bluuebunny/crossref_metadata_2025 huggingface dataset:
Circular RNA La‐related RNA‐binding protein 4 correlates with reduced tumor stage, as well as better prognosis, and promotes chemosensitivity to doxorubicin in breast cancer
Authors: Zhang Xiaoyi , Su Xinyu , Guo Zhe , Jiang Xueqing , Li Xun
Published: March 2020

Objective

We aimed to evaluate the correlation of circular RNA La‐related RNA‐binding protein 4 (circ‐LARP4) with tumor characteristics and prognosis, and its effect on chemosensitivity in breast cancer.

Methods

Circ‐LARP4 from tumor and adjacent tissues of 283 female breast cancer patients underwent resection was detected by reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR). Tumor features, disease‐free survival (DFS), and overall survival (OS) were recorded. In vitro, circ‐LARP4 in human normal mammary epithelial cells (HMEC) and breast cancer cell lines was detected by RT‐qPCR. MCF‐7 and MDA‐MB‐231 cells were transfected with circ‐LARP4 overexpression plasmid (as OE‐Circ group) and control overexpression plasmid (as OE‐Control group). Relative cell viability under different concentrations of doxorubicin was measured.

Results

Circ‐LARP4 was decreased in tumor tissues than adjacent tissues (P < .001). Tumor circ‐LARP4 negatively correlated with tumor size (P = .001), T stage (P = .009), N stage (P = .006), and TNM stage (P < .001), whereas positively correlated with DFS (P = .004) and OS (P < .001). In vitro, circ‐LARP4 was decreased MCF‐7, BT474, MDA‐MB‐231, and MDA‐MB‐468 cell lines than HMEC (allP < .001). Relatively cell viability of MCF‐7 cells (at 20 nmol/L [P < .05], 40 nmol/L [P < .01], 80 nmol/L [P < .05] of doxorubicin) and MDA‐MB‐231 cells (at 120 nmol/L [P < .05], 240 nmol/L [P < .05] of doxorubicin) was decreased in OE‐Circ group than OE‐Control group. IC50value of doxorubicin was decreased in OE‐Circ group than OE‐Control group in MCF‐7 and MDA‐MB‐231 cell lines (bothP < .01).

Conclusion

Circ‐LARP4 was a potential prognostic biomarker, which might improve the management of breast cancer.
Iodine mediated synthesis of some new imidazo[1,2‐a]pyridine derivatives and evaluation of their antimicrobial activity
Authors: Ashok Dongamanti , Ram Reddy M. , Ramakrishna Katta , Nagaraju Nalaparaju , Dharavath Ravinder , Sarasija Madderla
Published: March 2020

Herein, we reported a series of new 2‐(5‐methyl‐1‐aryl‐1H‐1,2,3‐triazol‐4‐yl)imidazo[1,2‐a]pyridines by using iodine and NH4OAc in good yields. The structures of the titled compounds were characterized by the elemental analysis, 1H NMR, 13C NMR, IR, and mass spectral analysis. All the titled compounds were screened for their in vitro antibacterial and antifungal activities by using streptomycin and Nystatin as standard drugs. The compounds 3k, 3l, 3g, and 3c exhibited potent activity against the tested bacterial strains and 3k, 3l, and 3c exhibited potent activity against the tested fungal strains than the reference drugs.
Effects of different probiotic combinations on the components and bioactivity of Spirulina
Authors: Yu Jinhui , Ma Deyuan , Qu Shujie , Liu Yunpeng , Xia Han , Bian Fei , Zhang Yan , Huang Chao , Wu Rina , Wu Junrui , You Shengbo , Bi Yuping
Published: March 2020

Spirulina acts as a good dietary nutritional supplement. However, few research studies have been conducted on its fermentation. Three groups of probiotic combinations, lactic acid bacteria, Bacillus strains, and their mixture, were used to investigate Spirulina fermentation. The results showed that lactic acid bacteria significantly increased the content of amino acids and the ratio of essential amino acids to total amino acids in the fermented Spirulina, compared with the unfermented Spirulina, and this trend was enhanced by the strains' mixture. However, compared to unfermented Spirulina, the amino acid levels were significantly decreased after fermentation with Bacillus strains and so was the total free amino acid and essential amino acid content. Fermentation significantly reduced the contents of the offensive components of Spirulina, with significant differences among the three mixed bacterial treatments. Moreover, Bacillus strain fermentation increased the contents of flavonoids and polyphenols compared to the unfermented Spirulina, and significantly enhanced 1,1‐diphenyl‐2‐trinitrophenylhydrazine free‐radical scavenging ability and total antioxidant ability. On the contrary, treatments with lactic acid bacteria and the mixture of lactic acid bacteria and Bacillus strains endowed the fermented supernatants with good antibacterial ability. The results showed that probiotic fermentation has a good effect on Spirulina and can serve as a new procedure for developing new Spirulina‐containing food items.
El Niño Southern Oscillation‐related precipitation anomaly variability over eastern subtropical South America: Atypical precipitation seasons
Authors: Hurtado Santiago I. , Agosta Eduardo A.
Published: March 2020

