bluuebunny/crossref_metadata_2025_split huggingface dataset:
Afatinib plus bevacizumab combination after acquired resistance to EGFR tyrosine kinase inhibitors in EGFR‐mutant non–small cell lung cancer: Multicenter, single‐arm, phase 2 trial (ABC Study)
Authors: Hata Akito , Katakami Nobuyuki , Kaji Reiko , Yokoyama Toshihide , Kaneda Toshihiko , Tamiya Motohiro , Inoue Takako , Kimura Hiromi , Yano Yukihiro , Tamura Daisuke , Morita Satoshi , Negoro Shunichi , the HANSHIN Oncology Group for 
Published: September 2018

BACKGROUNDPreclinical studies suggested that the addition of bevacizumab could overcome acquired resistance (AR) to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). The aim of this study was to evaluate the clinical efficacy and safety of a combination of afatinib and bevacizumab after AR.METHODSPatients with EGFR‐mutant non–small cell lung cancer after AR were enrolled during any line of therapy. Afatinib was prescribed at 30 mg, and 15 mg/kg bevacizumab was administered every 3 weeks until progression.RESULTSBetween October 2014 and May 2017, 32 eligible patients were evaluated. The mutation subtypes were Del‐19 (20 [63%]), L858R (11 [34%]), and L861Q (1 [3%]). T790M was detected in 14 patients (44%). The median number of prior regimens was 4 (range, 1‐10). Six patients obtained a partial response, and 23 had stable disease; this resulted in an objective response rate (ORR) of 18.8% (95% confidence interval [CI], 7.2%‐36.4%) and a disease control rate of 90.7% (95% CI, 75.0%‐98.0%). The median progression‐free survival (PFS) was 6.3 months (95% CI, 3.9‐8.7 months). The ORRs and median PFS times of T790M+ and T790M− patients were 14.3% and 22.2%, respectively, and 6.3 and 7.1 months, respectively; those of Del‐19 and L858R patients were 20.0% and 11.1%, respectively, and 6.3 and 5.1 months, respectively. Grade 3 or higher adverse events (incidence ≥ 10%) included paronychia (25%), hypertension (41%), and proteinuria (19%). There were no treatment‐related deaths, interstitial lung disease, or bevacizumab‐associated severe bleeding.CONCLUSIONSAfatinib plus bevacizumab demonstrated clinical efficacy and safety after AR to EGFR TKIs and could be a therapeutic salvage option for T790M− populations.
Toward colour rendering method of window glass
Authors: Arbab Shabnam , Matusiak Barbara Szybinska 
Published: September 2018

AbstractThe aim of this study was to expand the understanding of modern glazing materials' effects on the colour distortion in interiors and to develop a rather simple colour rendering method useful for any type of glazing and based on colorimetry measurements and mathematical calculations. The qualitative and quantitative aspects of different light sources on colour rendering are frequently discussed topics among the researchers, but one of the issues touched only sporadically is the impact of tinted glazing on colour rendering of daylight. The study started from the following question: Is the colour rendering method proposed by Lynes reliable also for present‐day high‐tech glazing types? The experiment was carried out in the Norwegian University of Science and Technology's (NTNU) with the artificial sky, which enables mimicking of skylight of the following correlated colour temperatures: 2700 K, 6500 K and 8000 K. Three high‐tech glazing types were used in five different transmittance scenarios. Colorimetric measurements were taken with the SpectraScan PR655 spectroradiometer. The findings indicated that the Lynes method is reliable to predict which glazing have the biggest impact on all aspects of colour but only in 6500 K. New set of measures have been proposed: average colour shift distance for hue gamut area for Chroma and median transmittance for Value. However, for higher precision regarding the direction of shift and the overall perception of the respective colours in building context, experiments with subjects are needed.
Hidden Dicarbene Nature of Acetylenes and Captodative Bonding on Carbon
Authors: Bijina Padinjare Veetil , Suresh Cherumuttathu H. 
Published: September 2018

