bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Dynamics Validation of Crizotinib Resistance to ALK Mutations (L1196M and G1269A) and Identification of Specific Inhibitors
Authors: Nagasundaram Nagarajan , Wilson Alphonse Carlton Ranjith , Samuel Gnana Prakash Vincent , Rajaretinam Rajesh Kannan 
Published: March 2017

ABSTRACTAnaplastic lymphoma kinase (ALK) positive non‐small cell lung cancer (NSCLC) patients are mostly treated with ALK tyrosine kinase inhibitors (TKIs). Crizotinib is the first generation ALK inhibitor practiced as a primary chemo to combat cancer cells followed by second generation inhibitor ceritinib which are effective against crizotinib resistant ALK mutations. However, patients treated with these drugs invariably relapsed because of the development of new drug resistance mutations. In this study we explored the crizotinib resistance in the presence of ALK mutations L1196M and G1269A through molecular dynamics simulation studies. Further mutation specific inhibitors CID 71748211 and CID 71728095 were identified to potentially inhibit ALK with mutations L1196M and G1269A, respectively. This computational investigation in‐sighted the molecular factors involved in crizotinib resistance which enhanced in the identification of new ALK drugs that brings individualized medicine to treat ALK positive NSCLC patients with specific mutations. J. Cell. Biochem. 118: 3462–3471, 2017. © 2017 Wiley Periodicals, Inc.
Targeting Immunotherapy to the Tumor Microenvironment
Authors: Dougan Michael , Dougan Stephanie K. 
Published: March 2017

ABSTRACTTargeting drugs to the tumor microenvironment has long been appreciated as a means of increasing local concentrations and decreasing systemic toxicities. How drug targeting might apply to immune‐based therapies is less clear. In this review, we explain the immunology of cancer, with a focus on the principles of in situ vaccination. Certain types of therapies are more amenable to local versus systemic delivery; these include cytokines, adjuvants, radiation, and agents targeting tumor‐resident cell populations. Several approaches for targeting the tumor microenvironment are under development. Nanoparticles, peptide or antibody‐based delivery, and exploitation of cellular influx are all promising ways to delivery immune modulating compounds to tumors. J. Cell. Biochem. 118: 3049–3054, 2017. © 2017 Wiley Periodicals, Inc.
hsa‐mir‐3199‐2 and hsa‐mir‐1293 as Novel Prognostic Biomarkers of Papillary Renal Cell Carcinoma by COX Ratio Risk Regression Model Screening
Authors: Luo Wen , Wang Lei , Luo Mao‐Hua , Huang Yu‐Zhu , Yang Hua , Zhou Yu , Jia Hong‐Tao , Wang Xiu‐Xin 
Published: March 2017

ABSTRACTPapillary renal cell carcinoma(PRCC) is the second most common and aggressive renal cell carcinoma. Identification of novel microRNA biomarkers could be beneficial for the diagnosis and prognosis of PRCC patients. We aimed to screen differentially expressed miRNAs that can act as prognostic factors and to predict the survival of PRCC patients. High‐throughput data of miRNAs of 274 PRCC samples were downloaded from TCGA (The Cancer Genome Atlas) dataset and interested miRNAs were identified. Hierarchical clustering and principal component analysis (PCA) were performed on these miRNAs. Critical genes that can act as prognostic factors were screened by LASSO. What's more, Kaplan–Meier survival analysis and ROC (Receiver Operating Characteristic) growth curve were used to testify the accuracy of the model. Biological processes of putative targets of miRNAs were analyzed by bioinformatics methods such as GO (Go Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis. A total of 105 differentially expressed miRNAs were screened out in PRCC samples compared with healthy controls. Two critical miRNAs, hsa‐mir‐3199‐2, and hsa‐mir‐1293, were screened out by LASSO (Least Absolute Shrinkage and Selection Operator), including 197 and 189 target genes, respectively. Furthermore, its’ accuracy was testified by ROC analysis with the AUC (Area under the curve) value of 0.7774968 and 0.6743466. These miRNAs were significantly enriched in pathways as platelet activating factor biosynthetic process, epithelial cell maturation, and IkappaB kinase complex. In conclusion, hsa‐mir‐3199‐2 and hsa‐mir‐1293 that can act as prognostic biomarkers of PRCC were screened out, which can provide new insights for the clinical treatment of the disease. J. Cell. Biochem. 118: 3488–3494, 2017. © 2017 Wiley Periodicals, Inc.
Overexpression of Hsa‐miR‐320 Is Associated With Invasion and Metastasis of Ovarian Cancer
Authors: Wang Wei , Yang Juan , Xiang Yuan‐Yuan , Pi Jie , Bian Jiang 
Published: March 2017

