bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the functional relationship between dung beetle traits and dung removal, burial, and seedling emergence
Authors: deCastro‐Arrazola Indradatta , Hortal Joaquín , Noriega Jorge Ari , Sánchez‐Piñero Francisco
Published: July 2020

The relationship between biodiversity and ecosystem functioning is often assessed through trait diversity. However, the relationship between traits and functions is typically assumed but seldom tested. We analyze the relationship between dung beetle traits and three ecological functions: dung removal, dung burial, and seedling emergence. We set up a laboratory experiment using nine Scarabaeidae species (three endocoprids, four paracoprids, and two telecoprids). We placed a sexual pair of beetles in each experimental unit, together with a mixture of dung and seeds, and measured the amount of dung removed and buried, burial depth, and the number of emerged seedlings. Sixteen morphological traits related to dung removal and burial were measured in each individual. Results indicate that these traits were related to dung beetle performance in dung removal and burial. Most traits were positively related to dung removal, indicating the existence of a general trait syndrome associated with dung manipulation and digging capability. Dung exploitation strategies did not provide further explanatory power. Seedling emergence showed a negative but weak relationship with dung burial amount and depth and species identity. This implies that specific differences in dung–soil interface activity may be important in secondary seed dispersal by dung beetles.
Human splenic polymorphonuclear myeloid‐derived suppressor cells (PMN‐MDSC) are strategically located immune regulatory cells in cancer
Authors: Tavukcuoglu Ece , Horzum Utku , Yanik Hamdullah , Uner Aysegul , Yoyen‐Ermis Digdem , Nural Safa K. , Aydin Busra , Sokmensuer Cenk , Karakoc Derya , Yilmaz Kerim Bora , Hamaloglu Erhan , Esendagli Gunes
Published: July 2020

In contrast to the mouse, functional assets of polymorphonuclear myeloid‐derived suppressor cells (PMN‐MDSC) in the human spleen remain to be better elucidated. Here, we report that the spleen in gastric and pancreatic cancer adopts an immune regulatory character, harbors excessive amount of PMN‐MDSC, and anatomically enables their interaction with T cells. Compared to the peripheral blood, the spleen from cancer patients contained significantly higher levels of low‐density PMN‐MDSC, but not early‐stage MDSC (e‐MDSC) and monocytic‐MDSC (M‐MDSC). Low‐density fraction of polymorphonuclear (PMN) cells was enriched in immature myeloid cells and displayed higher levels of CD10, CD16, and ROS than their blood‐derived counterparts. They were also positive for PD‐L1, LOX‐1, and pSTAT3. The white pulp and periarteriolar lymphoid sheath (PALS) were strategically surrounded by PMN cells that were in contact with T cells. Unlike those from the blood, both low‐density and normal‐density PMN cells from the human spleen suppressed T cell proliferation and IFN‐γ production. Independent of clinical grade, high PMN‐MDSC percentages were associated with decreased survival in gastric cancer. In summary, our results outline the immune regulatory role of the spleen in cancer where neutrophils acquire MDSC functions and feasibly interact with T cells.
Th17 lymphocyte‐dependent degradation of joint cartilage by synovial fibroblasts in a humanized mouse model of arthritis and reversal by secukinumab
Authors: Margheri Francesca , Maggi Laura , Biagioni Alessio , Chillà Anastasia , Laurenzana Anna , Bianchini Francesca , Bani Daniele , Capone Manuela , Mazzoni Alessio , Rossi Maria Caterina , Liotta Francesco , Cosmi Lorenzo , Giani Teresa , Cimaz Rolando , Fibbi Gabriella , Annunziato Francesco , Del Rosso Mario
Published: July 2020

How T‐helper (Th) lymphocyte subpopulations identified in synovial fluid from patients with juvenile idiopathic arthritis (JIA) (Th17, classic Th1, or nonclassic Th1) drive joint damage is of great interest for the possible use of biological drugs that inhibit the specific cytokines. Our objective was to clarify the role of such Th subpopulations in the pathogenesis of articular cartilage destruction by synovial fibroblasts (SFbs), and the effect of Th17 blockage in an animal model. SFbs were isolated from healthy subjects and patients with JIA, and peripheral blood Th lymphocytes subsets were obtained from healthy subjects. Fragments of human cartilage from healthy subjects in a collagen matrix containing JIA or normal SFbs grafted underskin in SCID mice were used to measure cartilage degradation under the effects of Th supernatants. JIA SFbs overexpress MMP9 and MMP2 and Th17 induce both MMPs in normal SFbs, while nonclassic Th1 upregulate urokinase plasminogen activator (uPA) activity. In vitro invasive phenotype of normal SFbs is stimulated with conditioned medium of Th17 and nonclassic‐Th1. In the in vivo “inverse wrap” model, normal SFbs stimulated with supernatants of Th17‐lymphocytes and nonclassic Th1 produced a cartilage invasion and degradation similar to JIA SFbs. Secukinumab inhibits the cartilage damage triggered by factors produced by Th17.
Novel Type of Carbon Nanotube Paste Electrode Modified by Sb2O3 for Square Wave Anodic Stripping Voltammetric Determination of Cd2+ and Pb2+
Authors: Majidian Mahsa , Raoof Jahan Bakhsh , Hosseini Sayed Reza , Ojani Reza , Barek Jiri , Fischer Jan
Published: July 2020

