bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of Rate‐Limiting Reactions for Growth‐Associated Production Using a Constraint‐Based Approach
Authors: Tokuyama Kento , Toya Yoshihiro , Shimizu Hiroshi
Published: June 2019

Identification of a rate‐limiting step in pathways is a key challenge in metabolic engineering. Although the prediction of rate‐limiting steps using a kinetic model is a powerful approach, there are several technical hurdles for developing a kinetic model. In this study, an in silico screening algorithm of key enzyme for metabolic engineering is developed to identify the possible rate‐limiting reactions for the growth‐coupled target production using a stoichiometric model without any experimental data and kinetic parameters. In this method, for each reaction, an upper‐bound flux constraint is imposed and the target production is predicted by linear programming. When the constraint decreases the target production at the optimal growth state, the reaction is thought to be a possible rate‐limiting step. For validation, this method is applied to the production of succinate or 1,4‐butanediol (1,4‐BDO) in Escherichia coli, in which the experimental engineering for eliminating rate‐limiting steps has been previously reported. In succinate production from glycerol, nine reactions including phosphoenolpyruvate carboxylase are predicted as the rate‐limiting steps. In 1,4‐BDO production from glucose, eight reactions including pyruvate dehydrogenase are predicted as the rate‐limiting steps. These predictions include experimentally identified rate‐limiting steps, which would contribute to metabolic engineering as a practical tool for screening candidates of rate‐limiting reactions.
Enhancing social sustainability at a business level: Organizational attractiveness is higher when organizations show responsibility towards employees
Authors: Carballo‐Penela Adolfo
Published: June 2019

Selecting employees considering their fit with organizations' values for sustainable development can be an effective way of enhancing sustainable development at a business level. Employers' commitment with sustainable development will be stronger if sustainable development initiatives help them to achieve organizational objectives as attracting talented employees.

This study discusses if recruitment messages including information on the social dimension of sustainable development are valued by prospective employees. In particular, we are interested in finding out if five actions showing employer responsibility towards employees influence prospective job applicants' perceptions of organizational attraction.

Results from a policy‐capturing study that combines nomothetic and ideographic designs confirm that organizational attractiveness is higher when organizations show responsibility towards employees. Our findings also show the relevance of each of the studied actions to explain organizational attractiveness and differences among participants' perceptions. Results from ideographic analysis underline differences on attractiveness perceptions among participants.
The immunostimulatory effects and pro‐apoptotic activity of rhCNB against Lewis lung cancer is mediated by Toll‐like receptor 4
Authors: Yang Jinju , Zhang Hongwei , Zhu Ziwei , Gao Yadan , Xiang Benqiong , Wei Qun
Published: June 2019

Background

Recombinant human calcineurin B subunit (rhCNB) has been shown to be an immune‐stimulatory protein promoting cytokine production and inducing phenotypic maturation of Dendritic cells (DCs). In vivo, it has good antitumor efficacy, and has potential as an antitumor drug. Exogenous rhCNB was found to be internalized into tumor cells via the Toll‐like receptor 4 (TLR4) complex, but it was not known whether its immuno‐modulatory and antitumor functions involved entry by this same route.

Methods

The production and secretion of the cytokines and chemokines in innate immune cells induced by rhCNB were determined by ELISA, and the expression of CD40, CD80, CD86, and MHCII was analyzed by FACs. Experimental Lewis lung cancer (LLC) model was prepared in C57 BL/6 wild‐type (WT) mice, TLR4−/− mice or their littermates by the inoculation of LLCs in their right armpit, and then administrated daily intraperitoneal injections (0.2 mL) of normal saline, rhCNB 20 mg/kg, and rhCNB 40 mg/kg, respectively.

Results

Recombinant human calcineurin B subunit promoted the production of antitumor cytokines by innate immune cells, and culture supernatants of rhCNB‐stimulated immune cells induced apoptosis of LLCs. In addition, rhCNB up‐regulated CD40, CD80, CD86, and MHCII expression in macrophages and DCs in TLR4+ cells but failed to do so in TLR4 deficient cells. rhCNB also induced the formation of CD4+ and CD8+T cells in splenocytes from WT mice, but not from TLR4‐deficient littermates. Intraperitoneal administration of WT C57BL/6 mice with rhCNB resulted in a 50% reduction in LLC tumor growth, but failed to inhibit tumor growth in TLR4−/− littermates.

Conclusions

The in vivo antitumor and immunomodulatory effects of rhCNB are mediated by the TLR4. This conclusion is important for the further understanding and development of rhCNB as an antitumor drug.
Metronomic combination chemotherapy using everolimus and etoposide for the treatment of non‐Hodgkin lymphoma
Authors: Wu Ke , Sun Xiao‐Qing , Wang Cai‐Qin , Gao Tian‐Xiao , Sun Peng , Wang Yu , Jiang Wen‐Qi , Li Zhi‐Ming , Huang Jia‐Jia
Published: June 2019

