bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic diversity of Solanum elaeagnifolium, an invasive problematic weed in Jordan
Authors: Qasem J R , Al Abdallat A M , Hasan S M
Published: April 2019

Solanum elaeagnifolium (silverleaf nightshade) is a problematic weed that is common in Jordan and difficult to control. The weed exhibits distinct morphological variations in growth habit, leaf shape, leaf margins, flower colour and presence or absence of spines between individuals among and within populations suggesting genetic differences. Genetic variations among 61 samples of S. elaeagnifolium collected from heavily infested sites in the central Jordan Valley were investigated using six simple sequence repeat (SSR) markers and eight amplified fragment length polymorphism (AFLP) primer combinations. Results showed that 111 out of 675 AFLP bands were polymorphic generating polymorphism information content (PIC) of 38.0%, while 23 SSR polymorphic alleles were detected generating a PIC of 30.8%. Phylogenetic analysis using RaxML software identified four major clades with a clear clustering of the samples with their collection sites. Genetic analysis using both techniques revealed high level of genetic diversity among S. elaeagnifolium samples collected from a small geographical area indicating that a range of genetic diversity may be detected in weed populations across the country that may complicate its management.
Heat Transfer Characteristics and Flow Pattern Visualization for Flow Boiling in a Vertical Narrow Microchannel
Authors: Zhou Kan , Zhu Hua , Li Wei , Li Junye , Sheng Kuang , Shao Shuai , Li Haiwang , Tao Zhi
Published: April 2019

Recently, microchannel heat sinks have been emerged as a kind of high performance cooling scheme to meet the heat dissipation requirement of electronics packaging and integration. In this study, an experimental investigation of subcooled flow boiling in a high-aspect-ratio rectangular microchannel was conducted with de-ionized water as the working fluid. In the experimental operations, the mass flux was varied from 200 to 400 kg/m2s and the imposed heat flux from 3 to 20 W/cm2 while the fluid inlet temperature was regulated constantly at 90 °C. The boiling curves, onset of nucleate boiling (ONB), and flow patterns of subcooled flow boiling were investigated with the aid of instrumental measurements and a high-speed camera. The slope of the boiling curves increased sharply once the superheat needed to initiate the onset of nucleate boiling was attained, with lower superheat required of boiling incipience for lower mass fluxes. Meanwhile, the initiative superheat and heat flux of onset of nucleate boiling were compared with the existing correlations in the literature with good agreement. As for the flow visualization images, slug flow and reverse backflow were observed, where transient local dryout as well as rewetting occurred. A facile image processing tool was developed to profile the transient development and progression of the liquid–vapor interface and partial dryout patches in microchannels, which proved that the physical quantities of bubble dynamics for the elongation period during subcooled boiling could be well detected and calculated.
Development of Molecular Methods for Rapid Differentiation of Mycoplasma gallisepticum Vaccine Strains from Field Isolates
Authors: Sulyok Kinga M. , Kreizinger Zsuzsa , Bekő Katinka , Forró Barbara , Marton Szilvia , Bányai Krisztián , Catania Salvatore , Ellis Christine , Bradbury Janet , Olaogun Olusola M. , Kovács Áron B. , Cserép Tibor , Gyuranecz Miklós
Published: April 2019

Mycoplasma gallisepticum
is among the most economically significant mycoplasmas causing production losses in poultry. Seven melt-curve and agarose gel-based mismatch amplification mutation assays (MAMAs) and one PCR are provided in the present study to distinguish the
M. gallisepticum
vaccine strains and field isolates based on mutations in the
crmA
,
gapA
,
lpd, plpA
,
potC
,
glpK
, and
hlp2
genes.
Characterizing a Murine Model for Astrovirus Using Viral Isolates from Persistently Infected Immunocompromised Mice
Authors: Cortez Valerie , Sharp Bridgett , Yao Jiangwei , Livingston Brandi , Vogel Peter , Schultz-Cherry Stacey
Published: April 2019

Astroviruses are widespread in both birds and mammals; however, little is known about the pathogenesis and the immune response to the virus due to the lack of a well-characterized small-animal model. Here we describe two distinct strains of murine astrovirus that cause infections in immunocompetent mice that mirror aspects of asymptomatic human infections, including minimal pathology and short-lived immunity. However, we noted that the duration of infection differed greatly between the strains, highlighting an important facet of these viruses that was not previously appreciated. The ubiquitous nature and diversity of murine astroviruses coupled with the continuous likelihood of reinfection raise the possibility of viral interference with other mouse models of disease.
Effects of three intravitreal injections of aflibercept on the ocular circulation in eyes with age-related maculopathy
Authors: Mursch-Edlmayr Anna Sophie , Luft Nikolaus , Podkowinski Dominika , Ring Michael , Schmetterer Leopold , Bolz Matthias
Published: April 2019

Aims

To investigate changes in ocular perfusion following three consecutive intravitreal injections with aflibercept for treatment of neovascular age-related macular degeneration (nAMD).

Methods

The study included 20 eyes from 20 Caucasian patients with unilateral nAMD and 20 fellow eyes. All nAMD eyes were treated with standard intravitreal injection of aflibercept (IVA; 2 mg). Measurements of ocular perfusion at the optic nerve head (ONH) and the choroid were performed with laser speckle flowgraphy (LSFG). Measurements were conducted at baseline, 1 week after the first injection, at the time point of the second and third injection as well as 1 month after the third injection.

Results

In treated eyes, mean blur rate (the main output parameter of LSFG) in the ONH microvasculature and in the choroid was significantly reduced 1 week after the first IVA treatment. The effect persisted throughout the entire follow-up period (p<0.001). No change in ocular perfusion was observed in fellow eyes.

