bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution of clinical pharmacy practice and pharmacy education in Taiwan, Vietnam, and Indonesia: A narrative review
Authors: Lin Hsiang‐Wen , Yang Lin‐Chun , Mafruhah Okti Ratna , Nguyen Hanh T.H. , Cao Thao T.B. , Yam Felix K.
Published: May 2020

In this narrative review, we trace the evolution of health care, clinical pharmacy practice, and pharmacy education in Taiwan and two Southeast Asian countries, Vietnam and Indonesia. In evaluating the current health‐care systems and progress toward health‐care reform, we review the major changes that have impacted pharmacy practice and pharmacy education in each of these countries. The lack of qualified and well‐trained pharmacists has been identified as one of the key barriers to advancement of clinical pharmacy in this region. This shortage is based on a number of factors which include having a pharmacy education system that needs reform and expansion to adequately meet the growing demands of global public health. Many initiatives from organizations such as the World Health Organization, the International Pharmaceutical Federation, and the Federation of Asian Pharmaceutical Associations have influenced the advancement of global pharmacy practice and education. Moreover, we highlight key legislative changes that have impacted clinical pharmacy development in these countries and discuss how foreign policy changes in Taiwan have increased its collaboration with foreign pharmacy schools in Vietnam and Indonesia. Understanding the history and progress of clinical pharmacy education in these countries is important to help shape future collaborations that advance pharmacy practice and improve global health.
A novel photostable near‐infrared‐to‐near‐infrared fluorescent nanoparticle for in vivo imaging
Authors: Fan Qi , Cui Xiaoxia , Wang Quan , Gao Peng , Shi Shengjia , Wen Weihua , Guo Haitao , Xu Yantao , Peng Bo
Published: May 2020

Water‐soluble K5HoLi2F10 (KHLF) nanoprobes with the excitation and emission both in the near‐infrared (NIR) region were developed and first demonstrated for in vivo imaging of living mice. The PEG400 coating endows the nanoprobes with good water solubility and biocompatibility. Doping with Ho3+ ions is capable of emitting NIR fluorescence with two peaks centered, respectively, at 887 and 1,180 nm once excited by a 808 nm laser; meanwhile, it also possess good photothermal conversion performance. The KHLF matrix with specifically structure of large ion‐distance and low photon energy imparts the nanoprobes low quenching effect and excellent photostability (fluorescence decrease <5% upon 120 min illumination of 808 nm continuous laser with a power density of 1 W/cm2). The nanoparticles (NPs) were tested for in vitro bioimaging with living mice. The results show the NPs have low biotoxicity, rapid metabolism, normal biodistribution, together with the photothermal imaging performance and a high‐contrast fluorescence images (signal‐to‐background ratio of 14:1). The superior performances of these nanoprobes in vivo imaging of mice proclaim the great potential of this type of probe for high‐contrast imaging and photothermal treatment in practical applications.
High porous electrospun poly(ε‐caprolactone)/gelatin/MgO scaffolds preseeded with endometrial stem cells promote tissue regeneration in full‐thickness skin wounds: An in vivo study
Authors: Ababzadeh Shima , Farzin Ali , Goodarzi Arash , Karimi Roya , Sagharjoghi Farahani Morteza , Eslami Farsani Mohsen , Gharibzad Kamelia , Zahiri Maria , Ai Jafar
Published: May 2020

In the current study, electrospun poly(ε‐caprolactone)‐gelatin (PCL‐Gel) fibrous scaffolds containing magnesium oxide (MgO) particles and preseeded with human endometrial stem cells (hEnSCs) were developed to use as wound care material in skin tissue engineering applications. Electrospun fibers were fabricated using PCL‐Gel (1:1 [wt/wt]) with different concentrations of MgO particles (1, 2, and 4 wt%). The fibrous scaffolds were evaluated regarding their microstructure, mechanical properties, surface wettability, and in vitro and in vivo performances. The full‐thickness excisional wound model was used to evaluate the in vivo wound healing ability of the fabricated scaffolds. Our findings confirmed that the wounds covered with PCL‐Gel fibrous scaffolds containing 2 wt% MgO and preseeded with hEnSCs have nearly 79% wound closure ability while sterile gauze showed 11% of wound size reduction. Our results can be employed for biomaterials aimed at the healing of full‐thickness skin wounds.
Study on the osteogenesis of rat mesenchymal stem cells and the long‐term antibacterial activity of Staphylococcus epidermidis on the surface of silver‐rich TiN/Ag modified titanium alloy
Authors: Wan Rongxin , Chu Shanshan , Wang Xiaojuan , Lei Li , Tang Huiqing , Hu Guoying , Dong Lei , Li Dejun , Gu Hanqing
Published: May 2020

The main causes of failure of orthopedic implants are infection and poor bone ingrowth. Surface modification of the implants to allow for long‐term antibacterial and osteogenic functions is an effective solution to prevent failure of the implants. We developed silver‐rich TiN/Ag nano‐multilayers on the surface of titanium alloy with different doses of Ag+. The antibacterial stability and osteogenesis of the silver‐rich surface were determined by evaluating the adhesion and proliferation of Staphylococcus epidermidis, and the adhesion, proliferation, alkaline phosphatase activity, extracellular matrix mineralization, and the expression level of genes involved in osteogenic differentiation of rat bone mesenchymal stem cells (BMSCs). The results demonstrated that the antibacterial rates (Ra) of 5 × 1016‐Ag, 1 × 1017‐Ag, 5 × 1017‐Ag, and 1 × 1018‐Ag were respectively 46.21%, 85.66%, 94.99%, 98.48%, and 99.99%. After subcutaneous implantation in rats or immersion in phosphate buffered saline for up to 12 weeks, the silver‐rich surface of the titanium alloy showed long‐term stable inhibition of Staphylococcus epidermidis. Furthermore, in vitro and in vivo studies indicated that the Ag‐implanted titanium did not show apparent cytotoxicity and that lower Ag+ implanted groups (5 × 1016‐Ag, 1 × 1017‐Ag) had better viability and biological safety when compared with higher Ag+ implanted groups. In addition, when compared with the Ti6Al4V‐group, all Ag‐implanted groups exhibited enhanced osteogenic indicators in rat BMSCs. Regarding osteogenic indicators, the surfaces of the 5 × 1017‐Ag group had better osteogenic effects than those of other groups. Therefore, the proper dose of Ag+ implanted TiN/Ag nano‐multilayers may be one of the options for the hard tissue replacement materials with antibacterial activity and osteogenic functions.
The current status of temporal network analysis for clinical science: Considerations as the paradigm shifts?
Authors: Jordan D. Gage , Winer E. Samuel , Salem Taban
Published: May 2020

