bluuebunny/crossref_metadata_2025 huggingface dataset:
Laser irradiation desorption of microcystins from protein complex in fish tissue and liquid chromatography‐tandem mass spectrometry analysis
Authors: Shen Qing , Feng Junli , Wang Jie , Li Shiyan , Wang Yang , Ma Jianfeng , Wang Haixing
Published: May 2019

Microcystins are a group of cyanotoxins which interact with the C‐terminal region of PP1 and PP2A proteins, so denaturation and inactivation are necessary for breaking covalent binding to release microcystins. In this study, a novel extraction method was developed by laser irradiation desorption of microcystins from fish protein. The sample was mixed with aqueous methanol and irradiated by a 450 nm laser, with an optimized value of laser power density at 8 W and exposure time at 5 min. ThenLC–MS/MS was applied for the determination of microcystins in fish extracts. The ionization behaviors of microcystins were investigated firstly, and doubly charged microcystins were selected as precursor ions in multiple reaction monitoring scan for quantification. This proposed quantitative method was well validated in terms of selectivity, linearity, sensitivity, accuracy, recovery, and stability. The successful application of this LC–MS/MS method showed its ability for the analysis of microcystins in low concentration, and it would be of significant interest for environmental and food safety applications to ensure the safety of fish and related products.
Sharpening the university brand to keep enrollment steady
Authors: Enos Gary
Published: May 2019

Some campuses are bucking the national trend toward declining enrollment, with a combination of innovative branding and curricular strategies largely responsible for their strong performance. Leaders at two Midwest universities that overcame uncommon challenges to see enrollment increases in the 2018–19 academic year — and have a positive outlook ahead — shared their strategies.
Develop an office staff with diverse experiences
Authors: Enos Gary
Published: May 2019

Few administrators can claim to have charted the same career path as Hege Ferguson, who never would have imagined as an international student that working in Florida State University's admissions office would lead years later to becoming the school's director of admissions.
A novel adaptive state of charge estimation method of full life cycling lithium‐ion batteries based on the multiple parameter optimization
Authors: Cao Wen , Wang Shun‐Li , Fernandez Carlos , Zou Chuan‐Yun , Yu Chun‐Mei , Li Xiao‐Xia
Published: May 2019

The state of charge (SoC) estimation is the safety management basis of the packing lithium‐ion batteries (LIB), and there is no effective solution yet. An improved splice equivalent modeling method is proposed to describe its working characteristics by using the state‐space description, in which the optimization strategy of the circuit structure is studied by using the aspects of equivalent mode, analog calculation, and component distribution adjustment, revealing the mathematical expression mechanism of different structural characteristics. A novel particle adaptive unscented Kalman filtering algorithm is introduced for the iterative calculation to explore the working state characterization mechanism of the packing LIB, in which the incorporate multiple information is considered and applied. The adaptive regulation is obtained by exploring the feature extraction and optimal representation, according to which the accurate SoC estimation model is constructed. The state of balance evaluation theory is explored, and the multiparameter correction strategy is carried out along with the experimental working characteristic analysis under complex conditions, according to which the optimization method is obtained for the SoC estimation model structure. When the remaining energy varies from 10% to 100%, the tracking voltage error is <0.035 V and the SoC estimation accuracy is 98.56%. The adaptive working state estimation is realized accurately, which lays a key breakthrough foundation for the safety management of the LIB packs.
Rhizobacteria Mediate the Phytotoxicity of a Range of Biorefinery-Relevant Compounds
Authors: Herbert Robin A. , Eng Thomas , Martinez Uriel , Wang Brenda , Langley Sasha , Wan Kenneth , Pidatala Venkataramana , Hoffman Elijah , Chen Joseph C. , Bissell Mina J. , Brown James B. , Mukhopadhyay Aindrila , Mortimer Jenny C.
Published: May 2019

Advances in engineering biology have expanded the list of renewable compounds that can be produced at scale via biological routes from plant biomass. In most cases, these chemical products have not been evaluated for effects on biological systems, defined in the present study as bioactivity, that may be relevant to their manufacture. For sustainable chemical and fuel production, the industry needs to transition from fossil to renewable carbon sources, resulting in unprecedented expansion in the production and environmental distribution of chemicals used in biomanufacturing. Further, although some chemicals have been assessed for mammalian toxicity, environmental and agricultural hazards are largely unknown. We assessed 6 compounds that are representative of the emerging biofuel and bioproduct manufacturing process for their effect on model plants (Arabidopsis thaliana, Sorghum bicolor) and show that several alter plant seedling physiology at submillimolar concentrations. However, these responses change in the presence of individual bacterial species from the A. thaliana root microbiome. We identified 2 individual microbes that change the effect of chemical treatment on root architecture and a pooled microbial community with different effects relative to its constituents individually. The present study indicates that screening industrial chemicals for bioactivity on model organisms in the presence of their microbiomes is important for biologically and ecologically relevant risk analyses. Environ Toxicol Chem 2019;38:1911–1922. © 2019 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.
Evaluating arcuate fasciculus laterality measurements across dataset and tractography pipelines
Authors: Bain Jonathan S. , Yeatman Jason D. , Schurr Roey , Rokem Ariel , Mezer Aviv A.
Published: May 2019