A novel type of carbon paste electrode modified by multi‐walled carbon nanotubes and antimony trioxide (Sb2O3/CNTCPE) was applied for square wave anodic stripping voltammetry (SWASV) of Cd2+ and Pb2+. Important parameters (deposition potential, deposition time, HCl concentration) were optimized and linear concentration dependence was obtained in the range of 10–100 ppb with LOD 1.7 ppb for Cd2+ and 1.2 ppb for Pb2+. The practical applicability was tested on the determination of Cd2+ and Pb2+ in tap water. The potentiometric stripping analysis at Sb2O3/CNTCPE was tested for the determination of Cd2+ and Pb2+ to compare this method with SWASV.
Electrochemical Study of Different Sensors for Simple and fast Quantification of Ciprofloxacin in Pharmaceutical Formulations and Bovine Milk
Authors: de Faria Lucas Vinícius , Lisboa Thalles Pedrosa , Alves Guilherme Figueira , de Farias Davi Marques , Matos Maria Auxiliadora Costa , Muñoz Rodrigo Alejandro Abarza , Matos Renato Camargo
Published: July 2020

In this paper, bare glassy carbon electrode (GCE), multi‐walled carbon nanotubes (MWCNT/GCE) and reduced graphene oxide (RGO/GCE) were to verify the ciprofloxacin oxidation process. The RGO/GCE electrode provided a 9‐fold increase in the analytical signal and a potential displacement of 50 mV. A method using flow injection analysis with amperometric detection has been developed for simple and fast detection of ciprofloxacin in pharmaceutical formulations and bovine milk. The method presented adequate analytical characteristics, limit of detection (LOD<0.1 μmol L−1), simple sample treatment (only dilution supporting electrolyte), analytical frequency (110 analyzes per hour), satisfactory linear range (1–100 μmol L−1) and good precision (RSD<3%). The method was applied in six samples with satisfactory accuracy (recovery values in the range of 101 to 113 %). The ciprofloxacin contents were in agreement with the values provided by the drug labels, while the levels in the milk samples were below the LOD. The results obtained for both applications were statistically equivalent to the results obtained by liquid chromatography, at a 95 % confidence level.
Boosting the Performance of Solid‐State Lithium Battery Based on Hybridizing Micron‐Sized LATP in a PEO/PVDF‐HFP Heterogeneous Polymer Matrix
Authors: Xue Xilai , Zhang Xiangxin , Liu Yongchuan , Chen Sujing , Chen Yuanqiang , Lin Junhong , Zhang Yining
Published: July 2020

Solid‐state poly(ethylene oxide) (PEO) electrolyte exhibits a low ionic conductivity at ambient conditions, and large interfacial resistance between PEO and electrodes obstructs its applications in lithium metal batteries. Heterogeneous solid electrolytes (HSEs) are an alluring solution for the exploitation of PEO. Herein, PEO/poly(vinylidene fluoride‐co‐hexafluoropropylene) (PVDF‐HFP)/micron‐sized Li1.4Al0.4Ti1.6(PO4)3 (LATP) heterogeneous solid electrolytes are originally prepared to decrease the crystallinity of PEO and interfacial resistance between HSEs and electrodes. Heterogeneous solid electrolyte composed of PEO/PVDF‐HFP/5% micron‐sized LATP (PPL‐5) exhibits superior electrochemical properties in ionic conductivity (3.01 × 10−5 S cm−1), lithium transference number (0.55) at 30 °C, and a broad potential window (5.31 V). Li/PPL‐5/Li symmetric cell displays a relatively stable potential response during 800 h cycling, authenticating long‐term compatibility between the as‐prepared electrolyte and lithium metal. LiFePO4 (LFP) is used as a cathode to test the chemical and electrochemical stability of PPL‐5. The discharge capacity of LFP/PPL‐5/Li coin cell maintains 97.9 mAh g−1 at 0.8 C after 500 cycles with capacity retention of 86.7%. Such excellent performance of PPL‐5 can be ascribed to the reduction of crystallinity of PEO and the improvement of the interfacial contact between electrolyte and electrodes, when PVDF‐HFP and micron‐sized LATP are simultaneously incorporated with PEO electrolyte.
Parametric optimization of direct injection CI engine to improve combustion characteristics
Authors: Ganji Prabhakara Rao , Kattela Siva Prasad , Vysyaraju Rajesh Khana Raju , Surapaneni Srinivasa Rao
Published: July 2020

To achieve emission standard norms and higher fuel efficiency conversion are the main concerns in diesel engines. The single parametric study approach might not attain the optimal combustion characteristics. In order to overcome this issue, multi objective study has been carried out to achieve the higher performance and simultaneously reduction of emissions. The main objective of present article is identifying the optimum set of the engine parameters for diesel fuel, which gives better performance and emissions. Numerical analysis was carried out by using CONVERGE CFD software. Numerical analysis were carried out by varying the Compression Ratio (CR) (12–16.5), Start of Injection (SOI) (0–25° bTDC), Fuel Injection Pressure (FIP) (500–1,400), and Exhaust Gas Recirculation (EGR) (0–40%). Response surface methodology was used for optimization. The parameters are optimized for minimizing the NOx, soot, and ISFC by using the Response Surface Methodology (RSM). Regression equations were developed for the responses such as ISFC, NOx, and soot. It was observed that the interaction effects also play a major role in determining the performance and emission characteristics of the engine. The optimum combination of operating parameters was found to be CR 14.55, SOI 16.29° bTDC, FIP 855 bar, and EGR 26.15% with a composite desirability of 0.94. The corresponding NOx and soot emissions are reduced by 40.3% and 52.38%, respectively, and a marginal reduction in the ISFC is accomplished. Mixture homogeneity (TFDI) was improved 27% for optimum case compared to baseline configuration.
Effects of Whole-Lake Additions of Ethynylestradiol on Leech Populations
Authors: Kidd Karen A. , Graves Stephanie D. , McKee Graydon I. , Dyszy Katarzyna , Podemski Cheryl L.
Published: July 2020