Precipitation anomalies over subtropical Argentina in eastern subtropical South America (ESSA) show significant signatures of the El Niño Southern Oscillation (ENSO) during the SONDJ (from September to January) season. The correlation maps between seasonal precipitation anomalies and the C‐index show a dipole structure with positive correlation over eastern ESSA and negative over South American convergence zone. Based on principal component analysis, precipitation anomalies within the SONDJ season during ENSO events were discriminated into three categories typical, atypical and nontypical, regarding their precipitation response. Typical (atypical) stands for precipitation anomalies similar (inverse) in comparison to the linear expected anomalies for El Niño or La Niña events. In the period 1979–2016, five (five) typical seasons, two (zero) atypical seasons and six (six) nontypical seasons were recorded under El Niño (La Niña) events. During typical SONDJ seasons under El Niño, precipitation over ESSA is mainly modulated by regional tropospheric circulation anomalies induced by quasi‐stationary Rossby wave propagation from the western South Pacific towards South America. The precipitation anomalies during the two atypical SONDJ seasons in El Niño were overall partly owing to shifts of the sea surface temperature (SST) gradient in the equatorial Pacific, and changes in the Atlantic basin SST anomalies.
Small‐Bowel Adaptation: A Case of Morphological Changes Induced by Teduglutide in Short‐Bowel Syndrome With Intestinal Failure
Authors: Mouillot Thomas , Boehm Vanessa , Treton Xavier , Ferrandi Emilie , Kapel Nathalie , Cazals‐Hatem Dominique , Joly Francisca
Published: March 2020

Teduglutide (TED) reduces the need for parenteral support (PS) in patients with short‐bowel syndrome with intestinal failure (SBS‐IF). It is a glucagon‐like peptide‐2 analog that improves absorption, induces the expansion of the absorptive epithelium in the small intestine, and may be used in patients with SBS‐IF after a 6‐ to 12‐month adaptation period, if PS is always necessary. We described the functional and morphological effect of TED in a 40‐year‐old female patient with SBS‐IF due to Crohn's disease who underwent terminal jejunostomy after 12 months of drug exposition. Marked hypertrophy of the villi was detected by endoscopic capsule and confirmed by histological measurements. This is the first publication demonstrating an increase in intestinal absorption in an SBS‐IF patient treated with TED because of a morphological adaptation of the small bowel, with hyperplasia confirmed by capsule endoscopy and histology. The capsule endoscopy, a noninvasive exploration of the gut, could be evaluated to monitor the real efficacy of treatments with growth factors in SBS patients.
Determination of oroxylin A, oroxylin A 7‐O‐glucuronide, and oroxylin A sodium sulfonate in beagle dogs by using UHPLC MS/MS Application in a pharmacokinetic study
Authors: Ren Guanghui , Chen Huili , Zhang Mei , Yang Nan , Yang Hui , Xu Chuanru , Li Jiaming , Ning Chen , Song Zhongjin , Zhou Shiyu , Zhang Siliang , Wang Xiaoqian , Lu Yang , Li Ning , Zhang Yongjie , Chen Xijing , Zhao Di
Published: March 2020

Oroxylin A, obtained from the root of Scutellaria baicalensis Georgi, is a flavonoid with antitumor and other pharmacological activities. Our previous studies showed for the first time that it is mainly metabolized to oroxylin A sodium sulfonate by sulfotransferase enzymes in beagle dogs. In this study, rapid, universal, selective, and robust ultra‐high‐performance liquid chromatography–tandem mass spectrometry methods were established and fully validated to quantitatively detect oroxylin A, oroxylin A 7‐O‐glucuronide, and oroxylin A sodium sulfonate in beagle dog plasma. The quantitative analysis for oroxylin A sodium sulfonate was reported for the first time. Plasma samples were processed with acetonitrile, a universal protein precipitant. Gradient elution was performed to resolve carryover effects and to achieve separation efficiency and sufficient chromatographic retention. The linear relationships of oroxylin A, oroxylin A 7‐O‐glucuronide, and oroxylin A sodium sulfonate in plasma were in the range of 2.0–500.0, 5.0–500.0, and 1.881–940.5 ng/mL, respectively. The assay method was successfully applied to pharmacokinetic study. This is the first paper that reveals the pharmacokinetic profile of oroxylin A, oroxylin A 7‐O‐glucuronide, and oroxylin A sodium sulfonate after single‐dose intravenous and oral administration of Oroxylin A in beagle dogs.
Dynamics of an intense diatom bloom in the Northern Antarctic Peninsula, February 2016
Authors: Costa Raul Rodrigo , Mendes Carlos Rafael Borges , Tavano Virginia Maria , Dotto Tiago Segabinazzi , Kerr Rodrigo , Monteiro Thiago , Odebrecht Clarisse , Secchi Eduardo Resende
Published: March 2020

Diatoms are considered the main base of the Southern Ocean food web as they are responsible for more than 85% of its annual primary production and play a crucial role in the Antarctic trophic structure and in the biogeochemical cycles. Within this context, an intense diatom bloom reaching > 45 mg m−3 of chlorophyll a was registered in the Northern Antarctic Peninsula (NAP) during a late summer study in February 2016. Given that nutrient concentrations and grazing activities were not identified here as limiting factors on the bloom development, the aim of this study was to evaluate the effect of water column structure (stability and upper mixed layer depth) on the phytoplankton biomass and composition in the NAP. The diatom bloom, mainly composed by the large centric Odontella weissflogii (mostly > 70 μm in length), was associated with a local ocean carbon dioxide uptake that reached values greater than −60 mmol m−2 d−1. We hypothesize that the presence of a vertically large water column stability barrier, just below the pycnocline, was the main driver allowing for the development of the intense diatom bloom, particularly in the Gerlache Strait. Contrarily, a shift from diatoms to dinoflagellates (mainly Gymnodiniales < 20 μm) was observed associated with conditions of a highly stable thin layer. The results suggest that a large fraction of this intense diatom bloom is in fast sinking process, associated with low grazing pressure, showing a crucial role of diatoms for the efficiency of the biological carbon pump in this region.
A Transcriptome Sequencing Study on Genome‐Wide Gene Expression Differences of 3D Cultured Chondrocytes in Hydrogel Scaffolds with Different Gel Density
Authors: Zhang Weiyuan , Xia Yujun , Ling Yang , Yang Wei , Dong Zuo‐Xiang , Wang Dong‐An , Fan Changjiang
Published: March 2020

