bluuebunny/crossref_metadata_2025 huggingface dataset:
Deoxyshikonin reversibly inhibits cytochrome P450 2B6
Authors: Kim Ju‐Hyun , Choi Su Min , Shreatha Riya , Jeong Gil‐Saeng , Jeong Tae Cheon , Lee Sangkyu
Published: May 2020

Deoxyshikonin, a natural shikonin derivative, is the major component of Lithospermum erythrorhizon and exhibits various pharmacological effects such as lymphangiogenetic, antibacterial, wound healing, and anticancer effects. To investigate the herb–drug interaction potential associated with deoxyshikonin, the inhibitory effects of deoxyshikonin on eight major cytochrome P450 (CYP) enzymes were examined using cocktail substrate‐incubated human liver microsomes. Deoxyshikonin strongly inhibited CYP2B6‐catalyzed bupropion hydroxylation, with a Ki value of 3.5 μM, and the inhibition was confirmed using purified human CYP2B6. The inhibition was reversible because the inhibitory effect of deoxyshikonin was not dependent on the preincubation time. The results indicated that deoxyshikonin‐induced drug–drug interaction should be considered when any herb containing deoxyshikonin is used for conventional medications.
Are Anaphase Events Really Irreversible? The Endmost Stages of Cell Division and the Paradox of the DNA Double‐Strand Break Repair
Authors: Machín Félix , Ayra‐Plasencia Jessel
Published: May 2020

It has been recently demonstrated that yeast cells are able to partially regress chromosome segregation in telophase as a response to DNA double‐strand breaks (DSBs), likely to find a donor sequence for homology‐directed repair (HDR). This regression challenges the traditional concept that establishes anaphase events as irreversible, hence opening a new field of research in cell biology. Here, the nature of this new behavior in yeast is summarized and the underlying mechanisms are speculated about. It is also discussed whether it can be reproduced in other eukaryotes. Overall, this work brings forwards the need of understanding how cells attempt to repair DSBs when transiting the latest stages of mitosis, i.e., anaphase and telophase.
Cell culture process metabolomics together with multivariate data analysis tools opens new routes for bioprocess development and glycosylation prediction
Authors: Zürcher Philipp , Sokolov Michael , Brühlmann David , Ducommun Raphael , Stettler Matthieu , Souquet Jonathan , Jordan Martin , Broly Hervé , Morbidelli Massimo , Butté Alessandro
Published: May 2020

Multivariate latent variable methods have become a popular and versatile toolset to analyze bioprocess data in industry and academia. This work spans such applications from the evaluation of the role of the standard process variables and metabolites to the metabolomics level, that is, to the extensive number metabolic compounds detectable in the extracellular and intracellular domains. Given the substantial effort currently required for the measurement of the latter groups, a tailored methodology is presented that is capable of providing valuable process insights as well as predicting the glycosylation profile based on only four experiments measured over 12 cell culture days. An important result of the work is the possibility to accurately predict many of the glycan variables based on the information of three experiments. An additional finding is that such predictive models can be generated from the more accessible process and extracellular information only, that is, without including the more experimentally cumbersome intracellular data. With regards to the incorporation of omics data in the standard process analytics framework in the future, this works provides a comprehensive data analysis pathway which can efficiently support numerous bioprocessing tasks.
Total Synthesis of Dictyodendrins A–F by the Gold‐Catalyzed Cascade Cyclization of Conjugated Diyne with Pyrrole
Authors: Matsuoka Junpei , Inuki Shinsuke , Matsuda Yuka , Miyamoto Yoichi , Otani Mayumi , Oka Masahiro , Oishi Shinya , Ohno Hiroaki
Published: May 2020

The total synthesis of dictyodendrins A–F was achieved by using the gold(I)‐catalyzed annulation of a conjugated diyne with N‐Boc‐pyrrole for direct construction of the pyrrolo[2,3‐c]carbazole scaffold. Late‐stage functionalization of the resulting pyrrolo[2,3‐c]carbazole to introduce various substituents provided divergent access to dictyodendrins. Some dictyodendrin analogues exhibited inhibitory activities toward CDK2/CycA2 and GSK3.
Molecular testing for lung adenocarcinoma: Is it time to adopt a “plasma‐first” approach?
Authors: Makarem Maisam , Leighl Natasha B.
Published: May 2020

There is growing evidence that plasma cell‐free DNA testing can aid in the diagnosis of targetable alterations at diagnosis in patients with advanced nonsquamous lung carcinoma. A plasma‐first approach will facilitate access to precision medicine, with studies suggesting that nearly 60% of patients could benefit compared with the current approach of tissue profiling alone.
A randomized phase 2 study of temsirolimus and cetuximab versus temsirolimus alone in recurrent/metastatic, cetuximab‐resistant head and neck cancer: The MAESTRO study
Authors: Seiwert Tanguy Y. , Kochanny Sara , Wood Kevin , Worden Francis P. , Adkins Douglas , Wade James L. , Sleckman Bethany G. , Anderson Daniel , Brisson Ryan J. , Karrison Theodore , Stadler Walter M. , Vokes Everett E.
Published: May 2020

Background

Patients with cetuximab‐resistant, recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) have poor outcomes. This study hypothesized that dual blockade of mammalian target of rapamycin and epidermal growth factor receptor (EGFR) would overcome cetuximab resistance on the basis of the role of phosphoinositide 3‐kinase signaling in preclinical models of EGFR resistance.

