bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of histone deacetylases sensitizes EGF receptor‐TK inhibitor‐resistant non‐small‐cell lung cancer cells to erlotinib in vitro and in vivo
Authors: Yu Weiwei , Lu Weiqiang , Chen Guoliang , Cheng Feixiong , Su Hui , Chen Yihua , Liu Mingyao , Pang Xiufeng 
Published: July 2017

Background and PurposeIntrinsic and/or acquired resistance of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) commonly occurs in patients with non‐small‐cell lung cancer (NSCLC). Here, we developed a combined therapy of histone deacetylase inhibition by a novel HDAC inhibitor, YF454A, with erlotinib to overcome EGFR‐TKI resistance in NSCLC.Experimental ApproachThe sensitization of the effects of erlotinib by YF454A was examined in a panel of EGFR‐TKI‐resistant NSCLC cell lines in vitro and two different erlotinib‐resistant NSCLC xenograft mouse models in vivo. Western blotting and Affymetrix GeneChip expression analysis were further performed to determine the underlying mechanisms for the effects of the combination of erlotinib and YF454A.Key ResultsYF454A and erlotinib showed a strong synergy in the suppression of cell growth by blocking the cell cycle and triggering cell apoptosis in EGFR‐TKI‐resistant NSCLC cells. The combined treatment led to a significant decrease in tumour growth and tumour weight compared with single agents alone. Mechanistically, this combination therapy dramatically down‐regulated the expression of several crucial EGFR‐TKI resistance‐related receptor tyrosine kinases, such as Her2, c‐Met, IGF1R and AXL, at both the transcriptional and protein levels and consequently blocked the activation of downstream molecules Akt and ERK. Transcriptomic profiling analysis further revealed that YF454A and erlotinib synergistically suppressed the cell cycle pathway and decreased the transcription of cell‐cycle related genes, such as MSH6 and MCM7.Conclusion and ImplicationsOur preclinical study of YF454A provides a rationale for combining erlotinib with a histone deacetylase inhibitor to treat NSCLC with EGFR‐TKI resistance.
Supergene and exotic Cu mineralization occur during periods of landscape stability in the Centinela Mining District, Atacama Desert
Authors: Riquelme Rodrigo , Tapia Miguel , Campos Eduardo , Mpodozis Constantino , Carretier Sebastien , González Rodrigo , Muñoz Sebastian , Fernández‐Mort Alberto , Sanchez Caroline , Marquardt Carlos 
Published: July 2017

AbstractThe Centinela Mining District (CMD), Atacama Desert (northern Chile), includes several mid‐late Eocene porphyry Cu deposits that contains supergene mineralization and provides access to a record of gravel deposits that host syn‐sedimentary exotic Cu mineralized bodies. By studying these gravels, we reconstruct the unroofing history and constrain the geomorphological conditions that produced supergene and exotic Cu mineralization. We present an integrated study based on stratigraphic and sedimentological data, lithology clast counts, 40Ar/39Ar and U/Pb ages from interbedded tuff layers and U/Pb detrital zircon geochronology data. To relate the gravel deposition episodes to the timing of the supergene mineralization, we provide in‐situ and exotic supergene mineral ages (40Ar/39Ar and K‐Ar). Six gravel units were deposited between the mid‐Eocene and the mid‐Miocene. The Esperanza gravels were deposited concurrently with the emplacement of porphyry Cu deposits at depth. The subsequent Tesoro I, II and III and Atravesado gravels register the unroofing of these deposits, from the advanced argillic zone to the sericitic and prophylitic hypogene zones. The Arrieros gravels register landscape pediplanation, that is, denudational removal and wear of the landscape to base level on a relatively stable tectonic regime, occurring roughly contemporaneous with supergene activity. The supergene mineral ages of the CMD define a time span (ca. 25–12 Ma) during which most of the supergene ages cluster in northern Chile. This time span corresponds with a period of warm and humid climate conditions in the southern hemisphere. We conclude that landscape pediplanation favours supergene mineralization and helps preserve the former supergene mineralized zones from significant erosion. Low erosion rates during pediplanation may constitute a necessary condition for the efficiency of the supergene processes in such semi‐arid climate.
Exploring quality of life of children with cerebral palsy and intellectual disability: What are the important domains of life?
Authors: Davis E. , Reddihough D. , Murphy N. , Epstein A. , Reid S. M. , Whitehouse A. , Williams K. , Leonard H. , Downs J. 
Published: July 2017

