bluuebunny/crossref_metadata_2025 huggingface dataset:
Amorphous Conjugated Polymers as Efficient Dual‐Mode MALDI Matrices for Low‐Molecular‐Weight Analytes
Authors: Horatz Kilian , Ditte Kristina , Prenveille Thomas , Zhang Ke‐Nan , Jehnichen Dieter , Kiriy Anton , Voit Brigitte , Lissel Franziska
Published: June 2019

Matrix‐assisted laser desorption/ionization mass spectrometry (MALDI MS) usually employs highly crystalline small‐molecule matrices, and the analyte is interpreted as being co‐crystallized with the matrix. We recently showed that semi‐crystalline polymers are efficient matrices for the detection of low‐molecular‐weight compounds (LMWCs) in MALDI MS and MALDI MS Imaging, and are dual‐mode, i. e., enabling both positive and negative modes. The matrix performances of two fluorene/napthalene diimide co‐polymers P(TNDIT‐Fl(C4C2)) and P(TNDIT‐Fl(C10C8)) were investigated and compared. Both are fully amorphous according to XRD measurements, show high relative absorption values at the wavelength of common MALDI lasers (λNd:YAG=355 nm: C4C2=73 %; C10C8=67 %), and are solution processable. As matrices, they are dual‐mode, and enable the detection of LMWCs while being mostly MALDI‐silent. Compared with semicrystalline polymer matrices, the amorphous matrices give similar or better signal intensities, thus indicating that analyte inclusion takes place in the amorphous part of the polymer matrix.
Post‐transcriptional control of immune responses and its potential application
Authors: Yoshinaga Masanori , Takeuchi Osamu
Published: June 2019

Inflammation is the host response against stresses such as infection. Although the inflammation process is required for the elimination of pathogens, uncontrolled inflammation leads to tissue destruction and inflammatory diseases. To avoid this, the inflammatory response is tightly controlled by multiple layers of regulation. Post‐transcriptional control of inflammatory mRNAs is increasingly understood to perform critical roles in this process. This is mediated primarily by a set of RNA binding proteins (RBPs) including tristetraprolin, Roquin and Regnase‐1, and RNA methylases. These key regulators coordinate the inflammatory response by modulating mRNA pools in both immune and local nonimmune cells. In this review, we provide an overview of the post‐transcriptional coordination of immune responses in various tissues and discuss how RBP‐mediated regulation of inflammation may be harnessed as a potential class of treatments for inflammatory diseases.
Microfilaria and Strongyloides larva diagnosed in cerebrospinal fluid and ascitic fluid, respectively: Approach to their morphology on cytology
Authors: Keloth Thara , Rajkumari Nonika , Gochhait Debasis , Gudivada Vijayalakshmi , Toi Pampa Ch , Siddaraju Neelaiah
Published: June 2019

Filariasis and Strongyloidiasis are two endemic parasitic infections seen in any tropical country. Filariasis, commonly caused by Wuchereria bancrofti, Brugia malayi, and Brugia timori is seen often in peripheral blood and lymphoid tissue. But it can be isolated from wide variety of soft tissue sites in the body like soft tissue lumps, breast, thyroid, body fluids. Strongyloides stercoralis, a helminthic infection, usually affects the respiratory and gastrointestinal (GI) tract, and frequently picked up in GI biopsies. However, in cases of hyper infection and patients with altered immunity, it can be isolated from other rare sites like body fluid samples. Accurate morphological Identification and confirmation are important for specific management. We report a case of microfilaria isolated from cerebrospinal fluid and a case of Strongyloides larva isolated from ascitic fluid in clinically unsuspected cases of these two parasitic infestations. We have also added a brief discussion on morphological differences between the two larval forms.
Long‐lasting behavioral and neuroendocrine changes provoked in rabbits by cancelling a single nursing bout in early lactation
Authors: García Fernández Hilda L. , Chavira‐Ramírez David R. , González‐Mariscal Gabriela
Published: June 2019

To restore estrus in lactating doe rabbits, nursing was prevented on lactation day 10 and allowed again from day 12 onward. This “biostimulation” procedure, used to accelerate reproduction, allows kit survival despite a 48 hr fast. Yet, the consequences of “biostimulation” on their psychobiological and neuroendocrine development are largely unknown. Therefore, we determined, in adult males and females, tested in the morning or afternoon: corticosteroid secretion (baseline and reactive), sexual behavior, and responses in six tests measuring stress/anxiety. The latter were not affected by maternal deprivation or time of testing in either sex. The lordosis quotient was reduced in deprived does (relative to controls), an effect eliminated when only non‐kins (of both groups) were compared. Deprived males showed altered sexual behavior, evidenced by a large number of mounts not culminating in ejaculation. Corticosterone and cortisol secretion increased (relative to baseline) following i.m. saline in all groups, but the magnitude of the response was affected by maternal deprivation, time of day, and sex. Results indicate that particular behaviors and reactivity to stress have different thresholds regarding the effects of mother–litter separation in early lactation.
Isolation calls in house mouse pups: Individual consistency across time and situations
Authors: Verjat Aurélie , Rödel Heiko G. , Féron Christophe
Published: June 2019

