bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic Performance of Shear Wave Elastography in Patients With Autoimmune Liver Disease
Authors: Li Changtian , Dhyani Manish , Bhan Atul K. , Grajo Joseph R. , Pratt Daniel S. , Gee Michael S. , Samir Anthony E.
Published: May 2018

Objectives

To assess performance of shear wave elastography for evaluation of fibrosis and the histologic stage in patients with autoimmune liver disease (ALD) and to validate previously established advanced fibrosis cutoff values in this cohort.

Methods

Shear wave elastography was performed on patients with ALD with an Aixplorer ultrasound system (SuperSonic Imagine, Aix‐en‐Provence, France) using an SC6‐1 transducer. The median estimated tissue Young modulus was calculated from sets of 8 to 10 elastograms. A blinded, subspecialty‐trained pathologist reviewed biopsy specimens. The METAVIR classification was used to stage liver fibrosis and necroinflammation. Steatosis was graded from 0 to 4+. The Kendall τ‐b correlation test was performed to identify the correlation between the estimated tissue Young modulus and fibrosis, steatosis, and the necroinflammatory score. The Spearman correlation test was performed to identify the correlation between the estimated tissue Young modulus and clinical data. The diagnostic performance of shear wave elastography for differentiating METAVIR stage F2 or higher from F0 and F1 fibrosis was evaluated by a receiver operating characteristic (ROC) curve analysis.

Results

Fifty‐one patients with ALD were analyzed. The estimated tissue Young modulus was positively correlated with the fibrosis stage and necroinflammation score (r = 0.386; P < .001; r = 0.338; P = .002, respectively) but not steatosis (r = −0.091; P = .527). Serum aspartate aminotransferase, alanine aminotransferase, and total bilirubin values were positively correlated with the estimated tissue Young modulus (r = 0.501; P < .001; r = 0.44; P = .001; r = 0.291; P = .038). The serum albumin value was negatively correlated (r = −0.309; P = .033). The area under the ROC curve was 0.781 (95% confidence interval, 0.641–0.921) for distinguishing F2 or greater fibrosis from F0 and F1 fibrosis. Based on the ROC curve, an optimal cutoff value of 9.15 kPa was identified (sensitivity, 83.3%; specificity, 72.7%).

Conclusions

Shear wave elastography is a novel noninvasive adjunct to liver biopsy in evaluation and staging of patients with ALD, showing the potential for serial evaluations of disease progression and treatment responses.
Boundedness in a fully parabolic chemotaxis‐consumption system with nonlinear diffusion and sensitivity, and logistic source
Authors: Marras Monica , Viglialoro Giuseppe
Published: May 2018

In this paper we study the zero‐flux chemotaxis‐system
urn:x-wiley:0025584X:media:mana201700172:mana201700172-math-0001Ω being a convex smooth and bounded domain of , , and where , and . For any the chemotactic sensitivity function is assumed to behave as the prototype , with and . We prove that for nonnegative and sufficiently regular initial data and , the corresponding initial‐boundary value problem admits a unique globally bounded classical solution provided μ is large enough.
Reconstruction of kernel depending also on space variable
Authors: Giorgi Claudio , Guidetti Davide
Published: May 2018

The paper deals with the reconstruction of the convolution kernel, together with the solution, in a mixed linear evolution system of hyperbolic type. This problem describes uniaxial deformations u of a cylindrical domain (0,π) × Ω, which is filled with a linear viscoelastic solid whose material properties are supposed to be uniform on Ω‐sections perpendicular to the x axis. Various types of boundary conditions in [0,T] × {0,π} × Ω are prescribed, whereas Dirichlet conditions are assumed in [0,T] × (0,π) × ∂Ω. To reconstruct both u and k, we suppose of knowing for any time tand any x ∈ (0,π) the flux of the viscoelastic stress vector through the boundary of the Ω‐section. The main novelty is that the unknown kernel k is allowed to depend, not only on the time variable t but also on the space variable x.
A Fokas approach to the coupled modified nonlinear Schrödinger equation on the half‐line
Authors: Hu Beibei , Xia Tiecheng
Published: May 2018

In this work, we discuss the coupled modified nonlinear Schrödinger (CMNLS) equation, which describe the pulse propagation in the picosecond or femtosecond regime of the birefringent optical fibers. By use of the Fokas approach, the initial‐boundary value problem for the CMNLS equation related to a 3×3 matrix Lax pair on the half‐line is to be analyzed. Assuming that the solution {u(x,t),v(x,t)} of CMNLS equation exists, we will prove that it can be expressed in terms of the unique solution of a 3×3 matrix Riemann‐Hilbert problem formulated in the plane of the complex spectral parameter λ. Moreover, we also get that some spectral functions s(λ) and S(λ) are not independent of each other but meet a global relationship.
Metagenomics Analysis of Gut Microbiota in a High Fat Diet–Induced Obesity Mouse Model Fed with (−)‐Epigallocatechin 3‐O‐(3‐O‐Methyl) Gallate (EGCG3″Me)
Authors: Zhang Xin , Chen Yuhui , Zhu Jieyu , Zhang Man , Ho Chi‐Tang , Huang Qingrong , Cao Jinxuan
Published: May 2018

Scope

(−)‐Epigallocatechin 3‐O‐(3‐O‐methyl) gallate (EGCG3″Me) has been shown to have a modulatory effect on human intestinal microbiota, and the relationship between intestinal flora and obesity has attracted more and more attention recently. Here, the potential link between EGCG3″Me and gut microbiota composition, as well as the underlying mechanisms of the anti‐obesity activity of EGCG3″Me are investigated.