Patients with Non‐Hodgkin lymphoma (NHL) treated by conventional chemotherapeutic drugs usually require a long recovery period. However, metronomic combination chemotherapy (MCC) enhances therapeutic efficacy and decreases side effects in the treatment of NHL. In this study, we tested and compared the effects of metronomic chemotherapy (MC) using podophyllotoxin derivative etoposide (VP‐16) alone and that of MCC using both VP‐16 and everolimus (RAD001) in the treatment of NHL. Two types of NHL cells, OCI‐LY‐10 and SU‐DHL‐6, were employed for the experiments. Cell proliferation, apoptosis, and cell senescence were measured to test the effects of drugs in each experiment. In addition, the influences of MC and MCC on the cell cycle and autophagy pathway were evaluated to study the functional mechanisms behind their effects. Finally, we conducted analyses of the growth inhibitory effect and synergistic activity for different MCC. The results showed that MC using low‐dose VP‐16 alone demonstrated strong treatment effects in terms of inducing apoptosis, cell senescence, and reducing tumor cell proliferation, and this treatment also led to changes of the cell cycle. Compared with MC, MCC using VP‐16 and RAD001 together demonstrated even stronger treatment effects, with both the cell cycle and autophagy‐related proteins being affected. Considering the synergistic activity, our results showed the MCC of VP‐16 48 hours + RAD001 24 hours is the optimal method for treating NHL.
Effects of somatic alterations at pathway level are more mechanism‐explanatory and clinically applicable to quantity of liver metastases of colorectal cancer
Authors: Zhang Zhong‐guo , Ma Fei , Zhao Shuang , Yang Xiaoyu , Liu Fang , Xue Chenghai , Liu Liren , Gu Jin , Piao Haozhe
Published: June 2019

Background

The quantity of metastases lesions is an important reference when it comes to making a more informed treatment decision for patients with colorectal cancer liver metastases. However, the molecular alterations in patients with different numbers of lesions have not been systematically studied.

Methods

We investigated somatic alterations and microsatellite instability (MSI) of liver metastases from patients with single, multiple or diffuse metastasis lesions. A new algorithm “Pathway Damage Score” was developed to comprehensively assess the functional impact of somatic alterations at the pathway level. Pathogenic pathways of different metastasis were identified and their prognosis effects were evaluated. Furthermore, the subnetworks and affected phenotypes of the altered genes in each pathogenic pathway were analyzed.

Results

Somatic alterations and altered genes occurred sporadically as well as in MSI state in different metastasis types, although MSS patients had more metastatic lesions than that of the MSI patients. Every metastasis group has their own pathogenic pathways and damaged “Cargo recognition for clathrin‐mediated endocytosis” is significantly associated with poor prognosis (P < 0.001). Further pathway subnetwork analysis showed that except conventional drivers, other genes could also contribute to metastasis formation.

Conclusions

Progression of liver metastasis could be driven by the coefficient of all altered genes belonging to the pathways. Thus, compared to somatic alterations and genes, pathway level analysis is more reasonable for functional interpretations of molecular alterations in clinical samples.
Pulmonary mucosa‐associated lymphoid tissue lymphoma mimicking lung cancer
Authors: Miyazaki Shinichi , Hachiya Kensuke , Nara Yoshiharu , Ikeda Takuya
Published: June 2019

Pulmonary mucosa‐associated lymphoid tissue (MALT) lymphoma is the most frequent subset of primary pulmonary lymphoma. MALT lymphoma may manifest as a solid mass, mimicking lung cancer.
Adaptive neuro‐fuzzy inference system–based energy conservation system for performance enhancement of MANET
Authors: Jegatheesan A , Kumar N Sathish , Palagan C Anna
Published: June 2019

A mobile ad hoc network (MANET) is a network with dynamic topology and mobile nodes. Due to its dynamic nature, there is no central control. Hence, nodes communicate with other nodes through intermediate nodes. The intermediate nodes are normal nodes in the same network and assume the responsibility of forwarding packets on the route from source to destination. Along these lines, a MANET requires vitality effective directing conventions to sort out the power use and to improve battery usage. In this paper, an equipped convention is recommended that expends less vitality of portable hubs in MANETs that depend on the remaining edge vitality of adaptive network‐based fuzzy inference systems (ANFIS). The edge esteem is resolved dependent on the fluffy participation capacities. Basically, the area hubs of source are figured utilizing two components: encased locale and transferring district. The neighbor hubs pondered by those elements receive the greatest edge esteem that started utilizing ANFIS. The hub with the most extreme estimations of edge and separation is favored as the following bounce for the exchange. The exploratory outcome delineates that our convention can recognizably diminish the aggregate vitality utilization for all effectively transmitted bundles and expand the lifetimes of hubs, overwhelmingly in the high versatility condition.
On low‐power SoCs as storage bricks for Bioinformatics
Authors: Morganti Lucia , Corni Elena , Lama Luca , Pellegrino Carmelo , Zanon Boito Francieli , Merelli Ivan , D'Agostino Daniele , Cesini Daniele
Published: June 2019

In the perspective of energy‐efficient storage solutions supporting scientific computing, we investigate the possibility of using low‐power Systems‐On‐Chip (SoCs) as storage bricks of a BeeGFS file system in support of a realistic genome sequencing pipeline from Bioinformatics. Metadata and data performances of such a file system made of low‐power devices are assessed via various benchmarks for an increasing number of clients accessing the data, and compared to those achieved with traditional power‐hungry architectures with a similar BeeGFS setup. Then, we show how the sequencing information streamed by portable sequencing devices, such as the Oxford Nanopore MinION, can be managed by the underlying BeeGFS file system built with low‐power SoCs.
Spiny rat SRY lacks a long Q‐rich domain and is not stable in transgenic mice
Authors: Ogata Yuka , Nishikata Mana , Kitada Kazuhiro , Mizushima Shusei , Jogahara Takamichi , Kuroiwa Asato
Published: June 2019

Background

Although Tokudaia muenninki has multiple extra copies of the Sry gene on the Y chromosome, loss of function of these sequences is indicated. To examine the Sry gene function for sex determining in T. muenninki, we screened a BAC library and identified a clone (SRY26) containing complete SRY coding and promoter sequences.