AbstractThe density functional theory derived molecular electrostatic potential (MESP), 13C NMR chemical shift (δ), bond order, and coordination reactions show that alkynes (RCCR) attain 1,2‐dicarbene nature during CCR angle bending. Alkyne carbon atoms of bent structures exhibit MESP features unique to lone‐pair bearing atoms, δ around 200 ppm typical for carbene centers and large reduction in CC triple bond character. Lone pair bearing atoms of R substituents enhance the carbene character. The bent alkynes can be trapped with Lewis acids (BH3, BF3, AlF3 and AlCl3) as the lone pairs developed on carbon centers provide strong donor type dative bonding. The dative bond gives a formal valence electron count six on carbon and suggests the for‐mation of acceptor type dative bonding to carbon from Lewis base (NH3). Reaction of alkynes with (Lewis acid)←(Lewis base) systems yield (Lewis acid)2←(Alkyne)←(Lewis base)2 complexes which are exothermic and exergonic for many cases. These complexes are examples of captodative carbon(II) compounds.
Predation‐mediated ecosystem services and disservices in agricultural landscapes
Authors: Tschumi Matthias , Ekroos Johan , Hjort Cecilia , Smith Henrik G. , Birkhofer Klaus 
Published: September 2018

AbstractEcological intensification may reduce environmental externalities of agriculture by harnessing biodiversity to benefit regulating ecosystem services. However, to propose management options for the production of such services, there is a need to understand the spatiotemporal dynamics of net effects between ecosystem services and disservices provided by wild organisms across taxonomic groups in relation to habitat and landscape management. We studied the contribution of predatory vertebrates and invertebrates (including both carnivores and seed herbivores) to regulating ecosystem services and disservices in 16 cereal fields in response to a local habitat contrast and a landscape complexity gradient. From May to November 2016, we provided weed (predation reflects an ecosystem service) and crop (predation reflects a disservice) seeds, as well as pest (predation reflects an ecosystem service) and beneficial (predation reflects a disservice) invertebrate prey to predators. Seed predation was dominated by vertebrates, while vertebrates and invertebrates contributed equally to predation of animal prey. Before harvest, predation steadily increased from very low levels in May to high levels in July independent of the resource type. After harvest, ecosystem services declined more rapidly than disservices. The presence of adjacent seminatural grasslands promoted crop seed predation, but reduced pest prey predation. Predation on beneficial prey decreased with increasing proportions of seminatural grassland in the landscape. Predatory vertebrates and invertebrates provide important ecosystem services due to the consumption of pests. However, beneficial invertebrates and crop seeds were often consumed to a similar or even higher extent than harmful invertebrates or weed seeds. Our results therefore raise concerns that management options aimed at enhancing service providers may simultaneously increase levels of disservices. By considering positive and negative effects simultaneously, this study addresses an important knowledge gap and highlights the importance of interactions between local management, landscape composition, and service and disservice provision across taxa and over time. Considering trade‐offs between ecosystem services and disservices when evaluating the net effects of biodiversity conservation measures on ecosystem service provision is crucial. Future agri‐environment schemes that offer payments for seminatural habitats may need to provide higher compensation for farmers in cases where net effects are likely to be negative.
Complex mathematical analysis of photobioreactor system
Authors: Scheufele Fabiano Bisinella , Hinterholz Camila Larissa , Zaharieva Maya M. , Najdenski Hristo M. , Módenes Aparecido Nivaldo , Trigueros Daniela Estelita Goes , Borba Carlos Eduardo , Espinoza‐Quiñones Fernando Rodolfo , Kroumov Alexander Dimitrov 
Published: September 2018

AbstractModeling as a tool solves extremely difficult tasks in life sciences. Recently, schemes of culturing of microalgae have received special attention because of its unique features and possible uses in many industrial applications for renewable energy production and high value products isolation. The goal of this review is to present the use of system analysis theory applied to microalgae culturing modeling and process development. The review mainly focuses on the modeling of the key steps of autotrophic growth under the integral biorefinery concept of the microalgae biomass. The system approach follows systematically a procedure showing the difficulties by modeling of sub‐systems. The development of microalgae kinetics and computational fluid dynamics (CFD) studies were analyzed in details as sub‐systems in advanced design of photobioreactor (PBR). This review logically follows the trends of the modeling procedure and clarifies how this approach may save time and money during the research efforts. The result of this work is a successful development of a complex PBR mathematical analysis in the frame of the integral biorefinery concept.
The Small Sellers of Program Evaluation Services in the United States
Authors: Hwalek Melanie A. , Straub Victoria L. 
Published: September 2018