Conclusions

IVA for treatment of nAMD leads to a reduction in perfusion of the ONH and the choroid in the treated eye with no apparent effect on the fellow eye.
Using Mendelian randomisation to assess causality in observational studies
Authors: Pagoni Panagiota , Dimou Niki L , Murphy Neil , Stergiakouli Evie
Published: April 2019

Objective

Mendelian randomisation (MR) is a technique that aims to assess causal effects of exposures on disease outcomes. The paper aims to present the main assumptions that underlie MR, the statistical methods used to estimate causal effects and how to account for potential violations of the key assumptions.

Methods

We discuss the key assumptions that should be satisfied in an MR setting. We list the statistical methodologies used in two-sample MR when summary data are available to estimate causal effects (ie, Wald ratio estimator, inverse-variance weighted and maximum likelihood method) and identify/adjust for potential violations of MR assumptions (ie, MR-Egger regression and weighted Median approach). We also present statistical methods and graphical tools used to evaluate the presence of heterogeneity.

Results

We use as an illustrative example of a published two-sample MR study, investigating the causal association of body mass index with three psychiatric disorders (ie, bipolar disorder, schizophrenia and major depressive disorder). We highlight the importance of assessing the results of all available methods rather than each method alone. We also demonstrate the impact of heterogeneity in the estimation of the causal effects.

Conclusions

MR is a useful tool to assess causality of risk factors in medical research. Assessment of the key assumptions underlying MR is crucial for a valid interpretation of the results.
Psychosocial and sexual characteristics associated with sexualised drug use and chemsex among men who have sex with men (MSM) in the UK
Authors: Hibbert Matthew Peter , Brett Caroline E , Porcellato Lorna A , Hope Vivian D
Published: April 2019

Objective

To understand how the emerging public health issue of chemsex relates to broader patterns of sexualised drug use (SDU) among men who have sex with men (MSM), which has been understudied.

Methods

Potential participants were invited to take part in an anonymous, cross-sectional online survey through Facebook advertising and community organisations’ social media posts (April–June 2018). Multivariable logistic regression was used to compare MSM who engaged in recent SDU (past 12 months) with those who did not, and those who engaged in chemsex (γ-hydroxybutyrate/γ-butyrolactone, crystal methamphetamine, mephedrone, ketamine) with those who engaged in other SDU (eg, poppers, cocaine, cannabis).

Results

Of the 1648 MSM included, 41% reported recent SDU; 15% of these (6% of total, n=99) reported chemsex. Factors associated with SDU were recent STI diagnosis (aOR=2.44, 95% CI 1.58 to 3.76), sexual health clinic attendance (aOR=2.46, 95% CI 1.90 to 3.20), image and performance-enhancing drug use (aOR=3.82, 95% CI 1.87 to 7.82), greater number of condomless anal male partners, lower satisfaction with life and greater sexual satisfaction. Predictors of chemsex compared with other SDU were not being UK-born (aOR=2.02, 95% CI 1.05 to 3.86), living in a densely populated area (aOR=2.69, 95% CI 1.26 to 5.74), low sexual self-efficacy (aOR=4.52, 95% CI 2.18 to 9.40) and greater number of condomless anal male partners. Living with HIV, taking pre-exposure prophylaxis (PrEP), and experiencing or being unsure of experiencing sexual contact without consent were significantly associated with SDU and chemsex in bivariate analyses but not in the multivariable.

Conclusion

Health and behavioural differences were observed between MSM engaging in chemsex, those engaging in SDU and those engaging in neither. While some MSM engaging in chemsex and SDU appeared content with these behaviours, the association with life satisfaction and sexual self-efficacy indicates psychosocial support is needed for some. The association with sexual risk and sexual consent also indicates the importance of promoting harm reduction among this population (eg, condoms, PrEP, drug knowledge).
Partition function for a mass dimension one fermionic field and the dark matter halo of galaxies
Authors: Pereira S. H. , Costa Richard S.
Published: April 2019

This work studies the finite temperature effects of a mass dimension one fermionic field, sometimes called Elko field. The equilibrium partition function was calculated by means of the imaginary time formalism and the result obtained was the same for a Dirac fermionic field, even though the Elko field does not satisfy a Dirac-like equation. The high and low temperature limits were obtained, and for the last case the degeneracy pressure due to Pauli exclusion principle can be responsible for the dark matter halos around galaxies to be greater than or of the same order of the galaxy radius. Also, for a light particle of about 1.0 eV and a density of just 1 particle per cubic centimeter, the value of the total dark matter mass due to Elko particles is of the same order of a typical galaxy. Such a result satisfactorily explains the dark matter as being formed just by Elko fermionic particles and also the existence of galactic halos that go beyond the observable limit.
Collision of particles near charged MSW black hole in 2 + 1 dimensions
Authors: Saha Pameli , Debnath Ujjal
Published: April 2019

Here, we explore the dynamics of particle near the horizon of charged Mandal–Sengupta–Wadia (MSW) black hole in 2 + 1 dimensions. We analyze angular momentum and potential energy for null and time-like geodesics. We also appraise the high center-of-mass energy of coming particles from rest at infinity near the horizon of the charged MSW black hole in 2 + 1 dimension for the extremal case. Finally, we study the ISCO and MBCO radii for this type of black hole.
Detailed study of the QCD Equation of State of a colorless partonic plasma in finite volume
Authors: Ladrem Madjid Lakhdar Hamou , Ahmed Mohammed Abdulmalek Abdulraheem , Cherif Salah , Alfull Zainab Zaki Mohammed , Almarashi Mosleh M.
Published: April 2019