Methods

In this multicenter, randomized clinical study, patients with recurrent/metastatic HNSCC with documented progression on cetuximab (in any line in the recurrent/metastatic setting) received 25 mg of temsirolimus weekly plus cetuximab at 400/250 mg/m2 weekly (TC) or single‐agent temsirolimus (T). The primary outcome was progression‐free survival (PFS) in the TC arm versus the T arm. Response rates, overall survival, and toxicity were secondary outcomes.

Results

Eighty patients were randomized to therapy with TC or T alone. There was no difference for the primary outcome of median PFS (TC arm, 3.5 months; T arm, 3.5 months). The response rate was 12.5% in the TC arm (5 responses, including 1 complete response [2.5%]) and 2.5% in the T arm (1 partial response; P = .10). Responses were clinically meaningful in the TC arm (range, 3.6‐9.1 months) but not in the T‐alone arm (1.9 months). Fatigue, electrolyte abnormalities, and leukopenia were the most common grade 3 or higher adverse events and occurred in less than 20% of patients in both arms.

Conclusions

The study did not meet its primary endpoint of improvement in PFS. However, TC induced responses in cetuximab‐refractory patients with good tolerability. The post hoc observation of activity in patients with acquired resistance (after prior benefit from cetuximab monotherapy) may warrant further investigation.
Hydroxyethyl cellulose‐based indicator labels to track freshness of anchovy (Engraulis encrasicolus)
Authors: Şen Ferhat , Uzunsoy İrem , Kahraman Memet Vezir
Published: May 2020

In this study, it was aimed to develop a freshness indicator label that changes color with spoilage of fish. Hydroxyethyl cellulose‐based indicator labels were prepared using two different mixed indicator (bromothymol blue/phenol red, cresol red/thymol blue) formulations. The functionality of prepared indicator labels was tested on anchovy (Engraulis encrasicolus) stored at 2°C and 10°C. Changes in total mesophilic aerobic bacteria, Pseudomonas spp., total yeast and mold counts, and total volatile basic nitrogen (TVB‐N) contents of anchovy during storage were examined. Color changes of prepared indicator films were measured by a colorimeter. Correlation between color changes of indicator labels with microorganism growth and content of TVB‐N was investigated. It is concluded that developed indicator labels change color with spoilage of anchovy and can be used as freshness indicator in fish industry.
Double‐weighted fuzzy clustering with samples and generalized entropy features
Authors: Lin Jiaxiang , Wu Liping , Chen Riqing , Wu Jianwei , Wang Xueping
Published: May 2020

For the dataset with different sample contributions and different feature importance, it is difficult to acquire a proper cluster structure that covers the entire features of the sample set. To improve the clustering result, a novel weighted fuzzy clustering algorithm based on both samples and generalized entropy features, called SGEF‐WFCM, is proposed in this article, among which a new objective function is developed on the basis of feature‐weighted generalized entropy regularization with a double‐weighting strategy of samples and features, the weighted coefficients of the features to each cluster, as well as the importance of the samples to the cluster are calculated dynamically, to obtain a better clustering result. Finally, experiments on both synthetic datasets and real‐world datasets from UCI are employed to verify the performance of the proposed SGEF‐WFCM algorithm. The results show that SGEF‐WFCM is superior to the conventional FCM algorithm in both the effectiveness and the usefulness during practices.
Accurate Backbone 13C and 15N Chemical Shift Tensors in Galectin‐3 Determined by MAS NMR and QM/MM: Details of Structure and Environment Matter
Authors: Kraus Jodi , Gupta Rupal , Lu Manman , Gronenborn Angela M. , Akke Mikael , Polenova Tatyana
Published: May 2020

Chemical shift tensors obtained from solid‐state NMR spectroscopy are very sensitive reporters of structure and dynamics in proteins. While accurate 13C and 15N chemical shift tensors are accessible by magic angle spinning (MAS) NMR, their quantum mechanical calculations remain challenging, particularly for 15N atoms. Here we compare experimentally determined backbone 13Cα and 15NH chemical shift tensors by MAS NMR with hybrid quantum mechanics/molecular mechanics/molecular dynamics (MD‐QM/MM) calculations for the carbohydrate‐binding domain of galectin‐3. Excellent agreement between experimental and computed 15NH chemical shift anisotropy values was obtained using the Amber ff15ipq force field when solvent dynamics was taken into account in the calculation. Our results establish important benchmark conditions for improving the accuracy of chemical shift calculations in proteins and may aid in the validation of protein structure models derived by MAS NMR.
Robust Guanidine Metal Catalysts for the Ring‐Opening Polymerization of Lactide under Industrially Relevant Conditions
Authors: Schäfer Pascal M. , Herres‐Pawlis Sonja
Published: May 2020

The increasing awareness of sustainability has led to enormous growth of the demand for bio‐based and biodegradable polymers such as poly(lactide) (PLA). In industry, polymerization of lactide is currently carried out using tin catalysts (e. g., tin(II) ethyl hexanoate, Sn(Oct)2). Since the catalyst remains in the polymer, it can accumulate in the soil or in the human body after degradation and cause damage due to its toxicity. Therefore, a search for a suitable substitute for this catalyst has been going on for decades. Guanidine metal complexes prove to be excellent catalysts in the polymerization of lactide. They are not only convincing because of their activity and the synthesis of high molar mass polymers, but also show a high robustness against high temperatures, oxidation as well as residual protic impurities in the monomer. Herein, key zinc and iron guanidine complexes are discussed with respect to their apparent rate constant (kapp) and rate constant of propagation (kp), produced molar masses and the mechanism involved.
Exploring the potential usefulness of U.S. maize expired Plant Variety Protection Act lines for maize breeding in sub‐Saharan Africa
Authors: Dao Abdalla , Sanou Jacob , Sanon R. Diane , Zeba Issiaka , Coulibaly Sarah , Lübberstedt Thomas
Published: May 2020

