bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydrological function of rapidly induced biocrusts
Authors: Fick Stephen E. , Barger Nichole N. , Duniway Michael C.
Published: March 2019

In dryland ecosystems, land degradation and erosion pose severe threats to ecosystem productivity and human well‐being. Bio‐inoculation of degraded soils with native biological soil crusts (“biocrusts”) is a promising yet relatively untested means to improve soil stability and hydrological function (i.e., increase infiltration and reduce run‐off). In a degraded semiarid grassland on the Colorado Plateau, we studied the establishment and hydrological function (via simulated rainfall) of induced biocrusts grown with and without an organic soil stabilizer (psyllium, derived from Plantago sp.), after a period of 4 months. We found evidence of biocrust establishment, including significantly higher biocrust cover, chlorophyll a, and exopolysaccharides in inoculated plots compared with controls. Plots inoculated with biocrust had higher run‐off and sediment yields than controls during rainfall simulation. However, this effect was mitigated in plots where stabilizer was added, resulting in greater soil aggregate stability and higher levels of infiltration (reduced total run‐off). The time to ponding was significantly greater than control for all inoculated plots, suggesting that induced biocrusts may be most effective at improving infiltration under low‐intensity, smaller precipitation events. Notably, the biocrusts in this study lacked rough surface microtopography, which is common in well‐developed biocrusts regionally and likely instrumental in slowing overland flow and increasing infiltration for larger rain events. These results highlight the temporal lag that may exist between apparent and functional restoration of biocrusts. In addition, the simultaneous additions of stabilizing amendments with biocrust inoculum may work collectively to achieve both short‐ and long‐term restoration targets.
Recruitment of hepatic macrophages from monocytes is independent of IL‐4Rα but is associated with ablation of resident macrophages in schistosomiasis
Authors: Rolot Marion , Dougall Annette M. , Javaux Justine , Lallemand François , Machiels Bénédicte , Martinive Philippe , Gillet Laurent , Dewals Benjamin G.
Published: March 2019

Alternatively activated Mφs (AAMφ) accumulate in hepatic granulomas during schistosomiasis and have been suggested to originate in the bone marrow. What is less understood is how these Mφ responses are regulated after S. mansoni infection. Here, we investigated the role of IL‐4 receptor α‐chain (IL‐4Rα)‐signalling in the dynamics of liver Mφ responses. We observed that IL‐4Rα signalling was dispensable for the recruitment of Ly6Chi monocytes and for their conversion into F4/80hiCD64hiCD11bhiMφ. Moreover, while IL‐4Rα provided an AAMφ phenotype to liver F4/80hiCD64hiCD11bhiMφ that was associated with regulation of granuloma formation, it was dispensable for host survival. Resident F4/80hiCD64hiCD11bloMφ did not upregulate the AAMφ signature gene Ym1. Rather, resident Mφ nearly disappeared by week 8 after infection and artificial ablation of resident Mφ in CD169DTR mice did not affect the response to S. mansoni infection. Interestingly, ablation of CD169+ cells in naive mice resulted in the accumulation of F4/80hiCD64hiCD11bhiMφ, which was amplified when ablation occurred during schistosomiasis. Altogether, our results suggest the ablation of resident KCs after S. mansoni infection to be associated with the recruitment and accumulation of F4/80hiCD64hiCD11bhiMφ with lyz2‐dependent IL‐4Rα contributing to the regulation of granuloma inflammation but being dispensable for host survival.
Brucella abortus nitric oxide metabolite regulates inflammasome activation and IL‐1β secretion in murine macrophages
Authors: Campos Priscila Carneiro , Gomes Marco Túlio Ribeiro , Marinho Fábio Antônio Vitarelli , Guimarães Erika Sousa , de Moura Lodi Cruz Mariza Gabriela Faleiro , Oliveira Sergio Costa
Published: March 2019

NLRP3 inflammasome is a protein complex crucial to caspase‐1 activation and IL‐1β and IL‐18 maturation. This receptor participates in innate immune responses to different pathogens, including the bacteria of genus Brucella. Our group recently demonstrated that Brucella abortus‐induced IL‐1β secretion involves NLRP3 inflammasome and it is partially dependent on mitochondrial ROS production. However, other factors could be involved, such as P2X7‐dependent potassium efflux, membrane destabilization, and cathepsin release. Moreover, there is increasing evidence that nitric oxide acts as a modulator of NLRP3 inflammasome. The aim of this study was to unravel the mechanism of NLRP3 inflammasome activation induced by B. abortus, as well as the involvement of bacterial nitric oxide (NO) as a modulator of this inflammasome pathway. We demonstrated that NO produced by B. abortus can be used by the bacteria to modulate IL‐1β secretion in infected murine macrophages. Additionally, our results suggest that B. abortus‐induced IL‐1β secretion depends on a P2X7‐independent potassium efflux, lysosomal acidification, cathepsin release, mechanisms clearly associated to NLRP3 inflammasome. In summary, our results help to elucidate the molecular mechanisms of NLRP3 activation and regulation during an intracellular bacterial infection.
Carbon Nanostructures in Rotaxane Architectures
Authors: Barrejón Myriam , Mateo‐Alonso Aurelio , Prato Maurizio
Published: March 2019

Considerable research efforts have been devoted to the development of rotaxanes and the study of their unique dynamic properties. This minireview provides an overview of the main advances that have been realized in rotaxane architectures involving different types of carbon nanostructures. In particular, rotaxanes based on fullerenes and carbon nanotubes will be discussed.
Physical activity as a prognostic factor of pain intensity and disability in patients with low back pain: A systematic review
Authors: Oliveira Crystian B. , Pinheiro Marina B. , Teixeira Renan J. , Franco Márcia R. , Silva Fernanda G. , Hisamatsu Thalysi M. , Ferreira Paulo H. , Pinto Rafael Z.
Published: March 2019

Background and objective

Identifying factors that influence the course of low back pain (LBP) is important to help clinicians to identify those patients at higher risk of non‐recovery. The objective of this systematic review was to investigate the prognostic role of physical activity in the course of LBP.

