bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural Analysis of Alkaline Pretreated Rice Straw for Ethanol Production
Authors: Phitsuwan Paripok , Permsriburasuk Chutidet , Baramee Sirilak , Teeravivattanakit Thitiporn , Ratanakhanokchai Khanok
Published: August 2017

Rice straw (RS) is an abundant, readily available agricultural waste, which shows promise as a potential feedstock for Asian ethanol production. To enhance release of glucose by enzymatic hydrolysis, RS was pretreated with aqueous ammonia (27% w/w) at two pretreatment temperatures: room temperature and 60°C. Statistical analysis indicated similarity of enzymatic glucose production at both pretreatment temperatures after 3-day incubation. Chemical composition, FTIR, and EDX analyses confirmed the retention of glucan and xylan in the pretreated solid, but significant reduction of lignin (60.7% removal) and silica. SEM analysis showed the disorganized surfaces and porosity of the pretreated RS fibers, thus improving cellulose accessibility for cellulase. The crystallinity index increased from 40.5 to 52.3%, indicating the higher exposure of cellulose. With 10% (w/v) solid loadings of pretreated RS, simultaneous saccharification and fermentation yielded a final ethanol concentration of 24.6 g/L, corresponding to 98% of maximum theoretical yield. Taken together, aqueous ammonia pretreatment is an effective method to generate highly digestible pretreated RS for bioethanol production and demonstrates potential application in biorefinery industry.
Chronic Osteomyelitis of the Distal Femur Treated with Resection and Delayed Endoprosthetic Reconstruction: A Report of Three Cases
Authors: Ryan Sean , Eward William , Brigman Brian , Zura Robert
Published: August 2017

Chronic osteomyelitis involving the distal femur often results in amputation or arthrodesis. This article presents three cases of chronic osteomyelitis treated with a staged approach culminating in endoprosthetic reconstruction. Stage one involved resection of infected bone and placement of an intramedullary nail spanning the bony defect between proximal femur and tibia, with antibiotic cement packed around the nail. Patients were then placed on long-term IV +/− oral antibiotics to clear the infection. A “cooldown” period was then used between stages where patients were off antibiotics and inflammatory markers were monitored for signs of remaining infection. Stage two then involved reconstruction of the distal femur and knee with an endoprosthesis. In the appropriate patient, this treatment strategy offers another option in this challenging population.
A Novel Dynamic Model Describing the Spread of the MERS-CoV and the Expression of Dipeptidyl Peptidase 4
Authors: Tang Siming , Ma Wanbiao , Bai Peifan
Published: August 2017

The Middle East respiratory syndrome (MERS) coronavirus, a newly identified pathogen, causes severe pneumonia in humans. MERS is caused by a coronavirus known as MERS-CoV, which attacks the respiratory system. The recently defined receptor for MERS-CoV, dipeptidyl peptidase 4 (DPP4), is generally expressed in endothelial and epithelial cells and has been shown to be present on cultured human nonciliated bronchiolar epithelium cells. In this paper, a class of novel four-dimensional dynamic model describing the infection of MERS-CoV is given, and then global stability of the equilibria of the model is discussed. Our results show that the spread of MERS-CoV can also be controlled by decreasing the expression rate of DPP4.
The Magic of Universal Quantum Computing with Permutations
Authors: Planat Michel , Ul Haq Rukhsan
Published: August 2017

The role of permutation gates for universal quantum computing is investigated. The “magic” of computation is clarified in the permutation gates, their eigenstates, the Wootters discrete Wigner function, and state-dependent contextuality (following many contributions on this subject). A first classification of a few types of resulting magic states in low dimensions d≤9 is performed.
Protein Posttranslational Modifications: Roles in Aging and Age‐Related Disease
Authors: Santos Ana L. , Lindner Ariel B.
Published: August 2017

Aging is characterized by the progressive decline of biochemical and physiological function in an individual. Consequently, aging is a major risk factor for diseases like cancer, obesity, and type 2 diabetes. The cellular and molecular mechanisms of aging are not well understood, nor is the relationship between aging and the onset of diseases. One of the hallmarks of aging is a decrease in cellular proteome homeostasis, allowing abnormal proteins to accumulate. This phenomenon is observed in both eukaryotes and prokaryotes, suggesting that the underlying molecular processes are evolutionarily conserved. Similar protein aggregation occurs in the pathogenesis of diseases like Alzheimer’s and Parkinson’s. Further, protein posttranslational modifications (PTMs), either spontaneous or physiological/pathological, are emerging as important markers of aging and aging‐related diseases, though clear causality has not yet been firmly established. This review presents an overview of the interplay of PTMs in aging‐associated molecular processes in eukaryotic aging models. Understanding PTM roles in aging could facilitate targeted therapies or interventions for age‐related diseases. In addition, the study of PTMs in prokaryotes is highlighted, revealing the potential of simple prokaryotic models to uncover complex aging‐associated molecular processes in the emerging field of microbiogerontology.
Esophageal Squamous Cell Carcinoma Presenting with Streptococcus intermedius Cerebral Abscess
Authors: Nayfe Rabih , Ascha Mustafa S. , Rehmus Esther H.
Published: August 2017

