bluuebunny/crossref_metadata_2025 huggingface dataset:
Verification of inflammation‐based prognostic marker as a prognostic indicator in hepatocellular carcinoma
Authors: Yamamoto Masateru , Kobayashi Tsuyoshi , Kuroda Shintaro , Hamaoka Michinori , Okimoto Sho , Honmyo Naruhiko , Yamaguchi Megumi , Ohdan Hideki
Published: September 2019

Aim

Although inflammation‐based markers in cancer have been used for prognostic prediction, the most useful marker for hepatocellular carcinoma (HCC) has not been established. We investigated the usefulness of various inflammation‐based markers in HCC patients after hepatectomy.

Methods

A total of 478 patients who underwent initial hepatectomy for HCC from 2009 to 2015 and were diagnosed with pathological HCC were included in this retrospective study. Inflammation‐based markers consisted of the C‐reactive protein to albumin ratio (CAR), Glasgow prognostic score (GPS), neutrophil to lymphocyte ratio, lymphocyte to monocyte ratio, platelet to lymphocyte ratio and prognostic index. Univariate and multivariate analyses for overall survival (OS) and disease‐free survival (DFS) using the Cox proportional hazard model were carried out. Kaplan‐Meier analysis and log‐rank test were used for comparison of OS and DFS. To reduce influences of selection bias and confounders for stratifying CAR, clinicopathological characteristics of patients were balanced by propensity score matching.

Results

Multivariate analysis identified only high CAR (>0.027) as an indicator of poor OS, and high CAR and high GPS (1‐2) as indicators of poor DFS among inflammation‐based markers. After propensity score matching, 124 patients each with low CAR and high CAR were matched. High CAR was correlated with both poor OS and DFS.

Conclusion

C‐reactive protein to albumin ratio was the most valuable prognostic indicator after hepatectomy for HCC among inflammation‐based markers.
Pathological complete response (pCR) with or without the residual intraductal carcinoma component following preoperative treatment for pancreatic cancer: Revisiting the definition of “pCR” from the prognostic standpoint
Authors: Yamada Daisaku , Takahashi Hidenori , Asukai Kei , Hasegawa Shinichiro , Tomokuni Akira , Wada Hiroshi , Akita Hirofumi , Yasui Masayohi , Miyata Hiroshi , Ishikawa Osamu
Published: September 2019

Background and Aim

There are no previous reports describing the prognostic significance of the residual intraductal carcinoma component (carcinoma in situ [CIS]) following preoperative treatment for pancreatic ductal adenocarcinoma (PDAC). The aim of the present study was to investigate the prognostic significance of a minimal residual CIS in cases with complete absence of an invasive component after preoperative treatment for PDAC.

Methods

Eighty‐one of 594 PDAC patients with preoperative treatment and subsequent surgery in our institute showed remarkable remission in the invasive component, which included 48 patients with the minimal residual invasive component (Min‐inv group) and 33 with absence of an invasive component (No‐inv group). We assessed the survival of these patients in association with the presence or absence of an invasive component and intraductal CIS.

Results

Five‐year overall survival in the No‐inv group patients was significantly better than that of the Min‐inv group patients (82%/66%, P = .041). Among the 33 patients in the No‐inv group, residual CIS was observed in 16 patients (CIS‐positive group), and the remaining 17 patients had no residual CIS (CIS‐negative group). There was no significant difference in survival between patients in the CIS‐positive and CIS‐negative groups (92%/78%, P = .31).

Conclusions

Residual CIS in the absence of an invasive component after preoperative treatment does not yield a prognostic impact after receiving perioperative treatment for PDAC. It might be reasonable to define pathological complete response (pCR) from the prognostic standpoint as follows: pCR is the complete absence of an invasive carcinoma component regardless of residual CIS.
Comparative analyses of workers' compensation claims of injury among temporary and permanent employed workers in Ohio
Authors: Al‐Tarawneh Ibraheem S. , Wurzelbacher Steven J. , Bertke Stephen J.
Published: September 2019

Background

A small but increasing number of studies have examined the risk of injury among temporary workers compared to that among workers in permanent employer arrangements. The purpose of this study was to conduct a comparative analysis of injury risk among temporary and permanent employer workers using a large dataset of workers' compensation (WC) claims of injury.

Methods

Over 1.3 million accepted WC claims in Ohio during the years 2001 to 2013 were analyzed, including 45 046 claims from workers employed by temporary services agencies. General descriptive statistics, injury rates and rate ratios (temporary to permanent workers) were calculated by injury type and event, industry group, and industry manual classes.

Results

Injured temporary workers were younger and had less tenure compared to injured permanent workers. Temporary workers had higher injury rates, and lower lost‐time and medical costs. Differences in injury rates between temporary and permanent workers varied by injury event, industry, and manual class.

Conclusion

Temporary workers had higher overall injury rates than permanent workers, controlling for industry manual class. These differences were pronounced for certain industries and injury events. We were not able to control for age and tenure of the worker, so it is not clear how these factors affected observed results. These findings were mostly similar to those from other studies using WC data from the states of Washington and Illinois. Together, these studies provide insights to improve injury prevention among temporary workers, however, additional research is still needed to improve safety and health programming for this group of workers.
Stabilized Carbenium Ions as Latent, Z‐type Ligands
Authors: Wilkins Lewis C. , Kim Youngmin , Litle Elishua D. , Gabbaï François P.
Published: September 2019

