bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterofusion: Fusing genomics data of different measurement scales
Authors: Smilde Age K. , Song Yipeng , Westerhuis Johan A. , Kiers Henk A. L. , Aben Nanne , Wessels Lodewyk F. A.
Published: February 2020

In systems biology, it is becoming increasingly common to measure biochemical entities at different levels of the same biological system. Hence, data fusion problems are abundant in the life sciences. With the availability of a multitude of measuring techniques, one of the central problems is the heterogeneity of the data. In this paper, we discuss a specific form of heterogeneity, namely, that of measurements obtained at different measurement scales, such as binary, ordinal, interval, and ratio‐scaled variables. Three generic fusion approaches are presented of which two are new to the systems biology community. The methods are presented, put in context, and illustrated with a real‐life genomics example.
Design, Sonosynthesis, Quantum‐Chemical Calculations, and Evaluation of New Mono‐ and Bis‐pyridine Dicarbonitriles as Antiproliferative Agents
Authors: Arafa Wael Abdelgayd Ahmed , Hussein Modather F.
Published: February 2020

Summary of main observation and conclusion

A highly efficient, simple, and clean single‐step sonosynthetic procedure has been sophisticated for assembling new series of mono‐ and bis‐pyridine dicarbonitriles from ketones, HCl, and tetracyanoethylene. The presented protocol is applicable for the preparation of a broad range of uniquely substituted pyridine dicarbonitriles and seems to be superior in comparison with other previously reported methods. The antiproliferative impact of the newly synthesized derivatives was screened towards three representative cancer cell lines (MCF‐7, A549, and HCT116). Most of the evaluated derivatives showed a moderate to excellent anti‐proliferative activity towards the selected cell lines. Of these, compounds 4h, 4k, 10, 12a, and 12b showed both potent anticancer activity (IC50<10 μM) and lower cytotoxic effect (IC50 > 58 μM) on non‐tumorigenic cells (MCF‐10A and NCM460), suggesting their promising potential to be lead molecules for future antitumor drug discovery. The structure‐activity relationships have been also discussed. Moreover, quantum chemical studies based on Density Functional Theory (DFT) of the synthesized compounds were investigated and found to be consistent with the in vitro inhibitory activities.
Protonated Poly(ethylene imine)‐Coated Silica Nanoparticles for Promoting Hydrogen Generation by Hydrolysis of Sodium Borohydride
Authors: Yang Lijing , Huang Xiaoshan , Zhang Jiapeng , Dong Hua
Published: February 2020

Invited for this month's cover is the group of Dr. Hua Dong from Chengdu University of Technology, China. The cover picture shows a nonmetal catalyst (SiO2@H+PEI) that promotes hydrogen production by hydrolysis of NaBH4. This newly developed catalyst, which is fabricated by covalently modifying SiO2 nanoparticles with protonated poly(ethylene imime), provides a promising choice for the cheap and efficient catalysis of NaBH4 hydrolysis. Read the full text of the article at 10.1002/cplu.201900609.
Mutational analysis of genes with ureteric progenitor cell‐specific expression in branching morphogenesis of the mouse kidney
Authors: Rutledge Elisabeth A. , McMahon Andrew P.
Published: February 2020

Background

Ureteric progenitor cells (UPCs) within the branch tips of the arborizing ureteric epithelium of the kidney's developing collecting system establish the shape and cellular organization of the collecting network, and drive the nephrogenic program through their interactions with nephron progenitor cells. In a previous study, expression screening identified a cohort of genes showing UPC‐enriched expression including D17H6S56E‐5, Hs3st3a1, Hs3st3b1, and Tmem59l. Each of these is also enriched in branch tips of assembling airways of the developing lungs. Here, we used Crispr‐CAS9 directed gene editing to mutate each of these targets to address their potential role(s) in UPC programs.

Results

Single (D17H6S56E‐5 and Tmem59l) and double (Hs3st3a1 and Hs3st3b1) mutants were viable, fertile, and displayed varying frequencies of ureter duplications and no overt lung phenotype. Ureter duplications arise spontaneously through multiple outgrowths of the ureteric bud at the onset of kidney development. Tmem59l mutants and Hs3st3a1/Hs3st3b1 compound mutants showed a weakly penetrant, but statistically significant increase in duplicated ureters compared to C57BL6/J and SW wild‐type mouse strains.

Conclusions

Tmem59l and Hs3st3a1/Hs3st3b1 activities contribute to the regulatory programs restricting ureteric outgrowth in the developing mouse kidney. However, the low penetrance of the observed phenotype precludes a detailed analysis of their specific actions.
Long‐term reevaluation of spatially explicit models as a means for adaptive wildlife management
Authors: Maor Cohen Mia , Shamon Hila , Dolev Amit , Reichman Alon , David Shirli Bar , Saltz David
Published: February 2020