The arcuate fasciculi are white‐matter pathways that connect frontal and temporal lobes in each hemisphere. The arcuate plays a key role in the language network and is believed to be left‐lateralized, in line with left hemisphere dominance for language. Measuring the arcuate in vivo requires diffusion magnetic resonance imaging–based tractography, but asymmetry of the in vivo arcuate is not always reliably detected in previous studies. It is unknown how the choice of tractography algorithm, with each method's freedoms, constraints, and vulnerabilities to false‐positive and ‐negative errors, impacts findings of arcuate asymmetry. Here, we identify the arcuate in two independent datasets using a number of tractography strategies and methodological constraints, and assess their impact on estimates of arcuate laterality. We test three tractography methods: a deterministic, a probabilistic, and a tractography‐evaluation (LiFE) algorithm. We extract the arcuate from the whole‐brain tractogram, and compare it to an arcuate bundle constrained even further by selecting only those streamlines that connect to anatomically relevant cortical regions. We test arcuate macrostructure laterality, and also evaluate microstructure profiles for properties such as fractional anisotropy and quantitative R1. We find that both tractography choice and implementing the cortical constraints substantially impact estimates of all indices of arcuate laterality. Together, these results emphasize the effect of the tractography pipeline on estimates of arcuate laterality in both macrostructure and microstructure.
Estimating daily inflows of large lakes using a water‐balance‐based runoff coefficient scaling approach
Authors: Peng Zhaoliang , Hu Weiping , Liu Gang , Gao Rui , Wei Wei
Published: May 2019

Daily river inflow time series are highly valuable for water resources and water environment management of large lakes. However, the availability of continuous inflow data for large lakes is still relatively limited, especially for large lakes situated within humid plain regions with tens or even hundreds of tributaries. In this study, we choose the fifth largest freshwater Lake Chaohu in China as our study area to introduce a new approach to reconstruct historical daily inflows at ungauged subcatchments of large lakes. This approach makes use of water level, lake surface rainfall, evaporation from the lake, and catchment rainfall observations. Rainfall–runoff relationship at a reference catchment was analysed to select rainfall input and estimate run‐off coefficient firstly, and the run‐off coefficient was then transferred to ungauged subcatchments to initially estimate daily inflows. Run‐off coefficient was scaled to adjust daily inflows at ungauged subcatchments according to water balance of the lake. This approach was evaluated using sparsely measured inflows at eight subcatchments of Lake Chaohu and compared with the commonly used drainage area ratio method. Results suggest that the inflow time series reconstructed from this approach consistent well to corresponding observations, with mean R2 and Nash–Sutcliffe efficiency values of 0.69 and 0.6, respectively. This approach outperforms drainage area ratio method in terms of mean R2 and Nash–Sutcliffe efficiency values. Accuracy of this approach holds well when the number of water‐level station being used decreased from four to one.
Consumption of nuts and seeds and pancreatic ductal adenocarcinoma risk in the European Prospective Investigation into Cancer and Nutrition
Authors: Obón‐Santacana Mireia , Luján‐Barroso Leila , Freisling Heinz , Naudin Sabine , Boutron‐Ruault Marie‐Christine , Mancini Francesca Romana , Rebours Vinciane , Kühn Tilman , Katzke Verena , Boeing Heiner , Tjønneland Anne , Olsen Anja , Overvad Kim , Lasheras Cristina , Rodríguez‐Barranco Miguel , Amiano Pilar , Santiuste Carmen , Ardanaz Eva , Khaw Kay‐Thee , Wareham Nicholas J. , Schmidt Julie A. , Aune Dagfinn , Trichopoulou Antonia , Thriskos Paschalis , Peppa Eleni , Masala Giovanna , Grioni Sara , Tumino Rosario , Panico Salvatore , Bueno‐de‐Mesquita Bas , Sciannameo Veronica , Vermeulen Roel , Sonestedt Emily , Sund Malin , Weiderpass Elisabete , Skeie Guri , González Carlos A. , Riboli Elio , Duell Eric J.
Published: May 2019

Four epidemiologic studies have assessed the association between nut intake and pancreatic cancer risk with contradictory results. The present study aims to investigate the relation between nut intake (including seeds) and pancreatic ductal adenocarcinoma (PDAC) risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Cox proportional hazards models were used to estimate hazards ratio (HR) and 95% confidence intervals (95% CI) for nut intake and PDAC risk. Information on intake of nuts was obtained from the EPIC country‐specific dietary questionnaires. After a mean follow‐up of 14 years, 476,160 participants were eligible for the present study and included 1,283 PDAC cases. No association was observed between consumption of nuts and PDAC risk (highest intake vs nonconsumers: HR, 0.89; 95% CI, 0.72–1.10; p‐trend = 0.70). Furthermore, no evidence for effect‐measure modification was observed when different subgroups were analyzed. Overall, in EPIC, the highest intake of nuts was not statistically significantly associated with PDAC risk.
The previously uncharacterized lncRNA APP promotes prostate cancer progression by acting as a competing endogenous RNA
Authors: Shi Xiaolei , Zhang Wei , Nian Xinwen , Lu Xin , Li Yaoming , Liu Fei , Wang Fubo , He Biming , Zhao Lin , Zhu Yasheng , Ren Shancheng , Sun Yinghao
Published: May 2019

