bluuebunny/crossref_metadata_2025 huggingface dataset:
Substance P in Dorsal Root Ganglion Neurons in Young and Adult Rats, after Nociceptive Stimulation during the Neonatal Period
Authors: Simões Ana Leda Bertoncini , Silva Greice Anne Rodrigues , Giorgetto Carolina , de Cassia do Carmo‐Campos Elisabete , Dias Fernando José , Fazan Valéria Paula Sassoli
Published: December 2017

The nervous system is highly plastic during the neonatal period, being sensitive to noxious stimuli, which may cause short‐ and long‐term pain responsivity changes. Understanding plasticity in peripheral pain pathways is crucial, particularly when the nervous system is still under development and remodeling process. Substance P (SP) is widely used as a marker for peripheral neurons with unmyelinated and small myelinated fibers. We investigated the number of SP immunoreactive neurons in the dorsal root ganglion (DRG) of male and female Wistar rats, 15 and 180 days after nociceptive stimulation during the neonatal period. Right and left 5th lumbar (L5) DRG were incubated in rabbit polyclonal anti‐substance P primary followed by biotinylated donkey anti‐rabbit secondary antibodies. Reaction was revealed with a nickel‐diaminobenzidine solution. Labeled neurons were counted and compared between ages, genders and groups. Gender differences were present in both ages, with the number of SP‐positive DRG neurons being larger in 15‐days‐old males on both sides. After 180 days, males showed a larger number of SP‐positive neurons than females only on the nociceptive stimulated side. An increased number of SP‐positive neurons in the DRG on the stimulated side was present in females, immediately after nociceptive stimulation, but not after 180 days. In conclusion, neonatal noxious stimulation caused a permanent increase in SP‐positive DRG neurons in males that was not observed in females, suggesting that differences in pain processing/responsivity between genders could be related to morphological alterations of the nervous system. Anat Rec, 301:849–861, 2018. © 2017 Wiley Periodicals, Inc.
Increased Expression and Modulated Regulatory Activity of Coinhibitory Receptors PD‐1, TIGIT, and TIM‐3 in Lymphocytes From Patients With Systemic Sclerosis
Authors: Fleury Michelle , Belkina Anna C. , Proctor Elizabeth A. , Zammitti Christopher , Simms Robert W. , Lauffenburger Douglas A. , Snyder‐Cappione Jennifer E. , Lafyatis Robert , Dooms Hans
Published: December 2017

Objective

Immune dysfunction is an important component of the disease process underlying systemic sclerosis (SSc), but the mechanisms contributing to altered immune cell function in SSc remain poorly defined. This study was undertaken to measure the expression and function of the coinhibitory receptors (co‐IRs) programmed cell death 1 (PD‐1), T cell immunoglobulin and ITIM domain (TIGIT), T cell immunoglobulin and mucin domain 3 (TIM‐3), and lymphocyte activation gene 3 (LAG‐3) in lymphocyte subsets from the peripheral blood of patients with SSc.

Methods

Co‐IR expression levels on subsets of immune cells were analyzed using a 16‐color flow cytometry panel. The functional role of co‐IRs was determined by measuring cytokine production after in vitro stimulation of SSc and healthy control peripheral blood mononuclear cells (PBMCs) in the presence of co‐IR–blocking antibodies. Supernatants from cultures of stimulated PBMCs were added to SSc fibroblasts, and their impact on fibroblast gene expression was measured. Mathematical modeling was used to reveal differences between co‐IR functions in SSc patients and healthy controls.

Results

Levels of the co‐IRs PD‐1 and TIGIT were increased, and each was coexpressed, in distinct T cell subsets from SSc patients compared to healthy controls. Levels of TIM‐3 were increased in SSc natural killer cells. PD‐1, TIGIT, and TIM‐3 antibody blockade revealed patient‐specific roles of each of these co‐IRs in modulating activation‐induced T cell cytokine production. In contrast to healthy subjects, blockade of TIGIT and TIM‐3, but not PD‐1, failed to reverse inhibited cytokine production in SSc patients, indicating that enhanced T cell exhaustion is present in SSc. Finally, cytokines secreted in anti–TIM‐3–treated PBMC cultures distinctly changed the gene expression profile in SSc fibroblasts.

Conclusion

The altered expression and regulatory capacity of co‐IRs in SSc lymphocytes may contribute to disease pathophysiology by modulating the cytokine‐mediated cross‐talk of immune cells and fibroblasts at sites of inflammation and/or fibrosis.
Analysis, Verification and Comparison on Feedback‐Aided MA Equivalence and Zhang Equivalency of Minimum‐Kinetic‐Energy Type for Kinematic Control of Redundant Robot Manipulators
Authors: Qiu Binbin , Zhang Yunong , Yang Zhi
Published: December 2017

By following and generalizing Ma et al.'s inspiring work and Zhang et al.'s inspiring work, this paper proposes and investigates three kinds of equivalent relationships with error‐feedback information incorporated for the minimum‐kinetic‐energy (MKE) redundancy resolution. Specifically, these three equivalent relationships are divided into two big classes in terms of scheme formulations: one is termed MKE‐type Ma equivalence (MKE‐ME); the other is MKE‐type Zhang equivalency (MKE‐ZE), which can be further subdivided into MKE‐ZE‐I and MKE‐ZE‐II. Also, the equivalent analyses as well as the primary distinctions about three such equivalent relationships are presented. The simulation results based on a PUMA560 robot manipulator and a three‐link planar robot manipulator not only verify the efficacy of the corresponding velocity‐level and acceleration‐level schemes of MKE‐ME, MKE‐ZE‐I and MKE‐ZE‐II, but also substantiate their reasonableness and effectiveness of these three equivalent relationships. More importantly, the comparative numerical results show their respective characteristics and advantages for kinematic control of redundant robot manipulators.
Biosynthesis of the Nylon 12 Monomer, ω‐Aminododecanoic Acid with Novel CYP153A, AlkJ, and ω‐TA Enzymes
Authors: Ahsan Md. Murshidul , Jeon Hyunwoo , P. Nadarajan Saravanan , Chung Taeowan , Yoo Hee‐Wang , Kim Byung‐Gee , Patil Mahesh D. , Yun Hyungdon
Published: December 2017