Objective

Network analysis in psychology has ushered in a potentially revolutionary way of analyzing clinical data. One novel methodology is in the construction of temporal networks, models that examine directionality between symptoms over time. This paper provides context for how these models are applied to clinically‐relevant longitudinal data.

Methods

We provide a survey of statistical and methodological issues involved in temporal network analysis, providing a description of available estimation tools and applications for conducting such analyses. Further, we provide supplemental R code and discuss simulations examining temporal networks that vary in sample size, number of variables, and number of time points.

Results

The following packages and software are reviewed: graphicalVAR, mlVAR, gimme, SparseTSCGM, mgm, psychonetrics, and the Mplus dynamic structural equation modeling module. We discuss the utility each procedure has for specific design considerations.

Conclusion

We conclude with notes on resources for estimating these models, emphasizing how temporal networks best approximate network theory.
Histone H4 variant, H4G, drives ribosomal RNA transcription and breast cancer cell proliferation by loosening nucleolar chromatin structure
Authors: Pang Matthew Y. H. , Sun Xulun , Ausió Juan , Ishibashi Toyotaka
Published: May 2020

The hominidae‐specific histone variant H4G is expressed in breast cancer patients in a stage‐dependent manner. H4G localizes primarily in the nucleoli via its interaction with nucleophosmin (NPM1). H4G is involved in rDNA transcription and ribosome biogenesis, which facilitates breast cancer cell proliferation. However, the molecular mechanism underlying this process remains unknown. Here, we show that H4G is not stably incorporated into nucleolar chromatin, even with the chaperoning assistance of NPM1. H4G likely form transient nucleosome‐like‐structure that undergoes rapid dissociation. In addition, the nucleolar chromatin in H4GKO cells is more compact than WT cells. Altogether, our results suggest that H4G relaxes the nucleolar chromatin and enhances rRNA transcription by forming destabilized nucleosome in breast cancer cells.
Biotechnological recycling of critical metals from waste printed circuit boards
Authors: Srivastava Rajiv R , Ilyas Sadia , Kim Hyunjung , Choi Sowon , Trinh Ha B , Ghauri Muhammad A , Ilyas Nimra
Published: May 2020

Critical metals are key raw materials for new generation clean energy production. The extraction of critical metals often follows the difficult processing of primary ores and they are many times recovered as the companion metals. With the depletion of primary reserves, the focus has now shifted to processing the urban mines, like electronic (e‐)waste. Among the different types of e‐waste, the waste printed circuit boards (WPCBs) are the major reservoir of high‐value critical metals and are usually treated by the traditional pyro‐ and/or hydro‐metallurgical techniques. However, the application of microbial activities in metals recycling is rapidly emerging as a green technology in comparison to smelter or chemical processing. The application of microorganisms (bacteria/fungi) in WPCBs’ recycling is being increasingly explored in order to meet the parallel objectives of resource recovery and pollution mitigation. Therefore, the present article assesses the current frontiers in bioleaching of critical metals from WPCBs and contains discussions on process fundamentals, challenges, and perspectives. The applicability of microbial recycling of WPCBs at a higher scale in terms of a circular economy and urban mining notion, the techno‐economic analysis, and environmental sustainability in comparison to the chemical processing route are also discussed. © 2020 Society of Chemical Industry
miR‐874‐3p inhibits cell migration through targeting RGS4 in osteosarcoma
Authors: Liu Wei‐Gang , Zhuo Lei , Lu Yun , Wang Lin , Ji Yan‐Xia , Guo Qing
Published: May 2020

Background

The present study explored the role and mechanism of microRNA‐874‐3p (miR‐874‐3p) in the migration of the osteosarcoma cell line, U‐2 OS.

Methods

The expression profile of osteosarcoma (OS) microRNA (GSE65071) datasets was downloaded from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo) to identify differentially expressed miRNAs in OS and its biological functions. A quantitative reverse transcription‐polymerase chain reaction was performed to detect the expression of miR‐874‐3p and its target gene regulator of G protein 4 (RGS4) in human osteosarcoma cells U‐2 OS and normal osteoblast hFOB1.19. Plasmid overexpression miR‐874‐3p and pcDNA‐RGS4 were transfected into U‐2 OS using Lipofectamine 2000 (Thermo Fisher, Waltham, MA, USA). Cell migration was measured using Transwell migration assays. Bioinformatic analysis and luciferase reporter assay were conducted to search for the target gene of miR‐874‐3p.

Results

In total, 167 differentially expressed miRNAs were detected after the analysis of GSE65071; of which 78 were up‐regulated genes and 89 were down‐regulated. miR‐874‐3p was down‐regulated and selected for further analysis. The expression level of miR‐874‐3p in U‐2 OS cells was significantly decreased compared to the hFOB1.19 cell line (p < 0.05). Overexpression of miR‐874‐3p significantly inhibited the proliferation and migration of U‐2 OS cells and overexpression of RGS4 reversed the inhibitory effect of miR‐874‐3p on U‐2 OS cells. Through luciferase report analyses and bioinformatic analysis, RGS4 may be the candidate target gene of miR‐874‐3p.