Hydrogel is considered as a promising cell delivery vehicle in cartilage tissue engineering, whose tunable microenvironments may influence the function and fate of encapsulated chondrocytes. Here, the transcriptomes of chondrocytes that are encapsulated and cultured in hydrogel constructs respectively made of 0.8% and 4% alginate solution are investigated. Differences in chondrocyte transcriptome are detected via RNA‐sequencing from these two cultural conditions. The differentially expressed genes (DEGs) are reflected in extracellular matrix (ECM) secretion, cell cycle, proliferation, cartilage development, and so on. Significantly, the expression of DEGs associated with cartilage ECM and cell proliferation are upregulated in 0.8% constructs; whilst the expressions of DEGs involved in cell cycle and matrix degradation are upregulated in 4% constructs. Moreover, interestingly, the expressions of chondrocyte hypertrophy markers are upregulated in 0.8% constructs; while 4% constructs seemingly favor the long‐term maintenance of chondrocyte phenotype. Taken together, this study confirms on transcriptomic level that gel density affects gene expression and phenotype of the encapsulated chondrocytes; therefore, it may provide guidance for future design and fabrication of cartilage tissue engineering scaffolds.
Dihydromethysticin, a natural molecule from Kava, suppresses the growth of colorectal cancer via the NLRC3/PI3K pathway
Authors: Pan Huayang , Liu Fukai , Wang Jinge , Zhao Ming , Wang Dawei , Jia Chen , Wang Tong , Chen Ze , Fan Yuying , Liang Desen , Meng Qinghui
Published: March 2020

Dihydromethysticin (DHM), a natural compound derived from Kava, has been reported to be effective against mental disorders and some malignant tumors. However, little is known about the inhibitory effect of DHM on colorectal cancer (CRC). First, we examined the impact of DHM on human colon cancer cell lines, which demonstrated that DHM inhibits proliferation, migration, and invasion and promotes apoptosis and cell cycle arrest in colon cancer cells in vitro. Using small hairpin RNA, we inhibited nucleotide‐oligomerization domain‐like receptor subfamily C3 (NLRC3)/phosphoinositide 3‐kinase (PI3K) pathway to elucidate the partial signaling of DHM‐mediated tumor suppression. Additionally, using an ectopic human CRC model, we verified whether DHM inhibits tumor growth and angiogenesis via the NLRC3/PI3K pathway in vivo. Overall, DHM showed an inhibitory effect on CRC by altering cell proliferation, migration, invasion, apoptosis, cell cycle, and angiogenesis, possibly via the NLRC3/PI3K pathway. Thus, DHM may be a promising candidate for CRC therapy.
Near‐optimal control of a stochastic vegetation‐water system with reaction diffusion
Authors: Pan Shiliang , Zhang Qimin , Anke Meyer‐Baese
Published: March 2020

In this article, we study the near‐optimal control of a class of stochastic vegetation‐water model. The near‐optimal control is one problem in which the density of vegetation and water is higher at the lowest cost. We have provided a priori estimates of the vegetation and water densities and obtained the sufficient and necessary conditions for the system's near‐optimal control problem by applying the maximum condition of the Hamiltonian function and the Ekeland principle. A numerical simulation is presented to verify our theoretical results.
Microbial survival and growth modeling in frame of nonsingular fractional derivatives
Authors: Ozarslan Ramazan
Published: March 2020

In this article, the two‐parameter Weibull model (3) is considered for microbial survival curves by new fractional differential operators to analyze some microbial, common reasons of illnesses, and outbreaks, such as Salmonella spp. cocktail in ground turkey thigh, pork shoulder, and turkey breast at isothermal cooking conditions in 50°C, 54°C, 58°C, 62°C, and 66°C, then Listeria monocytogenes and Escherichia coli O157:H7 are considered in ground beef in the same thermal conditions. Results obtained with nonsingular fractional derivatives, including exponential decay and Mittag‐Leffler kernel, are analyzed comparatively with Caputo fractional and integer‐order derivatives for survival ratio of microbial cells. In the sequel, E. coli O157:H7 in ground beef, Salmonella typhimurium and S. enteritidis in boneless pork chops, and background flora in ground pork and at room temperature, 10°C, 7.2°C, and 4.4°C are considered for microbial growth curves by nonsingular fractional operators, and results obtained are compared with Caputo fractional and integer‐order derivatives. All results for advantage and disadvantage of Atangana‐Baleanu and Caputo‐Fabrizio fractional derivatives are discussed in detail.
2D Diffusion‐Ordered 1H‐NMR Spectroscopy Lipidomic Profiling after Oral Single Macronutrient Loads: Influence of Obesity, Sex, and Female Androgen Excess
Authors: Insenser María , Moncayo Samuel , Martínez‐García M. Ángeles , Fernández‐Durán Elena , Samino Sara , Álvarez‐Blasco Francisco , Luque‐Ramírez Manuel , Escobar‐Morreale Héctor F.
Published: March 2020

Scope

Postprandial dysmetabolism plays a major role in the pathogenesis of metabolic disorders such as obesity and the polycystic ovary syndrome (PCOS). The aim is to characterize the circulating lipoprotein particle profiles in response to oral glucose, lipid, and protein challenges.