Maize (Zea mays L.) inbred lines with expired Plant Variety Protection Act (ExPVP) certificates are publicly available and potentially represent a new germplasm resource for many public and private breeding programs. The use of these inbred lines for maize breeding in sub‐Saharan African (SSA) was little investigated. Hence, this study was conducted to explore their potential usefulness. Ninety‐six ExPVP lines, two temperate public lines, and 14 tropical lines were evaluated in five different trials from 2016 to 2018 in Burkina Faso to determine their phenotypic characteristics; resistance to drought, heat, and three diseases; and to identify elite ExPVP lines for local maize breeding programs. Cluster analysis based on phenotypic traits highlighted a clear distinction between the different groups (nonstiff stalk [NS] vs. Iowa Stiff Stalk Synthetic [SS] heterotic groups and temperate vs. tropical germplasms). The screening showed that 3, 28, and 68% of ExPVP lines were resistant, tolerant, and susceptible to maize leaf blight disease, respectively. However, the lines were either tolerant or resistant to Curvularia leaf spot and maize streak virus. Approximately 30% of ExPVP lines presented a tolerance to the three maize diseases tested and 8% of the lines were tolerant to drought. Heat stress was severe to both ExPVP and tropical lines. Yield potential of ExPVP lines varied from 1.68 to 2635.63 kg ha−1 vs. 798.76 to 1707.56 kg ha−1 for tropical lines. The ExPVP lines identified showing tolerance to stresses and a high‐yield performance can be integrated in inbred‐hybrid development program.
Across the Board: Federico Bella on Electrochemical Nitrogen Reduction
Authors: Bella Federico
Published: May 2020

In this series of articles, the board members of ChemSusChem discuss recent research articles that they consider of exceptional quality and importance for sustainability. This entry features Prof. F. Bella, who discusses the electrochemical reduction of nitrogen to produce ammonia through the addition of protons and electrons under mild conditions (25 °C, 1 atm). This reaction has the potential to replace the energy‐intensive traditional Haber–Bosch process but faces several challenges and pitfalls.
Minute tubercles in bitterling larvae: Developmental dynamic structures to prevent premature ejection by host mussels
Authors: Kim Hyeong Su
Published: May 2020

Bitterlings are small freshwater fish that use long ovipositors to lay eggs in host mussels, and they have morphological adaptations to increase larval survival. The most well‐known adaptation is the minute tubercles on the skin surface of larvae; they are developed in early‐stage larvae with weak swimming ability and disappear in free‐swimming larvae before they leave the host mussel.

In the present study, I comprehensively analyzed the developmental stages ofRhodeus pseudosericeuslarvae, their morphological and physiological characteristics, their migration inside mussels, and the development of minute tubercle in order to elucidate the morphological function of the minute tubercles. These tubercles began to develop 1 day after hatching (formation stage), grew for 2–5 days (growth stage), reached the peak height after 6–7 days (peak stage), abruptly reduced in height after 8–10 days (abrupt reduction stage), and gradually reduced in height (reduction stage) until completely disappearing 27 days after hatching (disappearance stage).

The larvae remained in the mussels’ interlamellar space of the gill demibranchs until 10 days after hatching and began to migrate to the suprabranchial cavity 11 days after hatching. At this time, the larvae had a heart rate and the caudal fin began to develop. At 24 days after hatching, the minute tubercles had almost disappeared, and some individuals were observed swimming out of the mussels.

The results presented herein elucidate that the minute tubercles are the developmental dynamic structures that the bitterling larvae have morphologically adapted to prevent premature ejection from the mussel.
Old age‐associated enrichment of peripheral T regulatory cells and altered redox status in pulmonary tuberculosis patients
Authors: Namdeo Manju , Kandel Ramesh , Thakur Prabhakar Kumar , Mohan Anant , Dey Aparajit Ballav , Mitra Dipendra Kumar
Published: May 2020

Aging influences the susceptibility and prognosis to various infectious diseases including tuberculosis (TB). Despite the impairment of T‐cell function and immunity in older individuals, the mechanism for the higher incidence of TB in the elderly remains largely unknown. Here, we evaluated the age‐associated immune alterations, particularly in effector and Treg responses in pulmonary TB patients. We also evaluated the impact of redox status and its modulation with N‐acetyl‐cysteine (NAC) in elderly TB. Higher frequency of Treg cells and reduced IFN‐γ positive T cells were observed among older TB patients. The elevated number of Treg cells correlated tightly with bacillary load (i.e. disease severity); which declined significantly in response to successful anti‐tubercular treatment. We could rescue Myobacterium tuberculosis‐specific effector T cell (Th1) responses through various in vitro approaches, for example, Treg cell depletion and co‐culture experiments, blocking experiments using antibodies against IL‐10, TGF‐β, and programmed death‐1 (PD‐1) as well as NAC supplementation. We report old age‐associated enrichment of Treg cells and suppression of M. tuberculosis‐specific effector T (Th1) cell immune responses. Monitoring these immune imbalances in older patients may assist in immune potentiation through selectively targeting Treg cells and/or optimizing redox status by NAC supplementation.
Ligand Field Theory for Planar Complexes: First Principles Validation of the Critical Effects of Coordination Voids
Authors: Deeth Robert J.
Published: May 2020