Bioplastics are derived from renewable biomass sources, such as vegetable oils, cellulose, and starches. An important and high‐performance member of the bioplastic family is Nylon 12. The biosynthesis of ω‐amino dodecanoic acid (ω‐AmDDA), the monomer of Nylon 12 from vegetable oil derivatives is considered as an alternative to petroleum‐based monomer synthesis. In this study, for the production of ω‐AmDDA from dodecanoic acid (DDA), the cascade of novel P450 (CYP153A), alcohol dehydrogenase (AlkJ), and ω‐transaminase (ω‐TA) is developed. The regioselective ω‐hydroxylation of 1 mM DDA with near complete conversion (>99%) is achieved using a whole‐cell biocatalyst co‐expressing CYP153A, ferredoxin reductase and ferredoxin. When the consecutive biotransformation of ω‐hydroxy dodecanoic acid (ω‐OHDDA) is carried out using a whole‐cell biocatalyst co‐expressing AlkJ and ω‐TA, 1.8 mM ω‐OHDDA is converted into ω‐AmDDA with 87% conversion in 3 h. Finally, when a one‐pot reaction is carried out with 2 mM DDA using both whole‐cell systems, 0.6 mM ω‐AmDDA is produced after a 5 h reaction. The results demonstrated the scope of the potential cascade reaction of novel CYP153A, AlkJ, and ω‐TA for the production of industrially important bioplastic monomers, amino fatty acids, from FFAs.
Simultaneous quantification of multiple components in rat plasma by UPLC‐MS/MS and pharmacokinetic study after oral administration of Huangqi decoction
Authors: Zeng Jia‐Kai , Li Yuan‐Yuan , Wang Tian‐Ming , Zhong Jie , Wu Jia‐Sheng , Liu Ping , Zhang Hua , Ma Yue‐Ming
Published: December 2017

A rapid, sensitive and accurate UPLC‐MS/MS method was developed for the simultaneous quantification of components of Huangqi decoction (HQD), such as calycosin‐7‐O‐β‐d‐glucoside, calycosin‐glucuronide, liquiritin, formononetin‐glucuronide, isoliquiritin, liquiritigenin, ononin, calycosin, isoliquiritigenin, formononetin, glycyrrhizic acid, astragaloside IV, cycloastragenol, and glycyrrhetinic acid, in rat plasma. After plasma samples were extracted by protein precipitation, chromatographic separation was performed with a C18 column, using a gradient of methanol and 0.05% acetic acid containing 4mm ammonium acetate as the mobile phase. Multiple reaction monitoring scanning was performed to quantify the analytes, and the electrospray ion source polarity was switched between positive and negative modes in a single run of 10 min. Method validation showed that specificity, linearity, accuracy, precision, extraction recovery, matrix effect and stability for 14 components met the requirements for their quantitation in biological samples. The established method was successfully applied to the pharmacokinetic study of multiple components in rats after intragastric administration of HQD. The results clarified the pharmacokinetic characteristics of multiple components found in HQD. This research provides useful information for understanding the relation between the chemical components of HQD and their therapeutic effects.
Action video gaming and the brain: fMRI effects without behavioral effects in visual and verbal cognitive tasks
Authors: Richlan Fabio , Schubert Juliane , Mayer Rebecca , Hutzler Florian , Kronbichler Martin
Published: December 2017

Introduction

In this functional magnetic resonance imaging (fMRI) study, we compared task performance together with brain activation in a visuospatial task (VST) and a letter detection task (LDT) between longtime action video gamers (N = 14) and nongamers (N = 14) in order to investigate possible effects of gaming on cognitive and brain abilities.

Methods

Based on previous research, we expected advantages in performance for experienced action video gamers accompanied by less activation (due to higher efficiency) as measured by fMRI in the frontoparietal attention network.

Results

Contrary to these expectations, we did not find differences in overall task performance, nor in brain activation during the VST. We identified, however, a significantly different increase in the BOLD signal from a baseline task to the LDT in action video gamers compared with nongamers. This increased activation was evident in a number of frontoparietal regions including the left middle paracingulate cortex, the left superior frontal sulcus, the opercular part of the left inferior frontal gyrus, and the left and right posterior parietal cortex. Furthermore, we found increased activation in the triangular part of the left inferior frontal gyrus in gamers relative to nongamers when activation during the LDT was compared with activation during the VST.

Conclusions

In sum, the expected positive relation between action video game experience and cognitive performance could not be confirmed. Despite their comparable task performance, however, gamers and nongamers exhibited clear‐cut differences in brain activation patterns presumably reflecting differences in neural engagement, especially during verbal cognitive tasks.
Bombesin receptor subtype‐3‐expressing neurons regulate energy homeostasis through a novel neuronal pathway in the hypothalamus
Authors: Maruyama Minoru , Hotta Natsu , Nio Yasunori , Hamagami Kenichi , Nagi Toshimi , Funata Masaaki , Sakamoto Junichi , Nakakariya Masanori , Amano Nobuyuki , Nishida Mayumi , Okawa Tomohiro , Arikawa Yasuyoshi , Sasaki Shinobu , Kasai Shizuo , Nagisa Yasutaka , Habata Yugo , Mori Masaaki
Published: December 2017

Objectives

Bombesin receptor subtype‐3 (BRS‐3) has been suggested to play a potential role in energy homeostasis. However, the physiological mechanism of BRS‐3 on energy homeostasis remains unknown. Thus, we investigated the BRS‐3‐mediated neuronal pathway involved in food intake and energy expenditure.