Results

SRY26 showed high identity to mouse and rat SRY. In an in vitro reporter gene assay, SRY26 was unable to activate testis‐specific enhancer of Sox9. Four lines of BAC transgenic mice carrying SRY26 were generated. Although the embryonic gonads of XX transgenic mice displayed sufficient expression levels of SRY26 mRNA, these mice exhibited normal female phenotypes in the external and internal genitalia, and up‐regulation of Sox9 was not observed. Expression of the SRY26 protein was confirmed in primate‐derived COS7 cells transfected with a SRY26 expression vector. However, the SRY26 protein was not expressed in the gonads of BAC transgenic mice.

Conclusions

Overall, these results support a previous study demonstrated a long Q‐rich domain plays essential roles in protein stabilization in mice. Therefore, the original aim of this study, to examine the function of the Sry gene of this species, was not achieved by creating TG mice.
Phylogeography of Dendrolimus punctatus (Lepidoptera: Lasiocampidae): Population differentiation and last glacial maximum survival
Authors: Li Jing , Jin Qian , Zhu Geng‐ping , Jiang Chong , Zhang Ai‐bing
Published: June 2019

Although the Masson pine moth, Dendrolimus punctatus, is one of the most destructive forest pest insects and is an endemic condition in China, we still do not fully understand the patterns of how its distribution range varies in response to Quaternary climatic oscillations. Here, we sequenced one maternally inherited mitochondrial gene (COI) and biparentally inherited nuclear data (ITS1 and ITS2) among 23 natural populations across the entire range of the species in China. A total of 51 mitotypes and 38 ribotypes were separately obtained using mtDNA and ITS1 data. Furthermore, significant phylogeographical structure (NST > GST, p < 0.01) were detected. The spatial distribution of mitotypes implied that two distinct groups existed in the species: one in the southwest distribution, including 10 locations, and the other located in the northeast region of China. It is suggested, therefore, that each group was derived from ancestors that occupied different isolated refugia during previous periods, possibly last glacial maximum. Mismatch distribution and Bayesian population dynamics analysis suggested the population size underwent sudden expansion, which is consistent with the results of ecological niche modeling. As a typical phytophagous insect, the history of population expansion was in accordance with the host plants, providing abundant food resources and habitat. Intraspecific success rate of barcoding identification was lower than interspecific ones, indicating a level of difficulty in barcoding individuals from different populations. However, it still provides an early insight into the pattern of genetic diversity within a species.

OPEN RESEARCH BADGES

This article has been awarded an Open Data and Open Materials. All materials and data are publicly accessible via the Open Science Framework at https://doi.org/10.5061/dryad.2df87g2. Learn more about the Open Practices badges from the Center for Open Science: https://osf.io/tvyxz/wiki.
Null model analyses of temporal patterns of bird assemblages and their foraging guilds revealed the predominance of positive and random associations
Authors: Korňan Martin , Svitok Marek , Krištín Anton
Published: June 2019

Patterns of species associations have been commonly used to infer interactions among species. If species positively co‐occur, they may form predominantly neutral assemblages, and such patterns suggest a relatively weak role for compensatory dynamics. The main objective of this study was to test this prediction on temporal samples of bird assemblages (n = 19, 10–57 years) by the presence/absence and quantitative null models on assemblage and guild levels. These null model outcomes were further analyzed to evaluate the effects of various data set characteristics on the outcomes of the null models. The analysis of two binary null models in combination with three association indices revealed 20% with significant aggregations, 61% with random associations, and only 19% with significant segregations (n = 95 simulations). The results of the quantitative null model simulations detected more none‐random associations: 61% aggregations, 6% random associations, and 33% segregations (n = 114 simulations). Similarly, quantitative analyses on guild levels showed 58% aggregations, 20% segregations, and 22% random associations (n = 450 simulations). Bayesian GLMs detected that the outcomes of the binary and quantitative null models applied to the assemblage analyses were significantly related to census plot size, whereas the outcomes of the quantitative analyses were also related to the mean population densities of species in the data matrices. In guild‐level analyses, only 9% of the GLMs showed a significant influence of matrix properties (plot size, matrix size, species richness, and mean species population densities) on the null model outcomes. The results did not show the prevalence of negative associations that would have supported compensatory dynamics. Instead, we assume that a similar response of the majority of species to climate‐driven and stochastic factors may be responsible for the revealed predominance of positive associations.
Integration of ground survey and remote sensing derived data: Producing robust indicators of habitat extent and condition
Authors: Henrys Peter A. , Jarvis Susan G.
Published: June 2019

The availability of suitable habitat is a key predictor of the changing status of biodiversity. Quantifying habitat availability over large spatial scales is, however, challenging. Although remote sensing techniques have high spatial coverage, there is uncertainty associated with these estimates due to errors in classification. Alternatively, the extent of habitats can be estimated from ground‐based field survey. Financial and logistical constraints mean that on‐the‐ground surveys have much lower coverage, but they can produce much higher quality estimates of habitat extent in the areas that are surveyed. Here, we demonstrate a new combined model which uses both types of data to produce unified national estimates of the extent of four key habitats across Great Britain based on Countryside Survey and Land Cover Map. This approach considers that the true proportion of habitat per km2 (Zi) is unobserved, but both ground survey and remote sensing can be used to estimate Zi. The model allows the relationship between remote sensing data and Zi to be spatially biased while ground survey is assumed to be unbiased. Taking a statistical model‐based approach to integrating field survey and remote sensing data allows for information on bias and precision to be captured and propagated such that estimates produced and parameters estimated are robust and interpretable. A simulation study shows that the combined model should perform best when error in the ground survey data is low. We use repeat surveys to parameterize the variance of ground survey data and demonstrate that error in this data source is small. The model produced revised national estimates of broadleaved woodland, arable land, bog, and fen, marsh and swamp extent across Britain in 2007.
A review of protocols for the experimental release of kelp (Laminariales) zoospores
Authors: Alsuwaiyan Nahlah A. , Mohring Margaret B. , Cambridge Marion , Coleman Melinda A. , Kendrick Gary A. , Wernberg Thomas
Published: June 2019