AbstractBackgroundAlthough it is estimated that half of all children with cerebral palsy also have comorbid intellectual disability, the domains of quality of life (QOL) important for these children are not well understood. The aim of this study was to identify important domains of QOL for these children and adolescents.MethodsDue to the children's communication impairments, qualitative semi‐structured interviews were conducted with 18 parents. The children (9 males) had a median age of 12 (range 7 to 17) years at interview and nearly two thirds were classified as Gross Motor Function Classification System IV or V. A grounded theory approach was used to identify domains of QOL.ResultsThe 11 domains identified as important to QOL were physical health, body comfort, behaviour and emotion, communication, predictability and routine, movement and physical activity, nature and outdoors, variety of activity, independence and autonomy, social connectedness, and access to services.ConclusionsThe domains of QOL that emerged from this study will be useful for professionals who support children with cerebral palsy and their families. They will also be important for developing a QOL instrument essential for informing the development of interventions and their monitoring and evaluation.
Particulate matter adheres to human hair exposed to severe aerial pollution: consequences for certain hair surface properties
Authors: Galliano A. , Ye C. , Su F. , Wang C. , Wang Y. , Liu C. , Wagle A. , Guerin M. , Flament F. , Steel A. 
Published: July 2017

AbstractBackgroundThe deposit and adherence of particulate matter (PM) from aerial pollution onto the surface of human hair is a poorly studied phenomenon.Objectives(i) To reproduce in vitro the deposit of known PM on standardized hair swatches in a closed box, (ii) to compare in vitro data with those obtained under ‘real‐life’ conditions of severe aerial pollution and (iii) to assess the changes of the hair surface properties, potentially caused by the adherence of airborne PM onto the hair.MethodsIn vitro: a PM was sprayed onto untreated or sebum‐coated hair swatches. Real‐life conditions: other swatches were exposed to a severely polluted environment, for 24 to 72 h, in Baoding (PR China). In both cases, swatches were examined using scanning electron microscopy. The shine, the frictional properties and the level of metals were measured and compared to those same properties for the unexposed swatches.ResultsThis work clearly indicates that, under real‐life conditions, a large number of PM of various sizes are deposited onto the hair surface. This phenomenon is increased by the presence of sebum and longer exposure times. The in vitro level of PM deposited onto the hair surface is comparable to the in vivo level. The presence of sebum seems to favour the deposit of larger PM. The shine of the exposed swatches is significantly decreased, whereas their respective friction coefficients are significantly increased. Both the presence of sebum and length of exposure time increased the amount of analysed metals present on the exposed hair surface (Al, Fe, Cu, Ba and Zn).ConclusionThis work indicates that a very high amount (e.g. billions) of PM can be deposited on a full head of hair for subjects living in a severely aerially polluted environment. This process can be reproduced in vitro. In real‐life, pollution has a strong impact on hair surface properties, leading to a modification of the visual aspect (loss of shine) and the alteration of hair surface (increase in friction force). This work may be used to pave the way for prevention and cleansing studies in the field of hair care.
The diagnosis and management of male genital lichen sclerosus: a retrospective review of 301 patients
Authors: Kravvas G. , Shim T.N. , Doiron P.R. , Freeman A. , Jameson C. , Minhas S. , Muneer A. , Bunker C.B. 
Published: July 2017