Multi reference CASSCF/NEVPT2 wavefunction calculations on planar cis‐[MA2B2] complexes show that large dxz/dyz splittings are a feature of the symmetry of the ligand field and are not due to the Orgel effect or phase coupled ligation as previously proposed based on the MO version of the angular overlap model. Instead, the splitting can be attributed to the π components of the local ligand fields in the “void” regions above and below the molecular plane. The potential in these regions is lower than the d orbital barycentre leading to negative parameter values which is fully consistent with the cellular ligand field interpretation of ligand field theory. The wider implications of ligand field effects from coordination voids are considered.
Chemical Synthesis and Isolation of Trans‐Palmitoleic Acid (Trans‐C16:1 n‐7) Suitable for Nutritional Studies
Authors: Guillocheau Etienne , Drouin Gaëtan , Catheline Daniel , Orione Clément , Legrand Philippe , Rioux Vincent
Published: May 2020

Trans‐palmitoleic acid (trans‐9 C16:1, or trans‐C16:1 n‐7, TPA) is typically found in ruminant‐derived foods (milk and meat). Of note, previous epidemiological studies associated high levels of circulating TPA with a lower risk of type 2 diabetes and metabolic syndrome in humans. At the current time, TPA intakes in humans are ensured by ruminant‐derived foods. However, due to the very low commercial availability of TPA, there are no supplementation studies carried out so far. Therefore, the ability for dietary TPA to prevent type 2 diabetes and metabolic syndrome has never been experimentally assessed. Here, a method (among others) to get dozens of grams of pure TPA as ethyl ester, to perform dedicated supplementation studies, is reported. For that purpose, it starts from food sources containing high amounts of cis‐palmitoleic acid (cis‐9 C16:1, or cis‐C16:1 n‐7, CPA), dealing with fatty acids ethyl esters all along the experiment. CPA is purified with flash liquid chromatography, then submitted to a cis/trans isomerization step. Finally, TPA is separated from CPA by low‐temperature crystallization in methanol. The final product is fully characterized by 1H and 13C nuclear magnetic resonance spectrometry. It is possible to produce ≈70 g of 85%‐purity TPA suitable for nutritional studies.

Practical Applications: The synthesized trans‐palmitoleic acid may serve for supplementation (or nutritional) studies aiming at unravelling its physiological impacts suggested by epidemiological work. Depending on the amount of synthesized trans‐palmitoleic acid, one may carry out nutritional studies on rodents or even on humans.
Testing the basic socio‐structural assumptions of social identity theory in the gender context: Evidence from correlational studies on women's leadership
Authors: Scheifele Carolin , Ehrke Franziska , Viladot Maria Angels , Van Laar Colette , Steffens Melanie C.
Published: May 2020

Given negative social identity, different perceptions of the structure of an intergroup relation (i.e., stability, legitimacy, permeability) should be related to different identity‐management strategies (i.e., social competition, social creativity, or individual mobility) depending on group identification. This is among the basic tenets of social identity theory (SIT). There is surprisingly little empirical support for these postulates in the context of one of the most central group identities: gender. Using a sample of women in leadership positions in Spain (N = 649), we tested relations between structural perceptions and identity‐management strategies in a pilot study. Structural equation modeling yielded empirical support regarding social competition, but little for social creativity or individual mobility. Identity‐management strategies were related to one organizational outcome (i.e., identification with the organization). The preregistered main study is intended to replicate and extend these findings using a different sample while improving several of the measures used.
Scalable Multilayer Printing of Graphene Interfacial Layers for Ultrahigh Power Lithium‐Ion Storage
Authors: Lee Sang Ho , Johnston Colin , Grant Patrick S.
Published: May 2020

A low resistance graphene‐based interfacial layer is developed for multilayered lithium‐ion capacitor electrodes using a layer‐by‐layer printing approach, with the goal of boosting energy storage performance at ultrafast charge/discharge rates (≥100 C). The electrochemical behavior of spray printed Li4Ti5O12‐based heterostructure electrodes is investigated as a thin, discrete graphene layer is placed: 1) at the base of the Li4Ti5O12 (at the electrode/current collector interface); 2) on the top of the Li4Ti5O12 (at the electrode/separator junction); and 3) both at the base and on the top of the Li4Ti5O12 (sandwich configuration), with marked improved electrode performance at >50 C when the graphene layer is interleaved at the Li4Ti5O12/current collector interface. This best performing heterostructure negative electrode is then coupled with a spray printed activated carbon positive electrode in a lithium‐ion capacitor configuration, showing an attractive power density of ≈8000 W kg−1 at 350 C. The fabrication of double‐sided graphene/Li4Ti5O12 multilayered heteroelectrodes is successfully demonstrated over areas of 20 cm × 15 cm and in various patterned configurations.
A high‐resolution bilevel skew‐tstochastic generator for assessing Saudi Arabia's wind energy resources
Authors: Tagle Felipe , Genton Marc G. , Yip Andrew , Mostamandi Suleiman , Stenchikov Georgiy , Castruccio Stefano
Published: May 2020