Databases and data treatment

Literature searches were conducted in five electronic databases from their inception to February 2018. Prospective cohort studies investigating the influence of any type of physical activity in people with LBP were considered eligible. The primary outcomes were pain intensity and disability. Two independent reviewers extracted the data and assessed the methodological quality of the included studies. Results were stratified according to participants’ symptoms duration at baseline.

Results

Twelve studies were considered eligible for this review. Of these, six included patients with chronic LBP, four studies did not specify the patients’ duration of symptoms, one study included patients with acute LBP, and one study included patients with subacute LBP. Included studies were heterogeneous in terms of physical activity assessment, outcomes, follow‐up duration, and statistical methods, therefore, pooling of results was not performed. We found limited evidence to support the prognostic role of physical activity in the course of LBP.

Conclusions

Our review identified limited evidence supporting physical activity as a prognostic factor in LBP. Future cohort studies are needed to clarify the strength and importance of this association.

Significance

Despite recent research in the area, this systematic review shows that there is low quality evidence that physical activity may not be a prognostic factor for predicting pain and disability in patients with LBP.
Toxin gene profiles, genetic diversity, antimicrobial resistance, and coagulase type of Staphylococcus aureus from cream‐filled bakery products
Authors: Cho Yong Sun , Lee Myung Ki , Hwang Sun Hye
Published: March 2019

We determined the toxin gene profile, toxin production, antibiotic resistance coagulase serotype, and genetic diversity of 42 coagulase‐positive Staphylococcus aureus (CPS) isolates collected from 1,464 cream‐filled bakery products in Korea. Among the CPS isolates, 37 (88.1%) produced enterotoxin genes in combination with another toxin; 26 (61.9%) of the strains were positive for sea, 1 (2.4%) for sea‐seb, and 4 (9.5%) for sea‐sec. Among the strains showing antibiotic resistance, 28 (66.7%) showed resistance to only one antibiotic, whereas nine (21.4%) showed resistance to multiple antibiotics: 4 (9.5%) strains were both mecA‐positive and oxacillin‐resistant. Most strains are resistant to at least one antibiotic—benzyl penicillin. The CPS isolates were classified into eight coagulase serotypes. This information will be valuable for assessing the capability risks of CPS food poisoning, contributing a better known of the epidemiology result associated with CPS contamination in bakery products.
Intrastrata geochemical variability of a Paleolithic bone assemblage: The case of single‐phase Gravettian site Jaksice II, southern Poland
Authors: Krajcarz Maciej T. , Wilczyński Jarosław
Published: March 2019

Bone remains constitute the portion of an archaeological assemblage that may record a geochemical signature of the depositional environment and may be used as an indicator of the homogeneity of the assemblage. However, the range of the inner chemical variability inside a single depositional bone assemblage has not been sufficiently studied. In this study, the chemical composition of 60 fossil bones excavated from a single component Paleolithic site was measured and the statistical variability of the set established via multivariate analysis. Fossil bones from a single stratum exhibited weak internal chemical variability, compared with that shown by fresh recent bones, although fossil material is significantly enriched in trace elements. Data presented here may be used as one example of chemical variability for Late Pleistocene fossil bone assemblages.
The situation or the person? Individual and task‐evoked differences in BOLD activity
Authors: Bolt Taylor , Nomi Jason S. , Bainter Sierra A. , Cole Michael W. , Uddin Lucina Q.
Published: March 2019

Investigations of between‐person variability are enjoying a recent resurgence in functional magnetic resonance imaging (fMRI) research. Several recent studies have found persistent between‐person differences in blood‐oxygenated‐level dependent (BOLD) activation patterns and resting‐state functional connectivity. Conflicting findings have been reported regarding the extent to which (a) between‐person or (b) within‐person cognitive state differences explain differences in BOLD activation patterns. These discrepancies may arise due to statistical analysis choices, parcellation resolution, and limited sampling of task‐fMRI datasets. We attempt to address these issues in a large‐scale analysis of several task‐fMRI paradigms. Using a novel application of multivariate distance matrix regression, we examine between‐person and task‐condition variability estimates across varying levels of “resolution”, from a coarse region‐of‐interest level to the vertex‐level, and across different distance metrics. These analyses revealed that under most circumstances, differences in task conditions explained a greater amount of variance in activation map differences than between‐person differences. However, this finding was reversed when comparing activation maps at a “high‐resolution” vertex level. More generally, we observed that when moving from “low” to “high” resolutions, the variance explained by between‐person differences increased while variance explained by task conditions decreased. We further analyzed the relationships among subject‐level activation maps across all task‐conditions using an unsupervised clustering approach and identified a superordinate task structure. This structure went beyond conventional task labels and highlighted those experimental manipulations across task conditions that produce contrasting versus similar whole‐brain activation patterns. Overall, these analyses suggest that the question of the subject‐ versus task‐effects on BOLD activation patterns is nontrivial, and depends on the comparison “resolution,” choice of distance metric, and the coding of task‐conditions.
Looking Into the Crystal Ball: Predicting the Future Challenges of Fibrotic NASH Treatment
Authors: Alkhouri Naim , Lawitz Eric , Noureddin Mazen
Published: March 2019

Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease worldwide, and its aggressive form of nonalcoholic steatohepatitis (NASH) is becoming a leading cause for end‐stage liver disease and liver transplantation in the United States. In patients with NASH, the presence of advanced fibrosis is considered the most important prognostic factor in predicting liver‐related morbidity and mortality. Unfortunately, there are no US Food and Drug Administration (FDA)–approved medications to treat patients with NASH‐induced advanced fibrosis. However, the field of drug development to treat NASH and fibrosis has witnessed major advances over the past 5 years with several medications in phase III trials. Results from some of these trials are expected in 2019 with potential FDA approval in 2020. Clinicians who treat patients with NAFLD are likely to face several challenges over the next few years related to identifying patients with advanced fibrosis who may derive most benefit from pharmacologic treatment, the requirement for liver biopsy to assess histologic severity and response to treatment, and the urgent need to validate noninvasive tests to replace liver biopsy—to determine treatment initiation, response, futility, and the need for combination therapy with multiple drugs. Conclusion: In this review, we aim to dissect each of these challenges and attempt to provide suggested solutions while fully realizing that knowledge gaps still exist where future research is likely to provide urgently needed answers.
Synthesis and characterization of biomimetic bioceramic nanoparticles with optimized physicochemical properties for bone tissue engineering
Authors: Ebrahimi Mehdi , Botelho Michael , Lu William , Monmaturapoj Naruporn
Published: March 2019

Calcium phosphate bioceramics nanoparticles such as nano‐hydroxyapatite (nHA) and nano‐tricalcium phosphate (nTCP) are the main focus of basic and applied research for bone tissue regeneration. In particular, a combination of these two phases (nHA + nTCP) which refers to as “nano‐biphasic calcium phosphates (nBCP)” is of interest due to the preferred biodegradation nature compared to single‐phase bioceramics. However, the available synthesis processes are challenging and the biomaterials properties are yet to be optimized to mimic the physiochemical properties of the natural nanoscale bone apatite. In this study, a new approach was developed for the production of optimized bioceramic nanoparticles aiming to improve their biomimecity for better biological performances. Nanoparticles were synthesized through a carefully controlled and modified wet mechano‐chemical method combined with a controlled solid‐state synthesis. Different processing variables have been analyzed including; milling parameters, post‐synthesis treatment, and calcination phase. Detailed physicochemical characterizations of nanoparticles revealed higher crystallinity (∼100%), lower crystallite/particle size (58 nm), higher homogeneity, reduced particle agglomeration size (6 μm), and a closer molar ratio (1.8) to biological apatite compared to control and standard samples. Furthermore, the study group was confirmed as calcium‐deficient carbonate‐substituted BCP nanoparticles (nHA/nβ‐TCP: 92/8%). As such, the introduced method can afford an easier and accurate control over nanoparticle physiochemical properties including the composition phase which can be used for better customization of biomaterials for clinical applications. The findings of this article will also help researchers in the further advancement of production strategies of biomaterials. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1654–1666, 2019.
In vivo systemic toxicity assessment of an oxidized dextrin‐based hydrogel and its effectiveness as a carrier and stabilizer of granular synthetic bone substitutes
Authors: Pereira Isabel , Fraga Sónia , Maltez Luís , Requicha João , Guardão Luísa , Oliveira Joana , Prada Justina , Alves Helena , Santos José Domingos , Teixeira João Paulo , Pereira José Eduardo , Soares Raquel , Gama Francisco Miguel
Published: March 2019

The worldwide incidence of bone disorders is raising, mainly due to aging population. The lack of effective treatments is pushing the development of synthetic bone substitutes (SBSs). Most ceramic‐based SBSs commercially available display limited handling properties. Attempting to solve these issues and achieve wider acceptance by the clinicians, granular ceramics have been associated with hydrogels (HGs) to produce injectable/moldable SBSs. Dextrin, a low‐molecular‐weight carbohydrate, was used to develop a fully resorbable and injectable HG. It was first oxidized with sodium periodate and then cross‐linked with adipic acid dihydrazide. The in vivo biocompatibility and safety of the dextrin‐based HG was assessed by subacute systemic toxicity and skin sensitization tests, using rodent models. The results showed that the HG did not induce any systemic toxic effect, skin reaction, or genotoxicity, neither impaired the bone repair/regeneration process. Then, the HG was successfully combined with granular bone substitute, registered as Bonelike (250–500 μm) to obtain a moldable/injectable SBS, which was implanted in tibial fractures in goats for 3 and 6 weeks. The obtained results showed that HG allowed the stabilization of the granules into the defect, ensuring effective handling, and molding properties of the formulation, as well as an efficient cohesion of the granules. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1678–1689, 2019.
Relationship Between Bone Mineral Density T-Score and Nonvertebral Fracture Risk Over 10 Years of Denosumab Treatment
Authors: Ferrari S , Libanati C , Lin Celia Jow Fang , Brown JP , Cosman F , Czerwiński E , de Gregόrio LH , Malouf-Sierra J , Reginster J-Y , Wang A , Wagman RB , Lewiecki EM
Published: March 2019