Controlling the reactivity of transition metals using secondary, σ‐accepting ligands is an active area of investigation that is impacting molecular catalysis. Herein we describe the phosphine gold complexes [(o‐Ph2P(C6H4)Acr)AuCl]+ ([3]+; Acr=9‐N‐methylacridinium) and [(o‐Ph2P(C6H4)Xan)AuCl]+ ([4]+; Xan=9‐xanthylium) where the electrophilic carbenium moiety is juxtaposed with the metal atom. While only weak interactions occur between the gold atom and the carbenium moiety of these complexes, the more Lewis acidic complex [4]+ readily reacts with chloride to afford a trivalent phosphine gold dichloride derivative (7) in which the metal atom is covalently bound to the former carbocationic center. This anion‐induced AuI/AuIII oxidation is accompanied by a conversion of the Lewis acidic carbocationic center in [4]+ into an X‐type ligand in 7. We conclude that the carbenium moiety of this complex acts as a latent Z‐type ligand poised to increase the Lewis acidity of the gold center, a notion supported by the carbophilic reactivity of these complexes.
A Supramolecular Electrolyte for Lithium‐Metal Batteries
Authors: Xie Jin , Li Bo‐Quan , Song Yun‐Wei , Peng Hong‐Jie , Zhang Qiang
Published: September 2019

Lithium‐metal batteries are regarded as one of the most promising energy storage systems, but they suffer from safety and stability problems owing to unstable liquid electrolytes. To solidify the electrolyte is an effective strategy to promote the strength and stability of the electrolyte‐electrode interfaces. However, solidified electrolytes are commonly inferior in bulk and interfacial ion conductivity, rendering unsatisfactory battery performances. Herein, a novel supramolecular electrolyte with high bulk and interfacial ion conductivity is proposed for Li‐metal batteries. Supramolecular interactions with oriented assembly and moderate bonding energies endow the lithium‐ion transport with low resistance. Additional advantages of flexibility and plasticity improve the interfacial properties. Consequently, the prototype supramolecular electrolyte affords a promising bulk lithium‐ion conductivity of 2.9×10−4 S cm−1, comparable interfacial resistance of 60 Ω, and a low polarity of 152 mV at 0.2 C in LiFePO4 half‐cells at room temperature (25 °C). The supramolecular electrolyte provides not only a new family of electrolyte, but also an effective strategy to promote ion transportation and reduce the interfacial resistance of lithium‐based energy storage systems.
Evaluation of Radiofrequency and Extremely Low‐Frequency Field Levels at Children's Playground Sites in Greece From 2013 to 2018
Authors: Christopoulou Maria , Karabetsos Efthymios
Published: September 2019

From 2013 to 2018, in‐situ measurements of radiofrequency (RF) electromagnetic fields (EMF) and extremely low‐frequency (ELF) electric and magnetic fields in 317 existing and under‐construction children's playground facilities, in 16 municipalities all over Greece, were carried out by the Greek Atomic Energy Commission (EEAE). These measurements were conducted following legislative framework established in 2009, which requires that compliance with the established exposure limits for EMFs should be verified in playground areas. The results are presented by the value of the electric field (E) and exposure ratio (Λ) for the RF EMF, as well as the value of the electric field (E) and magnetic flux density (B) for the ELF electric and magnetic fields. Statistical analysis tools were applied on measurement data and conclusions have been made, taking into consideration: (i) environment type (urban/suburban), and (ii) vicinity to any transmitting installations. Measurement results correspond to the typical EMF background levels for each environment type. Concerning the environment type, RF EMF, and ELF electric/magnetic field measurements reveal no differentiation between urban and suburban environments. Bioelectromagnetics. 2019;40:602–605. © 2019 Bioelectromagnetics Society.
The efficacy and safety of botulinum toxin type A in treatment of trigeminal neuralgia and peripheral neuropathic pain: A meta‐analysis of randomized controlled trials
Authors: Wei Jiangshan , Zhu Xiangyu , Yang Guang , Shen Jun , Xie Peng , Zuo Xiaohua , Xia Lei , Han Qiu , Zhao Ying
Published: September 2019

Background

Although recent studies have shown that botulinum toxin‐A (BTX‐A) has a good analgesic effect on trigeminal neuralgia (TN) and peripheral neuropathic pain (PNP), the quality of evidence is low due to limited data. This meta‐analysis is used to synthesize existing evidence for the treatment of these conditions with BTX‐A.

Methods

Relevant trials were accessed by using an electronic search in databases (Web of Science, PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov). Data from included randomized controlled trials (RCTs) on the efficacy and safety of BTX‐A in treating TN and PNP were extracted for meta‐analysis.

Results

Finally, 10 RCTs (n = 391) were included in this meta‐analysis. The pooled effect of BTX‐A was superior to placebo based on pain intensity (SMD = −0.48, 95% CI [−0.74, 0.23] at 1 month, SMD = −0.58, 95% CI [−0.91, −0.24] at 2 months, and SMD = −0.55, 95% CI [−0.87, −0.22] at 3 months). Number needed to treat (NNT) for 50% pain intensity reduction showed better effect of BTX‐A on TN and postherpetic neuralgia (PN). Adverse events associated with BTX‐A were similar to placebo (OR = 1.58, 95% CI [0.51, 4.87], p = .424).

