bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic population structure and demography of an apex predator, the tiger shark Galeocerdo cuvier
Authors: Pirog Agathe , Jaquemet Sébastien , Ravigné Virginie , Cliff Geremy , Clua Eric , Holmes Bonnie J. , Hussey Nigel E. , Nevill John E. G. , Temple Andrew J. , Berggren Per , Vigliola Laurent , Magalon Hélène
Published: May 2019

Population genetics has been increasingly applied to study large sharks over the last decade. Whilst large shark species are often difficult to study with direct methods, improved knowledge is needed for both population management and conservation, especially for species vulnerable to anthropogenic and climatic impacts. The tiger shark, Galeocerdo cuvier, is an apex predator known to play important direct and indirect roles in tropical and subtropical marine ecosystems. While the global and Indo‐West Pacific population genetic structure of this species has recently been investigated, questions remain over population structure and demographic history within the western Indian (WIO) and within the western Pacific Oceans (WPO). To address the knowledge gap in tiger shark regional population structures, the genetic diversity of 286 individuals sampled in seven localities was investigated using 27 microsatellite loci and three mitochondrial genes (CR, COI, and cytb). A weak genetic differentiation was observed between the WIO and the WPO, suggesting high genetic connectivity. This result agrees with previous studies and highlights the importance of the pelagic behavior of this species to ensure gene flow. Using approximate Bayesian computation to couple information from both nuclear and mitochondrial markers, evidence of a recent bottleneck in the Holocene (2,000–3,000 years ago) was found, which is the most probable cause for the low genetic diversity observed. A contemporary effective population size as low as 111 [43,369] was estimated during the bottleneck. Together, these results indicate low genetic diversity that may reflect a vulnerable population sensitive to regional pressures. Conservation measures are thus needed to protect a species that is classified as Near Threatened.
Resolving the heading‐direction ambiguity in vertical‐beam radar observations of migrating insects
Authors: Hao Zhenhua , Drake Vincent Alistair , Taylor John R.
Published: May 2019

Each year, massive numbers of insects fly across the continents at heights of hundreds of meters, carried by the wind, bringing both environmental benefits and serious economic and social costs. To investigate the insects' flight behavior and their response to winds, entomological radar has proved to be a particularly valuable tool; however, its observations of insect orientation are ambiguous with regard to the head/tail direction, and this greatly hinders interpretation of the migrants' flight behavior.

We have developed two related methods of using wind data to resolve the head/tail ambiguity, and we have compared their outputs with those from simply assigning the heading direction to be that which is closer to the track direction. We applied all three methods to observations of Australian plague locust migrations made with an insect monitoring radar.

For the study dataset, some of the headings selected by the simpler method are shown to be clearly incorrect. The two new methods generally agree and reveal a significantly different, and presumably more accurate, relationship of heading direction to track direction. However, use of these methods leads to quite a large proportion of the sample being lost because the wind values, which derive from a regional‐scale numerical model, are shown to be incompatible with the radar observations. This exploratory study has moreover demonstrated that locusts are frequently oriented at a large angle to their track and that quite often their movement is at least slightly tailfirst.

Both new methods appear to be a significant improvement on the simpler method. As well as providing an accurate representation of migratory flight behavior, they allow occasions when the model wind values are unreliable to be eliminated from the data sample.
Occupied and abandoned structures from ecosystem engineering differentially facilitate stream community colonization
Authors: Tumolo Benjamin B. , Albertson Lindsey K. , Cross Wyatt F. , Daniels Melinda D. , Sklar Leonard S.
Published: May 2019

Ecosystem engineers transform habitats in ways that facilitate a diversity of species; however, few investigations have isolated short‐term effects of engineers from the longer‐term legacy effects of their engineered structures. We investigated how initial presence of net‐spinning caddisflies (Hydropsychidae) and their structures that provide and modify habitat differentially influence benthic community colonization in a headwater stream by conducting an in situ experiment that included three treatments: (1) initial engineering organism with its habitat modification structure occupied (hereafter caddisfly); (2) initial habitat modification structure alone (hereafter silk); and (3) a control with the initial absence of both engineer and habitat modification structure (hereafter control). Total invertebrate colonization density and biomass was higher in caddisfly and silk treatments compared to controls (~25% and 35%, respectively). However, finer‐scale patterns of taxonomy revealed that density for one of the taxa, Chironomidae, was ~19% higher in caddisfly compared to silk treatments. Additionally, conspecific biomass was higher by an average of 50% in silk treatments compared to controls; however, no differences in Hydropsyche sp. biomass were detected between caddisfly treatments and controls, indicating initially abandoned silk structures elevated conspecific biomass. These findings suggest that the positive effects of the habitat modification structures that were occupied for the entirety of the experiment may outweigh any potential negative impacts from the engineer, which is known to be territorial. Importantly, these results reveal that the initial presence of the engineer itself may be important in maintaining the ecological significance of habitat modifications. Furthermore, the habitat modifications that were initially abandoned (silk) had similar positive effects on conspecific biomass compared to caddisfly treatments, suggesting legacy effects of these engineering structures may have pertinent intraspecific feedbacks of the same magnitude to that of occupied habitat modifications. Elucidating how engineers and their habitat modifications differentially facilitate organisms will allow for a clearer mechanistic understanding of the extent to which animal engineers and their actions influence aspects of community organization such as colonization.
Engineering antigen‐specific NK cell lines against the melanoma‐associated antigen tyrosinase via TCR gene transfer
Authors: Parlar Ayhan , Sayitoglu Ece Canan , Ozkazanc Didem , Georgoudaki Anna‐Maria , Pamukcu Cevriye , Aras Mertkaya , Josey Benjamin J. , Chrobok Michael , Branecki Suzanne , Zahedimaram Pegah , Ikromzoda Lolai , Alici Evren , Erman Batu , Duru Adil D. , Sutlu Tolga
Published: May 2019

