bluuebunny/crossref_metadata_2025 huggingface dataset:
Primers for complete chloroplast genome sequencing in Magnolia
Authors: Song Eunji , Park Suhyeon , Kim Sangtae
Published: September 2019

Premise

A new set of primers was developed for sequencing of whole chloroplast genomes of Magnolia species and gap‐filling of unfinished genomes.

Methods and Results

Two hundred and fifty primers were newly designed based on two previously reported chloroplast genomes from two different genera in Magnoliaceae. A total of 134 primer pairs, including the ones developed in this study and 18 previously reported ones, were enough to cover the entire chloroplast genome sequences in Magnoliaceae. Four species from different sections of Magnolia (M. dealbata, M. fraseri var. pyramidata, M. liliiflora, and M. odora) were used to show the general application of these primers to chloroplast genome sequencing in Magnolia.

Conclusions

Using the developed primers, four Magnolia chloroplast genomes were successfully assembled. These results show the utility of these primers across Magnolia and their potential use for phylogenetic studies, DNA barcoding, and population genetics in this group.
Sulfonatocalixarene Counterion Exchange Binding Model in Action: Metal‐Ion Catalysis Through Host‐Guest Complexation
Authors: Basílio Nuno , Pessêgo Márcia , Acuña Angel , García‐Río Luis
Published: September 2019

p‐Sulfonatocalixarene water soluble macrocyclic host receptors are known to form cooperative ternary complexes with complementary organic guest and metal cations. This property may be explored to enhance the interaction of weak nitrogen ligands with metal cations in a confined space showing some resemblance to metal‐containing enzymes. However, the best of our knowledge, catalytic potential of this property remains unexplored. In this work the Ni2+ catalyzed hydrolysis of a picolinate ester (2,4‐dinitrophenyl picolinate, 1) was used as a model reaction to evaluate the effect of sulfonatocalixarene macrocycles in the kinetics of this reaction. The results show that the host molecules promote the reaction through simultaneous complexation of the metal cation and the substrate and, in the case of the larger calixarenes containing more basic phenol groups, substantially higher rate enhancements are observed owing to additional assistance provided by base/nucleophilic catalysis. However, due the ionic nature of these receptors auto‐inhibition of the reaction is observed at higher concentrations due counterion (Na+) binding that competes with the catalytically active Ni2+ ‐complexes.
Devisable POM/Ni Foam Composite: Precisely Control Synthesis toward Enhanced Hydrogen Evolution Reaction at High pH
Authors: Jia Xueying , Streb Carsten , Song Yu‐Fei
Published: September 2019

Polyoxometalates (POMs) are promising catalysts for the electrochemical hydrogen production from water owing to their high intrinsic catalytic activity and chemical tunability. However, poor electrical conductivity and easy detachment of the POMs from the electrode cause significant challenges under operating condition. Herein, a simple one‐step hydrothermal method is reported to synthesize a series of Dexter–Silverton POM/Ni foam composites (denoted as NiM‐POM/Ni; M=Co, Zn, Mn), in which the stable linkage between the POM catalysts and the Ni foam electrodes lead to high activity for the hydrogen evolution reaction (HER). Among them, the highest HER performance can be observed in the NiCo‐POM/Ni, featuring an overpotential of 64 mV (at 10 mA cm−2, vs. reversible hydrogen electrode), and a Tafel slope of 75 mV dec−1 in 1.0 m aqueous KOH. Moreover, the NiCo‐POM/Ni catalyst showed a high faradaic efficiency ≈97 % for HER. Post‐catalytic of NiCo‐POM/Ni analyses showed virtually no mechanical or chemical degradation. The findings propose a facile and inexpensive method to design stable and effective POM‐based catalysts for HER in alkaline water electrolysis.
Chemical Modification of β‐Cyclodextrins: Balancing Soft and Rigid Domains in Complex Structures
Authors: Luppi Federico , Mai Nathalie , Kister Guillaume , Gill Philip P. , Gaulter Sally E. , Stennett Christopher , Dossi Eleftheria
Published: September 2019

Crystalline polymers such as β‐cyclodextrin (βCD) can be modified with polyethylene glycol (PEG) diglycidyl ether cross‐linkers (262, 394, 500 Da). In this work, the authors show that the quantity and length of the PEG soft segments influence the solubility and malleability of the products, which are water soluble and easily converted to nitrated analogues under standard reaction conditions. Inert and nitrated derivatives containing longer PEG segments showed the ability to self‐heal. The degree of cross‐linking and decomposition temperatures and energies depended on the quantity and length of the soft segment. Nitrated cross‐linked βCD containing longer PEG segments did not ignite following an electrostatic discharge of 4.5 J. The chemical stability of βCD/PEG binders was tested by heat flow calorimetry at 80 °C. The balanced incorporation of soft PEG and rigid βCD segments was found to improve the processability of cross‐linked βCDs and desensitised their nitrated derivatives, offering new solutions for inert and energetic binders.
Influence of Different Silica Nanoparticles on Drop Size Distributions in Agitated Liquid‐Liquid Systems
Authors: Röhl Susanne , Hohl Lena , Kempin Maresa , Enders Frauke , Jurtz Nico , Kraume Matthias
Published: September 2019