Conclusion

Pooled data from our meta‐analysis suggest that BTX‐A is efficacious and safe in treating TN and PNP. However, due to the limited sample size and heterogeneity, further larger and well‐designed RCTs are imperative to validate these findings.
Bis‐Cyclometalated Indazole Chiral‐at‐Rhodium Catalyst for Asymmetric Photoredox Cyanoalkylations
Authors: Steinlandt Philipp S. , Zuo Wei , Harms Klaus , Meggers Eric
Published: September 2019

A new class of bis‐cyclometalated rhodium(III) catalysts containing two inert cyclometalated 6‐tert‐butyl‐2‐phenyl‐2H‐indazole ligands and two labile acetonitriles is introduced. Single enantiomers (>99 % ee) were obtained through a chiral‐auxiliary‐mediated approach using a monofluorinated salicyloxazoline. The new chiral‐at‐metal complex is capable of catalyzing the visible‐light‐induced enantioselective α‐cyanoalkylation of 2‐acyl imidazoles in which it serves a dual function as the chiral Lewis acid catalyst for the asymmetric radical chemistry and at the same time as the photoredox catalyst for the visible‐light‐induced redox chemistry (up to 80 % yield, 4:1 d.r., and 95 % ee, 12 examples).
Fluorescent Short‐Stranded Helical Foldamers Based on L‐shaped Dibenzopyrrolo[1,2‐a][1,8]naphthyridine
Authors: Tateno Kotaro , Ono Kosuke , Kawai Hidetoshi
Published: September 2019

Helical structures were constructed by using π‐spacer‐bridged dimers of dibenzopyrrolo[1,2‐a][1,8]naphthyridine, which has a highly fluorescent L‐shaped π‐extended skeleton. Three dimers with biphenylene (dimer 1), phenanthrene (dimer 2), and m‐phenylene (dimer 3) spacers, as well as a fixed‐helical dimer 4 where two quinolone rings were covalently cross‐linked, were designed and prepared. 1H NMR and ROESY spectra revealed that dimers 1 and 2 adopted helical forms in solution, whereas dimer 3 did not. The helical conformation of 1 was strengthened by addition of either polar or nonpolar solvents to the chloroform solution, which suggested that π–π stacking was the main contributor to the stabilization of the helical structure. All of the dimers, including fixed‐helical dimer 4, emitted fluorescence with high quantum yields (ϕ=0.79–0.86).
Microalgae and Clean Technologies: A Review
Authors: de Souza Maiara Priscilla , Hoeltz Michele , Brittes Benitez Lisianne , Machado Ênio Leandro , de Souza Schneider Rosana de Cassia
Published: September 2019

The search for clean technologies needs to be continued to offer alternatives for achieving sustainable energy production and a sustainable economy. This concern is particularly related to the demands of both producing enough renewable energy to meet future needs and reducing greenhouse gas (GHG) emissions. Microalgae are recognized for several benefits they offer, and in recent years, the use of life cycle assessment (LCA) to evaluate the benefits resulting from microalgae cultivation, harvesting/dewatering, biomass drying, extraction, and byproduct development has stimulated research in this area. Considering the importance of microalgae and clean technologies and the increasing number of publications on these subjects, this review aims to perform bibliometric mapping of such studies from 2008 to 2018. Web of Science and Scopus databases are used to identify leading trends. Visualization of similarities viewer (VOSviewer) software is applied to analyze the interactions among keywords. The results of this study indicate an association of microalgae and clean technologies and demonstrate that LCA is one of the most common tools used for such analyses. Bibliometric mapping provides relevant data to reinforce this association and understand the main bottlenecks that must be overcome in this field for future progress to be made.
Using MetaboAnalyst 4.0 for Comprehensive and Integrative Metabolomics Data Analysis
Authors: Chong Jasmine , Wishart David S. , Xia Jianguo
Published: September 2019

MetaboAnalyst (https://www.metaboanalyst.ca) is an easy‐to‐use web‐based tool suite for comprehensive metabolomic data analysis, interpretation, and integration with other omics data. Since its first release in 2009, MetaboAnalyst has evolved significantly to meet the ever‐expanding bioinformatics demands from the rapidly growing metabolomics community. In addition to providing a variety of data processing and normalization procedures, MetaboAnalyst supports a wide array of functions for statistical, functional, as well as data visualization tasks. Some of the most widely used approaches include PCA (principal component analysis), PLS‐DA (partial least squares discriminant analysis), clustering analysis and visualization, MSEA (metabolite set enrichment analysis), MetPA (metabolic pathway analysis), biomarker selection via ROC (receiver operating characteristic) curve analysis, as well as time series and power analysis. The current version of MetaboAnalyst (4.0) features a complete overhaul of the user interface and significantly expanded underlying knowledge bases (compound database, pathway libraries, and metabolite sets). Three new modules have been added to support pathway activity prediction directly from mass peaks, biomarker meta‐analysis, and network‐based multi‐omics data integration. To enable more transparent and reproducible analysis of metabolomic data, we have released a companion R package (MetaboAnalystR) to complement the web‐based application. This article provides an overview of the main functional modules and the general workflow of MetaboAnalyst 4.0, followed by 12 detailed protocols: © 2019 by John Wiley & Sons, Inc.

Basic Protocol 1: Data uploading, processing, and normalization

Basic Protocol 2: Identification of significant variables

Basic Protocol 3: Multivariate exploratory data analysis

Basic Protocol 4: Functional interpretation of metabolomic data

Basic Protocol 5: Biomarker analysis based on receiver operating characteristic (ROC) curves

Basic Protocol 6: Time‐series and two‐factor data analysis

Basic Protocol 7: Sample size estimation and power analysis

Basic Protocol 8: Joint pathway analysis

Basic Protocol 9: MS peaks to pathway activities

Basic Protocol 10: Biomarker meta‐analysis

Basic Protocol 11: Knowledge‐based network exploration of multi‐omics data

Basic Protocol 12: MetaboAnalystR introduction
Characterization of Human Mucosal‐associated Invariant T (MAIT) Cells
Authors: Souter Michael N.T. , Loh Liyen , Li Shihan , Meehan Bronwyn S. , Gherardin Nicholas A. , Godfrey Dale I. , Rossjohn Jamie , Fairlie David P. , Kedzierska Katherine , Pellicci Daniel G. , Chen Zhenjun , Kjer‐Nielsen Lars , Corbett Alexandra J. , McCluskey James , Eckle Sidonia B. G.
Published: September 2019

