bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutational profiles of persistent/recurrent laryngeal squamous cell carcinoma
Authors: Smith Joshua D. , Birkeland Andrew C. , Rosko Andrew J. , Hoesli Rebecca C. , Foltin Susan K. , Swiecicki Paul , Mierzwa Michelle , Chinn Steven B. , Shuman Andrew G. , Malloy Kelly M. , Casper Keith A. , McLean Scott A. , Wolf Gregory T. , Bradford Carol R. , Prince Mark E. , Brenner John Chad , Spector Matthew E. 
Published: December 2018

AbstractBackgroundWe sought to describe targeted DNA sequencing data of persistent/recurrent laryngeal squamous cell carcinoma (LSCC) and to compare gene‐specific alteration frequencies with that of primary, untreated LSCC specimens from The Cancer Genome Atlas (TCGA).MethodsThe tumors of 21 patients with persistent/recurrent LSCC were subjected to targeted DNA sequencing using the Ion AmpliSeq Comprehensive Cancer Panel. Gene‐specific alteration frequencies were compared (Chi‐Square test) to primary, untreated LSCC sequencing data from TCGA using the cBioPortal platform.ResultsPersistent/recurrent LSCC was characterized by a high rate of inactivating alterations in TP53 (38.1%) and CDKN2A (33%), amplification events of CCND1 (19.1%), and ERBB2 (14.3%), and NOTCH1 (19.1%) mutations. Comparison of primary vs persistent/recurrent LSCC revealed significant differences in alteration frequencies of eight critical genes: BAP1, CDKN2A, DCUN1D1, MSH2, MTOR, PIK3CA, TET2, and TP53.ConclusionsOur results provide preliminary support for a distinct mutational profile of persistent/recurrent LSCC that requires validation in larger cohorts.
Long‐term changes in vocal function after supracricoid partial laryngectomy with cricohyoidoepiglottopexy for laryngeal cancer
Authors: Miyamaru Satoru , Minoda Ryosei , Kodama Narihiro 
Published: December 2018

AbstractBackgroundThe purpose of this study was to assess changes in vocal function over time following supracricoid partial laryngectomy with cricohyoidoepiglottopexy (SCL‐CHEP).MethodsA total of 17 patients who underwent SCL‐CHEP for laryngeal squamous cell carcinoma between 2007 and 2015 were reviewed. We examined maximum phonation time (MPT), mean airflow rate (MFR), voice intensity, the grade, roughness, breathiness, asthenia, and strain (GRBAS) scale, Voice Handicap Index‐10 (VHI‐10), and voice‐related quality of life (V‐RQOL) scores. To assess changes over time in these parameters, we set 3 evaluation periods after surgery: within the first 12 months (term A), 13‐36 months (term B), and after 37 months (term C).ResultsThe mean MPT, MFR, G and B GRBAS subscale, VHI‐10, and V‐RQOL scores improved significantly over time postoperatively.ConclusionMultiple vocal function parameters improved significantly with time due to self‐adaptation to a newly created glottis after surgery.
Pathway based prognostic gene expression profile of buccal and gingivo‐buccal oral squamous cell carcinoma in smokeless tobacco chewers
Authors: Prasad Kavitha , Rao Roopa , Augustine Dominic , Sowmya Samudrala Venkatesiah , Haragannavar Vanishri , Sagar Parimala , Sreedhar Prathibha 
Published: December 2018

AbstractBackgroundThe objective was to study comprehensive mRNA expression profiles of buccal mucosa oral squamous cell carcinoma (OSCC‐BM) and gingivo‐buccal OSCC (OSCC‐GB) in smokeless tobacco chewers to understand the biological behavior of OSCC at these specific sites and identify diagnostic and prognostic markers.MethodsHigh throughput RNA sequencing transcriptome of fresh buccal mucosa (4 samples) and gingivo‐buccal (4 samples) OSCC with normal oral mucosa (3 samples) was performed on Illumina NextSeq500 paired end sequencing with 75x2bp.ResultsIn the comparison between OSCC and normal, there were 402 differentially expressed genes (DEGs); between OSCC‐BM and normal, there were 467 DEGs; and between OSCC‐GB and normal oral tissue, there were 608 DEGs. Pathway‐based analysis of gene expression was done. The inflammation mediated by chemokine and cytokine signaling pathway had the maximum gene hits.ConclusionsFZD2 and its interactions with the cadherins have a role in invasion and metastasis. immunosurveillance is evident in OSCC‐GB with the downregulation of CADM1.
Comparative assessment of the intrinsic sensitivity of crop species and wild plant species to plant protection products and their active substances and potential implications for the risk assessment: A literature review
Authors: Christl Heino , Morilla Jaime , Hoen Thierry , Zumkier Ulrich 
Published: December 2018