Methods and results

17 women with PCOS, 17 control women, and 19 healthy men selected to have similar age and body mass index are studied. Blood samples are collected following the ingestion of 300 kcal in the form of glucose, lipids, or proteins, and they are submitted to two‐dimensional (2D) diffusion‐ordered 1H‐NMR spectroscopy. Regardless of macronutrient administered, the number of very low‐density (VLDL) particles increases whereas low density‐lipoprotein (LDL) decreases. High density‐lipoprotein (HDL) particles increase only after lipid ingestion. Obese subjects show an increase in the number of large VLDL particles and a decrease in large LDL particles, with a significant reduction in the average particle size of LDL. Patients with PCOS show a particularly unfavorably smaller LDL particle size response to oral lipid intake, regardless of obesity.

Conclusions

Oral macronutrient challenges induce immediate class‐specific postprandial changes in particle number and size of lipoproteins, with lipids inducing a more pro‐atherogenic lipoprotein profile compared to glucose and proteins, particularly in obese subjects and women with PCOS.
Use of mobile apps for controlling of the urinary incontinence: A systematic review
Authors: Leme Nagib Anita Bellotto , Riccetto Cássio , Martinho Natalia Miguel , Camargos Pennisi Pedro Rogério , Blumenberg Cauane , Paranhos Luiz Renato , Botelho Simone
Published: March 2020

Objective

The primary objective was to evaluate the impact of app use on urinary incontinence control through pelvic floor muscle training when compared to the postal treatment plan. The secondary objectives were to evaluate how app use may affect the quality of life (QoL) of users and treatment adherence.

Material and Methods

Eight databases (PubMed, SciELO, Embase, Web of Science, LILACS, Open Gray, Open Thesis, and OATD) were used as research sources. The protocol was registered in PROSPERO (CRD 42020145709). Randomized controlled trials assessing urinary incontinence (UI) control with app use, with no restriction of year, language, and status of publication were included. The JBI Systematic Reviews Checklist for Randomized Controlled Trials assessed the risk of bias of the studies selected. The mean scores of QoL between the pre‐ and postintervention periods were compared through standardized mean differences, which were weighted according to the number of months between the two periods.

Results

Only three studies met the eligibility criteria and were included. The methodological quality of the studies was from “low” to “moderate” risk of bias. The full sample included 203 patients with app‐based treatment e 203 controls of postal treatment. All studies showed the reduction of urinary symptoms. In addition, two studies showed a reduction of QoL scores specific for the condition, while one study presented increased scores.

Conclusion

Reminder therapy seems to be a promising strategy for controlling UI.
Robust tensor completion using transformed tensor singular value decomposition
Authors: Song Guangjing , Ng Michael K. , Zhang Xiongjun
Published: March 2020

In this article, we study robust tensor completion by using transformed tensor singular value decomposition (SVD), which employs unitary transform matrices instead of discrete Fourier transform matrix that is used in the traditional tensor SVD. The main motivation is that a lower tubal rank tensor can be obtained by using other unitary transform matrices than that by using discrete Fourier transform matrix. This would be more effective for robust tensor completion. Experimental results for hyperspectral, video and face datasets have shown that the recovery performance for the robust tensor completion problem by using transformed tensor SVD is better in peak signal‐to‐noise ratio than that by using Fourier transform and other robust tensor completion methods.
Optimal maintenance planning in building retrofitting with interacting energy effects
Authors: Wang Bo , Xia Xiaohua , Cheng Zhongtao , Liu Lei
Published: March 2020

This paper extends a control system framework for the maintenance planning investment decision for building energy retrofitting. The interacting energy and reliability effects that are ignored by previous models are incorporated in the current study. A set of energy efficiency and population decay models with interacting parameters and decision variables are established, and a state‐space model with coupled nonlinear equations is obtained. The control objectives are maximizing the energy savings and financial paybacks with limited budget during a finite time period. An model predictive control (MPC) controller is designed for the problem. The interacting effects and effectiveness of the proposed approach are verified by the case study, where improvements from the modeling considering interaction are revealed.
Influence of short‐term dexamethasone on the efficacy of 177Lu‐PSMA‐617 in patients with metastatic castration‐resistant prostate cancer
Authors: Derlin Thorsten , Sommerlath Sohns Jan M. , Schmuck Sebastian , Henkenberens Christoph , von Klot Christoph A. J. , Ross Tobias L. , Bengel Frank M.
Published: March 2020

Background and Aim

Corticosteroids alone or in combination therapy are associated with favorable biochemical responses in metastatic castration‐resistant prostate cancer (mCRPC). We speculated that the intermittent addition of dexamethasone may also enhance the antitumor effect of radioligand therapy (RLT) with 177Lu‐prostate‐specific membrane antigen (PSMA)‐617.

Patients and Methods

Seventy‐one patients with mCRPC were treated with 1 to 5 cycles of 177Lu‐PSMA‐617 (6.0‐7.4 GBq per cycle) at 6 to 8 weeks intervals. Based on the clinical decision (eg, in the case of vertebral metastases), 56% of patients received 4 mg of dexamethasone for the first 5 days of each cycle. Biochemical response rates, PSA decline and progression‐free survival (PFS) were analyzed after one, three, and five cycles of RLT.

Results

PSA response rates were not significantly different between patients receiving 177Lu‐PSMA‐617 plus dexamethasone and those receiving 177Lu‐PSMA‐617 alone after one, three, and five cycles (33% vs 39%, P = .62; 45% vs 45%, P = 1.0; and 38% vs 42%, P = .81). However, there was a nonsignificant trend for a more pronounced PSA decline in patients with bone metastases receiving adjunct dexamethasone (−21% ± 50% vs +11% ± 90%, P = .08; −21% ± 69% vs +22% ± 116%, P = .07; −13% ± 76% vs +32% ± 119%, P = .07). Median PFS tended to be longer in patients with bone metastases receiving 177Lu‐PSMA‐617 plus dexamethasone (146 vs 81 days; hazard ratio: 0.87 [95% confidence interval: 0.47‐1.61]; P = .20). Multiple regression analysis showed that age (P = .0110), alkaline phosphatase levels (P = .0380) and adjunct dexamethasone (P = .0285) were independent predictors of changes in PSA in patients with bone metastases.