The impact of different silica nanoparticles on rheology, interfacial tension and drop size distributions in liquid‐liquid systems is determined experimentally. The particles vary in wettability and specific surface area. In contrast to commonly used high‐energy devices for Pickering emulsion preparation, low energy input by stirring allows to quantify drop breakage and coalescence in steady state and dynamic conditions. The experiments can provide essential information for drop size model development in nanoparticle‐stabilized emulsions.
Systemic treatments in MDM2 positive intimal sarcoma: A multicentre experience with anthracycline, gemcitabine, and pazopanib within the World Sarcoma Network
Authors: Frezza Anna Maria , Assi Tarek , Lo Vullo Salvatore , Ben‐Ami Eytan , Dufresne Armelle , Yonemori Kan , Noguchi Emi , Siontis Brittany , Ferraro Richard , Teterycz Pawel , Duffaud Florence , Ravi Vinod , Vincenzi Bruno , Gelderblom Hans , Pantaleo Maria A. , Baldi Giacomo G. , Desar Ingrid , Fedenko Alexander , Maki Robert G. , Jones Robin L. , Benjamin Robert S. , Blay Jean Yves , Kawai Akira , Gounder Mrinal , Gronchi Alessandro , Le Cesne Axel , Mir Olivier , Czarnecka Anna M. , Schuetze Scott , Wagner Andrew J. , Adam Julien , Barisella Marta , Sbaraglia Marta , Hornick Jason L. , Meurgey Alexandra , Mariani Luigi , Casali Paolo G. , Thornton Katherine , Stacchiotti Silvia
Published: September 2019

Background

Intimal sarcoma (InS) is an exceedingly rare neoplasm with an unfavorable prognosis, for which new potentially active treatments are under development. We report on the activity of anthracycline‐based regimens, gemcitabine‐based regimens, and pazopanib in patients with InS.

Methods

Seventeen sarcoma reference centers in Europe, the United States, and Japan contributed data to this retrospective analysis. Patients with MDM2‐positive InS who were treated with anthracycline‐based regimens, gemcitabine‐based regimens, or pazopanib between October 2001 and January 2018 were selected. Local pathological review was performed to confirm diagnosis. Response was assessed by RECIST1.1. Recurrence‐free survival (RFS), progression‐free survival (PFS) and overall survival were computed by Kaplan‐Meier method.

Results

Seventy‐two patients were included (66 anthracycline‐based regimens; 26 gemcitabine‐based regimens; 12 pazopanib). In the anthracycline‐based group, 24 (36%) patients were treated for localized disease, and 42 (64%) patients were treated for advanced disease. The real‐world overall response rate (rwORR) was 38%. For patients with localized disease, the median RFS was 14.6 months. For patients with advanced disease, the median PFS was 7.7 months. No anthracycline‐related cardiac toxicity was reported in patients with cardiac InS (n = 26). For gemcitabine and pazopanib, the rwORR was 8%, and the median PFS was 3.2 and 3.7 months, respectively.

Conclusion

This retrospective series shows the activity of anthracycline‐based regimens in InS. Of note, anthracyclines were used in patients with cardiac InS with no significant cardiac toxicity. The prognosis in patients with InS remains poor, and new active drugs and treatment strategies are needed.
Modeling the distribution of a wide‐ranging invasive species using the sampling efforts of expert and citizen scientists
Authors: Roy‐Dufresne Emilie , Saltré Frédérik , Cooke Brian D. , Mellin Camille , Mutze Greg , Cox Tarnya , Fordham Damien A.
Published: September 2019

In its invasive range in Australia, the European rabbit threatens the persistence of native flora and fauna and damages agricultural production. Understanding its distribution and ecological niche is critical for developing management plans to reduce populations and avoid further biodiversity and economic losses.

We developed an ensemble of species distribution models (SDMs) to determine the geographic range limits and habitat suitability of the rabbit in Australia. We examined the advantage of incorporating data collected by citizens (separately and jointly with expert data) and explored issues of spatial biases in occurrence data by implementing different approaches to generate pseudo‐absences. We evaluated the skill of our model using three approaches: cross‐validation, out‐of‐region validation, and evaluation of the covariate response curves according to expert knowledge of rabbit ecology.

Combining citizen and expert occurrence data improved model skill based on cross‐validation, spatially reproduced important aspects of rabbit ecology, and reduced the need to extrapolate results beyond the studied areas.

Our ensemble model projects that rabbits are distributed across approximately two thirds of Australia. Annual maximum temperatures >25°C and annual minimum temperatures >10°C define, respectively, the southern and northern most range limits of its distribution. In the arid and central regions, close access to permanent water (≤~ 0.4 km) and reduced clay soil composition (~20%–50%) were the major factors influencing the probability of occurrence of rabbits.

Synthesis and applications. Our results show that citizen science data can play an important role in managing invasive species by providing missing information on occurrences in regions not surveyed by experts because of logistics or financial constraints. The additional sampling effort provided by citizens can improve the capacity of SDMs to capture important elements of a species ecological niche, improving the capacity of statistical models to accurately predict the geographic range of invasive species.
Lipid Composition and State of Oxidation of Fortified Infant Flours in Low‐Income Countries Are Not Optimal and Strongly Affected by the Time of Storage
Authors: Moustiés Célia , Bourlieu Claire , Barea Bruno , Servent Adrien , Alter Pascaline , Lebrun Marc , Hemery Youna Morgane , Laillou Arnaud , Avallone Sylvie
Published: September 2019

Food fortification is widely used to address the public health problem of nutrient deficiencies. This study's purpose is to assess the lipid profile and nutritional quality of 13 fortified infant flours (FI) collected “in the field” in Africa and Asia after different periods of storage. The lipid content, fatty acid profiles, lipophilic vitamin content, and lipid oxidation state (peroxide values, secondary oxidation products) are determined. Mycotoxins and packaging materials are also characterized. The lipid content averages 9.1 ± 3.5 g/100 g. Fatty acid profiles are dominated by linoleic (43.3 ± 8.8%), oleic (29.5 ± 7.4%), and palmitic acid (17.8 ± 6.7%) and result in an average ω6/ω3 ratio of 12.2 ± 5.9 but with high values for some FI. Very high overages in vitamins A, D, and E are observed in products stored for short periods (1–6 months), whereas FI stored for more than 12 months has insufficient vitamin content. Lipid oxidation is acceptable but for six products presenting excessive peroxide values. Most products are contaminated by low amounts of mycotoxins but only two FI do not abide by the regulation. A strong correlation between peroxide values, hexanal content, and time of storage is observed.