Abstract

A comprehensive critical review was undertaken aiming to compare the intrinsic sensitivity of terrestrial plant species (crop species and noncrop wild species) with published literature and unpublished proprietary data generated for the registration of plant protection products (PPPs), and a database was compiled. Data were assessed to answer the question whether crops differ from noncrop plants in their intrinsic sensitivity to PPPs. Endpoints were assessed considering further potentially relevant parameters by means of different methods, including a quotient approach, in which overall crop endpoints were divided by matching wild species endpoints. Quotients above 1 indicated that wild species were more sensitive than crops, quotients below 1 the opposite. Further methods included a multiple regression analysis and different approaches to assess the statistical power. The overall finding was that there were no consistent differences in sensitivity between wild plant species and crop species, based on ER50, ER25, and ER10 vegetative endpoints (the largest fraction of data). This was also true when censored endpoints, seedling emergence data, and other measured variables such as shoot height were included. Statistically significant differences occurred in both directions and were balanced, that is, there was no clear trend for either crops or noncrop species to be more sensitive than the other. On the basis of multivariate regression analysis, crops were found to be significantly more sensitive than wild plant species, albeit by a small margin (factor ≈1.4). Minimum detectable difference (MDD) analysis and multivariate regression analysis of modified datasets indicated that when using a data set of this size and heterogeneity, any dissimilarity between crop and wild species was detectable if exceeding a factor of 1.4 in either direction. For the taxonomic groups assessed here (i.e., with data), no intrinsic difference in sensitivity to PPPs between crop species and wild plant species was found. Integr Environ Assess Manag 2019;15:176–189. © 2018 SETAC
Effects of co‐exposure of lipopolysaccharide and β‐glucan (Zymosan A) in exacerbating murine allergic asthma associated with Asian sand dust
Authors: Sadakane Kaori , Ichinose Takamichi , Nishikawa Masataka 
Published: December 2018

AbstractDuring the 2000s, Asian sand dust (ASD) was implicated in the increasing prevalence of respiratory disorders, including asthma. We previously demonstrated that a fungus from ASD aerosol exacerbated ovalbumin (OVA)‐induced airways inflammation. Exposure to heat‐inactivated ASD (H‐ASD) and either Zymosan A (ZymA, containing β‐glucan) or lipopolysaccharide (LPS) exacerbated allergic airways inflammation in a mouse model, but the effects of co‐exposure of LPS and β‐glucan are unclear. We investigated the effects of co‐exposure of LPS and ZymA in OVA‐induced allergic airways inflammation with ASD using BALB/c mice. Exposure to OVA + LPS enhanced the recruitment of inflammatory cells to the lungs, particularly neutrophils; exposure to OVA + LPS + H‐ASD potentiated this effect. Exposure to OVA + ZymA + H‐ASD stimulated the recruitment of inflammatory cells to the lungs, particularly eosinophils, and serum levels of OVA‐specific IgE and IgG1 antibodies, whereas exposure to OVA + ZymA did not affect most indicators of lung inflammation. Although exposure to OVA + LPS + ZymA + H‐ASD affected a few allergic parameters additively or synergistically, most allergic parameters in this group indicated the same level of exposure to OVA + LPS + H‐ASD or OVA + ZymA + H‐ASD. These results suggest that LPS and ZymA play different roles in allergic airways inflammation with ASD; LPS mainly enhances neutrophil recruitment through H‐ASD, and ZymA enhances eosinophil recruitment through H‐ASD.
Poly‐allylamine hydrochloride and fucoidan‐based self‐assembled polyelectrolyte complex nanoparticles for cancer therapeutics
Authors: Wang Pei , Kankala Ranjith Kumar , Chen Biaoqi , Long Ruimin , Cai Duanhua , Liu Yuangang , Wang Shibin 
Published: December 2018