Background. Cerebral abscess is caused by inoculation of an organism into the brain parenchyma from a site distant from the central nervous system. Streptococcus intermedius (S. intermedius) is a commensal organism that is normally present in the aerodigestive tract and was reported to be the cause of brain abscesses after esophageal dilatation or upper endoscopy. Case Presentation. We report the case of a 53-year-old female who presented with hematemesis and melena followed by left-sided weakness. Initially, her hemiplegia was found to be secondary to a right thalamic brain abscess caused by S. intermedius. Investigations led to the diagnosis of a mid-esophageal squamous cell carcinoma. We hypothesize that the cause of the abscess with this bacterium that naturally resides in the digestive tract and oral cavity is secondary to hematogenous spread from breach in the mucosal integrity from ulceration due to the cancer. Conclusion. To our knowledge, our case is the first in the literature to describe a brain abscess caused by S. intermedius in association with a previously undiagnosed esophageal squamous cell carcinoma without any prior esophageal intervention.
Estimating Train Choices of Rail Transit Passengers with Real Timetable and Automatic Fare Collection Data
Authors: Zhu Wei , Wang Wei , Huang Zhaodong
Published: August 2017

An urban rail transit (URT) system is operated according to relatively punctual schedule, which is one of the most important constraints for a URT passenger’s travel. Thus, it is the key to estimate passengers’ train choices based on which passenger route choices as well as flow distribution on the URT network can be deduced. In this paper we propose a methodology that can estimate individual passenger’s train choices with real timetable and automatic fare collection (AFC) data. First, we formulate the addressed problem using Manski’s paradigm on modelling choice. Then, an integrated framework for estimating individual passenger’s train choices is developed through a data-driven approach. The approach links each passenger trip to the most feasible train itinerary. Initial case study on Shanghai metro shows that the proposed approach works well and can be further used for deducing other important operational indicators like route choices, passenger flows on section, load factor of train, and so forth.
Corneal Nerve Regeneration after Self-Retained Cryopreserved Amniotic Membrane in Dry Eye Disease
Authors: John Thomas , Tighe Sean , Sheha Hosam , Hamrah Pedram , Salem Zeina M. , Cheng Anny M. S. , Wang Ming X. , Rock Nathan D.
Published: August 2017

Purpose. To evaluate the efficacy of self-retained cryopreserved amniotic membrane (CAM) in promoting corneal nerve regeneration and improving corneal sensitivity in dry eye disease (DED).Methods. In this prospective randomized clinical trial, subjects with DED were randomized to receive CAM (study group) or conventional maximum treatment (control). Changes in signs and symptoms, corneal sensitivity, topography, and in vivo confocal microscopy (IVCM) were evaluated at baseline, 1 month, and 3 months.Results. Twenty subjects (age 66.9 ± 8.9) were enrolled and 17 completed all follow-up visits. Signs and symptoms were significantly improved in the study group yet remained constant in the control. IVCM showed a significant increase in corneal nerve density in the study group (12,241 ± 5083 μm/mm2at baseline, 16,364 ± 3734 μm/mm2at 1 month, and 18,827 ± 5453 μm/mm2at 3 months,p=0.015) but was unchanged in the control. This improvement was accompanied with a significant increase in corneal sensitivity (3.25 ± 0.6 cm at baseline, 5.2 ± 0.5 cm at 1 month, and 5.6 ± 0.4 cm at 3 months,p<0.001) and corneal topography only in the study group.Conclusions. Self-retained CAM is a promising therapy for corneal nerve regeneration and accelerated recovery of the ocular surface health in patients with DED. The study is registered at clinicaltrials.gov with trial identifier:NCT02764814.
A Novel Strategy for Minimum Attribute Reduction Based on Rough Set Theory and Fish Swarm Algorithm
Authors: Su Yuebin , Guo Jin
Published: August 2017

For data mining, reducing the unnecessary redundant attributes which was known as attribute reduction (AR), in particular, reducts with minimal cardinality, is an important preprocessing step. In the paper, by a coding method of combination subset of attributes set, a novel search strategy for minimal attribute reduction based on rough set theory (RST) and fish swarm algorithm (FSA) is proposed. The method identifies the core attributes by discernibility matrix firstly and all the subsets of noncore attribute sets with the same cardinality were encoded into integers as the individuals of FSA. Then, the evolutionary direction of the individual is limited to a certain extent by the coding method. The fitness function of an individual is defined based on the attribute dependency of RST, and FSA was used to find the optimal set of reducts. In each loop, if the maximum attribute dependency and the attribute dependency of condition attribute set are equal, then the algorithm terminates, otherwise adding a single attribute to the next loop. Some well-known datasets from UCI were selected to verify this method. The experimental results show that the proposed method searches the minimal attribute reduction set effectively and it has the excellent global search ability.
Maturation, Refinement, and Serotonergic Modulation of Cerebellar Cortical Circuits in Normal Development and in Murine Models of Autism
Authors: Hoxha Eriola , Lippiello Pellegrino , Scelfo Bibiana , Tempia Filippo , Ghirardi Mirella , Miniaci Maria Concetta
Published: August 2017