Saudi Arabia has recently established its renewable energy targets as part of its “Vision 2030” proposal, which represents a roadmap for reducing the country's dependence on oil over the next decade. This study provides a foundational assessment of the wind resource in Saudi Arabia that serves as a guide for the development of the outlined wind energy component. The assessment is based on a new high‐resolution weather simulation of the region generated with the Weather Research and Forecasting (WRF) model. Furthermore, we propose a spatiotemporal stochastic generator of daily wind speeds that assists in characterizing the uncertainty of the energy estimates. The stochastic generator considers a vector autoregressive structure in time, with innovations from a novel biresolution model based on a skew‐tdistribution with a low‐dimensional latent structure. Estimation of the spatial model parameters is performed using a Monte Carlo expectation‐maximization (EM) algorithm, which achieves inference over approximately 184 million points and enables to capture the spatial patterns of the higher order moments that typically characterize high‐resolution wind fields. Our results identify regions along the western mountain ranges and central escarpments that are suitable for the deployment of wind energy infrastructure. According to the assessment, between 30 and 70% of the national electricity demand could be met by wind energy.
Conventional weight loss interventions across the different BMI obesity classes: A systematic review and quantitative comparative analysis
Authors: Bauer Kerstin , Lau Teresa , Schwille‐Kiuntke Juliane , Schild Sandra , Hauner Hans , Stengel Andreas , Zipfel Stephan , Mack Isabelle
Published: May 2020

Objective

The recommendation for conventional body weight loss (BWL) treatment in obesity is 5–10%. It is not clear whether BWL is similar across the three different body mass index (BMI) obesity classes. The aim was to provide an overview on BWL across these classes in moderate lifestyle/diet intervention programs.

Method

A systematic literature search was conducted and the evidence of randomized controlled trials (RCTs) and pre‐post design studies synthesized. The outcome was BWL.

Results

For RCTs, mean BWL in the intervention group was 3.6 kg (class I) and 5.3 kg (class II), which equates to 4 and 5% BWL, respectively. None of the assessed class III obesity studies met the inclusion criteria. For pre‐post design studies, mean BWL was 5.4 kg (class I), 5.5 kg (class II) and 7.9 kg (class III), with high variation within and across studies in the latter. This equates to 6, 5 and, 6% BWL, respectively.

Conclusions

BWL of moderate BWL programs are similar across the different obesity classes. For class I obesity, the results differ between RCT and pre‐post design studies by 2% BWL. The high variation of BWL in class III obesity might reflect different states of motivation such as the attitude towards bariatric surgery.
Provenance‐based data flow control mechanism for Internet of things
Authors: Rong‐na Xie , Hui Li , Guo‐zhen Shi , Yun‐chuan Guo , Ben Niu , Mang Su
Published: May 2020

In the Internet of things (IoT), the flow and sharing of data between different devices has become a trend. However, determining how to ensure the controlled flow and sharing of data is an urgent problem to address to ensure data security and privacy in the IoT environment. To address the above problem, we propose a provenance‐based data flow control mechanism (PDFC) that includes flow control and further control to realize data flow control and further control after flow. The mechanism implements both direct and indirect control of data flow based on provenance data, which reduces the risk of indirect leakage. As data flow and are shared between different devices, the provenance data become increasingly large, consequently, indirect control on the provenance data takes increasing amounts of time, seriously affecting control efficiency. To improve the control efficiency of data flow, the provenance data are simplified according to the type of operation generating the data and the association degree of data and their provenance data. To reduce the storage space occupied by the provenance data and improve the efficiency of querying the provenance data, we propose a provenance tree that records the relationship between data and their provenance data. A theoretical analysis demonstrates the security and effectiveness of PDFC, which can solve the fine‐grained controlled sharing problem in IoT. Using the data flow in a smart healthcare system as an example, we demonstrate the implementation and optimization method of PDFC, and the result shows PDFC has obvious flexibility and performance advantages.
Britain and Brexit: A forecast of the future of employment protection during corporate insolvency
Authors: Gant Jennifer L. L.
Published: May 2020

Brexit has produced a lot of uncertainties in the UK, not the least of which are the future of protections that have been derived from EU social policy Directives. Arguably, the UK's membership in the EU has pushed it further into a socially liberal and protective framework that it might not have adopted had it remained outside of the EU's sphere of influence. The question now is what direction the UK will take with regard to both the rescue culture and the social protections, both of which have been highly influenced by EU law and policy. The UK has ever been the “odd man out” in the EU, springing as it does from a significantly different legal origin than the Franco/German model at the heart of the EU. Examining the developmental path of other common law jurisdictions (America, Canada, and Australia) whose legal systems are derived from the British may be instructive in relation to the direction the UK might have taken had it not joined the EU, with a particular focus on the employment protections derived from the EU which are often applicable during insolvency and rescue procedures. An analysis of this counterfactual position may then also provide a clue or forecast as to the direction that the UK may take following Brexit.
Cumulative risk of cervical intraepithelial neoplasia for women with normal cytology but positive for human papillomavirus: Systematic review and meta‐analysis
Authors: Malagón Talía , Volesky Karena D. , Bouten Sheila , Laprise Claudie , El‐Zein Mariam , Franco Eduardo L.
Published: May 2020