Conclusions

We observed high response rates to 177Lu‐PSMA‐617 RLT in men with mCRPC. The short‐term addition of dexamethasone to 177Lu‐PSMA‐617 had no striking antitumor effect but might enhance biochemical responses in patients with bone metastases. Future trials are warranted to test this hypothesis in a prospective setting.
Interface Engineering of CsPbBr3 Nanocrystal Light‐Emitting Diodes via Atomic Layer Deposition
Authors: Zhou Binze , Wang Zhaojie , Geng Shicai , Li Yun , Wang Kai , Cao Kun , Wen Yanwei , Chen Rong
Published: March 2020

Perovskite nanocrystal (PNC) suffers from solution corrosion and water/oxygen oxidation when used in light‐emitting diodes (LEDs). Atomic layer deposition (ALD) is applied to introduce Al2O3 infilling and interface engineering for the CsPbBr3 nanocrystal emission layers, and the inorganic electron transport layer‐based CsPbBr3–ZnMgO LED device is fabricated. The introduction of Al2O3 ALD layers significantly improves the tolerance of CsPbBr3 PNC thin films to polar solvents ethanol of ZnMgO during spin coating. The operation lifetime of ALD‐treated CsPbBr3 PNC–ZnMgO LED is prolonged to about two orders of magnitude greater than that of the CsPbBr3 PNC‐TPBi LED device with a largely improved external quantum efficiency (EQE) value. Moreover, the infilling of Al2O3 into the CsPbBr3 layer boosts the carrier mobility for more than 40 times inside the light‐emission layer. However, the interfacial carrier transport between different functional layers is hindered by the insulated Al2O3 layer, which provides an effective barrier for excess electron transport. Such a favorable band alignment facilitates the carrier balance of the device and contributes to the improved electroluminescent performance of the device with ALD Al2O3 interface engineering, which is further supported by theoretical device modeling. Herein, a facile method is provided to fabricate PNC‐LED devices with both high efficiency and long‐term lifetime.
Ursolic acid promotes apoptosis, autophagy, and chemosensitivity in gemcitabine‐resistant human pancreatic cancer cells
Authors: Lin Ji‐Hua , Chen Sheng‐Yi , Lu Chi‐Cheng , Lin Jer‐An , Yen Gow‐Chin
Published: March 2020

Gemcitabine (GEM) resistance in pancreatic adenocarcinoma mediated by the receptor for advanced glycation end products (RAGE) has been demonstrated. Therefore, investigating the safety and the potential of new auxiliary methods for pancreatic cancer treatment is urgent. Ursolic acid (UA), a natural pentacyclic triterpenoid found in apple peels, rosemary, and thyme, has been reported to have anticancer capacity. This study aimed to reveal the underlying mechanisms of UA in cell death and drug enhancement, especially in GEM‐resistant pancreatic cancer cells. First, GEM‐resistant cells (MIA Paca‐2GEMR cells) were established by incrementally increasing GEM culture concentrations. UA treatment reduced cell viability through cell cycle arrest and endoplasmic reticulum (ER) stress, resulting in apoptosis and autophagy in a dose‐dependent manner in MIA Paca‐2 and MIA Paca‐2GEMR cells. High RAGE expression in MIA Paca‐2GEMR cells was suppressed by UA treatment. Interestingly, knocking down RAGE expression showed similar UA‐induced effects in both cell lines. Remarkably, UA had a drug‐enhancing effect by decreasing cell viability and increasing cell cytotoxicity when combined with GEM treatment. In conclusions, UA triggered ER stress, subsequently regulating apoptosis‐ and autophagy‐related pathways and increasing GEM chemosensitivity in pancreatic cancer cells by inhibiting the expression of RAGE.
Wearable and Ultrasensitive Strain Sensor Based on High‐Quality GaN pn Junction Microwire Arrays
Authors: Cheng Shiduo , Han Sancan , Cao Ziyang , Xu Chenchao , Fang Xiaosheng , Wang Xianying
Published: March 2020

With the rapid growth in wearable electronics sensing devices, flexible sensing devices that monitor the human body have shown great promise in personalized healthcare. In the study, high‐quality GaN pn junction microwire arrays with different aspect ratios and large‐area uniformity are fabricated through an easy, repeatable fabrication process. The piezoelectric coefficient (d33) of GaN pn junction microwire arrays increases from 7.23 to 14.46 pm V−1 with the increasing of the aspect ratio, which is several times higher than that of GaN bulk material. Furthermore, flexible ultrasensitive strain sensor based on GaN microwires with the highest d33 is demonstrated to achieve the maximum open circuit voltage of 10.4 V, and presents excellent durability with stable output signals over 10 000 cycles with a response time of 50 ms. As a flexible and wearable sensor attached to the human skin, the GaN microwire pn junction arrays with such a high degree of uniformity can precisely monitor subtle human pulse and motions, which show great promise in future personalized healthcare.
Safety‐by‐Design of Metal Oxide Nanoparticles Based on the Regulation of their Energy Edges
Authors: Feng Yanlin , Chang Yun , Xu Keqiang , Zheng Runxiao , Wu Xiaqing , Cheng Yan , Zhang Haiyuan
Published: March 2020