Materials and Methods

Expression of BRS‐3 in the rat brain was histologically examined. The BRS‐3 neurons activated by refeeding‐induced satiety or a BRS‐3 agonist were identified by c‐Fos immunostaining. We also analyzed expression changes in feeding‐relating peptides in the brain of fasted rats administered with the BRS‐3 agonist.

Results

In the paraventricular hypothalamic nucleus (PVH), dorsomedial hypothalamic nucleus (DMH), and medial preoptic area (MPA), strong c‐Fos induction was observed in the BRS‐3 neurons especially in PVH after refeeding. However, the BRS‐3 neurons in the PVH did not express feeding‐regulating peptides, while the BRS‐3 agonist administration induced c‐Fos expression in the DMH and MPA, which were not refeeding‐sensitive, as well as in the PVH. The BRS‐3 agonist administration changed the Pomc and Cart mRNA level in several brain regions of fasted rats.

Conclusion

These results suggest that BRS‐3 neurons in the PVH are a novel functional subdivision in the PVH that regulates feeding behavior. As the MPA and DMH are reportedly involved in thermoregulation and energy metabolism, the BRS‐3 neurons in the MPA/DMH might mediate the energy expenditure control. POMC and CART may contribute to BRS‐3 neuron‐mediated energy homeostasis regulation. In summary, BRS‐3‐expressing neurons could regulate energy homeostasis through a novel neuronal pathway.
Vascular surgery of aortic thrombosis in a dog using Fogarty maneuver – technical feasibility
Authors: Schwede Maartje , Richter Olaf , Alef Michaele , Theuß Tobias , Loderstedt Shenja
Published: December 2017

Key Clinical Message

Aortic thromboembolism is a rare and life‐threatening disease in dogs. This report aims to describe the successful surgical treatment by use of a Fogarty Thrombectomy Catheter in an 8‐year‐old patient. The postsurgical intensive care therapy to prevent ischemia‐reperfusion syndrome is specified, despite poor outcome in our case (owner elected euthanasia).
In Situ Prepared Flexible 3D Polymer Film Photocatalyst for Highly Selective Solar Fuel Production from CO2
Authors: Yadav Rajesh K. , Kumar Abhishek , Yadav Dolly , Park No‐Joong , Kim Jae Young , Baeg Jin‐Ook
Published: December 2017

The conversion of CO2 to valuable solar fuels by means of solar energy using metal‐free flexible film photocatalysts is an appealing strategy. Here we demonstrate a three dimensional aromatic polymer (3DAP) derived from triptycene (TC) as a metal free, stable and highly efficient visible light responsive flexible film photocatalyst for selective solar fuel production from CO2. For this research work, the polymerization of TC by the Diels–Alder reaction is exploited for the first time as a new synthetic approach for the construction of three dimensional aromatic polymer photocatalyst. The visible‐light harvesting ability, band gap suitability, high Brunauer–Emmett–Teller (BET) surface area and electron transfer capability via interconnecting 3D chain of 3DAP contribute to the excellent performance of the film photocatalyst as evident from 91.09 % NADH regeneration and 225.12 μmol of formic acid production. This work provides important insights into the design of flexible polymer film photocatalyst for selective solar fuel formation from CO2 and is expected to trigger further interest in sustainable solar energy conversion applications such as tailorable and wearable devices.
New Electrode and Electrolyte Configurations for Lithium‐Oxygen Battery
Authors: Ulissi Ulderico , Elia Giuseppe Antonio , Jeong Sangsik , Reiter Jakub , Tsiouvaras Nikolaos , Passerini Stefano , Hassoun Jusef
Published: December 2017

Cathode configurations reported herein are alternative to the most diffused ones for application in lithium‐oxygen batteries, using an ionic liquid‐based electrolyte. The electrodes employ high surface area conductive carbon as the reaction host, and polytetrafluoroethylene as the binding agent to enhance the oxygen reduction reaction (ORR)/oxygen evolution reaction (OER) reversibility. Roll‐pressed, self‐standing electrodes (SSEs) and thinner, spray deposited electrodes (SDEs) are characterized in lithium‐oxygen cells using an ionic liquid (IL) based electrolyte formed by mixing lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) salt and N,N‐diethyl‐N‐(2‐methoxyethyl)‐N‐methylammonium bis(trifluoromethanesulfonyl)imide (DEMETFSI). The electrochemical results reveal reversible reactions for both electrode configurations, but improved electrochemical performance for the self‐standing electrodes in lithium‐oxygen cells. These electrodes show charge/discharge polarizations at 60 °C limited to 0.4 V, with capacity up to 1 mAh cm−2 and energy efficiency of about 88 %, while the spray deposited electrodes reveal, under the same conditions, a polarization of 0.6 V and energy efficiency of 80 %. The roll pressed electrode combined with the DEMETFSI‐LiTFSI electrolyte and a composite LixSn‐C alloy anode forms a full Li‐ion oxygen cell showing extremely limited polarization, and remarkable energy efficiency.
Fluorine‐Containing Silsesquioxane‐Based Hybrid Porous Polymers Mediated by Bases and Their Use in Water Remediation
Authors: Ge Mingtao , Liu Hongzhi
Published: December 2017

Two different silsesquioxane‐based porous polymers (FHPPs), namely FHPP‐1 and FHPP‐2, have been prepared, respectively, by changing the acid scavenger from sodium bicarbonate to triethylamine in the Heck reaction between octavinylsilsesquioxane (OVS) and 1,4‐dibromotetrafluorobenzene. It was observed that defluorination occurred in the case of triethylamine. FHPP‐1 possesses a higher surface area of 600 m2 g−1 and a hierarchical porous structure; in contrast, FHPP‐2 possesses a SBET value of 325 m2 g−1 and a microporous structure. This work provides a new approach to the preparation and tuning of fluorine‐containing porous polymers based on silsesquioxanes. These porous materials were employed to remove dyes and a heavy metal from water, showing good binding efficiencies.
Culprit plaque characteristics in women vs men with a first ST‐segment elevation myocardial infarction: In vivo optical coherence tomography insights
Authors: Sun Rong , Sun Liping , Fu Yandong , Liu Huimin , Xu Maoen , Ren Xuefeng , Yu Huai , Dong Hui , Liu Yang , Zhu Yinchun , Tian Jinwei , Yu Bo
Published: December 2017

Background

It is unclear whether more severe coronary atherosclerosis is a prerequisite to an initial acute coronary event in women vs men.

