bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural Determination of Antioxidant and Anticancer Flavonoid Rutin in Solution through DFT Calculations of 1H NMR Chemical Shifts
Authors: De Souza Leonardo A. , Da Silva Haroldo C. , De Almeida Wagner B. 
Published: November 2018

AbstractAs the knowledge of the predominant molecular structure of antioxidant and anticancer flavonoid rutin in solution is very important for understanding the mechanism of action, a quantum chemical investigation of plausible rutin structures including solvent effects is of relevance. In this work, DFT calculations were performed to find possible minimum energy structures for the rutin molecule. 1H NMR chemical shift DFT calculations were carried out in DMSO solution using the polarizable continuum model (PCM) to simulate the solvent effect. Analysis of the experimental and theoretical 1H NMR chemical shift profiles offers a powerful fingerprint criterion to determine the predominant molecular structure in solution. Therefore, our aim is to find the best match between experimental (in DMSO‐d) and theoretical (PCM–DMSO) 1H NMR spectrum profiles. Among 34 optimized structures located on the potential energy surface, we found that structure 32, with a B‐ring deviated 30° from a planar configuration (geometry usually assumed for polyphenols), showed an almost perfect agreement with experimental the 1H NMR pattern when compared to the corresponding fully optimized planar geometry. This structure is also predicted as the global minimum based on room‐temperature Gibbs free energy calculations in solution and, therefore, should be experimentally observed. This is new and valuable structural information regarding structure–activity relationship studies, and such information is hard to obtain by experimentalists without the aid of the X‐ray diffraction technique.
A systematic review: the appraisal of the effects of metformin on lipoprotein modification and function
Authors: Kheniser K. G. , Kashyap S. R. , Kasumov T. 
Published: November 2018

SummaryAimsMetformin is a commonly prescribed anti‐hyperglycaemic pharmacological agent, and it remains a staple in the management of type II diabetes. In addition to metformin's glucose lowering effects, research has indicated that metformin inhibits glycation‐mediated and oxidative modification of lipoprotein residues. The purpose was to discuss the effects of metformin as it relates to high‐density lipoprotein (HDL) and low‐density lipoprotein (LDL) modification.Materials and methodsThe purpose was to conduct a narrative and pragmatic review on the effects of metformin as it pertains to HDL and LDL modification.ResultsHigh‐density lipoprotein (HDL) concentration is a quantitative measure and therefore does not provide insight into its function, which is a qualitative property. Dysfunctional HDLs are unable to carry out functions normally associated with HDL because they can be modified by glycating agents. Metformin may counteract HDL dysfunction by abating HDL modification. Reductions in HDL modification may improve reverse cholesterol transport ability and thus possibly diminish cardiovascular risk. Similarly, metformin‐mediated attenuations in LDL modification may reduce their atherogenic potency.ConclusionMetformin may partially ameliorate HDL dysfunction and reduce LDL modification by inhibiting alpha‐dicarbonyl‐mediated modification of apolipoprotein residues; consequently, the results are salient because cardiovascular disease incidence may be reduced given that reverse cholesterol transport activity predicts risk, and modified LDL are proatherogenic.
Doxorubicin‐induced cardiotoxicity involves IFNγ‐mediated metabolic reprogramming in cardiomyocytes
Authors: Ni Chen , Ma Pan , Wang Ruirui , Lou Xiaohan , Liu Xiaomeng , Qin Yue , Xue Rui , Blasig Ingolf , Erben Ulrike , Qin Zhihai 
Published: November 2018