Mucosal‐associated invariant T (MAIT) cells are a subset of unconventional T cells restricted by the major histocompatibility complex (MHC) class I–like molecule MHC‐related protein 1 (MR1). MAIT cells are found throughout the body, especially in human blood and liver. Unlike conventional T cells, which are stimulated by peptide antigens presented by MHC molecules, MAIT cells recognize metabolite antigens derived from an intermediate in the microbial biosynthesis of riboflavin. MAIT cells mediate protective immunity to infections by riboflavin‐producing microbes via the production of cytokines and cytotoxicity. The discovery of stimulating MAIT cell antigens allowed for the development of an analytical tool, the MR1 tetramer, that binds specifically to the MAIT T cell receptor (TCR) and is becoming the gold standard for identification of MAIT cells by flow cytometry. This article describes protocols to characterize the phenotype of human MAIT cells in blood and tissues by flow cytometry using fluorescently labeled human MR1 tetramers alongside antibodies specific for MAIT cell markers. © 2019 by John Wiley & Sons, Inc.

The main protocols include:

Basic Protocol 1: Determining the frequency and steady‐state surface phenotype of human MAIT cells

Basic Protocol 2: Determining the activation phenotype of human MAIT cells in blood

Basic Protocol 3: Characterizing MAIT cell TCRs using TCR‐positive reporter cell lines

Alternate protocols are provided for determining the absolute number, transcription factor phenotype, and TCR usage of human MAIT cells; and determining activation phenotype by staining for intracellular markers, measuring secreted cytokines, and measuring fluorescent dye dilution due to proliferation. Additional methods are provided for determining the capacity of MAIT cells to produce cytokine independently of antigen using plate‐bound or bead‐immobilized CD3/CD28 stimulation; and determining the MR1‐Ag dependence of MAIT cell activation using MR1‐blocking antibody or competitive inhibition. For TCR‐positive reporter cell lines, methods are also provided for evaluating the MAIT TCR‐mediated MR1‐Ag response, determining the capacity of the reporter lines to produce cytokine independently of antigen, determining the MR1‐Ag dependence of the reporter lines, and evaluating the MR1‐Ag response of the reporter lines using IL‐2 secretion.

Support Protocols describe the preparation of PBMCs from human blood, the preparation of single‐cell suspensions from tissue, the isolation of MAIT cells by FACS and MACS, cloning MAIT TCRα and β chain genes and MR1 genes for transduction, generating stably and transiently transfected cells lines, generating a stable MR1 knockout antigen‐presenting cell line, and generating monocyte‐derived dendritic cells.
Nonrandomized Real‐World Evidence to Support Regulatory Decision Making: Process for a Randomized Trial Replication Project
Authors: Franklin Jessica M. , Pawar Ajinkya , Martin David , Glynn Robert J. , Levenson Mark , Temple Robert , Schneeweiss Sebastian
Published: September 2019

Recent legislation mandates that the US Food and Drug Administration issue guidance regarding when real‐world evidence (RWE) could be used to support regulatory decision making. Although RWE could come from randomized or nonrandomized designs, there are significant concerns about the validity of RWE assessing medication effectiveness based on nonrandomized designs. We propose an initiative using healthcare claims data to assess the ability of nonrandomized RWE to provide results that are comparable with those from randomized controlled trials (RCTs). We selected 40 RCTs, and we estimate that approximately 30 attempted replications will be completed after feasibility analyses. We designed an implementation process to ensure that each attempted replication is consistent, transparent, and reproducible. This initiative is the first to systematically evaluate the ability of nonrandomized RWE to replicate multiple RCTs using a structured process. Results from this study should provide insight on the strengths and limitations of using nonrandomized RWE from claims for regulatory decision making.
A Mechanism Investigation of how the Alloying Effect Improves the Photocatalytic Nitrate Reduction Activity of Bismuth Oxyhalide Nanosheets
Authors: Wang Liyan , Guo Sheng‐qi , Chen Yantao , Pan Meilan , Ang Edison Huixiang , Yuan Zhi‐hao
Published: September 2019

Alloyed bismuth oxyhalides have been widely used in photocatalytic water treatment processes due to their superior photocatalytic activity. However, there is no report on the removal of NO3− for alloyed bismuth oxyhalides, and the mechanism of the effect of alloying on NO3− reduction activity is still unclear. In this work, we prepared a series of BiOClnBr1‐n (0≤n≤1) with different Cl/Br ratios but with controlled similar morphologies, and explored their catalytic activities on reducing NO3− under visible light irradiation. Density functional theory investigations revealed that the formation energy for an oxygen (O) vacancy on the surface of BiOClnBr1‐n alloys is clearly reduced in comparison with the monohalide, illustrating that more O vacancies can be produced on the surface of BiOClnBr1‐n alloys. A high concentration of O vacancies not only promotes the adsorption of NO3− but also enhances the separation efficiency of the photogenerated electron‐hole (e–h) pairs, with both being beneficial to enhance the photocatalytic activity of BiOClnBr1‐n alloys for NO3− reduction. These new discoveries not only promote the design and development of new photocatalysts with excellent NO3− reduction properties, but also help to understand the relationship between alloying effects and semiconductor photocatalytic properties.
Reported Participation Benefits in International HIV Prevention Research with People Who Inject Drugs
Authors: Sugarman Jeremy , Trumble Ilana , Hamilton Erica , Sarasvita Riza , Dumchev Kostyantyn , Viet Ha , Hoffman Irving , Miller William , Hanscom Brett
Published: September 2019