Practical Applications: The expiration dates for FI commercialized in low‐income countries should be shortened from 36 to 12 months so as to guarantee their nutritional quality of these functional foods and to abide by the fortified infant flour legislation. Indeed, FI quality significantly decreases over time of storage. The use of high barrier packaging materials must be generalized, although it is a necessary criterion but not sufficient to ensure the long‐term stability of FI. Special attention should be given to reduce lipophilic vitamin overages and to improve their lipid profile, especially the ω6/ω3 ratio, which has to be lower than 15.
A Review of the Prospects and Benefits of Smart Gridding Technology Adoption in Bangladesh's Power Sector
Authors: Murshed Muntasir
Published: September 2019

Smart gridding of conventional power grids is key to ensuring the optimal use of electricity. Incorporation of contemporary smart gridding technologies (SGTs) within the power sector of Bangladesh can lead to expansion of the national grid infrastructure, improvement in energy‐use efficiencies, betterment of the reliability of power supply, and reduction in the monetary values of system losses. In addition, the accommodation of renewable energy within smart grids can raise the share of renewable electricity as a percentage of total electricity output of Bangladesh. This, in turn, is anticipated to provide off‐grid electrification opportunities and play a critically important role in mitigating the urban‐rural divide in access to electricity.
Near‐Infrared Spectroscopy Reveals Brain Hypoxia and Cerebrovascular Dysregulation in Primary Biliary Cholangitis
Authors: Duszynski Chris C. , Avati V. , Lapointe A.P. , Scholkmann F. , Dunn J.F. , Swain M.G.
Published: September 2019

Background and Aims

Primary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease linked to symptoms including fatigue and altered mood/cognition, indicating that chronic liver inflammation associated with PBC can impact brain function. We employed near‐infrared spectroscopy (NIRS), a noninvasive neuroimaging technique, to determine whether patients with PBC exhibit reduced cerebral oxygen saturation (StO2) and altered patterns of microvascular cerebral blood perfusion and whether these alterations were associated with clinical phenotype. This observational case–control study was conducted at a tertiary hospital clinic (University of Calgary Liver Unit).

Approach and Results

Thirteen female patients with noncirrhotic PBC, seven female patients with cirrhotic PBC, and 11 healthy female controls were recruited by physician referral and word of mouth, respectively. NIRS was used to measure cerebral hemoglobin and oxygen saturation. A wavelet phase coherence method was used to estimate the coherent frequency coupling of temporal changes in cerebral hemodynamics. The PBC group demonstrated significantly reduced cerebral StO2 (P = 0.01, d = 0.84), indicating cerebral hypoxia, significantly increased cerebral deoxygenated hemoglobin concentration (P < 0.01, d = 0.86), and significantly reduced hemodynamic coherence in the low‐frequency band (0.08‐0.15 Hz) for oxygenated hemoglobin concentration (P = 0.02, d = 0.99) and total hemoglobin (tHb) concentration (P = 0.02, d = 0.50), indicating alterations in cerebrovascular activity. Complete biochemical response to ursodeoxycholic acid (UDCA) therapy in early patients with PBC was associated with increased cerebral tHb concentration and decreased hemodynamic coherence.

Conclusions

Using NIRS, patients with PBC were found to have hypoxia, increased cerebral hemoglobin concentration, and altered cerebrovascular activity, which were reversed in part in UDCA responders. In addition, symptoms and quality‐of‐life measures did not correlate with brain hypoxia or cerebrovascular dysregulation in patients with PBC.
Ribosomal protein small subunit 15A (RPS15A) inhibits the apoptosis of breast cancer MDA‐MB‐231 cells via upregulating phosphorylated ERK1/2, Bad, and Chk1
Authors: Kong Lingsuo , Wei Qing , Hu Xianwen , Chen Lanren , Li Juan
Published: September 2019

Aim

To detect the expression and identify the role of Ribosomal protein S15A (RPS15A) in human breast cancer (BC).

Methods

Immunohistochemistry (IHC) was carried out for detecting the levels of RPS15A protein. Quantitative PCR was used to evaluate the mRNA level of RPS15A in one normal breast and three BC cell lines. Lentivirus‐mediated shRNA targeting RPS15A was designed to investigate the impact of silencing RPS15A in MDA‐MB‐231 cell.

Results

Higher RPS15A expression was detected in tumor tissues than in para‐cancer tissues, and higher RPS15A expression was related to larger tumor size and higher TNM stage. Also, RPS15A mRNA expression in all three BC cell lines was higher than that in normal breast cell (all P < .005). Further, RPS15A knockdown significantly suppressed MDA‐MB‐231 cell proliferation and induced apoptosis. Moreover, RPS15A knockdown increased the caspase‐3/‐7 activity, and suppressed the phosphorylated levels of ERK1/2, Bad, and Chk1 (all P < .01).