Kelps (order Laminariales) are foundation species in temperate and arctic seas globally, but they are in decline in many places. Laminarian kelp have an alternation of generations and this poses challenges for experimental studies due to the difficulties in achieving zoospore release and gametophyte growth. Here, we review and synthesize the protocols that have been used to induce zoospore release in kelps to identify commonalities and provide guidance on best practices. We found 171 papers, where zoospore release was induced in four kelp families from 35 different ecoregions. The most commonly treated family was Laminariaceae, followed by Lessoniaceae and the most studied ecoregion was Central Chile, followed by the Southern California Bight. Zoospore release generally involved three steps: a pretreatment which included cleaning of the reproductive tissue to eliminate epiphytic organisms, followed by desiccation of the tissue, and finally a postdesiccation immersion of the reproductive material in a seawater medium for zoospore release. Despite these commonalities, there was a high degree of variation in the detail within each of these steps, even among studies within genera and from the same ecoregions. This suggests either that zoospore release may be relatively insensitive across the Laminariales or that little methods optimization has been undertaken. We suggest that greater attention to standardization of protocols and reporting of methodology and optimization would improve comparisons of kelp zoospore release across species and locations and facilitate a broader understanding of this key, but understudied life history stage.

Open Research Badges

This article has earned an Open Data Badge for making publicly available the digitally‐shareable data necessary to reproduce the reported results. The data is available at https://doi.org/10.5061/dryad.0kh1f8j.
Rationale and design of the EMPERIAL‐Preserved and EMPERIAL‐Reduced trials of empagliflozin in patients with chronic heart failure
Authors: Abraham William T. , Ponikowski Piotr , Brueckmann Martina , Zeller Cordula , Macesic Hemani , Peil Barbara , Brun Michèle , Ustyugova Anastasia , Jamal Waheed , Salsali Afshin , Lindenfeld JoAnn , Anker Stefan D. ,   on behalf of the EMPERIAL Investigators and National Coordinators
Published: June 2019

Aims

Heart failure (HF) is associated with considerable symptom burden and impairment in physical functioning and quality of life. The sodium–glucose co‐transporter 2 inhibitor empagliflozin reduced the risk of HF hospitalisation and cardiovascular death in patients with type 2 diabetes and established cardiovascular disease in the EMPA‐REG OUTCOME trial, and could potentially improve congestion symptoms and exercise capacity in patients with HF. We describe the designs of the EMPERIAL‐Preserved and EMPERIAL‐Reduced trials of empagliflozin in patients with chronic stable HF, with or without type 2 diabetes.

Methods

EMPERIAL‐Preserved and EMPERIAL‐Reduced are randomised, placebo‐controlled trials designed to investigate the effects of empagliflozin on exercise capacity and patient‐reported outcomes in patients with chronic stable HF with preserved ejection fraction [HFpEF; left ventricular ejection fraction (LVEF) > 40%] and HF with reduced ejection fraction (HFrEF; LVEF ≤ 40%), respectively. In each trial, approximately 300 patients will be randomised 1:1 to receive empagliflozin 10 mg or placebo once daily for 12 weeks. In both trials, the primary endpoint is the change from baseline in 6‐min walk test distance at week 12. Key secondary endpoints are the change from baseline in Kansas City Cardiomyopathy Questionnaire total symptom score and change from baseline in dyspnoea score of the Chronic Heart Failure Questionnaire at week 12.

Conclusion

The EMPERIAL‐Preserved and EMPERIAL‐Reduced trials will determine the effects of empagliflozin on exercise capacity and patient‐reported outcomes in patients with HFpEF and HFrEF, respectively, and provide insight into the potential of empagliflozin in the treatment of patients with HF.

Clinical Trial Registration: ClinicalTrials.gov ID: NCT03448406 (EMPERIAL‐Preserved), NCT03448419 (EMPERIAL‐Reduced).
Glacio‐eustasy and δ13C across the Mississippian–Pennsylvanian boundary in the eastern Paleo‐Tethys Ocean (South China): Implications for mid‐Carboniferous major glaciation
Authors: Tian Xiaoxu , Chen Jitao , Yao Le , Hu Keyi , Qi Yuping , Wang Xiangdong
Published: June 2019