The formation of the complex cerebellar cortical circuits follows different phases, with initial synaptogenesis and subsequent processes of refinement guided by a variety of mechanisms. The regularity of the cellular and synaptic organization of the cerebellar cortex allowed detailed studies of the structural plasticity mechanisms underlying the formation of new synapses and retraction of redundant ones. For the attainment of the monoinnervation of the Purkinje cell by a single climbing fiber, several signals are involved, including electrical activity, contact signals, homosynaptic and heterosynaptic interaction, calcium transients, postsynaptic receptors, and transduction pathways. An important role in this developmental program is played by serotonergic projections that, acting on temporally and spatially regulated postsynaptic receptors, induce and modulate the phases of synaptic formation and maturation. In the adult cerebellar cortex, many developmental mechanisms persist but play different roles, such as supporting synaptic plasticity during learning and formation of cerebellar memory traces. A dysfunction at any stage of this process can lead to disorders of cerebellar origin, which include autism spectrum disorders but are not limited to motor deficits. Recent evidence in animal models links impairment of Purkinje cell function with autism-like symptoms including sociability deficits, stereotyped movements, and interspecific communication by vocalization.
Idiopathic Myointimal Hyperplasia of Mesenteric Veins of the Ileum and Colon in a Patient with Crohn’s Disease: A Case Report and Brief Review of the Literature
Authors: Song Sharon J. , Shroff Stuti G.
Published: August 2017

Idiopathic myointimal hyperplasia of the mesenteric veins (IMHMV) is a rare disease characterized by intimal smooth muscle proliferation, leading to the thickening of small to medium-sized mesenteric veins. This vascular disease mimics inflammatory bowel disease (IBD) clinically and endoscopically, while showing ischemic mucosal changes without the classic features of IBD on biopsy. Given the mixed picture, this entity is frequently misdiagnosed. Surgical resection of the diseased bowel segment reveals the true etiology of the pathology and is curative. We describe a case of a 59-year-old man with a long-standing history of Crohn’s disease refractory to medical therapy and status after multiple small bowel resections. The patient underwent a subtotal abdominal colectomy with pathology showing dense, indurated mesenteric adipose tissue, significant muscularis propria hypertrophy, and myointimal hyperplasia of the mesenteric veins in a peri-ileal and pericolic distribution, as confirmed by elastin stain. No evidence of mucosal ischemic changes or findings of chronicity or acuity were seen. IMHMV, a rare disease with a mixed presentation, poses a significant diagnostic challenge to clinicians and pathologists.
Peripheral Inhibitor of AChE, Neostigmine, Prevents the Inflammatory Dependent Suppression of GnRH/LH Secretion during the Follicular Phase of the Estrous Cycle
Authors: Herman Andrzej P. , Skipor Janina , Krawczyńska Agata , Bochenek Joanna , Wojtulewicz Karolina , Antushevich Hanna , Herman Anna , Paczesna Kamila , Romanowicz Katarzyna , Tomaszewska-Zaremba Dorota
Published: August 2017

The study was designed to test the hypothesis that the inhibition of acetylcholinesterase (AChE) activity at the periphery by Neostigmine (0.5 mg/animal) will be sufficient to prevent inflammatory dependent suppression of the gonadotropin-releasing hormone (GnRH)/luteinising hormone (LH) secretion in ewes in the follicular phase of the estrous cycle, and this effect will be comparable with the systemic AChE inhibitor, Donepezil (2.5 mg/animal). An immune/inflammatory challenge was induced by peripheral administration of lipopolysaccharide (LPS; 400 ng/kg). Peripheral treatment with Donepezil and Neostigmine prevented the LPS-induced decrease (P<0.05) in LHβgene expression in the anterior pituitary gland (AP) and in LH release. Moreover, Donepezil completely abolished (P<0.05) the suppressory effect of inflammation on GnRH synthesis in the preoptic area, when pretreatment with Neostigmine reduced (P<0.05) the decrease in GnRH content in this hypothalamic structure. Moreover, administration of both AChE inhibitors diminished (P<0.05) the inhibitory effect of LPS treatment on the expression of GnRH receptor in the AP. Our study shows that inflammatory dependent changes in the GnRH/LH secretion may be eliminated or reduced by AChE inhibitors suppressing inflammatory reaction only at the periphery such as Neostigmine, without the need for interfering in the central nervous system.
Thermal Effect on Structural Interaction between Energy Pile and Its Host Soil
Authors: Li Qingwen , Chen Lu , Qiao Lan
Published: August 2017

Energy pile is one of the promising areas in the burgeoning green power technology; it is gradually gaining attention and will have wide applications in the future. Because of its specific structure, the energy pile has the functions of both a structural element and a heat exchanger. However, most researchers have been paying attention to only the heat transfer process and its efficiency. Very few studies have been done on the structural interaction between the energy pile and its host soil. As the behavior of the host soil is complicated and uncertain, thermal stresses appear with inhomogeneous distribution along the pile, and the peak value and distribution of stress will be affected by the thermal and physical properties and thermal conductivities of the structure and the host soil. In view of the above, it is important to determine thermal-mechanical coupled behavior under these conditions. In this study, a comprehensive method using theoretical derivations and numerical simulation was adopted to analyze the structural interaction between the energy pile and its host soil. The results of this study could provide technical guidance for the construction of energy piles.
Assessment of the Adequacy of Gauge Repeatability and Reproducibility Study Using a Monte Carlo Simulation
Authors: Ha Chunghun , Kim David S. , Park SeJoon
Published: August 2017