We evaluated a 20‐yr‐old spatially explicit model (SEM) that predicted the spatial expansion of reintroduced Persian fallow deer in northern Israel. Using the current distribution of the deer and based on multi‐model inference we assessed the accuracy of theSEM's prediction and what other factors affected the population's current distribution. If theSEM's projection was still valid, the leading model in the multi‐model inference would include only theSEM's projection as an explanatory variable with a good fit. Different leading models would reveal key variables overlooked when theSEMwas constructed or changes in the landscape unforeseen at the time, thus assisting adaptive management and decision‐making. We assessed deer presence from camera trap encounter counts analyzed using N‐mixture models. Models included various combinations of seven predictors: the 20‐yr predictions of anSEMdeveloped during the initial phases of the reintroduction, three key landscape characteristics on which theSEMwas originally based but updated to reflect current conditions, distance from the release site, elevation, and the distribution of gray wolves (a predator that was absent from the area when theSEMwas developed). Competing models were ranked by Akaike information criterion (AIC). Wolf distribution was the key predictor explaining the current deer distribution, appearing in all three leading models (∆AIC < 2.0) and carrying 71% of theAICweight (coefficient = −14.86 ± 5.6 [mean ± SE]). Of these three models, theSEM20‐yr prediction appeared in two, but explained only a fraction of the variance (coefficient = 0.001 ± 0.08). The contribution of all other predictors was negligible. While theSEMfailed to accurately predict the 20‐yr deer distribution, the divergence between its projection and reality pointed to the probable cause (wolves) of this discrepancy. The inclusion of theSEMprediction in the leading models indicates that had the wolves not spread to the study area, the predictions would still have merit suggesting that long‐termSEMs can potentially be robust. Long‐term reevaluation ofSEMs can be beneficial even if model projections fail, as the process can uncover the specific factors driving this failure, supporting adaptive management procedures.
Local‐ and landscape‐scale variables shape insect diversity in an urban biodiversity hot spot
Authors: Adams Benjamin J. , Li Enjie , Bahlai Christine A. , Meineke Emily K. , McGlynn Terrence P. , Brown Brian V.
Published: February 2020

Local community structure is shaped by processes acting at local and landscape scales. The relative importance of drivers operating across different spatial scales is difficult to test without observations across regional or latitudinal gradients. Cities exhibit strong but predictable environmental gradients overlaying a mosaic of highly variable but repeated habitat types within a constrained area. Thus, cities present a unique opportunity to explore how both local and landscape factors influence local biotic communities. We used insect communities to examine the interactions among local environmental variables (such as temperature and relative humidity), local habitat characteristics (such as plant community composition), and broad‐scale patterns of urbanization (including biophysical, human‐built, and socioeconomic variables) on local insect abundance, species richness, and species composition in Los Angeles, a hot, dry, near‐desert city. After accounting for seasonal trends, insect species richness and abundance were highest in drier and hotter sites, but the magnitude of local environmental effects varied with the degree of urbanization. In contrast, insect species composition was best predicted by broad‐scale urbanization trends, with the more native communities occurring in less urbanized sites and more cosmopolitan insects occurring in highly urbanized sites. However, insect species richness and abundance were >30% higher and insect composition was similar across sites that hosted either native or drought‐tolerant plants, regardless of the degree of urbanization. These results demonstrate that urban insect biodiversity is a product of interacting mechanisms working at both local and landscape scales. However, local‐scale changes to urban habitats, such as cultivating plants that are adapted to the natural environment nearest the city, can positively impact urban biodiversity regardless of location.
Maternal effects and urbanization: Variation of yolk androgens and immunoglobulin in city and forest blackbirds
Authors: Partecke Jesko , Hegyi Gergely , Fitze Patrick S. , Gasparini Julien , Schwabl Hubert
Published: February 2020

Wildlife inhabiting urban environments exhibit drastic changes in morphology, physiology, and behavior. It has often been argued that these phenotypic responses could be the result of micro‐evolutionary changes following the urbanization process. However, other mechanisms such as phenotypic plasticity, maternal effects, and developmental plasticity could be involved as well. To address maternal effects as potential mechanisms, we compared maternal hormone and antibody concentrations in eggs between city and forest populations of European blackbirds (Turdus merula), a widely distributed species for which previous research demonstrated differences in behavioral and physiological traits. We measured egg and yolk mass, yolk concentrations of androgens (androstenedione [A4], testosterone [T], 5α‐dihydrotestosterone [5α‐DHT], and immunoglobulins [IgY]) and related them to population, clutch size, laying order, embryo sex, and progress of breeding season. We show (a) earlier onset of laying in the city than forest population, but similar egg and clutch size; (b) higher overall yolk androgen concentrations in the forest than the city population (sex‐dependent for T); (c) greater among‐female variation of yolk T and 5α‐DHT concentrations in the forest than city population, but similar within‐clutch variation; (d) similar IgY concentrations with a seasonal decline in both populations; and (e) population‐specific positive (city) or negative (forest) association of yolk A4 and T with IgY concentrations. Our results are consistent with the hypotheses that hormone‐mediated maternal effects contribute to differences in behavioral and physiological traits between city and forest individuals and that yolk androgen and immunoglobulin levels can exhibit population‐specific relationships rather than trade‐off against each other.
Carbon Nanosheets Encapsulated NiSb Nanoparticles as Advanced Anode Materials for Lithium‐Ion Batteries
Authors: Pan Qichang , Wu Yanan , Zhong Wentao , Zheng Fenghua , Li Youpeng , Liu Yanzhen , Hu Junhua , Yang Chenghao
Published: February 2020

Metallic antimony (Sb) has been attracted much attentions as anode for lithium‐ion batteries due to its high capacity. Nevertheless, the large volume expansion during the lithiation process leads to poor electrochemical performance, which seriously limits the practical application in lithium‐ion batteries. Herein, NiSb nanoparticles encapsulated by carbon nanosheets have been developed via a facile strategy and as anode for lithium‐ion batteries. In this attractive structure, the carbon nanosheets can effectively avoid volume change of NiSb nanoparticles and inhibit the direct contact of NiSb nanoparticles to the electrolyte during the lithiation/delithiation process. As a result, the NiSb/C nanosheets display an outstanding long cycling performance (405 mA h g−1 after 1000 cycles at 1.0 A g−1) and excellent rate capability (305 mA h g−1 at 2.0 A g−1) when application in lithium‐ion batteries.
Exact solutions to the family of Fisher's reaction‐diffusion equation using Elzaki homotopy transformation perturbation method
Authors: Loyinmi Adedapo C. , Akinfe Timilehin K.
Published: February 2020