AbstractImmune responses contribute to a large extent to heart diseases. However, it is still not clear how the key inflammatory mediator interferon‐γ (IFNγ) plays a role in doxorubicin (DOX)‐induced cardiomyopathy. We report here that DOX‐induced heart dysfunction involves IFNγ signaling in mice. The IFNγ receptor was found to be highly expressed on cardiomyocytes, and its downstream signaling was activated in heart tissues upon DOX treatment. In vitro, IFNγ strongly aggravated the injury of cardiomyocytes exposed to DOX. Although not affecting DOX‐induced cell death, IFNγ disrupted mitochondrial respiration and fatty acid oxidation in DOX‐exposed cardiomyocytes. IFNγ extended the suppression of the AMP‐activated protein kinase (AMPK)/acetyl‐CoA carboxylase (ACC) axis by DOX to a p38‐dependent branch. Activation of AMPK or inhibition of p38 inhibited the enhancing effect of IFNγ on the DOX‐induced cardiotoxicity and prolonged the survival time in DOX‐treated mice. Taken together, our results indicate that reprogramming of cardiac metabolism by IFNγ represents a previously unidentified key step for DOX‐induced cardiomyopathy. This unavoidable impact of IFNγ on cardiomyocyte metabolism during chemotherapy redirects our attention to the balance between beneficial immunosurveillance of cancer cells and unwanted toxic side‐effects. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Identification and validation of DOCK4 as a potential biomarker for risk of bone metastasis development in patients with early breast cancer
Authors: Westbrook Jules A , Wood Steven L , Cairns David A , McMahon Kathryn , Gahlaut Renu , Thygesen Helene , Shires Mike , Roberts Stephanie , Marshall Helen , Oliva Maria R , Dunning Mark J , Hanby Andrew M , Selby Peter J , Speirs Valerie , Mavria Georgia , Coleman Robert E , Brown Janet E 
Published: November 2018

AbstractSkeletal metastasis occurs in around 75% of advanced breast cancers, with the disease incurable once cancer cells disseminate to bone, but there remains an unmet need for biomarkers to identify patients at high risk of bone recurrence. This study aimed to identify such a biomarker and to assess its utility in predicting response to adjuvant zoledronic acid (zoledronate). We used quantitative proteomics (stable isotope labelling by amino acids in cell culture‐mass spectrometry; SILAC‐MS) to compare protein expression in a bone‐homing variant (BM1) of the human breast cancer cell line MDA‐MB‐231 with parental non‐bone‐homing cells to identify novel biomarkers for risk of subsequent bone metastasis in early breast cancer. SILAC‐MS showed that dedicator of cytokinesis protein 4 (DOCK4) was upregulated in bone‐homing BM1 cells, confirmed by western blotting. BM1 cells also had enhanced invasive ability compared with parental cells, which could be reduced by DOCK4‐shRNA. In a training tissue microarray (TMA) comprising 345 patients with early breast cancer, immunohistochemistry followed by Cox regression revealed that high DOCK4 expression correlated with histological grade (p = 0.004) but not oestrogen receptor status (p = 0.19) or lymph node involvement (p = 0.15). A clinical validation TMA used tissue samples and the clinical database from the large AZURE adjuvant study (n = 689). Adjusted Cox regression analyses showed that high DOCK4 expression in the control arm (no zoledronate) was significantly prognostic for first recurrence in bone (HR 2.13, 95%CI 1.06–4.30, p = 0.034). No corresponding association was found in patients who received zoledronate (HR 0.812, 95%CI 0.176–3.76, p = 0.790), suggesting that treatment with zoledronate may counteract the higher risk for bone relapse from high DOCK4‐expressing tumours. High DOCK4 expression was not associated with metastasis to non‐skeletal sites when these were assessed collectively. In conclusion, high DOCK4 in early breast cancer is significantly associated with aggressive disease and with future bone metastasis and is a potentially useful biomarker for subsequent bone metastasis risk. Copyright © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
UCP2‐dependent improvement of mitochondrial dynamics protects against acute kidney injury
Authors: Qin Nan , Cai Ting , Ke Qingqing , Yuan Qi , Luo Jing , Mao Xiaoming , Jiang Lei , Cao Hongdi , Wen Ping , Zen Ke , Zhou Yang , Yang Junwei 
Published: November 2018