A positive carbonate δ13C excursion (by ~1.5–3.0‰) has been reported across the Mississippian–Pennsylvanian boundary (MPB) from Euramerican epicontinental seas, implying a coeval atmospheric pCO2 decrease and Gondwanan glaciation at that time. This excursion was mainly observed in carbonate platforms which experienced repeated subaerial exposure. The South China Block was located in the middle of the Paleo‐Tethys Ocean and the Panthalassic Ocean during the Carboniferous and contains well‐preserved carbonate slope strata across the MPB. Four lithofacies were defined in the studied Naqing, Narao, and Dianzishang sections, including thin‐bedded lime mudstones, laminated wackestones to packstones, normally‐graded packstones, and slumped limestones. Immediately above the MPB, a bed of normally‐graded packstones or slump masses occurs in the studied sections, which together with coeval subaerial‐exposure features in shallow‐water carbonate platform of South China, suggests a significant sea‐level fall across the MPB. Carbonate δ13C records show a consistent value of ~3.0‰ below the MPB in the Naqing and Narao sections, and both sections show an obvious rise in δ13C across the MPB (by ~0.5–1.0‰). The relatively small‐magnitude rise in δ13C would have resulted from well‐mixed seawater induced by intensified upwelling in the eastern Paleo‐Tethys Ocean during the glacial peak. Hence, the carbonate δ13C values recorded in the South China Block may represent a mean δ13C of the dissolved inorganic carbon in global ocean water at that time. Correlation between carbonate δ13C and previously published conodont δ18O and 87Sr/86Sr records suggests that the MPB glaciation was mainly driven by enhanced continental weathering, rather than increased organic carbon burial, although further quantitative simulation is required to better understand the interlinked processes during the Earth's penultimate icehouse.
Ledipasvir‐Sofosbuvir for 12 Weeks in Children 3 to <6 Years Old With Chronic Hepatitis C
Authors: Schwarz Kathleen B. , Rosenthal Philip , Murray Karen F. , Honegger Jonathan R. , Hardikar Winita , Hague Rosie , Mittal Naveen , Massetto Benedetta , Brainard Diana M. , Hsueh Chia‐Hsiang , Shao Jiang , Parhy Bandita , Narkewicz Michael R. , Rao Girish S. , Whitworth Suzanne , Bansal Sanjay , Balistreri William F.
Published: June 2019

For children under 12 years of age who have chronic hepatitis C virus (HCV) infection, there are currently no approved treatments with direct‐acting antiviral agents. We therefore evaluated the safety and efficacy of ledipasvir‐sofosbuvir in HCV‐infected children aged 3 to <6 years. In an open‐label study, patients 3 to <6 years old chronically infected with HCV genotype 1 (n = 33) or 4 (n = 1) received weight‐based doses of combined ledipasvir‐sofosbuvir as granules (33.75 mg/150 mg for weights <17 kg or 45 mg/200 mg for weights ≥17 kg) for 12 weeks. The primary endpoint was sustained virological response 12 weeks after treatment (SVR12). For the first 14 patients, intensive pharmacokinetic sampling was done on day 10 of treatment. All patients had been infected through perinatal transmission and were treatment naïve. No patients had known cirrhosis. Ten patients (29%) weighed <17 kg. SVR12 was achieved in 97% of patients (33 of 34); the patient who did not achieve SVR12 was 3 years old and discontinued treatment after 5 days because of an adverse event “abnormal drug taste.” The most common adverse events were vomiting (24% of patients), cough (21%), and pyrexia (21%). No patients experienced a serious adverse event. Intensive pharmacokinetic analysis of 13 patients for whom data were evaluable confirmed that the doses selected were appropriate. Conclusion: Ledipasvir‐sofosbuvir was well tolerated and highly effective in children 3 to <6 years old with chronic HCV infection.
Total Recoverable Aluminum: Not Totally Relevant for Water Quality Standards
Authors: Ryan Adam C , Santore Robert C , Tobiason Scott , WoldeGabriel Giday , Groffman Armand R
Published: June 2019

A large water quality data set, representing more than 100 surface-water locations sampled from 2007 to 2017 in the Los Alamos area of New Mexico, USA's Pajarito Plateau, was assembled to evaluate Al concentrations in unfiltered and filtered samples. Aluminum concentrations often exceeded United States Environmental Protection Agency (USEPA) and New Mexico ambient water quality criteria (AWQC), regardless of filter size and sample location. However, AWQC are based on laboratory toxicity studies using soluble Al salts and do not reflect natural conditions in Pajarito Plateau surface waters. The plateau is predominately covered by glassy and recrystallized volcanic ashes (e.g., Bandelier Tuff) containing colloidal to sand-sized aluminosilicates. Samples from natural background drainages and areas downstream of developed regions exhibited similar Al concentrations, suggesting that AWQC exceedances are caused by naturally elevated Al concentrations. Solubility calculations indicated that most samples were oversaturated with respect to amorphous Al(OH)3(s). Therefore, AWQC exceedances are likely artifacts of the “total recoverable” sample preparation, which includes acidification and partial digestion, thereby liberating nonbioavailable Al from aluminosilicates. Accordingly, Al concentrations were strongly associated with suspended sediment concentrations (SSCs), implying that aluminosilicates in suspended sediment contributed to AWQC exceedances and Al oversaturation. Solid-phase particle characterization, using X-ray diffraction (XRD) and scanning electron microscopy with electron dispersive spectroscopy (SEM/EDS) did not identify potentially bioavailable amorphous Al(OH)3(s) in any sample tested. Thus, current sample collection and analysis protocols should not be used to evaluate attainment of Al AWQC on the Pajarito Plateau or locations where aluminosilicates are substantial contributors to total recoverable Al. A sample preparation method (e.g., pH 4 extraction) capable of differentiating nonbioavailable and bioavailable forms of Al is recommended. Otherwise, current New Mexico and USEPA sample preparation approaches will continue to generate artifactual AWQC exceedances in surface waters that contain aluminosilicates. Integr Environ Assess Manag 2019;00:1–14. © 2019 SETAC
SIMULATION OF SOIL WATER CONTENT FOR IRRIGATION MANAGEMENT BASED ON ON‐FIELD AND CERES‐WHEAT SIMULATED DATA IN WINTER WHEAT IN THE NORTH CHINA PLAIN
Authors: Zhou Lili , Liao Shuhua , Wang Zhimin , Wang Pu , Yan Haijun , Zhang Yinghua , Zhang Li , Zhao Xue , Lin Shan , Zhou Shunli
Published: June 2019