Given ethical concerns about research involving people who inject drugs and those affected by HIV, identifying potential participation benefits is important. We evaluated participant‐reported benefits in a trial conducted in Indonesia, Ukraine, and Vietnam that assessed an intervention combining psychosocial counseling and referral for antiretroviral therapy and substance use treatment for HIV‐infected people who use drugs. Reported benefits were aggregated into three groups: clinical (antiretroviral therapy, reduced cravings, reduced drug use, lab testing, medical referral, mental health, physical health), social (employment, financial, relationships, reduced stigma), and general (gained knowledge, life improvement). Overall, 438 index participants (90.5%) and 642 injection partners (83.1%) reported at least one benefit. Significantly more index participants who received the study intervention reported at least one benefit versus those who received the standard of care. Clinical trial participation can provide broad direct and indirect benefits for stigmatized populations, which has implications for assessing the ethical appropriateness of studies with such populations.
Randomization Among: The Other Randomization
Authors: Barnbaum Deborah R.
Published: September 2019

A valid informed consent process for a randomized controlled trial requires the disclosure to potential participants that they will be randomized to receive the study intervention or a control intervention. This is a case of randomizationwithina trial, a type of randomization that has received significant attention in research ethics. When institutions recruit large numbers of research participants for multisite clinical trials, a different, hidden form of randomization may occur: randomizationamongclinical trials. If it is essential to disclose to potential participants randomizationwithina clinical trial, then it may be the case that randomizationamongclinical trials recruiting individuals from the same cohort of eligible participants should also be disclosed. This article examines how randomization among clinical trials might take place and the ethical issues such randomization raises about informed consent to research participation.
The cresting wave: larval settlement and ocean temperatures predict change in the American lobster harvest
Authors: Oppenheim Noah G. , Wahle Richard A. , Brady Damian C. , Goode Andrew G. , Pershing Andrew J.
Published: September 2019

Adding to the challenge of predicting fishery recruitment in a changing environment is downscaling predictions to capture locally divergent trends over a species’ range. In recent decades, the American lobster (Homarus americanus) fishery has shifted poleward along the northwest Atlantic coast, one of the most rapidly warming regions of the world's oceans. Building on evidence that early post‐settlement life stages predict future fishery recruitment, we describe enhancements to a forecasting model that predict landings using an annual larval settlement index from 62 fixed sites among 10 study areas from Rhode Island, USA to New Brunswick, Canada. The model is novel because it incorporates local bottom temperature and disease prevalence to scale spatial and temporal changes in growth and mortality. For nine of these areas, adding environmental predictors significantly improved model performance, capturing a landings surge in the eastern Gulf of Maine, and collapse in southern New England. On the strength of these analyses, we project landings within the next decade to decline to near historical levels in the Gulf of Maine and no recovery in the south. This approach is timely as downscaled ocean temperature projections enable decision makers to assess their options under future climate scenarios at finer spatial scales.
Temperature and storage time strongly affect the germination success of perennial Euphorbia species in Mediterranean regions
Authors: Cristaudo Antonia , Catara Stefania , Mingo Antonio , Restuccia Alessia , Onofri Andrea
Published: September 2019

This study aims to explore the effect of environmental factors (temperature, light, storage time) on germination response and dormancy patterns in eight Mediterranean native wildplants, belonging to the Euphorbia L. genus. In detail, we considered E. amygdaloides subsp. arbuscula, E. bivonae subsp. bivonae, E. ceratocarpa, E. characias, E. dendroides, E. melapetala, E. myrsinites, and E. rigida. We collected seeds from natural plant populations and performed germination assays in climatic chambers at seven constant temperatures (from 5 to 35°C, with 5°C increments), and four fluctuating temperature regimes (8/15, 8/20, 8/25, and 8/30°C, with a 12/12 hr thermoperiod). Germination assays were set up both in dark (D) and in light/dark conditions (L/D, 12/12 hr photoperiod), after short and long seed storage (SS around 30 days and LS around 150 days). For all these species, except E. amygdaloides subsp. arbuscula, results show that the final germinated proportions were improved by a long storage period (>150 days), which supports the existence of nondeep physiological dormancy. Optimal temperature levels ranged from 14.3 to 21.3°C and base temperatures ranged from 5.6 to 12.1°C, while ceiling temperatures from 25.6 to 34.7°C. For none of these species, germinations were favored by an alternating daily temperature regime, while in several instances, germinations were quicker and more complete in darkness, than in an alternating light/dark regime. In some instances, extreme temperature levels (5 and 30°C) induced dormancy and germinations did not resume when seeds were exposed at optimal temperature levels. Results are discussed in terms of the dynamics of emergences and how this might be affected by climate changes.
Host plant use of a polyphagous mirid, Apolygus lucorum: Molecular evidence from migratory individuals
Authors: Wang Qian , Bao Weifang , Zhang Qian , Fu Xiaowei , Yang Yizhong , Lu Yanhui
Published: September 2019

While the host plant use of insect herbivores is important for understanding their interactions and coevolution, field evidence of these preferences is limited for generalist species. Molecular diet analysis provides an effective option for gaining such information, but data from field‐sampled individuals are often greatly affected by the local composition of their host plants. The polyphagous mirid bug Apolygus lucorum (Meyer‐Dür) seasonally migrates across the Bohai Sea, and molecular analysis of migrant bugs collected on crop‐free islands can be used to estimate the host plant use of A. lucorum across the large area (northern China) from where these individuals come. In this study, the host plant use of A. lucorum adults was determined by identifying plant DNA using a three‐locus DNA barcode (rbcL, trnH‐psbA, and ITS) in the gut of migrant individuals collected on Beihuang Island. We successfully identified the host plant families of A. lucorum adults, and the results indicated that captured bugs fed on at least 17 plant families. In addition, gut analyses revealed that 35.9% of A. lucorum individuals fed on multiple host plants but that most individuals (64.1%) fed on only one plant species. Cotton, Gossypium hirsutum L., DNA was found in 35.8% of the A. lucorum bugs examined, which was much higher than the percentage of bugs in which other host plants were found. Our work provides a new understanding of multiple host plant use by A. lucorum under natural conditions, and these findings are available for developing effective management strategies against this polyphagous pest species.
Synthesis, Solid State, Solution and ESI‐MS Studies of Zinc(II) Cluster Complexes with a Branched Mixed Donor Thiolate Ligand
Authors: Ritz Mikhaila D. , Gerhard Alison C. , Pike Robert D. , Bebout Deborah C.
Published: September 2019