ANOVA gauge repeatability and reproducibility study is the most popular tool for measurement system analysis. Two experimental designs can be applied depending on the durability of the objects. If repeated measurements are possible or sufficient homogeneous nonrepeatable samples are available, crossed design is appropriate; otherwise, nested design should be used. In this paper, we investigated the adequacy of ANOVA gauge repeatability and reproducibility study from the perspective of practitioners. We proposed a Monte Carlo simulation that is close to the realistic procedure to evaluate the adequacy of both structures. During the evaluation, we considered the average performance metrics, percentage of correct decision, histogram shape, and symmetric mean absolute percentage error for the four popular performance metrics, namely, % Study Variation, % Contribution, % Tolerance, and the number of distinct categories. The experimental results show that the nested design fails to judge the precision of the gauge while the crossed design succeeds.
Clinical Factors of Delayed Perforation after Endoscopic Submucosal Dissection for Gastric Neoplasms
Authors: Yamamoto Yoshinobu , Nishisaki Hogara , Sakai Hideki , Tokuyama Nagahiro , Sawai Hiroaki , Sakai Aya , Mimura Takuya , Kushida Saeko , Tsumura Hidetaka , Sakamoto Takeshi , Miki Ikuya , Tsuda Masahiro , Inokuchi Hideto
Published: August 2017

Background. Delayed perforation is a rare but severe complication of endoscopic submucosal dissection (ESD) for early gastric neoplasm (EGN). The aim of this study was to clarify clinical factors related to delayed perforation after ESD. Methods. A total of 1158 consecutive patients with 1199 EGNs underwent ESD at our hospital between January 2000 and December 2015. Univariate analysis was used to identify clinicopathological factors related to delayed perforation. Moreover, duration of cautery needed for hemostasis was measured by comparison between perforated and nonperforated points in patients with delayed perforation. Results. Delayed perforation occurred in 5 of 1158 consecutive patients with 1199 EGNs who underwent ESD (0.42%). All cases were diagnosed within 24 h after ESD and recovered with conservative management. On univariate analysis, location in the upper stomach was the factor most significantly associated with delayed perforation (P<0.01). Duration of cautery needed for hemostasis was significantly longer at perforated points (9 s) than at nonperforated points (3.5 s) in five patients. Conclusions. Location in the upper stomach was the risk factor most prominently associated with delayed perforation after ESD for EGNs. In addition, delayed perforation appears associated with excessive electrocautery for hemostasis.
Racial and Socioeconomic Disparities Are More Pronounced in Inflammatory Breast Cancer Than Other Breast Cancers
Authors: Denu Ryan A. , Hampton John M. , Currey Adam , Anderson Roger T. , Cress Rosemary D. , Fleming Steven T. , Lipscomb Joseph , Wu Xiao-Cheng , Wilson J. Frank , Trentham-Dietz Amy
Published: August 2017

Inflammatory breast cancer (IBC) is a rare yet aggressive form of breast cancer. We examined differences in patient demographics and outcomes in IBC compared to locally advanced breast cancer (LABC) and all other breast cancer patients from the Breast and Prostate Cancer Data Quality and Patterns of Care Study (POC-BP), containing information from cancer registries in seven states. Out of 7,624 cases of invasive carcinoma, IBC and LABC accounted for 2.2% (N=170) and 4.9% (N=375), respectively. IBC patients were more likely to have a higher number (P=0.03) and severity (P=0.01) of comorbidities than other breast cancer patients. Among IBC patients, a higher percentage of patients with metastatic disease versus nonmetastatic disease were black, on Medicaid, and from areas of higher poverty and more urban areas. Black and Hispanic IBC patients had worse overall and breast cancer-specific survival than white patients; moreover, IBC patients with Medicaid, patients from urban areas, and patients from areas of higher poverty and lower education had worse outcomes. These data highlight the effects of disparities in race and socioeconomic status on the incidence of IBC as well as IBC outcomes. Further work is needed to reveal the causes behind these disparities and methods to improve IBC outcomes.
The Evaluation of Antioxidant and Anti‐Inflammatory Effects of Eucommia ulmoides Flavones Using Diquat‐Challenged Piglet Models
Authors: Yuan Daixiu , Hussain Tarique , Tan Bie , Liu Yanhong , Ji Peng , Yin Yulong
Published: August 2017

This study was designed to evaluate the antioxidant and anti‐inflammatory effects of Eucommia ulmoides flavones (EUF) using diquat‐challenged piglet models. A total of 96 weaned piglets were randomly allotted to 1 of 3 treatments with 8 replication pens per treatment and 4 piglets per pen. The treatments were basal diet, basal diet + diquat, and 100 mg/kg EUF diet + diquat. On day 7 after the initiation of treatment, the piglets were injected intraperitoneally with diquat at 8 mg/kg BW or the same amount of sterilized saline. The experiment was conducted for 21 days. EUF supplementation improved the growth performance of diquat‐treated piglets from day 14 to 21. Diquat also induced oxidative stress and inflammatory responses and then impaired intestinal morphology. But EUF addition alleviated these negative effects induced by diquat that showed decreasing serum concentrations of proinflammatory cytokines but increasing antioxidant indexes and anti‐inflammatory cytokines on day 14. Supplementation of EUF also increased villi height and villous height, crypt depth, but decreased the histopathological score and MPO activity compared with those of diquat‐challenged pigs fed with the basal diet on day 14. Results indicated that EUF attenuated the inflammation and oxidative stress of piglets caused by diquat injection.
Nonlinear Elasticity of Borocarbide Superconductor YNi2B2C: A First-Principles Study
Authors: Liu Lili , Chen Cai , Liu Dingxing , Hu Zhengquan , Xu Gang , Wang Rui
Published: August 2017