AbstractHerein, we fabricated the novel drug delivery system based on the self‐assembly of two polyelectrolytes, poly‐allylamine hydrochloride (PAH) and fucoidan, as the polycation and polyanion, respectively, under mild conditions for cancer therapeutics. Furthermore, the designed polyelectrolyte complex nanoparticles as well as the methotrexate (MTX) disodium salt‐loaded composites were systematically characterized using various techniques. The MTX loading in the nanoparticles was confirmed by zeta potential values that changed from −36.2 ± 2.2 to −28.3 ± 3.1 mV at a loading amount of 13.3 ± 1.2%. Furthermore, the obtained eventual particle sizes of nanoparticles were various with different concentrations and ratios of polyelectrolytes. The particle size also has increased from 130 ± 2.6 to 162.9 ± 2.3 nm after loading MTX. The drug release investigations in vitro at a pH value of 6.0 (acid environment) showed that the release of MTX was sustained in the conditions provided. Finally, we investigated the anticancer efficacy of MTX‐loaded nanoparticles on MCF‐7 cells and HeLa cells and the satisfactory results were obtained. Together, these self‐assembled PAH/fucoidan nanoparticles with sustained drug release property will become the promising delivery system for cancer therapeutics. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 339–347, 2019.
Ectopic expression of CC chemokine receptor 7 promotes prostate cancer cells metastasis via Notch1 signaling
Authors: Du Ruoyang , Tang Guanlin , Tang Zhaobing , Kuang Youlin 
Published: December 2018

AbstractThere currently exists no satisfactory treatment for patients with prostate cancer with local evolution and distant metastasis. Previous studies have confirmed the importance of CC chemokine receptor 7 (CCR7) in the invasion and metastasis of prostate cancer. And increasing evidence prove that Notch1 can play diametrically opposite roles in the development and progression of different tumors. To demonstrate the correlation between CCR7 and Notch1, PC‐3 cells were transfected with pcDNA3.1‐CCR7 or CCR7 si‐RNA, respectively. Then Western blot analysis was used to detect the expressions of Notch1, ERK, P38, JNK, NF‐κB, MMP‐9, and epithelial‐mesenchymal transition (EMT)‐related proteins. Moreover, matrigel invasion assays were performed to assess the migratory and invasive activities of PC‐3 cells. PcDNA3.1‐CCR7 increased the expression of Notch1, phospho‐MAPK, phospho‐P65, MMP‐9, N‐cadherin, and Snail in PC‐3 cells, but decreased the expression of E‐cadherin. PcDNA3.1‐CCR7 also promoted the migration and invasion of PC‐3 cells. However, CCR7 si‐RNA reversed the effect of pcDNA3.1‐CCR7 in PC‐3 cells. And MAPK and NF‐κB pathway inhibitors were used to testify that activation of Notch1 induces EMT through MAPK and NF‐κB pathway. All these results indicate that upregulation of Notch1 by CCR7 can accelerate the evolution of EMT and develop the invasion and metastasis in prostate cancer cells by activating MAPK and NF‐κB signaling pathways in prostate cancer cells, which provides a new molecular evidence for targeted therapy in metastatic prostate cancer.
Long noncoding RNA OIP5‐AS1 causes cisplatin resistance in osteosarcoma through inducing the LPAATβ/PI3K/AKT/mTOR signaling pathway by sponging the miR‐340‐5p
Authors: Song Lei , Zhou Zhigang , Gan Yibo , Li Pei , Xu Yuan , Zhang Zehua , Luo Fei , Xu Jianzhong , Zhou Qiang , Dai Fei 
Published: December 2018

AbstractThe abnormal expression of long noncoding RNAs (lncRNAs) plays an important role in the regulation of human cancer progression and drug resistance. The lncRNA OPI5‐AS1 is a crucial regulator in some cancers; however, its role in cisplatin resistance of osteosarcoma remains unclear. We found that OIP5‐AS1 was significantly upregulated in cisplatin‐resistant (CR) osteosarcoma cells MG63‐CR and SaOS2‐CR compared with the corresponding parental cells. OIP5‐AS1 silencing suppressed cell growth in vitro and in vivo, and promoted apoptosis of MG63‐CR and SaOS2‐CR cells, indicating that knockdown of OIP5‐AS1 significantly decreased cisplatin resistance in MG63‐CR and SaOS2‐CR cells. This conclusion was supported by the decreased expression of the drug resistance‐related factors multidrug resistance‐associated protein 1 (MRP1) and P‐glycoprotein (P‐gp) upon OIP5‐AS1 silencing. In addition, OIP5‐AS1 downregulation suppressed the PI3K/AKT/mTOR signaling pathway. Importantly, we demonstrated that OIP5‐AS1 functions as a competing endogenous RNA of miR‐340‐5p and regulates the expression of lysophosphatidic acid acyltransferase (LPAATβ), which is a target of miR‐340‐5p. Moreover, downregulation of miR‐340‐5p partly reversed the inhibitory effect of OIP5‐AS1 knockdown on the PI3K/AKT/mTOR pathway and therefore counteracted cisplatin resistance in MG63‐CR and SaOS2‐CR cells. In conclusion, OIP5‐AS1 causes cisplatin resistance in osteosarcoma through inducing the LPAATβ/PI3K/AKT/mTOR signaling pathway by sponging the miR‐340‐5p. Our results contribute to a better understanding of the function and mechanism of OIP5‐AS1 in osteosarcoma cisplatin resistance.
PACAP through EGFR transactivation preserves human corneal endothelial integrity
Authors: Maugeri Grazia , D'Amico Agata Grazia , Castrogiovanni Paola , Saccone Salvatore , Federico Concetta , Reibaldi Michele , Russo Andrea , Bonfiglio Vincenza , Avitabile Teresio , Longo Antonio , D'Agata Velia 
Published: December 2018