Methods and results

EGCG3″Me was prepared from oolong tea by column chromatography, and the influence of EGCG3″Me on intestinal microbiota was analyzed using a human‐flora‐associated high fat diet (HFD)‐induced obesity mouse model by metagenomics. EGCG3″Me showed a weight reducing effect, ameliorated the HFD‐induced gut dysbiosis, and significantly decreased the ratio of Firmicutes/Bacteroidetes. Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) database provided significant differences in differentially expressed genes in response to EGCG3″Me treatment. The results showed enrichment of genes involved in the biosynthesis of amino acids, the two‐component system, ATP‐binding cassette (ABC) transporters, purine metabolism, and carbon metabolism.

Conclusion

An EGCG3″Me supplemented diet produces promising effects on gut microecology by enhancing beneficial microbial populations and by affecting metabolic pathways including amino acids biosynthesis, the two‐component system, and ABC transporters, contributing to the improvement of host health.
Impact of cardiosynchronous brain pulsations on Monte Carlo calculated doses for synchrotron micro‐ and minibeam radiation therapy
Authors: Manchado de Sola Francisco , Vilches Manuel , Prezado Yolanda , Lallena Antonio M.
Published: May 2018

Purpose

The purpose of this study was to assess the effects of brain movements induced by heartbeat on dose distributions in synchrotron micro‐ and minibeam radiation therapy and to develop a model to help guide decisions and planning for future clinical trials.

Methods

The Monte Carlo code PENELOPE was used to simulate the irradiation of a human head phantom with a variety of micro‐ and minibeam arrays, with beams narrower than 100 μm and above 500 μm, respectively, and with radiation fields of 1 × 2 cm and 2 × 2 cm. The dose in the phantom due to these beams was calculated by superposing the dose profiles obtained for a single beam of 1 μm × 2 cm. A parameter δ, accounting for the total displacement of the brain during the irradiation and due to the cardiosynchronous pulsation, was used to quantify the impact on peak‐to‐valley dose ratios and the full width at half maximum.

Results

The difference between the maximum (at the phantom entrance) and the minimum (at the phantom exit) values of the peak‐to‐valley dose ratio reduces when the parameter δ increases. The full width at half maximum remains almost constant with depth for any δ value. Sudden changes in the two quantities are observed at the interfaces between the various tissues (brain, skull, and skin) present in the head phantom. The peak‐to‐valley dose ratio at the center of the head phantom reduces when δ increases, remaining above 70% of the static value only for minibeams and δ smaller than ∼200 μm.

Conclusions

Optimal setups for brain treatments with synchrotron radiation micro‐ and minibeam combs depend on the brain displacement due to cardiosynchronous pulsation. Peak‐to‐valley dose ratios larger than 90% of the maximum values obtained in the static case occur only for minibeams and relatively large dose rates.
Handwriting assessment to distinguish comorbid learning difficulties from attention deficit hyperactivity disorder in Chinese adolescents: A case–control study
Authors: Li‐Tsang Cecilia W.P. , Li Tim M.H. , Lau Mandy S.W. , Ho Choco H.Y. , Leung Howard W.H.
Published: May 2018

Objectives

Attention deficit hyperactivity disorder (ADHD) and learning difficulties (LDs) are proposed as 2 overlapping disorders. The objective of this study was to investigate the handwriting performance in ADHD and comorbid ADHD‐LD adolescents.

Methods

The study examined the Chinese and English handwriting performance and sensorimotor skills of 32 ADHD, 12 ADHD‐LD, and their matched controls.

Results

Participants with ADHD had comparable writing time and speed, but the readability was lower than their controls. Participants with ADHD‐LD had lower writing speeds in both Chinese and English handwriting than their controls. The ADHD and ADHD‐LD groups also showed larger variations in either speed or pen pressure than their controls. Chinese handwriting assessment effectively classified ADHD and ADHD‐LD with good sensitivity and positive predictive value.

Conclusions

Clinicians should be aware of the fundamental difference between the 2 disorders and make good use of handwriting assessment as a reference to deliver effective therapies and trainings.
Reduction of Parenteral Nutrition and Hydration Support and Safety With Long‐Term Teduglutide Treatment in Patients With Short Bowel Syndrome−Associated Intestinal Failure: STEPS‐3 Study
Authors: Seidner Douglas L. , Fujioka Ken , Boullata Joseph I. , Iyer Kishore , Lee Hak‐Myung , Ziegler Thomas R.
Published: May 2018

Background

Patients with intestinal failure associated with short bowel syndrome (SBS–IF) require parenteral support (PS) to maintain fluid balance or nutrition. Teduglutide (TED) reduced PS requirements in patients with SBS–IF in the randomized, placebo (PBO)‐controlled STEPS study (NCT00798967) and its 2‐year, open‐label extension, STEPS‐2 (NCT00930644).

Methods

STEPS‐3 (NCT01560403), a 1‐year, open‐label extension study in patients with SBS–IF who completed STEPS‐2, further monitored the safety and efficacy of TED (0.05 mg/kg/day). Baseline was the start of TED treatment, in either STEPS or STEPS‐2. At the end of STEPS‐3, patients treated with TED in both STEPS and STEPS‐2 (TED–TED) received TED for ≤42 months, and patients treated with TED only in STEPS‐2 (no TED treatment [NT]/PBO–TED) received TED for ≤36 months.