Isolation calls are emitted by the offspring of many mammalian species when separated from caregivers and siblings. Some studies indicate that isolation call rates constitute a consistent individual trait; others show that the young adjust their vocalization rate to the current situation. We studied this in the house mouse (Mus musculus domesticus) by exploring individual consistencies in pup isolation call rates and their potential modulation in different social situations. We carried out experiments including three treatments (repeated measurements) during consecutive days, all starting with an initial isolation of the pup, followed by (a) a reunion with mother and littermates and a second isolation hereafter, (b) the confrontation of isolated pup with cues of its own nest or (c) with cues of an unfamiliar adult male. The first treatment induced a significant increase, while the others induced significant decreases in pup isolation call rates. Pups showed consistent individual differences in initial call rates across the three days of testing (postnatal days 9–11), which were significantly associated with individual differences in call rates during the different treatments. We conclude that pup isolation calls represent a consistent, trait‐like behaviour in the house mouse, which can also express flexibility in response to social cues.
Late Pleistocene speciation of three closely related tree peonies endemic to the Qinling–Daba Mountains, a major glacial refugium in Central China
Authors: Xu Xing‐Xing , Cheng Fang‐Yun , Peng Li‐Ping , Sun Yan‐Qiang , Hu Xian‐Ge , Li San‐Yuan , Xian Hong‐Li , Jia Kai‐Hua , Abbott Richard J. , Mao Jian‐Feng
Published: June 2019

Determining the factors promoting speciation is a major task in ecological and evolutionary research and can be aided by phylogeographic analysis. The Qinling–Daba Mountains (QDM) located in central China form an important geographic barrier between southern subtropical and northern temperate regions, and exhibit complex topography, climatic, and ecological diversity. Surprisingly, few phylogeographic analyses and studies of plant speciation in this region have been conducted. To address this issue, we investigated the genetic divergence and evolutionary histories of three closely related tree peony species (Paeonia qiui, P. jishanensis, and P. rockii) endemic to the QDM. Forty populations of the three tree peony species were genotyped using 22 nuclear simple sequence repeat markers (nSSRs) and three chloroplast DNA sequences to assess genetic structure and phylogenetic relationships, supplemented by morphological characterization and ecological niche modeling (ENM). Morphological and molecular genetic analyses showed the three species to be clearly differentiated from each other. In addition, coalescent analyses using DIYABC conducted on nSSR variation indicated that the species diverged from each other in the late Pleistocene, while ecological niche modeling (ENM) suggested they occupied a larger area during the Last Glacial Maximum (LGM) than at present. The combined genetic evidence from nuclear and chloroplast DNA and the results of ENM indicate that each species persisted through the late Pleistocene in multiple refugia in the Qinling, Daba, and Taihang Mountains with divergence favored by restricted gene flow caused by geographic isolation, ecological divergence, and limited pollen and seed dispersal. Our study contributes to a growing understanding of the origin and population structure of tree peonies and provides insights into the high level of plant endemism present in the Qinling–Daba Mountains of Central China.
Population structure of avian malaria parasites
Authors: Humphries Meghann B. , Stacy Matthew T. , Ricklefs Robert E.
Published: June 2019

The geographic distribution of genetic diversity in malaria parasite populations (Apicomplexa: Haemosporida) presumably influences local patterns of virulence and the evolution of host‐resistance, but little is known about population genetic structure in these parasites. We assess the distribution of genetic diversity in the partial Domain I of apical membrane antigen 1 (AMA1) in three mtDNA‐defined lineages of avian Plasmodium to determine spatial population structure and host–parasite genetic relationships. We find that one parasite lineage is genetically differentiated in association with a single host genus and among some locations, but not with respect to other hosts. Two other parasite lineages are undifferentiated with respect to host species but exhibit geographic differentiation that is inconsistent with shared geographic barriers or with isolation‐by‐distance. Additional differentiation within two other lineages is unassociated with host species or location; in one case, we tentatively interpret this differentiation as the result of mitochondrial introgression from one of the lineages into a second lineage. More sampling of nuclear genetic diversity within populations of avian Plasmodium is needed to rule out coinfection as a possible confounding factor. If coinfections are not responsible for these findings, further assessment is needed to determine the frequency of mitonuclear discordance and its implications for defining parasite lineages based on mitochondrial genetic variation.

OPEN RESEARCH BADGES

This article has earned an Open Data Badge for making publicly available the digitally‐shareable data necessary to reproduce the reported results. The data is available at Genbank https://www.ncbi.nlm.nih.gov/genbank/, accession numbers MK965548‐MK965653 and MK929797‐MK930264.
Experimental nitrogen addition alters structure and function of a boreal bog: critical load and thresholds revealed
Authors: Wieder R. Kelman , Vitt Dale H. , Vile Melanie A. , Graham Jeremy A. , Hartsock Jeremy A. , Fillingim Hope , House Melissa , Quinn James C. , Scott Kimberli D. , Petix Meaghan , McMillen Kelly J.
Published: June 2019

