bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoadjuvant treatment strategy for locally advanced thoracic esophageal cancer
Authors: Mayanagi Shuhei , Irino Tomoyuki , Kawakubo Hirofumi , Kitagawa Yuko 
Published: March 2019

AbstractMultimodal treatment combining surgery with chemotherapy and/or radiotherapy is necessary to improve the chances of survival in patients with locally advanced thoracic esophageal cancer. Based on the results of the Japan Clinical Oncology Group 9907 (JCOG9907) trial, neoadjuvant chemotherapy, two courses of cisplatin and 5‐fluorouracil (5‐FU), followed by esophagectomy with D2 lymphadenectomy is the recommended treatment in Japan. Alternatively, neoadjuvant chemoradiotherapy (NACRT) typified by carboplatin and paclitaxel plus concurrent radiotherapy with 41.4 Gy (Chemoradiotherapy for Esophageal Cancer followed by Surgery Study [CROSS]) has shown promising outcomes in some Western countries. Currently, several clinical trials are being conducted within and outside of Japan to confirm the best neoadjuvant treatment regimen. For instance, a three‐arm phase III randomized controlled trial (JCOG1109) is ongoing in Japan. The three arms comprise a doublet regimen (two courses of cisplatin 80 mg/m2 day 1 and 5‐FU 800 mg/m2 days 1‐5; repeated every 3 weeks) versus a triplet regimen (three courses of docetaxel, 70 mg/m2 day 1; cisplatin 70 mg/m2 day 1; and 5‐FU 750 mg/m2 days 1‐5; repeated every 3 weeks) versus a chemoradiotherapy (CRT) regimen (radiotherapy of 41.4 Gy/23 fractions with two courses of cisplatin 75 mg/m2 day 1 and 5‐FU 1000 mg/m2 days 1‐4; repeated every 4 weeks). Development of a multimodal strategy for neoadjuvant therapy is expected to receive the continuous focus of research in the hope of achieving better outcomes from treatment of patients with advanced thoracic esophageal cancer.
A Peptide‐Induced Self‐Cleavage Reaction Initiates the Activation of Tyrosinase
Authors: Kampatsikas Ioannis , Bijelic Aleksandar , Pretzler Matthias , Rompel Annette 
Published: March 2019

AbstractThe conversion of inactive pro‐polyphenol oxidases (pro‐PPOs) into the active enzyme results from the proteolytic cleavage of its C‐terminal domain. Herein, a peptide‐mediated cleavage process that activates pro‐MdPPO1 (Malus domestica) is reported. Mass spectrometry, mutagenesis studies, and X‐ray crystal‐structure analysis of pro‐MdPPO1 (1.35 Å) and two separated C‐terminal domains, one obtained upon self‐cleavage of pro‐MdPPO1 and the other one produced independently, were applied to study the observed self‐cleavage. The sequence Lys 355–Val 370 located in the linker between the active and the C‐terminal domain is indispensable for the self‐cleavage. Partial introduction (Lys 352–Ala 360) of this peptide into the sequence of two other PPOs, MdPPO2 and aurone synthase (CgAUS1), triggered self‐cleavage in the resulting mutants. This is the first experimental proof of a self‐cleavage‐inducing peptide in PPOs, unveiling a new mode of activation for this enzyme class that is independent of any external protease.
Preparation and characterization of rice bran protein‐stabilized emulsion by using ultrasound homogenization
Authors: Sun Li‐Hui , Lv Shi‐Wen , Chen Ci‐Hang , Wang Can 
Published: March 2019