Results

Fourteen patients enrolled (TED‒TED, n = 5; NT/PBO‒TED, n = 9) and 13 completed STEPS‐3. At the last dosing visit, mean (SD) PS was reduced from baseline by 9.8 (14.4 [50%]) and 3.9 (2.8 [48%]) L/week in TED‒TED and NT/PBO‒TED, respectively. Mean (SD) PS infusions decreased by 3.0 (4.6) and 2.1 (2.2) days per week from baseline in TED‒TED and NT/PBO‒TED, respectively. Two patients achieved PS independence; 2 additional patients who achieved independence in STEPS‐2 maintained enteral autonomy throughout STEPS‐3. All patients reported ≥1 treatment‐emergent adverse event (TEAE); 3 patients had TEAEs that were reported as treatment related. No patient had a treatment‐related treatment‐emergent serious AE.

Conclusions

Long‐term TED treatment yielded a safety profile consistent with previous studies, sustained efficacy, and a further decline in PS requirements.
Development of an algorithm to identify pregnancy episodes and related outcomes in health care claims databases: An application to antiepileptic drug use in 4.9 million pregnant women in France
Authors: Blotière Pierre‐Olivier , Weill Alain , Dalichampt Marie , Billionnet Cécile , Mezzarobba Myriam , Raguideau Fanny , Dray‐Spira Rosemary , Zureik Mahmoud , Coste Joël , Alla François
Published: May 2018

Purpose

Access to claims databases provides an opportunity to study medication use and safety during pregnancy. We developed an algorithm to identify pregnancy episodes in the French health care databases and applied it to study antiepileptic drug (AED) use during pregnancy between 2007 and 2014.

Methods

The algorithm searched the French health care databases for discharge diagnoses and medical procedures indicative of completion of a pregnancy. To differentiate claims associated with separate pregnancies, an interval of at least 28 weeks was required between 2 consecutive pregnancies resulting in a birth and 6 weeks for terminations of pregnancy. Pregnancy outcomes were categorized into live births, stillbirths, elective abortions, therapeutic abortions, spontaneous abortions, and ectopic pregnancies. Outcome dates and gestational ages were used to calculate pregnancy start dates.

Results

According to our algorithm, live birth was the most common pregnancy outcome (73.9%), followed by elective abortion (17.2%), spontaneous abortion (4.2%), ectopic pregnancy (1.1%), therapeutic abortion (1.0%), and stillbirth (0.4%). These results were globally consistent with French official data. Among 7 559 701 pregnancies starting between 2007 and 2014, corresponding to 4 900 139 women, 6.7 per 1000 pregnancies were exposed to an AED. The number of pregnancies exposed to older AEDs, comprising the most teratogenic AEDs, decreased throughout the study period (−69.4%), while the use of newer AEDs increased (+73.4%).

Conclusions

We have developed an algorithm that allows identification of a large number of pregnancies and all types of pregnancy outcomes. Pregnancy outcome and start dates were accurately identified, and maternal data could be linked to neonatal data.
Amino‐terminated polylactide micelles with an external poly(ethylene oxide) corona as carriers of drug‐loaded anionic liposomes
Authors: Sybachin Andrey V , Khlynina Polina O , Spiridonov Vasiliy V , Panova Irina G , Melik‐Nubarov Nikolay S , Yaroslavov Alexander A
Published: May 2018

Micelles were prepared from a mixture of NH2‐terminated poly(l‐lactide) and poly(d,l‐lactide)‐block‐poly(ethylene oxide) (molar ratio of 3:7). The micelles were complexed with bilayer lipid vesicles (liposomes) composed of anionic palmitoyloleoylphosphatidylserine and zwitterionic dioleoylphosphatidylcholine in a molar ratio of 3:7. The micelles and micelle–liposome complexes were characterized using dynamic light scattering, laser electrophoresis, fluorimetry, transmission electron microscopy, enzymatic hydrolysis and cell viability with the following main findings. (i) Average diameter of micelle cores was found to be 70 ± 10 nm. (ii) Each micelle carried ca 20 000 amino groups. (iii) In a pH 7 solution the impact of the protonated NH2 groups in the total surface of micelles was negligible owing to their screening by bulky poly(ethylene oxide) blocks. (iv) The micelles were stable in slightly acidic and neutral aqueous solutions, but aggregated in slightly alkaline solutions. (v) The micelles showed no cytotoxicity up to 0.04 mg mL−1 concentration (the maximum concentration in the experiment). (vi) Each micelle adsorbed ca 30 anionic liposomes loaded with the antitumor antibiotic doxorubicin; the liposomes retained their integrity upon binding with micelles. (vii) The initial micelles and the micelle–liposome complexes showed two‐week stability to enzymatic hydrolysis. © 2018 Society of Chemical Industry
Predicting academic achievement by class‐level emotions and perceived homeroom teachers’ emotional support
Authors: Kashy‐Rosenbaum Gabriela , Kaplan Oren , Israel‐Cohen Yael
Published: May 2018

Using a multilevel approach, this study examined the role of classroom emotional climate on students' academic achievement. Positive and negative emotions and homeroom teachers' support were used to assess the classroom emotional climate on the individual and class levels. To our knowledge, no study to date has investigated these specific aspects of the classroom emotional climate in relation to students' GPA. Data were collected from 73 classrooms in grades 7‐12 (N = 1,641, students; 53% female) across three schools in Israel. Findings revealed that aggregated levels of both positive affect and perceived homeroom teacher support were positively tied to GPA and that aggregated levels of negative affect were negatively tied to GPA. The final model included gender, teacher support, individual and class emotions and explained 14% of within‐class GPA. A central implication of this study is the relevance of having an emotionally supportive homeroom teacher for students' academic achievement.
Psychological distress in lung cancer survivors at least 1 year after diagnosis—Results of a German multicenter cross‐sectional study
Authors: Eichler Martin , Hechtner Marlene , Wehler Beatrice , Buhl Roland , Stratmann Jan , Sebastian Martin , Schmidberger Heinz , Peuser Jessica , Kortsik Cornelius , Nestle Ursula , Wiesemann Sebastian , Wirtz Hubert , Wehler Thomas , Blettner Maria , Singer Susanne
Published: May 2018

Objective

Despite the high incidence of lung cancer, little is known about distress in lung cancer survivors and patients who have survived diagnose for at least 1 year. We investigated distress prevalence and associated factors.