In this research work, we propose an unprecedented hybrid algorithm which involves the coupling of a new integral transform, namely, the Elzaki transform and the well‐known homotopy perturbation method called the Elzaki homotopy transformation perturbation method (EHTPM) to solve for the exact solution of three distinct types of Fisher's equation, namely, the Fisher's equation of two cases, the sixth‐order Fisher's equation and the nonlinear diffusion equation of the Fisher type. These equations are prominent in mathematical biology and highly applicable in genetic propagation, population dynamics, stochastic processes, combustion theory, as well as a prototype model for a spreading flame, and so on. The efficacy and authenticity of this method was established via convergence and error analysis, and shows that the solutions obtained from EHTPM are unique and convergent. The results of EHTPM when compared with the exact results, homotopy results, and results from the other existing literature via table of comparison, 3D plots, and the convergence plots validates that EHTPM is an efficient and reliable tool of providing exact solutions to a wider class of nonlinear partial differential equations in a simple and straightforward manner, with no discretization, linearization, computation of Adomian polynomials, and devoid of errors.
Sustainably‐derived hierarchical porous carbon from spent honeycomb for high‐performance lithium‐ion battery and ultracapacitors
Authors: Duraisamy Ezhumalai , Prasath Arul , Sankar Devi Vaithiyanathan , Ansari Mohamed N. M. , Elumalai Perumal
Published: February 2020

Spent honeycomb biomass as sustainable source is used to generate value added product, such as activated carbon. The generated activated carbon is characterized by X‐ray diffraction, Fourier transformed infra‐red spectroscopy, Raman spectroscopy, Scanning electron microscope, High‐resolution transmission electron microscope, and Brunauer‐Emmett‐Teller analyses. The activated carbon is explored as intercalation anode material for lithium‐ion battery in half‐cell and full cell as electrodes for ultracapacitor in aqueous and non‐aqueous electrolytes. The coin‐type CR‐2032 full cell lithium‐ion battery consists of the honeycomb‐derived carbon as anode and commercial LiCoO2 as cathode delivers discharge capacity of 140 mAh/g at C/5 rate with excellent cycling stability. On the other hand, the symmetric ultracapacitor consists of the carbon electrode exhibits energy density of 72 Wh/kg at a power density of 4800 W/kg with excellent coulombic efficiency as well as stability. The laboratory proto‐type battery and ultracapacitor devices are demonstrated to power a consumer electronics, namely green light emitting diode bulb for more than 3 hours and 20 minutes, respectively.
The effects of dry cultivation on grain‐filling and chalky grains of upland rice and paddy rice
Authors: Zhang Yajie , Liu Gaosheng , Cheng Yadan , Xu Jingnan , Wang Chen , Yang Jianchang
Published: February 2020

An important challenge facing rice production in China is to solve the problem of declining freshwater supply without affecting grain yield and quality. The purpose of this study was to investigate the effects of cultivation methods on the grain‐filling and chalk grains of Zhonghan 3 (Japonica) upland rice and Wuxiangjing 99–8 (Japonica) paddy rice. Both cultivars were cultivated in fields under three cultivation methods: continuous flooding (CF) as a control, bare dry cultivation (BC), and plastic film mulching dry cultivation (PFMC). Compared with CF, the yield of the upland rice decreased significantly, and the yield of paddy rice did not differ significantly under PFMC. The yields of both cultivars decreased significantly under BC. Superior and inferior grains of the two cultivars under PFMC had a greater mean grain‐filling rate (G) and a shorter active grain‐filling time (D). Under PFMC, the two cultivars had a higher export translocation rate of the matter from the stem and sheath and a slower decrease of the chlorophyll content in the flag leaves and nitrogen content in the plants after heading. Upland rice had a higher grain weight, and paddy rice had a lower grain weight compared to CF. The chalkiness of the two cultivars was significantly lower under dry cultivation than under CF. The correlation analysis showed that the percentage of chalky grains was negatively correlated with G and positively correlated with D, indicating that dry cultivation could improve the grain‐filling rate and appearance quality of the two cultivars.
Effect of red pepper (Zanthoxylum bungeanum Maxim.) leaf extract on volatile flavor compounds of salted silver carp
Authors: Li Junke , Liu Qiyi , Wang Jing , Liu Quanwen , Peng Zengqi
Published: February 2020

Chinese red pepper (Zanthoxylum bungeanum Maxim.) leaf (ZML) extract was added to salted silver carp. The effect of ZML extract on volatile compounds formation of both dorsal and ventral muscle of salted fish was investigated. Lipid oxidation of salted fish with ZML extract was alleviated with lower peroxide value (PV) and thiobarbituric acid reactive substance (TBARS) values than that of the control. Therefore, the contents of some volatile compounds formed mainly by oxidation such as benzene, methylbenzene, 1‐octene‐3‐ol, hexanal, and methyl ketone, which attributed off‐odor of salted fish, were reduced. Principal component analysis results showed that the first principal component (PC1) and the second principal component (PC2) explained 62% and 31% of total variance, respectively, and volatile compounds of the dorsal and ventral of control group differentiated from treatment group. These results showed that ZML extract can be a source of natural antioxidants and food additives for improving flavor of salted fish.
Effects of cognitive reappraisal and expressive suppression on daily work‐related outcomes: Comparison between younger and older Chinese workers
Authors: Yeung Dannii Y. , Wong Sowan
Published: February 2020