Hypothesis

Women may have more severe coronary atherosclerosis than men in patients with acute coronary event.

Methods

We used intravascular optical coherence tomography (OCT) to evaluate gender differences in culprit‐plaque morphology in patients with a first ST‐segment elevation myocardial infarction (STEMI).We retrospectively enrolled 211 consecutive patients who experienced a first STEMI and underwent an OCT examination of their infarct‐related artery before primary percutaneous coronary intervention.

Results

Of the 211 patients enrolled, 162 (76.7%) were men and 49 (23.2%) were women. The women were significantly older than the men (mean age, 60.2 ± 8.2 vs 55.7 ± 11.2 years; P = 0.01) and less likely to be current smokers (P = 0.02). Moreover, the delay from symptom onset to reperfusion was longer in women than in men (7.6 ± 6.1 vs 5.5 ± 4.4 hours; P = 0.01). The OCT data indicated that there were no gender differences in culprit‐plaque morphology, including lipid length, lipid arc, minimum fibrous cap thickness, or minimum lumen area. Additionally, no gender differences were found in the prevalence of plaque rupture, thin‐cap fibroatheroma, residual thrombus, microvessels, macrophages, cholesterol crystals, or calcification.

Conclusions

Among patients presenting with a first STEMI, there were no differences in culprit plaque features between women and men.
Treatment deintensification in human papillomavirus‐positive oropharynx cancer: Outcomes from the National Cancer Data Base
Authors: Cheraghlou Shayan , Yu Phoebe K. , Otremba Michael D. , Park Henry S. , Bhatia Aarti , Zogg Cheryl K. , Mehra Saral , Yarbrough Wendell G. , Judson Benjamin L.
Published: December 2017

BACKGROUND

The growing epidemic of human papillomavirus‐positive (HPV+) oropharyngeal cancer and the favorable prognosis of this disease etiology have led to a call for deintensified treatment for some patients with HPV+ cancers. One of the proposed methods of treatment deintensification is the avoidance of chemotherapy concurrent with definitive/adjuvant radiotherapy. To the authors' knowledge, the safety of this form of treatment de‐escalation is unknown and the current literature in this area is sparse. The authors investigated outcomes after various treatment combinations stratified by American Joint Committee on Cancer (AJCC) eighth edition disease stage using patients from the National Cancer Data Base.

METHODS

A retrospective study of 4443 patients with HPV+ oropharyngeal cancer in the National Cancer Data Base was conducted. Patients were stratified into AJCC eighth edition disease stage groups. Multivariate Cox regressions as well as univariate Kaplan‐Meier analyses were conducted.

RESULTS

For patients with stage I disease, treatment with definitive radiotherapy was associated with diminished survival compared with chemoradiotherapy (hazard ratio [HR], 1.798; P = .029), surgery with adjuvant radiotherapy (HR, 2.563; P = .002), or surgery with adjuvant chemoradiotherapy (HR, 2.427; P = .001). For patients with stage II disease, compared with treatment with chemoradiotherapy, patients treated with a single‐modality (either surgery [HR, 2.539; P = .009] or radiotherapy [HR, 2.200; P = .030]) were found to have poorer survival. Among patients with stage III disease, triple‐modality therapy was associated with improved survival (HR, 0.518; P = .024) compared with treatment with chemoradiotherapy.

CONCLUSIONS

Deintensification of treatment from chemoradiotherapy to radiotherapy or surgery alone in cases of HPV+ AJCC eighth edition stage I or stage II disease may compromise patient safety. Treatment intensification to triple‐modality therapy for patients with stage III disease may improve survival in this group. Cancer 2018;124:717‐26. © 2017 American Cancer Society.
An efficient parallel simulation of unsteady blood flows in patient‐specific pulmonary artery
Authors: Kong Fande , Kheyfets Vitaly , Finol Ender , Cai Xiao‐Chuan
Published: December 2017

Simulation of blood flows in the pulmonary artery provides some insight into certain diseases by examining the relationship between some continuum metrics, eg, the wall shear stress acting on the vascular endothelium, which responds to flow‐induced mechanical forces by releasing vasodilators/constrictors. V. Kheyfets, in his previous work, studies numerically a patient‐specific pulmonary circulation to show that decreasing wall shear stress is correlated with increasing pulmonary vascular impedance. In this paper, we develop a scalable parallel algorithm based on domain decomposition methods to investigate an unsteady model with patient‐specific pulsatile waveforms as the inlet boundary condition. The unsteady model offers tremendously more information about the dynamic behavior of the flow field, but computationally speaking, the simulation is a lot more expensive since a problem which is similar to the steady‐state problem has to be solved many times, and therefore, the traditional sequential approach is not suitable anymore. We show computationally that simulations using the proposed parallel approach with up to 10 000 processor cores can be obtained with much reduced compute time. This makes the technology potentially usable for the routine study of the dynamic behavior of blood flows in the pulmonary artery, in particular, the changes of the blood flows and the wall shear stress in the spatial and temporal dimensions.
Deoxythymidine–Pterin Fluorescent Adduct Formation through a Photosensitized Process
Authors: Estébanez Sandra , Thomas Andrés H. , Lorente Carolina
Published: December 2017