AbstractIntroductionMale genital lichen sclerosus (MGLSc) is an acquired, chronic, inflammatory skin disease that is associated with significant morbidity and squamous cell carcinoma of the penis (PSCC). However, some clinical, diagnostic and management controversies endure, including the relationship with penile intraepithelial neoplasia (PeIN).ObjectivesTo clarify clinical presentations, diagnostic approaches, histological findings, response to treatment and the relationship with PeIN.MethodsRetrospective review of patients with a diagnosis of MGLSc who attended a specialist male genital dermatoses clinic.Results301 patients were identified: 260 had isolated MGLSc and 41 both MGLSc and PeIN. Referrals were made from the local Urology and Andrology departments (128), primary care (89), GUM (54), other dermatology departments (28) and other specialties (2). In isolated MGLSc, 94.6% were diagnosed clinically with 93.5% accuracy (based on data from subsequent circumcisions). In combined MGLSc/PeIN, 85.4% were diagnosed following diagnostic biopsy and 14.6% retrospectively after circumcision. In isolated MGLSc, 50% were treated topically, and 50% required surgery. In MGLSc/PeIN, 78% required surgical interventions. In isolated MGLSc, 92.2% achieved resolution of symptoms, 3.5% were awaiting procedures, and 4.8% were receiving ongoing topical therapy. In MGLSc/PeIN, 90.2% achieved clearance, 2.4% were waiting surgery, and 7.3% were treated topically. Only 2.7% reported ongoing symptoms, all in patients treated surgically. None progressed to PSCC.DiscussionMGLSc is generally a disease of the uncircumcised; the majority of cases of MGLSc are accurately diagnosed clinically; suspected PeIN or PSCC requires histological confirmation; circumcision histology can be non‐specific; most men are either cured by topical treatment with ultrapotent corticosteroid (53.1%) or by circumcision (46.9%); surgical intervention is required in most cases of concomitant MGLSc and PeIN; the majority of patients with MGLSc alone or with MGLSc and PeIN remit with this approach; effective management appears to negate the risk of malignant transformation to PSCC.
Therapy of ulcus cruris of venous and mixed venous arterial origin with autologous, adult, native progenitor cells from subcutaneous adipose tissue: a prospective clinical pilot study
Authors: Konstantinow A. , Arnold A. , Djabali K. , Kempf W. , Gutermuth J. , Fischer T. , Biedermann T. 
Published: July 2017

AbstractBackgroundThe stromal vascular fraction (SVF) of adipose tissue consists of cellular subpopulations with distinct regenerative potential.ObjectiveTo investigate the regenerative capacities of autologous SVF cells in the treatment of chronic leg ulcers of venous (VLU) and arterial‐venous (AVLU) origin.MethodsMultimorbid ulcer patients received a singular topical treatment with 9–15 × 106 SVF cells, separated from abdominal lipoaspirates by digestion with collagenase and neutral protease and applied immediately after isolation. The primary endpoints were the change in wound size 12 weeks after treatment and evaluation of adverse events. Secondary endpoints included the time to complete wound epithelialization and change in pain levels. Postoperative wound treatment modalities and treatment of comorbidities were not intensified compared with pre‐operative management. Follow‐up period was at least 6 months.ResultsSixteen elderly ulcer patients (seven with VLU, nine with AVLU) were treated as described. All VLU patients (median ulcer size: 48.25 cm2) and four of nine AVLU patients showed complete epithelialization of the ulcers within 71–174 days. In three patients with large ulcerations on both legs, ulcerations on the non‐treated, contralateral leg also epithelialized. Patients reported a considerable rapid decrease in pain intensity by 2.5 points on average on a visual scale from 1 to 5 within the first 2 weeks after treatment. The patients were followed up for 9–44 months (median: 30 months). No severe side‐effects were observed.ConclusionsThe use of SVF cells presents an effective, minimally invasive option for the treatment of VLU and AVLU even in multimorbid patients. In patients with larger predominantly ischaemic AVLU and comorbidities, one‐time application of the used amounts of SVF cells was not sufficient in the majority of cases.
Emergent programme theories of a national quality register – a longitudinal study in Swedish elderly care
Authors: Nordin Annika , Andersson Gäre Boel , Andersson Ann‐Christine 
Published: July 2017