The existing models of emotion regulation (ER) do not make any specific prediction about the differential effects of the same ER strategy among individuals of different ages. However, such assumption may not be necessarily true, given that older adults emphasise emotional goals greater than their younger counterparts. Using a daily diary approach, this study investigated whether the effects of cognitive reappraisal (CR) and expressive suppression (ES) on daily work‐related outcomes would vary by age when individuals were experiencing negative events at work. A total of 141 Chinese managerial employees (Mage = 42.40, SD = 9.16) completed the diary report for 15 consecutive workdays by recording their daily work experiences. The results of the multilevel analyses showed that age moderated the effects of ES on daily negative emotions, perceived work stress, and job satisfaction. More beneficial effects were observed among older workers than among younger workers. By contrast, the use of CR significantly lowered the levels of negative emotions and perceived work stress for both younger and older workers. These findings revealed the importance of considering the role of age in evaluating the effects of ES on work‐related outcomes, which provides important implications for future research and training programs in ER.
Risky decision making and cognitive flexibility among online sports bettors in Nigeria
Authors: Nweze Tochukwu , Agu Ethelbert , Lange Florian
Published: February 2020

Online sports betting is a popular recreational activity in Nigeria. Like other forms of gambling, risk of pathological progression exists for gamblers who continue betting despite severe financial and psychosocial consequences. In the present study, we examined whether this population of gamblers shows deficits in decision making and cognitive flexibility that have been documented in Western gambling populations. Thirty‐six online sports bettors and 42 non‐gambling participants completed a version of the Iowa gambling task (IGT) and an established set‐shifting task for the assessment of cognitive flexibility. The two groups did not differ significantly in the selection of disadvantageous decks on the IGT. In contrast, sports bettors committed significantly more errors on the set‐shifting task than non‐gambling control participants. As this performance deficit was not specific to trials requiring a set shift, it most likely resulted from gambling‐related changes in general cognitive or motivational abilities that are required to successfully complete challenging mental tasks. While our results illustrate that findings from Western populations cannot automatically be generalised to other contexts, it should be noted that we focused on only one particular type of gambling and included mostly participants with mild gambling‐related problems.
Nanotoxicological study of downconversion Y2O3:Eu3+luminescent nanoparticles functionalized with folic acid for cancer cells bioimaging
Authors: Chávez‐García Dalia , Juarez‐Moreno Karla , Calderón‐Osuna Itamar , Navarro Patricia , Hirata Gustavo A.
Published: February 2020

Luminescent lanthanide downconversion nanoparticles (DCNPs) provide a combination of high luminescence intensity, sharp emission peaks with narrow bandwidth and a large Stokes' shift, leading to high‐performance biomedical applications mainly for imaging. The purpose of this study is to present a nanotoxicological study of DCNPs Y2O3codoped with Eu3+and functionalized with folic acid (FA). These assessments include cytotoxicity, genotoxicity, hemocompatibility, and in vitro inflammatory studies. We demonstrated by flow cytometry and confocal microscope the internalization of FA‐DCNPs in breast cancer and melanoma cells. They were synthesized by sol–gel method and coated with a thin silica shell to make them biocompatible; also they were functionalized with amino groups and FA ligands that bind to the folate receptors (FR) located on the surface of the cancer cells studied. This functionalization enables the DCNPs to be internalized into the cancer cells via endocytosis by the conjugation FA‐FR. The DCNPs were characterized with transmission electron microscope, Fourier transform infrared spectroscopy and photoluminescence. The nanotoxicological assessments demonstrated that both nanoparticles (bare and functionalized) are no cytotoxic and no genotoxic at the tested concentrations (0.01–20 μg/mL) in three cell lines (breast, skin cancer, and osteoblasts). Also they are hemocompatible and do not exert nitric oxide productionin vitroby macrophages. The FA‐DCNPs were clearly localized into the cell cytoplasm with bright red luminescence. Thus, herein we present a complete nanotoxicological study of FA‐DCNPs Y2O3codoped with Eu3+and we conclude that these nanoparticles are biocompatible and can be further used for cancer cells bioimaging.
Improving the handling properties and long‐term stability of polyelectrolyte complex by freeze‐drying technique for low‐dose bone morphogenetic protein 2 delivery
Authors: Liu Ling , Lam Wing M. R. , Yang Zheng , Wang Ming , Ren Xiafei , Hu Tao , Li Jun , Goh James Cho‐Hong , Wong Hee‐Kit
Published: February 2020

A variety of controlled release carriers for bone morphogenetic protein 2 (BMP‐2) delivery have been developed and tested in animal models. An alginate‐based polyelectrolyte complex (PEC) for controlled release of low‐dose BMP‐2 has shown promising results in preclinical research. However, the poor handling properties and long‐term stability of PEC need to be improved for translational applications. This study aimed to address these limitations of alginate‐based PEC by employing a freeze‐drying technique. The size and structure of freeze‐dried PEC (FD‐PEC) were maintained with the addition of a cryoprotectant, trehalose. The release profile of BMP‐2 from FD‐PEC was similar to that of freshly prepared PEC. In vitro bioactivity analysis of the released BMP‐2 showed that the carrier performance of PEC was not compromised by freeze‐drying up to three‐month storage at room temperature. BMP‐2‐bound FD‐PEC induced comparable bone formation to that using freshly prepared regular PEC in a rat posterolateral spinal fusion model. These results suggest that FD‐PEC is capable of delivering low‐dose BMP‐2 and could be developed as an off‐the‐shelf product for translational applications. The simplicity of this preservation method provides promise for the translational application of PEC.
Synthesis and biological evaluation of some novel 1‐alkyl‐3‐methylimidazolium carboxylate ionic liquids as potential antifungal agents
Authors: Perez Ser John Lynon P. , Atayde Eduardo C. , Arco Susan D.
Published: February 2020