AbstractAcute kidney injury (AKI) is a public health concern, with high morbidity and mortality rates in hospitalized patients and because survivors have an increased risk of progression to chronic kidney disease. Mitochondrial damage is the critical driver of AKI‐associated dysfunction and loss of tubular epithelial cells; however, the pathways that mediate these events are poorly defined. Here, in murine ischemia/reperfusion (I/R)‐induced AKI, we determined that mitochondrial damage is associated with the level of renal uncoupling protein 2 (UCP2). In hypoxia‐damaged proximal tubular cells, a disruption of mitochondrial dynamics demonstrated by mitochondrial fragmentation and disturbance between fusion and fission was clearly indicated. Ucp2‐deficient mice (knockout mice) with I/R injury experienced more severe AKI and mitochondrial fragmentation than wild‐type mice. Moreover, genetic or pharmacological treatment increased UCP2 expression, improved renal function, reduced tubular injury and limited mitochondrial fission. In cultured proximal tubular epithelial cells, hypoxia‐induced mitochondrial fission was exacerbated in cells with UCP2 deletion, whereas an increase in UCP2 ameliorated the hypoxia‐induced disturbance of the balance between mitochondrial fusion and fission. Furthermore, results following modulation of UCP2 suggested it has a role in preserving mitochondrial integrity by preventing loss of membrane potential and reducing subsequent mitophagy. Taken together, our results indicate that UCP2 is protective against AKI and suggest that enhancing UCP2 to improve mitochondrial dynamics has potential as a strategy for improving outcomes of renal injury. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Intraductal patient‐derived xenografts of estrogen receptor α‐positive breast cancer recapitulate the histopathological spectrum and metastatic potential of human lesions
Authors: Fiche Maryse , Scabia Valentina , Aouad Patrick , Battista Laura , Treboux Assia , Stravodimou Athina , Zaman Khalil ,   RLS, Dormoy Valerian , Ayyanan Ayyakkannu , Sflomos George , Brisken Cathrin 
Published: November 2018

AbstractEstrogen receptor α‐positive (ER‐positive) or ‘luminal’ breast cancers were notoriously difficult to establish as patient‐derived xenografts (PDXs). We and others recently demonstrated that the microenvironment is critical for ER‐positive tumor cells; when grafted as single cells into milk ducts of NOD Scid gamma females, >90% of ER‐positive tumors can be established as xenografts and recapitulate many features of the human disease in vivo. This intraductal approach holds promise for personalized medicine, yet human and murine stroma are organized differently and this and other species specificities may limit the value of this model. Here, we analyzed 21 ER‐positive intraductal PDXs histopathologically. We found that intraductal PDXs vary in extent and define four histopathological patterns: flat, lobular, in situ and invasive, which occur in pure and combined forms. The intraductal PDXs replicate earlier stages of tumor development than their clinical counterparts. Micrometastases are already detected when lesions appear in situ. Tumor extent, histopathological patterns and micrometastatic load correlate with biological properties of their tumors of origin. Our findings add evidence to the validity of the intraductal model for in vivo studies of ER‐positive breast cancer and raise the intriguing possibility that tumor cell dissemination may occur earlier than currently thought. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Social adjustment of adolescent cancer patients transitioning off active treatment: A short‐term prospective mixed methods study
Authors: Chan Sherilynn F. , Hoag Jennifer A. , Karst Jeffrey S. , Bingen Kristin M. 
Published: November 2018

AbstractBackgroundPsychosocial follow‐up in survivorship is a standard of care in pediatric oncology; however, little is known about patients’ psychosocial functioning during the transition off active treatment, a unique time in the cancer journey. This study examined the social adjustment of adolescent cancer patients during this transition period, which has been understudied to date.ProcedureParticipants were 21 patients (ages 12–18 years; age M = 14.71 years; 62% female, 81% White) with various cancer diagnoses. Patients and their parents completed the Social Competence subscale of the Youth Self‐Report (YSR) and Child Behavior Checklist (CBCL), respectively, PedsQL Social Functioning subscale, and a semistructured interview 1–2 months prior to ending treatment (time 1) and 3–7 months after ending treatment (time 2).ResultsYSR and CBCL social competence scores were within the normal range at both time points. PedsQL social functioning scores were more consistent with norms for pediatric cancer samples at time 1 and norms for healthy children at time 2, with self‐reported scores significantly improving from time 1 to time 2. A subset of patients had elevated social concerns at time 1, a number that decreased by time 2. Interviews revealed both positive and negative themes related to peer relationships and support, quantity of friends, and socialization.ConclusionsMost adolescent cancer patients are socially well adjusted as they transition off treatment, although a subset have elevated concerns. Interviews provide insight into complex social experiences not captured on questionnaires. Patients may benefit from screening and support during this unique time.
Metabolomic study of bioactive compounds in strawberries preserved under controlled atmosphere based on GC‐MS and DI‐ESI‐QqQ‐TOF‐MS
Authors: Ramírez‐Acosta Sara , Arias‐Borrego Ana , Gómez‐Ariza José Luis , García‐Barrera Tamara 
Published: November 2018