Introduction of Chimeric Antigen Receptors to NK cells has so far been the main practical method for targeting NK cells to specific surface antigens. In contrast, T cell receptor (TCR) gene delivery can supply large populations of cytotoxic T‐lymphocytes (CTL) targeted against intracellular antigens. However, a major barrier in the development of safe CTL‐TCR therapies exists, wherein the mispairing of endogenous and genetically transferred TCR subunits leads to formation of TCRs with off‐target specificity. To overcome this and enable specific intracellular antigen targeting, we have tested the use of NK cells for TCR gene transfer to human cells. Our results show that ectopic expression of TCR α/β chains, along with CD3 subunits, enables the functional expression of an antigen‐specific TCR complex on NK cell lines NK‐92 and YTS, demonstrated by using a TCR against the HLA‐A2‐restricted tyrosinase‐derived melanoma epitope, Tyr368‐377. Most importantly, the introduction of a TCR complex to NK cell lines enables MHC‐restricted, antigen‐specific killing of tumor cells both in vitro and in vivo. Targeting of NK cells via TCR gene delivery stands out as a novel tool in the field of adoptive immunotherapy which can also overcome the major hurdle of “mispairing” in TCR gene therapy.
Selective Preparation of Sterically Encumbered Diaryltin Dihalides from Grignard Reagents via Salt Metathesis and Halide Exchange
Authors: Steller Beate G. , Fischer Roland C.
Published: May 2019

A general route for the selective preparation of diaryltin dichlorides, dibromides, and diiodides from readily accessible but sterically demanding, 2,6‐disubstituted or 2,4,6‐trisubstituted aryl Grignard reagents ArylMgBr and tin tetrachloride was developed. During work‐up, the initially obtained mixture of halides is converted into a single species. The thus obtained diaryltin dichlorides were reacted to yield the dihydrides Aryl2SnH2. These exhibit high thermal stability and moderate oxygen tolerance.
Pseudo‐Solid‐State Suzuki–Miyaura Reaction and the Role of Water Formed by Dehydration of Arylboronic Acids
Authors: Pentsak Evgeniy O. , Ananikov Valentine P.
Published: May 2019

Solvent‐free reactions belong to a very attractive area of organic chemistry. The solvent‐free Suzuki–Miyaura coupling is of special importance due to the problem of catalyst leaching in the presence of a solvent. This study investigates the course of reaction of solid aryl halides with arylboronic acids in the absence of a solvent and without any liquid additives. For the first time, a number of important conditions for performing a solid‐state Suzuki–Miyaura reaction were analyzed in details. The results indicate a prominent role of water, which is formed as a by‐product in the side reaction of arylboronic acid trimerization. Electron microscopy study revealed surprising changes occurring within the reaction mixture during the reaction and indicated the formation of spherical nano‐sized particles containing the reaction product. Catalyst recycling was easily performed in the developed system and the product was isolated by sublimation, thus providing a possibility to completely avoid the use of solvents at all stages.
Scalable and Straightforward Synthesis of All Isomeric (Cyclo)alkylpiperidines
Authors: Subota Andrii I. , Lutsenko Anton O. , Vashchenko Bohdan V. , Volochnyuk Dmitriy M. , Levchenko Vitalina , Dmytriv Yurii V. , Rusanov Eduard B. , Gorlova Alina O. , Ryabukhin Sergey V. , Grygorenko Oleksandr O.
Published: May 2019

An efficient approach towards introducing (cyclo)alkyl substituents at C‐2, C‐3 or C‐4 positions of the piperidine ring was described. The method relied on the straightforward two‐step reaction sequence based on the formal sp3–sp3 retrosynthetic disconnection. The procedure commenced with selective directed ortho metalation of 2‐ and 3‐bromopyridine, followed by reaction with aldehydes or ketones. The optimized methods were developed for all three isomers of hydroxyalkyl‐substituted pyridines, which were synthesized in 28–84 % overall yield (20 examples). Catalytic hydrogenation of these adducts could be performed selectively with or without retention of the hydroxyl group in their molecules, so that either (cyclo)alkylpiperidines (14 examples) or the corresponding saturated amino alcohols (16 examples) were obtained (28–96 % and 82–96 % yield, respectively). After minor modifications, the developed method was also implemented in a flow reactor and a 5 L autoclave, which allowed for the preparation of up to 0.5 kg of the representative (cyclo)alkylpiperidines.
Cp*IrIII‐Catalyzed [3+2] Annulations of N‐Aryl‐2‐aminopyrimidines with Sulfoxonium Ylides to Access 2‐Alkyl Indoles Through C–H Bond Activation
Authors: Luo Yi , Guo Lingmei , Yu Xinling , Ding Haosheng , Wang Huijing , Wu Yong
Published: May 2019

The iridium‐catalyzed aromatic C–H alkylation followed by intramolecular annulation reactions between N‐aryl‐2‐aminopyridines and sulfoxonium ylides for the synthesis of 2‐alkyl indoles is described. This highly efficient and step‐economical cyclization reaction displays excellent functional group compatibility and regioselectivity. Afterwards, the directing group in C–H alkylation can be readily removed to obtain the free N–H indoles. Thus, the sulfoxonium ylide, a carbene precursor, is proved as a useful surrogate of diazo compounds in C–H activation chemistry.
Palladium‐Catalyzed Carboxy‐Alkynylation of Propargylic Amines Using Carbonate Salts as Carbon Dioxide Source
Authors: Greenwood Phillip D. G. , Waser Jerome
Published: May 2019