ABSTRACTOvarian cancer is one of the most common malignant tumor of female genital organs which ranks the third morbidity. We aimed to provide a better understanding of the mechanism of invasion and metastasis of ovarian cancer. The ovarian cancer samples were downloaded from GEO. Then clustering was performed to classify the stage of miRNAs based on the difference of prognosis and metastasis. Furthermore, the miRNAs model was build and the survival analysis processes was performed to observe the influence on prognosis, invasion and metastasis. At last, miRNAs co‐expression network was built to explore the core miRNAs and the risk classification model was built to perform the risk assessment based on these core miRNAs. A total of 17 significantly differential expressed miRNAs were obtained. Functional enrichment of 1,488 target genes, pathways like cell cycle, focal adhesion, and pathways in cancer, which are closely related to the proliferation and metastasis of cancer cells were highly enriched, this indicate that these miRNAs are related to the proliferation and metastasis of cancer cells. The co‐expressed network shows that the high expression of hsa‐miR‐320 indicated negative prognosis and high risk of metastasis. In conclusion, the expression level of hsa‐miR‐320 is highly related to the migration and invasion of cancer. The high expression of hsa‐miR‐320 directly indicated negative prognosis and high risk of metastasis. These findings reveal that hsa‐miR‐320 may serve as an important therapeutic target in ovarian cancer therapy. J. Cell. Biochem. 118: 3654–3661, 2017. © 2017 Wiley Periodicals, Inc.
Neuroprotective Effects of Loganin on MPTP‐Induced Parkinson's Disease Mice: Neurochemistry, Glial Reaction and Autophagy Studies
Authors: Xu Yi‐Da , Cui Chun , Sun Meng‐Fei , Zhu Ying‐Li , Chu Min , Shi Yun‐Wei , Lin Stanley Li , Yang Xu‐Sheng , Shen Yan‐Qin 
Published: March 2017

ABSTRACTParkinson's disease (PD) is a progressive neurodegenerative disease, involving resting tremor and bradykinesia, for which no recognized therapies or drugs are available to halt or slow progression. In recent years, natural botanic products have been considered relatively safe, with limited side effects, and are expected to become an important source for clinical mediation of PD in the future. Our study focuses on the ability of loganin, a compound derived from fruits of cornus, to mediate neuroprotection in a mouse model of PD. Mice were administered 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) with a dosage of 30 mg/kg daily for 5 days to establish a subacute PD model and treated with loganin. Locomotor activity was assessed by a pole test, then mice were euthanized at 1 and 3 days after the last treatment, and brain tissue was prepared for subsequent assays. Loganin rescued decrease of dopamine levels and tyrosine hydroxylase (TH) expression in the striatum, and shortened total locomotor activity (TLA) time of mice. Furthermore, loganin alleviated microglia and astrocyte activation, and suppressed TNF‐α and caspase‐3 expression through a c‐Abl‐p38‐NFκB pathway. Loganin also downregulated LC3‐II and Drp1 expression, and decreased the level of acidic vesicular organelles (AVOs). Loganin exerts neuroprotective effects on MPTP‐induced PD mice by decreasing inflammation, autophagy, and apoptosis, suggesting that loganin could serve as a therapeutic drug to ameliorate PD. J. Cell. Biochem. 118: 3495–3510, 2017. © 2017 Wiley Periodicals, Inc.
Chemoenzymatic synthesis of poly(phenylene disulfides) with insulating properties and resistant to high temperatures
Authors: Sierra Estefanía , Miranda‐Molina Alfonso , Castillo Edmundo , Hu Hailin , Ayala Marcela 
Published: March 2017