Synthesis of the unusual spirobicyclic pentanuclear complex [Zn((ZnL)2(µ‐OH))2](ClO4)4·CH3CN·7H2O (1) (LH = N‐(2‐pyridylmethyl)‐N‐(2‐(methylthio)ethyl)‐N‐(2‐thioethyl)‐amine is described. Compound 1 was thoroughly characterized by a combination of X‐ray crystallography, XPRD, IR, variable temperature 1H NMR and ESI‐MS. The peripheral zinc ions of 1 have distorted trigonal bipyramidal coordination geometry provided by the NN′SS′ donor set of one L and a µ2‐hydroxido bridge to another peripheral zinc ion. The central zinc atom has a distorted tetrahedral Zn(SR)4 coordination environment provided by four µ2‐thiolate bridges from L. In crystalline form, the complex ions of 1 are largely insulated from contact by an elaborate hydrogen bond network involving µ2‐hydroxido bridges, perchlorate ions and all the solvent molecules. Dissociation of 1 in CD3CN solution and recombination to form other multinuclear complexes was investigated by variable temperature 1H NMR.
RPB5‐Mediating Protein Promotes Cholangiocarcinoma Tumorigenesis and Drug Resistance by Competing With NRF2 for KEAP1 Binding
Authors: Wan Zheng‐Hua , Jiang Tian‐Yi , Shi Yuan‐Yuan , Pan Yu‐Fei , Lin Yun‐Kai , Ma Yun‐Han , Yang Chun , Feng Xiao‐Fan , Huang Li‐Feng , Kong Xiao‐Ni , Ding Zhi‐Wen , Tan Ye‐Xiong , Dong Li‐Wei , Wang Hong‐Yang
Published: September 2019

Background and Aims

Cancer cell survival depends on the balance between reactive oxygen species production and scavenging, which is regulated primarily by NRF2 during tumorigenesis. Here, we demonstrate that deletion of RBP5‐mediating protein (RMP) in an autonomous mouse model of intrahepatic cholangiocarcinoma (ICC) delays tumor progression.

Approach and Results

RMP‐overexpressing tumor cells exhibited enhanced tolerance to oxidative stress and apoptosis. Mechanistically, RMP competes with NRF2 for binding to the Kelch domain of KEAP1 (Kelch‐like ECH‐associated protein 1) through the E**E motif, leading to decreased NRF2 degradation via ubiquitination, thus increasing NRF2 nuclear translocation and downstream transactivation of antioxidant genes. This RMP‐KEAP1‐NRF2 axis promotes ICC tumorigenesis, metastasis, and drug resistance. Consistent with these findings, the RMP level in human ICC is positively correlated with the protein level of NRF2 and is associated with poor prognosis.

Conclusion

These findings reveal that RMP is involved in the oxidative stress defense program and could be exploited for targeted cancer therapies.
Twenty‐five years after its publication, innovative solutions to the three delays model are essential
Authors: Harrison Margo S. , Yarinbab Teklemariam , Liyew Tewodros , Kirub Ephrem , Teshome Biruk , Muldrow Margaret
Published: September 2019

Twenty‐five years after its publication, the Three Delays Model still appears to be a relevant model for rural southwest Ethiopia.
Analysis of differential expression profile of miRNA in peripheral blood of patients with lung cancer
Authors: He Qingfang , Fang Yirong , Lu Feng , Pan Jin , Wang Lixin , Gong Weiwei , Fei Fangrong , Cui Jingjie , Zhong Jieming , Hu Ruying , Liang Mingbin , Fang Le , Wang Hao , Yu Min , Zhang Zuo‐Feng
Published: September 2019

Purpose

To identify potential molecular targets for lung cancer intervention and diagnosis, we analyzed the differential miRNA expression of peripheral blood between lung cancer patients and healthy controls.

Methods

Three pairs of cases’ and controls’ peripheral blood samples were evaluated for miRNA expression by microarray. 12 miRNAs were selected for RT‐PCR validation and target genes prediction. In addition, 4 miRNAs were selected for future validation by RT‐PCR in a large sample of 145 cases and 55 frequency‐matched healthy controls.

Results

A total of 338 differentially expressed miRNAs were screened and identified by microarray. According to the fold changes, the top ten upregulated miRNAs were hsa‐miR‐124‐3p, hsa‐miR‐379‐5p, hsa‐miR‐3655, hsa‐miR‐450b‐5p, hsa‐miR‐29a‐5p, hsa‐miR‐200a‐3p, hsa‐miR‐542‐3p, hsa‐miR‐138‐5p, hsa‐miR‐219a‐2‐3p, and hsa‐miR‐4701‐3p, and the top ten downregulated miRNAs were hsa‐miR‐34c‐5p, hsa‐miR‐135a‐5p, hsa‐miR‐132‐3p, hsa‐miR‐3178, hsa‐miR‐4449, hsa‐miR‐4999‐3p, hsa‐miR‐1246, hsa‐miR‐4424, hsa‐miR‐1252‐5p, and hsa‐miR‐24‐2‐5p. RT‐PCR verification of the 12 miRNAs revealed that 5 of 8 upregulated miRNAs, 2 of 4 downregulated miRNAs showed a significant difference between the cases and controls (P < .05). A large number of target genes and their functional set showed overlapping among the 453 predicted target genes of the 12 miRNAs (P < .01). RT‐PCR in the large sample confirmed the significant differential expression level of hsa‐miR‐29a‐5p, hsa‐miR‐135a‐5p, hsa‐miR‐542‐3p, and hsa‐miR‐4491 between cases and controls (P < .05), and three of these microRNA, except hsa‐miR‐29a‐5p, were significant after Bonferroni correction for adjustment of multiple comparisons.