A palladium‐catalyzed multicomponent reaction of propargylic amines, alkynyl bromides and cesium hydrogen carbonate to access oxazolidinones is reported. In contrast to previous reports, only a slight excess of cesium hydrogen carbonate is used as a surrogate of carbon dioxide. The reaction gives access to oxazolidinones bearing alkyl‐ and aryl polysubstituted enynes in good yield and very high E stereoselectivity.
Evolution toward the utilization of mango leaves as lignocellulosic material in bioethanol production: A review of process parameter and integrated technologies
Authors: Tarrsini Mahadevan , Teoh Yi P. , Shuit Siew H. , Ooi Zhong X. , Ng Qi H. , Kunasundari Balakrishnan
Published: May 2019

Recently, the production of bioethanol is shifted to secondary bioethanol which is produced from nonedible lignocellulosic feedstock to avoid the food versus fuel issue. Mango leaves, a kind of nonedible lignocellulosic material (LCM) that possess a relatively 80.7% of holocellulose (inclusive of cellulose and hemicellulose), appear to be potential candidate to serve as cheap substrate source for bioethanol production. Hence, the objective of this article is to present the current scenario and the potential of mango leaves as a substrate source for bioethanol production. This article also provides an overview on various process parameters such as temperature, pH, substrate concentration, and incubation time that required to be optimized for an efficient fermentation process in the bioethanol production from LCM. Apart from that, several integrated fermentation technologies in bioethanol production which include separate hydrolysis and fermentation, simultaneous saccharification and fermentation, simultaneous saccharification and co‐fermentation, and consolidated bioprocessing will also be discussed in this article. Based on the findings, it is clear that mango leaves have the potential to serve as feedstock for bioethanol production.
Evaluation of the single and combined antibacterial efficiency of essential oils for controlling Campylobacter coli, Campylobacter jejuni, Escherichia coli, Staphylococcus aureus, and mixed cultures
Authors: Mutlu‐Ingok Aysegul , Tasir Seda , Seven Ayse , Akgun Necibe , Karbancioglu‐Guler Funda
Published: May 2019

Single and combined antibacterial activities of cumin, cardamom, and dill weed essential oils against Campylobacter jejuni, Campylobacter coli, Escherichia coli, Staphylococcus aureus, and mixed cultures were determined by using the broth microdilution method for determining minimum inhibition concentrations. Among the bacteria tested, C. coli and C. jejuni were generally more susceptible to essential oils, with lower minimum inhibition concentrations. The minimum inhibition concentration values were obtained against Gram‐negative and Gram‐positive bacteria tested within the range of 0.012–15.00 and 3.75–15.00 μL/mL, respectively. Fractional inhibitory concentrations (FICs) were also calculated to evaluate the antimicrobial activities of essential oil combinations. Although the combined effects of essential oils changed depending on the strain and the type of essential oils used, generally the use of combinations increased the efficacy of the essential oils. Interestingly, according to the FIC index, the most synergetic effect was against C. coli and C. jejuni. This study has demonstrated the potential use of cardamom, cumin, and dill weed essential oils, and their combinations, against important pathogenic bacteria and their mixed cultures.
GPR124 regulates microtubule assembly, mitotic progression, and glioblastoma cell proliferation
Authors: Cherry Allison E. , Vicente Juan Jesus , Xu Cong , Morrison Richard S. , Ong Shao‐En , Wordeman Linda , Stella Nephi
Published: May 2019

GPR124 is involved in embryonic development and remains expressed by select organs. The importance of GPR124 during development suggests that its aberrant expression might participate in tumor growth. Here we show that both increases and decreases in GPR124 expression in glioblastoma cells reduce cell proliferation by differentially altering the duration mitotic progression. Using mass spectrometry‐based proteomics, we discovered that GPR124 interacts with ch‐TOG, a known regulator of both microtubule (MT)‐plus‐end assembly and mitotic progression. Accordingly, changes in GPR124 expression and ch‐TOG similarly affect MT assembly measured by real‐time microscopy in cells. Our study describes a novel molecular interaction involving GPR124 and ch‐TOG at the plasma membrane that controls glioblastoma cell proliferation by modifying MT assembly rates and controlling the progression of distinct phases of mitosis.
The trajectory of C‐reactive protein serum levels in older hip fracture patients with postoperative delirium
Authors: Slor Chantal J. , Witlox Joost , Adamis Dimitrios , Jansen Rene W.M.M. , Houdijk Alexander P.J. , van Gool Willem A. , de Jonghe Jos F.M. , Eikelenboom Piet
Published: May 2019

Objectives

Important precipitating risk factors for delirium such as infections, vascular disorders, and surgery are accompanied by a systemic inflammatory response. Systemic inflammatory mediators can induce delirium in susceptible individuals. Little is known about the trajectory of systemic inflammatory markers and their role in the development and outcome of delirium.

Methods

This is a prospective cohort study of older patients undergoing acute surgery for hip fracture.

Baseline characteristics were assessed preoperatively. During hospital admission, presence of delirium was assessed daily according to the Confusion Assessment Method criteria. This study compared the trajectory of serum levels of the C‐reactive protein (CRP) between people with and without postoperative delirium. Blood samples were taken at baseline and at postoperative day 1 through postoperative day 5.