Although treat-to-target strategies are being discussed in osteoporosis, there is little evidence of what the target should be to reduce fracture risk maximally. We investigated the relationship between total hip BMD T-score and the incidence of nonvertebral fracture in women who received up to 10 years of continued denosumab therapy in the FREEDOM (3 years) study and its long-term Extension (up to 7 years) study. We report the percentages of women who achieved a range of T-scores at the total hip or femoral neck over 10 years of denosumab treatment (1343 women completed 10 years of treatment). The incidence of nonvertebral fractures was lower with higher total hip T-score. This relationship plateaued at a T-score between -2.0 and -1.5 and was independent of age and prevalent vertebral fractures, similar to observations in treatment-naïve subjects. Reaching a specific T-score during denosumab treatment was dependent on the baseline T-score, with higher T-scores at baseline more likely to result in higher T-scores at each time point during the study. Our findings highlight the importance of follow-up BMD measurements in patients receiving denosumab therapy because BMD remains a robust indicator of fracture risk. These data support the notion of a specific T-score threshold as a practical target for therapy in osteoporosis. © 2019 The Authors Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR)
Fluoride and diethylnitrosamine coexposure enhances oxido‐inflammatory responses and caspase‐3 activation in liver and kidney of adult rats
Authors: Owumi Solomon E. , Aliyu‐Banjo Nazirat O. , Danso Olabisi F.
Published: March 2019

The present study investigated the impact of coexposure to fluoride and diethylnitrosamine (DEN) on hepatorenal function in adult rats. The animals were exposed to fluoride (15 mg/L in drinking water) and DEN (10 mg/kg) singly or coexposed to both compounds for 14 days. Results demonstrated that the fluoride or DEN mediated increase in hepatorenal toxicity was intensified in the coexposure group. Additionally, the decrease in antioxidant enzyme activities as well as the elevation in reactive oxygen and nitrogen species, and lipid peroxidation was markedly aggravated in rats coexposed to DEN and fluoride. Furthermore, the increase in levels of nitric oxide, tumor necrosis factor‐α and interleukin‐1β, myeloperoxidase and caspase‐3 activities as well as histological lesions was more pronounced in the liver and kidney of rats coexposed to DEN and fluoride. Conclusively, coexposure to fluoride and DEN exacerbated hepatorenal damage via enhancement of oxido‐inflammatory responses and caspase‐3 activation in rats.
lncRNA mortal obligate RNA transcript was downregulated in ovarian carcinoma and inhibits cancer cell proliferation by downregulating miRNA‐21
Authors: Chen Xiao , Wu Wanyin , Cao Xiaolong , Zhao Xiaoshan , Li Weizhan , Deng Caijiu , Huang Zhen
Published: March 2019

microRNA‐21 (miRNA‐21) is a well‐characterized oncogenic miRNA in human cancers. In the present study, we found that miRNA‐21 was upregulated, while long noncoding RNA Mortal Obligate RNA Transcript (lncRNA MORT), which has been reported to be silenced in 16 types of cancers, was downregulated in tumor tissues than in adjacent healthy tissues of patients with ovarian carcinoma. Expression of lncRNA MORT in tumor tissues was found to be significantly affected by tumor size but not by tumor metastasis. Expression levels of lncRNA MORT and miRNA‐21 were significantly and inversely correlated in both tumor tissues and adjacent healthy tissues. Overexpression of lncRNA MORT inhibited miRNA‐21, while miRNA‐21 overexpression failed to significantly affect lncRNA MORT expression. Overexpression of lncRNA MORT inhibited, while miRNA‐21 overexpression promoted the proliferation of cells of ovarian cancer cell lines. In addition, miRNA‐21 overexpression partially reversed the inhibitory effects of lncRNA MORT overexpression on cancer cell proliferation. However, overexpression of lncRNA MORT showed no significant effects on cancer cell migration and invasion. Therefore, lncRNA MORT was downregulated in ovarian carcinoma and lncRNA MORT overexpression inhibited cancer cell proliferation, possibly by downregulating miRNA‐21.
Interaction and molecular dynamics simulation study of Osimertinib (AstraZeneca 9291) anticancer drug with the EGFR kinase domain in native protein and mutated L844V and C797S
Authors: Assadollahi Vahideh , Rashidieh Behnam , Alasvand Masoud , Abdolahi Alina , Lopez J. Alejandro
Published: March 2019

Background

Targeted therapy is a novel, promising approach to anticancer treatment that endeavors to overcome drug resistance to traditional chemotherapies. Patients with the L858R mutation in epidermal growth factor receptor (EGFR) respond to the first generation tyrosine kinase inhibitors (TKIs); however, after one year of treatment, they may become resistant. The T790M mutation is the most probable cause for drug resistance. Third generation drugs, including Osimertinib (AZD9291), are more effective against T790M and other sensitive mutations. Osimertinib is effective against the L844V mutation, has conditional effectiveness for the L718Q mutation, and is ineffective for the Cys797Ser (C797S) mutation. Cells that have both the T790M and C797 mutations are more resistant to third generation drugs. Although research has shown that Osimertinib is an effective treatment for EGFR L844V cells, this has not been shown for cells that have the C797S mutation. This molecular mechanism has not been well‐studied.

Methods

In the present study, we used the GROMACS software for molecular dynamics simulation to identify interactions between Osimertinib and the kinase part of EGFR in L844V and C797S mutants.

Results

We evaluated native EGFR protein and the L844V and C797S mutations’ docking and binding energy, kI, intermolecular, internal, and torsional energy parameters. Osimertinib was effective for the EGFR L844V mutation, but not for EGFR C797S. All simulations were validated by root‐mean‐square deviation (RMSD), root‐mean square fluctuation (RMSF), and radius of gyration (ROG).