Long noncoding RNAs (lncRNAs) promote cell proliferation, migration, invasion and castration resistance in prostate cancer (PCa). Understanding the inherited molecular mechanisms by which lncRNAs contribute to the progression of PCa to a lethal disease could have an important impact on cancer detection, diagnosis and prognosis. In our study, PCa‐associated lncRNA transcripts from RNA‐seq data were identified and screened via bioinformatics analysis, NCBI annotations and literature review. We identified a novel lncRNA, lncAPP (lncRNA activated in PCa progression), which activates in PCa progression and is expressed in primary tumor tissues and urine samples of patients with localized or advanced PCa. Urinary‐based lncAPP is a promising biomarker for predicting PCa progression. In vitro and in vivo studies demonstrated that lncAPP enhanced cell proliferation and promoted migration and invasion. The underlying mechanism of lncRNA was investigated by RNA immunoprecipitation, dual‐luciferase reporter system assay, etc. Upregulation of lncAPP promoted cell migration and invasion via competitively binding miR218 to facilitate ZEB2/CDH2 expression. In addition, in vivo subcutaneous tumor xenograft models and tail intravenously injection metastatic models were constructed to evaluate lncRNA function. Targeting lncAPP/miR218 axis in cell lines and tumor xenografts restrained tumor progression properties both in vitro and in vivo. These results establish that lncAPP/miR218 axis plays a critical role in PCa progression, and they also suggest new strategies to prevent tumor progression for therapeutic purposes.
Attenuation of NF-κB in Intestinal Epithelial Cells Is Sufficient to Mitigate the Bone Loss Comorbidity of Experimental Mouse Colitis
Authors: Ke Ke , Chen Tim (Hung-Po) , Arra Manoj , Mbalaviele Gabriel , Swarnkar Gaurav , Abu-Amer Yousef
Published: May 2019

Skeletal abnormalities are common comorbidities of inflammatory bowel disease (IBD). Patients suffering from IBD, including ulcerative colitis and Crohn's disease, present with skeletal complications. However, the mechanism underpinning IBD-associated bone loss remains vague. Intestinal inflammation generates an inflammatory milieu at the intestinal epithelium that leads to dysregulation of mucosal immunity through gut-residing innate lymphoid cells (ILCs) and other cell types. ILCs are recently identified mucosal cells considered as the gatekeeper of gut immunity and their function is regulated by intestinal epithelial cell (IEC)-secreted cytokines in response to the inflammatory microenvironment. We first demonstrate that serum as well as IECs collected from the intestine of dextran sulfate sodium (DSS)-induced colitis mice contain high levels of inflammatory and osteoclastogenic cytokines. Mechanistically, heightened inflammatory response of IECs was associated with significant intrinsic activation of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) in IECs and increased frequency of ILC1, ILC3, and myeloid osteoclast progenitors. Validating the central role of IEC-specific NF-κB activation in this phenomenon, conditional expression of constitutively active inhibitor kappa B kinase 2 (IKK2) in IECs in mice recapitulates the majority of the cellular, inflammatory, and osteolytic phenotypes observed in the chemically induced colitis. Furthermore, conditional deletion of IKK2 from IECs significantly attenuated inflammation and bone loss in DSS-induced colitis. Finally, using the DSS-induced colitis model, pharmacologic inhibition of IKK2 was effective in reducing frequency of ILC1 and ILC3 cells, attenuated circulating levels of inflammatory cytokines, and halted colitis-associated bone loss. Our findings identify IKK2 in IECs as viable therapeutic target for colitis-associated osteopenia.
High mobility group box 1 protein regulates osteoclastogenesis through direct actions on osteocytes and osteoclasts in vitro
Authors: Davis Hannah M. , Valdez Sinai , Gomez Leland , Malicky Peter , White Fletcher A. , Subler Mark A. , Windle Jolene J. , Bidwell Joseph P. , Bruzzaniti Angela , Plotkin Lilian I.
Published: May 2019

Old age and Cx43 deletion in osteocytes are associated with increased osteocyte apoptosis and osteoclastogenesis. We previously demonstrated that apoptotic osteocytes release elevated concentrations of the proinflammatory cytokine, high mobility group box 1 protein (HMGB1) and apoptotic osteocyte conditioned media (CM) promotes osteoclast differentiation. Further, prevention of osteocyte apoptosis blocks osteoclast differentiation and attenuates the extracellular release of HMGB1 and RANKL. Moreover, sequestration of HMGB1, in turn, reduces RANKL production/release by MLO‐Y4 osteocytic cells silenced for Cx43 (Cx43def), highlighting the possibility that HMGB1 promotes apoptotic osteocyte‐induced osteoclastogenesis. However, the role of HMGB1 signaling in osteocytes has not been well studied. Further, the mechanisms underlying its release and the receptor(s) responsible for its actions is not clear. We now report that a neutralizing HMGB1 antibody reduces osteoclast formation in RANKL/M‐CSF treated bone marrow cells. In bone marrow macrophages (BMMs), toll‐like receptor 4 (TLR4) inhibition with LPS‐RS, but not receptor for advanced glycation end products (RAGE) inhibition with Azeliragon attenuated osteoclast differentiation. Further, inhibition of RAGE but not of TLR4 in osteoclast precursors reduced osteoclast number, suggesting that HGMB1 produced by osteoclasts directly affects differentiation by activating TLR4 in BMMs and RAGE in preosteoclasts. Our findings also suggest that increased osteoclastogenesis induced by apoptotic osteocytes CM is not mediated through HMGB1/RAGE activation and that direct HMGB1 actions in osteocytes stimulate pro‐osteoclastogenic signal release from Cx43def osteocytes. Based on these findings, we propose that HMGB1 exerts dual effects on osteoclasts, directly by inducing differentiation through TLR4 and RAGE activation and indirectly by increasing pro‐osteoclastogenic cytokine secretion from osteocytes.
Muscle‐bone crosstalk and potential therapies for sarco‐osteoporosis
Authors: Li GuoBin , Zhang Lan , Wang DongEn , AIQudsy Luban , Jiang Jean X. , Xu HuiYun , Shang Peng
Published: May 2019