Results

Forty‐one out of 121 patients developed postoperative delirium after hip fracture surgery. Longitudinal analysis of the trajectory of serum CRP levels using the Generalized Estimating Equations (GEE) method identified that higher CRP levels were associated with postoperative delirium. CRP levels were higher from postoperative day 2 through postoperative day 5. No significant differences in serum CRP levels were found when we compared patients with short (1‐2 days) and more prolonged delirium (3 days or more).

Conclusions

Delirium is associated with an increased systemic inflammatory response, and our results suggest that CRP plays a role in the underlying (inflammatory‐vascular) pathological pathway of postoperative delirium.
Somatosensory cortical representation of the body size
Authors: Giurgola Serena , Pisoni Alberto , Maravita Angelo , Vallar Giuseppe , Bolognini Nadia
Published: May 2019

The knowledge of the size of our own body parts is essential for accurately moving in space and efficiently interact with objects. A distorted perceptual representation of the body size often represents a core diagnostic criterion for some psychopathological conditions. The metric representation of the body was shown to depend on somatosensory afferences: local deafferentation indeed causes a perceptual distortion of the size of the anesthetized body part. A specular effect can be induced by altering the cortical map of body parts in the primary somatosensory cortex. Indeed, the present study demonstrates, in healthy adult participants, that repetitive Transcranial Magnetic Stimulation to the somatosensory cortical map of the hand in both hemispheres causes a perceptual distortion (i.e., an overestimation) of the size of the participants' own hand (Experiments 1–3), which does not involve other body parts (i.e., the foot, Experiment 2). Instead, the stimulation of the inferior parietal lobule of both hemispheres does not affect the perception of the own body size (Experiment 4). These results highlight the role of the primary somatosensory cortex in the building up and updating of the metric of body parts: somatosensory cortical activity not only shapes our somatosensation, it also affects how we perceive the dimension of our body.
Multi‐target attention and visual short‐term memory capacity are closely linked in the intraparietal sulcus
Authors: Praß Maren , de Haan Bianca
Published: May 2019

The existing literature suggests a critical role for both the right intraparietal sulcus (IPS) and the right temporo‐parietal junction (TPJ) in our ability to attend to multiple simultaneously‐presented lateralized targets (multi‐target attention), and the failure of this ability in extinction patients. Currently, however, the precise role of each of these areas in multi‐target attention is unclear. In this study, we combined the theory of visual attention (TVA) with functional magnetic resonance imaging (fMRI) guided continuous theta burst stimulation (cTBS) in neurologically healthy subjects to directly investigate the role of the right IPS and TPJ in multi‐target attention. Our results show that cTBS at an area of the right IPS associated with multi‐target attention elicits a reduction of visual short‐term memory capacity. This suggests that the right IPS is associated with a general capacity‐limited encoding mechanism that is engaged regardless of whether targets have to be attended or remembered. Curiously, however, cTBS to the right IPS failed to elicit extinction‐like behavior in our study, supporting previous suggestions that different areas of the right IPS may provide different contributions to multi‐target attention. CTBS to the right TPJ failed to induce a change in either TVA parameters or extinction‐like behavior.
Ipsilateral neck radiotherapy in N2b well‐lateralized tonsil cancer – Approach with caution
Authors: Maskell David , Buckley Hannah , Sission Katherine , Roques Tom , Geropantas Konstantinos
Published: May 2019

Background

Treatment of the uninvolved neck in well‐lateralized tonsillar squamous cell carcinoma is controversial. We became concerned after a number of contralateral neck recurrences (CNRs) in patients receiving ipsilateral radiotherapy (RT).

Methods

This is a single center retrospective series including patients with well‐lateralized tonsillar cancer treated with ipsilateral neck RT between 2004 and 2011.

Results

We identified 53 patients treated with ipsilateral neck RT during the study period. The rate of CNR was 7.5% (4 of 53). All four patients had p16‐positive, T1, N2b, M0 tumors. The subgroup of patients with N2b disease (28 of 53) had a CNR of 14.3%. We subsequently switched to treat patients with N2b with bilateral neck RT. We analyzed the outcomes of 23 patients with N2b treated with bilateral neck intensity‐modulated RT (IMRT) and observed no CNRs.

Conclusions

We observed a higher than expected rate of CNR in the N2b population. Bilateral neck IMRT for these patients represents a safe alternative.
Hepatocellular Carcinoma Xenografts Established From Needle Biopsies Preserve the Characteristics of the Originating Tumors
Authors: Blumer Tanja , Fofana Isabel , Matter Matthias S. , Wang Xueya , Montazeri Hesam , Calabrese Diego , Coto‐Llerena Mairene , Boldanova Tujana , Nuciforo Sandro , Kancherla Venkatesh , Tornillo Luigi , Piscuoglio Salvatore , Wieland Stefan , Terracciano Luigi M. , Ng Charlotte K.Y. , Heim Markus H.
Published: May 2019