Accurate forecasting of the soil water in crop growth is crucial for developing an irrigation management strategy and saving water resources. The CERES model can be used to quantitatively predict the soil water content (SWC), but its accuracy and stability should be improved. The objectives of this research were to assess the CERES‐Wheat model for its ability to simulate the SWC in the winter wheat growth season and to study the possibility of improving simulation accuracy by building a modified model through introducing on‐field data and simulated values of CERES‐Wheat. Field experiment data of the varieties ShiJiaZhuang 8 and JiMai 22 from three to four irrigation treatments conducted over 4 years were used to compare precision of the CERES‐Wheat model and the modified model for SWC in the North China Plain. On average across all soil layers between 20 and 120 cm and two winter wheat varieties, the NRMSE decreased from 20.3% with the CERES‐Wheat model to 13.2% with the modified model. The results showed that the further improvement of SWC based on on‐field data and simulated data of CERES‐Wheat may be possible. Application prospects of dynamic water management of the modified model by introducing on‐field data during the wheat growth season were also discussed. © 2019 John Wiley & Sons, Ltd.
Gene and protein delivery using four cell penetrating peptides for HIV‐1 vaccine development
Authors: Rostami Bahareh , Irani Shiva , Bolhassani Azam , Cohan Reza Ahangari
Published: June 2019

Cell penetrating peptides (CPPs) can potently transport therapeutic molecules to target cells for treatment of a variety of diseases. Thus, their use is critical to improve therapeutic vaccines. Histidine‐rich nona‐arginine (HR9) and primary amphipathic peptide (MPG) showed the ability to transfer DNA into the cells. Moreover, the peptide derived from the C‐terminal of the tumor suppressor protein p14ARF (M918) and arginine‐rich peptide (penetratin) were utilized to deliver polypeptides and proteins into the living cells. In this study, the immunostimulatory properties of HIV‐1 Nef DNA and protein constructs were evaluated using small heat shock protein 20 (sHsp20) and Freund's emulsion as an adjuvant, and four CPPs (HR9, MPG, M918, and penetratin) as a gene or protein carrier in BALB/c mice. Our data indicated that the HR9/DNA, MPG/DNA, M918/protein, and penetratin/protein complexes formed the stable nanoparticles that were effectively delivered in HEK‐293T cell line at certain ratios. Moreover, a heterologous Hsp20‐Nef DNA + MPG prime/rHsp20‐Nef protein+M918 boost regimen significantly elicited higher levels of IgG2a, IgG2b, IFN‐gamma, and Granzyme B directed toward Th1 responses in a long period (3 months) after the last immunization compared to other groups. Furthermore, the effective role of Hsp20 was detected as a natural adjuvant in enhancing immune responses against HIV‐1 Nef antigen. These findings demonstrated that the simultaneous use of M918 and MPG CPPs as protein and gene carriers improves HIV‐1 Nef‐specific B‐ and T‐cell immune responses as a promising approach for development of HIV‐1 monovalent vaccine.
Analgesic effect of Photobiomodulation Therapy: An in vitro and in vivo study
Authors: Zupin Luisa , Ottaviani Giulia , Rupel Katia , Biasotto Matteo , Zacchigna Serena , Crovella Sergio , Celsi Fulvio
Published: June 2019

Laser therapy, also known as Photobiomodulation (PBM) is indicated to reduce pain associated with different pathologies and applied using protocols that vary in wavelength, irradiance and fluence. Its mechanisms of action are still unclear and possibly able to directly impact on pain transmission, reducing nociceptor response. In our study, we examined the effect of two specific laser wavelengths, 800 and 970 nm, extensively applied in the clinical context and known to exert important analgesic effects. Our results point to mitochondria as the primary target of laser light in isolated dorsal root ganglion (DRG) neurons, reducing adenosine triphosphate content and increasing reactive oxygen species levels. Specifically, the 800 nm laser wavelength induced mitochondrial dysregulation, that is, increased superoxide generation and mitochondrial membrane potential. When DRG neurons were firstly illuminated by the different laser protocols and then stimulated with the natural transient receptor potential cation channel subfamily V member 1 (TRPV1) ligand capsaicin, only the 970 nm wavelength reduced the calcium response, in both amplitude and frequency. Consistent results were obtained in vivo in mice, by subcutaneous injection of capsaicin. Our findings demonstrate that the effect of PBM depends on the wavelength used, with 800 nm light mainly acting on mitochondrial metabolism and 970 nm light on nociceptive signal transmission.
Urolithin B suppresses tumor growth in hepatocellular carcinoma through inducing the inactivation of Wnt/β‐catenin signaling
Authors: Lv Min‐yi , Shi Chuan‐jian , Pan Fei‐fei , Shao Jiang , Feng Lu , Chen Guoqin , Ou Caiwen , Zhang Jin‐fang , Fu Wei‐ming
Published: June 2019