AbstractRationale, aim, and objectiveThis study aimed to explore programme theories of a national quality register. A programme theory is a bundle of assumptions underpinning how and why an improvement initiative functions. The purpose was to examine and establish programme theories of a national quality register widely used in Sweden: Senior alert. The paper reports on how programme theories among change recipients emerge in relation to the established programme theory of the initiator.MethodsA qualitative approach and a longitudinal research design were used. To develop programme theories among change recipients, individual semistructured interviews were conducted. Three sets of interviews were conducted in the period of 2011 to 2013, totalling 22 interviews. In addition, 4 participant observations were made. To develop the initiator's programme theory, an iterative multistage collaboration process between the researchers and the initiator was used. A directed content analysis was used to analyse data.FindingsThe initiator and change recipients described similar programme logics, but differing programme theories. With time, change recipients' programme theories emerged. Their programme theories converged and became more like the programme theory of the initiator.ConclusionsThis study has demonstrated the importance of making both the initiator's and change recipients' programme theories explicit. To learn about conditions for improvement initiatives, comparisons between their programme theories are valuable. Differences in programme theories provide information on how initiators can customize support for their improvement initiatives. Similar programme logics can be underpinned by different programme theories, which can be deceptive. Programme theories emerge over time and need to be understood as dynamic phenomena.
Melatonin suppresses platelet activation and function against cardiac ischemia/reperfusion injury via PPARγ/FUNDC1/mitophagy pathways
Authors: Zhou Hao , Li Dandan , Zhu Pingjun , Hu Shunying , Hu Nan , Ma Sai , Zhang Ying , Han Tianwen , Ren Jun , Cao Feng , Chen Yundai 
Published: July 2017

AbstractPlatelet activation is a major (patho‐) physiological mechanism that underlies ischemia/reperfusion (I/R) injury. In this study, we explored the molecular signals for platelet hyperactivity and investigated the beneficial effects of melatonin on platelet reactivity in response to I/R injury. After reperfusion, peroxisome proliferator‐activated receptor γ (PPARγ) was progressively downregulated in patients with acute myocardial infarction undergoing coronary artery bypass grafting (CABG) surgery and in mice with I/R injury model. Loss of PPARγ was closely associated with FUN14 domain containing 1 (FUNDC1) dephosphorylation and mitophagy activation, leading to increased mitochondrial electron transport chain complex (ETC.) activity, enhanced mitochondrial respiratory function, and elevated ATP production. The improved mitochondrial function strongly contributed to platelet aggregation, spreading, expression of P‐selectin, and final formation of micro‐thromboses, eventually resulting in myocardial dysfunction and microvascular structural destruction. However, melatonin powerfully suppressed platelet activation via restoration of the PPARγ content in platelets, which subsequently blocked FUNDC1‐required mitophagy, mitochondrial energy production, platelet hyperactivity, and cardiac I/R injury. In contrast, genetic ablation of PPARγ in platelet abolished the beneficial effects of melatonin on mitophagy, mitochondrial ATP supply, and platelet activation. Our results lay the foundation for the molecular mechanism of platelet activation in response to I/R injury and highlight that the manipulation of the PPARγ/FUNDC1/mitophagy pathway by melatonin could be a novel strategy for cardioprotection in the setting of cardiac I/R injury.
Evidence that auxin is required for normal seed size and starch synthesis in pea
Authors: McAdam Erin L. , Meitzel Tobias , Quittenden Laura J. , Davidson Sandra E. , Dalmais Marion , Bendahmane Abdelhafid I. , Thompson Richard , Smith Jennifer J. , Nichols David S. , Urquhart Shelley , Gélinas‐Marion Ariane , Aubert Gregoire , Ross John J. 
Published: July 2017

Summary

In recent years the biosynthesis of auxin has been clarified with the aid of mutations in auxin biosynthesis genes. However, we know little about the effects of these mutations on the seed‐filling stage of seed development.

Here we investigate a key auxin biosynthesis mutation of the garden pea, which results in auxin deficiency in developing seeds. We exploit the large seed size of this model species, which facilitates the measurement of compounds in individual seeds.

The mutation results in small seeds with reduced starch content and a wrinkled phenotype at the dry stage. The phenotypic effects of the mutation were fully reversed by introduction of the wild‐type gene as a transgene, and partially reversed by auxin application.

The results indicate that auxin is required for normal seed size and starch accumulation in pea, an important grain legume crop.
“Assessment of relationship between xerostomia and oral health‐related quality of life in patients with rheumatoid arthritis”
Authors: Chamani G , Shakibi MR , Zarei MR , Rad M , Pouyafard A , Parhizkar A , Mansoori M 
Published: July 2017