The color confinement in Quantum Chromodynamics (QCD) remains an interesting and intriguing phenomenon. It is considered as a very important nonperturbative effect to be taken into account in all models intended to describe the QCD many-parton system. During the deconfinement phase transition, the non-Abelian character of the partonic plasma manifests itself in an important manner. A direct consequence of color confinement is that all states of any partonic system must be colorless and the requirement of the colorlessness condition is more than necessary. Indeed, the colorless state is a result of the multiparton interactions, from which collective phenomena can emerge, inducing strong correlations and giving rise to a long-range order of liquid-like phase, a behavior fundamentally different from that of a conformal ideal gas. Within our Colorless QCD MIT-Bag Model and using the [Formula: see text]-method, three Thermal Response Functions, related to the Equation of State, like pressure [Formula: see text], sound velocity [Formula: see text] and energy density [Formula: see text] are calculated and studied as functions of temperature [Formula: see text] and volume [Formula: see text]. Also and in the same context, two relevant correlation forms [Formula: see text] and [Formula: see text] are calculated and studied intensively as functions of [Formula: see text] at different volumes. A detailed comparative study between our results and those obtained from lattice QCD simulation, hot QCD and other phenomenological models is carried out. We find that the Liquid Partonic Plasma Model is the model which fits our Equation of State very well, in which the Bag constant term is revealed very important. Our Colorless Partonic Plasma, just beyond the finite volume transition point, is found in a state where the different partons interact strongly showing a liquid behavior in agreement with the estimate of the plasma parameter [Formula: see text] and supporting the result obtained from the fitting work. This allows us to understand experimental observations in Ultra-Relativistic Heavy-Ion Collisions and to interpret lattice QCD results.
Looking for nonperturbative effects of the electroweak interaction at the LHC
Authors: Arbuzov Boris A. , Zaitsev Ivan V.
Published: April 2019

We are considering a possibility for detecting nonperturbative effect in process of top pair production in association with a high [Formula: see text] photon. Starting from previous results on two solutions for a spontaneous generation of an effective interaction of a top pair with a pair of electroweak bosons, we show that a solution with effective cutoff [Formula: see text] is already contradicting to the existing data, while the other one with [Formula: see text] (just the Planck scale) could be reconciled with data and give predictions for process [Formula: see text], which could be effectively checked at the LHC with [Formula: see text]. The confirmation of the predictions would mean a strong support for the existence of nonperturbative effects in the electroweak interaction.
A digital MEMS gyroscope with 40∘/h instability variation in −40∘C to 85∘C
Authors: Huang Fuxiang , Fu Qiang , Liu Xiaowei , Zhang Yufeng , Mao Zhigang
Published: April 2019

This paper presents a digital MEMS gyroscope with 40[Formula: see text]/h instability variation in −40[Formula: see text]C to 85[Formula: see text]C, performing 5[Formula: see text]/h instability variation at normal temperature and 0.01% nonlinearity in the range of ±400[Formula: see text]/s. This stability was achieved by using temperature compensation for the zero-output value changed after the temperature signal. As the resonant frequency of the mechanical structure varied according to the temperature linearly, a frequency calculator was adopted to detect the temperature of the mechanical structure. And the resolution of the frequency could be up to 0.01 Hz with a 1 MHz clock frequency used, obtaining a 10 Hz bandwidth. The driving mode used a PI controller to control a VGA to maintain at a fixed effective value of the driving signal. The sensing mode contained a low noise C/V convertor and a switch demodulation, which could give the angular velocity signal to the A/D convertor. Then the output data of A/D will be compensated in the digital domain. Finally, the digital output of the gyroscope will be available through a normal SPI serial port. The whole circuit was realized on one chip with an active circuit area of 3.5 mm × 5.2 mm fabricated in a 0.35 [Formula: see text]m CMOS technology. And the MEMS structure and circuit are packaged in a 2.5 cm × 2.5 cm × 2.5 cm aluminum mold. The digital output of the gyroscope earned a noise floor of 0.0024[Formula: see text]/s.
Wideband and multiband electromagnetically induced transparency in graphene metamaterials
Authors: Ning Renxia , Gao Xiang , Chen Zhenhai
Published: April 2019

A multiband tunable electromagnetic induced transparency (EIT) effect in metamaterial at microwave frequency range is investigated. The sandwich structure contains silicon dioxide and gold layers. The metamaterial structure has multiband EIT phenomenon due to coupling with U-Shaped split-ring resonators (SRRs) and cut wire (CW). Two different modes can be obtained in CW and a single band EIT effects in SRRs. Results show that the different resonances in the structure lead to multiband EIT. By adding the finding of the graphene layer on top of the structures, EIT window can be changed obviously. It is shown that the graphene can adjust EIT phenomenon. The group index is calculated to exhibit the slow light effect. The demonstrated phenomenon can provide valuable variety of important applications, including microwave communication technology, microwave devices, slow light and switch devices.
Electronic and magnetic properties of alkali metal chlorides A2MCl6 (A = K, Rb, Cs; M = Mn, Mo): A density functional theory study
Authors: Faizan M. , Khan S. H. , Murtaza G. , Khan A. , Laref A.
Published: April 2019

Detailed first-principles calculations of the electronic structure and magnetic properties of alkali metal chlorides of the type A2MCl6 (A = K, Rb, Cs; M = Mn, Mo) have been performed using the density functional theory (DFT). The calculated optimized lattice constants show close agreement with experimental results. The electronic band structure and density of states (DOS) were investigated for the first time using different schemes of generalized gradient approximation (GGA) such as Wu–Cohen GGA, modified Becke Johnson potential and GGA plus Hubbard U parameter method. We found that the Hubbard U correction significantly improves the current DFT results. The calculated band structures of K2MoCl6 or Cs2MoCl6 indicate that the spin up electrons have metallic structure while the spin down configurations have semi-conducting nature together resulting in a half-metallic behavior. Finally, the analysis of magnetic properties indicates a ferromagnetic nature for all these compounds. These findings indicate that the alkali metal chlorides K2MoCl6 and Cs2MoCl6 are potentially promising candidates for future applications in the field of spintronics.
Current transfer length in 2G HTS tape considering multi-layers
Authors: Chen Hao , Wang Yinshun , Yuan Xi , Liu Mingchuang , Hu Yidan
Published: April 2019