Leeches are widespread, found in many freshwater habitats, and have diverse dietary habits. Despite their close phylogenetic relationships to Mollusca, a phylum with species affected by exogenous estrogens, it is unclear whether Hirudinea may also be impacted. A whole-lake experiment was done at the Experimental Lakes Area in Ontario, Canada, to assess whether 17α-ethynylestradiol (EE2) affected fishes and other species. Herein, we examined whether EE2 impacted leech community composition, species abundance, growth rates, gonad size, and cocoon production, when compared with reference lakes using a before-after-control-impact design. Each month baited leech traps were set overnight in the littoral zone at 10 sites around experimental Lake 260 and 2 reference lakes, and individuals were identified, weighed, and measured. Male and female organs of common species Haemopis marmorata were measured. Across all lakes, 9 species representing 3 families were collected. There were no apparent effects of EE2 on numbers, species richness, or community composition; however, condition in 1 of 5 species increased significantly after EE2 exposures. Total gonadosomatic index (GSI) and the GSI for all male or all female organs combined for H. marmorata were not affected by EE2 additions. However, some individual reproductive organs including relative sperm sac length (+), relative epididymis weight (–), relative vaginal bulb length (+), and relative ovisac + albumen gland length (+) changed after EE2 additions. Finally, whereas overall cocoon production was similar, it occurred earlier in the EE2-amended lake. In summary, few individual through community measures of leeches responded to low ng/L concentrations of EE2, suggesting that Hirudinea are less sensitive to this endocrine disruptor than other invertebrates and vertebrates. Environ Toxicol Chem 2020;39:1608–1619. © 2020 SETAC
Identification and characterization of key aroma compounds in Chinese high altitude and northernmost black tea (Camellia sinensis) using distillation extraction and sensory analysis methods
Authors: Chen Xiaohua , Sun Haiyan , Qu Dong , Yan Fei , Jin Wengang , Jiang Hai , Chen Chen , Zhang Yifan , Li Chongyong , Xu Zhimin
Published: July 2020

The studied Chinese northernmost black tea made of the tea leaves harvested at high altitude and low climatic temperature location and special tea manufacturing process presented strong honey‐like, moderated green/grass and weak floral and fruity aromas. Its aroma was significantly different from other black tea. The key compounds responsible for these aromas were identified and quantified by gas chromatography‐mass spectrometry (GC‐MS), gas chromatography‐olfactometry (GC‐O), aroma extract dilution analysis (AEDA), aroma reconstitution and exclusion experiments methods. A total of fifty‐eight aroma compounds were found in the black tea. Among them, phenylacetaldehyde, E‐2‐hexenal, E,E‐2,4‐nonadienal, 2‐methylbutanoic acid ethyl ester, β‐ionone, linalool, α‐ionone and geraniol were mainly responsible for the black tea aroma. They offered honey‐like, floral, green/grassy, violet‐like and fruity aromas in the tea infusion. Although E,Z‐2,6‐nonadienal was one of the major volatile compounds, its unique cucumber‐like odour was not perceived in the tea fusion. The special growing location and processing for the tea leaves may contribute to the unique aroma of the black tea.
Application of electrospinning technique in development of intelligent food packaging: A short review of recent trends
Authors: Aman Mohammadi Masoud , Hosseini Seyede Marzieh , Yousefi Mohammad
Published: July 2020

Intelligent food packaging refers to packages with the ability to sense foodstuff changes and to inform customers of the packaging content variations. They are often accompanied by smart detecting devices. Providing a suitable platform to include these devices into packaging polymers has always been discussing. Electrospun nanofibers produced through the electrospinning have been recently utilized as an outstanding and novel platforms for this purpose. Thus, the main aim of this study is to investigate recent trends in producing intelligent food packaging using electrospinning technique. In this regard, this paper was categorized into two chief sections, including (a) the principal of electrospinning technique to fabricate fine nanofibers and the parameters affecting the quality of electrospun fibers, and (b) the role of nanofibers as a platform to cover pH indicators in intelligent food packaging.
Timing of deformation along theTan‐LuFault Zone in eastern China: Constraints from zircon U–Pb geochronology of the Malongshan Shear Zone
Authors: Li Zhenwei , Song Chuanzhong , Li Jiahao , Huang Peng , Wang Yangyang , Yuan Fang , Wang Wei , Li Hailong
Published: July 2020

The Tan‐Lu Fault Zone is a major fault system in eastern China, and its timing of activity has been the focus of much research. We studied a ductile segment of the Tan‐Lu Fault Zone, the Malongshan Shear Zone, which is located in the Feidong Complex (the southern part of the Zhangbaling Uplift). A dark biotite‐adamellite mylonite has been recognized in the Malongshan Shear Zone, and the mylonitic foliation strikes NNE, consistent with the regional orientation of the Tan‐Lu Fault Zone. The occurrence of abundant syn‐tectonic leucocratic veins within the biotite‐adamellite mylonite indicates that ductile shearing was accompanied by hydrothermal activity. To constrain the timing of deformation along the Malongshan Shear Zone, we dated the biotite‐adamellite mylonite and the leucocratic veins using zircon U–Pb geochronology. The weighted mean ages of zircon grains from the biotite‐adamellite mylonite (159.0 ± 5.5 Ma) and the captured Group 2 (156.3 ± 3.7 Ma and 173.2 ± 4.2 Ma) of leucocratic veins are interpreted as the ages of protoliths of the biotite‐adamellite mylonite during the Jurassic. Additional weighted mean age of the hydrothermal zircon grains (130.9 ± 3.6 Ma) represents the timing of crystallization of the veins. Therefore, the results indicate that the Malongshan Shear Zone (and hence the southern segment of the Tan‐Lu Fault Zone) was active during the Early Cretaceous (~131 Ma). Based on the present results and existing data, we consider that sinistral shearing of the Tan‐Lu Fault Zone during the Early Cretaceous was controlled by oblique subduction of the Pacific Plate at a high angle.
Stereotactic body radiotherapy as primary treatment for elderly and medically inoperable patients with head and neck cancer
Authors: Gogineni Emile , Rana Zaker , Vempati Prashant , Karten Jessie , Sharma Anurag , Taylor Peter , Pereira Lucio , Frank Douglas , Paul Doru , Seetharamu Nagashree , Ghaly Maged
Published: July 2020

Background

Patients with head and neck cancer (HNC) who are not candidates for definitive treatment represent an increasing challenge, with limited data to guide management. Conventional local therapies such as surgery and chemoradiation can significantly impact quality of life (QoL). There has been limited data published using stereotactic body radiotherapy (SBRT) as primary treatment in previously unirradiated patients. We hypothesize that SBRT provides high rates of control while limiting toxicity.