In an effort to discover lead compounds that may be of importance as potent antifungal agents, a series of novel 1‐alkyl‐3‐methylimidazolium carboxylate ionic liquids were efficiently synthesized through a solvent‐free ultrasound‐assisted quaternization reaction of 1‐methylimidazole and alkyl bromides RBr (R = hexyl, octyl) followed by an anion exchange process with selected carboxylate anions (cinnamate, salicylate, crotonate, and oxalate). Quantitative yields obtained were in the range of 86–94%. Structure characterization was done using FT‐IR, 1H‐NMR, and 13C‐NMR spectroscopic techniques. All the synthesized compounds showed in vitro antifungal activity against the fungus Candida albicans with the minimum inhibitory concentrations found to be less than or equal to 1%. Preliminary cytotoxicity assays (trypan blue exclusion and MTT) were performed on all ionic liquids and findings revealed higher lymphocyte viability in 1‐hexyl‐3‐methylimidazolium carboxylate ionic liquids than in 1‐octyl‐3‐methylimidazolium counterparts. No extensive toxicity effect was observed with the carboxylate anion variation. Among the tested compounds, 1‐hexyl‐3‐methylimidazolium crotonate and 1‐hexyl‐3‐methylimidazolium oxalate exhibited the lowest cytotoxicity in the trypan blue exclusion and MTT assays, respectively. Together, our results highlight the potential of carboxylate‐based ionic liquids in the development of next‐generation antifungal drugs.
High level of D‐dimer predicts ischemic stroke in patients with infective endocarditis
Authors: Xu Nan , Fu Yakun , Wang Shuanglin , Li Shenghui , Cai Dong
Published: February 2020

Background

Ischemic stroke is one of the most prominent and serious neurological complications of infective endocarditis (IE). Our study was designed to evaluate the predictive value of higher level of plasma D‐dimer on admission for the development of ischemic stroke in patients with IE.

Methods

In this prospective study, a total of 173 consecutive patients with IE were recruited from January 2016 to December 2018. Plasma D‐dimer and other clinical indexes of IE patients were measured after admission. The number of patients who developed ischemic stroke during 6‐month follow‐up was recorded, as well as the occurrence time of ischemic stroke.

Results

Ischemic stroke was observed in 38 (22%) patients during 6‐month follow‐up since definite diagnosis of IE. Patients with ischemic stroke had significantly higher levels of plasma D‐dimer than those of patients without stroke (4982 vs 2205 μg/L, P < .001). In addition, Staphylococcus aureus infection (HR: 1.96, 95% CI: 1.51‐2.42), mitral valve vegetation (HR: 1.52, 95% CI: 1.32‐1.75), and higher levels of on‐admission plasma D‐dimer (HR: 1.35, 95% CI: 1.27‐1.43) were significantly associated with ischemic stroke. Moreover, D‐dimer levels ≥3393 μg/L served as a strong predictor for ischemic stroke in patients with IE, and the sensitivity and specificity were 78% and 83%, respectively.

Conclusion

Our study suggested that higher level of D‐dimer on admission was an independent predictor for ischemic stroke in patients with IE. These patients may require special attention, in particular within the first trimester after IE diagnosis.
Decreased glucose bioavailability and elevated aspartate metabolism in prostate cancer cells undergoing epithelial‐mesenchymal transition
Authors: Chen Yule , Wang Ke , Liu Tianjie , Chen Jiaqi , Lv Wei , Yang Wenjie , Xu Shan , Wang Xinyang , Li Lei
Published: February 2020

Prostate cancer (PCa) is a common malignancy with a high tendency for metastasis. Epithelial‐mesenchymal transition (EMT) plays a crucial role in PCa metastasis. Metabolic reprogramming offers metabolic advantages for cancer development and could result in the discovery of novel targets for cancer therapy. However, the metabolic features of PCa cells undergoing EMT remain unclear. We used metabolome and transcriptome analyses and found that PCa cells undergoing EMT showed impaired glucose utilization. In vitro studies demonstrated that PCa cells undergoing EMT were less addicted to glucose than epithelial‐like PCa cells. However, cells that underwent EMT had higher levels of aspartate and its downstream metabolites, indicative of upregulated aspartate metabolism. As aspartate is a contributor for EMT and metastasis in human cancer cells, we conclude that this metabolic reprogramming may play a vital role in EMT and PCa progression.
CCL21/CCR7 interaction promotes EMT and enhances the stemness of OSCC via a JAK2/STAT3 signaling pathway
Authors: Chen Yang , Shao Zhe , Jiang Erhui , Zhou Xiaocheng , Wang Lin , Wang Hui , Luo Xinyue , Chen Qingli , Liu Ke , Shang Zhengjun
Published: February 2020