First-principles calculations combined with homogeneous deformation methods are used to investigate the second- and third-order elastic constants of YNi2B2C with tetragonal structure. The predicted lattice constants and second-order elastic constants of YNi2B2C agree well with the available data. The effective second-order elastic constants are obtained from the second- and third-order elastic constants for YNi2B2C. Based on the effective second-order elastic constants, Pugh’s modulus ratio, Poisson’s ratio, and Vickers hardness of YNi2B2C under high pressure are further investigated. It is shown that the ductility of YNi2B2C increases with increasing pressure.
PRC2-Mediated Transcriptomic Alterations at the Embryonic Stage Govern Tumorigenesis and Clinical Outcome in MYCN-Driven Neuroblastoma
Authors: Tsubota Shoma , Kishida Satoshi , Shimamura Teppei , Ohira Miki , Yamashita Satoshi , Cao Dongliang , Kiyonari Shinichi , Ushijima Toshikazu , Kadomatsu Kenji
Published: August 2017

Pediatric cancers such as neuroblastoma are thought to involve a dysregulation of embryonic development. However, it has been difficult to identify the critical events that trigger tumorigenesis and differentiate them from normal development. In this study, we report the establishment of a spheroid culture method that enriches early-stage tumor cells from TH-MYCN mice, a preclinical model of neuroblastoma. Using this method, we found that tumorigenic cells were evident as early as day E13.5 during embryo development, when the MYC and PRC2 transcriptomes were significantly altered. Ezh2, an essential component of PRC2, was expressed in embryonic and postnatal tumor lesions and physically associated with N-MYC and we observed that H3K27me3 was increased at PRC2 target genes. PRC2 inhibition suppressed in vitro sphere formation, derepressed its target genes, and suppressed in situ tumor growth. In clinical specimens, expression of MYC and PRC2 target genes correlated strongly and predicted survival outcomes. Together, our findings highlighted PRC2-mediated transcriptional control during embryogenesis as a critical step in the development and clinical outcome of neuroblastoma. Cancer Res; 77(19); 5259–71. ©2017 AACR.
Nuclear FAK and Runx1 Cooperate to Regulate IGFBP3, Cell-Cycle Progression, and Tumor Growth
Authors: Canel Marta , Byron Adam , Sims Andrew H. , Cartier Jessy , Patel Hitesh , Frame Margaret C. , Brunton Valerie G. , Serrels Bryan , Serrels Alan
Published: August 2017

Nuclear focal adhesion kinase (FAK) is a potentially important regulator of gene expression in cancer, impacting both cellular function and the composition of the surrounding tumor microenvironment. Here, we report in a murine model of skin squamous cell carcinoma (SCC) that nuclear FAK regulates Runx1-dependent transcription of insulin-like growth factor binding protein 3 (IGFBP3), and that this regulates SCC cell-cycle progression and tumor growth in vivo. Furthermore, we identified a novel molecular complex between FAK and Runx1 in the nucleus of SCC cells and showed that FAK interacted with a number of Runx1-regulatory proteins, including Sin3a and other epigenetic modifiers known to alter Runx1 transcriptional function through posttranslational modification. These findings provide important new insights into the role of FAK as a scaffolding protein in molecular complexes that regulate gene transcription. Cancer Res; 77(19); 5301–12. ©2017 AACR.
HNF1B Loss Exacerbates the Development of Chromophobe Renal Cell Carcinomas
Authors: Sun Mianen , Tong Pan , Kong Wen , Dong Baijun , Huang Yiran , Park In Young , Zhou Lijun , Liu Xian-De , Ding Zhiyong , Zhang Xuesong , Bai Shanshan , German Peter , Powell Reid , Wang Quan , Tong Xuefei , Tannir Nizar M. , Matin Surena F. , Rathmell W. Kimryn , Fuller Gregory N. , McCutcheon Ian E. , Walker Cheryl L. , Wang Jing , Jonasch Eric
Published: August 2017

Chromophobe renal cell carcinoma (ChRCC) is characterized by major changes in chromosomal copy number (CN). No model is available to precisely elucidate the molecular drivers of this tumor type. HNF1B is a master regulator of gene expression. Here, we report that the transcription factor HNF1B is downregulated in the majority of ChRCC and that the magnitude of HNF1B loss is unique to ChRCC. We also observed a strong correlation between reduced HNF1B expression and aneuploidy in ChRCC patients. In murine embryonic fibroblasts or ACHN cells, HNF1B deficiency reduced expression of the spindle checkpoint proteins MAD2L1 and BUB1B, and the cell-cycle checkpoint proteins RB1 and p27. Furthermore, it altered the chromatin accessibility of Mad2l1, Bub1b, and Rb1 genes and triggered aneuploidy development. Analysis of The Cancer Genome Atlas database revealed TP53 mutations in 33% of ChRCC where HNF1B expression was repressed. In clinical specimens, combining HNF1B loss with TP53 mutation produced an association with poor patient prognosis. In cells, combining HNF1B loss and TP53 mutation increased cell proliferation and aneuploidy. Our results show how HNF1B loss leads to abnormal mitotic protein regulation and induction of aneuploidy. We propose that coordinate loss of HNF1B and TP53 may enhance cellular survival and confer an aggressive phenotype in ChRCC. Cancer Res; 77(19); 5313–26. ©2017 AACR.
The Phosphatidylinositol 3-Kinase Pathway as a Potential Therapeutic Target in Bladder Cancer
Authors: Zeng Shu-Xiong , Zhu Yanjun , Ma Ai-Hong , Yu Weimin , Zhang Hongyong , Lin Tzu-Yin , Shi Wei , Tepper Clifford G. , Henderson Paul T. , Airhart Susan , Guo Jian-Ming , Xu Chuan-Liang , deVere White Ralph W. , Pan Chong-Xian
Published: August 2017

Purpose: Activation of the PI3K pathway occurs in over 40% of bladder urothelial cancers. The aim of this study is to determine the therapeutic potential, the underlying action, and the resistance mechanisms of drugs targeting the PI3K pathway.