Conclusions

In conclusion, overexpression of miR‐874‐3p suppressed OS cell proliferation and migration. Thus, miR‐874‐3p might present a therapeutic agent for the treatment of OS.
Synthesis of novel isoxazole functionalized pyrazolo[3,4‐b]pyridine derivatives; their anticancer activity
Authors: Ravula Sampath , Bobbala Ramana Reddy , Kolli Balakrishna
Published: May 2020

A series of novel isoxazole functionalized pyrazolo[3,4‐b]pyridine derivatives 5a‐n were prepared, respectively, initiated from 6‐thiophenyl‐4‐(trifluoromethyl)‐1H‐pyrazolo[3,4‐b]pyridin‐3‐amine 3 through selective N‐propargylation, and these N‐propargylated compounds 4 were cyclized with aryloximes by using of sodium hypochlorite, and obtained the title products 5a‐n. All the final products 5a‐n were submitted for anticancer activity against four cancer cell lines such as “HeLa—cervical cancer (CCL‐2); COLO 205—colon cancer (CCL‐222); HepG2—liver cancer (HB‐8065); MCF7—breast cancer (HTB‐22)”; Compounds 5c, 5d, and 5h are found to have more prominent anticancer activity at micro molar concentration.
Chiral benzimidazole derived bis‐phenyl triazoles as chiroptical sensors for iodide and chiral amines
Authors: John Marina E. , Karnik Anil V.
Published: May 2020

A series of chiral 2‐hydroxy ethyl/benzyl benzimidazole based aryl triazole tweezers have been prepared using click chemistry in high yields. Chiral pool strategy has been used to obtain the benzimidazole‐based tweezers in very high enantiomerically enriched form. The aryl triazole tweezers, S‐(−)‐5a and S‐(+)‐8a displayed a high degree of selectivity for iodide anion over other anions, including other halides. The aryl triazole tweezers, S‐(−)‐5a and S‐(+)‐8a display significant enantio‐discrimination for chiral amines. The chiral recognition studies were carried out using UV and circular dichroism (CD) spectroscopy. NMR analysis has been used for establishing the sites for ligation of the iodide anion.
Convenient synthesis of functionalized thieno[2,3‐d]pyrimidine‐4‐ones and thieno[2,3‐b]pyridine‐4‐ones bearing a pyridine moiety with anticipated antioxidant activity
Authors: El‐Mekabaty Ahmed , Fouda Abd El‐Aziz S. , Shaaban Ibrahim E. I.
Published: May 2020

In the present study, ethyl 2‐amino‐4‐methyl‐5‐(pyridin‐2‐ylcarbamoyl)thiophene‐3‐carboxylate(2) has been achieved using the Gewald's methodology and served as a synthon for the synthesis of various derivatives of thieno[2,3‐d]pyrimidine‐4‐one and thieno[2,3‐b]pyridine‐4‐one bearing a pyridine moiety via its reactions with the convenient chemical reagents. The antioxidant performance has been tested using the ABTS method and the results disclosed that thienopyrimidinone 5 and thienopyridinones 18 and 19 have the most potent antioxidant efficiency with inhibition percentage at 84.41%, 80.95%, and 76.93%, respectively, compared with ascorbic acid as a reference drug.
Trophoblast-secreted soluble-PD-L1 modulates macrophage polarization and function
Authors: Zhang Yong-Hong , Aldo Paulomi , You Yuan , Ding Jiahui , Kaislasuo Janina , Petersen Jesper F , Lokkegaard Ellen , Peng Gang , Paidas Michael J , Simpson Samantha , Pal Lubna , Guller Seth , Liu Hong , Liao Ai Hua , Mor Gil
Published: May 2020

Decidual macrophages are in close contact with trophoblast cells during placenta development, and an appropriate crosstalk between these cellular compartments is crucial for the establishment and maintenance of a healthy pregnancy. During different phases of gestation, macrophages undergo dynamic changes to adjust to the different stages of fetal development. Trophoblast-secreted factors are considered the main modulators responsible for macrophage differentiation and function. However, the phenotype of these macrophages induced by trophoblast-secreted factors and the factors responsible for their polarization has not been elucidated. In this study, we characterized the phenotype and function of human trophoblast-induced macrophages. Using in vitro models, we found that human trophoblast-educated macrophages were CD14+CD206+CD86− and presented an unusual transcriptional profile in response to TLR4/LPS activation characterized by the expression of type I IFN-β expression. IFN-β further enhances the constitutive production of soluble programmed cell death ligand 1 (PD-L1) from trophoblast cells. PD-1 blockage inhibited trophoblast-induced macrophage differentiation. Soluble PD-L1 (sPD-L1) was detected in the blood of pregnant women and increased throughout the gestation. Collectively, our data suggest the existence of a regulatory circuit at the maternal fetal interface wherein IFN-β promotes sPD-L1 expression/secretion by trophoblast cells, which can then initiate a PD-L1/PD-1-mediated macrophage polarization toward an M2 phenotype, consequently decreasing inflammation. Macrophages then maintain the expression of sPD-L1 by the trophoblasts through IFN-β production induced through TLR4 ligation.
PB1-F2 protein of highly pathogenic influenza A (H7N9) virus selectively suppresses RNA-induced NLRP3 inflammasome activation through inhibition of MAVS-NLRP3 interaction
Authors: Cheung Pak-Hin Hinson , Ye Zi-Wei , Lee Tak-Wang Terence , Chen Honglin , Chan Chi-Ping , Jin Dong-Yan
Published: May 2020