A novel numerical method of calculating the current transfer length (CTL) from several matrices to superconducting region has been proposed in this paper, there are two ways to calculate the CTL corresponding to two criteria of CTL: E-based criterion and I-based criterion, and the relationship between these criteria have been given again. The method of calculating the CTL from several matrices to superconducting region has high accuracy compared with the method introduced by Stenvall, and simulation and experiments of measuring the CTL have been carried out to compare with the ones calculated by the numerical method. The results show that the novel numerical method has high accuracy in calculating the CTL of superconducting tape and is useful for generalizing to calculate the CTL of superconducting cable.
Single-Cell Protein Secretion Detection and Profiling
Authors: Chen Zhuo , Chen Jonathan J. , Fan Rong
Published: April 2019

Secreted proteins play important roles in mediating various biological processes such as cell–cell communication, differentiation, migration, and homeostasis at the population or tissue level. Here, we review bioanalytical technologies and devices for detecting protein secretions from single cells. We begin by discussing conventional approaches followed by detailing the latest advances in microengineered systems for detecting single-cell protein secretions with an emphasis on multiplex measurement. These platforms include droplet microfluidics, micro-/nanowell-based assays, and microchamber-based assays, among which the advantages and limitations are compared. Microscale systems also enable the tracking of protein secretion dynamics in single cells, further empowering the study of the cell–cell communication network. Looking forward, we discuss the remaining challenges and future opportunities that will transform basic research of cellular secretion functions at the systems level and the clinical applications for immune monitoring and cancer treatment.
Xenin-25 induces anion secretion by activating noncholinergic secretomotor neurons in the rat ileum
Authors: Kuwahara Atsukazu , Kuwahara Yuko , Kato Ikuo , Kawaguchi Kotoku , Harata Daiki , Asano Shinji , Inui Toshio , Marunaka Yoshinori
Published: April 2019

Xenin-25 is a neurotensin-like peptide that is secreted by enteroendocrine cells in the small intestine. Xenin-8 is reported to augment duodenal anion secretion by activating afferent neural pathways. The intrinsic neuronal circuits mediating the xenin-25-induced anion secretion were characterized using the Ussing-chambered, mucosa-submucosa preparation from the rat ileum. Serosal application of xenin-25 increased the short-circuit current in a concentration-dependent manner. The responses were abolished by the combination of Cl−-free and [Formula: see text]-free solutions. The responses were almost completely blocked by TTX (10−6M) but not by atropine (10−5M) or hexamethonium (10−4M). The selective antagonists for neurotensin receptor 1 (NTSR1), neurokinin 1 (NK1), vasoactive intestinal polypeptide (VIP) receptors 1 and 2 (VPAC1 and VPAC2, respectively), and capsaicin, but not 5-hydroxyltryptamine receptors 3 and 4 (5-HT3and 5-HT4), NTSR2, and A803467, inhibited the responses to xenin-25. The expression of VIP receptors ( Vipr) in rat ileum was examined using RT-PCR. The Vipr1 PCR products were detected in the submucosal plexus and mucosa. Immunohistochemical staining showed the colocalization of NTSR1 and NK1 with substance P (SP)- and calbindin-immunoreactive neurons in the submucosal plexus, respectively. In addition, NK1 was colocalized with noncholinergic VIP secretomotor neurons. Based on the results from the present study, xenin-25-induced Cl−/[Formula: see text] secretion is involved in NTSR1 activation on intrinsic and extrinsic afferent neurons, followed by the release of SP and subsequent activation of NK1 expressed on noncholinergic VIP secretomotor neurons. Finally, the secreted VIP may activate VPAC1 on epithelial cells to induce Cl−/[Formula: see text] secretion in the rat ileum. Activation of noncholinergic VIP secretomotor neurons by intrinsic primary afferent neurons and extrinsic afferent neurons by postprandially released xenin-25 may account for most of the neurogenic secretory response induced by xenin-25.

NEW & NOTEWORTHY This study is the first to investigate the intrinsic neuronal circuit responsible for xenin-25-induced anion secretion in the rat small intestine. We have found that nutrient-stimulated xenin-25 release may activate noncholinergic vasoactive intestinal polypeptide (VIP) secretomotor neurons to promote Cl−/[Formula: see text] secretion through the activation of VIP receptor 1 on epithelial cells. Moreover, the xenin-25-induced secretory responses are mainly linked with intrinsic primary afferent neurons, which are involved in the activation of neurotensin receptor 1 and neurokinin 1 receptor.
Inhibition of jejunal protein synthesis and breakdown in Pseudomonas aeruginosa-induced sepsis pig model
Authors: Ten Have Gabriëlla A. M. , Engelen Mariëlle P. K. J. , Wolfe Robert R. , Deutz Nicolaas E. P.
Published: April 2019