Conclusion

RPS15A inhibits apoptosis via upregulating phosphorylated ERK1/2, Bad, and Chk1 in MDA‐MB‐231 cell line.
Mesenchymal stem cells combined with traditional Chinese medicine (qi‐fang‐bi‐min‐tang) alleviates rodent allergic rhinitis
Authors: Fu Yanxia , Kong Yanhua , Li Jun , Wang Yi , Li Mengdi , Wang Ying , Wang Yinyin , Ren Fangli , Ni Jian , Li Youlin , Chang Zhijie
Published: September 2019

Mesenchymal stem cells (MSCs) have been proved to exert anti‐inflammatory effects and regulate immune reactions. Traditional Chinese medicine (TCM), qi‐fang‐bi‐min‐tang, is effective for some patients with allergic diseases. However, it remains unclear whether MSCs combined with TCM could benefit the treatment of allergic rhinitis (AR). In this study, we reported an additional effect of TCM (qi‐fang‐bi‐min‐tang) on the therapy of AR under MSCs treatment. Intriguingly, we observed that TCM‐treated MSCs significantly inhibited the symptoms of AR and reduced the pathological changes of nasal mucosa in ovalbumin (OVA)‐induced rats. The expression levels of interferon γ (IFN‐γ), interleukin‐17 (IL‐17), and IL‐4 were significantly decreased in the plasma of AR rats after injection of TCM‐treated MSCs. TCM‐treated MSCs reduced the levels of histamine secreted by mast cells and immunoglobulin E (IgE) secreted by plasma cells. In addition, we found that MSCs combined with TCM had a better therapeutic effect than TCM alone on AR in an OVA‐induced mouse model. After OVA induction, MSCs combined with TCM significantly reduced the ratio of T helper type 1 (Th1), Th2, and Th17, but increased the proportion of Treg in the spleen of mice. Consistently, the expression levels of IFN‐γ, IL‐4, and IL‐17 were significantly decreased, but transforming growth factor‐β1 was significantly increased in the plasma of AR mice after treated with TCM and MSCs. Our results from both rats and mice indicated that the effects of TCM combined with MSCs on the AR might be through regulating the secretion of Th1, Th2, and Th17 cytokines. This study suggested that TCM (qi‐fang‐bi‐min‐tang)‐treated MSCs could be used in the clinical therapy of AR.
Identification of key candidate genes in neuropathic pain by integrated bioinformatic analysis
Authors: Tang Simin , Jing Huan , Huang Zhenxing , Huang Teng , Lin Sen , Liao Meijuan , Zhou Jun
Published: September 2019

This study aimed to disclose differentially expressed genes (DEGs) in dorsal root ganglia (DRGs) of neuropathic pain (NP) from spared nerve injury (SNI) model, thereby identifying specific and meaningful genetic targets for the diagnosis and treatment of NP. The GSE89224 was downloaded from the GEO database. DEGs were screened using the GEO2R online tool. Functional enrichment analysis of DEGs was then performed using the DAVID and constructed using the R ggplot2 package. Protein‐protein interaction (PPI) network was constructed from the STRING database and visualized in Cytoscape software. MicroRNA targeting these DEGs was obtained from the TarBase and miRTarBase database, while transcription factor (TF)‐targeting DEGs were predicted from the ENCODE database, both of which utilized the visual analytics platform NetworkAnayst. Finally, a merged microRNA‐TF network was constructed based on the above two networks and was then analyzed with Cytoscape. Eighty DEGs were screened, only Vstm2b and Htr3a were downregulated and 78 genes were upregulated. The real‐time polymerase chain reaction was applied to validate the gene expression of the top five DEGs (Npy, Atf3, Gpr151, Sprr1a, and Cckbr) in the DRG tissue 5 days after SNI surgery. It was found that Npy, Atf3, and Sprr1a have a significant increase after SNI stimulation, while Gpr151 and Cckbr showed a slight upward trend. Functional analysis was performed on all DEGs, of which 58 biological processes were enriched by gene ontology analysis, and 11 signaling pathways were enriched by KEGG analysis. In the PPI network, Atf3, Jun, Timp, and Npy had a higher degree. Thus, combined with various bioinformatic analyses, Npy and Atf3 may serve as the prognostic and therapeutic targets of NP. Key microRNA (mmu‐mir‐16‐5p) and TF (MEF2A) were predicted to be associated with the pathogenetic process of NP with microRNA‐TF regulatory network analysis, which were also identified as key regulators in the progression of NP.
CHI3L1 promotes proliferation and improves sensitivity to cetuximab in colon cancer cells by down‐regulating p53
Authors: Liu Kaitai , Jin Ming , Ye Shuang , Yan Senxiang
Published: September 2019

Background

Chitinase 3‐like protein 1 (CHI3L1) is most likely a malignant tumor metastasis‐associated gene. However, the functions of CHI3L1 in colon cancer cell proliferation and its cetuximab sensitivity are still unclear. We aimed to investigate the mechanism of CHI3L1 in promoting colon cancer cell proliferation and its sensitivity to cetuximab.

Methods

The expression of CHI3L1 in colon cancer and adjacent tissues were detected by immunohistochemistry. CHI3L1 was overexpressed in colon cancer cell lines by lentiviral technology. Cell proliferation and sensitivity to cetuximab were measured by MTT assay, cell cycle was analyzed by flow cytometry, and expression of cell cycle‐related proteins was analyzed by immunoblotting.

Results

The results showed that the level of CHI3L1 in colon cancer tissue was significantly higher than that in adjacent tissue, which was also correlated with overall survival. The cell proliferation rate was significantly increased after overexpression of CHI3L1, and the sensitivity to cetuximab was significantly increased. The expression of p53 was down‐regulated while the EGFR was up‐regulated significantly in CHI3L1 overexpressed cells. When rescued the expression of p53 in HCT116‐CHI3L1 cells, the cell proliferation and sensitivity to cetuximab could be restored.