Infection with seasonal as well as highly pathogenic avian influenza A virus (IAV) causes significant morbidity and mortality worldwide. As a major virulence factor, PB1-F2 protein of IAV affects the severity of disease through multiple mechanisms including perturbation of host innate immune response. Macrophages are known to phagocytose extracellular PB1-F2 protein aggregate, leading to hyperactivation of NLRP3 inflammasome and excessive production of IL-1β and IL-18. On the other hand, when expressed intracellularly PB1-F2 suppresses NLRP3 inflammasome maturation. How extracellular and intracellular PB1-F2 orchestrates to drive viral pathogenesis remains unclear. In this study, we demonstrated the suppression of NLRP3 inflammasome activation and IL-1β secretion by PB1-F2 of highly pathogenic influenza A (H7N9) virus in infected human monocyte-derived macrophages. Mechanistically, H7N9 PB1-F2 selectively mitigated RNA-induced NLRP3 inflammasome activation by inhibiting the interaction between NLRP3 and MAVS. Intracellular PB1-F2 of H7N9 virus did not affect extracellular PB1-F2-induced NLRP3 inflammasome maturation. In contrast, PB1-F2 of WSN laboratory strain of human IAV effectively suppressed IL-1β processing and secretion induced by various stimuli including NLRP3, AIM2, and pro-IL-1β. This subtype-specific effect of PB1-F2 on inflammasome activation correlates with the induction of a proinflammatory cytokine storm by H7N9 but not WSN virus. Our findings on selective suppression of MAVS-dependent activation of NLRP3 inflammasome by H7N9 PB1-F2 have implications in viral pathogenesis and antiviral development.
Frontline Science: Kindlin-3 is essential for patrolling and phagocytosis functions of nonclassical monocytes during metastatic cancer surveillance
Authors: Marcovecchio Paola M. , Zhu Yanfang Peipei , Hanna Richard N. , Dinh Huy Q. , Tacke Robert , Wu Runpei , McArdle Sara , Reynolds Sophia , Araujo Daniel J. , Ley Klaus , Hedrick Catherine C.
Published: May 2020

Nonclassical monocytes maintain vascular homeostasis by patrolling the vascular endothelium, responding to inflammatory signals, and scavenging cellular debris. Nonclassical monocytes also prevent metastatic tumor cells from seeding new tissues, but whether the patrolling function of nonclassical monocytes is required for this process is unknown. To answer this question, we utilized an inducible-knockout mouse that exhibits loss of the integrin-adaptor protein Kindlin-3 specifically in nonclassical monocytes. We show that Kindlin-3-deficient nonclassical monocytes are unable to patrol the vascular endothelium in either the lungs or periphery. We also find that Kindlin-3-deficient nonclassical monocytes cannot firmly adhere to, and instead “slip” along, the vascular endothelium. Loss of patrolling activity by nonclassical monocytes was phenocopied by ablation of LFA-1, an integrin-binding partner of Kindlin-3. When B16F10 murine melanoma tumor cells were introduced into Kindlin-3-deficient mice, nonclassical monocytes showed defective patrolling towards tumor cells and failure to ingest tumor particles in vivo. Consequently, we observed a significant, 4-fold increase in lung tumor metastases in mice possessing Kindlin-3-deficient nonclassical monocytes. Thus, we conclude that the patrolling function of nonclassical monocytes is mediated by Kindlin-3 and essential for these cells to maintain vascular endothelial homeostasis and prevent tumor metastasis to the lung.
Evaluation of Cardiac Shunts With 4D Flow Cardiac Magnetic Resonance: Intra‐ and Interobserver Variability
Authors: Urmeneta Ulloa Javier , Álvarez Vázquez Ana , Martínez de Vega Vicente , Cabrera José Ángel
Published: May 2020

Background

In the last decade, the capacity of magnetic resonance (MR) to evaluate congenital anomalies has improved substantially. To date, only a few studies have evaluated the value of 4D‐flow MRI in shunt assessments.

Purpose/Hypothesis

To assess the intra‐ and interobserver variability of 4D‐flow MRI in patients diagnosed with cardiac/extracardiac shunt. Secondarily, to assess the feasibility of directly measuring the shunt and to determine the prognostic correlation with the pulmonary‐to‐systemic (Qp/Qs) flow ratio.

Study Type

Retrospective.

Population

In all, 18 patients with cardiac shunt diagnosis.

Field Strength/Sequence

1.5 T/4D phase‐contrast MRI.

Assessment

Pulmonary and systemic flows were measured at different locations to assess the internal consistency by two observers (twice by one, and once by the other). The Qp/Qs ratio was calculated. When feasible, direct flow was quantified by planimetry.

Statistical Tests

Spearman's rho correlation coefficient was used to assess the relationship between pulmonary/systemic flows measured at different levels and to compare the jet characteristics with prognostic data as right ventricle volume. Intra‐ and interobserver variability were determined by Bland–Altman plots and interobserver correlation.

Results

The most common shunt type (n = 10; 55.5%) was ostium secundum atrial septal defect (ASD). Direct visualization and quantification of shunt flow was possible in all studies. Pulmonary and systemic flows showed a strong correlation between these measures (Spearman's rho [r] of 0.872 and 0.899). The mean Qp/Qs ratio was 1.61(0.62). Mean flow rate was 2.01(1.68) l/min. The mean jet diameter was 11.88 (5.44) mm. Intraobserver (r = 0.97) and interobserver correlation (ICC = 0.95) for the Qp/Qs calculation were both excellent. Direct measurement of flow was strongly correlated (r = 0.98; ICC = 0.95). Correlation was strong between Qp/Qs and direct jet flow (r = 0.76 and 0.77), Qp/Qs and mean jet diameter (r = 0.79 and 0.94), and Qp/Qs with jet area (r = 0.77 and 0.94).