AbstractBackground and objectivesThe ultrasound homogenization, an emerging technology with cost‐effectiveness, is widely used in food industry. Rice bran protein is a high‐quality protein with hypoallergenic and attracts a growing interesting in exploring its application. In this study, ultrasound homogenization was used to produce rice bran protein‐stabilized emulsions and the effects of ultrasound power and ultrasound time on characterizations of emulsion were then investigated.FindingsResults indicated that the emulsions prepared by ultrasound homogenization at 20% power for 20 min had a higher interfacial protein concentration and a smaller droplet size, leading to an increase in stability against creaming. Subsequently, the effects of environmental conditions on emulsion stability were explored, and results demonstrated that emulsion exhibited excellent tolerance for high concentration of NaCl (500 mM) and high temperature (90°C). However, emulsion stability was destroyed under acid conditions.ConclusionsThe ultrasound homogenization technique was an effective method to prepare rice bran protein‐stabilized emulsion, and the emulsions prepared by ultrasound homogenization at 20% power for 20 min possessed good stability against creaming.Significance and noveltyRice bran protein isolate showed good emulsifying properties. Ultrasound homogenization could produce an emulsion with good stability and tolerance for high concentration of NaCl and high temperature.
Timing of folic acid/vitamin B12 supplementation and hematologic toxicity during first‐line treatment of patients with nonsquamous non–small cell lung cancer using pemetrexed‐based chemotherapy: The PEMVITASTART randomized trial
Authors: Singh Navneet , Baldi Milind , Kaur Jyotdeep , Muthu Valliappan , Prasad Kuruswamy T. , Behera Digambar , Bal Amanjit , Gupta Nalini , Kapoor Rakesh 
Published: March 2019

BackgroundVitamin B12 and folic acid (FA) supplementation (B12‐FAS) reduces hematologic toxicity with pemetrexed‐based chemotherapy (PEM). However, the basis for recommending 1 week of B12‐FAS before PEM initiation has never been proven in a randomized trial.MethodsAn open‐label, randomized trial (PEMVITASTART; clinicaltrials.gov identifier NCT02679443) was conducted to compare hematologic toxicity between patients with locally advanced/metastatic nonsquamous non–small cell lung cancer who initiated PEM after 5 to 7 days of B12‐FAS (delayed arm [DA]) versus those who received B12‐FAS simultaneously (≤24 hours) with PEM initiation (immediate arm [IA]). Every 3 weeks, all enrolled patients received pemetrexed (500 mg/m2) AND either cisplatin (65 mg/m2) OR carboplatin (area under the curve = 5.0 mg/mL per minute) on day 1 for a maximum of 6 cycles. Supplementation consisted of oral FA 1000 μg daily and intramuscular vitamin B12 1000 μg every 3 weeks. The primary outcome was any grade of hematologic toxicity and secondary outcomes included grade 3/4 hematologic toxicity, the relative dose intensity delivered, and changes in serum levels of B12/FA/homocysteine.ResultsOf 161 patients (IA, n = 81; DA, n = 80) recruited, 150 (IA, n = 77; DA, n = 73) received ≥1 cycle and were included in a modified intention‐to‐treat analysis. Baseline anemia prevalence was 34.7% (IA, 32.5%; DA, 37%; P = .56). The incidence of any grade anemia, leukopenia, neutropenia, and thrombocytopenia was 87% versus 87.7% (P = .90), 37.7% versus 28.8% (P = .25), 20.8% versus 15.1% (P = .36), and 31.2% versus 16.4% (P = .04), respectively, in the IA and DA, respectively. Grade 3/4 cytopenias and median relative dose intensities delivered (pemetrexed, 93.5%; platinum, 91%) were similar in both arms. After cycle 3 (compared with baseline), serum homocysteine levels were lower, whereas FA and B12 levels were higher. In the DA, serum FA and B12 levels on day 1 of cycle 1 (after 5‐7 days of B12‐FAS) were significantly higher than at baseline, but homocysteine levels were similar.ConclusionsSimultaneous B12‐FAS initiation with a pemetrexed‐platinum doublet chemotherapy regimen is feasible and does not lead to enhanced hematologic toxicity. Serum homocysteine levels are unaffected by 5 to 7 days of B12‐FAS.
A retrospective validation of the FocalPoint GS slide profiler NFR technology by analysis of interval disease outcomes compared with manual cytology
Authors: Nuttall David S. , Hillier Sharon , Clayton Helen R. , Savage Amanda J. , Martin Cara M. , O’Leary John J. 
Published: March 2019