The nature of muscle‐bone crosstalk has been historically considered to be only mechanical, where the muscle is the load applier while bone provides the attachment sites. However, this dogma has been challenged with the emerging notion that bone and muscle act as secretory endocrine organs affect the function of each other. Biochemical crosstalk occurs through myokines such as myostatin, irisin, interleukin (IL)‐6, IL‐7, IL‐15, insulin‐like growth factor‐1, fibroblast growth factor (FGF)‐2, and β‐aminoisobutyric acid and through bone‐derived factors including FGF23, prostaglandin E2, transforming growth factor β, osteocalcin, and sclerostin. Aside from the biochemical and mechanical interaction, additional factors including aging, circadian rhythm, nervous system network, nutrition intake, and exosomes also have effects on bone‐muscle crosstalk. Here, we summarize the current research progress in the area, which may be conductive to identify potential novel therapies for the osteoporosis and sarcopenia, especially when they develop in parallel.
Targeted genomic integration of EGFP under tubulin beta 3 class III promoter and mEos2 under tryptophan hydroxylase 2 promoter does not produce sufficient levels of reporter gene expression
Authors: Menzorov Aleksei G. , Orishchenko Konstantin E. , Fishman Veniamin S. , Shevtsova Anastasia A. , Mungalov Roman V. , Pristyazhnyuk Inna E. , Kizilova Elena A. , Matveeva Natalia M. , Alenina Natalia , Bader Michael , Rubtsov Nikolai B. , Serov Oleg L.
Published: May 2019

Neuronal tracing is a modern technology that is based on the expression of fluorescent proteins under the control of cell type–specific promoters. However, random genomic integration of the reporter construct often leads to incorrect spatial and temporal expression of the marker protein. Targeted integration (or knock‐in) of the reporter coding sequence is supposed to provide better expression control by exploiting endogenous regulatory elements. Here we describe the generation of two fluorescent reporter systems: enhanced green fluorescent protein (EGFP) under pan‐neural marker class III β‐tubulin (Tubb3) promoter and mEos2 under serotonergic neuron‐specific tryptophan hydroxylase 2 (Tph2) promoter. Differentiation of Tubb3‐EGFP embryonic stem (ES) cells into neurons revealed that though Tubb3‐positive cells express EGFP, its expression level is not sufficient for the neuronal tracing by routine fluorescent microscopy. Similarly, the expression levels of mEos2‐TPH2 in differentiated ES cells was very low and could be detected only on messenger RNA level using polymerase chain reaction‐based methods. Our data shows that the use of endogenous regulatory elements to control transgene expression is not always beneficial compared with the random genomic integration.
Total flavonoids from the Carya cathayensis Sarg. leaves inhibit HUVEC senescence through the miR‐34a/SIRT1 pathway
Authors: Guo Yan , Xing Liwan , Chen Nipi , Gao Chengxian , Ding Zhishan , Jin Bo
Published: May 2019

Aging shows a significant relationship with changed vascular structure and function, and advancing age is a major nonmodifiable risk factor in the occurrence of cardiovascular diseases. The senescence of endothelial cells is one of the hallmarks of vascular aging and can induce vascular dysfunction. This study aimed to investigate the effect of total flavonoids (TFs) on human umbilical vein endothelial cells (HUVEC) senescence and identify the potential mechanisms involved. A HUVEC senescence model was induced by angiotensin II. The senescence markers, including senescence‐associated β‐galactosidase (SA‐β‐gal), p53, p21, and stagnate G0/G1, were measured. The effects of TFs on miR‐34/ SIRT1 were examined by quantitative polymerase chain reaction analysis and Western blot analysis. TFs decreased the percentage of SA‐β‐gal‐positive cells and resulted in G0/G1 cell cycle arrest, while the percentage of cells in the S phase increased. Furthermore, TFs reduced miR‐34a expression and increased the expression of SIRT1. After treatment with TFs and a miR‐34a inhibitor, the percentage of SA‐β‐gal‐positive cells and the expression of miR‐34a decreased, and the expression of SIRT1 increased. The TFs inhibited HUVEC senescence, and the mechanism was related to the miR‐34a/Sirtuin1 pathway.
Downregulation of microRNA‐92b‐3p suppresses proliferation, migration, and invasion of gastric cancer SGC‐7901 cells by targeting Homeobox D10
Authors: Li Cheng , Huo Binliang , Wang Yongheng , Cheng Chong
Published: May 2019

To investigate the effect and mechanism of microRNA‐92b‐3p (miR‐92b‐3p) targeting Homeobox D10 (HOXD10) on proliferation, migration, and invasion of gastric cancer, we detected the expression of miR‐92b‐3p and HOXD10 in SGC‐7901 cells. The effects of miR‐92b‐3p or HOXD10 on proliferation, migration, invasion, and matrix metalloproteinase (MMP)‐2/9 expression in SGC‐7901 cells were measured by the Cell Counting Kit‐8 assay, Transwell assay, and Western blot, respectively. The results showed that miR‐92b‐3p expression was increased, and HOXD10 expression was decreased in SGC‐7901 cells, compared with human normal gastric epithelial cells GES‐1. Functional experiments demonstrated that cell proliferation, migration, invasion, and expression of MMP‐2/9 in SGC‐7901 cells were significantly inhibited by miR‐92b‐3p silencing and HOXD10 overexpression. Moreover, HOXD10 was a potential target gene of miR‐92b‐3p as evidenced by the TargetScan software and double luciferase reporter assay. In the rescue experiment, knockdown of HOXD10, accompanied by higher expression of MMP‐2/9, could significantly eliminate the inhibitory effects of miR‐92b‐3p silencing on cell proliferation, migration, and invasion. In conclusion, miR‐92b‐3p is highly expressed in gastric cancer SGC‐7901 cells, and interfering with its expression might inhibit SGC‐7901 cell proliferation, migration, and invasion via downregulating MMP‐2/9 expression and targeting HOXD10.
Serum galectin‐3 concentrations in patients with ankylosing spondylitis
Authors: Cao Ming‐Yu , Wang Jiang , Gao Xiao‐Liang , Hu Ya‐Bin
Published: May 2019

Objective

The aim of our study was to assess potential correlations between serum galectin‐3 concentrations and Ankylosing Spondylitis Disease Activity (ASDAS) index in patients with ankylosing spondylitis (AS).