Conclusion

High levels of CHI3L1 are associated with poor prognosis and accelerate the proliferation of colon cancer cells and increase the sensitivity to cetuximab. Its mechanism of increasing the cell proliferation and sensitivity to cetuximab may be explained by down‐regulating p53 expression and then, up‐regulating the expression of EGFR.
Role of liraglutide in brain repair promotion through Sirt1‐mediated mitochondrial improvement in stroke
Authors: He Weiliang , Wang Haoyuan , Zhao Congying , Tian Xiaochao , Li Litao , Wang Hebo
Published: September 2019

Brain repair, especially axonal sprouting, is critical to restore motor function in disabled stroke patients. Liraglutide (LG) is a new kind of long‐acting analogue of glucagon‐like peptide‐1 (GLP‐1) and has potential protective effects in stroke. The mitochondria participate in brain repair after cerebral injury. However, the mechanism of the effect of LG on brain repair and its potential influence on mitochondria in stroke remains obscure. Here, in focal cerebral cortical ischemic mice model, LG improved the motor functional recovery and promoted axonal sprouting by restoring the activities of isocitrate dehydrogenase, α‐ketoglutarate dehydrogenase, and succinate dehydrogenase. Moreover, LG remarkably increased the cell survival rate and revived the NeuN and GAP‐43 levels in cortical neurons under hydrogen peroxide (H2O2) exposure. It was also observed that LG reduced the generation of reactive oxygen species, stabilized the mitochondrial membrane potential, enhanced the levels of adenosine triphosphate, enhanced activities of mitochondrial complex‐I, and decreased protein expression levels of fission‐1 in H2O2‐injured cortical neurons. Additionally, LG suppressed the expressions of sirtuin 1 (Sirt1) in cortical neurons exposed to H2O2. Furthermore, knockdown of Sirt1 by short interfering RNA facilitated the LG‐mediated mitochondrial protection in cortical neurons under H2O2. Collectively, this data from the present study illustrated that LG exerted a promoting influence on brain repair, after cerebral ischemic injury, through Sirt1‐mediated mitochondrial improvement.
Effect of Aromatase Inhibition (Exemestane) on Urine Concentration of Osteoprotegerin in Healthy Postmenopausal Women
Authors: Garcia Allison P. , Hatvany Jacob B. , Murphy Michael A. , Atchley Daniel H. , Gurley Bill J. , Kamdem Landry K.
Published: September 2019

This pilot study examined how exemestane (an aromatase inhibitor [AI]) affected osteoprotegerin (OPG) urine concentrations in postmenopausal women. Exemestane (25 mg, single dose) was given to 14 disease‐free women past menopause in this nonrandomized, open‐label study. Before dosing, urine specimens were gathered. Three days later, these women returned to provide urine specimens for pharmacokinetic (measurement of major parent drug and enzymatic product) and pharmacodynamic (profiling of OPG) analysis. Urine concentrations of the major parent drug (exemestane) and enzymatic product (17‐hydroexemestane) were quantified using liquid chromatography‐tandem mass spectrometry. An analyst software package was used for data processing. Following the manufacturer's guidelines, OPG urine concentrations were quantified using a human osteoprotegerin TNFRSF11b ELISA kit from Sigma‐Aldrich. A microplate reader helped to carry out OPG data analysis and processing. Our results highlight that OPG urine concentrations were decreased 3 days after drug dosage (mean predosage OPG concentration, 61.4 ± 24.1 pg/mL; vs mean postdosage OPG concentration, 45.7 ± 22.1 pg/mL; P = .02, Wilcoxon rank test). Among the 14 volunteers enrolled in the study, 4 subjects had an increase of less than 1‐fold, and the rest showed an average of a 2‐fold decrease in OPG concentration (range, 1.1‐5.4; standard deviation, 1.3) after exemestane administration. There was no association between fold decrease in OPG urine concentration and the pharmacokinetics of the major parent drug (exemestane) and its enzymatic product (17‐hydroexemestane). We concluded that one of the off‐target pharmacological effects of AIs (eg ,exemestane) may result in the reduction of osteoprotegerin.
Liver cirrhosis in HIV/HCV‐coinfected individuals is related to NK cell dysfunction and exhaustion, but not to an impaired NK cell modulation by CD4+ T‐cells
Authors: Polo María L , Ghiglione Yanina A , Salido Jimena P , Urioste Alejandra , Poblete Gabriela , Sisto Alicia E , Martinez Ana , Rolón María J , Ojeda Diego S , Cahn Pedro E , Turk Gabriela J , Laufer Natalia L
Published: September 2019

Introduction

HIV worsens HCV‐related liver disease by accelerating fibrosis progression; however, progression rates are extremely variable among HIV/HCV‐coinfected individuals. NK cells are associated with modulation of liver fibrosis and are profoundly altered during HCV and HIV infections. CD4+ T‐cells modulate NK cell function, and are also affected by HIV infection. Here, we aim to characterize the association of hepatic fibrosis with both the phenotype and function of peripheral NK cells and their regulation by CD4+ T‐cells, in HIV/HCV‐coinfected individuals.

Methods

Thirty‐four HIV/HCV‐coinfected individuals with minimal (n = 16) and advanced (n = 18) fibrosis (METAVIR F0/F1 and F4 scores respectively) and 20 healthy volunteers were enrolled. PBMC were obtained from peripheral blood samples and NK and CD4+ T‐cells were isolated and analysed. NK cell phenotype (CD25, CD69, Nkp46, NKG2D, PD‐1), degranulation (CD107a) and IFN‐γ and TNF‐α production, as well as CD4+ T‐cell activation (CD69, CD25 and CD38) were measured by flow cytometry. CD4+ T‐cell conditioned medium (CM) derived from F0/F1 or F4 individuals was assessed for IL‐2 levels by ELISA. Modulation of NK cell functionality by these CMs was also analysed.