Hepatocellular carcinoma (HCC) is the second leading cause of cancer‐related deaths worldwide. Treatment options for patients with advanced‐stage disease are limited. A major obstacle in drug development is the lack of an in vivo model that accurately reflects the broad spectrum of human HCC. Patient‐derived xenograft (PDX) tumor mouse models could overcome the limitations of cancer cell lines. PDX tumors maintain the genetic and histologic heterogeneity of the originating tumors and are used for preclinical drug development in various cancers. Controversy exists about their genetic and molecular stability through serial passaging in mice. We aimed to establish PDX models from human HCC biopsies and to characterize their histologic and molecular stability during serial passaging. A total of 54 human HCC needle biopsies that were derived from patients with various underlying liver diseases and tumor stages were transplanted subcutaneously into immunodeficient, nonobese, diabetic/severe combined immunodeficiency gamma‐c mice; 11 successfully engrafted. All successfully transplanted HCCs were Edmondson grade III or IV. HCC PDX tumors retained the histopathologic, transcriptomic, and genomic characteristics of the original HCC biopsies over 6 generations of retransplantation. These characteristics included Edmondson grade, expression of tumor markers, tumor gene signature, tumor‐associated mutations, and copy number alterations. Conclusion: PDX mouse models can be established from undifferentiated HCCs, with an overall success rate of approximately 20%. The transplanted tumors represent the entire spectrum of the molecular landscape of HCCs and preserve the characteristics of the originating tumors through serial passaging. HCC PDX models are a promising tool for preclinical personalized drug development.
Mixed convective peristaltic flow of Eyring‐Prandtl fluid with chemical reaction and variable electrical conductivity in a tapered asymmetric channel
Authors: Eldabe Nabil T. , Moatimid Galal M. , ElShekhipy Abdelhafeez A. , Aballah Naglaa F.
Published: May 2019

The influence of inconstant electrical conductivity and chemical reaction on the peristaltic motion of non‐Newtonian Eyring‐Prandtl fluid inside a tapered asymmetric channel is investigated. The system is concerned by a uniform external magnetic field. The heat and mass transfer are considered. The problem is controlled mathematically by a system of nonlinear partial differential equations which describe the velocity, temperature, and nanoparticle concentration of the fluid. By means of long wavelength and low Reynolds numbers, our system is simplified. It is explained by using the multi‐step differential transform method as a semi‐analytical technique. The distributions of velocity, temperature, nanoparticle concentration, as well as pressure gradient and pressure rise are obtained as a function of the physical parameters of the problem. The effects of these parameters on these distributions are deliberated numerically and illustrated graphically through a set of figures. The results indicate that the parameters play a significant role in controlling the velocity, temperature, nanoparticle concentration, pressure gradient, and pressure rise.
Stefan Blowing and Slip Effects on Unsteady Nanofluid Transport Past a Shrinking Sheet: Multiple Solutions
Authors: Dero Sumera , Uddin Md. Jashim , Rohni Azizah Mohd
Published: May 2019

The aim of a present article is to investigate the laminar unsteady two‐dimensional boundary layer flow of a nanofluid with Stefan blowing and slip effect. First, governing boundary layer equations are converted in the ordinary form of the differential equations (ODEs) from partial differential equations using appropriate coordinate transformations. The obtained ODEs are then solved by applying a shooting method with the Runge‐Kutta fourth order method by implementation of the Maple software. The influences of different controlling dimensionless parameters over the dimensionless velocity, temperature, concentration, friction factor, local heat as well as mass transfer have been discussed and represented by plots. It is found that there exist dual solutions for the different applied nanofluid parameters along with the blowing parameter. The results reveal that by increasing the values of the Brownian motion (Nb), thermophoresis (Nt) and blowing parameters (fw), the skin friction increases (decreases) in the first (second) solution.
Parental occupational exposure to pesticides, animals and organic dust and risk of childhood leukemia and central nervous system tumors: Findings from the International Childhood Cancer Cohort Consortium (I4C)
Authors: Patel Deven M. , Jones Rena R. , Booth Benjamin J. , Olsson Ann C. , Kromhout Hans , Straif Kurt , Vermeulen Roel , Tikellis Gabriella , Paltiel Ora , Golding Jean , Northstone Kate , Stoltenberg Camilla , Håberg Siri E. , Schüz Joachim , Friesen Melissa C. , Ponsonby Anne‐Louise , Lemeshow Stanley , Linet Martha S. , Magnus Per , Olsen Jørn , Olsen Sjurdur F. , Dwyer Terence , Stayner Leslie T. , Ward Mary H. ,   on behalf of the International Childhood Cancer Cohort Consortium
Published: May 2019

Parental occupational exposures to pesticides, animals and organic dust have been associated with an increased risk of childhood cancer based mostly on case–control studies. We prospectively evaluated parental occupational exposures and risk of childhood leukemia and central nervous system (CNS) tumors in the International Childhood Cancer Cohort Consortium. We pooled data on 329,658 participants from birth cohorts in five countries (Australia, Denmark, Israel, Norway and United Kingdom). Parental occupational exposures during pregnancy were estimated by linking International Standard Classification of Occupations‐1988 job codes to the ALOHA+ job exposure matrix. Risk of childhood (<15 years) acute lymphoblastic leukemia (ALL; n = 129), acute myeloid leukemia (AML; n = 31) and CNS tumors (n = 158) was estimated using Cox proportional hazards models to generate hazard ratios (HR) and 95% confidence intervals (CI). Paternal exposures to pesticides and animals were associated with increased risk of childhood AML (herbicides HR = 3.22, 95% CI = 0.97–10.68; insecticides HR = 2.86, 95% CI = 0.99–8.23; animals HR = 3.89, 95% CI = 1.18–12.90), but not ALL or CNS tumors. Paternal exposure to organic dust was positively associated with AML (HR = 2.38 95% CI = 1.12–5.07), inversely associated with ALL (HR = 0.55, 95% CI = 0.31–0.99) and not associated with CNS tumors. Low exposure prevalence precluded evaluation of maternal pesticide and animal exposures; we observed no significant associations with organic dust exposure. This first prospective analysis of pooled birth cohorts and parental occupational exposures provides evidence for paternal agricultural exposures as childhood AML risk factors. The different risks for childhood ALL associated with maternal and paternal organic dust exposures should be investigated further.
Screening for hereditary cancers in patients with endometrial cancer reveals a high frequency of germline mutations in cancer predisposition genes
Authors: Tian Wenjuan , Bi Rui , Ren Yulan , He Hongsheng , Shi Shanfu , Shan Boer , Yang Wentao , Wang Qing , Wang Huaying
Published: May 2019