BackgroundTo the authors’ knowledge, published studies reporting on the performance of the FocalPoint GS (FPGS) imaging system have yielded conflicting results to date. However, the results of the MAVARIC study indicated that the FPGS “No Further Review” (NFR) aspect of the technology demonstrated potential and warranted further investigation. The current validation study was performed prior to implementing the NFR slide reporting technology within the routine cervical screening program in Wales, United Kingdom.MethodsA total of 45,317 SurePath liquid‐based cytology cervical screening samples were submitted for FPGS scanning by 4 Welsh laboratories between 2006 and 2011. The current study (Computer Assisted Evaluation, Screening and Reporting [CAESAR]), reports on a comparison between slides categorized as NFR (8130 slides) and slides manually screened as negative (93,473 slides). Both interventions had a subsequent negative quality control screen.ResultsThe histological outcome rates of cervical intraepithelial neoplasia 2 (CIN‐2) (high‐grade squamous intraepithelial lesion or worse [HSIL+]) at 2 years and subsequently 3 years after an FPGS NFR result versus a manually screened negative result were compared. Significantly fewer cases were detected in the NFR cohort compared with the manually screened cohort (P = .043 at 2 years and P = .027 at 3 years). When these cases were subcategorized as cancers and precancers, the interval cancer prevalence between NFR and manually screened samples at 2 years and 3 years was similar; however, the interval precancer prevalence for FPGS NFR was significantly lower (P = .023 at 2 years and P = .026 at 3 years) at approximately one‐half that of manual screening.ConclusionsThe negative predictive potential of the FPGS NFR technology is higher than that of manual screening, and the technology has quality/throughput benefits to support and enhance a laboratory cervical screening service.
Conservation of genetic diversity hotspots of the high‐valued relic yellowhorn (Xanthoceras sorbifolium) considering climate change predictions
Authors: Zhu Ren‐Bin , Wang Qing , Guan Wen‐Bin , Mao Yanjia , Tian Bin , Cheng Ji‐Min , El‐Kassaby Yousry A. 
Published: March 2019

AbstractGenetic structure and major climate factors may contribute to the distribution of genetic diversity of a highly valued oil tree species Xanthoceras sorbifolium (yellowhorn). Long‐term over utilization along with climate change is affecting the viability of yellowhorn wild populations. To preserve the species known and unknown valuable gene pools, the identification of genetic diversity “hotspots” is a prerequisite for their consideration as in situ conservation high priority. Chloroplast DNA (cpDNA) diversity was high among 38 natural populations (Hd = 0.717, K = 4.616, Tajmas’ D = −0.22) and characterized by high genetic divergence (FST = 0.765) and relatively low gene flow (Nm = 0.03), indicating populations isolation reflecting the species’ habitat fragmentation and inbreeding depression. Six out of the studied 38 populations are defined as genetic diversity “hotspots.” The number and geographic direction of cpDNA mutation steps supported the species southwest to northeast migration history. Climatic factors such as extreme minimum temperature over 30 years indicated that the identified genetic “hotspots” are expected to experience 5°C temperature increase in next following 50 years. The results identified vulnerable genetic diversity “hotspots” and provided fundamental information for the species’ future conservation and breeding activities under the anticipated climate change. More specifically, the role of breeding as a component of a gene resource management strategy aimed at fulfilling both utilization and conservation goals.
Seasonal and spatial variations of water use among riparian vegetation in tropical monsoon region of SW China
Authors: Wang Pingyuan , Liu Wenjie , Zhang Jiaolin , Yang Bin , Singh Ashutosh Kumar , Wu Junen , Jiang Xiaojin 
Published: March 2019

