bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cowpea Mosaic Virus Immunotherapy Combined with Cyclophosphamide Reduces Breast Cancer Tumor Burden and Inhibits Lung Metastasis
Authors: Cai Hui , Wang Chao , Shukla Sourabh , Steinmetz Nicole F. 
Published: June 2019

AbstractPatients with metastatic triple‐negative breast cancer (TNBC) have a poor prognosis, so new therapies or drug combinations that achieve more effective and durable responses are urgently needed. Here, a combination therapy using cowpea mosaic virus (CPMV) and low doses of cyclophosphamide (CPA) is developed with remarkable synergistic efficacy against 4T1 mouse tumors in vivo. The combination therapy not only attenuates the growth of primary tumor and increases survival, but also suppresses distant tumor growth and reduces lung metastasis. Mechanistic analysis indicates that the combination of CPMV and CPA increases the secretion of several cytokines, activates antigen‐presenting cells, increases the abundance of tumor infiltrating T cells, and systematically reverses the immunosuppression. These results show that the combination of CPMV in situ vaccination with chemotherapy may become a potent new strategy for the treatment of TNBC.
Maternal nutrient intake and fetal gastroschisis: A case‐control study
Authors: Centofanti Sandra F. , Francisco Rossana P. V. , Phillippi Sonia T. , Galletta Marco A. K. , Sousa Ana M. S. , Rodrigues Agatha S. , Curi Rui , Brizot Maria L. 
Published: June 2019

AbstractFetal gastroschisis is a paraumbilical abdominal wall defect with herniation of the abdominal organs. This multifactorial malformation occurs in young pregnant women, and the underlying cause of the disease remains unknown; however, nutritional factors may play a role in its development. This case‐control study explored the association of maternal nutrient intake with the occurrence of gastroschisis. The gastroschisis group (GG) comprised 57 pregnant women with fetuses with gastroschisis, and the control group (CG) comprised 114 pregnant women with normal fetuses matched for maternal age, gestational age, and preconception body mass index classification. Nutritional assessments related to the preconception period were obtained using the food consumption frequency questionnaire, and nutrient intakes were calculated using nutrition programs. The median daily calorie intake was higher (2,382.43 vs. 2,198.81; p = .041) in the GG than in the CG. The median intake of methionine (763.89 vs. 906.34; p = .036) and threonine (1,248.34 vs. 1,437.01; p = .018) was lower in the GG than in the CG. Pregnant women with fetuses with gastroschisis have a diet characterized by higher calorie intake and lower levels of essential amino acids (methionine and threonine) during the preconception period than pregnant women with normal fetuses.
Towards anticancer fluoroquinolones: A review article
Authors: Abdel‐Aal Mohamed A. A. , Abdel‐Aziz Salah A. , Shaykoon Montaser Sh. A. , Abuo‐Rahma Gamal El‐Din A. 
Published: June 2019

AbstractDifferent studies about the anticancer potential of several medically used antibacterial fluoroquinolones have been established. Fluoroquinolone derivatives, like some anti‐cancer drugs, such as doxorubicin, can achieve antitumor activity via poisoning of type II human DNA topoisomerases. Interestingly, structural features required for the anticancer activity of quinolones have been determined. Most of the chemical modifications required to convert antibacterially acting fluoroquinolones into their anticancer analogs were at position 7 and the carboxylic group at position 3. This review highlights the antitumor potential of fluoroquinolones in general and summarizes the chemical modifications carried out on fluoroquinolones to become anticancer agents. Moreover, the review gives a quick recap on metal ion chelates with fluoroquinolones and their substantial role in topoisomerase poisoning and antitumor potential improvement. Hence, it should be highly interesting for researchers attempting to design and synthesize novel anticancer fluoroquinolone candidates.
The population‐attributable fraction for time‐dependent exposures using dynamic prediction and landmarking
Authors: von Cube Maja , Schumacher Martin , Putter Hein , Timsit Jéan‐François , van de Velde Cornelis , Wolkewitz Martin 
Published: June 2019