Conclusion

According to our computational simulation, the results supported the experimental models and, therefore, could confirm and predict the molecular mechanism of drug efficacy.
Suppressive effect of exogenous miR‐16 and miR‐34a on tumorigenesis of breast cancer cells
Authors: Haghi Mehdi , Taha Masoumeh F. , Javeri Arash
Published: March 2019

Recent investigations have shown tumor‐suppressive roles for miR‐16 and miR‐34a. They also share some features in regard to targeting cancer cell signaling pathways which they control. Therefore, in this study, we aimed to further scrutinize whether exogenous induction of mature miR‐34a and miR‐16 can collaborate in breast tumor suppression. MDA‐MB‐231 and SK‐BR‐3 human breast cancer cell lines were cultured and transfected twice with hsa‐miR‐16‐5p and hsa‐miR‐34a‐5p mimics individually or in combination. The cells were analyzed for apoptosis rate and cell cycle indices by flow cytometry. Also, the expression of several invasion and the epithelial‐mesenchymal transition markers was evaluated at gene and protein levels by quantitative real‐time polymerase chain reaction and western blot analysis, respectively. Assessment of invasiveness and migratory potential of the transfected cells was performed using three‐dimensional spheroid formation and wound‐healing assay, respectively. In both cell lines, miR‐16 and miR‐34a induced apoptosis and cell‐cycle arrest and also suppressed invasion and migration. Some of these effects, like cell‐cycle arrest and induction of apoptosis, were significantly higher when using both microRNAs than when using them individually for transfection of the cells. Our results are indicating that miR‐16 and miR‐34a can collaborate in breast tumor suppression.
Retracted: The long noncoding RNA cardiac hypertrophy‐related factor plays oncogenic roles in hepatocellular carcinoma by downregulating microRNA‐211
Authors: Li Yichun , Li Yannan , Xu Xiangsu
Published: March 2019

Background

Hepatocellular carcinoma (HCC) is the most major type of primary hepatic cancer. This study aimed to explore the possible oncogenic effects of the long noncoding RNA cardiac hypertrophy–related factor (CHRF) on HCC, as well as the underlying possible mechanism.

Methods

The expression levels of CHRF and microRNA‐211 (miR‐211) in HCC tissues and/or cell lines HepG2 and Huh‐7 were measured using quantitative reverse transcription polymerase chain reaction. Cell transfection was conducted to change the expression levels of CHRF and miR‐211 in cells. Cell viability and apoptosis were assessed using the cell counting kit‐8 assay and annexin V‐phycoerythrin staining, respectively. The pull‐down assay and RNA immunoprecipitation were performed to analyze the association between CHRF and miR‐211. The expression of the key factors involving in cell proliferation, cell apoptosis, and epithelial‐mesenchymal transition (EMT) process, as well as the phosphoinositide‐3‐kinase (PI3K)/protein kinase B (AKT) and Wnt/β‐catenin pathways, were evaluated by Western blot analysis.

Results

CHRF was highly expressed in HCC tissues and positively associated with the TNM stage, differentiation, and size of tumors. Overexpression of CHRF promoted HepG2 cell viability, proliferation, and EMT process. CHRF knockdown had opposite effects. Moreover, CHRF negatively regulated the expression of miR‐21, and miR‐21 was a direct target of CHRF. Overexpression of miR‐211 reversed the effects of CHRF on HepG2 and Huh‐7 cell viability, proliferation, and EMT process. Furthermore, overexpression of CHRF activated the PI3K/AKT and Wnt/β‐catenin pathways in HepG2 cells by downregulating miR‐211.

Conclusion

CHRF played oncogenic roles in HCC. The overexpression of CHRF promoted HepG2 and Huh‐7 cell viability, proliferation, and EMT process by downregulating miR‐211 and then activating the PI3K/AKT and Wnt/β‐catenin pathways.
Retracted: Upregulation of long noncoding RNA TUG1 contributes to the development of laryngocarcinoma by targeting miR‐145‐5p/ROCK1 axis
Authors: Zhuang Shenfa , Liu Fengxian , Wu Pingping
Published: March 2019

Laryngocarcinoma is the most common head and neck cancer and has a high incidence and mortality, causing about 83 000 deaths per year worldwide. Our research aimed to investigate the possible role of long noncoding RNA (lncRNA) taurine upregulated gene 1 (TUG1) in laryngocarcinoma development. The messenger RNA (mRNA) levels of TUG1 in tumor tissues and control (plasma) samples of laryngocarcinoma patients as well as in laryngocarcinoma cells were detected. The influences of TUG1 suppression on cell biological processes (viability, apoptosis, migration, and invasion) and cytoskeleton rearrangement in laryngocarcinoma cells were tested. Moreover, we investigated the regulatory interaction between TUG1 and miR‐145‐5p, and identified the target gene of miR‐145‐5p. The association between TUG1 and the protein expressions of RhoA/rho associated coiled‐coil containing protein kinase (ROCK)/matrix metalloproteinases (MMPs) pathway‐associated factors were detected. TUG1 was found to be highly expressed in tumor tissues and plasma samples of laryngocarcinoma patients as well as in laryngocarcinoma cells. Suppression of TUG1 decreased laryngocarcinoma cell viability, increased apoptosis, and suppression migration, invasion, and cytoskeleton rearrangement. Moreover, TUG1 negatively regulated miR‐145‐5p. TUG1 regulated tumor growth (viability and apoptosis) and metastasis through miR‐145‐5p. Furthermore, ROCK1 was targeted by miR‐145‐5p, and miR‐145‐5p/ROCK1 partner was involved in the process of tumor growth and metastasis. Finally, we found that TUG1 functioned on laryngocarcinoma by activating RhoA/ROCK/MMPs pathway. Our study reveals that lncRNA TUG1 is upregulated in laryngocarcinoma and may be involved in the process of laryngocarcinoma through miR‐145‐5p downregulation and activating the RhoA/ROCK/MMPs signals.
LncRNA PAPAS promotes hepatocellular carcinoma by interacting with miR‐188‐5p
Authors: Ma Jincai , Qin Chengyong , Yuan Zhenguo , Liu Shaoling
Published: March 2019