AbstractRiparian vegetation is an important inhabitant of numerous forest ecosystems, although it is vulnerable and affected by the changes in climate or microclimate. Due to the fluctuation in rainfall and surface water availability, riparian plants usually exposed to two different seasons throughout the year: a dry season and a rainy season. However, water use patterns among riparian plants are still poorly understood in the tropical monsoon region. In this study, we used stable isotope techniques (δD and δ18O) coupled with MixSIAR model to identify the water sources for riparian plants in a tropical forest of SW China. The results showed an apparent seasonal variation in water use patterns for most trees, and the spatial variations were less pronounced between the terrace and floodplain sites. Among most riparian trees, deep soil (below 50 cm) was the main water source in the dry season, and shallow soil (above 15 cm) was the primary water source during the rainy season. However, there was no change in water source for herbs and other shallow‐rooted species with the fluctuation in water availability. This result indicates that shallow‐rooted plants (i.e., herbs and seedlings) struggle for their survivability in a riparian ecosystem because of the water scarcity in shallow soil during the dry season. Thus, lower rainfall and/or extended dry period may affect the productivity and sustainability of riparian vegetation under a future climate change scenario.
Validity of the Seattle Heart Failure Model after heart failure hospitalization
Authors: Li Song , Marcus Patrick , Núñez Julio , Núñez Eduardo , Sanchis Juan , Levy Wayne C. 
Published: March 2019

AbstractAimsHeart failure hospitalization is a sentinel event associated with increased mortality risk. Whether long‐term heart failure risk models such as the Seattle Heart Failure Model (SHFM) accurately assess risk in the post‐hospital setting is unknown.Methods and resultsThe SHFM was applied to a cohort of 2242 consecutive patients (50% women; mean age 73) on discharge after acute heart failure hospitalization and analysed for the primary endpoint of all‐cause mortality. Model discrimination and calibration were assessed. Direct patient‐level comparison between our study cohort and the original SHFM cohorts was also performed to confirm and quantify the degree and extent of increased mortality risk attributable to post‐hospital status. The SHFM demonstrated good overall risk discrimination (area under the receiver operating characteristic curve 0.704) and was well calibrated in patients <65 years old. The SHFM significantly underestimated mortality risk in patients ≥65 years old post‐hospitalization. Direct patient‐level comparison revealed a stepwise increase in adjusted mortality risk attributable to post‐hospital status for each advancing age group ≥65 years old. This heightened mortality risk showed a diminishing trend over 18 months after discharge.ConclusionsThe SHFM accurately predicts mortality risk in younger patients after acute heart failure hospitalization. However, patients ≥65 years old had increased adjusted mortality risk for up to 18 months after discharge compared with ambulatory heart failure patients, a pattern consistent with the well‐described post‐hospital syndrome.
Punica granatum (Pomegranate) Seed Oil and Momordica charantia (Bitter Melon) Extract Affect the Lipid's Profile and Oxidative Stability of Femoral Muscles of Rats
Authors: Białek Małgorzata , Białek Agnieszka , Lepionka Tomasz , Paśko Paweł , Galanty Agnieszka , Tokarz Andrzej , Czauderna Marian 
Published: March 2019