AbstractBACKGROUNDCyclic aromatic disulfides (CAD) can be used as cross‐linking agents or precursors for the synthesis of high temperature resistant polymers such as poly(phenylene disulfides) (PPD). Chemical synthesis of CAD relies on the use of corrosive agents, detrimental for the environment. This paper reports an environment friendly chemoenzymatic procedure to obtain PPD starting from simple aromatic dithiols.RESULTSThe enzymatic reaction was carried out in an aqueous mixture with acetonitrile as co‐solvent, using 1,4‐ and 1,3‐benzenedithiol as monomers and a fungal laccase (EC 1.10.3.2) as catalyst. The products obtained were identified as mainly cyclic aromatic disulfides. Thermal analysis suggested that the enzymatically‐synthesized CAD display thermal stability and are amenable precursors of high molecular weight sulfur‐containing polymers through solvent‐free, melt ring opening polymerization (mROP). After mROP, polymeric molecules around 12.8 kDa were obtained and identified as PPD. The resultant PPD shows uniform size, resistance to temperatures up to 400 °C and electrical insulating properties.CONCLUSIONLaccase‐catalyzed synthesis of CAD represents a novel reaction, not previously described elsewhere for oxidoreductases. A 100% substrate conversion was achieved under mild reaction conditions and no over‐oxidation of CAD was observed, representing an advantage over chemical synthesis. The CAD products precipitated completely from the reaction medium, thus simplifying the purification process. © 2017 Society of Chemical Industry
Proteome comparison for discrimination between honeydew and floral honeys from botanical species Mimosa scabrella Bentham by principal component analysis
Authors: Azevedo Mônia Stremel , Valentim‐Neto Pedro Alexandre , Seraglio Siluana Katia Tischer , da Luz Cynthia Fernandes Pinto , Arisi Ana Carolina Maisonnave , Costa Ana Carolina Oliveira 
Published: March 2017

AbstractBACKGROUNDDue to the increasing valuation and appreciation of honeydew honey in many European countries and also to existing contamination among different types of honeys, authentication is an important aspect of quality control with regard to guaranteeing the origin in terms of source (honeydew or floral) and needs to be determined. Furthermore, proteins are minor components of the honey, despite the importance of their physiological effects, and can differ according to the source of the honey. In this context, the aims of this study were to carry out protein extraction from honeydew and floral honeys and to discriminate these honeys from the same botanical species, Mimosa scabrella Bentham, through proteome comparison using two‐dimensional gel electrophoresis and principal component analysis.RESULTSThe results showed that the proteome profile and principal component analysis can be a useful tool for discrimination between these types of honey using matched proteins (45 matched spots). Also, the proteome profile showed 160 protein spots in honeydew honey and 84 spots in the floral honey.CONCLUSIONThe protein profile can be a differential characteristic of this type of honey, in view of the importance of proteins as bioactive compounds in honey. © 2017 Society of Chemical Industry
Impact of drying and micronization on the physicochemical properties and antioxidant activities of celery stalk
Authors: Ramachandraiah Karna , Chin Koo Bok 
Published: March 2017

AbstractBACKGROUNDThe influence of convective drying and ball‐mill treatment of celery stalk on particle size distribution, physicochemical properties, bioactive compounds and antioxidant activities were analyzed in this study.RESULTSBall‐milling of celery stalk dried at temperatures of 50, 75 and 100 °C resulted in decreased average particle sizes of 48.8, 10.5 and 7.2 µm, respectively. Bulk density was increased with reduced particle size. Darker (L*) and reddish (a*) powders were formed at higher temperatures, while ball‐milling increased greenness (−a*) of powders dried at 50 and 75 °C. Total content of phenol compounds increased with increasing temperature. 2,2‐Diphenyl‐1‐picrylhydrazyl radical scavenging activity and reducing power were affected by ball‐milling for 24 h and drying at elevated temperatures. Iron chelating ability was unaffected by increasing temperature or reduced particle size.CONCLUSIONIncreasing drying temperatures not only decreased the average particle size of powders, but also increasingly reduced particle size after ball‐milling. Micronization of celery stalk dried at the highest temperature had the best antioxidant activities. Drying and ball‐milling were not highly deleterious to the major phenolic structures. © 2017 Society of Chemical Industry
Reporting of mitotic rate in cutaneous melanoma: A study using the national cancer data base
Authors: Lorimer Patrick D. , Benham Emily C. , Walsh Kendall , Han Yimei , Forster Meghan R. , Sarantou Terry , White Richard L. , Hill Joshua S. 
Published: March 2017