Methods

A total of 66 medically unfit previously unirradiated patients with HNC were treated with SBRT, consisting of 35‐40 Gy to gross tumor volume and 30 Gy to clinical target volume in five fractions.

Results

Median age was 80 years. Local control (LC) and overall survival (OS) at 1 year were 73% and 64%. Two patients experienced grade 3 toxicity.

Conclusion

SBRT shows acceptable outcomes with relatively low toxicity in previously unirradiated patients with HNC who are medically unfit for conventional treatment. SBRT may provide an aggressive local therapy with high rates of LC and OS while maintaining QoL.
Behavior of slip boundary conditions for the flow of nanofluid in the presence of an inclined magnetic field
Authors: Nayak B. , Tripathy R. S. , Mishra S. R.
Published: July 2020

The inflated heat transport rate of nanofluids is of great interest to researchers. Conviction of nanosuspension with an enhanced model under the consideration of inclined magnetic field is also vital for the enhancement of heat transport rate. Therefore, in this article, an inclined magnetic field has been considered during a boundary layer flow over an extending sheet, with the sheet being permeable. The sequels of heat radiation, thermophoresis, and Brownian parameters are also taken into consideration in this study. The importance of the study is the slip boundary conditions used for velocity, temperature, and concentration. A set of nonlinear partial differential equations is transformed into ordinary differential equations with a suitable choice of similarity variables. The set of first‐order differential equations is quite difficult to solve analytically. Therefore, the numerical Runge‐Kutta‐Fehlberg method, accompanied with shooting technique, is used. The results of the physical components characterizing the flow phenomena, such as magnetic parameter, thermal radiation, thermophoresis, Brownian parameter, and slip parameters, are elaborated through graphs. The numerical results of physical quantities of attention are presented in tables. The existing outcome conforms to that of the previous published result in a particular case.
Evaluating the function of social interaction using time allocation as a dependent measure: A replication and extension
Authors: Morris Samuel L. , Vollmer Timothy R.
Published: July 2020

Call et al. (2013) described a method of assessing the function of social interactions that used time allocation as a dependent measure. The current study replicated the method described by Call et al. and evaluated several extensions aimed at increasing the feasibility and efficiency of the assessment and the utility of its results. Seven children diagnosed with Autism Spectrum Disorder (ASD) participated. Social interactions were concluded to be reinforcing for 5 participants and aversive for 2 partcipants. Time allocation data for all participants are presented as well as additional analyses related to patterns of switching toward or away from social contact and session duration. Implications of this study and its methodology as well as future directions in this line of research are discussed.
Optogenetic cardiac pacing in cultured mouse embryos under imaging guidance
Authors: Lopez Andrew L. , Wang Shang , Larina Irina V.
Published: July 2020

The mouse embryo is an established model for investigation of regulatory mechanisms controlling cardiac development and congenital heart defects in humans. Since cultured mouse embryos are very sensitive to any manipulations and environmental fluctuations, controlled alterations in mouse embryonic cardiac function are extremely challenging, which is a major hurdle in mammalian cardiac biomechanics research. This manuscript presents first optogenetic manipulation of cardiodynamics and hemodynamics in cultured mouse embryos. Optogenetic pacing was combined with 4D (3D + time) optical coherence tomography structural and Doppler imaging, demonstrating that embryonic hearts under optogenetic pacing can function efficiently and produce strong blood flows. This study demonstrates that the presented method is a powerful tool giving quick, consistent, reversible control over heart dynamics and blood flow under real time visualization, enabling various live cardiac biomechanics studies toward better understanding of normal cardiogenesis and congenital heart defects in humans.
Zinc oxide nanoparticles from Cyperus rotundus attenuates diabetic retinopathy by inhibiting NLRP3 inflammasome activation in STZ‐induced diabetic rats
Authors: Zhang Liwei , Chu Wen , Zheng Lei , Li Juanjuan , Ren Yuling , Xue Liping , Duan Wenhua , Wang Qing , Li Hua
Published: July 2020