A new fluorescent compound was isolated from UVA‐irradiated aqueous solutions containing pterin (Ptr) and 2′deoxythymidine (dT) in anaerobic conditions. Pterins are widespread in living systems in small amounts, but they are accumulated in some pathological situations. Under UVA radiation, pterins are photochemically active, fluorescent, and photosensitize the generation of singlet oxygen [1O2(1Δg)]. The isolated compound was structurally characterized by using liquid chromatography coupled to tandem mass spectrometry, and its photophysical properties were studied with the time‐correlated single‐photon‐counting technique. The molecular weight and the analysis of the fragmentation correspond to a molecule where the pterinic moiety is attached to the thymine nucleobase. The product exhibits photophysical properties similar to those of Ptr, including relatively high fluorescence and 1O2 production quantum yields.
Population Modeling of Tumor Kinetics and Overall Survival to Identify Prognostic and Predictive Biomarkers of Efficacy for Durvalumab in Patients With Urothelial Carcinoma
Authors: Zheng Yanan , Narwal Rajesh , Jin ChaoYu , Baverel Paul G. , Jin Xiaoping , Gupta Ashok , Ben Yong , Wang Bing , Mukhopadhyay Pralay , Higgs Brandon W. , Roskos Lorin
Published: December 2017

Durvalumab is an anti‐PD‐L1 monoclonal antibody approved for patients with locally advanced or metastatic urothelial carcinoma (UC) that has progressed after platinum‐containing chemotherapy. A population tumor kinetic model, coupled with dropout and survival models, was developed to describe longitudinal tumor size data and predict overall survival in UC patients treated with durvalumab (NCT01693562) and to identify prognostic and predictive biomarkers of clinical outcomes. Model‐based covariate analysis identified liver metastasis as the most influential factor for tumor growth and immune‐cell PD‐L1 expression and baseline tumor burden as predictive factors for tumor killing. Tumor or immune‐cell PD‐L1 expression, liver metastasis, baseline hemoglobin, and albumin levels were identified as significant covariates for overall survival. These model simulations provided further insights into the impact of PD‐L1 cutoff values on treatment outcomes. The modeling framework can be a useful tool to guide patient selection and enrichment strategies for immunotherapies across various cancer indications.
Human innate lymphoid cells (ILCs): Toward a uniform immune‐phenotyping
Authors: Trabanelli Sara , Gomez‐Cadena Alejandra , Salomé Bérengère , Michaud Katarzyna , Mavilio Domenico , Landis Basile Nicolas , Jandus Peter , Jandus Camilla
Published: December 2017

Helper innate lymphoid cells (ILCs), the most recently identified population of the ILC family, play a fundamental role in the restoration of tissue integrity, in the protection against infiltrating pathogens as well as in tumor immune‐surveillance. ILCs have been divided into three main subsets, ILC1, ILC2, and ILC3, that can be specifically activated by different signals coming either indirectly from pathogens or from other cell populations, including cancer cells. Following activation, ILCs are in turn able to promptly secrete a wide range of soluble mediators that modulate effector cell functions. The discovery and the study of these immune cells is now offering important opportunities for innovative therapies of allergic airway diseases, inflammatory disorders and might be crucial for the discovery of new targets for the therapy of cancer. It is therefore fundamental that the scientific community establishes harmonized guidelines to obtain a consensus in the identification and phenotypical and functional characterization of ILCs. © 2018 International Clinical Cytometry Society
Randomized crossover trial comparing EUS‐guided fine‐needle aspiration with EUS‐guided fine‐needle biopsy for gastric subepithelial tumors
Authors: Iwai Tomohisa , Kida Mitsuhiro , Imaizumi Hiroshi , Miyazawa Shiro , Okuwaki Kosuke , Yamauchi Hiroshi , Kaneko Toru , Hasegawa Rikiya , Miyata Eiji , Koizumi Wasaburo
Published: December 2017

Aim

The purpose of this study is to compare the diagnostic yield of endoscopic ultrasound (EUS)‐guided fine‐needle aspiration (EUS‐FNA) and EUS‐guided fine‐needle biopsy (EUS‐FNB) for gastric subepithelial tumors (SET).

Methods

Patients diagnosed SET derived from fourth layer of the stomach were prospectively enrolled and randomly assigned to undergo both EUS‐FNA using standard needle and EUS‐FNB using a core biopsy needle alternatively to the same lesion a total of four times per session. The specimen was carefully examined for the presence of a macroscopic visible core, appearing as threadlike yellowish or bloody pieces of tissue and blinded histocytologic analyses were conducted. For spindle cell lesions by hematoxylin and eosin staining (H&E) on histologic evaluation, immunohistochemical staining was performed in all cases to confirm the pathological diagnosis.

Results

A total of 23 patients were enrolled and underwent paired EUS‐FNA and ‐FNB sampling. The diagnostic rate due to immunohistochemical staining was 73.9% and 91.3%, respectively (P = .120). The rate of obtaining specimens with a macroscopic yellowish core and only a bloody core among the tissue specimens were respectively 43.5% and 52.2% for EUS‐FNA and 69.6% and 30.4% for EUS‐FNB. The diagnostic rate for a yellowish core (84.6%) and a bloody core (84.2%, P = .971) did not differ significantly.