BackgroundThe seventh edition of the American Joint Commission on Cancer staging manual (AJCC7, published 2009), updated thin cutaneous melanoma staging protocols with the incorporation of mitotic rate (MR). In these patients, higher MR is associated with decreased survival. This study utilizes the National Cancer Data Base (NCDB) to evaluate MR reporting since AJCC7.MethodsThe NCDB was queried for patients with primary cutaneous melanoma from 1998 to 2013. Because MR reporting was infrequent prior to implementing AJCC7, records from 2010 to 2013 were analyzed. Categorical variables were compared with chi‐square tests; univariate and multivariate logistic regression models were constructed to determine the effects of covariates on MR reporting.ResultsA total of 107,134 patients met inclusion criteria. From 2010 to 2013, MR reporting increased dramatically (64.3–80.9%). On multivariate analysis, factors significantly related to increased MR reporting include later diagnosis year, T‐classification (T1a and b vs. T1), facility type (academic vs. other specified types of cancer programs), facility volume, patient income, level of education, and county population (metropolitan vs. urban and rural).ConclusionsMR reporting increased dramatically after the introduction of AJCC7; however, disparities in reporting remain across facility types. Further investigation of procedures performed in academic settings that may influence reporting of MR is warranted. J. Surg. Oncol. 2017;115:281–286. © 2017 Wiley Periodicals, Inc.
RBC transfusion is associated with increased risk of respiratory failure after pneumonectomy
Authors: Kidane Biniam , Plourde Madelaine , Leydier Larissa , Chadi Sami A. , Eckert Kathleen , Srinathan Sadeesh , Fortin Dalilah , Frechette Eric , Inculet Richard I. , Malthaner Richard A. 
Published: March 2017

Background and ObjectivesPneumonectomy is associated with high risk of respiratory complications. Our objective was to determine if transfusions are associated with increased rate of ARDS and respiratory failure in adults undergoing elective pneumonectomy.MethodsRetrospective cohort study of consecutive pneumonectomies undertaken at a tertiary hospital (2003‐2013). Multivariable logistic regression was performed to adjust for confounding factors.ResultsARDS and respiratory failure occurred in 12.4% (n = 20) and 19.2% (n = 31) of 161 pneumonectomy patients, respectively, and were more likely to occur in transfused patients (P = 0.03, P < 0.001). pRBCs, FFP and platelets were transfused in 27% (n = 43), 6% (n = 9), and 2% (n = 3), respectively. On multivariable analyses utilizing blood products as continuous and binary variables, pRBC use was the only independent predictor of ARDS with odds ratio (OR) = 1.23 (95%CI:1.08‐1.39, P = 0.002) and OR = 2.45 (95%CI:1.10‐5.49, P = 0.03), respectively. On multivariable analyses utilizing blood products as continuous and binary variables, pRBCs were the only independent predictor of respiratory failure with OR = 1.37 (95%CI:1.16‐1.60, P < 0.001) and OR = 3.17 (95%CI:1.25‐8.02, P = 0.02), respectively.ConclusionsPeri‐operative pRBC use appears to be an independent risk factor for ARDS and respiratory failure after pneumonectomy. There is a significant dose‐response relationship. Platelets and FFP did not appear to increase ARDS risk but this may be due to low utilization.
Liver parenchyma transection‐first approach in hemihepatectomy with en bloc caudate lobectomy for hilar cholangiocarcinoma: A safe technique to secure favorable surgical outcomes
Authors: Kawabata Yasunari , Hayashi Hikota , Yano Seiji , Tajima Yoshitsugu 
Published: March 2017

BackgroundAlthough hemihepatectomy with total caudate lobectomy (hemiHx‐tc) is essential for the surgical treatment of hilar cholangiocarcinoma, the advantage of an anterior approach for hemiHx‐tc has not been fully discussed technically; the significance of an anterior approach without liver mobilization for preventing infectious complications also remains unknown.MethodsThe liver parenchyma transection‐first approach (Hp‐first) technique is an early transection of the hepatic parenchyma without mobilization of the liver that utilizes a modified liver‐hanging maneuver to avoid damaging the future remnant liver.ResultsBetween May 2010 and August 2016, a total of 40 consecutive patients underwent surgery for hilar cholangiocarcinoma. Of these, 19 patients underwent a conventional hemihepatectomy with total caudate lobectomy (cHx), while 21 patients received a Hp‐first. The patients in the Hp‐first group had significantly less intraoperative blood loss (P < 0.001) and blood transfusion (P < 0.001), a lower incidence of postoperative hyperbilirubinemia (p = 0.023), a lower incidence of liver failure (p = 0.038), a lower hospital death rate (p = 0.042), and a better 2‐year disease‐free survival rate (p = 0.010) than those in the cHx group.ConclusionsThe liver parenchyma transection‐first approach is the preferred technique for hemiHx‐tc in hilar cholangiocarcinoma because it resulted in improved surgical outcomes as compared with the conventional approach.
Impact of neoadjuvant chemoradiation on perioperative outcomes in patients with rectal cancer
Authors: Chapman Brandon C. , Hosokawa Patrick , Henderson William , Paniccia Alessandro , Overbey Douglas M. , Messersmith Wells , Lieu Christopher , Stiegmann Greg V. , Schulick Richard D. , Gajdos Csaba 
Published: March 2017