AbstractThis chapter attempts to deepen the understanding of small sellers of evaluation services through a survey of the American Evaluation Association's Independent Consulting Topical Interest Group members, delving into the inner workings of their organizations. The chapter examines where boutique evaluators in the United States generate their revenues, how some have survived as independent evaluators for 10 or more years, how they differentiate themselves from their competition, whether they do subcontract work with large sellers, and how they deliver high‐quality evaluation services. A case example of one small seller, SPEC Associates, is used to elucidate the survey findings.
The Big Evaluation Enterprises in the United States
Authors: Peck Laura R. 
Published: September 2018

AbstractThis issue of New Directions for Evaluation addresses the market for evaluation, where demand and supply intersect to generate knowledge relevant to decisions for policy‐making and program practice. Lemire et al. (this issue) elaborated on the U.S. federal evaluation market. This chapter examines the “big evaluation enterprises” within that market.
The combined effects of yogurt and exercise in healthy adults: Implications for biomarkers of depression and cardiovascular diseases
Authors: Kim Hyun‐Kyung , Kim Soo‐Hwan , Jang Chul‐Soo , Kim Sung‐In , Kweon Chang‐Oh , Kim Byung‐Won , Ryu Jae‐Ki 
Published: September 2018

AbstractSeveral studies have reported individual benefits of yogurt and exercise on health; however, their combined effects remain unclear. Twenty‐four healthy individuals participated in the study and were randomly assigned to the following four groups: control, yogurt, exercise, and combination. The participants consumed yogurt and exercised for 2 weeks, and we examined the combined effects of yogurt and exercise on physiological biomarkers. Individually, yogurt and exercise did not exert a significant effect on biomarkers of depression or cardiovascular disease, although vitamin D levels increased in the exercise group. However, in the combination group, serotonin levels increased, while levels of triglycerides and high‐sensitivity C‐reactive protein, which are biomarkers for cardiovascular diseases, decreased. In conclusion, the results of the study showed that, in healthy individuals, a combination of yogurt and exercise led to greater increases in serotonin levels and reductions in triglyceride and high‐sensitivity C‐reactive protein levels, relative to those observed for yogurt or exercise alone; therefore, this combination could have implications for the prevention of depression and cardiovascular disease.
Systematic variation in evapotranspiration trends and drivers across the Northeastern United States
Authors: Vadeboncoeur Matthew A. , Green Mark B. , Asbjornsen Heidi , Campbell John L. , Adams Mary Beth , Boyer Elizabeth W. , Burns Douglas A. , Fernandez Ivan J. , Mitchell Myron J. , Shanley James B. 
Published: September 2018

AbstractThe direction and magnitude of responses of evapotranspiration (ET) to climate change are important to understand, as ET represents a major water and energy flux from terrestrial ecosystems, with consequences that feed back to the climate system. We inferred multidecadal trends in water balance in 11 river basins (1940–2012) and eight smaller watersheds (with records ranging from 18 to 61 years in length) in the Northeastern United States. Trends in river basin actual ET (AET) varied across the region, with an apparent latitudinal pattern: AET increased in the cooler northern part of the region (Maine) but decreased in some warmer regions to the southwest (Pennsylvania–Ohio). Of the four small watersheds with records longer than 45 years, two fit this geographic pattern in AET trends. The differential effects of the warming climate on AET across the region may indicate different mechanisms of change in more‐ vs. less‐energy‐limited watersheds, even though annual precipitation greatly exceeds potential ET across the entire region. Correlations between AET and time series of temperature and precipitation also indicate differences in limiting factors for AET across the Northeastern U.S. climate gradient. At many sites across the climate gradient, water‐year AET correlated with summer precipitation, implying that water limitation is at least transiently important in some years, whereas correlations with temperature indices were more prominent in northern than southern sites within the region.
Zika virus exposure in pregnancy and its association with newborn visual anomalies and hearing loss
Authors: Peloggia Alessandra , Ali Moazzam , Nanda Kavita , Bahamondes Luis 
Published: September 2018