Conclusion

There was a significant difference in miRNAs expression in the peripheral blood between lung cancer patients and healthy controls, and 4 miRNAs were validated by a large‐size sample.
Emergence and transmission of New Delhi metallo‐beta‐lactamase‐5‐producing Escherichia coli Sequence Type 361 in a Tertiary Hospital in South Korea
Authors: Park Yumi , Choi Qute , Kwon Gye Cheol , Koo Sun Hoe
Published: September 2019

Background

The emergence of carbapenem‐resistant Escherichia coli (E coli) is a serious global health threat, but little is known about carbapenemase‐producing E coli in Daejeon, South Korea. The aim of this study was to investigate characteristics of thirteen carbapenem‐resistant E coli isolates in a tertiary hospital.

Methods

Thirteen non‐duplicate carbapenem‐resistant E coli strains were collected from October 2017 to January 2018. Antimicrobial susceptibility was determined with the E test or disk diffusion method. The carbapenem minimum inhibitory concentrations (MICs) were determined by the agar dilution method. The colistin and tigecycline MICs were determined by broth microdilution. The resistance genes, including carbapenemase genes, were evaluated by polymerase chain reaction, and DNA sequencing was performed to characterize the genes. Pulsed‐field gel electrophoresis and multilocus sequence typing (MLST) were performed to evaluate the clonal relatedness of isolates. The clinical data of patients were retrospectively reviewed.

Results

All the E coli isolates harbored blaNDM‐5 gene and were resistant to most of the antimicrobial agents, such as carbapenem, cephalosporins, ciprofloxacin, and chloramphenicol, excluding amikacin and colistin. Other resistant genes, such as blaTEM‐1, blaCTX‐M‐15, blaCMY‐2, aac(6')‐Ib‐cr, and qepA, were detected. The E coli isolates harboring blaNDM‐5 belonged to ST361 (n = 11), ST12 (n = 1), ST410 (n = 1), and PFGE types A (n = 11), B (n = 1), and C (n = 1).

Conclusions

This study reports on an outbreak of a predominant epidemic clone, the NDM‐5 producing, multidrug‐resistant E coli ST361 isolate. These findings suggest that we should pay attention to infection control measures to limit the spread of NDM‐5‐producing pathogens.
Linc‐ROR regulates apoptosis in esophageal squamous cell carcinoma via modulation of p53 ubiquitination by targeting miR‐204‐5p/MDM2
Authors: Gao Han , Wang Tian , Zhang Peng , Shang Muhe , Gao Zhikui , Yang Fei , Liu Ran
Published: September 2019

The long intergenic noncoding RNA, regulator of reprogramming (linc‐ROR) has been reported to participate in tumorigenesis, while its functions and fundamental mechanisms in esophageal squamous cell carcinoma (ESCC) remain unclear. In this study, gain‐of‐function assays showed that linc‐ROR upregulation enhanced cell viability, promoted cell proliferation, and inhibited apoptosis. Mechanistically, the regulatory network of linc‐ROR/miR‐204‐5p/MDM2 was established with bioinformatics analysis and online databases, then validated via dual‐luciferase reporter assays, RNA immunoprecipitation assays in ESCC cells. Linc‐ROR positively regulates the expression of MDM2 as a molecular sponge of miR‐204‐5p. Moreover, results of western blot and coimmunoprecipitation indicated that linc‐ROR overexpression enhanced the ubiquitination level of p53, and its downstream apoptosis‐related genes have showed higher bcl‐2 expression, lower bax, and cleaved caspase‐3 expressions, while miR‐204‐5p could counteract with this effect. Finally, small interfering RNAs tailored to linc‐ROR were established to further evaluate its effects on ESCC comprehensively. In summary, this study revealed that linc‐ROR modulated cell apoptosis and regulated p53 ubiquitination via targeting miR‐204‐5p/MDM2 axis, which provides a novel therapeutic insight into treatments for ESCC.
MicroRNA‐188‐5p promotes apoptosis and inhibits cell proliferation of breast cancer cells via the MAPK signaling pathway by targeting Rap2c
Authors: Zhu Xinying , Qiu Jinxia , Zhang Tao , Yang Yaping , Guo Shuai , Li Tianshun , Jiang Kangfeng , Zahoor Arshad , Deng Ganzhen , Qiu Changwei
Published: September 2019

Breast cancer is a common malignancy that is highly lethal with poor survival rates and immature therapeutics that urgently needs more effective and efficient therapies. MicroRNAs are intrinsically involved in different cancer remedies, but their mechanism in breast cancer has not been elucidated for prospective treatment. The function and mechanism of microRNA‐188‐5p (miR‐188) have not been thoroughly investigated in breast cancer. In our study, we found that the expression of miR‐188 in breast cancer tissues was obviously reduced. Our findings also revealed the abnormal overexpression of miR‐188 in 4T1 and MCF‐7 cells significantly suppressed cell proliferation and migration and also enhanced apoptosis. miR‐188 induced cell cycle arrest in the G1 phase. To illuminate the molecular mechanism of miR‐188, Rap2c was screened as a single target gene by bioinformatics database analysis and was further confirmed by dual‐luciferase assay. Moreover, Rap2c was found to be a vital molecular switch for the mitogen‐activated protein kinase signaling pathway in tumor progression by decreasing apoptosis and promoting proliferation and migration. In conclusion, our results revealed that miR‐188 is a cancer progression suppressor and a promising future target for breast cancer therapy.
JNK‐IN‐8, a c‐Jun N‐terminal kinase inhibitor, improves functional recovery through suppressing neuroinflammation in ischemic stroke
Authors: Zheng Jianjian , Dai Qinxue , Han Kunyuan , Hong Wandong , Jia Danyun , Mo Yunchang , Lv Ya , Tang Hongli , Fu Hongxing , Geng Wujun
Published: September 2019