Chemokines and their receptors show a strong relationship with poor clinical outcomes in various cancers. However, their underlying mechanisms remain to be fully elucidated. In our research, we found C‐C chemokine receptor 7 (CCR7) and its ligand chemokine ligand 21 (CCL21) were abnormally abundant in oral squamous cell carcinoma (OSCC) tissues, and CCR7 expression was correlated with poor prognosis of OSCC. After exogenous CCL21 stimulation, epithelial–mesenchymal transition (EMT) was promoted in OSCC cells, and cancer stem cell‐related markers CD133, CD44, BMI1, ALDH1A1, and OCT4 increased. The migration, invasion, tumorsphere formation, and colony formation abilities of OSCC cells were enhanced, indicating that the stemness of OSCC cells was also improved. The knockdown and overexpression of CCR7 efficiently affected the CCL21‐induced EMT and stemness of OSCC cells. When treated with CCL21, the phospho‐JAK2 and phospho‐STAT3 markedly increased. The inhibitor of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) significantly suppressed CCL21‐induced EMT and stemness of OSCC cells. In conclusion, CCL21/CCR7 axis regulated EMT progress and promoted the stemness of OSCC by activating the JAK2/STAT3 signaling pathway. CCL21/CCR7 might be an effective target for OSCC prevention and treatment.
Inhibition of HDAC6 by tubastatin A disrupts mouse oocyte meiosis via regulating histone modifications and mRNA expression
Authors: Sui Liyan , Huang Rong , Yu Hao , Zhang Sheng , Li Ziyi
Published: February 2020

Histone deacetylase 6 (HDAC6) participates in mouse oocyte maturation by deacetylating α‐tubulin. However, how HDAC6 expression is regulated in oocytes remains unknown. In the present study, we discovered that mouse oocytes had a high level of HDAC6 expression and a low level of DNA methylation status in their promoter region. Then, a selective HDAC6 inhibitor, tubastatin A (Tub‐A) was chosen to investigate the role of HDAC6 in oocyte maturation. Our results revealed that inhibition of HDAC6 caused meiotic progression arrest, disturbed spindle/chromosome organization, and kinetochore–microtubule attachments without impairing spindle assembly checkpoint function. Moreover, inhibition of HDAC6 not only increased the acetylation of α‐tubulin but also elevated the acetylation status of H4K16 and decreased the phosphorylation level of H3T3 and H3S10. Conversely, depressed H3T3 phosphorylation by its kinase inhibitor increased the acetylation level of H4K16. Finally, single cell RNA‐seq analysis revealed that the cell cycle‐related genes CCNB1, CDK2, SMAD3, YWHAZ and the methylation‐related genes DNMT1 and DNMT3B were strongly repressed in Tub‐A treated oocytes. Taken together, our results indicate that HDAC6 plays important roles in chromosome condensation and kinetochore function via regulating several key histone modifications and messenger RNA transcription during oocyte meiosis.
HTRA1 expression profile and activity on TGF‐β signaling in HTRA1 mutation carriers
Authors: Fasano Alessandro , Formichi Patrizia , Taglia Ilaria , Bianchi Silvia , Di Donato Ilaria , Battisti Carla , Federico Antonio , Dotti Maria Teresa
Published: February 2020

High temperature requirement A1 (HTRA1) is a serine protease playing a modulatory role in various cell processes, particularly in the regulation of transforming growth factor‐β (TGF‐β) signaling. A deleterious role in late‐onset cerebral small vessel diseases (CSVDs) of heterozygous HTRA1 mutations, otherwise causative in homozygosity of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy, was recently suggested. However, the pathomechanism of these heterozygous mutations is still undefined. Our aim is to evaluate the expression profile and activity of HTRA1 on TGF‐β signaling in fibroblasts from four subjects carrying the HTRA1 heterozygous mutations—p.E42Dfs*173, p.A321T, p.G295R, and p.Q151K. We found a 50% reduction of HTRA1 expression in HTRA1 mutation carriers compared to the control. Moreover, we showed no changes in TGF‐β signaling pathway downstream intermediate, Phospho Smad2/3. However, we found overexpression of genes involved in the extracellular matrix formation in two heterozygous HTRA1 carriers. Our results suggest that each heterozygous HTRA1 missense mutation displays a different and peculiar HTRA1 expression pattern and that CSVD phenotype may also result from 50% of HTRA1 expression.
Muscle and bone mass in middle‐aged women: role of menopausal status and physical activity
Authors: Sipilä Sarianna , Törmäkangas Timo , Sillanpää Elina , Aukee Pauliina , Kujala Urho M. , Kovanen Vuokko , Laakkonen Eija K.
Published: February 2020

Background

Women experience drastic hormonal changes during midlife due to the menopausal transition. Menopausal hormonal changes are known to lead to bone loss and potentially also to loss of lean mass. The loss of muscle and bone tissue coincide due to the functional relationship and interaction between these tissues. If and how physical activity counteracts deterioration in muscle and bone during the menopausal transition remains partly unresolved. This study investigated differences between premenopausal, early perimenopausal, late perimenopausal, and postmenopausal women in appendicular lean mass (ALM), appendicular lean mass index (ALMI), femoral neck bone mineral density (BMD) and T score. Furthermore, we investigated the simultaneous associations of ALM and BMD with physical activity in the above‐mentioned menopausal groups.

Methods

Data from the Estrogen Regulation of Muscle Apoptosis study were utilized. In total, 1393 women aged 47–55 years were assigned to premenopausal, early perimenopausal, late perimenopausal, and postmenopausal groups based on follicle‐stimulating hormone concentration and bleeding diaries. Of them, 897 were scanned for ALM and femoral neck BMD by dual‐energy X‐ray absorptiometry and ALMI (ALM/height2) and neck T scores calculated. Current level of leisure‐time physical activity was estimated by a validated self‐report questionnaire and categorized as sedentary, low, medium, and high.