Pomegranate seed oil (PSO) and bitter melon extract (BM), used in folk medicine nowadays are available as dietary supplements, but information about consequences of their simultaneous usage are still scarce. This study aims to evaluate the influence of supplementation of rats’ diet with PSO separately or jointly with BM on the fatty acid (FA), cholesterol, malondialdehyde (MDA), and tocopherols concentrations in femoral muscles. Sprague‐Dawley rats (n = 36) are fed control diet (group C) or experimental diets supplemented only with 0.15 ml PSO/day (group G) or together with BM (group GM). After 21 weeks of supplementation, muscles are subjected to either gas (FA and cholesterol) or liquid (conjugated FA, tocopherols, and MDA) chromatographic analyses. Applied diets do not influence negatively health and welfare of animals. Conjugated linolenic acid (CLnA) isomers, predominating in PSO, are converted into ct/tc conjugated dienes (CD), with rumenic acid being the main CD, and incorporated into muscles. Supplementation of diet with PSO decreases the cholesterol and MDA contents in muscles. Influence of PSO and BM on activity of desaturases results in varied polyunsaturated FA (PUFA) content. Some PUFA may be converted into conjugated FA either exogenously or as a result of enzymatic or non‐enzymatic processes.Practical Applications: Dietary sources of conjugated linolenic acid isomer, e.g., PSO and BM, are known for their beneficial properties and thus willingly consumed world‐wide. Limited safety information of their simultaneous use is available despite their over‐consumption and may probably cause adverse effects. PSO and BM given to rats improves a lipid profile of femoral muscles, decreases cholesterol, increases polyunsaturated fatty acids and rumenic acid content, and counteracts lipid oxidation. These results may be a starting point for experiments conducted on farm animals considering their supplementation with PSO in order to possible improvement of nutritional value of their meat. After detailed surveys confirming beneficial influence of both supplements on human health and well‐being, these botanicals may be safely introduced into human diet.This study evaluates the influence of supplementation of rats’ diet with pomegranate seed oil separately or jointly with bitter melon extract on fatty acid, cholesterol, malondialdehyde, and tocopherols concentrations in femoral muscles. After 21 weeks of supplementation, muscles are subjected to either gas or liquid chromatographic analyses. Supplementation of diet with pomegranate seed oil decreases cholesterol and malondialdehyde contents.
Molecular profile of ultrastructure changes of the ligamentum flavum related to lumbar spinal canal stenosis
Authors: Sidon Eliezer , Shemesh Shai S. , Mor‐Yossef Moldovan Lisa , Wiesenfeld Yarden , Ohana Nissim , Benayahu Dafna 
Published: March 2019

AbstractLumbar spinal canal stenosis (LSCS) is a degenerative disease observed by hypertrophy of the ligamentum flavum (LF) that cause compression of the lumbar neural content. Diabetes mellitus (DM) is a risk factor for the disease and we have shown previously that DM increases the fibrosis and elastic fiber loss in patients with LSCS. The purpose of this study was to find the proteins that play a role in the development of this clinical pathogenesis and the effect of DM on protein expression. LF tissue retrieved from patients diagnosed with LSCS, some were also diagnosed with DM, were compared with LF from patients diagnosed with herniated nucleus pulposus (HNP). The tissues were analyzed by mass spectrometry for proteins profile alteration. We found that LF of LSCS/DM patients exhibited significantly higher levels of proteoglycan proteins and latent transforming growth factor β‐binding protein (LTBP2 and LTBP4). Additionally, an increase of HTRA serine protease 1 and insulin‐like growth factor binding protein‐5 were noted. The higher fibrosis was also associated with proteins related to inflammation and slower tissue repair. Collagen 6 and transforming growth factor inhibitor are related to activation of the anti‐inflammatory M2 pathway that is associated with tissue repair. The decrease of these proteins expression in LSCS/DM is associated with increased levels and activation of M1 pro‐inflammatory pathways. Interestingly, C3 and C4b members of the complement complex and mannose receptor‐like protein (CLEC18) paralogous proteins were detectable solely at the LSCS/DM patients’ samples. Histology analysis shows that inflammatory was induced by the hyperglycemic conditions in diabetic patients involve in altering the matrix compositions. Thus, the protein profiles associated with inflammatory pathways affecting the LF suggested increasing susceptibility of developing the degeneration under hyperglycemic conditions.
Induction of cell‐cycle arrest and apoptosis in human cholangiocarcinoma cells by pristimerin
Authors: Sun Jian‐min , Xu Hai‐tao , Zhao Liang , Zhang Yu‐bao , Kang Peng‐cheng , Song Zeng‐fu , Liu Hai‐shi , Cui Yun‐Fu 
Published: March 2019