Consumption of dietary ellagitannins (ETs) has been proven to benefit multiple chronic health disorders including cancers and cardiovascular diseases. Urolithins, gut microbiota metabolites derived from ETs, are considered as the molecules responsible for these health effects. Previous studies have demonstrated that urolithins exhibit antiproliferative effects on prostate, breast, and colon cancers. However, as for hepatocellular carcinoma (HCC), it remains elusive. Herein, we aim to investigate the function of urolithin B (UB), a member of urolithins family, in HCC. The effects of UB on cell viability, cell cycle and apoptosis were evaluated in HCC cells, and we found UB could inhibit the proliferation of HCC cells, which resulted from cell cycle arrest and apoptosis. Furthermore, UB could increase phosphorylated β‐catenin expression and block its translocation from nuclear to cytoplasm, thus inducing the inactivation of Wnt/β‐catenin signaling. Using a xenograft mice model, UB was found to suppress tumor growth in vivo. In conclusion, our data demonstrated that UB could inhibit the proliferation of HCC cells in vitro and in vivo via inactivating Wnt/β‐catenin signaling, suggesting UB could be a promising candidate in the development of anticancer drugs targeting HCC.
Comparison of performance characteristics between high‐performance liquid chromatography and latex agglutination turbidimetric immunoassay for therapeutic drug monitoring of zonisamide
Authors: Eto Daiki , Tanaka Ryota , Suzuki Yosuke , Sato Yuhki , Itoh Hiroki
Published: June 2019

Background

Recently, the Nanopia® TDM Zonisamide reagent using the latex particle‐enhanced turbidimetric immunoassay (LTIA) method was developed. The aim of this study was to compare the differences in serum zonisamide (ZNS) concentrations quantified by the high‐performance liquid chromatography (HPLC) method and the LTIA method using a TBA‐25FR analyzer.

Methods

A total of 78 samples from 33 patients were quantified by both HPLC and LTIA methods. Deproteinization was used as pretreatment for the HPLC method. The ZNS concentrations quantified by two methods were compared.

Results

The HPLC method had intra‐ and inter‐day precision lower than 1.86% and 9.00%, and accuracy better than 2.44% and 6.33%, respectively. The LTIA method showed intra‐ and inter‐day precision lower than 2.50% and 5.20%, and accuracy better than 15.80% and 10.60%, respectively. The lower limits of quantification for the HPLC and LTIA methods were 1.0 and 5.0 µg/mL, respectively. The ZNS concentration quantified by the HPLC method correlated strongly with that by the LTIA method (r = 0.953, P < 0.001). A Bland‐Altman plot suggested no systematic error between ZNS concentrations quantified by HPLC and LTIA methods.

Conclusion

This study confirmed no differences between the concentrations quantified by the HPLC and LTIA methods at both high and low concentrations, demonstrating the confidence of measurement by the LTIA method.
A comparison study between wide‐range and high‐sensitivity C‐reactive protein assays (Roche Cobas c702) for low C‐reactive protein concentration in patients with cardiovascular risk
Authors: Li Runqing , Xue Yajun , Wang Tengjiao , Gong Lijun , Peng Peng , Xiong Pan , Dai Mingzhu , Shao Tongju , Hu Yuhan , Ye Xinchen
Published: June 2019

Background

Low concentration C‐reactive protein (CRP) has favorable prognostic significance in patients with cardiovascular risks.

Methods

We compared the wr‐CRP method with the hs‐CRP method both on Roche Cobas c702 analyzer for the determination of low CRP concentration (<20 mg/L) including 200 patients treated in Cardiology Department in Beijing Tsinghua Changgung Hospital (Beijing, China) from December 2018 to March 2019.

Results

The two methods were highly correlated (Spearman's rho = 0.995). Deming regression was used to fit the regression analysis model, giving a slope of 1.058 with an intercept of 0.008. The median method difference (wr‐CRP − hr‐CRP) was 0.120 mg/L (95% CI, 0.086‐0.200 mg/L), and the median percent differences were 7.34% (95% CI, 4.27%‐8.47%). The percent bias between both methods at the given cutoff CRP values of 1, 3, and 10 mg/L evaluated by Deming regression was 6.60%, 6.07%, and 5.88%, respectively, all of which were less than the acceptable standard (12.50%). The percentage of sample results concordant by both methods for the risk stratification was 96.0% (kappa = 0.937, P < 0.001).

Conclusions

Roche wr‐CRP and hs‐CRP assays are highly concordant in determining low concentration CRP. Wr‐CRP may be used as an alternative to hs‐CRP assay on Roche Cobas c702 analyzer to assess the cardiovascular risk, considering its convenience and lower costs.
Potential prognostic factors for predicting the chemotherapeutic outcomes and prognosis of patients with metastatic colorectal cancer
Authors: Zhang Liqun , Zhang Jingdong , Wang Yuanhe , Dong Qian , Piao Haiyan , Wang Qiwei , Zhou Yang , Ding Yang
Published: June 2019

Objectives

The purpose of this study was to explore whether pretreatment potential prognostic factors are related to chemotherapeutic outcomes and the prognosis of inpatients with metastatic colorectal cancer (mCRC) undergoing chemotherapy.

Materials and methods

Data from 71 patients with mCRC were analyzed retrospectively. The relationship between the potential prognostic factors before first‐line chemotherapy and the clinicopathological characteristics and chemotherapy response of the patients was calculated using Fisher's exact test and the chi‐square test. The prognostic factors were analyzed using univariate and multivariate analyses. We analyzed the subgroups using the Mann‐Whitney U test.

Results

Four factors were eventually used as prognostic factors, namely the albumin‐to‐globulin ratio (AGR), the fibrinogen‐to‐albumin ratio (FAR), the prealbumin‐to‐globulin ratio (PGR), and the fibrinogen‐to‐prealbumin ratio (FPR); the cutoff values of the four potential prognostic factors were 1.40, 10.63, 5.44, and 18.49, respectively. The high AGR and PGR groups had a higher response rate than that of the low groups. Patients in the low FAR and FPR groups showed a higher objective response rate than the high FAR and FPR groups. Patients with low FPR were associated with a higher disease control rate than patients with high FPR. Higher progression‐free survival (PFS) was observed in the high AGR and PGR and low FAR and FPR groups. The AGR, FAR, PGR, and FPR were considered reliable prognostic factors for PFS in a univariate analysis.