AbstractThe corneal endothelium is composed of a single hexagonal‐shaped cells layer adherent to the Descemet's membrane. The primary function of these cells is maintaining of tissue clarity by regulating its hydration. Trauma, aging or other pathologies cause their loss, counterbalanced by enlargement of survived cells unable to guarantee an efficient fluid pumping to and from the stroma. Regenerative medicine using human corneal endothelial cells (HCECs) isolated from peripheral corneal‐scleral tissue of a donor could be an attractive solution, overcoming transplantation problems. In a previous study, we have demonstrated that HCECs treatment with pituitary adenylate cyclase–activating polypeptide (PACAP) following growth factors deprivation prevents their degeneration. However, the molecular mechanism mediating this effect has not been clarified, yet. Here, we have shown for the first time the expression of PACAP and its receptor (PAC1R) in human corneal endothelium and demonstrated that this peptide, selectively binding to PAC1R, induces epidermal growth factor receptor (EGFR) phosphorylation and the MAPK/ERK1/2 signaling pathway activation. In conclusion, our data have suggested that PACAP could represent an important trophic factor in maintaining human corneal endothelial integrity through EGFR transactivation. Therefore, PACAP, as well as epidermal growth factor and fibroblast growth factor, could co‐operate to guarantee tissue physiological functioning by supporting corneal endothelial barrier integrity.
Safety, Tolerability, and Pharmacodynamics of Intrathecal Injection of Recombinant Human HGF (KP‐100) in Subjects With Amyotrophic Lateral Sclerosis: A Phase I Trial
Authors: Warita Hitoshi , Kato Masaaki , Asada Ryuta , Yamashita Atsuko , Hayata Daichika , Adachi Kiichi , Aoki Masashi 
Published: December 2018

AbstractHepatocyte growth factor is an endogenous pleiotropic factor shown to act as a potent neuroprotectant against disease progression in animal models of amyotrophic lateral sclerosis, which is a devastating, adult‐onset motor neuron disease. To evaluate the safety, tolerability, and pharmacokinetics of recombinant 5‐residue‐deleted human hepatocyte growth factor (KP‐100) injected intrathecally through an implantable catheter connected to a subcutaneous port, we conducted a first‐in‐human phase I trial of intrathecal KP‐100 in 15 Japanese patients with amyotrophic lateral sclerosis. The regimen was a single injection of 3 escalating doses (0.2, 0.6, and 2.0 mg/body) in 9 subjects followed by 2 doses (0.6 and 2.0 mg/body) repeated 5 times at 1‐week intervals in 6 subjects (3 subjects/group). With single‐dose administration, the mean half‐life of KP‐100 in the cerebrospinal fluid was 1.2 to 1.4 days, with its maximum concentration increasing in a dose‐dependent manner. With multiple‐dose administration, the trough KP‐100 concentrations in the cerebrospinal fluid generally remained constant for any dose, despite multiple dosing. There were no deaths, serious adverse events, or device malfunctions leading to discontinuation. In all subjects, plasma KP‐100 concentrations were <1 ng/mL, or below the lower limit of detection at all time points of measurement. Anti–KP‐100 antibody was not detected in the cerebrospinal fluid or plasma specimens from any of the subjects throughout the KP‐100 dosing period. These results suggest that KP‐100, as well as the device used to administer it, is safe and tolerable. A phase II trial is warranted in patients with various central nervous system diseases such as amyotrophic lateral sclerosis.
Pharmaceutical quality by design in academic nanomedicine research: stifling innovation or creativity through constraint?
Authors: Dailey Lea Ann 
Published: December 2018