AbstractPristimerin, a triterpenoid isolated from Celastraceae and Hippocrateaceae, is known to induce cytotoxicity in several cancer cell lines. However, whether pristimerin can induce apoptosis in cholangiocarcinoma cells and the underlying mechanism remain unexplored. We assessed the function of human cholangiocarcinoma QBC and RBE cell lines using various experimental methods such as the cell viability assay to elucidate the viability of cells, flow cytometry to detect the death rate of cells, and Western blot analysis to evaluate the expression of cell cycle‐related proteins and autophagy‐related proteins. Human cholangiocarcinoma QBC cells were transplanted to nude mice to establish an animal model, and the effect of pristimerin on tumor growth in this model was observed. QBC and RBE cell lines treated with pristimerin (0, 5, 10, and 20 μmol/L) demonstrated the induction of apoptosis in a dose‐dependent manner. The cell viability assay revealed a reduction in the cell viability with an increase in the pristimerin concentration. Similarly, flow cytometry revealed a gradual increase in the cell death rate with an increase in the pristimerin concentration. In addition, pristimerin significantly lowered the expression of apoptosis‐related proteins (Bcl‐2, Bcl‐xL, and procaspase‐3), but increased the Bax expression. Furthermore, pristimerin resulted in the G0/G1 cell‐cycle arrest, reducing the expression of cell cycle‐related proteins (cyclin E, CDK2, and CDK4), and increased the expression of autophagy‐related proteins (LC3) in QBC cell line. Treatment with pristimerin could inhibit tumor growth in the nude mouse model.Overall, this study suggests the potential effect of pristimerin on the cell‐cycle arrest and apoptosis in human cholangiocarcinoma cells.
Epigenetic modifications but not genetic polymorphisms regulate KEAP1 expression in colorectal cancer
Authors: Gao Linbo , Yuan Fang , Che Guanglu , Xiao Xiao , Nie Xinwen , Wang Yanyun , Jia Jin , Kong Ah‐Ng , Zhang Lin 
Published: March 2019

AbstractKelch‐like ECH‐associated protein 1 (KEAP1), as a negative regulator of nuclear factor erythroid 2 like 2 (
NRF2), plays a pivotal role in
NRF2 signaling pathway and involves in tumorigenesis. Polymorphisms and methylation in gene promoter region may influence its expression and be related to cancer susceptibility. In this study, we examined the effect of the
KEAP1‐NRF2 interaction on the risk of colorectal cancer (CRC). The polymorphisms of
NRF2 and
KEAP1 were genotyped using the improved multiplex ligase detection reaction assay.
KEAP1 promoter methylation and histone modification were analyzed using bisulfite genome sequencing and chromatin immunoprecipitation (ChIP) assay, respectively. The
KEAP1 rs1048290 CC genotype and C allele were associated with increased risks of CRC (CC vs GG: odds ratio [OR] = 1.39; 95% confidence interval [CI], 1.08‐1.78; CC vs GG/GC: OR = 1.29; 95% CI, 1.05‐1.58; C vs G: OR = 1.18; 95% CI, 1.04‐1.34). The rs1048290‐rs11545829 GT haplotype was associated with a reduced risk of CRC.
KEAP1‐NRF2 interaction analysis revealed that the rs6721961, rs35652124, rs1048290, and rs11545829 conferred the susceptibility to CRC. The hypermethylation of
KEAP1 promoter resulted in lower levels of
KEAP1 messenger RNA (mRNA). After treatment with 5‐aza‐2′‐deoxycytidine/trichostatin A,
KEAP1 promoter methylation was decreased and
KEAP1 mRNA levels were increased. ChIP‐quantitative polymerase chain reaction results showed an enhanced enrichment of H3K4Me3 and H3K27Ac to the promoter of
KEAP1. In vitro methylation analysis showed that the methylated plasmid decreased the transcriptional activity by 70%‐84%. These findings suggest that the
KEAP1‐
NRF2 pathway could potentially impact CRC risk and the downregulation of
KEAP1 could be explained in part by epigenetic modifications.