Methods

A total of 112 patients with AS were included, and 130 healthy subjects were considered as controls. We collected the detailed medical history, and ASDAS index was used to assess the disease severity in patients with AS.

Results

The serum galectin concentrations were higher in AS patients compared to the health groups (14.1 ± 9.6 vs 9.2 ± 3.7, P < 0.001). The correlation analysis showed that serum galectin concentrations were significantly positively correlated with C‐reactive protein and erythrocyte sedimentation rate (r = 0.369, P < 0.001; r = 0.240, P = 0.011). In addition, the positively correlation of serum galectin‐3 with global pain index (r = 0.238, P = 0.011) was observed in AS patients. A significant positively correlation between serum galectin and ASDAS index in AS patients was found (r = 0.367; P < 0.001). In multiple linear regression analysis, the results indicated that increased serum galectin still was correlated with ASDAS index (r = 0.322, P < 0.001) in patients with AS.

Conclusions

Serum galectin concentrations were found to be correlated with ASDAS index in patients with AS.
Iron and the heart: A paradigm shift from systemic to cardiomyocyte abnormalities
Authors: Paterek Aleksandra , Mackiewicz Urszula , Mączewski Michał
Published: May 2019

Iron is a key micronutrient for the human body and participates in biological processes, such as oxygen transport, storage, and utilization. Iron homeostasis plays a crucial role in the function of the heart and both iron deficiency and iron overload are harmful to the heart, which is partly mediated by increased oxidative stress. Iron enters the cardiomyocyte through the classic pathway, by binding to the transferrin 1 receptor (TfR1), but also through other routes: T‐type calcium channel (TTCC), divalent metal transporter 1 (DMT1), L‐type calcium channel (LTCC), Zrt‐, Irt‐like Proteins (ZIP) 8 and 14. Only one protein, ferroportin (FPN), extrudes iron from cardiomyocytes. Intracellular iron is utilized, stored bound to cytoplasmic ferritin or imported by mitochondria. This cardiomyocyte iron homeostasis is controlled by iron regulatory proteins (IRP). When the cellular iron level is low, expression of IRPs increases and they reduce expression of FPN, inhibiting iron efflux, reduce ferritin expression, inhibiting iron storage and augment expression of TfR1, increasing cellular iron availability. Such cellular iron homeostasis explains why the heart is very susceptible to iron overload: while cardiomyocytes possess redundant iron importing mechanisms, they are equipped with only one iron exporting protein, ferroportin. Furthermore, abnormalities of iron homeostasis have been found in heart failure and coronary artery disease, however, no clear picture is emerging yet in this area. If we better understand iron homeostasis in the cardiomyocyte, we may be able to develop better therapies for a variety of heart diseases to which abnormalities of iron homeostasis may contribute.
Impact of different ectopic fat depots on cardiovascular and metabolic diseases
Authors: Ferrara Daniele , Montecucco Fabrizio , Dallegri Franco , Carbone Federico
Published: May 2019

A growing body of evidence is pointing out the pathophysiological role of fat accumulation in different organs. Ectopic fat depots within heart, liver, skeletal muscle, kidney, and pancreas as well as around blood vessels might be more associated to cardiometabolic risk than classical variables, such as body mass index. Among different mechanisms, lipid metabolism appears to be particularly influenced by ectopic fat depots. Indeed, intracellular accumulation of nonesterified fatty acids, and triglycerides promotes endoplasmic reticulum stress, mitochondrial uncoupling, oxidative stress, and altered membrane composition/function, finally promoting inflammatory response and cell death. The dysfunctional adipose tissue was shown to induce both local and systemic effects, with relevant clinical consequences. Epicardial fat and myocardial steatosis have been associated with the development of atrial fibrillation and ventricular dysfunction. Similarly perivascular adipose tissue appears to trigger atherosclerosis and hypertension. Nonalcoholic fatty liver disease has been recognized both as the hepatic manifestation of metabolic syndrome and as a cardiovascular (CV) risk factor. Importantly, the renal sinus fat emerged as a potential player in kidney dysfunction. Finally, both skeletal muscle and pancreatic fat depots have been indicated as potential endocrine modulators of insulin resistance. Considering the global rise in the prevalence of obesity, the understanding of mechanisms underlying ectopic fat accumulation represents an urgent need, with potential clinical implications for CV risk stratification. Here, we attempt to update the current knowledge of the different ectopic fat depots, focusing on underlying mechanisms and potential clinical implications.
Epithelial–mesenchymal transition in the formation of hypertrophic scars and keloids
Authors: Yuan Feng‐Lai , Sun Zi‐Li , Feng Yi , Liu Si‐Yu , Du Yong , Yu Shun , Yang Ming‐Lie , Lv Guo‐Zhong
Published: May 2019