Conclusion

Both techniques were equivalently safe and successful in terms of a high diagnostic yield for gastric SET. And the tissue that can be immunohistochemically stained is present even in the specimens that appear to be a macroscopically bloody core.
Investigations of LiP(SiMe2CH2SiMe3)–PtBu2, the Surprising Byproduct in the Metalation of (Me3Si)2P–PtBu2
Authors: Sattler Ewald , Szilvási Tibor , Matern Eberhard , Bombicz Petra , Gamer Michael , Okrut Alexander , Kovács Ilona
Published: December 2017

During the metalation reaction of (Me3Si)2P–PtBu2 with nBuLi, a byproduct with the sum formula Li(thf)nP(SiMe2CH2SiMe3)–PtBu2 (2, n = 2.7–1) was detected. The formation of the unexpected substituent SiMe2CH2SiMe3 was investigated, a possible reaction mechanism based on DFT calculations established, and the compound synthesized following an independent route. Compound 2 eliminated thf in vacuo to yield the dimeric [Li(thf)P(SiMe2CH2SiMe3)–PtBu2]2 (2a). Exchange of thf with tmeda [Me2N(CH2)2NMe2] in 2 led to the solvent‐separated ion pair [Li(tmeda)2]+[(SiMe2CH2SiMe3)P–PtBu2]– (4). The solid‐state structures of 2a, 4, and the contact ion pair Li(thf)(tmeda)P(SiMe2CH2SiMe3)–PtBu2 (5) were determined by single‐crystal X‐ray diffraction analysis. Extensive variable‐temperature multinuclear NMR studies were carried out to elucidate the structures of these compounds in solution and to compare them with the solid‐state structures.
Interactions of Ascorbic Acid with Satraplatin and its trans Analog JM576: DFT Computational Study
Authors: Šebesta Filip , Burda Jaroslav V.
Published: December 2017

Knowledge of the mechanisms for the reduction of PtIV anticancer prodrugs is of great importance, since the reduction process is considered as a necessary step for their activation. Therefore, in this study, we investigate the reduction of satraplatin {JM216, cis,trans,cis‐[PtCl2(OAc)2(cha)(NH3)], cha = cyclohexylamine} by ascorbic acid (AA) where proton‐assisted electron‐transfer and outer‐sphere electron‐transfer mechanisms are employed. Also, the presence of an additional base, which should increase the concentration of the deprotonated AA2– form, is discussed. Structures are optimized at the B3LYP‐GD3BJ/6‐31+G(d)/MWB60/C‐PCM/Klamt level and single‐point calculations are performed in the larger 6‐311++G(2df,2pd)/MWB60 basis set, together with the better implicit solvation model – IEF‐PCM/scaled‐UAKS. All three protonation states of ascorbic acid are taken into consideration. An effective rate constant of 2.6 × 10–3 m–1 s–1 is obtained from the kinetic formalism for side reactions, as described recently. For the reduction of satraplatin by fully deprotonated ascorbic acid, changes of the electron‐density distribution along the reaction coordinate are further investigated using NPA, QTAIM, and reaction electronic‐flux analysis. Both electron‐transfer mechanisms are also explored for the satraplatin trans analog JM576 {trans,trans,trans‐[PtCl2(OAc)2(cha)(NH3)]}. The resulting effective rate constant of 5.1 × 10–2 m–1 s–1 is compared with available experimental data.
Ruthenium‐Catalyzed Reductive Amidation without an External Hydrogen Source
Authors: Yagafarov Niyaz Z. , Muratov Karim M. , Biriukov Klim , Usanov Dmitry L. , Chusova Olga , Perekalin Dmitry S. , Chusov Denis
Published: December 2017

A catalytic reaction between aldehydes and primary amides that leads to N‐alkylated amides was investigated. The developed protocol employs carbon monoxide as a deoxygenative agent and, therefore, avoids the use of an external hydrogen source. Cyclopentadienyl ruthenium complexes provided excellent catalytic efficiency and could be used with loadings as low as 0.5–1 mol‐%. A representative number of secondary amides were successfully prepared in yields of 70–84 %.
Sulfinate Allenyl Carbenoids: Synthesis of 2,5‐Dihydrofurans by Domino Rearrangement and Cyclization
Authors: Tata Rama Rao , Harmata Michael
Published: December 2017

Propargylic sulfinates can be successfully deprotonated at the acetylenic carbon with lithium hexamethyldisilazide. The resulting anions add successfully to aldehydes and ketones. Treatment of these adducts with a silver cation results in both a 2,3‐sigmatropic shift and a cyclization of the resulting allene to afford 2,5‐dihydrofurans in excellent yields.
Genotoxic and mutagenic properties of Ni and NiO nanoparticles investigated by comet assay, γ‐H2AX staining, Hprt mutation assay and ToxTracker reporter cell lines
Authors: Åkerlund Emma , Cappellini Francesca , Di Bucchianico Sebastiano , Islam Shafiqul , Skoglund Sara , Derr Remco , Odnevall Wallinder Inger , Hendriks Giel , Karlsson Hanna L.
Published: December 2017

Nickel (Ni) compounds are classified as carcinogenic to humans but the underlying mechanisms are still poorly understood. Furthermore, effects related to nanoparticles (NPs) of Ni have not been fully elucidated. The aim of this study was to investigate genotoxicity and mutagenicity of Ni and NiO NPs and compare the effect to soluble Ni from NiCl2. We employed different models; i.e., exposure of (1) human bronchial epithelial cells (HBEC) followed by DNA strand break analysis (comet assay and γ‐H2AX staining); (2) six different mouse embryonic stem (mES) reporter cell lines (ToxTracker) that are constructed to exhibit fluorescence upon the induction of various pathways of relevance for (geno)toxicity and cancer; and (3) mES cells followed by mutagenicity testing (Hprt assay). The results showed increased DNA strand breaks (comet assay) for the NiO NPs and at higher doses also for the Ni NPs whereas no effects were observed for Ni ions/complexes from NiCl2. By employing the reporter cell lines, oxidative stress was observed as the main toxic mechanism and protein unfolding occurred at cytotoxic doses for all three Ni‐containing materials. Oxidative stress was also detected in the HBEC cells following NP‐exposure. None of these materials induced the reporter related to direct DNA damage and stalled replication forks. A small but statistically significant increase in Hprt mutations was observed for NiO but only at one dose. We conclude that Ni and NiO NPs show more pronounced (geno)toxic effects compared to Ni ions/complexes, indicating more serious health concerns. Environ. Mol. Mutagen. 59:211–222, 2018. © 2017 The Authors Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society
Focused ultrasound brain stimulation to anesthetized rats induces long‐term changes in somatosensory evoked potentials
Authors: Yoo Seung‐Schik , Yoon Kyungho , Croce Phillip , Cammalleri Amanda , Margolin Ryan W. , Lee Wonhye
Published: December 2017