Data Conclusion

Measurement of the Qp/Qs ratio and direct shunt quantification using 4D‐flow MRI was feasible, and highly reproducible. Internal consistency was excellent, with low intra‐ and interobserver variability. Correlation between the Qp/Qs ratio, direct flow measurement, mean diameter, and jet area was strong.

Evidence Level

3

Technical Efficacy

Stage 2 J. Magn. Reson. Imaging 2020;52:1055–1063.
Future evolution of the hydroclimatic conditions favouring floods in the south‐east of Belgium by 2100 using a regional climate model
Authors: Wyard Coraline , Scholzen Chloé , Doutreloup Sébastien , Hallot Éric , Fettweis Xavier
Published: May 2020

In Belgium, most flood events occur in winter as a result of intense precipitation events but also through the abrupt melting of the snowpack that covers the Ardennes summits. These conditions favourable to floods exhibit a decreasing trend over 1959–2010 resulting from the reduction in snow accumulation, although extreme precipitation events show a positive, albeit non‐significant signal. In this study, the evolution of these trends in warmer climates is investigated by using future projections performed with the regional climate model MAR (‘Modèle Atmosphérique Régional’) forced by two global models NorESM1‐M and MIROC5 under the RCP8.5 scenario. These models were selected from the CMIP5 archive after evaluation of their ability to represent the current (1976–2005) mean climate over Europe. By the end of the century, the results show an acceleration of the snow depletion resulting in fewer snowmelt‐associated flood risk days depending on the warming rate from the global models forcing MAR. Regarding the impact of the evolution of extreme precipitation events on hydroclimatic conditions favouring floods, no significant change was found although these trends are subject to uncertainties due to model physics and natural variability.
Assessment of South America summer rainfall climatology and trends in a set of global climate models large ensembles
Authors: Díaz Leandro B. , Saurral Ramiro I. , Vera Carolina S.
Published: May 2020

The purpose of this study is to assess the ability of a set of large ensembles (LE) of Global Climate Model (GCM) simulations from the Multi‐Model Large Ensemble Archive, Coupled Model Intercomparison Project Phase 6 (CMIP6) and database for Policy Decision making for Future climate change in reproducing the variability and change of the austral summer precipitation observed in South America along the second part of the 20th century and beginning of the 21st. LE show similar biases in the mean austral summer rainfall and interannual variability than those detected in previous model sets, such as the Coupled Model Intercomparison Project Phase 5 (CMIP5). The positive trends in south‐eastern South America (SESA) and negative ones in the southern Andes (SAn), that are the most significant observed regional features, are identified to some extent in LE simulations. The negative trend in SAn is a feature consistently shown among different models. For all models, mean trend is negative in that particular region and larger than the inter‐member dispersion for each large ensemble. Trend magnitudes in the SESA region show a larger dispersion between models than the SAn region. While the mean trend among models is consistent with the observations, models underestimate the observed trend. The multi‐model ensemble of selected models that best reproduce both mean and interannual variability features of rainfall in South America shows an 18% larger positive mean trend in SESA rainfall than those that have the worst performance. However, internal variability uncertainty is still higher than the mean trend for both sets of multi‐model ensembles [5% (18%) for selected (non‐selected) models]. Improvements in the representation of the main features of mean rainfall and variability are needed in order to better describe and reduce the uncertainties associated with the main climate change related signals in the continent.
Interleukin‐10 and Zonulin Are Associated With Postoperative Delayed Gastric Emptying in Critically Ill Surgical Pediatric Patients: A Prospective Pilot Study
Authors: Martinez Enid E. , Zurakowski David , Pereira Luis , Freire Rachel , Emans John B. , Nurko Samuel , Duggan Christopher P. , Fasano Alessio , Mehta Nilesh M.
Published: May 2020

Background

Impaired gastric emptying (GE) is associated with morbidity in surgical critically ill children. The relationship between inflammation, gut barrier integrity (lipopolysaccharide binding protein [LBP]; zonulin), and GE has not been described in this cohort.

Methods

Children ≥2 years of age and requiring critical care after surgery were enrolled. Preoperative and postoperative levels of serum cytokines, LBP, and zonulin, and GE by the acetaminophen absorption test, were measured, allowing patients to serve as their own controls. Postoperative delayed GE was defined as a decrease in GE by ≥20% compared with preoperative GE. The following were examined : comparison between postoperative andpreoperative values, correlations between fold change (postoperative/preoperative) in study variables, and fold change in study variables between patients with and without postoperative delayed GE.

Results

Twenty patients, median age 14 years (12.25, 18), 12 female, were included. Eight of 20 patients had postoperative delayed GE. Postoperative interleukin‐6 (IL‐6), IL‐8, IL‐10, and LBP were increased, and zonulin was decreased (P‐values < .05). Fold change in IL‐10 and zonulin were inversely correlated (ρ −0.618,P= .004). Patients with postoperative delayed GE had greater fold increase in IL‐10 (P= .0159) and fold decrease in zonulin (P= .0160). Five of 7 (71%) patients with both fold increase in IL‐10 and decrease in zonulin had delayed GE.