Most women positive for human papillomavirus (HPV) are cytology normal. The optimal screen‐management of these women is unclear given their risk of developing precancer. We performed a systematic review and meta‐analysis of progression rates to precancer and cancer for HPV‐positive, cytology normal women. We searched MEDLINE, EMBASE and Scopus for prospective studies measuring the cumulative incidence of precancer and cervical cancer in HPV‐positive, cytology/histology normal women. Record screening was performed independently by two reviewers. We modeled the cumulative incidence over time using a multilevel random‐effects meta‐regression model. We used the model to predict HPV type‐specific risks of precancer and cancer over follow‐up. Data from 162 unique records were used in our analysis. The average incidence rate of cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) in high‐risk HPV positive but cytology/histology normal women was 1.0 per 100 women‐years (95% CI: 1.0‐1.1). This corresponds to an average cumulative risk at 1, 3 and 5 years of 2.1% (95% prediction interval 0.0‐9.5), 4.3% (95% prediction interval 0.0‐11.5) and 6.4% (95% prediction interval 0.0‐13.5). HPV type was a strong predictor of the risk of oncogenic progression. There was substantial heterogeneity in the background precancer risk across studies (P‐value < .0001). Our HPV type‐specific progression risk estimates can help inform risk‐based cervical cancer screening guidelines for HPV‐positive women. However, precancer and cervical cancer risks are highly variable and may not be generalizable between populations.
Study on the stability and cellular affinity of gelatin‐polysaccharide composite films
Authors: Liu Yang , Lv Shijie , Gao Jun , Zhang Ying , Zhao Shan , Guo Xin , Sun Guangwei
Published: May 2020

The gelatin film has great potential in biomedical applications, especially in wound healing. The combination of gelatin films and stem cells could further accelerate the skin regeneration. Although polysaccharide modification can improve the mechanical property and biological activity of gelatin films, information about the stability and cellular affinity is still limited. This study investigated the influence of polysaccharides on the stability and cellular affinity of gelatin films. Two kinds of gelatin‐polysaccharide composite films, including gelatin‐hyaluronic acid (G‐HA) and gelatin‐chitosan (G‐CS), were prepared in this study. It was found that G‐HA composite film had better short‐term and long‐term stability compared with G‐CS composite film. And G‐HA composite film also had better biological safety than G‐CS film. Moreover, the surface of G‐HA composite film supported the adhesion and growth of human umbilical cord Wharton's jelly‐derived mesenchymal stem cells (WJ MSCs) better than G‐CS film surface. These data illustrated that G‐HA composite film has better stability and cellular affinity compared with G‐CS film, which could be considered a promising delivery system of stem cells for further in vivo studies. Therefore, this work would be very helpful to optimize the preparation of gelatin‐polysaccharide composite films.
Synthesis of combinatorial Janus nanoparticles based on EpCAM‐PEG/PCL for targeted therapy of human colorectal adenocarcinoma
Authors: Khezrian Somayeh , Khoee Sepideh , Caceres Marleny
Published: May 2020

Active targeted nanotechnology‐based drug delivery systems have gained significant favor because they have the ability to decrease side effects, improve drug bioavailability, and the potency of anticancer treatment. In this study, functional amphiphilic Janus nanoparticles (JNPs), consisting of hydrophilic and hydrophobic biocompatible polymers as two distinct sides, have been prepared via a robust and simple synthesis method. The surface‐active hydrophilic side of this Janus platform is functionalized with an aptamer against epithelial cell adhesion molecule (EpCAM) to deliver Doxorubicin (DOX) for the treatment of metastasis colorectal adenocarcinoma HT29 cells. The Janus morphology of the nanoparticles and their cell penetration behavior are shown in microscopic evaluations. By evaluating the prepared DOX‐loaded aptamer–modified JNPs by cell‐toxicity assay and confocal microscopy, it was determined that the utilization of an internalization strategy to enhance cell uptake would increase the anticancer effect of the Janus nanocarrier and improve the capacity to deliver the chemotherapeutical drug site‐specifically.
Adsorption of serum proteins on titania nanotubes and its role on regulating adhesion and migration of mesenchymal stem cells
Authors: Wu Sai , Zhang Deteng , Bai Jun , Zheng Honghao , Deng Jun , Gou Zhongru , Gao Changyou
Published: May 2020

Migration and differentiation of bone marrow‐derived mesenchymal stem cells (BMSCs) is an important biological process in tissue regeneration. Nanostructured titanium materials are believed to play a fundamental role in dental and orthopedic applications. However, the protein adsorption on nanostructured titanium materials and its correlation with the subsequent cell behaviors have not been studied. In this work, the titania nanotube arrays with different tubular diameters ranging from 27.3 to 88.2 nm were fabricated by using an electrochemical etching method. The adsorbed amounts and types of cell adhesion‐related proteins (such as fibronectin, vitronectin, and laminin) from serum were investigated, revealing that these proteins were preferred to bind onto the surface with nanotubes of a smaller diameter. Adhesion and migration of BMSCs were studied as a function of different nanotube diameters in the presence or absence of serum proteins. Compared with the nanotube surface with a larger tubular diameter (88.2 nm), the surface with a smaller one could better support BMSCs in terms of adhesion and spreading. The pre‐adsorbed serum proteins significantly enhanced adhesion and migration abilities of BMSCs. However, the adequate interactions between cells and serum proteins on the nanotubes surface with smallest nanotubes in diameter weakened cell mobility. Arrangement of cytoskeleton and expressions of key genes and proteins were studied, revealing that the nanostructured surfaces and pre‐adsorbed proteins jointly mediated the adhesion and migration of BMSCs.
Development of nanocomposite collagen/ HA/β‐TCP scaffolds with tailored gradient porosity and permeability using vitamin E
Authors: Ebrahimi Mehdi , Botelho Michael , Lu William , Monmaturapoj Naruporn
Published: May 2020