Diabetic retinopathy (DRP) is a retinal disease caused by diabetes mellitus, which is categorized by microvascular lesions present in the retina such as vascular leakage, vascular proliferation, and retinal ischemia. The plan of the present study was to the synthesis of Cyperus rotundus‐loaded zinc oxide nanoparticles (CR‐ZnONPs) which was confirmed by the various characterization methods such as UV‐vis spectroscopy, energy dispersive X‐ray analysis, Fourier transform infrared, scanning electron microscope, and X‐ray diffraction. Also, the effect of CR‐ZnONPs on DRP‐induced rats was determined by food intake, fasting blood glucose (FBG), HbA1c, insulin, retina thickness, inner nuclear layer (INL), outer nuclear layer (ONL) thickness, lipid peroxidation (LPO), catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD). Furthermore, the status of oxidative stress marker genes (heme oxygenase‐1 [HO‐1] and nuclear factor erythroid 2‐related factor‐2 [Nrf2]) and inflammatory marker (procaspase‐1, cleaved‐caspase‐1, interleukin‐1β [IL‐1β], IL‐18, and ASC) expressions were examined by using real‐time polymerase chain reaction and Western blot analysis techniques. We noted that the synthesized CR‐ZnONPs have a crystalline structure, spherical shape, and present various functional groups. The administration of streptozotocin (STZ)‐induced DRP rats were increased in the levels of HbA1c, FBG, food intake, LPO, and reduced levels of insulin, SOD, GPx, and CAT. In addition, the gene and protein expression showed the downregulation of HO‐1 and Nrf2 and upregulation of procaspase‐1, IL‐1β, cleaved‐caspase‐1, IL‐18, and ASC in diabetic rats. Moreover, further histopathological analysis of retinal tissues again confirmed the results of biochemical parameters. In contrast, the DRP rats treated with CR‐ZnONPs significantly brought down all the parameters to normal, which indicated that the CR‐ZnONPs have better antidiabetic and anti‐inflammatory properties.
Multiple cutaneous infections caused by Prototheca wickerhamii
Authors: Zhao Feng , Chen Miaode , Fu Ying
Published: July 2020

Background

Prototheca species are a group of organisms ubiquitously existing in nature but have become a pathogenic threat to public health, which has aroused wide attention. Species identification and antifungal susceptibility have essential and valuable meanings to clinical diagnosis and treatment.

Methods

A case of an 84‐year‐old patient who had suffered from multiple cutaneous infections was reported. Tissue samples of the damaged skin were collected from the patient and used for microscopic examination and tissue culture. Staining methods, the VITEK system with YSD card and the molecular identification method based on partial mitochondrion‐encoded cytochrome b (cytb) gene amplification and sequencing were used for species identification. Antifungal susceptibility testing was completed by using YeastOne plate.

Results

The patient had type II diabetes mellitus. Round, grape‐like, and scattered morula forms were observed under the microscope in bright blue with lactophenol cotton blue staining and in green fluorescence with fungus fluorescence staining. Yeast‐like colonies were grown on both the blood plates and the Sabouraud agar. P wichehamii was identified and presented resistance to three echinocandins, fluconazole, and 5‐fluorocytosine, while was susceptible to amphotericin B, posaconazole, itraconazole, and voriconazole.

Conclusion

Our result revealed that an old patient with diabetes mellitus might be a dangerous population of cutaneous protothecosis. It also highlighted the contribution to microbial methodology on the diagnosis and treatment of such rare fungus infection.
Discordance Between Child‐Pugh and National Cancer Institute Classifications for Hepatic Dysfunction: Implications on Dosing Recommendations for Oncology Compounds
Authors: Elmeliegy Mohamed , Yang Derek Z. , Salama Engie , Parivar Kourosh , Wang Diane D.
Published: July 2020

Guidance from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency recommends using Child‐Pugh classification for pharmacokinetic evaluation in noncancer subjects with hepatic impairment (HI). Therefore, dosing recommendations for oncology compounds for patients with HI are commonly based on Child‐Pugh classification. In oncology clinical practice, National Cancer Institute classification (NCIc), is commonly used for evaluating hepatic function and dosing decisions for oncology patients. This work evaluated the discordance between the 2 systems and the impact on dosing recommendations. The classification system in HI studies was reviewed for FDA‐approved oncology compounds. Discordance between Child‐Pugh and NCIc was evaluated for sunitinib, dacomitinib, palbociclib, bosutinib, and axitinib. Pharmacokinetic (PK) analyses were conducted based on Child‐Pugh classification and NCIc. Review of 117 approved oncology compounds showed prevalent use of Child‐Pugh classification for dedicated HI studies in noncancer subjects. NCIc is commonly used in cancer patient studies. NCIc tended to classify subjects as less impaired versus Child‐Pugh (64.9%, 73.7%, and 61.5% of subjects with mild, moderate, and severe HI, respectively, via Child‐Pugh were classified as at least 1 category less impaired via NCIc). PK analyses by NCIc were consistent with Child‐Pugh for sunitinib, dacomitinib, and palbociclib. For bosutinib, NCIc showed less impact of HI than Child‐Pugh; an opposite trend was observed for axitinib. The impact of this considerable discordance between the 2 systems on dosing decisions bears consideration. When Child‐Pugh is used for HI study enrollment, exploratory PK analyses based on NCIc should be conducted. Prescribers should attempt to use the same classification system in the product label for dosing decisions.
Motoneuron deafferentation and gliosis occur in association with neuromuscular regressive changes during ageing in mice
Authors: Blasco Alba , Gras Sílvia , Mòdol‐Caballero Guillem , Tarabal Olga , Casanovas Anna , Piedrafita Lídia , Barranco Alejandro , Das Tapas , Pereira Suzette L. , Navarro Xavier , Rueda Ricardo , Esquerda Josep E. , Calderó Jordi
Published: July 2020

Background

The cellular mechanisms underlying the age‐associated loss of muscle mass and function (sarcopenia) are poorly understood, hampering the development of effective treatment strategies. Here, we performed a detailed characterization of age‐related pathophysiological changes in the mouse neuromuscular system.

Methods

Young, adult, middle‐aged, and old (1, 4, 14, and 24–30 months old, respectively) C57BL/6J mice were used. Motor behavioural and electrophysiological tests and histological and immunocytochemical procedures were carried out to simultaneously analyse structural, molecular, and functional age‐related changes in distinct cellular components of the neuromuscular system.