Conclusion

Postoperative changes in IL‐10 and zonulin were associated with delayed GE in surgical critically ill children, which might suggest a mechanism to for delayed GE in postoperative inflammation and gut barrier dysregulation after surgery.
Parenteral and Enteral Nutrition: A Bridge to Healing and Biological Therapy in a Patient With Enterocutaneous Fistula and Sepsis Complicated Crohn's Disease
Authors: Kucharski Marcin A. , Wierzbicka Adrianna , Tsibulski Alexander , Sotiri Emianka , Dobrowolska Agnieszka , Mańkowska‐Wierzbicka Dorota
Published: May 2020

Inflammatory bowel disease (IBD) patients with severe infections, abscess, or sepsis are ineligible for standard treatment using biological and immunosuppressive drug regimens. We report a case of complicated Crohn's disease with ruptured abdominal abscess, presence of enterocutaneous fistula, and sepsis. We also report and discuss patient management with parenteral nutrition (PN) and enteral nutrition (EN) and treatment outcomes. We report a case of a 31‐year‐old female with a 10‐year history of IBD in clinical remission, who, after previous total proctocolectomy with J‐pouch, presented to the clinic with severe abdominal pain of 2 days, unintentional weight loss, fatigue, fever, and abdominal abscess, which ruptured, and her clinical state became complicated by sepsis. PN was initiated using individually prepared admixture according to patient requirements, because of inability to tolerate any oral intake. Following the remittance of ileus symptoms, EN was added using a semielemental formula via a nasojejunal tube. Upon completion of the treatment, the fistula resolved, the wound had healed, and Crohn's Disease Activity Index score showed remission. This qualified the patient for initiation of biological therapy with infliximab. Patients with severe infections, abscesses, or sepsis are ineligible for standard IBD treatment using biological and immunosuppressive drug regimens. Furthermore, usually patients’ nutrition condition prevents them from combating infection and initiating proper healing process. This case demonstrates the importance of considering nutrition therapy—PN and EN—in unstable patients who cannot be treated with standard pharmacological therapy. Nutrition therapy offers a bridge that allows patients to stabilize and heal before starting standard pharmacological treatment with immunosuppressive agents or biological therapy.
Factors Associated With Central Line–Associated Bloodstream Infections in a Cohort of Adult Home Parenteral Nutrition Patients
Authors: Xue Zhigang , Coughlin Rachel , Amorosa Valerianna , Quinn Ryan , Schiavone Phyllis , Stoner Nancy , Kinosian Bruce , Compher Charlene
Published: May 2020

Background

Central line–associated bloodstream infection (CLABSI) is a potentially life‐threatening complication in home parenteral nutrition (HPN) patients. We investigated potential predictors of CLABSI in a cohort of adult HPN patients

Methods

Patients managed by the HPN service at the Hospital of University of Pennsylvania on January 1, 2018, were included and followed through June 30, 2019, using existing medical records to collect demographic and clinical data. CLABSIs were adjudicated prospectively by infectious disease experts. Variables with P ≤ .2, when comparing patients with CLABSIs and those without, were included in logistic regression models.

Results

Among 114 patients, mean age was 54 ± 16 years, 78/114 were female, and BMI was 25 ± 5.6. Median experience with HPN was 516 days (range, 15–10,281), and 30 had prior CLABSI. Catheter types were peripherally inserted central catheters (83/114), tunneled (27), and implanted (4). The incidence of CLABSI was 0.89 per 1000 catheter days. One multivariate model identified ostomy/wound (odds ratio [OR], 22.0; 95% CI, 4.8–101.7), tunneled/implanted catheter (OR, 4.4; 95% CI, 1.4–13.9), and BMI < 18.5 (OR, 5.9; 95% CI, 1.4–24.2) as predictors of CLABSI. A second model identified patients with 2 potential predictors (OR, 22.9; 95% CI, 5.6–93.5) and tunneled/implanted catheter (OR, 6.7; 95% CI, 2.1–21.8) at high risk of CLABSI. Whether CLABSIrates might be reduced by more intense training in wound or catheter care (especially for those with multiple predictors), different types of catheters, or rapid treatment of malnutrition will require further study.
Ultrasound for pectinase modification: an investigation into potential mechanisms
Authors: Ma Xiaobin , Cai Jingwen , Liu Donghong
Published: May 2020

BACKGROUND

Today, ultrasound is increasingly utilized in enzyme modification. Strongly dependent on the specific operational conditions, the modification effect brought by ultrasound can be activation and inactivation of enzymes. This work aims to study the ultrasound mechanisms under different conditions, to investigate the respective roles of free radical effect and mechanical effect in pectinase activation and inactivation, and to reveal the influence of pectinase concentration on the ultrasound‐modification effect.

RESULTS

When ultrasound was introduced to a liquid system, generation of free radicals was positively correlated with ultrasound intensity and treatment duration, but negatively correlated with temperature. Thiourea with a concentration of 4 mmol L–1 was selected as a free radical scavenger to effectively shield ultrasound free radicals. The highest enzyme activity of pectinase solutions at 0.1, 1.0, and 10.0 mg mL−1 was obtained at the same ultrasound intensity of 4.50 W mL−1 and time of 15 min, where the enzyme activity was increased by 68.24%, 20.98% and 18.83%, respectively. Furthermore, the addition of thiourea enhanced the enzyme activity at each tested ultrasound intensity and time, especially those exceeding the best conditions; it also eliminated the redshift phenomenon that was previously presented in the fluorescence spectra of pectinase samples.