The production of the biomimetic scaffolds with well‐designed porosity parameters is a critical and challenging factor in biomaterials processing. The porosity parameters (i.e., pore size, pore shape, and distribution pattern) impact scaffold permeability, proteins/cells infiltration, and angiogenesis. This study introduced a new approach for the production of gradient porous nanocomposite scaffolds with controllable porosity and permeability using basic biomaterials of collagen and nanobiphasic calcium phosphate (nBCP) powder consisting of nano HA/β‐TCP. A modified freeze‐drying method (i.e., variables; collagen/nBCP ratio and quenching rates) was integrated for the first time with the chemical foaming method with the use of vitamin E as a potential surfactant and porogen. Vitamin E successfully increased the range of pore size, pore interconnection, and scaffold permeability. Further control of collagen/nBCP ratios and quenching rates allowed modulation of the pore morphology, total porosity, and the surface roughness of the scaffold. Scaffolds produced using vitamin E with collagen/nBCP ratio of 92/8% at −80°C quenching rate displayed a multimodal heterogeneous pore network with a wide range of pore sizes of mostly round/oval and polygonal pore morphology. Furthermore, these scaffolds revealed a more consistent gradient porous network with peripheral large pores—that gradually become smaller toward scaffold central—that produced a significantly higher permeability and better support of initial cellular performances. Accordingly, considering the various potentials of vitamin E, this study would provide promising insight into the production of smart and customized scaffolds for regenerative and therapeutic applications.
Study on the transfection efficiency of chitosan‐based gene vectors modified with poly‐l‐arginine peptides
Authors: Zhang Yan , Chu Tianjiao , Sun Le , Chen Xiaotong , Zhang Wangwang , Zhang Haibin , Han Baoqin , Chang Jing , Feng Yilin , Song Fulai
Published: May 2020

Although in a series of studies, arginine peptides had shown the ability to promote the targeting delivery efficacy, the relationship between the transfection efficiency and the length of the poly‐l‐arginine chain had seldom been reported. This study was aimed to explore whether the chain length of poly‐l‐arginine grafted on chitosan had a great significance on the transfection efficiency of entering the cells. Herein, arginine and arginine peptide modified chitosan were synthesized as gene vectors (CS‐Arg and CS‐5Arg) and then the chemical structures were characterized by using 1H NMR. The CS‐Arg and CS‐5Arg were combined with plasmids by electrostatic interactions to form stable particles. The morphology features, Zeta potentials, and buffering capacity of the complex particles were analyzed. Afterward, the combination ability with DNA and the protection ability to DNase I were studied, and the gene transfection efficiency and cellular uptake were investigated in vitro. The results showed that the gene transfection efficiency of the chitosan was significantly enhanced by arginine‐graft modification. However, there were no significant differences between the CS‐Arg and the CS‐5Arg. The molecular simulation results indicated that the guanidine groups of grafted arginine were shielded by chitosan molecule and the guanidine groups contributed little to the gene transfection efficiency. The results demonstrated that the increased chain length of grafted arginine had no significantly enhanced effect on the transfection efficiency, which could provide convincing evidence for the construction and application of arginine and chitosan derivatives as gene vectors, and could promote the development of gene delivery system.
Computational studies on the conformational preference of N‐(Thiazol‐2‐yl) benzamide
Authors: Zonouzi Afsaneh , Kakeshpour Ali , Ranjbar Parviz Rashidi , Moradi Ashraf
Published: May 2020

N‐(Thiazol‐2‐yl) benzamide 1 substructures are found in some of bioactive compounds. In some of protein/ligand co‐crystals, the 1 moiety adopts a conformer in which the amide O and the thiazole S atoms are close. In fact, in the crystalline structure of 1, the O—S distance is even shorter than Van der Waals radius. Although the natural bond orbital analysis finds a weak stabilizing interaction between O and S atoms, the attractive dipole–dipole interaction between the amide N─H and thiazole N atom seems to play a more significant role. Moreover, an intramolecular O—H hydrogen bonding in dimeric forms found to have an important role in the conformation preference of 1. Computational details for the stability of conformers have been discussed using quantum theory of atoms in molecules, natural bond orbital (NBO) and noncovalent interaction index analysis.
New insight into experimental and theoretical mechanistic study on a green synthesis of functionalized 4H‐chromenes using magnetic nanoparticle catalyst
Authors: Ghavidel Hassan , Mirza Behrooz , Soleimani‐Amiri Somayeh , Manafi Mohammadreza
Published: May 2020

A green synthesis of functionalized 4H‐chromenes using one‐pot, three‐component reaction of salicylaldehyde (1), active methylene (2), and carbon‐based nucleophile (3) using Fe3O4@CONa nanoparticles in water has been performed at 60°C. The Fe3O4@CONa nanoparticle as an efficient, green, and magnetically reusable heterogeneous catalyst was applied in these reactions up to the nine runs. Green catalyst and solvent, short reaction time, high product yields, as well as simple work‐up procedure were found as some advantages of this methodology. The density functional theory calculations were applied to all‐inclusive perception of the one‐pot, three‐component reaction mechanism. The most reactions progressed through the following route: (a) nucleophilic addition of 2 to 1; (b) ring closing, dehydration; (c) nucleophilic substitution of 3 (2‐naphtol, 4‐hydroxycumarin) to intermediate. Sometimes mechanism mutated to: (a) nucleophilic addition of 3 (indole, 2‐methylindole) to 1, and dehydration; (b) nucleophilic addition of 2 to intermediate; and (c) ring closing, and dehydration. The frontier molecular orbitals, NBO analyses, molecular electrostatic potential of reactants, and intermediates confirmed the proposal mechanisms. Theoretical study could be so helpful to pick out suitable reactants of the reaction.
The value of platelet count in evaluating the degree of liver fibrosis in patients with chronic hepatitis B
Authors: Zhong Li‐Kun , Zhang Guo , Luo Shuang‐Yan , Yin Wu , Song Huai‐Yu
Published: May 2020

Objective

To investigate the value of platelet count in evaluating the degree of liver fibrosis in patients with chronic hepatitis B (CHB).