Results

Ageing was not accompanied by a significant loss of spinal motoneurons (MNs), although a proportion (~15%) of them in old mice exhibited an abnormally dark appearance. Dark MNs were also observed in adult (~9%) and young (~4%) animals, suggesting that during ageing, some MNs undergo early deleterious changes, which may not lead to MN death. Old MNs were depleted of cholinergic and glutamatergic inputs (~40% and ~45%, respectively, P < 0.01), suggestive of age‐associated alterations in MN excitability. Prominent microgliosis and astrogliosis [~93% (P < 0.001) and ~100% (P < 0.0001) increase vs. adults, respectively] were found in old spinal cords, with increased density of pro‐inflammatory M1 microglia and A1 astroglia (25‐fold and 4‐fold increase, respectively, P < 0.0001). Ageing resulted in significant reductions in the nerve conduction velocity and the compound muscle action potential amplitude (~30%, P < 0.05, vs. adults) in old distal plantar muscles. Compared with adult muscles, old muscles exhibited significantly higher numbers of both denervated and polyinnervated neuromuscular junctions, changes in fibre type composition, higher proportion of fibres showing central nuclei and lipofuscin aggregates, depletion of satellite cells, and augmented expression of different molecules related to development, plasticity, and maintenance of neuromuscular junctions, including calcitonin gene‐related peptide, growth associated protein 43, agrin, fibroblast growth factor binding protein 1, and transforming growth factor‐β1. Overall, these alterations occurred at varying degrees in all the muscles analysed, with no correlation between the age‐related changes observed and myofiber type composition or muscle topography.

Conclusions

Our data provide a global view of age‐associated neuromuscular changes in a mouse model of ageing and help to advance understanding of contributing pathways leading to development of sarcopenia.
Morphological assessment of glutamate zerovalent iron nanoparticles by scanning electron microscopy and its combined effect with indole acetic acid on amelioration of lead toxicity in maize (Zea mays L.)
Authors: Saeed Saleha , Ullah Sami , Nafees Muhammad , Bibi Fatima , Ullah Rehman
Published: July 2020

Food safety is a priority issue for sustainable global development that can be affected by heavy metals, contributing to morbidity and even mortality in crop growth. Heavy metals often accumulate in the soil due to the use of extensive chemical fertilizers and pesticides; therefore, the current experiment was aimed to determine the effect of glutamate zerovalent iron nanoparticles (Glu‐ZVFeNPs) and indole acetic acid (IAA) on physiological mechanism of lead (Pb+2) stress tolerance at 4 and 8 ppm in Zea mays variety. Seeds of the selected variety were collected from Cereal Crop Research Institute Persabaq Nowshera and planted in earthen pots in triplicate in the greenhouse of the Botany Department of the University of Peshawar. Nanoparticles were analyzed via scanning electron microscopy and energy dispersive X‐ray analysis. Maximum growth responses were recorded from T12 (untreated + NPs + IAA), while minimum were recorded from T5 (8 ppm) indicating from the minimum amplitude of chlorophyll “a” and “b” contents, root length, shoot length, and root/shoot ratio. T5 (8 ppm) enhanced the values of osmolytes and antioxidant enzymes peroxidase and superoxide dismutase which has been ameliorated by the combined application of Glu‐ZVFeNPs + IAA, indicating that the plant may resist the toxic effects of heavy metal stress at high concentration. From the present study, we concluded that adverse result of Pb+2 has been condensed by application of Glu‐ZVFeNPs + IAA treatment as compared to the foliar application of IAA and Glu‐ZVFeNPs individually.
Bats respond to simulated bacterial infection during the active phase by reducing food intake
Authors: Melhado Gabriel , Herrera M. L. Gerardo , da Cruz‐Neto Ariovaldo P.
Published: July 2020

Sickness triggers a series of behavioral and physiological processes collectively known as acute phase response (APR). Bats are known as reservoirs of a broad variety of pathogens and the physiological changes resulting from APR activation have been tested predominantly during the resting phase (daytime) in several species exposed to lipopolysaccharide (LPS). In contrast, behavioral consequences of sickness for bats and other wild mammals have received less attention. We examined the physiological and behavioral consequences of APR activation in a fruit‐eating bat (Carollia perspicillata) challenged with LPS during the active phase (nighttime). We measured changes in food intake, body mass, body temperature, total white blood cell counts, and the neutrophil/lymphocyte ratio (N/L). No fever and leukocytosis were observed in bats injected with LPS, but food intake decreased, bats lost body mass and their N/L ratio increased. The effect of LPS on daily energy balance is remarkable and, along with the increase in N/L ratio, it is assumed to be beneficial to fight disease. On the basis of our findings and those with other bats, it is probable that the physiological and behavioral components of the immune response to LPS follow circadian rhythms, but a formal test of this hypothesis is warranted.
Synthesis, anticancer screening, and in silico ADME prediction of novel 2‐pyridones as Pim inhibitors
Authors: Ismail Magda M. F. , Farrag Amel M. , Abou‐El‐Ela Dalal
Published: July 2020

A novel series of 26 substituted N‐(2‐ethylphenyl)‐2‐oxo‐pyridine‐3‐carbonitriles have been designed and synthesized via one‐pot synthesis of various aromatic aldehydes, different aromatic acetophenones, and 2‐cyano‐N‐(2‐ethylphenyl)acetamide 1. Moreover, cytotoxicity of the target compounds was evaluated by NCI, which selected 14 compounds for one‐dose screening. Among them, compound 21 was selected for five‐dose screening, which confirmed its potency against most of cancer cell lines. This compound elicited selectivity profile against human cell line WI‐38. Cell cycle analysis was carried out, revealed that compound 21 is an apoptosis inducer causing cell cycle arrest at G2/M. Further exploration on the mode of action by evaluating its effect against Pim‐1, Pim‐2, and Pim‐3 demonstrated its inhibitory effect on Pim‐1 and Pim‐3 rather than Pim‐2. Molecular docking showed that compound 21 binds with high affinity to the active site of Pim‐1 enzyme through three hydrogen bonds and two arene‐H bonds.
Pyrrolidine‐2,3‐diones: Synthesis, reactions and biological activity
Authors: Afsah Elsayed M. , Abdelmageed Soha M.
Published: July 2020