Methods

We performed a multicenter (n = 6 hospitals) cross‐sectional study. Data were collected using medical records, questionnaires, and a telephone interview. Distress was measured with the Patient Health Questionnaire (PHQ‐4). Odds ratios (OR) for factors potentially associated with distress were calculated using multivariable logistic regression.

Results

We included 561 complete case participants with a mean time since diagnosis of 4.4 years. Nineteen percent of them reported depression and 19% anxiety; 26% had 1 or both. Woman had nearly 2‐times the odds of being distressed than men (OR 1.92). Participants with UICC stage II or III at diagnosis had lower odds of being distress compared with stage I (ORs 0.41, 0.44). Participants in current treatment were less likely to be anxious or depressed than those off treatment (OR 0.32). Those with self‐reported progressing disease had 3‐times the odds of distress than people in complete remission (OR 3.00). Time since diagnosis, pain, dyspnea, lung cancer stigma as well as decreased physical functioning were related to increased distress (ORs per unit increase 0.90, 1.02, 1.03, 1.05, and 0.9, respectively).

Conclusions

With a quarter of patients affected, psychological distress is a common problem in this population. Being off treatment does not imply less distress. People with poor physical functioning and pain are especially affected. Treating these symptoms is therefore very important.
Latent class analysis differentiation of adjustment disorder and demoralization, more severe depressive and anxiety disorders, and somatic symptoms in patients with cancer
Authors: Bobevski I. , Kissane D.W. , Vehling S. , McKenzie D.P. , Glaesmer H. , Mehnert A.
Published: May 2018

Objectives

Demoralization as a form of existential distress involves poor coping, low morale, hopelessness, helplessness, and meaninglessness. In a secondary analysis of a cohort of German cancer patients, we aimed to explore latent class structure to assess the contribution that symptoms of demoralization make to anhedonic depression, anxiety, adjustment, and somatic disorders.

Methods

Measures of demoralization, depression, anxiety, physical symptoms, and functional impairment had been completed cross‐sectionally by 1527 patients with early or advanced cancer. Latent class analysis used maximum likelihood techniques to define the unobserved latent constructs that can be predicted as symptom clusters. Individual patients were assigned to the most probable class. Classes were compared on demographics, and logistic regression assessed the odds of individual items predicting each class.

Results

A 4‐class model provided the best fit. Class 1 (n = 829, 54.3%) was defined by the absence of distress; Classes 2 to 4 all carried functional impairment. Class 2 (n = 333, 21.8%) was differentiated by somatic symptoms (sleep, tiredness, and appetite); Class 3 (n = 163, 10.7%) by anhedonia, anxiety, and severe demoralization; and Class 4 (n = 202, 13.2%) by adjustment and moderate demoralization. Members of Class 3 were more likely to be younger, female, anhedonic, depressed, and anxious. In both Classes 3 and 4, functional impairment, physical symptom burden, and suicidal ideation were present.

Conclusions

In contrast with the severe symptom cluster carrying anhedonia, anxiety, and demoralization, the moderate symptom cluster was formed by patients with demoralization and impaired functioning, a clinical picture consistent with a unidimensional model of adjustment disorder.
Generation of active species and antimicrobial efficacy of an underwater plasma device equipped with a porous bubbler
Authors: Kim Taejung , Seo Hyemi , Bae Hanjun , Kim Taeyeol , Yang Sangsik , Moon Eunpyo
Published: May 2018

An increase in dissolved active species generated and spread using a nonthermal atmospheric plasma device increases water purification and the antimicrobial effect. We propose an underwater plasma device that generates fine bubbles in solution to increase the amount of dissolved active species. Our plasma device has a bubbler with a porosity of 30–50%. Analysis of the inherent active species via an optical emission spectrum, obtained with the developed plasma device shielded from the atmosphere. The underwater plasma from a bubbler with 30–50% porosity is shown to effectively inhibit growth of pathogenic bacteria such as Staphylococcus and Pseudomonas. Reactive oxygen species (ROS) is biological molecules that play an important role in bacterial death. The highest number of ROS is detected in the underwater plasma of the bubbler with 50% porosity. ROS signaling molecules, in particular, singlet oxygen and H2O2, could play a role in plasma‐mediated damage to bacteria. The underwater plasma solution of the bubbler with 50% porosity had a strong antimicrobial effect with a considerably low cytotoxic effect on cells, implying that the higher bubbler porosity is more promising for practical use in plasma medicine.
Interaction of antidiabetic α‐glucosidase inhibitors and gut bacteria α‐glucosidase
Authors: Tan Kemin , Tesar Christine , Wilton Rosemarie , Jedrzejczak Robert P. , Joachimiak Andrzej
Published: May 2018