Methods

A total of 158 CHB patients who underwent liver biopsy in our hospital were included, and the clinical characteristics of these patients were retrospectively analyzed. The diagnostic values of platelet count, aspartate aminotransferase‐to‐platelet ratio index (APRI), and the fibrosis index based on four factors (FIB‐4) for significant fibrosis (F ≥ 2) and early cirrhosis (F = 4) stages in CHB patients were assessed by the use of receiver operating characteristic (ROC) analysis.

Results

The median (F0: 221.0; F1: 210.0; F2: 188.0; F3: 171.0; and F4: 155.5) and mean rank (F0: 120.4; F1: 100.1; F2: 82.2; F3: 67.9; and F4: 49.5) of platelet count decreased along the aggravation of fibrosis (F0‐F4). The areas under the ROC curve for the platelet count in diagnosis of significant fibrosis stage was 0.70, which had no significant difference with FIB‐4 (0.73) and APRI (0.68) in diagnostic efficacy (P = .428). The areas under the ROC curve of platelet count in diagnosis of early cirrhosis were 0.72, which had no significant difference with FIB‐4 (0.76) and APRI (0.68) (P = .094).

Conclusion

The platelet count, as a simple and non‐invasive index, could evaluate the degree of liver fibrosis in CHB individuals. At the same time, the diagnostic efficiency of platelet count to evaluate the significant liver fibrosis and early cirrhosis is comparable to FIB‐4 and APRI.
Optimization and validation of patient‐based real‐time quality control procedure using moving average and average of normals with multi‐rules for TT3, TT4, FT3, FT3, and TSH on three analyzers
Authors: Song Chao , Zhou Jun , Xia Jun , Ye Deli , Chen Qian , Li Weixing
Published: May 2020

Background

We have designed a patient‐based real‐time quality control (PBRTQC) procedure to detect analytical shifts and review analytical trends of measurement procedures.

Methods

All the nine months' patient results of total thyroxine (TT4), total triiodothyronine (TT3), free thyroxine (FT4), free triiodothyronine (FT3), and thyrotropin (TSH) measured by three identical analyzers were divided into three groups according to the source of inpatient patients, outpatient patients, and healthy people. The data in each group were truncated by optimized Box‐Plot method and normalized by Box‐Cox method if necessary. The z‐score charts of internal quality control (IQC) samples' results and PBRTQC data were drawn by IQC levels and groups, respectively. The analytical shifts and analytical trends were detected by multi‐rules of 2‐2S rules and moving average rules. The performances of PBRTQC were compared with the BIQC in which IQC samples were measurand only once per day at the beginning of the analytical batch. Twelve quality control cases were listed to validate the performances.

Results

All the five analytes presented normal distributions when the parameter n of Box‐Plot method was 1.2. The percentages of excluded data ranged from 2.9% to 11.6%. 31 and 14 rejections triggered in PBRTQC and BIQC, respectively. 96.8% of the shift rejections in PBRTQC were trend‐related shifts and calibration‐related shifts, while the proportion was 85.7% in BIQC but 78.6% of the shift rejections in TSH. 25.7% and 8.6% of 105 calibration events which caused analytical shifts were detected by PBRTQC and BIQC, respectively. However, the performance of PBRTQC was not well in TSH because of its large coefficient of variation.

Conclusions

The optimized PBRTQC is high efficiency than BIQC in detecting analytical shifts, trends, and calibration events. The PBRTQC can be used as a low‐cost supplementary procedure to IQC every day, especially at the end of the analytical batch on that day when the within‐individual biological variation of analyte is not larger than its coefficient of variation in IQC. Further optimization and validation of PBRTQC are still needed.
Investigation of Leptin G19A polymorphism with bladder cancer risk: A case‐control study
Authors: Mao Fei , Niu Xiao‐Bing , Gu Shuo , Ji Lu , Wei Bing‐Jian , Wang Heng‐Bing
Published: May 2020

Background

A host of studies show Leptin (LEP) G19A polymorphism is correlated with the risk of various cancers, but the connection of this polymorphism with bladder cancer (BC) risk has not been reported.

Materials and methods

This association was in explored in a case‐control study involving 355 BC cases and 435 controls (all Chinese Han). Polymerase chain reaction‐restriction fragment length polymorphism was conducted to genotype LEP G19A polymorphism. Analyses of allele and genotype distribution were evaluated using chi‐square test. Continuous data were assessed by an independent samples t test or one‐way ANOVA test. Odds ratio (OR) and 95% confidence interval (CI) were determined by logistic regression.

Results

LEP G19A polymorphism was significantly associated with a lower risk of BC (AA vs GG: adjusted OR, 0.40, 95% CI, 0.20‐0.83, P = .013; AA + GA vs GG: adjusted OR, 0.70, 95% CI, 0.52‐0.93, P = .015; AA vs GA + GG: adjusted OR, 0.45, 95% CI, 0.22‐0.91, P = .026). In addition, A allele was associated with decreased risk for BC (A vs G: OR, 0.70, 95% CI, 0.55‐0.89, P = .003). Stratified analyses by females, non‐drinkers, and non‐smokers all returned considerable relations. Furthermore, LEP G19A polymorphism was correlated with tumor size, tumor node metastasis, and distant metastasis in BC patients.

Conclusions

LEP G19A polymorphism is associated with a less risk of BC.