AbstractExposure to Zika virus (ZIKV) in pregnancy leads to a spectrum of congenital effects in the newborn. Recent studies have begun to evaluate the impact of ZIKV during pregnancy. Among 39 relevant studies, nine were related specifically to clinical studies of ophthalmologic disorders and one was related to hearing loss impairment; most of these studies were case reports and case series reports. Importantly, congenital toxoplasmosis was ruled out in all studies. The data show that, in addition to microcephaly, ZIKV exposure in pregnancy may result in subtle ocular impairments in the newborn. The most common anomalies are macular pigment mottling and/or chorioretinal atrophy, and optic nerve disorders. Sensorineural hearing loss has also been noted in 5.8% of infants with microcephaly. The effects of ZIKV infection during pregnancy are potentially devastating to the fetus and newborn. Although microcephaly is an important signal, the current information emphasizes the importance of ocular and auditory screenings, otherwise sight and hearing anomalies may be underestimated. Healthcare providers should fully understand the spectrum of anomalies related to ZIKV exposure in pregnancy in order to counsel pregnant women living in high‐risk areas, in addition to those wanting to become pregnant.
Improving the annual yield of a wheat and maize system through irrigation at the maize sowing stage†
Authors: Feng Yupeng , Yang Meng , Shang Mengfei , Jia Hao , Chu Qingquan , Chen Fu 
Published: September 2018

AbstractTo achieve high‐yielding and eco‐friendly crop production, it is crucial to identify the critical water requirement period of crops, especially in annual crop production systems. A 2‐year experiment was established to study the annual yield, total water consumption and water productivity (WP) of a winter wheat (Triticum aestivum L.) and summer maize (Zea mays L.) system in the Huang‐Huai‐Hai Plain.The results showed that the annual yield of this crop system increased with irrigation frequency and was highest when irrigation was applied three times in the wheat season and once in the maize season (W3M1), though there was no significant difference in annual yield among W2M1, W3M1 and W4M1. And there is no evidence in this paper that irrigation scheduling substantially affects WP. W2M1 had the second highest annual yield (18.7 t ha−1 in 2013–2014 and 19.9 ha−1 in 2014–2015) with a low amount of irrigation compared with W3M1 and W4M1. The highest total water consumption was measured in W3M1 and reached 812 and 873 mm in the first and second years, respectively. Irrigation during the summer maize sowing stage is essential for improving the annual yield and WP. © 2018 John Wiley & Sons, Ltd.
Doxorubicin‐loaded poly(ε‐caprolactone)‐Pluronic micelle for targeted therapy of esophageal cancer
Authors: Dai Shujun , Ye Zhimin , Wang Fangzheng , Yan Fengqin , Wang Lei , Fang Jun , Wang Zhun , Fu Zhenfu 
Published: September 2018

AbstractThere is still lack of effective treatment of esophageal cancer, and it is urgently necessary to develop a new programs to treat this disease. More and more evidence suggests that the combination of 2 or more treatment strategies can enhance the antitumor activity in cancer treatment. We have established a new therapeutic strategy that combines doxorubicin‐loaded poly(ε‐caprolactone) (PCL)‐Pluronic micelles and miR‐34a to better combat esophageal cancer. Doxorubicin was loaded into PCL‐Pluronic micelle to achieve better uptake. Confocal microscopy was used to assess in vitro cellular uptake of PCL‐Pluronic micelle. Finally, the in vivo effect of this new combination therapy strategy was also studied. The results showed that PCL‐Plannick micelles significantly enhanced the uptake of doxorubicin in esophageal cancer cells in vitro, thereby improving the accumulation of doxorubicin in the cells. In vitro and in vivo combination of doxorubicin‐loaded PCL‐Pluronic micelles and miR‐34a, achieving a significantly synergistic therapeutic effect over the corresponding single treatment. These results suggested that the combinational therapy based on doxorubicin‐loaded PCL‐Pluronic micelle and miR‐34a may provide a reasonable strategy for improving the outcome of esophageal cancer treatment.
Epigenetic silencing of sonic hedgehog elicits antitumor immune response and suppresses tumor growth by inhibiting the hedgehog signaling pathway in metastatic spine tumors in Sprague‐Dawley rats
Authors: Shi Guang , Zhang Hong , Yu Qiong , Jin Hui , Hu Chun‐Mei , Li Shu‐Chun , Ji You‐Bo 
Published: September 2018