It has been observed that long noncoding RNA (lncRNA) PAPAS regulates rRNA synthesis, but its role in human diseases is unclear. Our study was carried out to investigate the role of PAPAS in hepatocellular carcinoma (HCC). In the present study, we found that PAPAS was upregulated both in plasma from patients with HCC and tumors compared with plasma from healthy people and tumor‐adjacent healthy tissues. Expression levels of PAPAS in tumor tissues and plasma of patients with HCC were significantly and positively correlated. Plasma levels of PAPAS effectively distinguished stage I patients from healthy controls. MicroRNA (miR)‐188‐5p was downregulated in tumor tissues than in tumor‐adjacent healthy tissues of patients with HCC, and was inversely correlated with PAPAS in tumor tissues but not in adjacent healthy tissues. PAPAS and miR‐188‐5p downregulated each other. PAPAS overexpression promoted, while miR‐188‐5p overexpression inhibited the HCC cell proliferation. Rescue experiment showed that miR‐34a overexpression attenuated the effects of PAPAS overexpression. However, PAPAS overexpression failed to affect significantly cancer cell migration and invasion. Therefore, lncRNA PAPAS promotes HCC by interacting with miR‐188‐5p.
Expression analysis of selected miR‐206 targets from the transforming growth factor‐β signaling pathway in breast cancer
Authors: Seifi‐Alan Mahnaz , Dianatpour Ali , Geranpayeh Lobat , Mirfakhraie Reza , Omrani Mir D. , Ghafouri‐Fard Soudeh
Published: March 2019

Breast cancer as a molecularly heterogeneous malignancy is associated with dysregulation of several signaling pathways, including transforming growth factor‐β (TGF‐β) signaling. On the other hand, several recent studies have demonstrated the role of microRNAs (miRNAs) in breast cancer pathogenesis. In the current study, we performed a computerized search to find miR‐206 target genes that are functionally linked to the TGF‐β signaling pathway. We selected LEF1,
Smad2, and
Snail2 genes to assess their expression in 65 breast cancer samples and their adjacent noncancerous tissues (ANCTs) in correlation with expression levels of miR‐206 as well as clinicopathological characteristics of patients. miR‐206 was significantly downregulated in (Estrogen receptor) ER‐positive breast cancer samples compared with their corresponding ANCTs. Association analysis between expression levels of genes and demographic features of patients showed significant association between expressions of
SMAD2 and
LEF1 genes and body mass index (
P values of 0.03 and 0.02, respectively). miR‐206 low‐expression levels were associated with TNM stage, mitotic rate, and lymph node involvement (
P values of 0.02, 0.01, and 0.01 respectively). In addition,
SMAD2 high‐expression levels were associated with HER2 status (
P = 0.02). Consequently, our data highlight the role of TGF‐β signaling dysregulation in the pathogenesis of breast cancer and warrant further evaluation of miRNAs and messenger RNA coding genes in this pathway to facilitate detection of cancer biomarkers and therapeutic targets.
Retracted: Long noncoding RNA ZBED3‐AS1 induces the differentiation of mesenchymal stem cells and enhances bone regeneration by repressing IL‐1β via Wnt/β‐catenin signaling pathway
Authors: Hu Kongzu , Jiang Wei , Sun Heyan , Li Zhenwei , Rong Genxiang , Yin Zongsheng
Published: March 2019

Bone regeneration, as a physiological process of bone formation, is regulated by multiple cytokines. Long noncoding RNAs are involved in the progress of bone formation. The present study investigated role by which ZBED3‐AS1 acts to control the differentiation of mesenchymal stem cells (MSCs) and bone regeneration. Bioinformatics prediction and dual luciferase reporter gene assay identified putative ZBED3‐AS1 binding sites on the 3′‐untranslated region of interleukin‐1β (IL‐1β). Then, RNA immunoprecipitation and chromatin immunoprecipitation assays confirmed that ZBED3‐AS1 could regulate the expression of IL‐1β by binding to the transcription factor CREB. Notably, ZBED3‐AS1 was shown to negatively regulate IL‐1β expression. After model establishment in rats simulating bone injury, MSCs were isolated and delivered with ZBED3‐AS1, Si‐ZBED3‐AS1, Si‐IL‐1β, or DKK (inhibitor of Wnt/β‐catenin signaling pathway) to identify their roles in osteogenic differentiation by evaluating MSC colony formation and proliferation. Then, number of mineralized nodules, alkaline phosphatase (ALP) activity and osteocalcin (OCN) expression, and expression of osteogenesis‐related genes were determined. Overexpression of ZBED3‐AS1 or silencing of IL‐1β was shown to accelerate ectopic osteogenesis, as reflected by increasing the number of mineralized nodules, ALP activity, and OCN expression, and promoting MSC colony formation and proliferation. Additionally, ZBED3‐AS1 activated the Wnt/β‐catenin signaling pathway by negatively regulating IL‐1β. IL‐1β inhibited osteogenic differentiation by suppressing the Wnt/β‐catenin signaling pathway. Furthermore, the effect of ZBED3‐AS1 and IL‐1β on osteogenic differentiation was confirmed in vivo. Taken together, upregulation of ZBED3‐AS1 could restore differentiation of MSCs and enhance bone regeneration via activation of Wnt/β‐catenin signaling pathway by repressing IL‐1β.
Regulatory networks upon neurogenesis induction in PC12 cell line by small molecules
Authors: Falsafi Nafiseh , Soleimani Tahereh , Fallahi Hossein , Azadbakht Mehri
Published: March 2019