AbstractThe public health impact of a harmful exposure can be quantified by the population‐attributable fraction (PAF). The PAF describes the attributable risk due to an exposure and is often interpreted as the proportion of preventable cases if the exposure was extinct. Difficulties in the definition and interpretation of the PAF arise when the exposure of interest depends on time. Then, the definition of exposed and unexposed individuals is not straightforward. We propose dynamic prediction and landmarking to define and estimate a PAF in this data situation. Two estimands are discussed which are based on two hypothetical interventions that could prevent the exposure in different ways. Considering the first estimand, at each landmark the estimation problem is reduced to a time‐independent setting. Then, estimation is simply performed by using a generalized‐linear model accounting for the current exposure state and further (time‐varying) covariates. The second estimand is based on counterfactual outcomes, estimation can be performed using pseudo‐values or inverse‐probability weights. The approach is explored in a simulation study and applied on two data examples. First, we study a large French database of intensive care unit patients to estimate the population‐benefit of a pathogen‐specific intervention that could prevent ventilator‐associated pneumonia caused by the pathogen Pseudomonas aeruginosa. Moreover, we quantify the population‐attributable burden of locoregional and distant recurrence in breast cancer patients.
Simultaneous determination of 19 constituents in Cimicifugae Rhizoma by HPLC–DAD and screening for antioxidants through DPPH free radical scavenging assay
Authors: Niu Xueni , Qin Rulan , Zhao Yudan , Han Ling , Lu Jincai , Lv Chongning 
Published: June 2019

AbstractCimicifugae Rhizoma (sheng ma) is a well‐known traditional Chinese medicine, which has been demonstrated to possess anti‐inflammatory, antipyretic and analgesic activities. In the present study, a simple and efficient HPLC–DAD (high‐performance liquid chromatography coupled with diode array detection) method was developed and validated for simultaneous quantification of 19 chemical components (including 16 phenolic acids, one coumarin and two alkaloids) in Cimicifugae Rhizoma. The result indicated that this method could effectively evaluate the quality of Cimicifugae Rhizoma and provide a valuable reference for further study. Additionally, the antioxidant activity of Cimicifugae Rhizoma was evaluated by DPPH (1,1‐diphenyl‐2‐picrylhydrazyl) radical scavenging assay. The results showed that the content of phenolic acids and antioxidant activity exhibited significant correlation coefficients.
Effects of medium composition on the growth and lipid production of microplasmodia of Physarum polycephalum
Authors: Truong Kiet A. , Stephenson Steven L. , Phung Trung V. , Tran Hanh T.M. 
Published: June 2019

AbstractPhysarum polycephalum is a plasmodial slime mold. One of the trophic stages in the life cycle of this organism is a plasmodium. In submerged culture, plasmodia are fragmented into microplasmodia. The latter both lack cell walls and are capable of rapid growth. There has been limited information on the effects of medium composition on the growth and lipid accumulation of microplasmodia. In this study, optimization of medium components by response surface methodology showed that tryptone and yeast extract concentrations had the most significant effects on lipid and biomass production; significant synergistic interactions between glucose and tryptone concentration on these responses were also recorded. The optimal medium was composed of 20 g/L of glucose, 6.59 g/L of tryptone, and 3.0 g/L of yeast extract. This medium yielded 13.86 g/L of dry biomass and 1.97 g/L of lipids. These amounts are threefold higher than those of the American Type Culture Collection (ATCC) medium. In addition, biomass and lipid production reached maximal values between only 4 and 5 days. Fatty acid compositions analysis by gas chromatography‐mass spectrometer (GC–MS) revealed that P. polycephalum lipids consisted mainly of oleic acid (40.5%), linoleic acid (10%), and octadecynoic (15.8%). This is the first report on the fatty acid composition of P. polycephalum microplasmodia. These results suggest that the biomass of microplasmodia could be used as a source of material for direct conversion into biodiesel because of the absence of cell walls or it could also be used as a supplemental source of beneficial fatty acids for humans, albeit with some further evaluation needed.
DACH1 suppresses epithelial to mesenchymal transition (EMT) through Notch1 pathway and reverses progestin resistance in endometrial carcinoma
Authors: Zhou Qing , Li Wenzhi , Kong Deshui , Liu Zhiming , Shi Zhengzheng , Ma Xiaohong , Li Yongmei , Jiang Jie 
Published: June 2019