As inherited genetic alterations are important etiological factors causing endometrial cancer (EC), our study aimed to outline the ethnic‐related prevalence and the associated clinical and biological characteristics of germline mutations in cancer predisposition genes in Chinese EC patients. One hundred ninety‐eight Chinese EC patients were screened for germline mutations in a panel of cancer susceptibility genes using next‐generation sequencing combined with multiplex ligation‐dependent probe amplification. First, we found that among patients under 50 years of age, 26% (18/69) carried germline genetic mutations, all involving mismatch repair (MMR) genes except for one mutation affecting BRCA1. Second, when we focused on Lynch syndrome (LS) with additional selected patients, 45 were identified to carry pathogenic mutations in MMR genes, with a higher frequency found in MSH2 and MSH6. We found that age at onset, personal and familial history together with immunohistochemical assay results were the most useful criteria for the diagnosis of LS although limitations in routine practice and the sensitivity and specificity of each parameter should be taken into account. One pathogenic mutation in the PALB2 gene was detected in a patient with no breast cancer in her family. Interestingly, we identified a family carrying pathogenic variant in both PMS2 and BRCA1 genes with distinct clinical phenotypes. Multigene panel testing should be recommended to patients based on their clinical information and tumor phenotype. Our study also showed the genetic complexity in EC, which requires further investigations.
Evaluation of cesarean delivery rates at three university hospital labor units using the Robson classification system
Authors: Zahumensky Jozef , Psenkova Petra , Nemethova Bianka , Halasova Dominika , Kascak Peter , Korbel Miroslav
Published: May 2019

Objective

To analyze the frequency of cesarean delivery using the Robson 10‐group classification.

Methods

A multicenter retrospective cohort study was conducted at three university hospital labor units in the Slovak Republic. The medical records of all women who gave birth at these centers from January 1 to December 31, 2017, were assessed.

Results

In all, 1437 of 3361 (42.8%), 729 of 2795 (26.1%), and 303 of 2080 (14.6%) births recorded at the three centers during the current study period were by cesarean delivery. Among the nulliparous term singleton vertex deliveries (Robson group 1 and 2), the frequency of cesarean delivery at the three centers was 613 of 1653 (37.1%), 278 of 1389 (20.0%), and 91 of 898 (10.1%). Among term multiparas with one fetus in a cephalic position and at least one previous cesarean delivery (Robson group 5), the frequency of cesarean delivery at the three centers was 405 of 418 (96.9%), 261 of 343 (76.1%), and 55 of 115 (47.8%).

Conclusion

Analysis of the frequency of cesarean delivery by Robson classification could help to identify possibilities for safely decreasing cesarean delivery rates in the clinic. Robson groups 1, 2, and 5 were the most modifiable groups.
Wide‐field optical property mapping and structured light imaging of the esophagus with spatial frequency domain imaging
Authors: Sweer Jordan A. , Chen Mason T. , Salimian Kevan J. , Battafarano Richard J. , Durr Nicholas J.
Published: May 2019

As the incidence of esophageal adenocarcinoma continues to rise, there is a need for improved imaging technologies with contrast to abnormal esophageal tissues. To inform the design of optical technologies that meet this need, we characterize the spatial distribution of the scattering and absorption properties from 471 to 851 nm of eight resected human esophagi tissues using Spatial Frequency Domain Imaging. Histopathology was used to categorize tissue types, including normal, inflammation, fibrotic, ulceration, Barrett's Esophagus and squamous cell carcinoma. Average absorption and reduced scattering coefficients of normal tissues were 0.211 ± 0.051 and 1.20 ± 0.18 mm−1, respectively at 471 nm, and both values decreased monotonically with increasing wavelength. Fibrotic tissue exhibited at least 68% larger scattering signal across all wavelengths, while squamous cell carcinoma exhibited a 36% decrease in scattering at 471 nm. We additionally image the esophagus with high spatial frequencies up to 0.5 mm−1 and show strong reflectance contrast to tissue treated with radiation. Lastly, we observe that esophageal absorption and scattering values change by an average of 9.4% and 2.7% respectively over a 30 minute duration post‐resection. These results may guide system design for the diagnosis, prevention and monitoring of esophageal pathologies.
Two‐photon excited lasing of Coumarin 307 for lysozyme amyloid fibrils detection
Authors: Hanczyc Piotr , Procyk Maciej , Radzewicz Czeslaw , Fita Piotr
Published: May 2019

Amyloid fibrils are a well‐recognized hallmark of neurodegeneration. A common approach to detect amyloid fibrils is staining with organic molecules and monitoring optical properties using fluorescence spectroscopy. However, the structural diversity of amyloids necessitates new sensitive methods and probes that can be reliably used to characterize them. Here, Coumarin 307 is applied for lysozyme fibrils detection by observation of laser action in the process of two‐photon excited stimulated emission. It is shown that the lasing threshold and spectrum significantly depend on the adopted structure (α‐helix or β‐sheet) of the lysozyme protein, whereas fluorescence spectrum is insensitive to the protein structure. The applications of coherent stimulated emission light that can be emitted deep inside a scattering medium can be particularly promising for imaging and therapeutic purposes in the neurodegeneration field. Two‐photon excitation with the near‐infrared light, which allows the deepest penetration of tissues, is an important advantage of the method.
Biomimetic proteoglycans diffuse throughout articular cartilage and localize within the pericellular matrix
Authors: Phillips Evan R. , Haislup Brett D. , Bertha Nicholas , Lefchak Maria , Sincavage Joseph , Prudnikova Katsiaryna , Shallop Brandon , Mulcahey Mary K. , Marcolongo Michele S.
Published: May 2019