Carbohydrate hydrolyzing α‐glucosidases are commonly found in microorganisms present in the human intestine microbiome. We have previously reported crystal structures of an α‐glucosidase from the human gut bacterium Blaubia (Ruminococcus) obeum (Ro‐αG1) and its substrate preference/specificity switch. This novel member of the GH31 family is a structural homolog of human intestinal maltase‐glucoamylase (MGAM) and sucrase–isomaltase (SI) with a highly conserved active site that is predicted to be common in Ro‐αG1 homologs among other species that colonize the human gut. In this report, we present structures of Ro‐αG1 in complex with the antidiabetic α‐glucosidase inhibitors voglibose, miglitol, and acarbose and supporting binding data. The in vitro binding of these antidiabetic drugs to Ro‐αG1 suggests the potential for unintended in vivo crossreaction of the α‐glucosidase inhibitors to bacterial α‐glucosidases that are present in gut microorganism communities. Moreover, analysis of these drug‐bound enzyme structures could benefit further antidiabetic drug development.
The 24th Annual Prostate Cancer Foundation scientific retreat report
Authors: Miyahira Andrea K. , Soule Howard R.
Published: May 2018

Introduction

The 24th Annual Prostate Cancer Foundation (PCF) Scientific Retreat was held from October 5‐7, 2017, at the Omni Shoreham Hotel in Washington, DC.

Methods

The PCF Scientific Retreat is a scientific conference that specifically focuses on cutting edge research deemed to have significant promise for accelerating advances in prostate cancer biology and treatment.

Results

Themes highlighted at this year's meeting included: (i) new understandings in prostate cancer biology and disease progression; (ii) new mechanisms and treatment targets in advanced prostate cancer; (iii) advances in precision medicine genomics, germline genetics, and selection of targeted therapies; (iv) PSMA‐targeted agents for PET imaging and radionuclide therapy; (v) approaches for improving the efficacy of immunotherapy in prostate cancer; (vi) applications of 3D Genomics in prostate cancer research; and (vii) potential applications of artificial intelligence in prostate cancer.

Discussion

This article reviews the research presented at the PCF Scientific Retreat, in order to improve understanding of the current state of prostate cancer research, encourage discourse and exchange of novel ideas, and stimulate new basic, translational, and clinical research that will ultimately improve the lives of patients.
Thrombotic characteristics of extracellular vesicles derived from prostate cancer cells
Authors: Al Saleh Hassan A. , Haas‐Neill Sandor , Al‐Hashimi Ali , Kapoor Anil , Shayegan Bobby , Austin Richard C. , Al‐Nedawi Khalid
Published: May 2018

Background

Prostate cancer (PC) patients in advanced stages of the disease have high risk of blood coagulation complications. The procoagulant molecule Tissue factor (TF), and the fibrinolysis inhibitor plasminogen activator inhibitor‐1 PAI‐1 play important role in this complication. Extracellular vesicles (EV) shed from cancer cells may contribute to the regulation of TF and PAI‐1. The procoagulant activity of EV can be associated with the oncogenic and metastatic characteristics of their cells.

Methods

We have expressed EGFRvIII in DU145 cells to assess the role of this oncogene in the procoagulant activity of EV. The intercellular exchange of TF via EV was assessed by downregulating its expression in DU145 cells using shRNA vector, and determining the transfer of TF via EV enriched with the protein. Two PC cell lines with different metastatic potential were used to assess the correlation between the procoagulant activity of EV and the metastatic potential of PC cells. Photometric assays were used to determine FXa‐activity and thrombin generation as indicators for the procoagulant activity of EV. Double‐tagged proteinase‐activated receptor 1(PAR‐1) expressed in CHO cells to assess its activation by EV.

Results

The expression of EGFRvIII in DU145 cells led to increased mRNA levels for TF and PAI‐1, but the increase in these proteins expression was detected mostly in the EV. EV with enhanced levels of TF protein conferred higher TF procoagulant activity on the acceptor cells by intercellular exchange of this protein. Procoagulant activity of EV, assessed by FXa activity, and thrombin generation, was correlated with the oncogenic and metastatic potential of PC cells. The ability of EV to generate thrombin led to the activation of PAR‐1, which was evident by the truncation of tagged‐PAR‐1.

Conclusion

The active oncogene EGFRvIII increases the concentration of TF and PAI‐1 in EV. The procoagulant activity of EV is associated with the oncogenic and metastatic characteristics of their PC cells. Also, EV may contribute to the high procoagulant activity in the tumour microenvironment by the intercellular exchange of TF. Finally, through the generation of thrombin, EV can activate PAR‐1, which evidently contributes to cancer progression, linking the coagulation system to tumor progression.
Predicting mammalian metabolism and toxicity of pesticides in silico
Authors: Clark Robert D
Published: May 2018

Pesticides must be effective to be commercially viable but they must also be reasonably safe for those who manufacture them, apply them, or consume the food they are used to produce. Animal testing is key to ensuring safety, but it comes late in the agrochemical development process, is expensive, and requires relatively large amounts of material. Surrogate assays used as in vitro models require less material and shift identification of potential mammalian toxicity back to earlier stages in development. Modern in silico methods are cost‐effective complements to such in vitro models that make it possible to predict mammalian metabolism, toxicity and exposure for a pesticide, crop residue or other metabolite before it has been synthesized. Their broader use could substantially reduce the amount of time and effort wasted in pesticide development. This contribution reviews the kind of in silico models that are currently available for vetting ideas about what to synthesize and how to focus development efforts; the limitations of those models; and the practical considerations that have slowed development in the area. Detailed discussions are provided of how bacterial mutagenicity, human cytochrome P450 (CYP) metabolism, and bioavailability in humans and rats can be predicted. © 2018 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Effects of biochar amendment on sorption, dissipation, and uptake of fenamiphos and cadusafos nematicides in sandy soil
Authors: Abdel Ghani Sherif B , Al‐Rehiayani Suloiman , El Agamy Moustafa , Lucini Luigi
Published: May 2018

BACKGROUND

The application of biochar to soil is supposed to alter its adsorption/desorption potential toward pesticides, thereby affecting their bioavailability and efficacy. This is particularly relevant in the case of nematicides because these pesticides are directly applied to soil.