Results

Appendicular lean mass, appendicular lean mass index, femoral neck bone mineral density, and and T score showed a significant linear declining trend across all four menopausal groups. Compared with the postmenopausal women, the premenopausal women showed greater ALM (18.2, SD 2.2 vs. 17.8, SD 2.1, P < 0.001), ALMI (6.73, SD 0.64 vs. 6.52, SD 0.62, P < 0.001), neck BMD (0.969, SD 0.117 vs. 0.925, SD 0.108, P < 0.001), and T score (−0.093, SD 0.977 vs −0.459, SD 0.902, P < 0.001). After adjusting for potential confounding pathways, a higher level of physical activity was associated with greater ALM among the premenopausal [β = 0.171; confidence interval (CI) 95% 0.063–0.280], late perimenopausal (β = 0.289; CI 95% 0.174–0.403), and postmenopausal (β=0.278; CI 95% 0.179–0.376) women. The positive association between femoral neck BMD and level of physical activity was significant only among the late perimenopausal women (β = 0.227; CI 95% 0.097–0.356).

Conclusions

Skeletal muscle and bone losses were associated with the menopausal transition. A higher level of physical activity during the different menopausal phases was beneficial, especially for skeletal muscle. Menopause‐related hormonal changes predispose women to sarcopenia and osteoporosis and further to mobility disability and fall‐related fractures in later life. New strategies are needed to promote physical activity among middle‐aged women. Longitudinal studies are needed to confirm these results.
Synthesis of [3H] and [14C]genipin
Authors: Queen Adele.E. , Hesk David , Lindsay David.M. , Kerr William.J. , Rehder Kenneth , Fennell Tim , Mascarella Wayne , Zhong Desong , Runyon Scott
Published: February 2020

[3H]Genipin was synthesized in a single step by Ir(I) catalyzed hydrogen isotope exchange. Conditions for selective exchange of the sp2 CH bond ortho to the methyl ester functionality were developed through deuterium modeling studies through a catalyst screen. Optimized conditions so obtained were then utilized with tritium gas to generate [3H]genipin at a specific activity of 18.5 Ci/mmol. Racemic [14C]genipin was prepared in eight steps in overall 5.4% radiochemical yield from potassium [14C]cyanide.
Structural insights into the intramolecular interactions of centromere protein CENP‐I
Authors: Zhang Yu , Zhao Congcong , Cao Beibei , Ye Jingjing , Huang Hao , Hu Liqiao , Tian Wei , He Xiaojing
Published: February 2020

In mitosis, the accurate segregation of sister chromosomes relies on kinetochore, a multiple subunits complex assembled on centromere of each sister chromosome. As a core component of inner kinetochore, CENP‐I plays important functions to mediate kinetochore assembly and supports the faithful chromosome segregation. The structures of the N‐terminus and C‐terminus of CENP‐I homologs in complex with CENP‐H/K have been reported, respectively. Unfortunately, the intramolecular interactions of CENP‐I are poorly understood, and how CENP‐I interacts with CENP‐M remains unknown. Here, we verified a unique helix α11, which forms the intramolecular interactions with N‐terminal HEAT repeats in fungal CENP‐I. Deletion of the helix α11 exposed the hydrophobic surface and resulted in the in vitro protein aggregation of N‐terminal HEAT repeats of fungal CENP‐I. The corresponding helix and its intramolecular interaction are highly conserved in human CENP‐I. Deletion of the corresponding helix in human CENP‐I dramatically reduced the functional activity to interact with CENP‐H and CENP‐M. Mutations of the conserved residues on the helix in human CENP‐I significantly weakened the binding to CENP‐M, but not CENP‐H, in HeLa cells. Therefore, our findings for the first time unveiled a conserved helix of CENP‐I, which is important for the intramolecular interaction and function, and would be helpful for understanding the structure basis of how CENP‐I mediates the kinetochore assembly during cell cycle and mitosis.
Predicting long‐term freedom from atrial fibrillation after catheter ablation by a machine learning algorithm: Validation of the CAAP‐AF score
Authors: Furui Koichi , Morishima Itsuro , Morita Yasuhiro , Kanzaki Yasunori , Takagi Kensuke , Yoshida Ruka , Nagai Hiroaki , Watanabe Naoki , Yoshioka Naoki , Yamauchi Ryota , Tsuboi Hideyuki , Murohara Toyoaki
Published: February 2020

Background

Preprocedural clinical predictors of the successful maintenance of sinus rhythm may contribute to optimal treatment strategies for atrial fibrillation (AF). The CAAP‐AF score, a novel simple tool scored as 0‐13 points (including six independent variables) has been proposed to predict long‐term freedom from AF after catheter ablation. To clarify its reproducibility, we examined the CAAP‐AF score's predictive performance and then created subgroups to best predict AF recurrence by using a machine learning algorithm.

Methods

We studied 583 consecutive patients who underwent initial AF catheter ablation at our institute (median CAAP‐AF score, 5; age, 66 ± 10 years old; female, 28.3%; coronary artery disease, 10.8%; left atrial diameter, 39.9 ± 6.6 mm; number of antiarrhythmic drugs failed, 0.4 ± 0.6; nonparoxysmal AF, 45.3%). All were systematically followed up with an endpoint of atrial tachyarrhythmia recurrence after the last ablation procedure.