Abnormal wound healing is likely to induce the formation of hypertrophic scars and keloids, which leads to dysfunction, deformity, and mental problem in the patients. Despite the advances in prevention and management of hypertrophic scar and keloids, the mechanism underlying scar and keloid formation has not been fully elucidated. Recent insights into the role of the epithelial–mesenchymal transition (EMT) in development, wound healing, stem cell regulation, fibrosis, and tumorigenesis have increased our understanding of the pathophysiology of hypertrophic scarring and keloids and suggested new therapeutic targets. This review summarizes recent progress in the elucidation of the role of EMT in physiologic wound healing and pathologic scar formation. This knowledge will facilitate an understanding of EMT roles in scar formation and shed new light on the modulation and potential treatment of hypertrophic scars and keloids.
The immunoreceptor CD300a controls the intensity of inflammation and dysfunction in a model of Ag-induced arthritis in mice
Authors: Valiate Bruno V S , Alvarez Rodrigo U , Karra Laila , Queiroz-Júnior Celso M , Amaral Flavio A , Levi-Schaffer Francesca , Teixeira Mauro M
Published: May 2019

CD300a is an inhibitory immunoreceptor expressed in lymphoid and myeloid cells. This study evaluates whether CD300a plays a role in the control of joint inflammation in a model of Ag-induced arthritis (AIA) in mice. CD300a was found to be expressed mostly on neutrophils and its expression was enhanced on neutrophils that migrated to the inflamed synovial cavity. Joint inflammation, as characterized by neutrophil accumulation, was significantly greater in CD300a KO (CD300a−/−) mice subjected to AIA, as compared to WT mice. This was associated with joint dysfunction, as measured by lower mechanical nociception threshold. There was greater production of the chemokine CXCL1 and the cytokine IL-6 in joints of CD300a−/− mice. In vitro, Mϕs from CD300a−/− mice released higher concentrations of CXCL1 and IL-6 in response to LPS. Splenocytes from immunized CD300a−/− mice produced increased levels of IFN-γ and IL-17 and lower levels of IL-10 when challenged with Ag than cells from WT mice. Neutrophils lacking the CD300a gene had greater chemotactic activity in response to fMLP, CXCL1, and LTB4 than WT neutrophils. In conclusion, these results reveal that the absence of CD300a promotes exacerbation of inflammation in a model of Ag-induced arthritis, suggesting that CD300a is an important receptor for negatively controlling the inflammatory response in this model. Mechanistically, CD300a seems to regulate the activity of various immune cells types involved in the process, including neutrophils, Mϕs, and lymphocytes.
Drought leads to reproductive quiescence in smooth‐billed anis: Phenotypic evidence for opportunistic breeding and reproductive readiness
Authors: Morais Mychel Raony Paiva Teixeira , Teófilo Tiago da Silva , Azevedo Bruna K. G. , Cavalcanti Diogo Manuel Lopes Paiva , Fontenele‐Neto José Domingues
Published: May 2019

Previous studies have suggested that the smooth‐billed ani (Crotophaga ani, Linnaeus, 1758) breeds opportunistically following unpredictable rainfall in drought areas. To obtain proof of this phenomenon, the present study described and compared reproductive morphology and cell proliferation in the gonads of free‐living smooth‐billed anis during a wet season (April to June 2012) and the following dry season (July to September 2012) in a semiarid area using light and electron microscopy (transmission and scanning) and the AgNOR method. The morphological findings indicated distinct levels of reproductive activity related to seasonal changes. Morphological and morphometric analyses of the gonads confirmed intense gametogenic activity during the wet season, whereas gonadal involution occurred after rainfall ceased. The sizes of the testes and ovaries were significantly reduced compared to those in the wet season. The volumetric fraction of the seminiferous tubules in the testis decreased considerably, and no preovulatory follicles were detected in the ovary in the dry season. Moreover, the AgNOR count in the gonads revealed a significant decline in cell recruitment for gametogenesis after rainfall ceased. The histological findings indicated partial gonadal activation throughout the dry season. The analysis of the seminiferous epithelium confirmed the early testicular recrudescence phase, and sporadic postovulatory follicles indicated random ovulation during this time. The excurrent ducts and the oviduct also underwent remarkable involution in the dry season. Taken together, these findings confirm opportunistic breeding by smooth‐billed anis in a semiarid habitat and suggest that gonadal recrudescence has been established as a reproductive strategy to cope with unexpected precipitation events.
Yield parameters and antioxidant compounds of tomato fruit: the role of plant defence inducers with or without Cucumber mosaic virus infection
Authors: Rendina Nunzia , Nuzzaci Maria , Sofo Adriano , Campiglia Pietro , Scopa Antonio , Sommella Eduardo , Pepe Giacomo , De Nisco Mauro , Basilicata Manuela Giovanna , Manfra Michele
Published: May 2019

BACKGROUND

The production of fruit and vegetables rich in health‐promoting components in an eco‐friendly context represents the winning answer to the world population demand for food. In this study, the effects of different treatments on the yield and fruit chemical characteristics of tomato (Solanum lycopersicum L.) are reported. The treatments included three inducers of plant defence responses (chitosan, Trichoderma harzianum T‐22 and Bacillus subtilis QST713) applied alone or before Cucumber mosaic virus infection. Fruit production and antioxidant compounds were investigated by ultrahigh‐performance liquid chromatography (UHPLC) and liquid chromatography–tandem mass spectrometry (LC–MS/MS).

RESULTS

Compared to control fruit harvested from untreated and healthy plants, treatment with QST713 increased the fruit number. Furthermore, plant treatments with T22, QST713 and chitosan alone enhanced fruit carotenoids (lutein and β‐carotene), ascorbic acid and phenolic acids (caffeoyl glucoside and p‐coumaroyl glucoside). In parallel, compared to fruit harvested from only CMV‐infected plants, treatments with T22, QST713 and chitosan before CMV enhanced fruit ascorbic acid and flavonoids (quercetin 3‐O‐xylosyl‐rutinoside and rutin).