AbstractProgestin resistance limits the effectiveness of progestin therapy in endometrial carcinoma for patients who desire to preserve fertility. To investigate the molecular mechanism of progestin resistance in endometrial carcinoma, we performed microarray analysis among Ishikawa and progestin resistant cell IshikawaPR cells. We found that epithelial to mesenchymal transition (EMT) was involved in progestin resistance and dachshund family transcription factor 1 (DACH1) is positively correlated with progesterone receptor (PGR). Knockdown of DACH1 in Ishikawa cell promoted proliferation, metastasis ability, and resistance to progestin. Conversely, overexpression of DACH1 in IshikawaPR cell rendered more sensitive to progestin treatment. Xenograft model assay also had similar results. In addition, our data showed that DACH1 overexpression inhibited EMT and decreased c‐Jun, Notch1 and Hes1expression. Our study demonstrated for the first time that EMT is involved in progestin resistance of EC. The response to progestin could be reserved by DACH1 suppressed EMT through Notch1 pathway via c‐Jun.
Chronic retinoic acid treatment induces differentiation and changes in the metabolite levels of brown (pre)adipocytes
Authors: Suzuki Mika , Chen Hsuan‐Ju , Tomonaga Shozo , Hashimoto Osamu , Kawada Teruo , Matsui Tohru , Funaba Masayuki 
Published: June 2019

Dietary vitamin A status affects energy metabolism. The present study explored the effect of all‐trans retinoic acid (ATRA) on the expression levels of molecules and metabolites of brown adipocytes. Chronic ATRA treatment was initiated during the early stage (days 0‐8) or late stage (days 8‐12) of adipogenesis. Treatment with ATRA during the early and late stage of adipogenesis resulted in an increase in the expression level of Ucp1 and Cidea, genes highly expressed in brown adipocytes, on day 8 and day 12, respectively, whereas expression of Pgc‐1α, another gene expressed during brown adipogenesis, was unaffected by ATRA. Non‐targeted metabolomic analyses indicated that the pathways related to the glucose metabolism were affected by ATRA, irrespective of the differentiation stage. Cellular levels of glucose 6‐phosphate, fructose 6‐phosphate, citric acid, and succinic acid decreased after ATRA treatment on days 8 and 12. In contrast, glucose level was higher in ATRA‐treated cells on day 8, but it was lower on day 12. ATRA decreased the cellular level of aconitic acid, fumaric acid, and malic acid on day 12 but not on day 8. Furthermore, ATRA increased the expression level of Hxk2 and downregulated the expressions of G6pdh and Pfkl/Pfkp on day 8 but not on day 12. Together, the results indicate that the chronic treatment with ATRA stimulated the formation of activated brown adipocytes, eventually leading to alterations in the levels of cellular metabolites related to glucose metabolism.Significance of the studySignificance of the study treatment with all‐trans retinoic acid (ATRA) during the early and late stage of adipogenesis increased the expression of Ucp1 and Cidea, genes highly expressed in brown adipocytes, on day 8 and day 12. Cellular levels of glucose 6‐phosphate, fructose 6‐phosphate, citric acid, and succinic acid decreased after ATRA treatment on days 8 and 12. In contrast, glucose level was higher in ATRA‐treated cells on day 8, but it was lower on day 12. The present results indicate that ATRA stimulated the formation of activated brown adipocytes, eventually leading to alterations in the levels of cellular metabolites related to glucose metabolism.
On the Enzymatic Formation of Metal Base Pairs with Thiolated and pKa‐Perturbed Nucleotides
Authors: Levi‐Acobas Fabienne , Röthlisberger Pascal , Sarac Ivo , Marlière Philippe , Herdewijn Piet , Hollenstein Marcel 
Published: June 2019

AbstractThe formation of artificial metal base pairs is an alluring and versatile method for the functionalization of nucleic acids. Access to DNA functionalized with metal base pairs is granted mainly by solid‐phase synthesis. An alternative, yet underexplored method, envisions the installation of metal base pairs through the polymerization of modified nucleoside triphosphates. Herein, we have explored the possibility of using thiolated and pKa‐perturbed nucleotides for the enzymatic construction of artificial metal base pairs. The thiolated nucleotides S2C, S6G, and S4T as well as the fluorinated analogue 5FU are readily incorporated opposite a templating S4T nucleotide through the guidance of metal cations. Multiple incorporation of the modified nucleotides along with polymerase bypass of the unnatural base pairs are also possible under certain conditions. The thiolated nucleotides S4T, S4T, S2C, and S6G were also shown to be compatible with the synthesis of modified, high molecular weight single‐stranded (ss)DNA products through TdT‐mediated tailing reactions. Thus, sulfur‐substitution and pKa perturbation represent alternative strategies for the design of modified nucleotides compatible with the enzymatic construction of metal base pairs.
Controlled sprouting in wheat increases quality and consumer acceptability of whole‐wheat bread
Authors: Johnston Rachel , Martin John M. , Vetch Justin M. , Byker‐Shanks Carmen , Finnie Sean , Giroux Michael J. 
Published: June 2019