CONCLUSION

Pectinase concentrations did not change the optimum ultrasound conditions for enzyme modification, but pectinase with a low concentration was more vulnerable to ultrasound treatment. During modification, ultrasound mechanical effects dominated in the pectinase activation, while free radical effects dominated in the inactivation process. © 2020 Society of Chemical Industry
Differentiating Westlake Longjing tea from the first‐ and second‐grade producing regions using ultra high performance liquid chromatography with quadrupole time‐of‐flight mass spectrometry‐based untargeted metabolomics in combination with chemometrics
Authors: Zhang Qian , Zhang Yu‐Ying , Liu Zhi , Zhang Yue‐Ming , Lu Ning , Hai Guo‐Qing , Shao Sheng‐Zhi , Zheng Qing‐Xia , Zhang Xia , Fu Hai‐Yan , Bai Chang‐Cai , Yu Yong‐Jie , She Yuanbin
Published: May 2020

There are numerous articles published for geographical discrimination of tea. However, few research works focused on the authentication and traceability of Westlake Longjing green tea from the first‐ and second‐grade producing regions because the tea trees are planted in a limited growing zone with identical cultivate condition. In this work, a comprehensive analytical strategy was proposed by ultrahigh performance liquid chromatography‐quadrupole time‐of‐flight mass spectrometry‐based untargeted metabolomics coupled with chemometrics. The automatic untargeted data analysis strategy was introduced to screen metabolites that expressed significantly among different regions. Chromatographic features of metabolites can be automatically and efficiently extracted and registered. Meanwhile, those that were valuable for geographical origin discrimination were screened based on statistical analysis and contents in samples. Metabolite identification was performed based on high‐resolution mass values and tandem mass spectra of screened peaks. Twenty metabolites were identified, based on which the two‐way encoding partial least squares discrimination analysis was built for geographical origin prediction. Monte Caro simulation results indicated that prediction accuracy was up to 99%. Our strategy can be applicable for practical applications in the quality control of Westlake Longjing green tea.
Ultrasound Findings of Breast Adenomas
Authors: Macedo Miguel , Bassaganyas Clara , Ganau Sergi , Sanfeliu Esther , Ubeda Belen , Bargallo Xavier
Published: May 2020

Objectives

Breast adenomas are rare benign tumors. The aim of this study was to describe the ultrasound findings of breast adenomas, including less common worrisome features that can mimic malignancy.

Methods

From November 2014 to November 2019, we performed 1605 core needle biopsies guided by ultrasound in our department. In all, 229 corresponded to fibroadenomas and 12 to breast adenomas.

Results

Breast adenomas represented 0.75% of all core needle biopsies; 50% (6 of 12) were tubular adenomas; 17% (2 of 12) were ductal adenomas; and 33% (4 of 12) were lactating adenomas. Tubular and lactating adenomas occurred in young women and ductal adenomas in postmenopausal women. Lactating adenomas occurred in pregnant or breastfeeding women and were larger than the other adenomas. Ultrasound showed a mass with an oval shape, a parallel orientation, circumscribed margins, and hypoechoic and homogeneous patterns in most cases. However, up to one‐third of them presented with suspicious findings.

Conclusions

Breast adenomas are rare benign entities with no specific clinical and radiologic features. Sometimes, they appear as suspicious tumors on radiologic modalities, requiring a histopathologic assessment to rule out malignancy. Radiologists need to be familiar with this entity to determine concordance between imaging and the final pathologic analysis.
Nasal Peak Inspiratory Flow in Healthy and Obstructed Patients: Systematic Review and Meta‐Analysis
Authors: Mo Shirley , Gupta Sai S. , Stroud Anna , Strazdins Erika , Hamizan Aneeza W. , Rimmer Janet , Alvarado Raquel , Kalish Larry , Harvey Richard J.
Published: May 2020

Objectives

Nasal peak inspiratory flow (NPIF) is a practical and affordable tool that measures maximum inspiratory flow rate through both nostrils. Although NPIF values for healthy controls and patients appear to differ considerably, a generally expected value for populations with and without nasal obstruction has yet to be established. The aim of this systematic review and meta‐analysis was to determine the mean NPIF value in populations with and without nasal obstruction.

Methods

Medline (1946–) and Embase (1947–) were searched until July 1, 2017. A search strategy was used to identify studies that reported NPIF values for defined healthy or disease states. All studies providing original data were included. The study population was defined as having either normal nasal breathing or nasal obstruction. A meta‐analysis of the mean data was presented in forest plots, and data were presented as mean (95% confidence interval [CI]).

Results

The search yielded 1,526 studies, of which 29 were included. The included studies involved 1,634 subjects with normal nasal breathing and 817 subjects with nasal obstruction. The mean NPIF value for populations with normal nasal breathing was 138.4 (95% CI: 127.9‐148.8) L/min. The mean value for populations with nasal obstruction was 97.5 (95% CI: 86.1‐108.8) L/min.

Conclusions

Current evidence confirms a difference between mean NPIF values of populations with and without nasal obstruction. The mean value of subjects with no nasal obstruction is 138.4 L/min, and the mean value of nasally obstructed populations is 97.5 L/min. Prospective studies adopting a standardized procedure are required to further assess normative NPIF values. Laryngoscope, 131:260–267, 2021
Squamous Cell Carcinoma Metastasis to the Supraclavicular Artery Island Flap Donor Site
Authors: West Jonathan D. , Martin Amanda N. , Kim James , Kokot Niels
Published: May 2020

A rare complication of flap reconstruction following oncologic ablation is metastasis to the donor site. We present a novel case of cutaneous squamous cell carcinoma (SCCA) recurrence at the right upper‐extremity donor site following tonsillar SCCA resection with supraclavicular artery island flap reconstruction. Following surgery, the patient presented with cutaneous recurrence at the right upper‐extremity donor site. Biopsy confirmed metastasis from the oropharyngeal primary. The patient developed two subsequent right upper‐extremity recurrences before he died. The most likely mechanism of metastasis is direct implantation via contamination. This case demonstrates the importance of maintaining separate surgical fields and instruments during oncologic ablation and reconstruction. Laryngoscope, 131:E440–E442, 2021
Quantification of isoprene in coastal ecosystems by gas chromatography–mass spectrometry using cumulative headspace injections
Authors: Hrebien Victoria , Deschaseaux Elisabeth , Eickhoff William , Swan Hilton B. , Eyre Bradley D.
Published: May 2020