AbstractPharmaceutical quality by design (QbD) is a systematic approach to drug development that begins with predefined objectives and emphasises product and process understanding and control based on sound science and quality risk management. First and foremost, QbD is an experimental design philosophy, which emphasises the value of thorough intellectual planning prior to the commencement of laboratory studies. Academic researchers whose ambitions lie in translational science may benefit from the lessons learned by the pharmaceutical industry following implementation of QbD into their development philosophy. However, because of the very interdisciplinary nature of academic nanomedicine research, it is likely that very few investigators are aware of QbD and how aspects of it may be judiciously implemented in an academic research setting. This review provides an introduction to the main elements of QbD and gives examples of case studies where QbD has been applied to nanomedicine research.
A high‐throughput glutathione trapping assay with combined high sensitivity and specificity in high‐resolution mass spectrometry by applying product ion extraction and data‐dependent neutral loss
Authors: Wang Qingping , Liu Hanlan , Slavsky Marina , Fitzgerald Maria , Lu Chuang , O'Shea Thomas 
Published: December 2018

AbstractReactive metabolites are thought to play a pivotal role in the pathogenesis of some drug‐induced liver injury (DILI) and idiosyncratic adverse drug reactions (IADRs), which is of concern to patient safety and has been a cause of drugs being withdrawn from the market place. To identify drugs with a lower propensity for causing DILI and/or IADRs, high‐throughput assays to capture reactive metabolites are required in pharmaceutical industry for early drug discovery risk assessment. We describe the development of an assay to detect glutathione adducts with combined high sensitivity, enhanced specificity, and rapid data analysis. In this assay, compounds were incubated with human liver microsomes and a mixture of 1:1 of GSH (γ‐GluCysGly): GSX(γ‐GluCysGly‐13C215N) in a 96‐well plate format. UPLC‐UV and LTQ Orbitrap XL were employed to detect GSH‐adducts using the following mass spectrometry setups: (a) selected ion monitoring (SIM) at m/z of 274 ± 3 Da in negative mode with in‐source fragmentation (SCID), which enables simultaneously monitoring two characteristic product ions of m/z 272.0888 (γ‐glutamyl‐dehydroalanyl‐glycine) and 275.0926 (γ‐glutamyl‐dehydroalanyl‐glycine‐13C215N); (b) full scan mode for acquisition of exact mass of glutathione adducts; (c) data‐dependent MS2 scan through isotopic matching (M:M + 3.00375 = 1:1) for monitoring neutral loss fragments (144 Da from dehydroalanyl‐glycine) and for structural information of glutathione adducts. This approach was qualified using eight compounds known to form GSH conjugates as reported in the literature. The high sensitivity and specificity were demonstrated in identifying unique CysGly adducts in the case of clozapine, diclofenac, and raloxifene and in identifying GSH‐adducts of fragmented parent molecules in the case of amodiaquine and troglitazone. In addition, LC‐UV chromatograms in the presence or absence of GSH/GSX allowed for identification of the rearranged glutathione adducts without aforementioned characteristic fragment ions. Implement of this assay in drug discovery small molecule programs has successfully guided drug design.
Hind‐ and midfoot bone morphology varies with foot type and sex
Authors: Moore Erik S. , Kindig Matthew W. , McKearney Daniel A. , Telfer Scott , Sangeorzan Bruce J. , Ledoux William R. 
Published: December 2018

ABSTRACTFoot type has been associated with pain, injury, and altered gait mechanics. Morphological variations in foot bones due to foot type variation may impact surgical and therapeutic treatments. The purpose of this study was to utilize principal component analysis (PCA) to determine how morphology of the hind‐ and midfoot bones differs among foot types and sex. The calcaneus, talus, navicular, and cuboid were segmented using previously obtained computed tomography (CT) scans and converted to surface models. The CTs were sorted into four foot types—cavus, neutrally aligned, asymptomatic planus, and symptomatic planus. Morphometric shape analysis software (Geomorph) was used to perform a PCA to determine which components varied between foot types and between sexes. The calcaneus showed planus feet of both types to have calcanei that have decreased height and increased length compared to neutrally aligned feet. The talus demonstrated increased posterior mass for cavus feet compared to neutrally aligned feet. For the navicular, symptomatic planus had a more posteriorly positioned tuberosity and were wider than asymptomatic planus feet. The cuboid did not exhibit any differences between foot types. Sex differences, found only at the talus and navicular, were subtle. PCA is an objective technique that helped elucidate differences in bone morphology between foot types and sex without needing to determine the features of interest before comparing groups. Understanding these variations can help inform diagnosis of foot pathologies and surgical protocols as well as improve computer models of the foot. Published 2018. This article is a U.S. Government work and is in the public domain in the USA. J Orthop Res 9999:1–16, 2019.