AbstractIntroductionThe storage of the vegetables products in a controlled atmosphere (CA) with low O2 and high CO2 concentrations, reduces respiration rates and delays the ripening process, and in some cases, improves their quality and organoleptic properties.ObjectiveTo obtain deep insight into strawberry fruit metabolic changes caused by these CA treatments.MethodologyFreshly harvested strawberries were preserved under different atmospheres enriched with 10%, 20% and 30% of CO2, for 2 days at 0°C, containing in all the cases 5% of O2 and were subjected to a metabolomic analysis based on gas chromatography‐mass spectrometry (GC–MS) and direct‐infusion with electrospray ionisation source equipped with triple quadrupole coupled to time of flight mass spectrometry (DI‐ESI‐QqQ‐TOF‐MS). Partial least square discriminant analysis (PLS‐DA) was employed to compare the control and treated samples for the identification of altered metabolites.ResultsSeveral metabolites related to CA treatment could be identified by databases and literature, which are mainly sugars, organic acids and phenolic compounds (bioactive compounds).ConclusionsGood correlation coefficients were obtained between discriminant metabolites and fruit quality parameters. These results suggest that treated strawberries under CA could be considered as bioactive healthy compounds, suggesting that treated strawberries under CA could be used as raw material for the preparation and formulation of food supplements and nutraceutical products.
Composition analysis of carotenoids and phenolic compounds and antioxidant activity from hibiscus calyces (Hibiscus sabdariffa L.) by HPLC‐DAD‐MS/MS
Authors: Piovesana Alessandra , Rodrigues Eliseu , Noreña Caciano Pelayo Zapata 
Published: November 2018

AbstractIntroductionThe hibiscus flower has received increasing interest because it contains high levels of bioactive compounds with remarkable functional properties. To the best of our knowledge, for the first time a detailed description of the carotenoid composition of hibiscus calyces is reported.ObjectivesIdentification and quantification of carotenoids, phenolic compounds and antioxidant activity from hibiscus calyces.Material and methodsThe composition of the carotenoids and phenolic compounds from hibiscus calyces was determined by high‐performance liquid chromatography coupled to a diode array detector and tandem mass spectrometry (HPLC‐DAD‐MS/MS). Antioxidant activity was assessed using 2,2'‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulphonic acid) (ABTS) radical scavenging and hydroxyl radicals scavenging assays.ResultsTwenty‐one carotenoids were found and from these compounds 15 were identified or tentatively identified. The major carotenoids were all‐trans‐lutein (316.43 ± 19.92 μg/100 g) and all‐trans‐β‐carotene (147.76 ± 5.59 μg/100 g). Twenty phenolic compounds were found, from which 14 compounds were identified or tentatively identified. The major phenolic compounds were delphinidin 3‐sambubioside (218.17 ± 12.69 mg/100 g) and 3‐caffeoylquinic acid (79.22 ± 7.01 mg/100 g), representing almost 60% (w/w) of the total phenolic compounds from hibiscus calyces. The hibiscus presented low vitamin A activity, measure as retinol activity equivalent (13.52 μg/100 g). The scavenging activity of ABTS and hydroxyl radicals were 7.8 μmol Trolox equivalent/g and 81%, respectively.ConclusionIn this study we have shown that the hibiscus calyces can be considered as a food rich in lutein, chlorogenic acids and anthocyanins (delphinidin 3‐sambubioside).
The Fine Art of Destruction: A Guide to In‐Depth Glycoproteomic Analyses—Exploiting the Diagnostic Potential of Fragment Ions
Authors: Hoffmann Marcus , Pioch Markus , Pralow Alexander , Hennig René , Kottler Robert , Reichl Udo , Rapp Erdmann 
Published: November 2018

AbstractThe unambiguous mass spectrometric identification and characterization of glycopeptides is crucial to elucidate the micro‐ and macroheterogeneity of glycoproteins. Here, combining lower and stepped collisional energy fragmentation for the in‐depth and site‐specific analysis of N‐ and O‐glycopeptides is proposed. Using a set of four representative and biopharmaceutically relevant glycoproteins (IgG, fibrinogen, lactotransferrin, and ribonuclease B), the benefits and limitations of the developed workflow are highlighted and a state‐of‐the‐art blueprint for conducting high‐quality in‐depth N‐ and O‐glycoproteomic analyses is provided. Further, a modified and improved version of cotton hydrophilic interaction liquid chromatography‐based solid phase extraction for glycopeptide enrichment is described. For the unambiguous identification of N‐glycopeptides, the use of a conserved yet, rarely employed‐fragmentation signature [Mpeptide+H+0,2X GlcNAc]+ is proposed. It is shown for the first time that this fragmentation signature can consistently be found across all N‐glycopeptides, but not on O‐glycopeptides. Moreover, the use of the relative abundance of oxonium ions to retrieve glycan structure information, for example, differentiation of hybrid‐ and high‐mannose‐type N‐glycans or differentiation between antenna GlcNAc and bisecting GlcNAc, is systematically and comprehensively evaluated. The findings may increase confidence and comprehensiveness in manual and software‐assisted glycoproteomics.
Maternal vitamin D and E intakes in pregnancy and asthma to age 15 years: A cohort study
Authors: Devereux Graham , Craig Leone , Seaton Anthony , Turner Steve 
Published: November 2018