CONCLUSION

Antioxidant compounds of tomato fruit can increase with the application of the plant defence inducers, thus protecting both the consumer and plant health. © 2019 Society of Chemical Industry
The assessment of the visual discomfort caused by vergence‐accommodation conflicts based on EEG
Authors: Zheng Yawen , Zhao Xiaojie , Yao Li
Published: May 2019

Stereoscopic displays have gained much popularity, while visual discomfort during watching stereoscopic displays is becoming an increasing concern. Vergence‐accommodation conflicts are one of factors inducing visual discomfort. How to properly assess the visual discomfort by vergence‐accommodation conflicts has been the focus of researchers. Compared with previous studies, this paper aims to address two problems: (1) designing an elaborate experiment to induce visual discomfort without interference of the long performance time and (2) objectively selecting fewer electrodes and extracting electroencephalogram (EEG) features much related to visual discomfort. The results show that, better than previous experimental paradigm, the designed experimental paradigm not only causes the visual discomfort properly but also shortens the performance time to less than an hour. Moreover, for the proposed model, the visual discomfort can be evaluated well based only on six selected electrodes or even better than previous models relying on much more electrodes.
Surgical technique in stapedotomy hearing outcome and complications
Authors: Pauli Nina , Strömbäck Karin , Lundman Lars , Dahlin‐Redfors Ylva
Published: May 2019

Objectives/Hypothesis

The aim of this study was to investigate different stapes surgery techniques in relation to hearing outcome and risk for complications such as tinnitus, hearing deterioration, dizziness, and taste disturbance.

Study Design

Retrospective database review.

Methods

The study was based on data from the Swedish Quality Register for Otosclerosis Surgery (SQOS). Two study protocols were completed by the surgeon, and a questionnaire was distributed to each patient 1 year after surgery. A total of 832 patients operated on during 2013 to 2016 were included. Pure‐tone audiometry was performed preoperatively and 1 year after surgery.

Results

There was no significant difference in postoperative high‐frequency hearing thresholds among the subgroups at the 1‐year follow‐up. The CO2 + drill laser group had the best hearing outcome according to the following criteria: air‐bone gap closure ≤10 dB, air‐conduction improvement >20 dB, and bone conduction not worsened >5 dB. The overall complication rate was low in all analyzed groups. The most commonly reported symptom after surgery was newly developed or worsened tinnitus (6%). Subjective hearing 1 year after surgery was reported to be better or much better in 91% of the patients.

Conclusions

The combination of a drill and CO2 laser or a drill and potassium‐titanyl‐phosphate laser resulted in the best hearing outcome in this study from the SQOS. There were no major differences in high‐frequency hearing outcome when comparing the different surgical techniques. Complications from surgery were rare, and patient satisfaction was very high 1 year after the operation.

Level of Evidence

NA

Laryngoscope, 130:790–796, 2020
Clinical Utility of a Risk‐Adapted Protocol for the Evaluation of Coronary Artery Disease in Liver Transplant Recipients
Authors: Romero‐Cristóbal Mario , Mombiela Teresa , Caballero Aranzazu , Clemente Ana , Fernández‐Yunquera Ainhoa , Diaz‐Fontenla Fernando , Rincón Diego , Ripoll Cristina , Bermejo Javier , Catalina María‐Vega , Matilla Ana‐María , Ibáñez‐Samaniego Luis , Pérez‐Peña José , López‐Baena José‐Ángel , Díaz‐Zorita Benjamín , Fernández‐Avilés Francisco , Salcedo M. Magdalena , Bañares Rafael
Published: May 2019

The prevalence and management of coronary artery disease (CAD) in liver transplantation (LT) candidates are not well characterized. The aims of this study were to evaluate the impact on clinical outcomes of a specifically designed protocol for the management of asymptomatic CAD in LT candidates and to investigate noninvasive risk profiles for obstructive and nonobstructive CAD for 202 LT candidates. Those with high baseline cardiovascular risk (CVR; defined by the presence of classic CVR factors and/or decreased ejection fraction) received coronary angiography and significant arterial stenosis and were treated with percutaneous stents. Patients were followed up after LT until death or coronary event (CE). There were 78 patients who received coronary evaluation (62 direct angiography, 14 computed tomography coronary angiography, and 2 both). Of them, 39 (50%) patients had CAD of any severity, and 6 (7.7%) had significant lesions (5 were amenable to be treated with stents, whereas 1 patient had diffuse lesions which contraindicated the LT). Insulin‐dependent diabetes was the only factor related to CAD of any severity (odds ratio, 3.44; 95% confidence interval [CI], 1.00‐11.97). A total of 69 patients (46 with coronary evaluation) received LT. The incidence of CEs and overall survival after LT were similar between patients with and without coronary evaluation. Furthermore, no differences occurred between these groups in a multivariate competing risk model (subhazard ratio, 0.84; 95% CI, 0.27‐2.61; P = 0.76). In conclusion, the application of an angiographic screening protocol of CAD in a selected high‐risk Mediterranean population is safe and effective. The short‐ and medium‐term incidence rates of CEs and death after LT in this population are similar to that observed in low‐risk patients.
Multiple positive fixed points for the sum of expansive mappings and k‐set contractions
Authors: Benzenati Lyna , Mebarki Karima
Published: May 2019