Biomimetic proteoglycan (BPG) diffusion into articular cartilage has the potential to restore the lost proteoglycan content in osteoarthritic cartilage given these molecules mimic the structure and properties of natural proteoglycans. We examined the diffusion characteristics of BPGs through cartilage with the use of a custom‐made in vitro cartilage diffusion model in both normal bovine and human osteoarthritic cartilage explants. BPGs were introduced into the cartilage through essentially one‐dimensional diffusion using osteochondral plugs. The molecular diffusion was shown to be size and concentration dependent. Diffusion profiles were found over different diffusion time intervals and the profiles were fit to a nonlinear Fickian diffusion model. Steady state 011012‐7diffusion coefficients for BPGs were found to be 4.01 and 3.53 μm2/s for 180 and 1600 kDa BPGs, respectfully, and these values are similar to other large molecule diffusion in cartilage. In both bovine and osteoarthritic human cartilage, BPGs were found localized around the chondrocytes. BPG localization was examined by labeling collagen type VI and soaking 5 μm thick sections of cartilage with BPG solutions demonstrating that the BPGs diffused into the cartilage and preferentially localized alongside collagen type VI in the pericellular matrix.
Matrix metalloproteinases as target genes for gene regulatory networks driving molecular and cellular pathways related to a multistep pathogenesis of cerebrovascular disease
Authors: Polonikov Alexey , Rymarova Larisa , Klyosova Elena , Volkova Anastasia , Azarova Iuliia , Bushueva Olga , Bykanova Marina , Bocharova Iuliia , Zhabin Sergey , Churnosov Mikhail , Laskov Vitaliy , Solodilova Maria
Published: May 2019

The present study investigated a joint contribution of matrix metalloproteinases (MMPs) genes to ischemic stroke (IS) development and analyzed interactions between MMP genes and genome‐wide associated loci for IS. A total of 1288 unrelated Russians (600 IS patients and 688 healthy individuals) from Central Russia were recruited for the study. Genotyping of seven single nucleotide polymorphisms (SNPs) of MMP genes (rs1799750, rs243865, rs3025058, rs11225395, rs17576, rs486055, and rs2276109) and eight genome‐wide associated loci for IS were done using Taq‐Man–based assays and MALDI‐TOF mass spectrometry iPLEX platform, respectively. Allele − 799T at rs11225395 of the MMP8 gene was significantly associated with a decreased risk of IS after adjustment for sex and age (OR = 0.82; 95%CI, 0.70‐0.96; P = 0.016). The model‐based multifactor dimensionality reduction method has revealed 21 two‐order, 124 three‐order, and 474 four‐order gene‐gene (G×G) interactions models meaningfully (Pperm < 0.05) associated with the IS risk. The bioinformatic analysis enabled establishing the studied MMP gene polymorphisms possess a clear regulatory potential and may be targeted by gene regulatory networks driving molecular and cellular pathways related to the pathogenesis of IS. In conclusion, the present study was the first to identify an association between polymorphism rs11225395 of the MMP8 gene and IS risk. The study findings also indicate that MMPs deserve special attention as a potential class of genes influencing the multistep mechanisms of cerebrovascular disease including atherosclerosis in cerebral arteries, acute cerebral artery occlusion as well as the ischemic injury of the brain and its recovery.
Insight into the possible role of miR‐214 in primary osteoporosis via osterix
Authors: Mohamad Nesma , Nabih Enas S. , Zakaria Zeiad M. , Nagaty Magda M. , Metwaly Radwan G.
Published: May 2019

Osteoporosis is a bone disease characterized by chronic pain and recurrent fractures. Osterix is a transcription factor regulating bone formation. miR‐214 was found to have a role in skeletogenesis. Our goal was to investigate the possible role of miR‐214 in primary osteoporosis through osterix. Their expression was determined in bone samples obtained from primary osteoporotic patients (n = 26) and age‐ and sex‐matched controls (n = 14). Additionally, their expression was correlated to the laboratory and clinical parameters of the study participants. Differential expression of osterix and miR‐214 was detected in the osteoporotic group compared to controls. While miR‐214 was significantly higher, osterix was significantly lower. In primary osteoporotic patients, relative quantification value of osterix was positively correlated with sex, body mass index, and ionized calcium and negatively correlated with miR‐214 and C‐reactive protein. Thus, the role of miR‐214 in primary osteoporosis could be through inhibiting osterix expression in bones and therefore both miR‐214 and osterix could be targets for future therapeutic intervention.
Comprehensive circular RNA profiling reveals circ_0002060 as a potential diagnostic biomarkers for osteoporosis
Authors: Huang Yongping , Xie Jie , Li Erjun
Published: May 2019