Isoprene is a biogenic volatile organic compound (BVOC), which is predominantly emitted by terrestrial plants but also from marine systems. However, the marine contribution to isoprene emissions is less understood due to the difficulty of measuring trace concentrations in seawater. Previous methods using “purge and trap” coupled with flame ionization detection and/or chemiluminescence have been developed, although these methods have limitations including large sample sizes, excessive manipulation, and potential interference from other BVOCs. These limitations could lead to overestimations or sample loss due to the high volatility and reactivity of isoprene. Here, we present an improved method for measuring isoprene in coastal marine ecosystems with elevated isoprene concentrations using cumulative headspace injection coupled with gas chromatography–mass spectrometry (GC‐MS). Sampling technique, preservation, and analytical conditions were tested and optimized using an analytical cycle time of 13 min. The analytical precision was 2.6% (n = 7), limit of detection was 15 pM, limit of quantification was 285 pM, accuracy based on recovery was 79% ± 2.8%, and reproducibility yielded a coefficient of variation of 15%. This method provides an improved way to measure isoprene from seawater using a simple sampling technique and fast, automated analysis, reducing isoprene loss through sample manipulation, and human error. This method meets analytical requirements to accurately measure isoprene at pM concentrations, which are typical of tropical coastal marine habitats. This method can also be adapted to measure other BVOCs in seawater such as dimethyl sulfide, providing a versatile method for marine research.
Corporate governance and stock price crash risk: Evidence from Taiwan
Authors: Wu Sheng‐Fu , Fang Chung‐Yi , Chen Wei
Published: May 2020

Managers are likely to withhold negative news to protect their own interests. When they can no longer withhold such news, extreme negative returns and a stock price crash (SPC) follow. This study explores whether a favorable corporate governance (CG) mechanism helps reduce SPC risk. The findings reveal that CG affects SPC risk. Moreover, the effects of institutional ownership, board size, and disclosure violation frequency are particularly significant in family‐owned businesses. We also examine the effectiveness of CG evaluation (CGE) in Taiwan and discover that companies with high rankings are substantially less likely to encounter an SPC. This study verifies that CGE can be considered an indicator of SPC risk.
5‐Heptadecylresorcinol, a Biomarker for Whole Grain Rye Consumption, Ameliorates Cognitive Impairments and Neuroinflammation in APP/PS1 Transgenic Mice
Authors: Liu Jie , Wang Yu , Wang Ziyuan , Hao Yiming , Bai Wanzhu , Wang Zongwei , Wang Jing
Published: May 2020

Scope

5‐heptadecylresorcinol (AR‐C17) is a biomarker for whole grain rye consumption, which is also an important active component with potential health benefits. The aim of this study is to investigate the protective effect of AR‐C17 on cognitive deficits in amyloid precursor protein (APP)/PS1 transgenic mice.

Methods and results

Cognitive function is evaluated using Morris water maze test. The result shows that oral administration of AR‐C17 (150 mg kg−1 day−1) for 5 months can ameliorate APP/PS1 transgenic mice memory impairment and improve learning ability. Moreover, AR‐C17 treatment can notably reduce β‐amyloid plaques accumulation and tau hyperphosphorylation while enhancing a disintegrin and metalloprotease 10 (ADAM10), postsynaptic density protein‐95 (PSD‐95), and synaptophysin protein expression in APP/PS1 transgenic mice. Furthermore, AR‐C17 treatment reduces neuroinflammation by inhibiting microglial activation and astrogliosis as well as decreasing NOD‐like receptor family, pyrin domain‐containing 3 (NLRP3) inflammasome‐mediated IL‐1β production and activating the sirtuin 3 (SIRT3)/superoxide dismutase 2 (SOD2) signaling pathway. Additionally, AR‐C17 consumption significantly modulated gut dysbiosis in APP/PS1 transgenic mice through improving the relative abundance of Akkermansia and Lactobacillus while reducing the abundance of Clostridium and Desulfovibr according to16S rRNA analysis.

Conclusion

AR‐C17 can be applied as a potential functional food ingredient to ameliorate cognitive impairments and prevent Alzheimer's disease.
Increasing Doses of Blueberry Polyphenols Alters Colonic Metabolism and Calcium Absorption in Ovariectomized Rats
Authors: Cladis Dennis P. , Debelo Hawi , Lachcik Pamela J. , Ferruzzi Mario G. , Weaver Connie M.
Published: May 2020

Scope

Blueberries are rich sources of bioactive polyphenols that may provide health benefits when consumed regularly, leading to their increased marketing as dietary supplements. However, the metabolic changes associated with consuming concentrated doses of purified polyphenols, as may be present in dietary supplements, are unknown, especially when considering the colonic metabolites formed. This study aimed to evaluate the pharmacokinetics of high doses of purified blueberry polyphenols.

Methods and results

5‐month old, ovariectomized Sprague‐Dawley rats are acutely dosed with purified blueberry polyphenols (0, 75, 350, and 1000 mg total polyphenols per kg body weight (bw)) and45Ca to measure calcium absorption. Blood and urine are collected for 48 h after dosing and phenolic metabolites measured via ultra high‐pressure liquid chromatography–tandem mass spectrometry (UPLC‐MS/MS). The most prominent metabolites are colonically generated cinnamic and hippuric acids. Smaller amounts of other phenolic acids, flavonols, and anthocyanins are also detected. Most metabolites follow a dose–response relationship, though several show saturated absorption. Maximal metabolite concentrations are reached within 12 h for a majority of compounds measured, while some (e.g., hippuric acid) peaked up to 24 h post‐dosing. Calcium absorption is significantly increased in the highest dose group (p= 0.03).

Conclusion

These results indicate that increased doses of blueberry polyphenols induce changes in intestinal phenolic metabolism and increase calcium absorption.