Maintenance of gut integrity has long been recognized as crucial for survival in sepsis, but alterations in protein metabolism have not previously been documented. Therefore, in the present study, we measured in a Pseudomonas aeruginosa-induced porcine sepsis model fractional protein synthesis (FSR) and breakdown rates (FBR) in jejunal mucosa in a fasted, conscious state. FSR was measured by the incorporation rate of stable tracer amino acid (l-[ ring-13C6]phenylalanine) into tissue protein. FBR was determined using the relation between blood arterial enrichment and intracellular enrichment of phenylalanine in consecutive mucosal biopsies after a pulse of l-[15N]phenylalanine. Additionally, we determined the FSR in jejunum, ileum, liver, muscle, and lung tissue. We found in this sham-controlled acute sepsis pig model (control: n = 9; sepsis: n = 13) that jejunal mucosal protein turnover is reduced with both decreased FSR (control: 3.29 ± 0.22; sepsis: 2.32 ± 0.12%/h, P = 0.0008) and FBR (control: 0.72 ± 0.12; sepsis: 0.34 ± 0.04%/h, P = 0.006). We also found that FSR was unchanged in ileum and muscle, whereas it was higher in the liver (control: 0.87 ± 0.05; sepsis: 1.05 ± 0.06%/h, P = 0.041). Our data, obtained with a translational acute sepsis model, suggest that jejunal mucosal protein metabolism is diminished in acute sepsis. Comparison with other tissues indicates that the most serious acute metabolic changes in sepsis occur in the jejunum rather than the muscle.

NEW & NOTEWORTHY In a highly translational acute sepsis model, presented data suggest that jejunal mucosal protein metabolism is diminished in acute sepsis, even if the origin of the sepsis is not located in the gut. Comparison with other tissues indicates that the most serious acute changes in the protein synthesis rates in sepsis occur in the gut rather than the muscle. Therefore, we hypothesize that preventing a compromised gut is critical to maintain gut function during sepsis.
Direct CD137 costimulation of CD8 T cells promotes retention and innate-like function within nascent atherogenic foci
Authors: Xu Maria M. , Ménoret Antoine , Nicholas Sarah-Anne E. , Günther Sebastian , Sundberg Eric J. , Zhou Beiyan , Rodriguez Annabelle , Murphy Patrick A. , Vella Anthony T.
Published: April 2019

Effector CD8 T cells infiltrate atherosclerotic lesions and are correlated with cardiovascular events, but the mechanisms regulating their recruitment and retention are not well understood. CD137 (4–1BB) is a costimulatory receptor induced on immune cells and expressed at sites of human atherosclerotic plaque. Genetic variants associated with decreased CD137 expression correlate with carotid-intimal thickness and its deficiency in animal models attenuates atherosclerosis. These effects have been attributed in part to endothelial responses to low and disturbed flow (LDF), but CD137 also generates robust effector CD8 T cells as a costimulatory signal. Thus, we asked whether CD8 T cell-specific CD137 stimulation contributes to their infiltration, retention, and IFNγ production in early atherogenesis. We tested this through adoptive transfer of CD8 T cells into recipient C57BL/6J mice that were then antigen primed and CD137 costimulated. We analyzed atherogenic LDF vessels in normolipidemic and PCSK9-mediated hyperlipidemic models and utilized a digestion protocol that allowed for lesional T-cell characterization via flow cytometry and in vitro stimulation. We found that CD137 activation, specifically of effector CD8 T cells, triggers their intimal infiltration into LDF vessels and promotes a persistent innate-like proinflammatory program. Residence of CD137+ effector CD8 T cells further promoted infiltration of endogenous CD8 T cells with IFNγ-producing potential, whereas CD137-deficient CD8 T cells exhibited impaired vessel infiltration, minimal IFNγ production, and reduced infiltration of endogenous CD8 T cells. Our studies thus provide novel insight into how CD137 costimulation of effector T cells, independent of plaque-antigen recognition, instigates their retention and promotes innate-like responses from immune infiltrates within atherogenic foci.

NEW & NOTEWORTHY Our studies identify CD137 costimulation as a stimulus for effector CD8 T-cell infiltration and persistence within atherogenic foci, regardless of atherosclerotic-antigen recognition. These costimulated effector cells, which are generated in pathological states such as viral infection and autoimmunity, have innate-like proinflammatory programs in circulation and within the atherosclerotic microenvironment, providing mechanistic context for clinical correlations of cardiovascular morbidity with increased CD8 T-cell infiltration and markers of activation in the absence of established antigen specificity.

Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/effector-cd8-t-cells-seed-atherogenic-foci/ .
Identification of suitable reference microRNA for qPCR analysis in pediatric inflammatory bowel disease
Authors: Buonpane Christie , Ares Guillermo , Benyamen Beshoy , Yuan Carrie , Hunter Catherine J.
Published: April 2019

Pediatric inflammatory bowel disease (IBD) accounts for 10–15% of IBD and is associated with considerable morbidity for patients. Dysregulated microRNAs (miRNA, miR), small noncoding RNA molecules that modulate gene expression, have been the target of research in IBD diagnosis, surveillance, and therapy. Proper selection of reference genes, which are a prerequisite for accurate measurement of miRNA expression, is currently lacking. We hypothesize that appropriate normalization requires unique reference genes for different tissue and disease types. Through the study of 28 pediatric intestinal samples, we sought to create a protocol for selection of suitable endogenous reference genes. Candidate reference genes (miR-16, 193a, 27a, 103a, 191) were analyzed by RT-quantitative (q)PCR. Criteria used for designation of suitable reference genes were as follows: 1) ubiquitous: present in all tissue samples with quantification cycle value 15–35; 2) uniform expression: no differential expression between control and disease samples ( P > 0.05); 3) stability: stability value <0.5 by NormFinder. Our results suggest the use of miR-27a/191 for Crohn’s disease small bowel, none of the five candidate genes for Crohn’s disease colon, and miR-16/27a for ulcerative colitis. Additionally, target miR-874 had differential expression when normalized with different reference genes. Our results demonstrate that reference gene choice for qPCR analysis has a significant effect on study results and that proper data normalization is imperative.
Noncanonical TGFβ Pathway Relieves the Blockade of IL1β/TGFβ-Mediated Crosstalk between Tumor and Stroma: TGFBR1 and TAK1 Inhibition in Colorectal Cancer
Authors: Guillén Díaz-Maroto Natalia , Sanz-Pamplona Rebeca , Berdiel-Acer Mireia , Cimas Francisco J. , García Elena , Gonçalves-Ribeiro Samuel , Albert Nerea , Garcia-Vicién Gemma , Capella Gabriel , Moreno Victor , Salazar Ramon , Villanueva Alberto , Molleví David G.
Published: April 2019

Purpose:

The aim of the study is blocking the recruitment of a protective stroma by altering the crosstalk between normal stromal cells and tumor cells for stripping tumors of the protection conferred by the microenvironment.

