding within their social and personal lives. As a case study, we selected Pakistani students as a convenient sample. Multiple social aspects like in‐person interaction of students with their family members, physical activities, religious knowledge, social capital, and level of students' trust in DSNs are considered. Considering the complex nature of the network, a Complex Adaptive System (CAS) approach is used to model the relationships between different nodes of the network. In addition, Linear Regression models are created to predict a node from the combination of different nodes based on their relationships.
Mitigation of cyber threats: Protection mechanisms in federated SDN/NFV infrastructures for 5G within FIRE+
Authors: Gil Pérez Manuel , Huertas Celdrán Alberto , Giardina Pietro G. , Bernini Giacomo , Pizzimenti Simone , García Clemente Félix J. , Martínez Perez Gregorio , Festa Giovanni , Paglianti Fabio
Published: January 2019

Cyber attacks are becoming a very common trend in existing networks, expecting to be even more acute in future 5G networks due to greater number of connected devices, higher mobile data volume, low latency, etc. Security mechanisms to tackle cyber threats should be updated when users, possibly carrying devices with some kind of malware, move in highly dynamic mobile networks in order to continue providing the same detection and mitigation capabilities along user's path. This paper presents BotsOnFIRE, an experiment of the EU H2020 SoftFIRE project for the detection and mitigation of botnets in the SoftFIRE federated testbed for 5G within FIRE+, by combining Software‐Defined Networking (SDN) and Network Functions Virtualization (NFV) technologies. Bots' mobility is considered to trigger reconfiguration of security‐related SDN/NFV applications, when needed, so as to update security capabilities of the SoftFIRE infrastructure. The BotsOnFIRE experiment contributes to the wider 5G objective of more secure and resilient networks and services, where botnets are actually one of the most powerful cyber threats capable of orchestrating the remote execution of cyber‐attacks. Experiments confirm that BotsOnFIRE is feasible to conduct the expected detection and mitigation procedures in the SoftFIRE federated environment, being evaluated through some Key Performance Indicators.
Optimal priority assignment for messages on controller area network with maximum system robustness
Authors: Bai Enci , Zhang Weizhe , Wu Yulong , He Hui
Published: January 2019

Controller Area Network (CAN) is broadly used for in‐vehicle networking. Each message on the CAN bus is given a unique identifier as its priority. When more than one node starts to transmit at the same time, the message with the highest priority will be sent. The schedulability of the message set is significantly affected by the priority assignment algorithms employed. To ensure that the CAN system tolerate additional interference, we propose system robustness, a concept to represent the total robustness of the message set. Maximum system robustness of message set problem is NP‐hard. We find that assigning a higher priority to the message with small transmission time or low utilization may lead to more system robustness. Based on this, this paper presents four optimal priority assignment approximation algorithms using the Audsley's priority assignment method: TMPA, UMPA, GTMPA, and GUMPA. TMPA and UMPA are heuristic algorithms. GTMPA and GUMPA are greedy algorithms. Experimental results show that, compared with the existing optimal algorithms, TMPA, GTMPA, and GUMPA can improve the system robustness of CAN message sets effectively.
A Facile Path to Graphene‐Wrapped Polydopamine‐Entwined Silicon Nanoparticles with High Electrochemical Performance
Authors: Liu Zechen , Huang Jialiang , Zhao Xuewen , Huang Hongyang , Fu Chengcheng , Li Zhihui , Cheng Yonghong , Niu Chunming , Zhang Jinying
Published: January 2019

Graphene‐coated silicon nanoparticles with polydopamine buffers have been designed and successfully fabricated as anodes for lithium ion batteries, where the polydopamine was grown on the silicon nanoparticles and then coated with graphene layers. The expansion cavities for silicon nanoparticles during charging and discharging process are provided by the polydopamine buffer layers. The outermost graphene coating layers not only keep the pulverized silicon particles together without disintegration, but also improve the electric conductivity of silicon nanoparticles. Silicon nanoparticles of an industrial product level with different size distributions and oxidation layers were used in this work. High electrochemical performances with specific capacities of 1100 mAh g−1 were achieved by the designed silicon composites with polydopamine and graphene after 550 cycles at a current rate of 200 mA g−1.
Monitoring of direct alcohol markers in alcohol use disorder patients during withdrawal treatment and successive rehabilitation
Authors: Luginbühl Marc , Weinmann Wolfgang , Butzke Ingo , Pfeifer Philippe
Published: January 2019