RESULTS

Biochar was produced from date palm (PB) and eucalyptus (EB) waste at 450 °C and added at a rate of 1% to a sandy soil. The half‐life (t½) of fenamiphos was increased from 2.7 to 18.3 and 18.6 days in PB‐ and EB‐amended soils, respectively. By contrast, the half‐life of cadusafos was unaffected. Freundlich Kf values increased from 1.22 and 0.39 (μg1–Nf g−1 mLNf) to 4.49 and 6.84 in 1% PB‐amended soil, and to 3.49 and 4.62 in 1% EB‐amended soil for cadusafos and fenamiphos, respectively. Plant uptake of both nematicides in tomato seedlings was reduced by approximately 97% (cadusafos) and 85% (fenamiphos). Although nematicide efficacy against Meloidogyne incognita was not altered at the recommended dosage, it was negatively affected at a half‐dose rate. Under these conditions, it decreased from 43.1% in unamended sandy soil to only 18.3% in 1% PB‐amended soil.

CONCLUSIONS

Biochar addition increased the sorption capacity of soil. This resulted in a decrease of nematicide bioavailability, together with a reduction of both the dissipation rate and uptake by tomato plants. © 2018 Society of Chemical Industry
Mechanism‐Based Disease Progression Model Describing Host‐Pathogen Interactions During the Pathogenesis of Acinetobacter baumannii Pneumonia
Authors: Diep John K. , Russo Thomas A. , Rao Gauri G.
Published: May 2018

The emergence of highly resistant bacteria is a serious threat to global public health. The host immune response is vital for clearing bacteria from the infected host; however, the current drug development paradigm does not take host‐pathogen interactions into consideration. Here, we used a systems‐based approach to develop a quantitative, mechanism‐based disease progression model to describe bacterial dynamics, host immune response, and lung injury in an immunocompetent rat pneumonia model. Previously, Long‐Evans rats were infected with Acinetobacter baumannii (A. baumannii) strain 307‐0294 at five different inocula and total lung bacteria, interleukin‐1beta (IL‐1β), tumor necrosis factor‐α (TNF‐α), cytokine‐induced neutrophil chemoattractant 1 (CINC‐1), neutrophil counts, and albumin were quantified. Model development was conducted in ADAPT5 version 5.0.54 using a pooled approach with maximum likelihood estimation; all data were co‐modeled. The final model characterized host‐pathogen interactions during the natural time course of bacterial pneumonia. Parameters were estimated with good precision. Our expandable model will integrate drug effects to aid in the design of optimized antibiotic regimens.
Perspective on the State of Pharmacometrics and Systems Pharmacology Integration
Authors: Trame Mirjam N. , Riggs Matthew , Biliouris Konstantinos , Marathe Dhananjay , Mettetal Jerome , Post Teun M. , Rizk Matthew L. , Visser Sandra A. G. , Musante Cynthia J.
Published: May 2018

Reliance on modeling and simulation in drug discovery and development has dramatically increased over the past decade. Two disciplines at the forefront of this activity, pharmacometrics and systems pharmacology (SP), emerged independently from different fields; consequently, a perception exists that only few examples integrate these approaches. Herein, we review the state of pharmacometrics and SP integration and describe benefits of combining these approaches in a model‐informed drug discovery and development framework.
Hepatitis B virus (HBV) reactivation—The potential role of direct‐acting agents for hepatitis C virus (HCV)
Authors: Blackard Jason T. , Sherman Kenneth E.
Published: May 2018

Hepatitis C virus (HCV) is known to inhibit hepatitis B virus (HBV) replication in patients with HBV/HCV coinfection. Reactivation of HBV in patients treated for HCV with direct‐acting agents (DAAs) has emerged recently as an important clinical consideration. A growing number of case reports and case series support the association between new HCV treatments and HBV reactivation. Yet, very little is known about the specific viral characteristics that facilitate reactivation as functional characterization of the reactivated HBV has been conducted only rarely. This review provides the most recent data on HBV reactivation in the context of DAA initiation and highlights the existing viral genomic data from reactivating viruses. Current functional studies of HBV reactivation are largely limited by the retrospective identification of cases, no standardization of genomic regions that are studied with respect to HBV reactivation, and the lack of inclusion of nonreactivating controls to establish specific viral mutations that are associated with HBV reactivation. Importantly, none of these sequencing studies included cases of HBV reactivation after initiation of DAAs.

While new HCV treatments have revolutionized care for HCV infected patients, HBV reactivation will likely increase in frequency, as DAAs are more commonly prescribed. Pretreatment determination of HBV status and thoughtful management of HBV coinfections will be necessary and lead to improved patient safety and yield optimal treatment results.
Quantum talk: How small‐group discussions may enhance students’ understanding in quantum physics
Authors: Bungum Berit , Bøe Maria Vetleseter , Henriksen Ellen Karoline
Published: May 2018