Experimental Design: Urothelial cancer cell lines and patient-derived xenografts (PDXs) were analyzed for alterations of the PI3K pathway and for their sensitivity to the small-molecule inhibitor pictilisib alone and in combination with cisplatin and/or gemcitabine. Potential predictive biomarkers for pictilisib were evaluated, and RNA sequencing was performed to explore drug resistance mechanisms.

Results: The bladder cancer cell line TCCSUP, which harbors a PIK3CA E545K mutation, was sensitive to pictilisib compared to cell lines with wild-type PIK3CA. Pictilisib exhibited stronger antitumor activity in bladder cancer PDX models with PI3KCA H1047R mutation or amplification than the control PDX model. Pictilisib synergized with cisplatin and/or gemcitabine in vitro, significantly delayed tumor growth, and prolonged survival compared with single-drug treatment in the PDX models. The phosphorylation of ribosomal protein S6 correlated with response to pictilisib both in vitro and in vivo, and could potentially serve as a biomarker to predict response to pictilisib. Pictilisib activated the compensatory MEK/ERK pathway that likely contributed to pictilisib resistance, which was reversed by cotreatment with the RAF inhibitor sorafenib. RNA sequencing of tumors resistant to treatment suggested that LSP1 downregulation correlated with drug resistance.

Conclusions: These preclinical results provide new insights into the therapeutic potential of targeting the PI3K pathway for the treatment of bladder cancer. Clin Cancer Res; 23(21); 6580–91. ©2017 AACR.
Fetal Sheep Mesenteric Resistance Arteries: Functional and Structural Maturation
Authors: Müller Julia J. , Schwab Matthias , Rosenfeld Charles R. , Antonow-Schlorke Iwa , Nathanielsz Peter W. , Rakers Florian , Schubert Harald , Witte Otto W. , Rupprecht Sven
Published: August 2017

Background: Fetal blood pressure increases during late gestation; however, the underlying vascular mechanisms are unclear. Knowledge of the maturation of resistance arteries is important to identify the mechanisms and vulnerable periods for the development of vascular dysfunction in adulthood. Methods: We determined the functional and structural development of fetal sheep mesenteric resistance arteries using wire myography and immunohistochemistry. Results: Media mass and distribution of myosin heavy-chain isoforms showed no changes between 0.7 (100 ± 3 days) and 0.9 (130 ± 3 days) gestation. However, from 0.7 to 0.9 gestation, the resting wall tension increased accompanied by non-receptor-dependent (potassium) and receptor-dependent (noradrenaline; endothelin-1) increases in vasocontraction. Angiotensin II had no contractile effect at both ages. Endothelium-dependent relaxation to acetylcholine and prostaglandin E2 was absent at 0.7 but present at 0.9 gestation. Augmented vascular responsiveness was paralleled by the maturation of sympathetic and sensory vascular innervation. Non-endothelium-dependent relaxation to nitric oxide showed no maturational changes. The expression of vasoregulator receptors/enzymes did not increase between 0.7 and 0.9 gestation. Conclusion: Vascular maturation during late ovine gestation involves an increase in resting wall tension and the vasoconstrictor and vasodilator capacity of the mesenteric resistance arteries. Absence of structural changes in the tunica media and the lack of an increase in vasoregulator receptor/enzyme expression suggest that vasoactive responses are due to the maturation of intracellular pathways at this gestational age.
Outcomes of Self-Expanding Metal Stents in Malignant Colonic Obstruction are Independent of Location or Length of the Stenosis: Results of a Retrospective, Single-Center Series
Authors: Schoonbeek Paul K. , Genzel Pim , van den Berg Eline H. , van Dobbenburgh O. Aart , ter Borg Frank
Published: August 2017

Aim: To evaluate the length and location of stenosis in the colon as predictors of technical and clinical outcomes of stent placement in patients presenting with obstructive colorectal cancer. Methods: A prospective single-center cohort study of patients treated with a colonic stent for malignant obstruction, regardless of stenosis length or location. Stenosis length was assessed globally on the appropriate CT slice as well as by 3D CT reconstruction. We analyzed whether outcomes were different in patients with a right sided-tumor and/or a stenosis >4 cm long. Results: One hundred forty-one patients were evaluated, 63 with a stenosis >4 cm, 48 with a stenosis proximal to the splenic flexure. Technical failure (n = 9) was mainly caused because of looping or due to the difficulty in engaging the stenosis precluding analysis of the relation between the stenosis length and technical success. Both measurement methods showed good agreement. Clinical outcomes were not associated with stenosis length or location. Conclusion: Clinical outcomes of stenting did not differ between groups regardless of stenosis length or location. Measuring stenosis length more precisely using 3D CT reconstructions is not of help.
A Prospective, Randomized, Open-Label, Blinded, Endpoint Study Exploring Platelet Response to Half-Dose Prasugrel and Ticagrelor in Patients with the Acute Coronary Syndrome: HOPE-TAILOR Study
Authors: Jin Cai De , Kim Moo Hyun , Bang Junghee , Serebruany Victor
Published: August 2017