Bogs and fens cover 6% and 21%, respectively, of the 140,329 km2Oil Sands Administrative Area in northern Alberta. Development of the oil sands has led to increasing atmospheric N deposition, with values as high as 17 kg N·ha−1·yr−1; regional background deposition is <2 kg N·ha−1·yr−1. Bogs, being ombrotrophic, may be especially susceptible to increasing N deposition. To examine responses to N deposition, over five years, we experimentally applied N (asNH4NO3) to a bog near Mariana Lake, Alberta, unaffected by oil sands activities, at rates of 0, 5, 10, 15, 20, and 25 kg N·ha−1·yr−1, plus controls (no water or N addition). Increasing N addition: (1) stimulated N2fixation at deposition <3.1 kg N·ha−1·yr−1, and progressively inhibited N2fixation as N deposition increased above this level; (2) had no effect onSphagnum fuscumnet primary production (NPP) in years 1, 2, and 4, but inhibitedS. fuscumNPPin years 3 and 5; (3) stimulated dominant shrub andPicea marianaNPP; (4) led to increased root biomass and production; (5) changedSphagnumspecies relative abundance (decrease inS. fuscum, increase inS. magellanicum, no effect onS. angustifolium); (6) led to increasing abundance ofRhododendron groenlandicumandAndromeda polifolia, and to vascular plants in general; (7) led to increasing shrub leaf N concentrations inAndromeda polifolia,Chamaedaphne calyculata,Vaccinium oxycoccos,V. vitis‐idaea, andPicea mariana; (8) stimulated cellulose decomposition, with no effect onS. fuscumpeat or mixed vascular plant litter decomposition; (9) had no effect on net N mineralization rates or on porewaterNH4+‐N,NO3−‐N, orDONconcentrations; and (10) had minimal effects on peat microbial community composition. Increasing experimental N addition led to a switch from new N being taken up primarily bySphagnumto being taken up primarily by shrubs. As shrub growth and cover increase,Sphagnumabundance andNPPdecrease. Because inhibition of N2fixation by increasing N deposition plays a key role in bog structural and functional responses, we recommend a N deposition critical load of 3 kg N·ha−1·yr−1for northern Alberta bogs.
Temporal dynamic analysis of a mountain ecosystem based on multi‐source and multi‐scale remote sensing data
Authors: Ibarrola‐Ulzurrun Edurne , Marcello Javier , Gonzalo‐Martín Consuelo , Martín‐Esquivel José Luis
Published: June 2019

During the last decades, ecosystems have suffered a decline in natural resources due to climate change and anthropogenic pressure. Specifically, the European rabbit introduced by humans, as well as drought episodes, have led to a change in the vegetation structure of a mountainous ecosystem: Teide National Park in Spain. Teide managers studied, with field‐based traditional methods, how the two keystone vegetation species, Spartocytisus supranubius and Pterocephalus lasiospermus, have changed their dynamics in this vulnerable and heterogenic ecosystem. However, remote sensing is an important tool for classifying, monitoring, and managing large areas in a fast and economic way. This work proposes a methodological framework to monitor the changes produced in this protected area using multi‐source remote sensing imagery. The results strengthen and extend the analysis followed by the National Park managers, demonstrating that S. supranubius has decreased its population while P. lasiospermus has increased. Moreover, this study presents thematic maps of the species of interest, as well as its specific coverage at different dates, providing quantitative data difficult to get with traditional approaches.
Definition and treatment of arrhythmogenic cardiomyopathy: an updated expert panel report
Authors: Elliott Perry M. , Anastasakis Aris , Asimaki Angeliki , Basso Cristina , Bauce Barbara , Brooke Matthew A. , Calkins Hugh , Corrado Domenico , Duru Firat , Green Kathleen J. , Judge Daniel P. , Kelsell David , Lambiase Pier D. , McKenna William J. , Pilichou Kalliopi , Protonotarios Alexandros , Saffitz Jeffrey E. , Syrris Petros , Tandri Hari , Te Riele Anneline , Thiene Gaetano , Tsatsopoulou Adalena , van Tintelen J. Peter
Published: June 2019

It is 35 years since the first description of arrhythmogenic right ventricular cardiomyopathy (ARVC) and more than 20 years since the first reports establishing desmosomal gene mutations as a major cause of the disease. Early advances in the understanding of the clinical, pathological and genetic architecture of ARVC resulted in consensus diagnostic criteria, which proved to be sensitive but not entirely specific for the disease. In more recent years, clinical and genetic data from families and the recognition of a much broader spectrum of structural disorders affecting both ventricles and associated with a propensity to ventricular arrhythmia have raised many questions about pathogenesis, disease terminology and clinical management. In this paper, we present the conclusions of an expert round table that aimed to summarise the current state of the art in arrhythmogenic cardiomyopathies and to define future research priorities.
Cyanoborates
Authors: Ignat'ev Nikolai V. , Finze Maik
Published: June 2019

Cyanoborate chemistry has emerged to an important topic during the last two decades, beginning with two independent reports on the successful synthesis of the tetracyanoborate anion [B(CN)4]–in 2000. A wealth of cyanoborate anions with different substituents in addition to CN group(s) bonded to boron,i.e. hydrogen, halogen, aryl, alkenyl, alkyl, perfluoroalkyl, and alkoxy, have been developed, which enable the tuning of properties of compounds and materials based on them. The readily accessible alkali metal cyanoborates are convenient starting materials for the preparation of cyanoborates with various organic, inorganic, and metal cations as well as cyanoborate coordination compounds. A focus has been on low‐viscosity room temperature cyanoborate‐ionic liquids that are of interest for various applications, especially for electrochemical devices such as dye sensitized solar cells (DSSC) and supercapacitors. Many other potential applications of these novel substances in chemistry and materials science have been studied. Furthermore, cyanoborates are promising starting compounds for the synthesis of other boron species, for example the weakly coordinating tetrakis(trifluoromethyl)borate anion [B(CF3)4]–and the boron‐centered nucleophile B(CN)32–. In this review the syntheses, chemical and physicochemical properties, and selected applications of cyanoborates are presented and discussed.
Development and validation of a novel SiFaSTRTM 23‐plex system
Authors: Zheng Hancheng , Tao Ruiyang , Zhang Jingyi , Zhang Jiashuo , Wang Shouyu , Yang Zihao , Xu Qiannan , Gao Yuzhen , Zhang Suhua , Li Chengtao
Published: June 2019