ObjectiveTo determine the relationship between xerostomia and oral health‐related quality of life in patients with rheumatoid arthritis.Materials and MethodTwo hundred patients with rheumatoid arthritis were assessed using Fox and OHIP‐14 questionnaires concerning xerostomia and oral health‐related quality of life, respectively. The sum of decayed, missing, and filled teeth (DMFT) was determined via an intra‐oral examination. In addition, intergroup comparisons were evaluated using t test, chi‐square, regression, and Tukey analysis.ResultAmong rheumatoid arthritis patients, 51% had been afflicted with xerostomia. We found a statistically significant relationship between xerostomia and oral health‐related quality of life (p‐value=.004), as xerostomia cases have significantly worse oral health‐related quality of life. Also, there was a statistically significant association between oral health‐related quality of life and gender as well as DMFT.ConclusionBecause there seem to be a high prevalence of xerostomia in patients with rheumatoid arthritis, screening in such population is highly recommended. Therefore, educational programs and/or workshops should be encouraged among healthcare providers to prevent worsening of oral health‐related quality of life.
Predictors and processes related to employees’ change‐related compliance and championing
Authors: Fugate Mel , Soenen Guillaume 
Published: July 2017

AbstractThis field study of a merger examines the antecedent factors and processes that explain two different forms of employee support for change—compliance and championing. Our overarching goal is to understand why some employees comply and others champion change efforts. We examine the combined effects of context and person factors on both positive and negative employee reactions to change, and then investigate the differential effects of these reactions on employee support for change. Results support our hypotheses and show that change management support (context factor) negatively predicts threat appraisals and positively predicts challenge appraisals. Both compliance and championing are positively predicted by challenge appraisals, and threat appraisals are negatively related to championing. Analyses also reveal that the positive relationship between change management support and challenge appraisal is stronger when dispositional resistance to change (person factor) is high. Moderated‐mediation analyses suggest employees’ compliance and championing for change are differentially affected by management actions, their own dispositional resistance, and that these effects are mediated through positive and negative appraisals.
De novo hepatocellular carcinoma post‐multivisceral transplantation in a child
Authors: Tran P. , Zhou S. , Wang L. , Finegold M. , Mascarenas L. , Alexopolous S. , Genyk Y. , Kerkar N. 
Published: July 2017

AbstractDe novo hepatocellular carcinoma (HCC) post‐transplantation in patients without viral hepatitis is extremely rare, with only three reported adult cases in the English literature. Here, we present a case of de novo HCC that developed in a 7‐year‐old female, who at 8 months of age received a liver, small bowel, spleen, and pancreas transplantation 6.5 years ago for gastroschisis and total parenteral nutrition (TPN)‐related cirrhosis. The post‐transplant course was complicated by Epstein‐Barr virus (EBV) infection, post‐transplant lymphoproliferative disease, and subsequent development of multifocal EBV‐associated post‐transplant smooth muscle tumors (EBV‐PTSMT) in the small bowel 1 year and 10 months after transplantation, respectively. This was managed by reducing immunosuppression with rituximab and EBV‐specific cytotoxic T‐cell therapy. She was noted to have a new lesion in her transplanted liver graft 6.5 years post‐transplantation that was diagnosed as HCC. The HCC was resected, and the patient remained clinically stable for 7 months. At that time, recurrence of the HCC was discovered on MRI. She passed away 6 months after. To the best of our knowledge, this is the first reported occurrence of de novo HCC post‐transplantation in the pediatric population that is unrelated to viral hepatitis in either recipient or donor.
Host discrimination modulates brood guarding behaviour and the adaptive superparasitism in the parasitoid wasp Trissolcus semistriatus (Hymenoptera: Scelionidae)
Authors: Todoroki Yusuke , Numata Hideharu 
Published: July 2017

AbstractBecause hosts utilized by parasitoids are vulnerable to further oviposition by conspecifics, host guarding benefits female wasps. The present study aims to test whether female adults regulate brood guarding behaviour by host discrimination in a solitary parasitoid Trissolcus semistriatus by presenting an intact or parasitized host egg mass to a female adult. Virgin females without oviposition experience have host discrimination ability, which enables them to adjust the number of eggs laid in the hosts. Mating experience increases superparasitism by female adults, whereas mated females achieve a higher discrimination ability as a result of oviposition experience and show a lower superparasitism rate. As expected, females exhibit brood guard after parasitizing an intact host egg mass, whereas those females visiting a previously parasitized host egg mass, do not. Because the survival of eggs in superparasitized hosts is relatively low, regulating brood guarding behaviour by host discrimination is adaptive for female wasps.