Experimental Design:

A transcriptomic analysis of cocultured normal colonic fibroblasts and colorectal tumor cells was performed. We focused on the study of molecules that mediate the communication between both compartments and that entail fibroblasts’ activation and the alteration of the sensitivity to chemotherapy. We identified targets for the blocking of the tumor–stroma interaction. Finally, we tested, in vivo, the blockade of the tumor–stroma interaction in orthotopic models derived from patients and in models of acquired resistance to oxaliplatin.

Results:

IL1β/TGFβ1 are the triggers for fibroblasts’ recruitment and conversion into carcinoma-associated fibroblasts (CAF) in colorectal cancer. CAFs then secrete proinflammatory factors that alter sensitivity in tumor cells, activating JAK/STAT and PI3KCA/AKT pathways. Blocking such crosstalk with a neutralizing IL1β antibody and a TGFBR1 inhibitor is relieved by the TAK1-mediated activation of the noncanonical TGFβ pathway, which induces a change in the cytokine/chemokine repertoire that maintains a sustained activation of AKT in tumor cells. TAK1 plus TGFBR1 inhibition blocks IL1β/TGFβ1-mediated fibroblast activation, decreasing the secretion of proinflammatory cytokines. In turn, tumor cells became more sensitive to chemotherapy. In vivo, the combination of a TAK1 inhibitor plus TGFBR1 inhibitor reduced the metastatic capacity of tumor cells and the recruitment of fibroblasts.

Conclusions:

Our findings provide a translational rationale for the inhibition of TAK1 and TGFBR1 to remove the chemoprotection conferred by CAFs.
Role of Ancillary Techniques in Cervical Biopsy and Endocervical Curettage Specimens as Follow-Up to Papanicolaou Test Results Indicating a Diagnosis of Atypical Squamous Cells, Cannot Exclude High-Grade Squamous Intraepithelial Lesion, or High-Grade Squamous Intraepithelial Lesion
Authors: Jenkins Taylor M. , Shojaei Hadi , Song Sharon J. , Schwartz Lauren E.
Published: April 2019

The Papanicolaou (PAP) test is widely used to screen for cervical cancer. All high-grade lesions such as atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H), and high-grade squamous intraepithelial lesion, identified on a PAP test should be followed-up by a confirmatory cervical biopsy. In this review, we discuss the challenges in interpreting cervical tissue specimens and the various ancillary techniques used in the evaluation of cervical dysplasia. Ancillary studies include deeper levels, p16 immunohistochemistry (IHC), human papillomavirus (HPV) testing, and, importantly, cyto-histologic correlation. Of these, p16 IHC is consistently sensitive and specific for detecting HSIL. HPV RNA in situ hybridization (ISH) is a newer technique with excellent sensitivity and specificity for detecting virally infected cells and it may be more broadly applicable to both low- and high-grade squamous intraepithelial lesions.
oXiris® Use in Septic Shock: Experience of Two French Centres
Authors: Schwindenhammer Victor , Girardot Thibaut , Chaulier Kevin , Grégoire Arnaud , Monard Céline , Huriaux Laetitia , Illinger Julien , Leray Véronique , Uberti Thomas , Crozon-Clauzel Jullien , Rimmelé Thomas
Published: April 2019

Background: Sepsis is a dysregulated host response to an infection and can result in organ dysfunctions and death. Extracorporeal blood purification techniques aim to improve the prognosis of these patients by modulating the unbalanced immune response. This study reports our experience with the use of the oXiris® membrane for septic shock patients requiring continuous renal replacement therapy (CRRT). Summary: Thirty-one patients were diagnosed with septic shock and underwent CRRT with the oXiris® membrane between 2014 and 2019. We compared the observed hospital mortality with that predicted by the Simplified Acute Physiology Score II (SAPS II). Change in the Sequential Organ Failure Assessment (SOFA) score and of the main clinical and biological parameters over time were analyzed. Hospital mortality was lower than predicted for the most severe patients (60 vs. 91% for the [74–87] SAPS II quartile and 70 vs. 98% for the [87–163] SAPS II quartile, p < 0.02). There was no significant improvement in the SOFA score from 0h to 48 h. An 88% relative decrease in norepinephrine infusion was observed (median at 0 h was 1.69 [0.52–2.45] µg/kg/min; at 48 h it was 0.20 [0.09–1.14] µg/kg/min, p = 0.002). Lactataemia and pH were significantly improved over time. Patients with intra-abdominal sepsis as well as those with Gram-negative bacilli (GNB) infections seemed to benefit the most from the therapy. Key Messages: CRRT with the oXiris® haemofilter resulted in higher observed survival than predicted by a severity score (SAPS II) for the most severe patients. Haemodynamic status and lactataemia appeared to improve, especially in intra-abdominal sepsis and GNB infections.
The Spectrum of Adverse Pregnancy Outcomes Based on Kidney Disease Diagnoses: A 20-Year Population Study
Authors: Fitzpatrick Alyssa , Venugopal Kamalesh , Scheil Wendy , McDonald Stephen P. , Jesudason Shilpanjali
Published: April 2019