Human identification and paternity testing are usually based on the study of STRs depending on their particular characteristics in the forensic investigation. In this paper, we developed a sensitive genotyping system, SiFaSTR™ 23‐plex, which is able to characterize 18 expanded Combined DNA Index System STRs (D3S1358, D5S818, D2S1338, TPOX, CSF1PO, TH01, vWA, D7S820, D21S11, D10S1248, D8S1179, D1S1656, D18S51, D12S391, D19S433, D16S539, D13S317, and FGA), three highly polymorphic STRs among Chinese people (Penta D, Penta E, and D6S1043), one Y‐chromosome Indel and amelogenin using a multiplex PCR; the PCR amplified products were analyzed using the Applied Biosystems 3500 Genetic Analyzer. Full genotyping profiles were obtained using only 31.25 pg of control DNA; various case‐type specimens, as well as ten‐year‐old samples were also successfully genotyped. Additionally, in the validation studies, this multiplex was demonstrated to be human‐specific and compatible with the interference of multiple PCR inhibitors. The system also enabled the detection of mixtures, and complete profiles could be obtained at the mixed ratios of 1:1, 1:3, and 3:1. The development and validation study here illustrated that the SiFaSTR™ 23‐plex system is accurate, powerful, and more sensitive than many other systems. What's more, the population data in our study not only illustrated that this 23‐plex typing system was straightforward and efficient but also expanded the Chinese STR database, which could facilitate the appropriate application of the 23 genetic markers in forensic genetics, especially in the Chinese population.
Exergoeconomic analysis for crude oil gathering and transportation system in matrix pattern
Authors: Cheng Qinglin , Li Zhidong , Yu Chunguang , Wu Hao , Lv Lili , Xie Hongjun , Ma Guoyu
Published: June 2019

Based on exergoeconomic theory, the energy consumption situation for a typical oil transfer station in eastern China is evaluated. According to the analysis of the distribution for logistics and exergy flow, the crude oil gathering and transportation system is divided into two subsystems: pipe network and oil transfer station. The unit exergoeconomic costs for each component exergy flow are calculated by computing method in matrix pattern, of which the pressure exergy and thermal exergy at the end of the process are 812.58 yuan/GJ and 1575.24 yuan/GJ, respectively. Simultaneously, exergoeconomic evaluation indicators such as exergy cost growth coefficient, relative cost difference, and exergoeconomic coefficient are calculated, which can conclude the weak link of technical system is heating furnace equipment. The growth value of its exergy cost growth coefficient is 14.988, the relative cost difference is 94.503, and the exergoeconomic coefficient is 9.046, so it has great potential for energy saving. Exergoeconomic analysis method can provide a scientific and effective method or basis during the energy‐saving reconstruction for oil gathering and transportation system.
Toxicity and Mechanisms of Action of Polycyclic Aromatic Hydrocarbon Pollution in Red Algae (Gracilaria corticata) from the Northern Coast of the Oman Sea
Authors: Sinaei Mahmood , Loghmani Mehran
Published: June 2019

The activities of selected biomarkers including 7-ethoxycoumarin-O-deethylase (ECOD) and glutathione S-transferase (GST) were measured in the red algae (Gracilaria corticata) obtained from the Oman Sea. Chemical analyses were used to assess the polycyclic aromatic hydrocarbons (PAHs) in the red algae. Total PAH concentrations in the red algae ranged from 3.61 to 8.14 ng g–1 dry weight. Mean GST and ECOD activity also varied from 8.87 to 15.32 nmol/mg protein/min and from 0.31 to 1.02 pmol/min/mg protein, respectively. Significant correlations were found between the total PAH levels and the selected biomarkers (p < 0.01). The results showed that ECOD and GST enzymes reacted to PAHs in phase I and II detoxification mechanisms of red algae (G. corticata), which extend the use of these biomarkers for investigation of the biological effects of PAH pollution as well as determination of pollution bioavailability. Environ Toxicol Chem 2019;38:1947–1953. © 2019 SETAC.

Abstract

Biomarkers of the biological effects of PAHs.
Is the Effect Assessment Approach for Fungicides as Laid Down in the European Food Safety Authority Aquatic Guidance Document Sufficiently Protective for Freshwater Ecosystems?
Authors: Rico Andreu , Brock Theo C.M. , Daam Michiel A.
Published: June 2019

In Europe, the European Food Safety Authority aquatic guidance document describes the procedures for the derivation of regulatory acceptable concentrations (RACs) for pesticides in edge-of-field surface waters on the basis of tier-1 (standard test species), tier-2 (geometric mean and species sensitivity distributions [SSDs]), and tier-3 (model ecosystem studies) approaches. In the present study, the protectiveness of such a tiered approach was evaluated for fungicides. Acute and chronic RACs for tier-1 and tier-2B (SSDs) were calculated using toxicity data for standard and additional test species, respectively. Tier-3 RACs based on ecological thresholds (not considering recovery) could be derived for 18 fungicides. We show that tier-1 RACs, in the majority of cases, are more conservative than RACs calculated based on model ecosystem experiments. However, acute tier-2B RACs do not show a sufficient protection level compared with tier-3 RACs from cosm studies that tested a repeated pulsed exposure regime or when relatively persistent compounds were tested. Chronic tier-2B RACs showed a sufficient protection level, although they could only be evaluated for 6 compounds. Finally, we evaluated the suitability of the calculated RACs for 8 compounds with toxicity data for fungi. The comparison shows that the current RACs for individual fungicides, with a few exceptions (e.g., tebuconazole), show a sufficient protection level for structural and functional fungal endpoints. However, more data are needed to extend this comparison to other fungicides with different modes of action. Environ Toxicol Chem 2019;38:2279–2293. © 2019 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.
Lethal and Sublethal Toxicity of Thiamethoxam and Clothianidin Commercial Formulations to Soil Invertebrates in a Natural Soil
Authors: Ritchie Ellyn E. , Maisonneuve France , Scroggins Rick P. , Princz Juliska I.
Published: June 2019