Results

When comparing to NK cells from individuals with minimal fibrosis, degranulation and cytokine secretion by NK cells from subjects with F4 scores was significantly impaired, while PD‐1 expression was augmented. On the one hand, neither the expression of activation markers nor IL‐2 secretion was distinctly induced in CD4+ T‐cells from subjects with F0/F1 or F4 METAVIR scores. Finally, NK cell degranulation and cytokine secretion were not differentially modulated by CD4+ T‐cell CM, whether CD4+ T‐cells derived from subjects with minimal or advanced fibrosis.

Conclusions

Low levels of NK and CD4+ T‐cells in HIV/HCV‐coinfected individuals with advanced liver fibrosis have been previously described. Here, we show that advanced liver fibrosis in coinfected individuals is associated to a defective function of NK cells and an increased expression of the exhaustion/senescence marker PD‐1. This NK signature could not be attributed to changes in the ability of CD4+ T‐cells to modulate NK cell function.
Clinical correlation of liver function tests with suppression of cytokine signaling (SOCS1) gene expression in HCV infected patients: A real‐world clinical experience
Authors: Bin Wahid Sohaib , Ain Qurat Ul , Quraishi Azra , Wahid Braira
Published: September 2019

Hepatitis C virus (HCV) is the leading cause of chronic liver complications globally and suppressor of cytokine signaling‐1 (SOCS‐1) is a gene triggered by cytokines that activates transcription of the JAK/STAT signal transduction pathway and negatively regulates Janus kinase‐signal transducer. Several studies have shown that the expression of SOCS1 and SOCS3 genes negatively regulate the response of HCV infection to interferon therapy and interferon‐free regimens. It has been reported that liver function enzymes elevate in CHC patients but the association of SOCS1 gene expression with LFTs haven't been studied. This study recruited 114 CHC patients and 112 normal healthy participants and analyzed the correlation of SOCS1 gene expression and liver function enzymes (LFEs). Herein, we observed that the expression of SOCS1 gene had a positive correlation with LFEs.
Impaired Fracture Healing in Sarco‐Osteoporotic Mice Can Be Rescued by Vibration Treatment Through Myostatin Suppression
Authors: Zhang Ning , Chim Yu Ning , Wang Jinyu , Wong Ronald Man Yeung , Chow Simon K. H. , Cheung Wing‐Hoi
Published: September 2019

Sarcopenia is highly prevalent in fragility fracture patients and is associated with delayed healing. In this study, we investigated the effect of low‐magnitude high‐frequency vibration (LMHFV) on osteoporotic fracture with sarcopenia and the potential role of myostatin. Osteoporotic fractures created in sarcopenic SAMP8, non‐sarcopenic SAMR1 were randomized to control or LMHFV (SAMP8, SAMR1, SAMP8‐V, or SAMR1‐V) groups. Healing and myostatin expression were evaluated at 2, 4, and 6 weeks post‐fracture. In vitro, conditioned‐media were collected from myofibers isolated from aged and young SAMP8 or C2C12 myoblasts with or without LMHFV. Osteoblastic MC3T3‐E1 under osteogenic differentiation were treated with plain or conditioned‐medium (±myostatin propeptide). LMHFV significantly enhanced callus formation was in non‐sarcopenic SAMR1 mice; but the enhancement effect was not significant in SAMP8 mice at week 2. Myostatin expressions in callus and biceps femoris of SAMP8 group were significantly higher all groups with significant negative correlation with callus size (R2 = 0.7256; p = 0.0004). Mechanical properties (week 4) and callus remodeling (week 6) were inferior in SAMP8 versus SAMR1 and were significantly enhanced by LMHFV. Alkaline Phosphatase (ALP) and Runx2 expression of MC3T3‐E1 was lower in aged myofiber compared with young, but upregulated by LMHFV or myostatin inhibition; also confirmed with C2C12. LMHFV enhanced early callus formation, microarchitecture, callus remodeling and mechanical properties of fracture healing in both SAMP8 and SAMR1; however, more effective in non‐sarcopenic SAMR1 mice. Impaired fracture healing in sarcopenic SAMP8 mice is attributed by elevated myostatin expression in callus and muscle, which correlated negatively with callus formation. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:277‐287, 2020
Phase 3 Pilot Randomized Controlled Trial Comparing Early Trophic Enteral Nutrition With “No Enteral Nutrition” in Mechanically Ventilated Patients With Septic Shock
Authors: Patel Jayshil J. , Kozeniecki Michelle , Peppard William J. , Peppard Sarah R. , Zellner‐Jones Stephanie , Graf Jeanette , Szabo Aniko , Heyland Daren K.
Published: September 2019

Background

The optimal dose and timing of enteral nutrition (EN) in septic shock are unclear.

Methods

We conducted a phase 3 single‐center randomized controlled pilot trial comparing early trophic EN with “no EN” in mechanically ventilated adults with septic shock, with the hypothesis that implementing a protocol comparing early trophic EN with “no EN” in patients with septic shock would be feasible. Patients were randomized to early trophic EN or “no EN” until off vasopressor for 3 hours. The primary outcome was feasibility in achieving >75% consent and compliance rate and <10% contamination rate.

Results

One hundred thirty‐one patients were eligible for enrollment, and 49 were available for consent. Thirty‐one (86%) consented and were randomized and 100% of patients in the early EN arm and 94% in the “no EN” arm completed their protocols. While on vasopressors, early EN group received median 384 kcal, and the “no EN” group received median 0 kcal. Contamination rate was 0 in the early trophic EN arm and 6% in the “no EN” arm. The early EN group had median 25 intensive care unit–free days, as compared with 12 in the “no EN” arm (P = .014). The early EN arm had median 27 ventilator‐free days, compared with 14 in “no EN” arm (P = .009).