Osteoporosis (OP) is a multifactorial and common bone disease worldwide. The clinical diagnosis and treatment of osteoporosis has limitations since changes in bone density occur slightly. Thus, it is critically needed to look for new biomarkers to identify and cure osteoporosis. CircRNAs are important molecular regulators that participate in various biological processes and present tremendous therapeutic potential. The role of circRNAs in osteoporosis remains largely unknown. Here, we explore the expression of circRNAs in osteoporosis using microarray analysis, and identify potential circRNAs associated with osteoporosis by quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) validation and statistical analysis in clinical samples. As a result, circ_0006873 and circ_0002060 were found to be significantly upregulated between nonosteoporotic controls and osteoporosis patients (n = 40, respectively). Pearson correlation analysis showed that the level of circ_0006873 and circ_0002060 were associated with the low‐bone mineral density in patients with osteoporosis. Furthermore, ROC analysis indicated that circ_0002060 showed potential diagnostic value for osteoporosis. Taken together results using bioinformatics, experimental analysis, and disease models, we revealed that circ_0002060 could be used as potential diagnostic biomarker and therapeutic target in osteoporosis
TiO2‐nanoparticles as efficient catalysts for the synthesis of pyridine dicarbonitriles
Authors: Shams‐Najafi Sayyed Jalal , Gholizadeh Mostafa , Ahmadpour Ali
Published: May 2019

The catalytic effects of two forms of nano‐TiO2, which are prepared via an ordinary or a magnetized process, are investigated in the synthesis of pyridine dicarbonitriles by one‐pot multicomponent reaction of 4‐methyl thiophenol, malononitrile, and aryl aldehydes. The results have shown that both prepared nano‐TiO2 exhibited high catalytic activities toward the synthesis of pyridine dicarbonitrile derivatives but the nano‐TiO2, which is prepared via a magnetized process, has shown better catalytic activity. Furthermore, this new catalytic method for the synthesis of pyridine dicarbonitriles provides rapid access to the desired compounds in high yields and so a simple work‐up procedure in the presence of water at room temperature. Therefore, this method represents a significant improvement incompatible of the other methods that are available for the synthesis of pyridine dicarbonitriles.
Evaluation of Elecsys HTLV‐I/II assay in comparison with ARCHITECT rHTLV‐I/II assay with Korean samples
Authors: Yun Seung Gyu , Kim Sang‐wook , Sohn Ji Yeon , Cho Yunjung
Published: May 2019

Background

The seroprevalence rate of human T‐lymphotropic virus I and II (HTLV‐I/II) in Korean blood donors has been known as 0.004%, and HTLV‐I/II Ab screening test has been performed since 2008 in Korea. Korea Ministry of Food and Drug Safety (MFDS) approved two chemiluminescent microparticle immunoassays (CMIA) for testing HTLV‐I/II antibody, ABBOTT PRISM HTLV‐I/HTLV‐II and ARCHITECT rHTLV‐I/II. A multicenter performance evaluation study in Europe and Japan was carried out with the new electrochemiluminescence immunoassay (ECLIA) for HTLV‐I/II antibody detection, Elecsys HTLV‐I/II assay which launched in 2017, but not in Korea. We aimed to evaluate the clinical performance of Elecsys HTLV‐I/II assay in comparison with ARCHITECT rHTLV‐I/II for the detection of HTLV‐I/II antibody with Korean samples.

Methods

For sensitivity evaluation, 100 HTLV‐I/II‐positive Korean standards from Korean Red Cross and two HTLV‐II‐positive samples that were purchased from Seracure were used. For the specificity, 500 potential donor specimens from Korea University Hospital healthcare center were used. All the samples were simultaneously analyzed by the two HTLV‐I/II assays, Elecsys HTLV‐I/II assay and ARCHITECT rHTLV‐I/II assay.

Results

Elecsys HTLV‐I/II assay and ARCHITECT rHTLV‐I/II assay showed a complete agrement. Elecsys HTLV‐I/II assay showed 100% sensitivity (95% CI: 96.38‐100.0) and specificity (95% CI: 99.26‐100.0).

Conclusions

Elecsys HTLV‐I/II assay is as reliable as ARCHITECT rTHLV‐I/II assay, and can be used as a screening test for HTLV‐I/II in Korea.
Zinc chelator TPEN induces pancreatic cancer cell death through causing oxidative stress and inhibiting cell autophagy
Authors: Yu Zhen , Yu Ze , Chen ZhenBao , Yang Lin , Ma MingJun , Lu ShouNan , Wang ChunSheng , Teng ChunBo , Nie YuZhe
Published: May 2019

The essential trace element zinc (Zn) is widely required in cellular functions, and abnormal Zn homeostasis causes a variety of health problems including immunodeficiency and sensory dysfunctions. Previous studies had shown that Zn availability was also important for tumor growth and progression. The aim of the present study was to investigate the potential mechanisms of N,N,N,N‐Tetrakis(2‐pyridylmethyl)‐ethylenediamine (TPEN) (a membrane permeable zinc chelator) induced pancreatic cancer cell death. The text of inductively coupled plasma‐mass spectrometry (ICP‐MS) showed in human pancreatic cancer samples that the zinc content in cancer was higher than that in adjacent tissues. The pancreatic cancer cell lines Panc‐1, 8988T, BxPc‐3, and L3.6 were used in this study. Our results indicated that TPEN markedly induced cell death, via increasing reactive oxygen species (ROS) and restraining autophagy. Our data also indicated that TPEN‐stimulated mitochondrial metabolism produced much ROS. Meanwhile, TPEN reduced the levels of glutathione (GSH) and triggered ROS outbreak, which were the main causes of cell death. In addition, cell autophagy was significantly depressed in Panc‐1 cells treated by TPEN, which was due to the ability of disrupting lysosomal by TPEN. Thus, we thought zinc depletion by TPEN was a potential therapeutic strategy for pancreatic cancer.