AbstractBackground and objectivesIntentional sprouting of grain to modify grain products nutritional composition and flavor has been in practice for thousands of years. However, few studies have tested the impact of controlled sprouting on wheat flour functionality and flavor. In this study, grain of nine hard red spring (HRS) wheat (Triticum aestivum L) cultivars was sprouted with the goal of attaining a falling number (FN) value of 200 from a starting FN of 350 s. Paired samples of sprouted and sound HRS grain were then assayed for nutritional composition, functionality in bread baking, and in bread taste tests.FindingsSprouting reduced grain hardness and test weight while increasing grain color brightness, yellowness, and redness. Whole‐sprouted grain flour had twice the alpha amylase activity and a large decrease in flour swelling power relative to sound grain flour. Sprouted flour also contained increased free amino acids and monosaccharides while having decreased sugar alcohol content. Total dietary fiber trended down in the sprouted grain flour while starch content remained unchanged. Whole‐grain flour color parameters were relatively unaltered by sprouting. Sprouting reduced dough mix times while increasing loaf volume. Sensory panel evaluations demonstrated that testers preferred bread prepared from sprouted grain flour to bread prepared from sound grain while also finding that sprouted grain bread tasted less bitter and grainy while also being perceived as sweeter and moister.ConclusionsThe results demonstrate that controlled sprouting of wheat grain could be used to increase whole‐grain flour functionality in bread baking and consumer acceptability of whole‐grain foods.Significance and noveltySprouting of wheat to a FN of ~200 increases loaf volume and consumer preference of whole‐grain bread. Greater consumer acceptability could lead to increased consumption of whole‐grain bread.
Two‐Photon Absorption and Cell Imaging of Fluorene‐Functionalized Epicocconone Analogues
Authors: Oger Samuel , Schapman Damien , Mougeot Romain , Leleu Stéphane , Lascoux Noëlle , Baldeck Patrice , Bénard Magalie , Gallavardin Thibault , Galas Ludovic , Franck Xavier 
Published: June 2019

AbstractEpicocconone 1 is a natural chromophore isolated from the fungus Epicoccum nigrum that has shown applications in proteomics and fluorescent microscopy thanks to its unique pro‐fluorescence properties. The modification of the skeleton of the natural product by replacing the triene side chain by a fluorenyl scaffold can noticeably increase the fluorophore's absorption coefficient. The synthesis of the analogues of the natural product has been made possible by the use of a palladium‐catalyzed carbonylation reaction, allowing the construction of the β‐keto‐dioxinone key intermediate. Two‐photon absorption cross‐section measurements of the fluorenyl epicocconone analogues show a structure dependency with values ranging from 60 to 280 GM and live cell imaging show intense staining of intracellular vesicle‐like structures around the nucleus.
Direct meta‐C−H Perfluoroalkenylation of Arenes Enabled by a Cleavable Pyrimidine‐Based Template
Authors: Brochetta Massimo , Borsari Tania , Bag Sukdev , Jana Sadhan , Maiti Siddhartha , Porta Alessio , Werz Daniel B. , Zanoni Giuseppe , Maiti Debabrata 
Published: June 2019

AbstractThe development of efficient and mild methods for the synthesis of organofluorine compounds is of foremost interest in various fields of chemistry. A direct pyrimidine‐based selective meta‐C−H perfluoroalkenylation of arenes involving several commercially available perfluoroolefins is described. The synthetic versatility of the protocol is demonstrated by an extensive substrate scope including different benzylsulfonyl, alkylarene and phenylacetic acid scaffolds. The generality of this methodology including the meta‐C−H perfluoroalkenylation of Ibuprofen, the facile cleavage of the directing group and gram‐scale reactions are presented.
Concordance in postsurgical radioactive iodine therapy recommendations between Watson for Oncology and clinical practice in patients with differentiated thyroid carcinoma
Authors: Kim Mijin , Kim Bo Hyun , Kim Jeong Mi , Kim Eun Heui , Kim Keunyoung , Pak Kyoungjune , Jeon Yun Kyung , Kim Sang Soo , Park Heeseung , Kang Taewoo , Lee Byung Joo , Kim In Joo 
Published: June 2019