The safety of metal oxide (MOx) nanoparticles (NPs) has been highly concerned because of their wide application and potential toxicological injury. The safe‐by‐design strategy is usually developed to make safer MOx NPs based on regulation of their physicochemical properties. In the present study, manganese oxide (Mn3O4) NPs, as a representative of insoluble toxic MOx NPs, are doped with a series of transition metal to regulate their conduction band energy (Ec) out of biological redox potential range (BRPR) or Fermi energy (Ef) far away from valence band energy (Ev), aiming at completely eliminating the toxicity or significantly reducing the toxicity. It is found that all these M‐doping cannot move Ec of Mn3O4 NPs out of the BRPR but zinc (Zn)‐, copper (Cu)‐, and chromium (Cr)‐doping do move Ef far away from Ev, where Zn‐doping results in the largest |Ef − Ev| value. Various abiotic, in vitro and in vivo assessments reveal that Zn‐, Cu‐, and Cr‐doped Mn3O4 NPs can generate lower amount of •OH and trigger weaker injury than Mn3O4 NPs, where Zn‐doped Mn3O4 NPs show the lowest toxicity. Regulating Ef far away from Ev becomes a feasible safe‐by‐design approach to achieve safe MOx NPs.
Development of Resistant Starch Film Coated Microparticles for an Oral Colon‐Specific Drug Delivery
Authors: Khan Anum , Bibi Amna , Ali Huma , ur Rehman Asim , Qindeel Maimoona , Irfan Muhammad , Shah Aamer Ali , Badshah Malik , Hasan Fariha , Khan Samiullah
Published: March 2020

In this study, novel enzymatically modified resistant starch type III (EM‐RSIII) derived drug loaded microspheres are developed for oral colon‐specific delivery of ciprofloxacin HCl, used as a model drug. EM‐RS III is enzymatically prepared using starch hydrolyzing enzymes amylase and pullulanase. The prebiotic effect of EM‐RSIII is successfully scrutinized for promoting the growth of probiotic bacteria, for example, Lactobacillus reuteri. Drug‐loaded microspheres are synthesized from the EM‐RSIII through a single emulsion evaporation method. The pH‐sensitive drug‐loaded microspheres are characterized through scanning electron microscopy, X‐ray diffraction, and Fourier‐transform infrared spectroscopy. Release studies confirm the stability of drug‐loaded microspheres at acidic pH while sustained release is observed at pH 7.8 demonstrating a site‐specific delivery of drug to the colon. The in vitro release mechanism of drug is evaluated using various kinetic models. The study also reveals that EM‐RSIII‐derived microspheres are biodegradable and are degraded by the natural microflora of the colon, which is indicated by stimulating growth of probiotic bacteria. The microspheres are exploited as drug carriers for the colon‐specific release of ciprofloxacin HCl, and its encapsulation is further confirmed from the antibacterial activity.
Principal interacting orbital: A chemically intuitive method for deciphering bonding interaction
Authors: Zhang Jing‐Xuan , Sheong Fu Kit , Lin Zhenyang
Published: March 2020

Modular bonding picture is a central part of chemical understanding as exemplified by the wide usage of Lewis structure as a chemical language to describe molecular electronic structures. A chemically intuitive bonding picture requires the descriptors to be localized and transferable. Molecular orbitals directly derived from quantum calculations are too delocalized to interpret in this regard, hence many efforts have been devoted to the development of bonding analysis methods. After a brief overview of various bonding analysis methods, this review outlines the framework of principal interacting orbital (PIO) analysis and presents its role in recovering intuitive chemical concepts and producing modular bonding pictures. The PIO analysis identifies the most important fragment orbitals that are involved in fragment interactions and characterizes a one‐to‐one orbital interaction pattern that underlies a unique set of bonding and anti‐bonding orbitals derived from pairwise orbital interactions between two fragments. By making use of the principal component analysis (PCA), PIO analysis can effectively combine complex delocalized interaction patterns involved in numerous molecular orbitals into a handful of localized PIOs to provide easily interpretable results with intimate connection to localized chemical concepts, while maintaining necessary delocalized features when dealing with systems that involve mutlicentered interactions such as cluster compounds and various reactions. Such adaptability guarantees the robustness of PIO analysis with respect to change of substituents and the transferability of obtained PIOs across different systems.

This article is categorized under:

Structure and Mechanism > Molecular Structures
Assessment of microbial contamination levels of water in hemodialysis centers in Baghdad, Iraq
Authors: Humudat Yasamen R. , Al‐Naseri Saadi K. , Al‐Fatlawy Yaaroub F.
Published: March 2020

Monitoring water quality in hemodialysis systems is extremely important to maintain adequate quality services for patients suffering from kidney failure. This work aims to examine and evaluate bacteriological characteristics and endotoxin contamination levels in hemodialysis water produced in dialysis centers. Forty‐eight water samples were collected and analyzed from four major hospitals in Baghdad for one year to evaluate seasonal effects. The analysis included the determination of total heterotrophic bacteria using the pour plate method, identification of bacterial isolate using the Vitek2 compact instrument, and the determination of endotoxins levels using Limulus amebocyte lysate (LAL) method. In addition, tap water samples (a source for the hemodialysis water) were also examined bacteriologically. Results showed that 44% of the tested samples for bacterial levels are higher than the maximum value of (100 CFU/ml) set out by the international standards. Endotoxin values for these centers fluctuated during the study period, and 44% of them exceeded the international standards (>0.25 EU/ml). These results call for applying improved technology to modify the existing water treatment units for better control and for national standardization of the microbiological quality of hemodialysis water.

Practitioner points

Four hemodialysis centers were assessed by measuring the bacteriological and endotoxins levels of their feed and product water.

Product water showed elevated levels of bacteria that exceeded the international guideline value of 100 CFU/ml.

Most of the identified bacterial species were Gram‐negative that arise the possibility of contributing to endotoxin generation.