Low‐intensity transcranial focused ultrasound (FUS) has emerged as a noninvasive brain stimulation modality that can reach deep brain areas with high spatial specificity. Previous studies have identified transient effects of FUS on the brain excitability and accompanying physiological responses. Yet the presence of long‐lasting effects of FUS, which extend on the order of half an hour or more, has not been probed. We transcranially applied FUS to the somatosensory areas of the anesthetized rats for 10 min at a low duty cycle (5%) and intensity, far below the level that could alter the tissue temperature. Concurrently, we measured electroencephalographic somatosensory evoked potentials (SEP) induced by the unilateral electrical stimulation of the hind limb before and after the sonication. Compared with the control sham condition that did not involve sonication, differential SEP features were evident and persisted beyond 35 min after the administration of FUS. The presence of this nontransient neuromodulatory effect may provide early evidence that FUS‐mediated brain stimulation has the potential to induce neuroplasticity.
Synthesis and antioxidant, antixanthine oxidase, and antielastase activities of novel N,S‐substituted polyhalogenated nitrobutadiene derivatives
Authors: Onul Nihal , Ertik Onur , Mermer Nese , Yanardag Refiye
Published: December 2017

In this study, three substituted polyhalogenated nitrobutadiene derivatives were synthesized. Compound 1‐[(2,3‐dibromopropyl)sulfanyl]‐1,3,4,4‐tetrachloro‐2‐nitrobuta‐1,3‐diene (4) was synthesized before by our group. Compounds 8‐{[1‐[(2,3‐dibromopropyl)sulfany]‐3,4,4‐trichloro‐2‐nitrobuta‐1,3‐butadien‐1‐yl}‐1,4‐dioxa‐8‐azaspiro[4.5]decane (5) and 1‐[(2,3‐dibromopropyl)sulfanyl]‐3,4,4‐trichloro‐N‐(4‐methylpiperazin‐1‐yl)‐2‐nitrobuta‐1,3‐diene‐1‐amine (6) were synthesized in this work as original compounds. Xanthine oxidase, elastase inhibition abilities, and antioxidant activities were investigated in this work for compounds 4, 5, and 6. In this study, compounds 4, 5, and 6 exhibited antixanthine oxidase, antielastase, and antioxidant activities. Among the compounds screened, compound 4 exhibited xanthine oxidase and elastase inhibitor effect similar to the standard compound. Among the three tested compounds, compound 6 showed potent DPPH radical scavenging and reducing power activities. Therefore, these three compounds (4, 5, and 6) may be useful as an antixanthine oxidase, antielastase, and antioxidant agent in pharmaceutical and cosmetic industry.
Three‐dimensional liver‐derived extracellular matrix hydrogel promotes liver organoids function
Authors: Saheli Mona , Sepantafar Mohammadmajid , Pournasr Behshad , Farzaneh Zahra , Vosough Massoud , Piryaei Abbas , Baharvand Hossein
Published: December 2017

An important advantage of employing extracellular matrix (ECM)‐derived biomaterials in tissue engineering is the ability to tailor the biochemical and biophysical microenvironment of the cells. This study aims to assess whether three‐dimensional (3D) liver‐derived ECM hydrogel (LEMgel) promotes physiological function of liver organoids generated by self‐organization of human hepatocarcinoma cells together with human mesenchymal and endothelial cells. We have optimized the decellularization method to fabricate liver ECM derived from sheep to preserve the greatest content of glycosaminoglycans, collagen, laminin, and fibronectin in produced LEMgel. During gelation, complex viscoelasticity modulus of the LEMgel (3 mg/mL) increased from 186.7 to 1570.5 Pa and Tan Delta decreased from 0.27 to 0.18. Scanning electron microscopy (SEM) determined that the LEMgel had a pore size of 382 ± 71 µm. Hepatocarcinoma cells in the self‐organized liver organoids in 3D LEMgel (LEMgel organoids) showed an epithelial phenotype and expressed ALB, CYP3A4, E‐cadherin, and ASGPR. The LEMgel organoid had significant upregulation of transcripts of ALB, CYP3A4, CYP3A7, and TAT as well as downregulation of AFP compared to collagen type I‐ and hydrogel‐free‐organoids or organoids in solubilized LEM and 2D culture of hepatocarcinoma cells. Generated 3D LEMgel organoids had significantly more ALB and AAT secretion, urea production, CYP3A4 enzyme activity, and inducibility. In conclusion, 3D LEMgel enhanced the functional activity of self‐organized liver organoids compared to traditional 2D, 3D, and collagen gel cultures. Our novel 3D LEMgel organoid could potentially be used in liver tissue engineering, drug discovery, toxicology studies, or bio‐artificial liver fabrication.
microRNA as a systemic intervention in the specific breast cancer subtypes with C‐MYC impacts; introducing subtype‐based appraisal tool
Authors: Pourteimoor Vida , Paryan Mahdi , Mohammadi‐Yeganeh Samira
Published: December 2017