Alteration in the normal regulatory pathway of differentiation can lead to the induction of programmed cell death. Accordingly, some chemicals like staurosporine, nerve growth factor, pituitary adenylate cyclase activating peptide, and trimethyltin are shown to be able to induce differentiation in vitro, via different mechanisms in the PC12 cell line. Hence, understanding the details of the molecular mechanisms of differentiation induction by these small molecules are important for further application of these molecules in neurogenesis. Therefore, we sought to determine these signaling pathways, using gene regulatory networks analysis. Then, we have conducted a comparative analysis of the alterations in the gene expression pattern of the PC12 cell lines in response to these chemicals at the early stages. Based on the comparative analysis and previous knowledge, we have proposed the affected pathways during differentiation and apoptosis. Our findings could be useful in the development of protocols to reprogramming of neurons by such small molecules with high efficiency.
Orphan disease status of cancer cachexia in the USA and in the European Union: a systematic review
Authors: Anker Markus S. , Holcomb Richard , Muscaritoli Maurizio , von Haehling Stephan , Haverkamp Wilhelm , Jatoi Aminah , Morley John E. , Strasser Florian , Landmesser Ulf , Coats Andrew J.S. , Anker Stefan D.
Published: March 2019

Background

Cachexia has significant impact on the patients' quality of life and prognosis. It is frequently observed in patients with cancer, especially in advanced stages, but prevalence data for the overall population are lacking. Good quality estimates of cancer cachexia in general and for each of the major cancer types would be highly relevant for potential treatment development efforts in this field. Both the USA and European Union (EU) have implemented special clinical development rules for such rare disorders what are called ‘orphan diseases’. The cut‐off level for a disease to be considered an orphan disease in the USA is 200 000 people (0.06% of the population) and EU is 5 per 10 000 people (0.05% of the population).

Methods

For this systematic review, we searched at PubMed (from inception to 31 January 2018) to identify clinical studies that assessed the prevalence of cachexia in cancer patients at risk. Studies reporting the prevalence of either cancer cachexia or wasting disease in the top‐10 cancer types and 4 other selected cancer types known to be particularly commonly complicated by cachexia were included in this analysis (i.e. prostate cancer, breast cancer, colorectal cancer, melanoma, endometrial cancer, thyroid cancer, urinary bladder cancer, non‐hodgkin lymphoma, lung cancer, kidney and renal pelvis cancer, head and neck cancer, gastric cancer, liver cancer, and pancreatic cancer). We calculated the current burden of cancer cachexia, disease by disease, in the USA and in the EU and compared them to the current guidelines for the definition of orphan disease status.

Results

We estimate that in 2014 in the USA, a total of 527 100 patients (16.5 subjects per 10 000 people of the total population), and in 2013 in the EU, a total of 800 300 patients (15.8 subjects per 10 000 people of the total population) suffered from cancer cachexia (of any kind). In the 14 separately analysed cancer types, the prevalence of cancer cachexia in the USA ranged between 11 300 (0.4/10 000, gastric cancer) and 92 000 patients (2.9/10 000, lung cancer) and in the EU between 14 300 (0.3/10 000, melanoma of the skin) and 150 100 (3.0/10 000, colorectal cancer).

Conclusions

The absolute number of patients affected by cancer cachexia in each cancer group is lower than the defined thresholds for orphan diseases in the USA and EU. Cancer cachexia in each subgroup separately should be considered an orphan disease.
The effectiveness of glass ionomer cement as a fiber post cementation system in endodontically treated teeth
Authors: Lorenzetti Camila C. , Bortolatto Janaina F. , Ramos Anna T. P. R. , Shinohara André L. , Saad Jose R. C. , Kuga Milton C.
Published: March 2019

This study compared the performance of a glass ionomer (GC Gold Label 1, GIC) as a fiber post cementation system for glass fiber posts with a self‐adhesive resin cement (Relyx U200, RUC) and a conventional resin cement system (Scotchbond Muli‐Purpose and Relyx ARC, RAC). Thirty endodontically treated canines were randomly divided in three groups (n = 10), according to the fiber post cementation system: (RAC)—Scotchbond Multi‐Purpose and Relyx X ARC; (RUC)—Relyx U200 and (GIC)—GC Gold Label 1 Luting & Lining. Rhodamine was incorporated into the cementation system prior to the fiber post cementation. After glass fiber post cementation, roots were incubated in artificial saliva for 6 months. After that, specimens from the cervical, middle, and apical thirds of the post space were prepared and analyzed using a push‐out bond strength test and confocal laser microscopy. ANOVA one way and Tukey tests showed that GIC and RUC demonstrated similar push‐out bond strength values, independently of the post space third (p > .05); however, values were greater than those shown by RAC (p < .05). For dentin penetrability, GIC and RUC also had similar results (p > 0.05) and lower than RAC (p < 0.05). Inside the root canal, the cementation system using glass ionomer cement (GC Gold Label 1 Luting & Lining) has similar push‐out bond strength to the self‐adhesive resin cement (Relyx U200) and these were higher than the conventional resin (Relyx ARC), despite its higher dentin penetrability.
Physiological investigations of management and genotype options for adapting rice production to iron toxicity in Madagascar
Authors: Rakotoson Tovohery , Ergezinger Lara , Rajonandraina Toavintsoa , Razafimbelo Tantely , Wu Lin-Bo , Frei Michael
Published: March 2019