Product water showed fluctuated values of endotoxins. About 44% of the measured samples were higher than the international guideline values of 0.25 EU/ml.
Bayesian spatial and spatiotemporal models based on multiscale factorizations
Authors: Ferreira Marco A. R.
Published: March 2020

We review the literature on spatial and spatiotemporal models based on spatial multiscale factorizations. Specifically, we review models based on wavelets and Kolaczyk–Huang factorizations for Gaussian and Poisson data. These multiscale models decompose spatial and spatiotemporal datasets into many small components, called multiscale coefficients, at multiple levels of spatial resolution. Then analysis proceeds independently for each multiscale coefficient. After that, aggregation equations are used to coherently combine the analyses from the multiple multiscale coefficients to obtain a statistical analysis at the original resolution level. The computational cost of such analysis grows linearly with sample size. Furthermore, computations for these models are scalable, parallelizable, and fast. Therefore, these multiscale models are tremendously useful for the analysis of massive spatial and spatiotemporal datasets.

This article is categorized under:

Statistical Learning and Exploratory Methods of the Data Sciences > Modeling Methods

Statistical Models > Bayesian Models

Data: Types and Structure > Image and Spatial Data
Political Science: Developing Effective Participants in the Democratic Process
Authors: Perruci Gama
Published: March 2020

Democratic governance has been a central tenant of leadership development in U.S. political science departments. The discipline of political science focuses on the development of engaged citizens and responsible leaders who can have a positive impact in their communities at all levels.
Emerging Themes in Disciplinary Based Leadership Education
Authors: Sowcik Matthew , Komives Susan R.
Published: March 2020

This chapter uses the categories of the International Leadership Association's (2009) Guiding Questions (i.e., context, conceptual framework, content, teaching and learning, and outcomes and assessment) to present themes about leadership education among academic disciplines. Recommendations for the development of leadership education in academic disciplines are included.
Geodetic Monitoring of the Variable Surface Deformation in Latin America
Authors: Sánchez Laura , Drewes Hermann
Published: March 2020

Based on 24 years of high-level GNSS data analysis, we present a sequence of crustal deformation models showing the varying surface kinematics in Latin America. The deformation models are inferred from GNSS station horizontal velocities using a least-squares collocation approach with empirically determined covariance functions. The main innovation of this study is the assumption of continuous surface deformation. We do not introduce rigid microplates, blocks or slivers which enforce constraints on the deformation model. Our results show that the only stable areas in Latin America are the Guiana, Brazilian and Atlantic shields; the other tectonic entities, like the Caribbean plate and the North Andes, Panama and Altiplano blocks are deforming. The present surface deformation is highly influenced by the effects of seven major earthquakes: Arequipa (Mw8.4, Jun 2001), Maule (Mw8.8, Feb 2010), Nicoya (Mw7.6, Sep 2012), Champerico (Mw7.4, Nov 2012), Pisagua (Mw8.2, Apr 2014), Illapel (Mw8.3, Sep 2015), and Pedernales (Mw7.8, Apr 2016). We see very significant kinematic variations: while the earthquakes in Champerico and Nicoya have modified the aseismic deformation regime in Central America by up to 5 and 12 mm/a, respectively, the earthquakes in the Andes have resulted in changes of up to 35 mm/a. Before the earthquakes, the deformation vectors are roughly in the direction of plate subduction. After the earthquakes, the deformation vectors describe a rotation counter-clockwise south of the epicentres and clockwise north of the epicentres. The deformation model series reveals that this kinematic pattern slowly disappears with post-seismic relaxation. The numerical results of this study are available at https://doi.pangaea.de/10.1594/PANGAEA.912349 and https://doi.pangaea.de/10.1594/PANGAEA.912350.
Towards the Realization of the International Height Reference Frame (IHRF) in Argentina
Authors: Tocho Claudia Noemi , Antokoletz Ezequiel Dario , Piñón Diego Alejandro
Published: March 2020

This paper describes a practical implementation of the International Height Reference System (IHRS) in Argentina. The contribution deals with the determination of potential values W(P) at five Argentinean stations proposed to be included in the reference network of the International Height Reference Frame (IHRF). All sites are materialized with GNSS stations of the Argentine continuous satellite monitoring network and most of them are included in the SIRGAS Continuously Operating Network. Not all the stations are connected to the National Vertical Reference System 2016 and most of them are near to an absolute gravity station measured with an A10 gravimeter.

This paper also discusses the approach for the computation of W(P) at the IHRF stations using the Argentinean geoid model GEOIDE-Ar 16 developed by the Instituto Geográfico Nacional, Argentina together with the Royal Melbourne Institute of Technology (RMIT) University, Australia using the remove-compute-restore technique and the GOCO05s satellite-only Global Gravity Model. Then, geoid undulations (N) were transformed to height anomalies (ζ) in order to infer W(P) at the stations located on the Earth’s surface. The transformation from N to ζ must be consistent with the hypothesis used for the geoid determination. Special emphasis is made on the standards, conventions and constants applied.
Cellular levels and molecular dynamics simulations of estragole DNA adducts point at inefficient repair resulting from limited distortion of the double-stranded DNA helix
Authors: Yang Shuo , Diem Matthias , Liu Jakob D. H. , Wesseling Sebastiaan , Vervoort Jacques , Oostenbrink Chris , Rietjens Ivonne M. C. M.
Published: March 2020