Pyrrolidine‐2,3‐diones are of continuing interest as intermediates in the synthesis of heterocycles related to pyrrolidine alkaloids, medicinally relevant compounds, and in the development of antibiotics and drugs. The present review deals with the most important literature on the synthesis and reactions of pyrrolidine‐2,3‐diones and the related biologically important compounds.
Primary stability of a press‐fit cup in combination with impaction grafting in an acetabular defect model
Authors: Schierjott Ronja A. , Hettich Georg , Baxmann Marc , Morosato Federico , Cristofolini Luca , Grupp Thomas M.
Published: July 2020

The objectives of this study were to (a) assess primary stability of a press‐fit cup in a simplified acetabular defect model, filled with compacted cancellous bone chips, and (b) to compare the results with primary stability of a press‐fit cup combined with two different types of bone graft substitute in the same defect model. A previously developed acetabular test model made of polyurethane foam was used, in which a mainly medial contained defect was implemented. Three test groups (N = 6 each) were prepared: Cancellous bone chips (bone chips), tricalciumphosphate tetrapods + collagen matrix (tetrapods + coll), bioactive glass S53P4 + polyethylene glycol‐glycerol matrix (b.a.glass + PEG). Each material was compacted into the acetabulum and a press‐fit cup was implanted. The specimens were loaded dynamically in the direction of the maximum resultant force during level walking. Relative motion between cup and test model was assessed with an optical measurement system. At the last load step (3000 N), inducible displacement was highest for bone chips with median [25th percentile; 75th percentile] value of 113 [110; 114] µm and lowest for b.a.glass + PEG with 91 [89; 93] µm. Migration at this load step was highest for b.a.glass + PEG with 868 [845; 936] µm and lowest for tetrapods + coll with 491 [487; 497] µm. The results show a comparable behavior under load of tetrapods + coll and bone chips and suggest that tetrapods + coll could be an attractive alternative to bone chips. However, so far, this was found for one specific defect type and primary stability should be further investigated in additional/more severe defects.
T2 analysis of the entire osteoarthritis initiative dataset
Authors: Razmjoo Alaleh , Caliva Francesco , Lee Jinhee , Liu Felix , Joseph Gabby B. , Link Thomas M. , Majumdar Sharmila , Pedoia Valentina
Published: July 2020

While substantial work has been done to understand the relationships between cartilage T2 relaxation times and osteoarthritis (OA), diagnostic and prognostic abilities of T2 on a large population yet need to be established. Using 3921 manually annotated 2D multi‐slice multi‐echo spin‐echo magnetic resonance imaging volume, a segmentation model for automatic knee cartilage segmentation was built and evaluated. The optimized model was then used to calculate T2 values on the entire osteoarthritis initiative (OAI) dataset composed of longitudinal acquisitions of 4796 unique patients, 25 729 magnetic resonance imaging studies in total. Cross‐sectional relationships between T2 values, OA risk factors, radiographic OA, and pain were analyzed in the entire OAI dataset. The performance of T2 values in predicting the future incidence of radiographic OA as well as total knee replacement (TKR) were also explored. Automatic T2 values were comparable with manual ones. Significant associations between T2 relaxation times and demographic and clinical variables were found. Subjects in the highest 25% quartile of tibio‐femoral T2 values had a five times higher risk of radiographic OA incidence 2 years later. Elevation of medial femur T2 values was significantly associated with TKR after 5 years (coeff = 0.10; P = .036; CI = [0.01,0.20]). Our investigation reinforces the predictive value of T2 for future incidence OA and TKR. The inclusion of T2 averages from the automatic segmentation model improved several evaluation metrics when compared to only using demographic and clinical variables.
The mechano‐response of murine annulus fibrosus cells to cyclic tensile strain is frequency dependent
Authors: Kim Min Kyu M. , Burns Marissa J. , Serjeant Meaghan E. , Séguin Cheryle A.
Published: July 2020

The intervertebral disk (IVD) is a composite structure essential for spine stabilization, load bearing, and movement. Biomechanical factors are important contributors to the IVD microenvironment regulating joint homeostasis; however, the cell type‐specific effectors of mechanotransduction in the IVD are not fully understood. The current study aimed to determine the effects of cyclic tensile strain (CTS) on annulus fibrosus (AF) cells and identify mechano‐sensitive pathways. Using a cell‐type specific reporter mouse to differentiation NP and AF cells from the murine IVD, we characterized AF cells in dynamic culture exposed to CTS (6% strain) at specific frequencies (0.1 Hz, 1.0 Hz, or 2.0 Hz). We demonstrate that our culture model maintains the phenotype of primary AF cells and that the bioreactor system delivers uniform biaxial strain across the cell culture surface. We show that exposure of AF cells to CTS induces cytoskeleton reorganization resulting in stress fiber formation, with acute exposure to CTS at 2.0 Hz inducing a significant yet transient increase ERK1/2 pathway activation. Using SYBPR‐based qPCR to assess the expression of extracellular matrix (ECM) genes, ECM‐remodeling genes, candidate mechano‐sensitive genes, inflammatory cytokines and cell surface receptors, we demonstrated that exposure of AF cells to CTS at 0.1 Hz increased Acan, Prg4, Col1a1 and Mmp3 expression. AF cells exposed to CTS at 1.0 Hz showed a significant increase in the expression of Acan, Myc, and Tnfα. Exposure of AF cells to CTS at 2.0 Hz induced a significant increase in Acan, Prg4, Cox2, Myc, Fos, and Tnfα expression. Among the cell surface receptors assessed, AF cells exposed to CTS at 2.0 Hz showed a significant increase in Itgβ1, Itgα5, and Trpv4 expression. Our findings demonstrate that the response of AF cells to CTS is frequency dependent and suggest that mechanical loading may directly contribute to matrix remodeling and the onset of local tissue inflammation in the murine IVD.
Kinetic study of the CN radical reaction with 2‐methylfuran
Authors: Lee James , Caster Kacee , Maddaleno Trey , Donnellan Zachery , Selby Talitha M. , Goulay Fabien
Published: July 2020