In this work, we are concerned with the existence of multiple positive fixed points for the sum of an expansive mapping with constant h > 1 and a k‐set contraction when 0 ≤ k < h − 1. In particular, the case of the sum of an expansive mapping with constant h > 1 and an e‐concave operator and an e‐convex operator is considered. Two examples of application illustrate some of the theoretical results.
Dynamical behaviour of SIR model with coinfection: The case of finite carrying capacity
Authors: Ghersheen Samia , Kozlov Vladimir , Tkachev Vladimir G. , Wennergren Uno
Published: May 2019

Multiple viruses are widely studied because of their negative effect on the health of host as well as on whole population. The dynamics of coinfection are important in this case. We formulated an susceptible infected recovered (SIR) model that describes the coinfection of the two viral strains in a single host population with an addition of limited growth of susceptible in terms of carrying capacity. The model describes five classes of a population: susceptible, infected by first virus, infected by second virus, infected by both viruses, and completely immune class. We proved that for any set of parameter values, there exists a globally stable equilibrium point. This guarantees that the disease always persists in the population with a deeper connection between the intensity of infection and carrying capacity of population. Increase in resources in terms of carrying capacity promotes the risk of infection, which may lead to destabilization of the population.
Approximating fractional derivative of Faddeeva function, Gaussian function, and Dawson's integral
Authors: Yarman Can Evren
Published: May 2019

A new method for approximating fractional derivatives of Faddeeva function, Gaussian function, and Dawson's integral are presented. Unlike previous approaches, which are dominantly based on some discretization of Riemann‐Liouville integral over a finite interval using polynomial or discrete Fourier basis, we take an alternative approach that is based on expressing computation of Riemann‐Liouville definition of the fractional integral for the semi‐infinite axis in terms of a moment problem. As a result, fractional derivatives of Faddeeva function, Gaussian function, and Dawson's integral are expressed as a weighted sum of complex scaled Gaussian and Dawson's integral. Error bounds for the approximations are provided. Another feature of the proposed method compared with the previous approaches is it can be extended to approximate partial derivatives with respect to the order of the fractional derivative that can be used in PDE constraint optimization problems.
Highly accelerated multishot echo planar imaging through synergistic machine learning and joint reconstruction
Authors: Bilgic Berkin , Chatnuntawech Itthi , Manhard Mary Kate , Tian Qiyuan , Liao Congyu , Iyer Siddharth S. , Cauley Stephen F. , Huang Susie Y. , Polimeni Jonathan R. , Wald Lawrence L. , Setsompop Kawin
Published: May 2019

Purpose

To introduce a combined machine learning (ML)‐ and physics‐based image reconstruction framework that enables navigator‐free, highly accelerated multishot echo planar imaging (msEPI) and demonstrate its application in high‐resolution structural and diffusion imaging.

Methods

Single‐shot EPI is an efficient encoding technique, but does not lend itself well to high‐resolution imaging because of severe distortion artifacts and blurring. Although msEPI can mitigate these artifacts, high‐quality msEPI has been elusive because of phase mismatch arising from shot‐to‐shot variations which preclude the combination of the multiple‐shot data into a single image. We utilize deep learning to obtain an interim image with minimal artifacts, which permits estimation of image phase variations attributed to shot‐to‐shot changes. These variations are then included in a joint virtual coil sensitivity encoding (JVC‐SENSE) reconstruction to utilize data from all shots and improve upon the ML solution.

Results

Our combined ML + physics approach enabled Rinplane × multiband (MB) = 8‐ × 2‐fold acceleration using 2 EPI shots for multiecho imaging, so that whole‐brain T2 and T2* parameter maps could be derived from an 8.3‐second acquisition at 1 × 1 × 3‐mm3 resolution. This has also allowed high‐resolution diffusion imaging with high geometrical fidelity using 5 shots at Rinplane × MB = 9‐ × 2‐fold acceleration. To make these possible, we extended the state‐of‐the‐art MUSSELS reconstruction technique to simultaneous multislice encoding and used it as an input to our ML network.

Conclusion

Combination of ML and JVC‐SENSE enabled navigator‐free msEPI at higher accelerations than previously possible while using fewer shots, with reduced vulnerability to poor generalizability and poor acceptance of end‐to‐end ML approaches.
Factors associated with overactive bladder symptom improvement after 1 year of monthly percutaneous tibial nerve stimulation therapy
Authors: Pincus Joseph , Rostaminia Ghazaleh , Chang Cecilia , Gafni‐Kane Adam , Goldberg Roger P.
Published: May 2019

Aims

To investigate patient characteristics associated with overactive bladder (OAB) symptom improvement after 1 year of monthly percutaneous tibial nerve stimulation (PTNS) therapy.

Methods

This was a retrospective chart review of women who underwent PTNS for refractory OAB symptoms between January 2011 and December 2017 in our tertiary center. Patients who received 12 monthly PTNS maintenance treatments after achieving success with 12 weekly PTNS treatments were included in the study. Reports on subjective changes in urinary frequency, nocturia, and urgency urinary incontinence were submitted at each visit. Patients were categorized to symptom improve and no improve groups. A multivariate analysis was performed to identify patient characteristics that predicted symptomatic improvement.

Results

Sixty‐six patients were identified. Average subjective improvement after 12 monthly sessions compared with 12 weekly sessions was 5.2% on a scale of −100% to +100%. A history of urogynecologic surgery remained a significant negative predictor of symptom change from 12 weekly sessions to 12 monthly treatment sessions (odds ratio, 0.19; P = .01).

Conclusions

OAB symptoms remain relatively stable after 12 monthly treatments of PTNS, as compared with the 12‐week time point. A history of urogynecologic surgery was a negative predictor of OAB symptom improvement in patients receiving monthly PTNS for at least 12 months.