Estragole, naturally occurring in a variety of herbs and spices, can form DNA adducts after bioactivation. Estragole DNA adduct formation and repair was studied in in vitro liver cell models, and a molecular dynamics simulation was used to investigate the conformation dependent (in)efficiency of N2-(trans-isoestragol-3′-yl)-2′-deoxyguanosine (E-3′-N2-dG) DNA adduct repair. HepG2, HepaRG cells, primary rat hepatocytes and CHO cells (including CHO wild-type and three NER-deficient mutants) were exposed to 50 μM estragole or 1′-hydroxyestragole and DNA adduct formation was quantified by LC–MS immediately following exposure and after a period of repair. Results obtained from CHO cell lines indicated that NER plays a role in repair of E-3′-N2-dG adducts, however, with limited efficiency since in the CHO wt cells 80% DNA adducts remained upon 24 h repair. Inefficiency of DNA repair was also found in HepaRG cells and primary rat hepatocytes. Changes in DNA structure resulting from E-3′-N2-dG adduct formation were investigated by molecular dynamics simulations. Results from molecular dynamics simulations revealed that conformational changes in double-stranded DNA by E-3′-N2-dG adduct formation are small, providing a possible explanation for the restrained repair, which may require larger distortions in the DNA structure. NER-mediated enzymatic repair of E-3′-N2-dG DNA adducts upon exposure to estragole will be limited, providing opportunities for accumulation of damage upon repeated daily exposure. The inability of this enzymatic repair is likely due to a limited distortion of the DNA double-stranded helix resulting in inefficient activation of nucleotide excision repair.
Predictors and Survival of Patients with Osteosarcoma After Limb Salvage versus Amputation: A Population‐Based Analysis with Propensity Score Matching
Authors: Qi Lin , Ren Xiaolei , Liu Zhongyue , Li Shuangqing , Zhang Wenchao , Chen Ruiqi , Chen Congzhou , Tu Chao , Li Zhihong
Published: March 2020

Background

Conflicting findings have been reported concerning the survival of patients treated with limb salvage and amputation for osteosarcoma. This study aimed to identify predictors associated with surgery types and survival difference.

Methods

Patients with osteosarcoma were selected from the Surveillance Epidemiology and End Results database (1975–2016). Multivariable logistic regression analysis was conducted, and a nomogram was further established. Propensity score matching (PSM)‐adjusted Kaplan–Meier curves, log‐rank tests, Cox proportional hazards regression analysis were performed to compare overall survival (OS) and cancer‐specific survival (CSS).

Results

Among 3363 patients with osteosarcoma, 2447 and 916 underwent limb salvage and amputation. Predictors associated with amputation in the nomogram included age, gender, primary tumor site, tumor grade, tumor stage, tumor size and radiotherapy. Totally 900 pairs of patients treated with limb salvage and amputation were matched after PSM. Limb salvage was significantly associated with improved OS (HR, 0.773; 95% CI, 0.670–0.892; p < 0.001) and CSS (HR, 0.795; 95% CI, 0.681–0.927; p = 0.003) in PSM‐adjusted cohort after adjusting for related variables. The significant treatment effect of limb salvage was consistent within most subgroups. Among patients treated with surgery for osteosarcoma, age between 41 and 60, age ≥ 61, pelvis as the primary site, high tumor grade (III/IV), regional and distant tumor stage, tumor size ≥ 92 mm and radiotherapy were independent prognostic factors in PSM cohort.

Conclusions

Limb salvage exhibits significant benefit on OS and CSS compared with amputation for osteosarcoma. Predicators and survival differences should be given full consideration for the treatment of osteosarcoma.
Impact of tumour size measurement inter-operator variability on model-based drug effect evaluation
Authors: Lombard Aurélie , Mistry Hitesh , Chapman Sonya C. , Gueoguieva Ivelina , Aarons Leon , Ogungbenro Kayode
Published: March 2020

Purpose

During oncology clinical trials, tumour size (TS) measurements are commonly used to monitor disease progression and to assess drug efficacy. We explored inter-operator variability within a subset of a phase III clinical trial conducted from August 1995 to February 1997 and its impact on drug effect evaluation using a tumour growth inhibition model.

Methods

One hundred twenty lesions were measured twice at each time point; once at the hospital and once at the centralised centre. A visual analysis was performed to identify trends within the profiles over time. Linear regression and relative error ratios were used to explore the inter-operator variability of raw TS measurements and model-based estimates.

Results

While correlation between patient-level estimates of drug effect was poor (r2 = 0.28), variability between the study-level estimates was much less affected (9%).

Conclusions

The global evaluation of drug effect using modelling approaches might not be affected by inter-operator variability. However, the exploration of covariates for drug effect and the characterisation of an exposure–tumour shrinkage relationship seems limited by the high measurement variability that translates to a poor correlation of individual drug effect estimates. This might be addressed by the use of more precise computer-aided measurement methods.
Implications of asymptomatic infection for the natural history of selected parasitic tropical diseases
Authors: Alvar Jorge , Alves Fabiana , Bucheton Bruno , Burrows Louise , Büscher Philippe , Carrillo Eugenia , Felger Ingrid , Hübner Marc P. , Moreno Javier , Pinazo Maria-Jesus , Ribeiro Isabela , Sosa-Estani Sergio , Specht Sabine , Tarral Antoine , Wourgaft Nathalie Strub , Bilbe Graeme
Published: March 2020

Progress has been made in the control or elimination of tropical diseases, with a significant reduction of incidence. However, there is a risk of re-emergence if the factors fueling transmission are not dealt with. Although it is essential to understand these underlying factors for each disease, asymptomatic carriers are a common element that may promote resurgence; their impact in terms of proportion in the population and role in transmission needs to be determined. In this paper, we review the current evidence on whether or not to treat asymptomatic carriers given the relevance of their role in the transmission of a specific disease, the efficacy and toxicity of existing drugs, the Public Health interest, and the benefit at an individual level, for example, in Chagas disease, to prevent irreversible organ damage. In the absence of other control tools such as vaccines, there is a need for safer drugs with good risk/benefit profiles in order to change the paradigm so that it addresses the complete infectious process beyond manifest disease to include treatment of non-symptomatic infected persons.