C‐Jun N‐terminal kinase (JNK) is a pivotal MAPK (mitogen‐activated protein kinase), which activated by ischemia brain injury and plays a fairly crucial function in cerebral ischemic injury. Emerging studies demonstrated that JNK‐IN‐8 (a JNK inhibitor with high specificity) regulates traumatic brain injury through controlling neuronal apoptosis and inflammation. However, the function of JNK‐IN‐8 in ischemic stroke and the mechanisms underlying of JNK‐IN‐8 about neuroprotection are not well understood. In this work, male rats were treated with JNK‐IN‐8 after transient middle cerebral artery occlusion, and then the modified improved neurological function score (mNSS), the foot‐fault test (FFT), interleukin‐1β (IL‐1β), IL‐6, and tumor necrosis factor‐α (TNF‐α) levels were assessed. We found that JNK‐IN‐8‐treated rats with MCAO exerted an observable melioration in space learning as tested by the improved mNSS, and showed sensorimotor functional recovery as measured by the FFT. JNK‐IN‐8 also played anti‐inflammatory roles as indicated through decreased activation of microglia and decreased IL‐6, IL‐1β, and TNF‐α expression. Furthermore, JNK‐IN‐8 suppressed the activation of JNK and nuclear factor‐κB (NF‐κB) signaling as indicated by the decreased level of phosphorylated‐JNK and p65. All data demonstrate that JNK‐IN‐8 inhibits neuroinflammation and improved neurological function by inhibiting JNK/NF‐κB and is a promising agent for the prevention of ischemic brain injury.
miR‐122‐5p promotes aggression and epithelial‐mesenchymal transition in triple‐negative breast cancer by suppressing charged multivesicular body protein 3 through mitogen‐activated protein kinase signaling
Authors: Wang Zheng , Wang Xiangyu
Published: September 2019

Triple‐negative breast cancer (TNBC) is highly metastatic and frequently has a poor prognosis. The lack of comprehension of TNBC and gene therapy targets has led to limitedly effective treatment for TNBC. This study was conducted to better understand the molecular mechanism behind TNBC progression, and to find out promising gene therapy targets for TNBC. Herein the influence of miR‐122‐5p's binding charged multivesicular body protein 3 (CHMP3) 3′‐untranslated region (3′‐UTR) on in TNBC cells was investigated. in vitro experiments quantitative real‐time polymerase chain reaction, immunoblot analysis, dual‐luciferase reporter gene assay, cell counting assay, transwell invasion assay, and flow cytometry‐determined cell apoptosis assay were employed. We also used TargetScan Human 7.2 database to find out the target relationship between miR‐122‐5p and CHMP3 3′‐UTR. TImer algorithm was used to provide an overview of the expression of CHMP3 gene across human pan‐cancer, to predict the survival outcome of breast cancer patients, and to predict the correlation between CHMP3 gene expression and epithelial‐mesenchymal transition (EMT) and mitogen‐activated protein kinase (MAPK)‐related gene expression. CHMP3 gene was significantly downregulated across a wide range of human cancers including breast cancer (BRCA). A higher level of CHMP3 gene predicted a better 3‐ and 5‐year survival outcome of patients with BRCA. In our experiments, miR‐122‐5p was significantly upregulated and CHMP3 gene was significantly downregulated in TNBC cells compared with normal cell line. miR‐122‐5p mimics enhanced TNBC cell viability, proliferation, and invasion whereas the upregulation of CHMP3 gene led to an opposite outcome. Forced expression of miR‐122‐5p suppressed cell apoptosis, compelled EMT and MAPK signaling whereas forced expression of CHMP3 did the opposite. We then conclude that miR‐122‐5p promotes aggression and EMT in TNBC by suppressing CHMP3 through MAPK signaling.
Exploiting yoeB‐yefM toxin‐antitoxin system of Streptococcus pneumoniae on the selective killing of miR‐21 overexpressing breast cancer cell line (MCF‐7)
Authors: Houri Hamidreza , Ghalavand Zohreh , Faghihloo Ebrahim , Fallah Fatemeh , Mohammadi‐Yeganeh Samira
Published: September 2019

Toxin‐antitoxin (TA) systems are two‐component genetic modules widespread in bacterial and archaeal genomes, in which the toxin module is rendered inactive under resting conditions by its antitoxin counterpart. Under stress conditions, however, the antitoxin is degraded, freeing the toxin to exert its lethal effects. Although not evolved to function in eukaryotes, some studies have established the lethal activity of these bacterial toxins by inducing apoptosis in mammalian cells, an effect that can be neutralized by its cognate antitoxin. Inspired by the way the toxin can become active in eukaryotes cells, we produced an engrained yoeB‐yefM TA system to selectively kill human breast cancer cells expressing a high level of miR‐21. Accordingly, we generated an engineered yefM antitoxin gene with eight miR‐21 target sites placed in its 3′untranslated region. The resulting TA system acts autonomously in human cells, distinguishing those that overexpress miR‐21, killed by YoeB, from those that do not, remaining protected by YefM. Thus, we indicated that microRNA‐control of the antitoxin protein of bacterial TA systems constitutes a novel strategy to enhance the selective killing of human cancer cells by the toxin module. The present study provides significant insights for developing novel anticancer strategies avoiding off‐target effects, a challenge that has been pursued by many investigators over the years.