Background and Objectives: Kidney disorders in pregnancy may be under-recognized and have variable impact on outcomes depending on diagnosis. Population-level data are limited, particularly for Australia, and comparison of impact of different kidney disorders on pregnancy has rarely been assessed. This study examined the prevalence and outcomes of varied kidney disorders using population-level perinatal data from a large cohort. Methods: Women with singleton pregnancies > 20 weeks’ gestation from the South Australian Pregnancy Outcomes Unit (1990–2012). Women with a kidney disorders diagnostic code were grouped into categories (immunological, cystic/genetic, urological, vesicoureteral reflux (VUR), pyelonephritis and “other”). Key pregnancy outcomes were assessed, with adjustment for demographic variables. Results: Kidney disorders were reported in 1,392 (0.3%) of 407,580 births. These pregnancies had increased risk of pregnancy-induced hypertension (OR 2.16, 95% CI 1.82–2.56), induction of labor (RRR vs. spontaneous birth 2.10, 95% CI 1.87–2.36), all Caesarean section (OR 1.31, 95% CI 1.17–1.47) as well as Caesarean section without labor (RRR 1.82, 95% CI 1.57–2.10), preterm birth (< 37 weeks; 2.76, 95% CI 2.40–3.18), low birth weight (< 2,500 g) infants (OR 2.43, 95% CI 2.07–2.84), and neonatal intensive care admission (OR 2.64, 95% CI 2.12–3.29). Diagnostic subgroups demonstrated differing patterns of adverse outcomes, enabling the development of a matrix of risk. Women with immunological renal conditions and VUR had greatest risk overall, and only women with immunological diseases had increased risk of small-for-gestational age < 10th centile (OR 2.36, 95% CI 1.26–4.42). Women with nonchronic urological conditions and pyelonephritis had increased risk of preterm birth, but not other adverse events. VUR conferred particularly increased risk of Caesarean section and induced labor. Conclusions: In a cohort of > 1,300 women with varied kidney disorders, increased adverse obstetric and perinatal events were observed, and the nature and magnitude of risk differed according to diagnosis. In particular, vesicoureteric reflux is not a benign condition in pregnancy. Women with nonchronic conditions still had increased risk of preterm birth. We confirm that women with kidney disorders warrant vigilant and tailored prepregnancy care and clinical care in pregnancy.
Оптимізація фіксації сітчастого імплантату при трансабдомінальній преперитонеальній алопластиці у хворих на пахвинну грижу
Authors: Feleshtinsky Ya. P. , Kokhanevich A. V.
Published: April 2019

Мета роботи: підвищити ефективність трансабдомінальної преперитонеальної алопластики (ТАРР) у хворих на пахвинну грижу шляхом оптимізації фіксації сітчастого імплантату.

Матеріали і методи. За період від 2010 по 2017 р. прооперовано 178 хворих на пахвинну грижу з використанням класичної та удосконаленої ТАРР. Залежно від методики ТАРР хворих розділили на дві групи. У І групі (89 хворих) виконували класичну методику ТАРР. В ІІ групі (89 хворих) за розробленим нами способом ТАРР із комбінованою фіксацією сітчастого імлантату (патент на корисну модель №113997 від 27.02.2017р.).

Результати досліджень та їх обговорення. Безпосередні результати показали: у 6 хворих (6,7 %) І групи спостерігався виражений післяопераційний біль, в ІІ групі в 1 хворого (1,1 %). У хворих І групи серома передочеревинного простору пахвинної ділянки виникла – у 5 пацієнтів (5,6 %), у ІІ групі – у 4 пацієнтів (4,5 %). Гематома калитки у І групі спостерігалася у 2 хворих (2,2 %), а у ІІ групі – у 3 пацієнтів (3,4 %). Віддаленні результати лікування: І група (81 хворий) – хронічний післяопераційний пахвинний біль спостерігався у 5 (6,1%), ІІ група (82 хворих) – у 2 (2,73 %). У 7 (8,6 %) хворих І групи (81 хворий) виявлено рецидив пахвинної грижі. ІІ група (82 хворих) – рецидив пахвинної грижі виявлено в одного хворого (1,2 %).
Порівняльна оцінка ефективності розробленого одномоментного лапароскопічного лікування жовчнокам’яної хвороби та супутньої хірургічної патології
Authors: Nechytailo M. Yu. , Halei M. M. , Dziubanovskyi O. I.
Published: April 2019

Мета роботи: визначити максимально ефективну технологію візуалізації при виконанні лапароскопічного операційного лікування жовчнокам’яної хвороби та супутньої хірургічної патології.

Матеріали і методи. Використано статистичні дані щодо лікування 411 хворих із ЖКХ та супутньою хірургічною патологією. Для обробки статистики використовували методи з нульовою гіпотезою. Для порівняння визначали зону візуалізації. Для порівняння взято власний метод і французький метод виконання лапароскопічної холецистектомії.