The use of neonicotinoids in agriculture is a critical environmental protection issue. Although there has been considerable research on pollinator exposure and aquatic toxicological effects, few studies have investigated the chronic impacts on soil-dwelling species. Given the application of neonicotinoids into soil systems, there is the potential for risk to soil invertebrates. The toxicity of 2 commercial formulations containing the active ingredients (a.i.) thiamethoxam (Actara® 240SC) or clothianidin (Titan™) was investigated using 3 soil invertebrate species: Oppia nitens, Eisenia andrei, and Folsomia candida. No adverse effects were observed for O. nitens at the highest tested concentrations (≥92 mg a.i./kg dry soil) after a 28-d exposure. Exposure to clothianidin resulted in a 28-d median inhibitory concentration (IC50) of 0.069 (95% confidence limits: 0.039–0.12) mg/kg dry soil for F. candida, and a 56-d IC50 of 0.26 (0.22–3.2) mg a.i./kg dry soil for E. andrei. Exposure to thiamethoxam was less toxic, with IC50s of 0.36 (0.19–0.66) and 3.0 (2.2–4.0) mg a.i./kg dry soil for F. candida and E. andrei reproduction, respectively. The observed toxicity for F. candida adult survival and reproduction and for E. andrei reproduction occurred at environmentally relevant concentrations. However, because clothianidin is a degradation product of thiamethoxam, and detection of clothianidin rose to levels of concern in the thiamethoxam-amended soils over time, the observed toxicity may be partly attributed to the presence of clothianidin. Environ Toxicol Chem 2019;38:2111–2120. © 2019 Crown in the right of Canada. Published by Wiley Periodicals Inc. on behalf of SETAC.
The pandora of network slicing: A multicriteria analysis
Authors: Rosa Raphael Vicente , Rothenberg Christian Esteve
Published: June 2019

The evolving requirements of 5G communication business cases around vertical markets in addition to rich content multimedia cloud applications call for advances in enabling technologies and standardization to realize tailor‐made end‐to‐end network services, an approach commonly referred to as network slicing. Different mappings between infrastructure capabilities and custom service requirements produce an overload of information that a network service provider must handle to rationalize possible slicing alternatives for a given business case. This article proposes a methodology exploring algorithms from multicriteria analysis (MCA) to digest a set of slicing criteria advantage points into a coherent set of slicing preferences. Through extensive experimental analysis, we reasoning about observed patterns in the slicing alternatives and discuss the utility of the proposed MCA process for the definition of classes of slices, slicing abstractions views, and recovery/scalability analysis. Altogether, the MCA methodology proposed in this article sheds light into candidate mechanisms to tackle the pandora behind the yet‐to‐be‐understood issues and unanticipated trade‐offs of alternative network slicing approaches. Contributions of this article include providing a prominent outlook towards different dimensioning angles of network slicing, scoping its criteria design, timing, and the quality of the criteria information.
Identification of a Pan‐Gamma‐Secretase Inhibitor Response Signature for Notch‐Driven Cholangiocarcinoma
Authors: O’Rourke Colm J. , Matter Matthias S. , Nepal Chirag , Caetano‐Oliveira Rui , Ton Phuongnga T. , Factor Valentina M. , Andersen Jesper B.
Published: June 2019

Cholangiocarcinoma (CCA) mortality rates are increasing as a result of rising incidence and limited curative treatment(s) for patients with advanced disease. NOTCH pathway reactivation has been reported in biliary malignancies to conflicting degrees, hindering prioritization of key therapeutic targets within the network and identification of candidate responder patients for NOTCH‐directed therapies. We analyzed genomic data from 341 patients with CCA and identified NOTCH1 significantly increased in a subgroup characterized by distinct stromal infiltration. Network‐wide imbalance of the NOTCH pathway was seen in CCA, including correlation of NOTCH1 with NOTCH3 and NOTCH ligands. Given the diversity of observed NOTCH receptor engagement, γ‐secretase modulation was rationalized as a therapeutic option. Indeed, subcutaneous transplantation of sensitive and resistant CCA cell lines pretreated with a γ‐secretase inhibitor (GSi) cocktail demonstrated the antineoplastic effects of GSi in a subset of CCA and led to the development of a 225‐gene responder signature. This signature was validated in an independent cohort of 119 patients. Further, this signature was enriched in liver tumors initiated by hydrodynamic injections of activated‐NOTCH as compared with the AKT‐RAS‐driven tumors. Candidate GSi‐responder patients were characterized by distinct transcriptomes overlapping with previous hepatobiliary metastasis and stemness, unique stromal properties, and dysfunctional intratumoral immune infiltration. Pan‐cancer analysis identified 41.9% of cancer types to harbor prospective GSi‐responder patients, which was adapted into a 20‐gene GSi‐sensitivity score metric capable of discriminating nanomolar versus micromolar sensitivity to a cell‐permeable GSi (Z‐LLNle‐CHO) across 60 diverse tumor lines (area under the curve = 1). Conclusion: We have established a GSi‐responder signature with evidence across several patient cohorts, as well as in vitro and in vivo models, to enable precision medicine application of NOTCH‐directed therapy in CCA as well as prospectively across diverse malignancies.
Exergy and energy analysis of a wavy fin radiator with variously shaped nanofluids as coolants
Authors: Kumar Vikash , Sahoo Rashmi Rekha
Published: June 2019

The present study deals with the energy and exergy analysis of a wavy fin radiator deploying various shapes of Al2O
3‐water as nanocoolant. The effects of radiator effectiveness, pumping power, heat transfer rate, and performance index with variously shaped nanoparticles, mainly spherical, brick, and platelet, on coolant flow rates and air velocities have been investigated. Also, the impacts of entropy, second law efficiency, entropy generation number, and irreversibility on radiator performance analysis have been considered with steady‐state assumptions.