AbstractThis study investigated whether the previously reported associations in this birth cohort between maternal vitamin D and E intakes during pregnancy and childhood wheeze/asthma outcomes at age 5 and 10 years are still evident at age 15 years. In a prospective study of 1924 children recruited in utero, maternal vitamin D and E intakes during pregnancy were assessed by food frequency questionnaire and the children completed raespiratory questionnaire at age 15 years. Treatment for asthma at age 15 was also ascertained using healthcare data. Maternal vitamin D and E intakes were also related to combined childhood asthma data collected at 1, 2, 5, 10, and 15 years of age. Symptom data were available for 747 (39%) 15‐year olds and healthcare data for 1689 (88%). There were no associations between maternal vitamin D and E intakes and childhood wheeze and asthma at age 15. Analysis of combined data collected between 1 and 15 years of age demonstrated that higher maternal vitamin D and E intakes during pregnancy were associated with a reduced likelihood of being diagnosed with asthma in the first 15 years: hazard ratio (95%CI) per quartile increase in vitamin intake of 0.87 (0.78,0.98) and 0.88 (0.78,0.98), respectively. Lower maternal vitamin D and E intakes during pregnancy are associated with increased risk of children wheezing and being diagnosed with asthma in the first 10 years but not after puberty, suggesting that post‐natal exposures predominate in the etiology of incident asthma as children transition through puberty into adulthood.
The roundabout way to disaster: Recognizing and responding to normalization of deviance
Authors: Mize Jennifer F. 
Published: November 2018

Humans develop processes to structure their activities to set and reach goals. Wherever a process exists, there will be always deviations from that process. Skipped steps, workarounds, shortcuts, improvements, and innovations can be incorporated over time, gradually resulting in new practices that are accepted as the norm. Small changes that seem insignificant can easily be overlooked and therefore not managed. To the extent that individuals, teams, and organizations tolerate nonconformance, normalization of deviation can be established. The cumulative effect of these deviations may be unmitigated hazards that can lead to a catastrophic process safety event.A CCPS project subcommittee (Project 269) was established to develop a text to address the initial and long‐term effects of normalization of deviations. The finished book, Recognizing and Responding to Normalization of Deviance, will be published in early 2018. This article will provide examples of the depth and breadth of normalization of deviation throughout processes, procedures, and organizations, and will illustrate techniques to address its potential impact. © 2018 American Institute of Chemical Engineers Process Saf Prog 38: e12014, 2019
The omega probability distribution and its applications in reliability theory
Authors: Dombi József , Jónás Tamás , Tóth Zsuzsanna E. , Árva Gábor 
Published: November 2018

AbstractA new three‐parameter probability distribution called the omega probability distribution is introduced, and its connection with the Weibull distribution is discussed. We show that the asymptotic omega distribution is just the Weibull distribution and point out that the mathematical properties of the novel distribution allow us to model bathtub‐shaped hazard functions in two ways. On the one hand, we demonstrate that the curve of the omega hazard function with special parameter settings is bathtub shaped and so it can be utilized to describe a complete bathtub‐shaped hazard curve. On the other hand, the omega probability distribution can be applied in the same way as the Weibull probability distribution to model each phase of a bathtub‐shaped hazard function. Here, we also propose two approaches for practical statistical estimation of distribution parameters. From a practical perspective, there are two notable properties of the novel distribution, namely, its simplicity and flexibility. Also, both the cumulative distribution function and the hazard function are composed of power functions, which on the basis of the results from analyses of real failure data, can be applied quite effectively in modeling bathtub‐shaped hazard curves.