Quantum physics challenges our views of the physical world and describes phenomena that cannot be directly observed. The use of language is hence essential in the teaching of quantum physics. With a sociocultural view of learning, we investigate characteristics of preuniversity students’ small‐group discussions and their potential for enhancing understanding of quantum physics. The empirical data are 96 small‐group discussions about two fundamental dilemmas: whether light can be both waves and particles, and whether the cat in Schrödinger's thought experiment can be considered to be both dead and alive. The discussions were analyzed by means of a framework of four categories, grouped as productive and nonproductive for learning, where “productive” means that students build constructively on each other's utterances and take the peers’ ideas into account. Results show that a total of 70% of the discussions were productive, indicating that small‐group discussions have a potential for enhancing understanding in quantum physics. This potential is constituted by leading students to (i) articulate conceptual difficulties, (ii) deepen their understanding through exchange of views, and (iii) formulate new questions. The paper concludes with a discussion on how the learning potential of small‐group discussions may be realized by combining dialogic and authoritative approaches.
A novel cognitive disease progression model for clinical trials in autosomal‐dominant Alzheimer's disease
Authors: Wang Guoqiao , Berry Scott , Xiong Chengjie , Hassenstab Jason , Quintana Melanie , McDade Eric M. , Delmar Paul , Vestrucci Matteo , Sethuraman Gopalan , Bateman Randall J. ,   For the Dominantly Inherited Alzheimer Network Trials Unit
Published: May 2018

Clinical trial outcomes for Alzheimer's disease are typically analyzed by using the mixed model for repeated measures (MMRM) or similar models that compare an efficacy scale change from baseline between treatment arms with or without participants' disease stage as a covariate. The MMRM focuses on a single‐point fixed follow‐up duration regardless of the exposure for each participant. In contrast to these typical models, we have developed a novel semiparametric cognitive disease progression model (DPM) for autosomal dominant Alzheimer's disease based on the Dominantly Inherited Alzheimer Network (DIAN) observational study. This model includes 3 novel features, in which the DPM (1) aligns and compares participants by disease stage, (2) uses a proportional treatment effect similar to the concept of the Cox proportional hazard ratio, and (3) incorporates extended follow‐up data from participants with different follow‐up durations using all data until last participant visit. We present the DPM model developed by using the DIAN observational study data and demonstrate through simulation that the cognitive DPM used in hypothetical intervention clinical trials produces substantial gains in power compared with the MMRM.
Impact of Stoichiometry on the Structure of van der Waals Layered GeTe/Sb2Te3 Superlattices Used in Interfacial Phase‐Change Memory (iPCM) Devices
Authors: Kowalczyk Philippe , Hippert Françoise , Bernier Nicolas , Mocuta Cristian , Sabbione Chiara , Batista‐Pessoa Walter , Noé Pierre
Published: May 2018

Van der Waals layered GeTe/Sb2Te3 superlattices (SLs) have demonstrated outstanding performances for use in resistive memories in so‐called interfacial phase‐change memory (iPCM) devices. GeTe/Sb2Te3 SLs are made by periodically stacking ultrathin GeTe and Sb2Te3 crystalline layers. The mechanism of the resistance change in iPCM devices is still highly debated. Recent experimental studies on SLs grown by molecular beam epitaxy or pulsed laser deposition indicate that the local structure does not correspond to any of the previously proposed structural models. Here, a new insight is given into the complex structure of prototypical GeTe/Sb2Te3 SLs deposited by magnetron sputtering, which is the used industrial technique for SL growth in iPCM devices. X‐ray diffraction analysis shows that the structural quality of the SL depends critically on its stoichiometry. Moreover, high‐angle annular dark‐field‐scanning transmission electron microscopy analysis of the local atomic order in a perfectly stoichiometric SL reveals the absence of GeTe layers, and that Ge atoms intermix with Sb atoms in, for instance, Ge2Sb2Te5 blocks. This result shows that an alternative structural model is required to explain the origin of the electrical contrast and the nature of the resistive switching mechanism observed in iPCM devices.
Monitoring Based on Narrow‐Band Resonance Raman for “Phase‐Shifting” π‐Conjugated Polydiacetylene Vesicles upon Host–Guest Interaction and Thermal Stimuli
Authors: Cui Chunzhi , Hong Na Yeon , Ahn Dong June
Published: May 2018

The present study reports a quantified monitoring by means of in situ resonance Raman scattering that analyzes phase‐shifting characteristics of π‐systems upon interacting with target analytes. A chemo‐ and thermochromic polydiacetylene vesicular probe is evaluated with multiple‐wavelength Raman scattering modes in resonance with its phases, respectively, and thus can trace the phase‐shifts. This Raman scattering‐based analytical quantification is also successful in monitoring host–guest recognition events by utilizing much narrower bands, compared to those in conventional absorption or photoluminescence (PL) methods. As one of the outcomes, the monitoring analysis overcomes the limitations based on widely used colorimetric response (%CR) or PL that failed in the case of interaction with a surfactant, CTAB.
Simultaneous Local Heating/Thermometry Based on Plasmonic Magnetochromic Nanoheaters
Authors: Li Zhi , Lopez‐Ortega Alberto , Aranda‐Ramos Antonio , Tajada José Luis , Sort Jordi , Nogues Carme , Vavassori Paolo , Nogues Josep , Sepulveda Borja
Published: May 2018