Theoretical analysis revealed that the spherical particle–based nanocoolant showed 21.9%, and 18.2% higher effectiveness than platelet and brick nanocoolants. However, minimization in the entropy generation is observed in the platelet shape of the nanoparticle. The second law efficiency is 13% higher for the spherical nanocoolant compared with the brick nanocoolant. An optimum entropy generation number is found at a coolant flow rate of 13 l/min and then gradually decreases with an increase in the coolant flow rate. For all the considered operating parameters, the spherical nanoparticle showed a better performance than brick and platelet nanofluids as a radiator coolant. Due to the enhanced overall performance for the spherical nanofluid, it may be considered as a potential candidate for a radiator coolant.
Decrease in number of mast cells in resected nasal polyps as an indicator for postoperative recurrence of chronic rhinosinusitis
Authors: Teranishi Yuichi , Jin Denan , Takano Sakurako , Sunami Kishiko , Takai Shinji
Published: June 2019

Background

In the clinical setting, chronic rhinosinusitis with nasal polyps (CRSwNP) is usually divided into eosinophilic‐CRS (ECRS) and non‐ECRS (NECRS) in Japan. Patients with the former are believed to be at risk for postoperative recurrence of CRS. However, some patients have been missed according to these phenotypic classifications due to the low number of infiltrating eosinophils in polyp tissues.

Objective

In the present study, we attempted to identify cellular or molecular candidate markers to predict nasal polyp recurrence.

Methods

Nasal polyps were collected from 32 patients with CRSwNP who had undergone an endoscopic sinus surgery. These patients were divided into ECRS and NECRS groups in accordance with the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) scoring system and the number of eosinophils in polyp tissues. Unclassifiable patients were referred to as the unknown group.

Results

Eosinophil infiltration in resected nasal polyps was most evident in the ECRS group. However, the number of mast cells and tryptase‐positive cells in nasal polyps were significantly lower in ECRS and unknown groups compared with the NECRS group. A significant positive correlation was detected between the JESREC score and number of eosinophils. The numbers of mast cells and tryptase‐positive cells were negatively correlated with the JESREC score in all included samples. Significant positive correlations were detected between the number of transforming growth factor β1‐positive cells and the number of mast cells, tryptase‐positive cells, and chymase‐positive cells mast cells.

Conclusions and clinical relevance

These findings indicated that the enumeration of mast cells in resected polyps may be another approach to predict postoperative polyp recurrence in CRSwNP patients.
Validating mental health assessment in Kenya using an innovative gold standard
Authors: Watson Leah K. , Kaiser Bonnie N. , Giusto Ali M. , Ayuku David , Puffer Eve S.
Published: June 2019

With the growing burden of mental health disorders worldwide, alongside efforts to expand availability of evidence‐based interventions, strategies are needed to ensure accurate identification of individuals suffering from mental disorders. Efforts to locally validate mental health assessments are of particular value, yet gold‐standard clinical validation is costly, time‐intensive, and reliant on available professionals. This study aimed to validate assessment items for mental distress in Kenya, using an innovative gold standard and a combination of culturally adapted and locally developed items. The mixed‐method study drew on surveys and semi‐structured interviews, conducted by lay interviewers, with 48 caregivers. Interviews were used to designate mental health “cases” or “non‐cases” based on emotional health problems, identified through a collaborative clinical rating process with local input. Individual mental health survey items were evaluated for their ability to discriminate between cases and non‐cases. Discriminant survey items included 23 items adapted from existing mental health assessment tools, as well as 6 new items developed for the specific cultural context. When items were combined into a scale, results showed good psychometric properties. The use of clinically rated semi‐structured interviews provides a promising alternative gold standard that can help address the challenges of conducting diagnostic clinical validation in low‐resource settings.
Truncated TEAD‐binding protein of TAZ inhibits glioma survival through the induction of apoptosis and repression of epithelial‐mesenchymal transition
Authors: Zhao Wei , Li Li‐Wen , Tian Rui‐Feng , Dong Qiu‐Feng , Li Peng‐Qi , Yan Zhi‐Feng , Yang Xin , Huo Jun‐Li , Fei Zhou , Zhen Hai‐Ning
Published: June 2019