Direct and indirect biomarkers are widely applied for the determination of alcohol consumption. They help to assess past or present alcohol consumption. Depending on the window of detection and sensitivity of the investigated marker, punctual alcohol consumption may remain undetected. In this study, different sampling strategies for the intermediary long‐term marker phosphatidylethanol (PEth) are evaluated and compared to the determination of the short‐term markers ethyl glucuronide (EtG) and ethyl sulfate (EtS) in urine. Samples from 19 patients undergoing alcohol use disorder treatment were collected during the withdrawal treatment and successive rehabilitation (33 ± 26 days (range: 3–74 days)). With liquid chromatography–tandem mass spectrometry (LC–MS/MS) EtG and EtS in urine, PEth in blood, PEth in dried blood spot (DBS) from venous blood, and PEth in DBS from capillary blood were quantified and compared. The use of volumetric capillary DBS, prepared from 20 μL of blood, provided the same results as the use of venous DBS (95% ± 10%, R2 0.9899 for PEth 16:0/18:1). Capillary DBS sampling has the advantage that it can be performed without venipuncture. The use of PEth in DBS proved to prevent post‐sampling degradation, providing a longer detection in comparison to PEth in liquid blood, which only showed 67% ± 24% of the PEth DBS 16:0/18:1 concentration. When compared with EtG and EtS in urine, PEth monitoring proved to be advantageous for the detection of relapse situations, as the accumulation of PEth in blood prolongs the detectability. In conclusion, volumetric capillary DBS sampling for PEth is a simple and useful tool for compliance monitoring, and avoids hematocrit issues.
Transactions among thinness expectancies, depression, and binge eating in the prediction of adolescent weight control behaviors
Authors: Ortiz Anna Marie L. , Davis Heather A. , Smith Gregory T.
Published: January 2019

Objective

Binge eating, the transdiagnostic risk associated with depression, and the eating disorder‐specific risk associated with expectancies for reinforcement from thinness have been identified as risk factors for the development of weight control behaviors. The purpose of this study was to examine if these risk factors transact to further predict risk in youth.

Method

Binge eating, depressive symptoms, thinness expectancies, and weight control behaviors were assessed in 1,758 adolescents three times during the transitional period between middle school and high school. We tested six different possible transactional processes.

Results

Mediation tests demonstrated that both 8th grade binge eating and 8th grade depressive symptoms predicted 10th grade weight control behaviors through their predictive influence on thinness expectancies in 9th grade. However, our results were not consistent with a mediational process in which 8th grade thinness expectancies predicted 9th grade depression to further predict 10th grade weight control behaviors. No interactions among binge eating, depressive symptoms, or thinness expectancies predicted weight control. Results did not differ between girls and boys.

Discussion

Thinness expectancies appear to mediate the predictive influence of binge eating and depressive symptoms on risk for engaging in weight control behaviors. These results add to theoretical understanding of risk and suggests potential intervention pathways for clinicians.
I didn't want them to see: Secretive eating among adults with binge‐eating disorder
Authors: Lydecker Janet A. , Grilo Carlos M.
Published: January 2019

Objective

Secretive eating is characterized by eating furtively and concealing the act and evidence of eating. Among youth, secretive eating is common and associated with eating‐disorder psychopathology. Yet, secretive eating among adults, including adults with eating disorders, is relatively unexplored.

Method

We assessed secretive eating among treatment‐seeking adults with binge‐eating disorder (BED) and examined demographic and clinical characteristics of patients with and without secretive eating. Patients (N = 755) were assessed for BED, eating‐disorder psychopathology, and depression by trained doctoral clinicians using established interviews and self‐report measures; height and weight were measured.

Results

Overall, 54% of patients reported secretive eating distinct (i.e., separate) from objective binge‐eating episodes (OBEs). A significantly greater proportion of women than men endorsed secretive eating; age, race, and education did not significantly differ. Patients with and without secretive eating did not significantly differ in body mass index (BMI), OBEs, overeating episodes, or restraint. Patients with secretive eating endorsed significantly more subjective binge‐eating episodes, greater eating concerns, shape concerns, and weight concerns and had higher depression scores than patients without secretive eating. Patients with secretive eating were significantly more likely to have overvaluation of shape/weight than patients without secretive eating. Results remained the same after adjusting for sex, race, and BMI.

Discussion

Findings suggest that, among patients with BED, secretive eating reflects greater eating‐disorder psychopathology but not increased frequency of OBEs or greater BMI. Understanding secretive eating can to inform determination of eating‐disorder severity contribute to treatment formulation and planning.
Patterns of frugivory in the columnar cactusPilosocereusleucocephalus
Authors: Vázquez‐Castillo Shamira , Miranda‐Jácome Antonio , Ruelas Inzunza Ernesto
Published: January 2019

In the frugivory networks of many arid and semi‐arid Mesoamerican ecosystems, columnar cacti act as keystone species that produce fruits with a high content of water and nutrients attractive to numerous vertebrates. The aim of this investigation was to assess the fruit removal patterns of two guilds of frugivores on the fruits of the woolly torchPilosocereus leucocephalus. We assessed fruit pulp removal in two ways: by estimating the consumption of seeds given the amount of pulp removed per visit and by estimating the percentage of pulp removal over time. We put exclosures on unripe, intact fruits to keep frugivores from removing material. Once ripe, we removed the exclosures and tracked animal visitation of 69 fruits using camera traps. We obtained a total of 2,162 hr of footage (14:47 hours of them with effective pulp removal). The highest number of visitors is that of diurnal species (n = 12, all birds) versus only four nocturnal (three bats, one rodent). The most effective species in pulp removal are birds. Bats play a modest role in frugivory of this cactus. The significance of this work is twofold: (a) birds and bats consume the fruit pulp of this cactus and likely disperse its seeds, and (b) although bats rank high in pulp removal effectiveness, birds as a guild far outweigh their importance in this system, as they are not only more frequent but also remove more pulp and seeds. Both groups are known to be important in cacti seed dispersal, and our findings are essential in understanding the population dynamics of the woolly torch and in elucidating its seed dispersal ecology.