Iron (Fe) toxicity is one of the major mineral disorders affecting rice (Oryza sativa L.) production in Madagascar. This study aimed at linking physiological and agronomic responses of diverse rice genotypes to Fe resistance mechanisms with different nutrient management practices. Twenty‐three local and exotic rice varieties were grown in Fe‐toxic soil in parallel greenhouse and field experiments and subjected to two treatments: (1) no fertilizer; (2) mineral and organic fertilizer application at recommended rates. Growth, straw and grain yield, symptom formation, and physiological responses including Fe uptake, root plaque formation, and lipid peroxidation were monitored. The application of fertilizer significantly decreased average shoot Fe concentrations partly due to Fe exclusion favored by enhanced root plaque formation. Visual symptoms negatively correlated with straw biomass in both experiments and grain yield in the greenhouse experiment, and positively correlated with lipid peroxidation. However, no plausible correlation occurred with grain yield in the field due to sterility in exotic varieties un‐adapted to local climate. Even though grain Fe concentrations were orders of magnitude lower than in vegetative tissue, some exotic varieties were significantly superior to local checks. Our results provide insight into management and genotype options for adapting rice to Fe toxicity under field conditions.
Introduction: Role of palliative care for the surgical patient
Authors: Fahy Bridget N.
Published: March 2019

Palliative care (PC) seeks to improve the quality of life for patients facing serious illness. Several oncology organizations have guidelines about PC, reflecting the need to integrate PC into standard oncology care. Many surgical patients do not receive PC despite the need for these services and established surgical PC competencies. Recent educational and research efforts reveal increased appreciation of the need and benefit of integrating PC services with cancer care in general, and surgical care, specifically.
Does paranasal sinus development affect olfactory fossa depth and lateral lamella length?
Authors: Kayabasi Serkan , Hizli Omer , Ozkan Deniz
Published: March 2019

Objectives

To investigate the olfactory fossa depths and lateral lamella lengths of patients with different types of developmental disorders of paranasal sinuses in comparison with normal controls.

Study Design

Retrospective, archival, radio‐anatomical study.

Methods

We included 58 patients with maxillary sinus hypoplasia, 50 patients with frontal sinus hypoplasia/aplasia, 50 patients with sphenoid sinus hypoplasia/aplasia, and 40 normal controls. Reviewing paranasal computerized tomography scans, we noted the olfactory fossa depths and lateral lamella lengths of all the groups and compared between the hypoplasia groups and the control group.

Results

Compared with the normal controls, the maxillary hypoplasia group (P < 0.001), frontal hypoplasia/aplasia group (P = 0.004), and sphenoid hypoplasia/aplasia group had significantly deeper olfactory fossa (P = 0.003). The mean lateral lamella lengths in the type 1, type 2, and type 3 hypoplastic maxillary sinus groups were significantly greater compared with that in the control group (P < 0.001). Additionally, the mean lateral lamella lengths in the hypoplastic frontal sinus, aplastic frontal sinus, and hypoplastic sphenoid sinus groups were significantly greater compared with that in the control group (P < 0.001).

Conclusion

The patients with pneumatization defects of the maxillary, frontal, and sphenoid sinuses had deeper olfactory fossa and longer lateral lamella related to increased risk of skull base injury during endoscopic sinus surgery.

Level of Evidence

3 Laryngoscope, 129:2458–2463, 2019
Grading upper tract urothelial carcinoma with the attenuation coefficient of in‐vivo optical coherence tomography
Authors: Freund Jan Erik , Faber Dirk J. , Bus Mieke T. , van Leeuwen Ton G. , de Bruin Daniel M.
Published: March 2019

Introduction

With catheter based optical coherence tomography (OCT), high resolution images of the upper urinary tract can be obtained, thereby facilitating the detection of upper tract urothelial carcinomas (UTUC). We hypothesized that the attenuation coefficient of the OCT signal (μOCT) is related to the histopathologic grade of the tumor.

Objectives

In this study, we aimed to define the μOCT cut‐off for discriminating high grade and low grade papillary UTUC.

Methods

For this post‐hoc analysis, data from OCT imaging of papillary UTUC was obtained from patients during ureterorenoscopy. OCT images and raw data were simultaneously analyzed with in‐house developed software. The μOCT determined in papillary UTUCs and corresponding histopathologic grading from either biopsies or radical resection specimens were compared.

Results

Thirty‐five papillary UTUC from 35 patients were included. μOCT analysis was feasible in all cases. The median μOCT was 3.3 mm−1 (IQR 2.7–3.7 mm−1) for low‐grade UTUC and 4.9 mm−1 (IQR 4.3–6.1 mm−1) for high‐grade UTUC (P = 0.004). ROC analysis yielded a μOCT cut‐off value of >4.0 mm−1 (AUC = 0.85, P < 0.001) with a sensitivity of 83% and a specificity of 94% for high‐grade papillary UTUC.

Conclusions

This study proposes a μOCT cut‐off of 4.0 mm−1 for quantitative grading of UTUC with ureterorenoscopic OCT imaging. The promising diagnostic accuracy calculations justify further studies to validate the proposed cut‐off value. Implementation of the software for the μOCT analysis in OCT systems may allow for μOCT assessment at real time during ureterorenoscopy. Lasers Surg. Med. 51:399–406, 2019. © 2019 Wiley Periodicals, Inc.