Transcriptional coactivator with PDZ‐binding motif (TAZ), a Hippo pathway downstream effector, promotes tumor progression by serving as a transcriptional coactivator with TEAD. Here, we introduced a new construct which can express the TEAD‐binding domain of TAZ protein (TAZBD), and determined its antitumor effect in malignant glioma both in vitro and in vivo. We first observed that TAZ was upregulated in glioma tissues and related to malignant clinicopathologic characteristic, indicating the crucial role of TAZ during glioma progression. In U87 and U251 cells, TAZBD expression increased the proportion of apoptotic cells, and suppressed the colony formation and tumorigenicity. Further, TAZBD also decreased cell metastasis through the repression of epithelial‐mesenchymal transition. The mechanistic study showed that TAZBD suppression of glioma cells was predominantly through blocking the TAZ‐TEAD complex formation by competing with endogenous TAZ. Thus, the gene therapy of malignant glioma through blocking TAZ‐TEAD complex by TAZBD may provide a new way for the targeted therapy of glioma.
A latent class analysis of cognitive empowerment and ethnic identity: An examination of heterogeneity between profile groups on dimensions of emotional psychological empowerment and social justice orientation among urban youth of color
Authors: Lardier David T. , Barrios Verónica R. , Garcia‐Reid Pauline , Reid Robert J.
Published: June 2019

Psychological empowerment (PE) encompasses key aspects of youth development and civic engagement. Empowerment scholarship has largely focused on the intrapersonal or emotional component of PE, which considers perceptions of control and self‐efficacy, specifically in the sociopolitical sphere. Fewer studies have assessed the interactional or cognitive component of PE. Even less have examined the empirical association aspects of PE, including cognitive empowerment, with conceptually related variables, such as ethnic identity. Those studies that are present have shown that the association between aspects of PE and ethnic identity are complex. The current study of urban high school students of color (N = 383; 53.1% female; 75% Hispanic/Latinx) investigates the heterogeneity present between cognitive empowerment and ethnic identity. Latent class cluster analyses were conducted and five distinct profile groups emerged. Differences were observed on the basis of profile groups of cognitive empowerment and ethnic identity on self‐reported dimensions of emotional PE (e.g., leadership and policy control) and social justice orientation. The majority of study participants were clustered in groups that identified moderate to high levels of both cognitive empowerment and ethnic identity. Results provide useful insights for theory and programming.
Parental‐perceived neighborhood characteristics and adolescent depressive symptoms: A multilevel moderation analysis
Authors: Dawson Christyl T. , Wu Wensong , Fennie Kristopher P. , Ibañez Gladys , Cano Miguel Á. , Pettit Jeremy W. , Trepka Mary Jo
Published: June 2019

Aims

This study examines the moderating role of parental neighborhood perceptions on the relationship between neighborhood structural disadvantage and adolescent depressive symptoms.

Methods

Data from the National Longitudinal Study of Adolescent to Adult Health (Add Health) consisting of 12,105 adolescents and their parents were used.

Results

Mixed effects multilevel modeling revealed that parental‐perceived neighborhood disorder was associated with higher levels of adolescent depressive symptoms (β = .27, p ≤ .001). The interaction between neighborhood concentrated poverty and parental‐perceived neighborhood disorder was also significant (β = −.14, p ≤ .01). Low and high levels of parental‐perceived neighborhood disorder were associated with lower (β = −.41, p < .05) and higher (β = .46, p ≤ .01) levels of adolescent depressive symptoms, respectively, with increasing concentrated poverty. Parental‐perceived collective efficacy was not associated with adolescent depressive symptoms nor was it a moderator.

Conclusion

Findings suggest that the neighborhood's social environment may mitigate adolescent depressive symptoms. Implications for structural interventions are discussed.
Single‐port versus conventional laparoscopic distal pancreatectomy: a propensity score matched analysis and a learning curve of single‐port approach
Authors: Park Pyoungjae , Han Hyung Joon , Song Tae‐Jin , Choi Sae Byeol , Kim Wan‐Bae , Yoo Young Dong , Kim Dong‐Sik , Cha Jae Hyung
Published: June 2019

Background

Single‐port laparoscopic approaches are well established in the field of minimally invasive surgery; however, single‐port laparoscopic distal pancreatectomy (SPLDP) has not been evaluated in a large number of distal pancreatic neoplasms. We aimed to compare single‐port laparoscopic distal pancreatectomy outcomes with conventional laparoscopic distal pancreatectomy (LDP) outcomes.

Methods

We retrospectively evaluated the medical records of 101 patients who underwent SPLDP (n = 26) or LDP (n = 75). We performed 1:1 propensity score matching between the two groups. Consequently, 26 patients were included in each group. We analyzed the learning curve based on the operation time in SPLDP.

Results

Single‐port laparoscopic distal pancreatectomy could be performed with fewer trocars (P < 0.001) and assistants (P < 0.001). However, compared to the LDP group, mean operation time was longer (278.9 vs. 178.7 min, P < 0.001) and splenic vessel preservation rates were lower (0% vs. 46.2%, P < 0.001) in the SPLDP group. The mean pain visual analogue scale score was significantly lower at postoperative day 1 (P < 0.001) and day 2 (P < 0.001) in the SPLDP group. The learning curve was determined in the 12th case for SPLDP.

Conclusions

Single‐port laparoscopic distal pancreatectomy is comparable in safety to conventional laparoscopic approaches for distal pancreatic neoplasms, with fewer trocars, assistants and less pain; however, operation time was longer.
Ginsenoside Rh2 reverses cyclophosphamide-induced immune deficiency by regulating fatty acid metabolism
Authors: Qian Ying , Huang Rongrong , Li Senlin , Xie Rui , Qian Bei , Zhang Zijun , Li Lei , Wang Baotian , Tian Cheng , Yang Jian , Xiang Ming
Published: June 2019