Background: The optimal dosing of novel oral P2Y12 receptor platelet inhibitors such as prasugrel or ticagrelor is unclear and especially challenging in East Asians. We hypothesize that half-dose prasugrel and ticagrelor may be sufficient for long-term maintenance management in Korean patients with the acute coronary syndrome (ACS) compared with conventional dosages. Design: HOPE-TAILOR (Half Dose of Prasugrel and Ticagrelor in Platelet Response after Acute Coronary Syndromes) is a prospective, randomized, open-label, blinded, endpoint (PROBE) single-center, clinical trial. A total of 100 patients with ACS undergoing drug-eluting stent implantation will be randomly assigned to prasugrel, ticagrelor, or clopidogrel, and the patients in each treatment group will receive 1-month therapy with 100 mg q.d. aspirin plus prasugrel 10 mg q.d., ticagrelor 90 mg b.i.d., or clopidogrel 75 mg q.d., followed by half-dose prasugrel 5 mg q.d. or ticagrelor 45 mg b.i.d. for maintenance treatment but without clopidogrel dose reduction. The primary endpoint will be optimal platelet reactivity 3 months after coronary intervention, defined by VerifyNow Analyzer (PRU: 85-208) and vasodilator-stimulated phosphoprotein P2Y12 flow cytometry assay (platelet reactivity indices: 16-50%). Clinical outcomes will also be assessed, including major efficacy (composite of cardiac death, nonfatal myocardial infarction, repeat revascularization, or stroke) and safety (bleeding ≥2 according to the Bleeding Academic Research Consortium). Conclusion: HOPE-TAILOR is a prospective, randomized, open-label, blinded, endpoint study to explore the efficacy and safety of novel P2Y12 receptor inhibitors administered orally at half the dose in Korean patients with ACS. The results will be available late in 2017.
Evaluating Critical Brain Radiation Doses in the Treatment of Multiple Brain Lesions with Gamma Knife Radiosurgery
Authors: Hatiboglu Mustafa Aziz , Akdur Kerime
Published: August 2017

Background: Treatment of patients with multiple brain metastases has shifted to stereotactic radiosurgery, withholding whole-brain (WB) radiation therapy. However, radiation toxicity to the brain is a concern when treating multiple brain lesions with single-fraction stereotactic radiosurgery. Objective: The purpose of this study was to determine the changes in brain radiation doses when treating various numbers of targets and lesion volumes. Methods: We simulated different treatment plans with different combinations of varying tumor volumes including 0.1, 0.5, 1, 2, and 5 cm3, and tumor numbers including 1, 3, 5, 10, 15, 20, and 25. Treatment planning was performed for all combinations in a computerized tomography of the head of a patient, using Leksell GammaPlan version 10.1.1 (Elekta AB, Stockholm, Sweden). Two different dosing strategies were used. In the lower-prescription dosing schedule, a marginal dose was given to the 50% isodose line, and 20 Gy were used when the number of lesions was less than 15 and 18 Gy were applied when the number of lesions was equal to or more than 15. In the higher-prescription dosing schedule, a marginal dose of 24 Gy was used for lesions of less than 5 cm3 and 20 Gy were applied for lesions equal to 5cm3. The mean WB dose, the WB integral dose, and the volume of brain receiving 12 Gy (V12 Gy) were calculated for each scenario. Also, the beam-on time of the Gamma Knife 4C unit was reported for all treatment scenarios. Results: Regression analysis showed that the total tumor volume was a more significant predictor of V12 Gy than the number of lesions, and a linear correlation between the total tumor volume and V12 Gy was found. We also found that the total tumor volume was a more significant predictor of the mean WB dose and the WB integral dose compared to the number of lesions. Conclusion: Our results suggest that multiple small to mid-sized lesions could be safely treated with a single-fraction gamma knife.
GPER Agonist G1 Attenuates Neuroinflammation and Dopaminergic Neurodegeneration in Parkinson Disease
Authors: Guan Jing , Yang Beibei , Fan Yi , Zhang Ji
Published: August 2017

Objective: Epidemiological studies have shown that women of reproductive age have much less possibility of developing Parkinson disease (PD) than men. The beneficial effect of estrogen also has been well-described in both culture and animal models of PD. G protein-coupled estrogen receptor (GPER) is a membrane-associated estrogen receptor, and displayed a neuroprotective role in a mouse model of PD. Since GPER is highly expressed in microglia, we speculate that GPER mediates the neuroprotective function of estradiol through suppressing the neuroinflammation of PD. Methods: We investigated the effects of GPER agonist G1 and GPER antagonist G15 on the neurodegeneration of dopaminergic neuron, the activation of microglia, and the production of IL-1β, TNF-α, and IL-6 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced animal model of parkinsonism. Furthermore, we confirmed the effects of GPER activation on the production of IL-1β, TNF-α, and IL-6 in an in vitro MPP+ model in BV2 microglial cells. Results: After 12-day treatment with G1, mice showed an increase in the number of tyrosine hydroxylase-immunoreactive cells, reduced activation of microglia, and the abatement of proinflammatory cytokines, and the anti-inflammatory effect of G1 was abolished by G15. Meanwhile, in vitro studies demonstrated that GPER activation also reduced the release of proinflammatory cytokines from BV2 microglial cells after MPP+ stimulation. Conclusion: Our data suggest that GPER mediates the anti-neuroinflammatory effect of estrogen in experimental PD progression.
Antibiotic Susceptibility and Molecular Characterization of Escherichia coli O157 Isolates from Urinary Tract Infections
Authors: Xie Zonglan , Dong Ziqiang , Zhu Ping , Zhang Lusheng , Chen Xiaobo , Dong Chuanjiang
Published: August 2017