Background and ObjectivesNeoadjuvant chemoradiation for rectal cancer is associated with lower local recurrence rates. The objective of this study is to assess the impact of neoadjuvant therapy on perioperative complications in patients with rectal cancer.MethodsUsing the ACS‐NSQIP database (2005‐2012), a propensity score was used to match 3592 patients with rectal cancer receiving neoadjuvant therapy to 3592 patients undergoing surgery alone. The association between neoadjuvant chemoradiation and perioperative outcomes was evaluated.ResultsAmong all patients, overall morbidity was significantly higher in the neoadjuvant therapy group (n = 1170, 29.9%) compared to the surgery alone (n = 2350, 26.4%; P < 0.0001), but 30‐day mortality was lower in the neoadjuvant group (n = 27, 0.7%) compared to the surgery alone group (n = 112, 1.3%; P = 0.0043). However, in propensity‐matched patients, there was no difference in overall morbidity (OR 0.912, 95% CI 0.825‐1.008) or 30‐day mortality (OR 0.639, 95% CI 0.38‐1.05). Overall morbidity and 30‐day mortality were 29.3% (n = 1054) and 0.7% (n = 25) in the neoadjuvant group, respectively, compared to 31.3% (n = 1124) and 1.1% (n = 39) in the surgery alone group, respectively.ConclusionPatients with newly diagnosed rectal cancer could be evaluated for neoadjuvant therapy prior to surgical resection without the fear of upfront therapy causing a significant increase in perioperative complications.
Characterization of blue light irradiation effects on pathogenic and nonpathogenic Escherichia coli
Authors: Abana Courtney M. , Brannon John R. , Ebbott Rebecca A. , Dunigan Taryn L. , Guckes Kirsten R. , Fuseini Hubaida , Powers Jennifer , Rogers Bridget R. , Hadjifrangiskou Maria 
Published: March 2017

AbstractBlue light irradiation (BLI) is an FDA‐approved method for treating certain types of infections, like acne, and is becoming increasingly attractive as an antimicrobial strategy as the prevalence of antibiotic‐resistant “superbugs” rises. However, no study has delineated the effectiveness of BLI throughout different bacterial growth phases, especially in more BLI‐tolerant organisms such as Escherichia coli. While the vast majority of E. coli strains are nonpathogenic, several E. coli pathotypes exist that cause infection within and outside the gastrointestinal tract. Here, we compared the response of E. coli strains from five phylogenetic groups to BLI with a 455 nm wavelength (BLI455), using colony‐forming unit and ATP measurement assays. Our results revealed that BLI455 is not bactericidal, but can retard E. coli growth in a manner that is dependent on culture age and strain background. This observation is critical, given that bacteria on and within mammalian hosts are found in different phases of growth.
Impact of maternal obesity on very preterm infants
Authors: Khalak Rubia , Rijhsinghani Asha , McCallum Sarah E. 
Published: March 2017

ObjectiveInfants born at less than  34 weeks' gestational age are at higher risk for morbidity and mortality. Data are limited on the impact of maternal obesity on the very preterm infant. This study reviewed whether maternal obesity further increases the intensive care needs of very preterm infants of less than 34 weeks' gestation.MethodsMaternal and neonatal data for live‐born singleton births of 23 0/7 to 33 6/7 weeks' gestation delivering in upstate New York were reviewed. BMI categorization followed the National Institutes of Health BMI classification that subdivides obesity into three ascending BMI groups.ResultsRecords were obtained on 1,224 women, of whom 31.6% were classified with obesity. Despite similar mean gestational age (31 to 31.6 weeks, P = 0.57) and birth weight (1,488 to 1,569 g, P = 0.51) of the infants in the BMI categories, delivery room (DR) resuscitation was more common for infants of women with level III obesity (63.2%, P = 0.04) with a trend toward the continued need for assisted ventilation (54.7%, P = 0.06).ConclusionsPreterm infants of women with level III obesity were more likely to require DR resuscitation with a trend to continued need for ventilatory support beyond 6 hours of age. This could impact utilization of DR resources at delivering hospitals.