AbstractBackground: Patients with metastatic spine tumors may suffer from pain or neurologic deficit, and the disease may be detected in patients with a known malignancy. Sonic hedgehog (SHH) has received special attention due to its role in cancers. Therefore, this study investigated the effects of epigenetic silencing of SHH on antitumor immune response and tumor growth by regulating the hedgehog (Hh) signaling pathway in metastatic spine tumors.Methods: Rat models of metastatic spine tumors were successfully established. We first calculated the tumor volume and the inhibition rate of tumor growth to investigate the effect of SHH on tumor growth. Afterwards, immunohistochemistry was used to determine whether proliferation was delayed by SHH depletion, and the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay was conducted to test the changes in the lymphocyte transformation rate in the spleen triggered by SHH silencing. Then, the influence of SHH depletion on immune function was investigated. Later, quantitative reverse transcription polymerase chain reaction and Western blot assay were performed to explore the Hh signaling pathway–related factors. Finally, we added the Hh signaling pathway inhibitor, GDC‐0449, to confirm the role of the pathway in tumor progression.Results: Initially, we observed that SHH depletion was a negative factor for tumor growth. Afterwards, it was revealed that epigenetic silencing of SHH served as an inhibitor factor for the function of spleen lymphocyte transformation and inflammation while promoting antitumor immune function.Conclusion: Our preliminary results indicate that epigenetic silencing of SHH elicits an antitumor immune response and suppresses tumor growth by inhibiting the Hh signaling pathway in metastatic spine tumors.
Hairless regulates p53 target genes to exert tumor suppressive functions in glioblastoma
Authors: Brook Lemlem , Palade Patricia , Maatough Anas , Whitfield Graham Kerr , Emeterio Lis San , Hsieh David , Hsieh Jui‐Cheng 
Published: September 2018

AbstractGlioblastoma (GBM) is the most common malignant brain tumor and is associated with a poor prognosis, with most patients living less than a year after diagnosis. Given that GBM nearly always recurs after conventional treatments, there is an urgent need to identify novel molecular targets. Hairless (HR) is a nuclear factor enriched in the skin and has been previously implicated in hair cycling. HR is also highly expressed in the brain, but its significance is unknown. We found that human hairless gene (HR) expression is significantly decreased in all GBM subtypes compared with normal brain tissue and is predictive of prognosis, which suggests that loss of
HR expression can contribute to GBM pathogenesis. HR was recently discovered to bind to and regulate p53 responsive elements, and thus we hypothesized that HR may have a tumor suppressive function in GBM by modulating p53 target gene expression. We found that HR indeed regulates p53 target genes, including those implicated in cell cycle progression and apoptosis in the GBM‐derived U87 cell line, and restoring
HR expression triggered G2/M arrest and apoptosis. An analysis of sequenced genomes from patients with GBM revealed 10 HR somatic mutations in patients with glioma, two of which are located in the histone demethylase domain of HR. These two mutations, P996S and K1004N, were reconstructed and found to have impaired p53 transactivating properties. Collectively, the results of our study suggest that HR has tumor suppressive functions in GBM, which may be clinically relevant and a potential avenue for therapeutic intervention.
Dihydroartemisinin increases gemcitabine therapeutic efficacy in ovarian cancer by inducing reactive oxygen species
Authors: Yang Shengcai , Zhang Dawei , Shen Na , Wang Guanyi , Tang Zhaohui , Chen Xuesi 
Published: September 2018

AbstractOvarian cancer is the major cause of death in women gynecological malignancy and gemcitabine (GEM) is commonly used in related chemotherapy. However, more than 90% GEM is catalyzed into an inactive metabolite 2′‐deoxy‐2′,2′‐difluorouridine by stromal and cellular cytidine deaminase (CDA). Dihydroartemisinin (DHA), which possesses an intramolecular endoperoxide bridge, could be activated by heme or ferrous iron to produce reactive oxygen species (ROS). The excess ROS generation will excite expression of heme oxygenase‐1 and suppress CDA expression. Under low CDA expression, the inactivation of GEM is decreased in turn to exert excellent therapeutic efficiency. Herein, we first studied the ROS generation by DHA in vitro with A2780 cells by means of flow cytometry and confocal laser scanning microscopy. Furthermore, cytotoxicity assay in vitro showed that DHA + GEM had synergistic effect, with molar ratio of DHA and GEM at 10. Eventually, in A2780 ovarian cancer xenograft tumor model, DHA + GEM exhibited significant antitumor efficiency with lower blood toxicity than GEM alone. Noteworthy, the combination treatment group completely eliminated the tumors on day 14.