Conclusion

Our protocol comparing early trophic EN with “no EN” in septic shock was feasible. Early trophic EN may be beneficial, but a larger multicenter trial is warranted to confirm the observed clinical benefits seen in this trial.
The role of adjuvant chemotherapy in stage II and III mucinous colon cancer
Authors: Fields Adam C. , Lu Pamela , Goldberg Joel , Irani Jennifer , Bleday Ronald , Melnitchouk Nelya
Published: September 2019

Introduction

Mucinous adenocarcinoma is a subtype of colonic adenocarcinoma associated with worse survival compared to nonmucinous adenocarcinoma. Prior studies on the effect of chemotherapy on survival in mucinous adenocarcinoma have shown mixed results. The aim of this study is to evaluate the effect of chemotherapy on the survival of patients with stage II and III mucinous adenocarcinoma.

Methods

The National Cancer Database was used to identify patients diagnosed with stage II or III nonmucinous adenocarcinoma or mucinous adenocarcinoma between 2004 and 2016. The primary outcome was overall survival.

Results

Fourteen thousand and three hundred patients with stage II mucinous colon adenocarcinoma and 16 741 patients with stage III mucinous colon adenocarcinoma were identified. There was no significant difference in survival between nonmucinous adenocarcinoma and mucinous adenocarcinoma patients in adjusted analysis for stage II disease (HR:1.00, 95%CI:0.98‐1.02, P = .99), but there was a significant difference for stage III disease (HR:1.05, 95%CI:1.03‐1.07, P < .001). In propensity‐matched cohorts of patients with mucinous adenocarcinoma, chemotherapy was significantly associated with survival in stage II (HR:0.79, 95%CI:0.69‐0.90, P < .001) and stage III disease (HR:0.56, 95%CI:0.52‐0.60, P < .001).

Conclusions

Patients with stage II or stage III mucinous adenocarcinoma of the colon who are given adjuvant chemotherapy have significantly improved survival compared to patients not given chemotherapy.
Treatment outcome of chest wall soft tissue sarcomas: Analysis of prognostic factors
Authors: Nakahashi Naoya , Emori Makoto , Tsuchie Hiroyuki , Nagasawa Hiroyuki , Sonoda Tomoko , Takada Kohichi , Miyajima Masahiro , Watanabe Atsushi , Shimada Yoichi , Yamashita Toshihiko
Published: September 2019

Background

Primary soft tissue sarcomas (STSs) involving the chest wall are uncommon. The aim of this study was to identify factors that influence the prognosis of patients with primary chest wall STS.

Methods

The records of 38 patients (23 men and 15 women) who were treated at our institutions during 2002 to 2018 were reviewed. The following variables were evaluated as potential prognostic factors: sex, tumor size, chemotherapy, and completeness of surgical margins. Multivariate analysis was conducted to identify predictors of overall survival (OS) and disease‐free survival (DFS).

Results

Of the 38 included patients, 5 had low‐grade tumors and 33 had high‐grade tumors. Five patients required chest wall reconstruction including rib resection. Thirty patients (79%) underwent R0 resection. The 5‐year OS and DFS rates were 45% and 27%, respectively. Local recurrence developed in 7 patients. Multivariate analysis identified tumor size (hazard ratio [HR]: 4.13; 95% confidence interval [CI]: 1.05‐16.24; P = .04) and R1/2 resection (HR: 3.92; 95% CI: 1.12‐13.66; P = .03) as predictors of OS.

Conclusions

Prognostic factors for survival included tumor size and completeness of surgical margins. Complete tumor excision is desirable, particularly in cases of early detection.
Photodynamic Therapy for the Treatment of Complex Anal Fistula
Authors: Arroyo Antonio , Sánchez‐Guillén Luis , Parra Pedro Antonio , García‐Catalá Luis , Peña‐Ros Emilio , Ferrer‐Márquez Manuel , Nofuentes Riera Carmen , Barber‐Valles Xavier , Romero‐Simó Manuel
Published: September 2019

Background and Objectives

To validate and analyze the results of intralesional photodynamic therapy in the treatment of complex anal fistula.

Study Design/Materials and Methods

This prospective multicentric observational study enrolled patients treated for complex anal fistula who underwent intralesional photodynamic therapy (i‐PDT). The included patients were treated from January 2016 to December 2018 with a minimum follow‐up of 1 year to evaluate recurrence, continence and postoperative morbidity. Intralesional 5‐aminolevulinic acid (ALA) gel (2%) was injected directly into the fistula. The internal and external orifices were closed. After an incubation period of 2 hours, the fistula was irradiated using an optical fiber connected to a red laser (Multidiode 630 PDT) operating at 1 W/cm for 3 minutes (180 J).

Results

In total, 49 patients were included (61.2% male). The mean age was 48 years, and the mean duration of fistula was 13 months. Of the fistulas included, 75.5% were medium transphincteric, and 24.5% were high transphincteric. The median fistula length was 4 ± 1,14 cm (range: 3–5). A total of 41 patients (83.7%) had a previous history of fistula surgery. Preoperatively, some degree of anal incontinence was found in 5 patients (10.2%). No center reported any other procedure‐related complications intraoperatively. Phototoxicity was found in one patient. In the first 48 hours after the procedure, fever was reported in 2 patients (4%). At the end of follow‐up, total healing was observed in 32/49 patients (65.3%). No patient reported new incontinence postoperatively.