Results

During the 1.8 ± 1.2‐year follow‐up, 157 patients had atrial tachyarrhythmia recurrence. Repeated procedures were performed (n = 115). Arrhythmia recurrence after the last session occurred in 69 patients. We created Kaplan‐Meier curves for freedom from AF after final AF ablation for ranges of CAAP‐AF scores; these confirmed the original study results. The machine learning using Classification and Regression Trees divided the patients into three categories by the risk score: low (score ≤5), intermediate (score 6‐8), and high (score ≥9).

Conclusions

The CAAP‐AF score was useful to stratify the atrial tachyarrhythmia recurrence risk in AF patients undergoing catheter ablation into three categories. The score should be considered when deciding whether to perform AF ablation in clinical practice.
Hemiarthroplasty implants should have very low stiffness to optimize cartilage contact stress
Authors: Berkmortel Carolyn , Langohr G. Daniel G. , King Graham , Johnson James
Published: February 2020

Hemiarthroplasty is often preferred to total arthroplasty as it preserves native tissue; however, accelerated wear of the opposing cartilage is problematic. This is thought to be caused by the stiffness mismatch between the implant and cartilage‐bone construct. Reducing the stiffness of the implant by changing the material has been hypothesized as a potential solution. This study employs a finite element model to study a concave‐convex hemiarthroplasty articulation for various implant materials (cobalt‐chrome, pyrolytic carbon, polyether ether ketone, ultra‐high‐molecular‐weight polyethylene, Bionate‐55D, Bionate‐75D, and Bionate‐80A). The effect of the radius of curvature and the degree of flexion‐extension was also investigated to ensure any relationships found between materials were generalizable. The implant material had a significant effect (P  < .001) for both contact area and maximum contact pressure on the cartilage surface. All of the materials were different from the native state except for Bionate‐80A at two of the different flexion angles. Bionate‐80A and Bionate‐75D, the materials with the lowest stiffnesses, were the closest to the native state for all flexion angles and radii of curvature. No evident difference between materials occurred unless the modulus was below that of Bionate‐55D (288 MPa), suggesting that hemiarthroplasty materials need to be less stiff than this material if they are to protect the opposing cartilage. This is clinically significant as the findings suggest that the development of new hemiarthroplasty implants should use materials with stiffnesses much lower than currently available devices.
Mildly decreased preoperative bilirubin levels are associated with infections after shoulder and knee arthroplasty
Authors: Laky Brenda , Alram Isabella , Frank Julia K. , Pauzenberger Leo , Anderl Werner , Wagner Karl‐Heinz , Heuberer Philipp R.
Published: February 2020

Increasing numbers of arthroplasties are also accompanied by postoperative infections. The main purpose was to evaluate preoperative serum bilirubin levels between patients with and without infections after shoulder and knee arthroplasties. For this retrospective case‐control single‐center study, a total of 108 patients were extracted from a prospectively collected database. Eighteen patients with infections after shoulder (n = 8) and knee (n = 10) arthroplasty were matched by age, gender, and implant type in a 1:5‐scenario to 90 patients (40 shoulders and 50 knees) without postoperative infection. Demographic data, preoperative blood parameters, and postoperative infection‐related outcomes were evaluated. Total bilirubin was the only preoperative parameter significantly different between the infection (8.21 ± 3.25 μmol/L or 0.48 ± 0.19 mg/dL) and noninfection (10.78 ± 4.62 μmol/L or 0.63 ± 0.27 mg/dL; P = .014) group, while C‐reactive protein and other liver parameters were similar between the groups. Significantly more controls (92.1%) had preoperative bilirubin levels above 8.72 μmol/L or 0.51 mg/dL than cases (7.9%; P = .007). The 5‐year infection survival‐rate was 65.6% for patients with preoperative bilirubin levels < 8.72 μmol/L or < 0.51 mg/dL and 91.2% with ≥ 8.72 μmol/L or ≥ 0.51 mg/dL. Mildly decreased preoperative bilirubin levels with a cutoff at 8.72 μmol/L or 0.51 mg/dL were significantly associated to patients with infections after shoulder and knee arthroplasty. There were no differences in other blood parameters or comorbidities between patients with infections and their matched‐controls.
Determining Viscosity of Blenderized Formula: A Novel Approach Using the International Dysphagia Diet Standardisation Initiative Framework
Authors: Weston Sharon , Clarke Tracie
Published: February 2020

Background

Blenderized formula (BF) can be used in place of standard enteral formula and is composed of blenderized whole foods and purees. Benefits of using BF include reduced vomiting and retching, in part related to a higher viscosity. Commercially prepared BFs vary significantly in viscosity when comparing available products. Viscosity can be measured using a viscometer, although this requires expensive and sophisticated equipment. We proposed an alternative method to describe viscosity of BFs using the International Dysphagia Diet Standardisation Initiative (IDDSI) framework. This flow test provides a simple and objective method to describe liquid thickness and requires only a 10‐mL luer tip syringe and stopwatch.

Methods

Full‐strength BFs were measured using the IDDSI flow test and compared with a standard enteral formula. BFs were then diluted until a slightly thick viscosity was achieved, which correlated to the viscosity of the reference formula.

Results

IDDSI flow‐test results indicated that undiluted BFs ranged in viscosity, from slightly thick to extremely thick, when measured at room temperature. The volume of water required to achieve a slightly thick viscosity ranged from 0 to 270 mL per serving, resulting in a wide variation in dilution of formula.

Conclusion

The IDDSI flow test was simple to perform and can serve as a tool to determine the viscosity of BFs.