BackgroundTo the authors' knowledge, the indications for radioactive iodine (RAI) therapy in patients with differentiated thyroid carcinoma (DTC) are unclear; treatment decisions are based on physician judgment. The objective of the current study was to identify the degree of concordance between postsurgical RAI therapy recommended by Watson for Oncology (WFO), a clinical decision support system for oncological therapy, and that recommended by physicians for patients with DTC.MethodsThe current retrospective cohort study included 207 patients with DTC who underwent thyroidectomy between 2017 and 2018. Treatment recommendations were considered concordant if WFO rendered recommendations consistent with those of the physicians.ResultsTreatment recommendations were concordant for 160 patients (77%). The concordance rate significantly differed according to the American Thyroid Association (ATA) risk category (P < .001) and American Joint Committee on Cancer TNM stage (seventh edition; P = .004). Logistic regression analysis demonstrated that treatment recommendations were significantly less likely to be concordant in patients with ATA intermediate‐risk and stage III disease compared with those with ATA low‐risk and stage I disease (odds ratio, 0.16 [P < .001] and OR, 0.35 [P = .004], respectively).ConclusionsThe authors believe the concordance rate between postsurgical RAI therapy recommendations rendered by WFO and those rendered by physicians was too low to justify adopting WFO for the comprehensive screening of patients with DTC. This is particularly true among patients with ATA intermediate‐risk and stage III disease, reflecting differences in practice patterns between the United States (where WFO was calibrated) and Korea. Hence, WFO is not a substitute for physicians, and also may require regional customization to improve its assistive capability.
Risk of Hypoglycemia and Concomitant Use of Repaglinide and Clopidogrel: A Population‐Based Nested Case‐Control Study
Authors: Wei Yun , Lin Fang‐Ju , Lin Shin‐Yi , Wang Chi‐Chuan 
Published: June 2019

This nested case‐control study evaluated the potential interaction between repaglinide and clopidogrel. Cases were defined by inpatient admissions or emergency department visits due to hypoglycemia. Concomitant use of repaglinide and clopidogrel within 3 days before the hypoglycemic event was the exposure of interest. For each case, up to four controls were randomly selected and matched by age, sex, type of glinide used (repaglinide or nateglinide), and time since cohort entry to the index date. Hypoglycemic risk was estimated by conditional logistic regressions. Concomitant use of repaglinide and clopidogrel was associated with an increased risk of hypoglycemia compared with repaglinide alone (adjusted odds ratio: 2.42; 95% confidence interval: 1.75−3.35). No significant associations were found with the two negative control object drug concomitants: nateglinide and clopidogrel and repaglinide and aspirin (without clopidogrel use). Our study suggests drug interaction between clopidogrel and repaglinide is clinically relevant and could increase the risk for hypoglycemia.
The motivational effect of multicolored dental restoration on dental behavior of first preliminary school children
Authors: Melebari Lojain Abdulaziz , Attas Seba Essam , Arafa Abla 
Published: June 2019

AbstractObjectivesTo assess the motivational effect of multi‐colored restoration on the anxiety level of pediatric patients at thedental clinic and its motivational effect on their oral hygiene status.Material and methodsA total of 30 participants.ResultsBoth groups revealed reduction in the anxiety level and improvement in their behavior at the dental office but did not reach significance. Plaque index showed a significant reduction per group and a near significance as compared between test groups.ConclusionsThe use of the multicolored restoration could provide a potential advantage to improve the oral health status of children and might aid in enhancing their behavior at dental clinic particularly younger age groups.
Transitioning towards the bio‐economy: Assessing the social dimension through a stakeholder lens
Authors: Falcone Pasquale Marcello , González García Sara , Imbert Enrica , Lijó Lucía , Moreira María Teresa , Tani Almona , Tartiu Valentina Elena , Morone Piergiuseppe 
Published: June 2019

AbstractInternational institutions are calling for a transition towards more sustainable systems of production and consumption. In this transition, sustainable innovations are expected to play an ever‐increasing role. In particular, the production of innovative bio‐based products—products wholly or partly derived from biological materials or from innovative production processes and/or innovative biomass such as food waste or forest residuals—will be part of this process. However, the sustainability of such products must be assured along their entire life cycle and across the three dimensions mentioned above. Against this background, our study aimed at identifying a social impact framework tailored to bio‐based products. It employed a two‐step methodological framework encompassing (a) identification of the relevant social impact categories, subcategories, and indicators and (b) validation of these factors, according to participatory stakeholder involvement. The validation exercise enabled us to consider a restricted number of social indicators so as to reduce the amount of data needed for assessing and decreasing related costs.