The gas phase reaction of the ground state cyano‐radical (CN (X2∑+)) with 2‐methylfuran (2‐MF) is investigated in a quasi‐static reaction cell at pressures ranging from 2.2 to 7.6 Torr and temperatures ranging from 304 to 440 K. The CN radicals are generated in their ground electronic state by pulsed laser photolysis of gaseous cyanogen iodide (ICN) at 266 nm. Their concentration is monitored as a function of reaction time using laser‐induced fluorescence at 387.3 nm on the B2∑+ (ν′ = 0) ← X2∑+ (ν″ = 0) vibronic band. The reaction rate coefficient is found to be rapid and independent of pressure and temperature. Over the investigated temperature and pressure ranges, the rate coefficient is measured to be 2.83 (± 0.18) × 10−10 cm3 molecules s−1. The enthalpies of the stationary points and transition states on the CN + 2‐MF potential energy surface are calculated using the CBS‐QB3 computational method. The kinetic results suggest the lack of a prereactive complex on the reaction entrance channel with either a very small or nonexistent entrance energy barrier. In addition, the potential energy surface calculations reveal only submerged barriers along the minimum energy path. Based on comparisons between previous CN reactions with unsaturated hydrocarbons, the most likely reaction pathway is CN addition onto one of the unsaturated carbons followed by either H or methyl elimination. The implications for the transformation of biomass‐derived fuels in nitrogen‐rich flames is discussed.
Clinical Versus Pathologic Laryngeal Cancer Staging and the Impact of Stage Change on Outcomes
Authors: Contrera Kevin J. , Hair Bryan B. , Prendes Brandon , Reddy Chandana A. , Zimmer David I. , Burkey Brian B. , Tassone Patrick
Published: July 2020

Objectives/Hypothesis

Evaluate the impact and accuracy of clinical laryngeal cancer staging.

Study Design

Retrospective cohort study.

Methods

Two hundred sixty‐five consecutive patients with laryngeal squamous cell carcinoma who underwent total laryngectomy from 2001 to 2017 were studied. Clinical versus pathologic tumor (T) and nodal (N) categories were compared. Logistic regression and Cox proportional hazards analyzed the association of stage change with perioperative factors and outcomes.

Results

Forty‐seven patients (17.7%, accuracy = 0.969 ± 0.010 [standard error]) changed between T1‐2 and T3‐4. Sixty‐four patients (24.1%, accuracy = 0.866 ± 0.020) had inaccurate N category. Salvage patients were less likely to have stage change (downstage: odds ratio [OR] = 0.20, 95% confidence interval [CI]: 0.08‐0.50, P < .001; upstage: OR = 0.41, 95% CI: 0.23‐0.74, P = .003), but more likely to have inaccurate nodal category (39.8% vs. 11.7%, P < .001). Patients with stage change tended to have greater odds of positive/close margins (upstage: OR = 1.78, 95% CI: 0.91‐3.5, P = .092) and chemotherapy (downstage: OR = 2.21, 95% CI: 0.80‐6.14, P = .128; upstage: OR = 1.87, 95% CI: 0.85‐4.11, P = .119). Stage change was associated with recurrence (P = .047) with downstaged patients less likely to recur (hazard ratio = 0.26, 95% CI: 0.08‐0.82, P = .021). Stage change was not associated with positron emission tomography scan, subsite, time to surgery, or mortality.

Conclusions

A third of laryngeal cancer patients were downstaged or upstaged after laryngectomy with 18% and 24% of clinical T and N categories inaccurate, respectively. Stage change was less common for salvage patients and associated with risk of recurrence.

Level of Evidence

3 Laryngoscope, 131:559–565, 2021
Alteration of Serum Phospholipid n‐6 Polyunsaturated Fatty Acid Compositions in Nonalcoholic Fatty Liver Disease in the Japanese Population: A Cross‐Sectional Study
Authors: Jiang Zhe , Hayashi Takuya , Kashima Kentaro , Kurotani Kayo , Shirouchi Bungo , Mizoue Tetsuya , Sato Masao
Published: July 2020

We performed a cross‐sectional study on 215 Japanese employees aged 20–68 years to investigate the association between NAFLD and serum phospholipid fatty acid composition. NAFLD was diagnosed by ultrasonography. The fatty acid composition between the control and NAFLD groups was compared, and the inverse probability of treatment weighting (IPTW) was performed to eliminate each confounding effect of sex, smoking status, BMI, insulin resistance, dietary cholesterol, and salt intake. A receiver operating characteristic (ROC) curve analysis was performed to evaluate the NAFLD prediction accuracy of fatty acids. Seventy‐one subjects were diagnosed with NAFLD. Their serum phospholipid dihomo‐γ‐linolenic acid (DGLA) level was significantly higher after adjusting for each variable using IPTW. In the ROC analysis, the ratio of ARA to DGLA had an area under the curve (AUC) of 0.763. By combining the ratio of ARA to DGLA with the ratio of AST to ALT, AUC increased to 0.871. In conclusion, NAFLD subjects in a Japanese working population have higher serum phospholipid DGLA. Results of the IPTW and ROC analysis indicated that serum PL DGLA and the ratio of ARA to DGLA provide diagnosis information on the fatty liver that is different to AST and ALT and improve the accuracy of fatty liver prediction, owning potential value as serum biomarkers.