Conclusion

i‐PDT could be considered a good choice in patients with complex anal fistulas to avoid surgery and its complications. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.
Gene expression responses of tomato inoculated with Pectobacterium carotovorum subsp. carotovorum
Authors: Djami‐Tchatchou Arnaud T. , Matsaunyane Lerato B. T. , Ntushelo Khayalethu
Published: September 2019

Defense responses of tomato (Solanum lycopersicum L.) against attack by Pectobacterium carotovorum subsp. carotovorum (Pcc), the causal agent of soft rot diseases, were studied. The expression of some tomato defense genes were evaluated by real‐time PCR quantification analysis, 24 and 72 hr after actively growing tomato plants were inoculated with Pcc. These included: MYB transcriptor factor, ethylene response element‐binding protein, suppressor of the G2 allele of Skp1, cytochrome P450, small Sar1 GTPase, hydroxycinnamoyl‐CoA:quinate hydroxycinnamoyl transferase, pathogenesis‐related protein 1a, endo‐1,3‐beta‐glucanase, chitinase, proteinase inhibitor, defensin, CC‐NBS‐LRR resistance protein, and phenylalanine ammonia lyase. The results showed dynamic transcriptomic changes, with transcripts exhibiting different expression kinetics at 24 and 72 hr to confer resistance to tomato against Pcc infection.
Integral quality monitor (IQM®) signal correction factors for small fields to predict larger irregular segment output signals
Authors: Mahuvava Courage , Du Plessis Frederik Carl Phillipus
Published: September 2019

Purpose

To develop a method of correcting for the inaccuracies of small adjoined field segments in their contribution to larger fields in order to get a better match between their combined signals and the measured integral quality monitor (IQM) open field signals. This would enable the pre‐calculation of known irregular segment output signals per monitor unit (MU), which would be later useful for patient‐based dose calculations for treatment verification during pre‐treatment treatment validation using the IQM output signal per MU.

Methods

Small fields exhibit source obscurity and loss of scatter, resulting in smaller signals being measured by the IQM and the subsequent underestimation of IQM output signals of larger segments obtained by combining small segment signals. Larger field segments were broken down into a set of smaller, regular, abutted segments, whose individual signals were added together to get the predicted output signal of the larger field. The signal/MU for each smaller constituent segment was extracted at its exact location from measured IQM response maps, generated by irradiating the IQM with small elementary segments ranging from 1 × 1 cm2 –5 × 5 cm2, shifting each segment 1 cm at a time and measuring its corresponding output signal/MU throughout the entire IQM sensitive area. The predicted signal was weighed against the IQM‐measured signal of the open field to calculate a signal correction factor (CF) of each elementary segment size. The CFs were applied to known signals of each set of elementary fields before summation in order to pre‐calculate signals of larger irregular fields more accurately. The dependence of CFs on elementary segment size, location of the open field, and beam energy was investigated.

Results

CFs exhibited an exponential decrease with increase in elementary segment size. CFs were also invariant with beam energy, changing by ≤1% from 6–15 MV. Uncorrected signals for regular fields had relative errors of above 5% whilst signal correction reduced these errors down to ~0.4% (i.e., 99.6% accuracy). For irregular fields, signal correction reduced calculation errors from ~10% to well below 1.5%. Larger signal prediction errors were found when smaller segments were used to reconstruct the field. Open field size and location had a great impact on measured signals but virtually no significance on CFs.

Conclusions

Results indicate that summation of small segment signals cannot sufficiently reproduce the same output given by an open field if individual elementary segment signals are not weighted with their respective CFs. This effect is particularly predominant for elementary segments 3 × 3 cm2 and for irregular fields. The method outlined enabled the calculation of signal CFs in order to match predicted signals with measured signals to 98.5% accuracy, thus enabling the pre‐calculation of irregular segment output signals/MU for future patient dose calculations.
Chronic Pancreatitis and Nutrition Therapy
Authors: O'Brien Stephen J. , Omer Endashaw
Published: September 2019

Chronic pancreatitis is a complex and irreversible disease of the pancreas and is associated with significant morbidity and mortality. Nutrition deficiencies in chronic pancreatitis are common and can be atypical in nature. As such, the management of these deficiencies can be individualized for patients. The aim of this review is to discuss the components of nutrition deficiencies in chronic pancreatitis, their management, and the current areas of research that are being explored. The clinical guidelines of major national and international societies were analyzed for recommendations on the nutrition management of chronic pancreatitis. The etiology of nutrition deficiencies in chronic pancreatitis is multifactorial and includes aspects of exocrine and/or endocrine dysfunction, significant abdominal pain, often persistent alcohol consumption, and increased metabolic activity. A large number of patients with nutrition deficiencies are underrecognized and undertreated. Although the majority of these patients can be managed by oral and pancreatic enzyme supplementation, some patients may require enteral tube feeding and, in rare cases, parenteral feeding. Current areas of research include the accurate identification of patients at risk for nutrition deficiencies, optimization of feeding regimens, and research into islet cell autotransplantation.
Nonalcoholic Fatty Pancreas Disease
Authors: Shah Nihar , Rocha Jason P. , Bhutiani Neal , Omer Endashaw
Published: September 2019

Nonalcoholic fatty pancreas disease (NAFPD) describes a phenotype of pancreatic steatosis (PS) that is not caused by alcohol consumption, viral infections, toxins, or congenital metabolic syndromes but is associated with insulin resistance, malnutrition, obesity, metabolic syndrome, or increasing age. NAFPD is a relatively new disease entity, as the clinical significance of fatty infiltration of pancreas has gained attention recently. Clinical consequences of NAFPD remain largely unknown despite clinical associations. This review aims to study similarities and differences between hepatic and PS and explore recent advances in NAFPD.