Ginsenoside Rh2 (G-Rh2) has well-established potent antitumor activity; yet, the effects of G-Rh2 on immune and metabolism regulation in cancer treatment, especially non-small cell lung cancer (NSCLC) remain unclear. We showed that G-Rh2 had a synergistic antitumor effect with cyclophosphamide (CY) on mice with NSCLC, and improved the immune deficiency caused by CY. Consistently, G-Rh2 exhibited no inhibitory effect on tumor growth of T cells-deficient nude mice. Furthermore, G-Rh2 treatment triggered the oxidative decomposition of fatty acid (FA), suppressed FA synthesis, increased ketone level, and decreased glucocorticoid (CORT) secretion. G-Rh2 significantly down-regulated the expression of fatty acid synthase (FASN). Of note, in liver-specific FASN knockout mice G-Rh2 failed to show the same immune enhancement effects. Further mechanistic exploration revealed that G-Rh2 suppressed the expression and nuclear translocation of sterol regulatory element binding protein 1 (SREBP-1), and disturbed the SREBP-1–FASN interaction in vitro.
Synthesis of carbon‐14–labelled peptides
Authors: Dell'isola Antonio , Brown Rodney T. , Jones Stuart , Kitson Sean L. , Moody Thomas S. , Syvret Jason , Upeandran Balasubramaniam , Watters William H.
Published: June 2019

Carbon‐14 (14C)–labelled active pharmaceutical ingredients (APIs) and investigational medicinal products (IMPs) are required for phase 0/I to phase III mass balance and micro‐dosing clinical trials. In some cases, this may involve the synthesis of 14C‐labelled peptides, and the analysis can be performed by accelerated mass spectrometry (AMS). The 14C‐peptide is typically prepared by the solid‐phase peptide synthesis (SPPS) approach using custom‐made glassware for the key coupling steps. Further modification of the purified 14C‐peptide can then be performed.
Troubleshooting in PM Leadless: How to manage an indissoluble knot
Authors: Morani Giovanni , Bolzan Bruna , Tomasi Luca , Zimelli Emma , Marini Paola , Ribichini Flavio Luciano
Published: June 2019

A 77‐year‐old patient, with permanent atrial fibrillation, underwent successful Micra transcatheter pacing system (MTPS) implantation. Once begun the pull‐back of the tether, an increasing resistance was felt by the operator until complete blockage. A challenging recapture of MTPS into the delivery system was performed. The retrieved MTPS showed an indissoluble knot close to the docking button that blocked the running of the tether, and a long clot inside the delivery system. The new design of internal handle components of MTPS recently updated seems to favor clot formation. We suggest a reconsideration of the standard recommendations about delivery system flushing and design of the inner flushing tube system.
Factors associated with professional healthcare advice seeking in breast cancer–related lymphedema
Authors: Lin Chia‐Yu , Liu Hsueh‐Erh , Cheng Ming‐Huei
Published: June 2019

Objectives

This study aimed to identify the cognitive factors associated with the professional healthcare advice (PHCA) seeking behavior in breast cancer‐related lymphedema (BCRL).

Methods

From January 2018 to December 2018, patients with BCRL were prospectively enrolled for a cross‐sectional survey of lymphedema‐related perceived risks, lymphedema quality of life (LYMQoL), knowledge scale of lymphedema, and PHCA behavior at first clinical visit, 3 and 6 months postbaseline.

Results

A total of 180 patients including 100 (55.6%) patients underwent a vascularized lymph node transfer (VLNT) and 80 (44.4%) patients received compressive decongestive therapy (CDT) were enrolled. At 6 months of follow‐up, mean episodes of cellulitis (from 2.2 to 0.2 times/year), mean circumferential difference (7.8 ± 3.9%), wearing compression garments (from 29% to 0 %) in the VLNT group were statistically reduced than those in the CDT group (p = .01, <.01, and <.01, respectively). The overall LYMQoL had statistical improvement in VLNT group (p < .01). The short symptom duration, greater education level, less episodes of cellulitis, and higher knowledge of lymphedema were associated with increased adherence to PHCA (p = .03, .03, .02, and .01, respectively).

Conclusion

BCRL patients who sought PHCA had great control of lymphedema and improve their quality of life.
Perioperative anxiety and depression in patients undergoing abdominal surgery for benign or malignant disease
Authors: Williams Hannah , Jajja Mohammad Raheel , Baer Wendy , Balch Glen C. , Maithel Shishir K. , Patel Ankit D. , Patel Dipan , Patel Snehal G. , Stetler Jamil L. , Winer Joshua H. , Gillespie Theresa W. , Kooby David A.
Published: June 2019

Background and Objectives

Etiologies, levels, and associated factors of psychological distress in cancer patients facing surgery are poorly defined. We conducted a prospective comparative study of perioperative anxiety and depression in patients undergoing abdominal surgery for either malignant or benign disease.

Methods

With Institutional Review Board approval, patients consenting for surgery at our institution were enrolled. Surveys were completed at a preoperative visit and within 2 weeks of a postoperative appointment. Participants listed their top three sources of anxiety, and completed the Patient Health Questionnaire‐9 and the General Anxiety Disorder‐7.

Results

A total of 79 patients completed the preoperative assessment and 44 (58.7%) finished the postoperative survey. Forty‐one were male (51.9%), 12 (15.2%) had a psychiatric comorbidity (PSYHx), and 47 (59.5%) had cancer. Perioperative anxiety and depression did not differ by malignancy status. Patients were most concerned about surgery (22.5%) preoperatively and finances (27.9%) postoperatively. PSYHx, frailty, insurance status, and opioid use were all associated with perioperative psychological distress.

Conclusions

Cancer patients did not have significantly higher levels of perioperative psychological distress compared with benign controls. Socioeconomic worries are prevalent throughout the perioperative period, and efforts to alleviate distress should focus on providing adequate counseling.