Breast cancer is indisputably a heterogeneous disease, in which a formidable combination of definitely dis‐regulated C‐MYC and microRNA (miRNA) profiles along with other factors are responsible to generate a specific type of breast cancer. C‐MYC as a master regulator of more than 20,000 genes can modify the expression of genes underlying to perform diverse conflicting functional frameworks. The functional spectra of miRNA in the new areas of the evolution of cell behaviors are identified. Here, we endeavor to summarize some recent advances of miRNA applications that can be recruited as combinatorial targeted therapy for patients with breast cancer. Also, it is important to indicate that some exosomal miRNAs including miR‐126, miR‐122, miR‐92‐1, miR‐19a, and miR‐29c together with circular miRNAs, such as miR‐21‐5p, miR‐96‐5p, and miR‐125b‐5p can provide a promising evaluation route in breast cancer prognosis. Furthermore, miR‐342, miR‐520 for triple negative and hormone receptor‐positive types of breast cancer, respectively in collaboration with two detected distinct cluster of miRNAs for different breast cancer cell lines can be applied for more dedicated miRNA‐based individualized targeted therapy. New DNA handling capacity of C‐MYC‐related oncogenic miRNAs through coordination with exosomal miRNAs and circulatory ones can be a potential appraisal tool in breast cancer management. Given the notion that genomic instability is a hallmark of breast cancer, the different horizons that are provided in this review can be employed for more precise and profound analyses to achieve an evaluation signature for breast cancer subtypes.
131I radiolabeled immune albumin nanospheres loaded with doxorubicin for in vivo combinatorial therapy
Authors: Ji Anping , Zhang Yuanchao , Lv Gaochao , Lin Jianguo , Qi Ning , Ji Faquan , Du Minghua
Published: December 2017

For the purpose of providing new insights for high‐efficiency radiochemotherapy of hepatoma, a radioimmunotherapy and chemotherapy combinatorial therapy albumin nanospheres 131I‐antiAFPMcAb‐DOX‐BSA‐NPs was designed and prepared. It was obtained in a high radiolabeling yield approximately 65% with the radiochemical purity of over 98%. The transmission electron microscope showed that the nanospheres obtained in good monodispersion with a diameter of approximately 230 nm. The doxorubicin (DOX) loading capacity of the DOX‐BSA‐NPs nanoparticles was determined to be approximately 180 μg/mg and 95.79 ± 3.89%. DOX was released gradually in 6 days. In vivo tumor‐growth inhibition experiments showed that after treating with 131I‐antiAFPMcAb‐DOX‐BSA‐NPs for 14 days, the tumor volume decreased more obvious than that of other 2 time points and the control groups. All the results indicated that the radiolabeled immune albumin nanospheres 131I‐antiAFPMcAb‐DOX‐BSA‐NPs could significantly inhibit the hepatoma tumor growth with the strategy of combinatorial radioimmunotherapy and chemotherapy.
Gas‐phase fragmentation reactions of protonated cocaine: New details to an old story
Authors: Dias Herbert J. , Bento Mariana V. B. , da Silva Éder H. , Saturnino‐Júnior Andrade , de Oliveira Marcelo F. , Vessecchi Ricardo , Parreira Renato L. T. , Crotti Antônio E. M.
Published: December 2017

We have used a combination of multiple stage mass spectrometry (MSn) experiments, hydrogen/deuterium exchange experiments, and thermochemical data estimated by computational chemistry calculations at the B3LYP/6‐31+G(d,p) level of theory to revisit the gas‐phase fragmentation of protonated cocaine. The lone pair of nitrogen participates in major fragmentation routes of protonated cocaine, to generate cyclic iminium ions. The structure of product ion m/z 182, which has been previously proposed in the literature, was shown to be unstable; therefore, we have decided to revisit it. Here, we propose another ion structures for the product ion m/z 182 that is supported by thermochemical data. Compared with the formation of other product ions, the formation of the most intense product ions in the collision‐induced dissociation spectrum of protonated cocaine (m/z 182 and m/z 82) is the most energetically favorable. We propose the structure and formation of m/z 122 and m/z 91 for the first time. We suggest that m/z 91 originates from m/z 122 instead of m/z 119, as fully supported by MSn experiments. The results of this study could help to study and quantify cocaine metabolites.
Fixed‐bearing medial unicompartmental knee arthroplasty restores neither the medial pivoting behavior nor the ligament forces of the intact knee in passive flexion
Authors: Kia Mohammad , Warth Lucian C. , Lipman Joseph D. , Wright Timothy M. , Westrich Geoffrey H. , Cross Michael B. , Mayman David J. , Pearle Andrew D. , Imhauser Carl W.
Published: December 2017

Medial unicompartmental knee arthroplasty (UKA) is an accepted treatment for isolated medial osteoarthritis. However, using an improper thickness for the tibial component may contribute to early failure of the prosthesis or disease progression in the unreplaced lateral compartment. Little is known of the effect of insert thickness on both knee kinematics and ligament forces. Therefore, a computational model of the tibiofemoral joint was used to determine how non‐conforming, fixed bearing medial UKA affects tibiofemoral kinematics, and tension in the medial collateral ligament (MCL) and the anterior cruciate ligament (ACL) during passive knee flexion. Fixed bearing medial UKA could not maintain the medial pivoting that occurred in the intact knee from 0° to 30° of passive flexion. Abnormal anterior–posterior (AP) translations of the femoral condyles relative to the tibia delayed coupled internal tibial rotation, which occurred in the intact knee from 0° to 30° of flexion, but occurred from 30° to 90° of flexion following UKA. Increasing or decreasing tibial insert thickness following medial UKA also failed to restore the medial pivoting behavior of the intact knee despite modulating MCL and ACL forces. Reduced AP constraint in non‐conforming medial UKA relative to the intact knee leads to abnormal condylar translations regardless of insert thickness even with intact cruciate and collateral ligaments. This finding suggests that the conformity of the medial compartment as driven by the medial meniscus and articular morphology plays an important role in controlling AP condylar translations in the intact tibiofemoral joint during passive flexion. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1868–1875, 2018.