Conclusions

The prechemotherapy AGR, FAR, PGR, and FPR were good prognostic factors to predict the chemotherapy response and PFS in patients with mCRC.
Chronic myeloid leukemia blast crisis presented with AML of t(9;22) and t(3;14) mimicking acute lymphocytic leukemia
Authors: Liu Keyu , Hu Jintian , Wang Xueqin , Li Li
Published: June 2019

Background

Clinically, 90%‐95% of cases of CML have the characteristic t(9;22) (q34.1;q11.2) translocation that leads to the Philadelphia (Ph) chromosome. Rarely, patients with CML can present directly in a blast crisis (BC). While most blast crises are of myeloid origin, myeloid BC with ALL‐like morphologic features and Ph‐positive acute myeloid leukemia (AML) is rare, especially at the time of CML diagnosis.

Case presentation

A 20‐year‐old man presented with Ph chromosome‐positive AML mimicking acute lymphocytic leukemia (ALL). Bone marrow (BM) aspiration revealed AML with ALL‐like morphologic features. The results of the immunophenotypic analysis suggested AML. Cytogenetic analysis of the BM cells revealed a 46,XY,t(3;14)(q21;q32),t(9;22)(q34;q11.2)[20] karyotype. Thus, we called the condition AML mimicking ALL. The patient was diagnosed with myeloid BC based on the combination of clinical, cytologic, and cytogenetic studies.

Conclusion

To date, no case reports of a patient diagnosed with CML BC presented with Ph chromosome‐positive AML mimicking ALL have been reported. We present the case given its rarity, easy misdiagnosis, and poor prognosis. It is important to combine clinical, cytologic, and cytogenetic analyses in distinguishing CML BC from de novo AML with the t(9;22)，and further cases should be accumulated to explore how to improve the prognosis of the patients.
Acetaminophen adsorption using a low‐cost adsorbent prepared from modified residues of Moringa oleifera Lam. seed husks
Authors: Quesada Heloise B , Cusioli Luís Fernando , de O Bezerra Charleston , Baptista Aline TA , Nishi Leticia , Gomes Raquel G , Bergamasco Rosângela
Published: June 2019

Background

The high consumption of acetaminophen leads to high concentrations in surface water causing impacts on aquatic organisms, which is highlighting the need for investigation of alternative water and wastewater treatments. Therefore, the present study objective was to evaluate the adsorption capacity of acetaminophen onto Moringa oleifera Lam. seed husks after chemical and thermal treatment.

Results

The characterization of the adsorbent revelaed heterogeneous morphology with the presence of micro‐ and mesopores. Adsorption studies showed that the adsorption did not altered between pH 3 and 9, and that there was no significant effect of the ionic strength, indicating that the mechanism does not involve electrostatic interactions. In fact, Fourier transform infrard spectra showed that acetaminophen was adsorbed by hydrogen bonds and π‐stacking. The kinetic data were adjusted to the pseudo‐first‐order model, indicating an equilibrium time of 18 h. The equilibrium study showed that adsorption occurred in a monolayer and was favoured by the increase in temperature. The maximum adsorption capacity was 17.48 mg g−1, at 318 K, higher than some capacities found in the literature. The thermodynamic parameters indicated that the process was spontaneous, endothermic and physical.

Conclusions

The characteristics and results found compared to the recent literature verified the possibility of applying this residue as a low‐cost adsorbent for the removal of acetaminophen. © 2019 Society of Chemical Industry
Management of the uncinate process via the artery first approach in laparoscopic pancreatoduodenectomy
Authors: Jiang Chong‐Yi , Liang Yun , Wang Hong‐Wei , Hu Peng‐Fei , Cai Zhi‐Wei , Wang Wei
Published: June 2019

Background

Uncinate process dissection is one of the major challenges for surgeons when performing laparoscopic pancreatoduodenectomy. This study aimed to evaluate the artery first approach for handling uncinate process dissection in laparoscopic pancreatoduodenectomy.

Methods

Between February 2015 and June 2018, a total of 91 consecutive patients without vascular encasement underwent selective laparoscopic pancreatoduodenectomy, including the first 26 consecutive cases treated with the conventional approach and the remaining 65 with the artery first approach applied for uncinate process dissection. Here, we present and analyze the surgical outcomes and the oncological results for the two groups.

Results

There was no significant difference between the two groups in operative time, intraoperative blood loss, the rate of conversion to open pancreatoduodenectomy, postoperative complications, mortality, as well as the number of lymph nodes retrieved in the malignancies. In contrast, the artery first approach group showed a statistically significant shorter resection time and a higher R0 resection rate when compared with the conventional group.

Conclusions

The artery first approach is a safe and feasible technique that can be used for uncinate process management in laparoscopic pancreatoduodenectomy for patients without vascular encasement. It also has the advantage of increased rate of radical resection in the surgical intervention of relevant malignancies.
Magnon mode in α‐MnS Raman spectrum
Authors: Gerasimova Julia V. , Abramova Galina M. , Zhandun Vyacheslav S. , Vtyurin Aleksandr N.
Published: June 2019

Raman spectra of manganese monosulphide (α‐MnS) with NaCl structure in the temperature range 5–300 К are presented. A new peak at 22 cm–1 has been found at low temperatures. The temperature dependence of this peak made possible to attribute it to the magnon mode at k = 0. This is in good agreement with the magnon wavenumber calculated with Munich SPRKKR‐package.