A crucial challenge in nanotherapies is achieving accurate and real‐time control of the therapeutic action, which is particularly relevant in local thermal therapies to minimize healthy tissue damage and necrotic cell deaths. Here, a nanoheater/thermometry concept is presented based on magnetoplasmonic (Co/Au or Fe/Au) nanodomes that merge exceptionally efficient plasmonic heating and simultaneous highly sensitive detection of the temperature variations. The temperature detection is based on precise optical monitoring of the magnetic‐induced rotation of the nanodomes in solution. It is shown that the phase lag between the optical signal and the driving magnetic field can be used to detect viscosity variations around the nanodomes with unprecedented accuracy (detection limit 0.0016 mPa s, i.e., 60‐fold smaller than state‐of‐the‐art plasmonic nanorheometers). This feature is exploited to monitor the viscosity reduction induced by optical heating in real‐time, even in highly inhomogeneous cell dispersions. The magnetochromic nanoheater/thermometers show higher optical stability, much higher heating efficiency and similar temperature detection limits (0.05 °C) compared to state‐of‐the art luminescent nanothermometers. The technological interest is also boosted by the simpler and lower cost temperature detection system, and the cost effectiveness and scalability of the nanofabrication process, thereby highlighting the biomedical potential of this nanotechnology.
Optimization of an In Vitro Starch Digestibility Assay for Rice
Authors: Khatun Amina , Waters Daniel L.E. , Liu Lei
Published: May 2018

In vitro starch digestibility assays are more reproducible and less expensive than in vivo assays and are therefore important tools which assist breeding cereal cultivars with desirable starch digestibility. However, current in vitro starch digestibility assays often use non‐mammalian digestive enzymes combined with the glucose oxidase peroxidase colorimetric (GOC) method of glucose detection which requires multiple steps. A new, simple, in vitro rice starch digestibility assay is developed by trialling several combinations of mammalian digestive enzymes and comparing blood glucose meter based glucose detection methods with the classic GOC method. The glucometer based detection methods had wider glucose concentration detection windows with good reproducibility compared with the GOC method. Digestion with a rat intestinal acetone powder (RIAP) alone was comparable (R2 > 0.99) with digestion using a combination of α‐amylase, pepsin, pancreatin, and RIAP. The optimized in vitro starch digestibility assay correctly estimated the digestibility of rice samples which differed by in vivo glycemic index (GI). This rapid accurate assay only requires a small quantity of sample (15 mg) and can meet the high‐throughput phenotyping requirement of breeding programs in order to develop healthy cereal grains such as low GI rice.
Fennel induces cytotoxic effects against testicular germ cells in mice; evidences for suppressed pre‐implantation embryo development
Authors: Minas Aram , Najafi Gholamreza , Jalali Ali Shalizar , Razi Mazdak
Published: May 2018

Foeniculum vulgare (FVE; fennel) is an aromatic plant belonging to Umbelliferae family, which is widely used in traditional societies because of its different pharmaceutical properties. To uncover the fennel‐derived essential oil (FVEO)‐induced effects on male reproductive potential, 24 mature male albino mice were divided into, control, 0.37, 0.75, and 1.5 mg kg−1 FVEO‐received groups. Following 35 days, the animals were euthanized and the testicular tissue and sperm samples were collected. The histological alterations, tubular differentiation (TDI), spermiogenesis (SPI) indices, apoptosis ratio, and RNA damage of germinal cells were analyzed. Moreover, the sperm count, motility, viability, chromatin condensation, and DNA fragmentation were assessed. Finally, the pre‐implantation embryo development including; the percentage of zygote, 2‐cell embryos and blastocysts were assessed. Observations showed that the FVEO, dose dependently, increased histological damages, resulted in germ cells dissociation, depletion, nuclear shrinkage and significantly (P < .05) decreased tubular differentiation and spermiogenesis ratios. Moreover, the FVEO‐received animals (more significantly in 1.5 mg kg−1‐received group) exhibited decreased sperm count, viability, and motility and represented enhanced percentage of sperms with decondensed chromatin and DNA fragmentation. Finally, the animals in FVEO‐received group showed diminished zygote formation and represented decreased pre‐implantation embryo development compared to control animals. In conclusion, our data showed that, FVEO albeit at higher doses, is able to adversely affect cellular DNA and RNA contents, which in turn is able to negatively affect the sperm count and morphology. All these impairments are able to negatively affect the fertilization potential as well as pre‐implantation embryo development.
What is a stem cell?
Authors: Slack Jonathan M. W.
Published: May 2018

The historical roots of the stem cell concept are traced with respect to its usage in embryology and in hematology. The modern consensus definition of stem cells, comprising both pluripotent stem cells in culture and tissue‐specific stem cells in vivo, is explained and explored. Methods for identifying stem cells are discussed with respect to cell surface markers, telomerase, label retention and transplantability, and properties of the stem cell niche are explored. The CreER method for identifying stem cells in vivo is explained, as is evidence in favor of a stochastic rather than an obligate asymmetric form of cell division. In conclusion, it is found that stem cells do not possess any unique and specific molecular markers; and stem cell behavior depends on the environment of the cell as well as the stem cell's intrinsic qualities. Furthermore, the stochastic mode of division implies that stem cell behavior is a property of a cell population not of an individual cell. In this sense, stem cells do not exist in isolation but only as a part of multicellular system.

This article is categorized under:

Adult Stem Cells, Tissue Renewal, and Regeneration > Tissue Stem Cells and Niches

Adult Stem Cells, Tissue Renewal, and Regeneration > Methods and Principles

Adult Stem Cells, Tissue Renewal, and Regeneration > Environmental Control of Stem Cells
Penalty and regularization method for variational‐hemivariational inequalities with application to frictional contact
Authors: Migórski Stanisław , Zeng Shengda
Published: May 2018

In this paper, we provide results on existence, uniqueness and convergence for a class of variational‐hemivariational inequalities of elliptic type involving a constraint set and a nondifferentiable potential. We introduce a penalized and regularized problem without constraints and with Gteaux differentiable potential. We prove that the solution to the original problem can be approached, as a parameter converges, by the solution of the approximated problem. An application to frictional contact problem with the Signorini contact condition and a static version of the Coulomb friction law illustrates the results.