Результати досліджень та їх обговорення. За результатами дослідження встановлено, що оцінене маргінальне середнє значення площі зони візуалізації при власному способі симультанних операційних втручань становить (15,24±3,76) см2 і більше на 62,6 % від відповідного показника французького способу – (9,54±2,27) см2 (р=0,715); при застосуванні лапароскопа з кутом спостереження 0 о відстань наближення лапароскопа при власному способі доступу в середньому становить (3,81±0,52) см і більше на 10,5 % порівняно з середнім значенням досліджуваного параметра при французькому способі (3,41±0,478) см (р=0,295); при застосуванні лапароскопа з кутом спостереження 30 о відстань наближення лапароскопа при власному способі доступу в середньому становить (3,64±0,36) см і більше на 9,12 % порівняно з показником французького способу – (3,34±0,728) см (р<0,001).
Малосимптомна гігантська міксома лівого передсердя: сучасний алгоритм діагностики та радикального оперативного лікування
Authors: Shved M. I. , Moroz V. S. , Humennyi I. Z. , Oryshchyn I. Yu. , Sydorenko O. L.
Published: April 2019

Вступ. Первинні пухлини серця (міксоми) досить рідкісні захворювання, що трапляються в структурі кардіальної патології з частотою від 0,0017 до 0,02 %. Аналіз бібліосемантики клінічних проявів міксом та власних клінічних спостережень свідчать про без- чи малосимптомний перебіг патології серця на ранніх стадіях розвитку міксоми та поліморфізм і неспецифічність симптоматики в подальшому, навіть при гігантських розмірах пухлини. Тому в діагностиці міксом серця визначальними є їх візуалізація за допомогою ехокардіоскопічного дослідження та комп’ютерної або магнітно-резонансної томографії для топічної діагностики і визначення рухомості пухлини, її розмірів, ступеня васкуляризації, оцінки стану клапанів серця. Радикальним методом лікування є резекція міксоми з прилеглими тканинами та наступною пластикою тканинного дефекту і корекцією супутньої дисфункції клапанів.
Селекція отриманої студентами медичного факультету наукової інформації для окреслення смислового поля основних поданих позицій
Authors: Matskevych V. M. , Solomchak D. B.
Published: April 2019

Мета роботы: визначення вправності пошуку літературних джерел із вибором відомостей, які мають оптимальну доказову базу, та здатності до виокремлення квінтесенції наукового повідомлення з подальшим розвитком аналітичного мислення у студентів факультетів природничих наук.

Матеріали і методи. Протягом 2016–2018 рр. у дослідженні брали участь 80 студентів медичного факультету, яким було дано тему для пошуку та опрацювання з встановленням найінформативніших матеріалів у межах встановленого часу, визначення семантичного поля статті, критичної оцінки тексту та написанні власного рейтингу опрацьованих статей згідно з наявною доказовою базою. Вивчено кількість опрацьованих статей респондентами, витрату продуктивного часу на матеріал, який опосередковано належить до пошукового запиту, правильність вибору квінтесенції текстів, визначення компонентів емпіричного циклу наукових досліджень.

Результати досліджень та їх обговорення.  Протягом відведеного часу 42,5 % анкетованих осіб опрацювали 10 і більше статей, 51,25 % – від 5 до 9 статей, 6,25 % – від 1 до 4 статей. Щодо заданих ключових слів у пошукових запитах, то 7,5 % студентів відвели близько третини часу на розгляд інформації, яка не була пов’язана з конкретним запитанням. З правильним вибором квінтесенції текстів справились 57 студентів (71,25 %). Визначили компоненти емпіричного циклу 24 особи (30 %).
Utility of Complementary Magnetic Resonance Plaque Imaging and Contrast‐Enhanced Ultrasound to Detect Carotid Vulnerable Plaques
Authors: Motoyama Rie , Saito Kozue , Tonomura Shuichi , Ishibashi‐Ueda Hatsue , Yamagami Hiroshi , Kataoka Hiroharu , Morita Yoshiaki , Uchihara Yuto , Iihara Koji , Takahashi Jun C. , Sugie Kazuma , Toyoda Kazunori , Nagatsuka Kazuyuki
Published: April 2019

Background

We aimed to improve the assessment quality of plaque vulnerability with combined use of magnetic resonance imaging and contrast‐enhanced ultrasound (
CEUS
).

Methods and Results

We prospectively enrolled 71 patients with internal carotid artery stenosis who underwent carotid endarterectomy and performed preoperative
CEUS
and magnetic resonance plaque imaging. We distinguished high–signal‐intensity plaques (
HIP
s) and non‐
HIP
s based on magnetization‐prepared rapid acquisition with gradient echo images. We graded them according to the
CEUS
contrast effect and compared the
CEUS
images with the carotid endarterectomy specimens. Among the 70 plaques, except 1 carotid endarterectomy tissue sample failure, 59 were classified as
HIP
s (43 symptomatic) and 11 were classified as non‐
HIP
s (5 symptomatic). Although the magnetization‐prepared rapid acquisition with gradient echo findings alone had no significant correlation with symptoms (
P
=0.07), concomitant use of magnetization‐prepared rapid acquisition with gradient echo and
CEUS
findings did show a significant correlation (
P
<0.0001).
CEUS
showed that all 5 symptomatic non‐
HIP
s had a high‐contrast effect. These 5 plaques were histopathologically confirmed as vulnerable, with extensive neovascularization but only a small amount of intraplaque hemorrhage.

Conclusions

Complementary use of magnetic resonance imaging and
CEUS
to detect intraplaque hemorrhage and neovascularization in plaques can be useful for evaluating plaque vulnerability, consistent with the destabilization process associated with neovessel formation and subsequent intraplaque hemorrhage.
A cladistic analysis of the Neotropical genus Sepedonea Steyskal (Diptera: Sciomyzidae)
Authors: MARINONI LUCIANE , MATHIS WAYNE N.
Published: April 2019

A cladistic analysis of the 13 known species of Sepedonea Steyskal, 1973, is presented and a new species, Sepedonea giovana sp. n., is described. The monophyly of the genus is confirmed, as is the genus’ sister-group relationship to Sepedomerus Steyskal, 1973. The cladistic analysis was done using NONA and a matrix of 27 adult morphological characters, including structures of the male and female terminalia. The relationships in parenthetic notation are: (S. guatemalana (S. veredae (S. lindneri (S. isthmi (S. lagoa ((S. barbosai+ S. canabravana) ((S. neffi (S. giovana+S. guianica))(S. telson (S. incipiens+S. trichotypa))))))))).