Background:Escherichia coli O157 is an important food-borne pathogen that can cause diarrhoea, hemorrhagic colitis, and hemolytic uraemic syndrome. Enterobacterial repetitive intergenic consensus sequence PCR (ERIC-PCR) and multilocus sequence typing (MLST) are good methods for molecular typing and the extensive use of antibiotics is a contributing factor to the increasing incidence of antimicrobial-resistant for these strains. Objectives: The aim of this study was to determine the prevalence, antimicrobial resistance, and genetic diversity of E. coli O157 based on the prevalence of urinary tract infection (UTI) in Hubei, China. Results: We obtained 23 (8.07%) E. coli O157 isolates from 285 UTI patients in Hubei, China. All isolates were subjected to antibiotic susceptibility analysis, and molecular typing was performed using ERIC-PCR and MLST. Antimicrobial susceptibility results indicated that most strains were resistant to penicillin (95.65%), chloramphenicol (73.91%), and ampicillin (69.57%). All isolates were discovered to be multiresistant (resistance to more than 3 antibiotics). Genetic variability analysis showed that all of the isolates were grouped into 4 clusters both by ERIC-PCR and MLST. Conclusion: Our findings demonstrated the presence of E. coli O157 in UTIs, provided insights into the dissemination of antibiotic-resistant strains, and improved our knowledge of E. coli O157 risk assessment in UTIs.
Insulin Influences LPS-Induced TNF-α and IL-6 Release Through Distinct Pathways in Mouse Macrophages from Different Compartments
Authors: Tessaro Fernando H. G. , Ayala Thais S. , Nolasco Eduardo L. , Bella Leonardo M. , Martins Joilson O.
Published: August 2017

Background/Aims: Diabetic subjects are more susceptible to infections, which is partially due to insulin deficiency and hyperglycemia. We hypothesized that insulin influences cytokine release by macrophages from diabetic C57BL/6 mice stimulated with lipopolysaccharides (LPS). Methods: Bone marrow-derived macrophages (BMDM) and tissue-specific macrophages from diabetic (alloxan 60 mg/kg, i.v.) male C57BL/6 mice were stimulated by LPS (100 ng/mL) and/or treated by insulin (1 mU/mL). Results: Using BMDM from diabetic mice, we showed that LPS induced an increase in TNF-α and IL-6 release and p38, SAPK/JNK, ERK 1/2, and Akt (308-Thr and 473-Ser) phosphorylation but not in PKCα/β II and delta. Insulin increased TNF-α and IL-6 secretion in LPS-stimulated macrophages as well as p-p38, p-SAPK/JNK, p-ERK 1/2, p-PI3K (p55) and p-Akt (473-Ser) expression. Furthermore, PI3-kinase inhibition by wortmannin decreased TNF-α release, and inhibition by LY294002 decreased both TNF-α and IL-6 levels after LPS-insulin treatment. PD98059, which inhibits the ERK upstream activators MAPK kinase (MKK) 1 and MKK2, reduced the effect promoted by insulin in BMDM stimulated by LPS In tissue-specific macrophages, insulin reduced LPS-induced TNF-α, IL-6 and IL-1β secretion in alveolar and peritoneal macrophages. Conclusion: These data suggest that insulin through the modulation of PI3-kinase and ERK 1/2 pathways drive different responses in macrophages, thereby enhancing our understanding of the plasticity of these cells.
Association Between C1q/TNF-Related Protein-1 Levels in Human Plasma and Epicardial Adipose Tissues and Congestive Heart Failure
Authors: Yang Ying , Liu Si , Zhang Rong-Yi , Luo Hui , Chen Ling , He Wen-Feng , Lei Rong , Liu Mu-Rong , Hu Hou-Xiang , Chen Mao
Published: August 2017

Background/Aims: C1q and tumour necrosis factor-related protein 1 (CTRP1) possesses anti-atherogenic and anti-inflammatory effects. This study investigated whether the CTRP1 levels in the plasma and epicardial adipose tissue (EAT) were associated with congestive heart failure (CHF) and to disclose possible molecular mechanisms. Methods: Plasma and tissue samples were obtained from subjects with or without CHF. Plasma levels of CTRP1 were measured by ELISA. The mRNA levels of CTRP1 and inflammatory cytokines were detected by RT-PCR. The protein levels of CTRP1, aldosterone synthase (CYP11B2) and mitogen-activated protein kinase were examined by Western blotting. Results: The levels of CTRP1 in the plasma and EAT were higher in the CHF patients than those in the controls. There were no differences in the CTRP1 levels in cardiomyocytes between the CHF group and the non-CHF group. An exploratory survival analysis showed that higher CTRP1 values at admission were associated with a worse prognosis after discharge. CTRP1 increased the IL-6 mRNA level in H295R cells. CTRP1 recruited ERK1/2 and Jak-2 for aldosterone release by modulating the CYP11B2 protein level, and brain natriuretic peptide repressed the CTRP1-induced aldosterone release through the JAK2-STAT3 signalling pathways. Conclusion: The CTRP1 levels in the plasma and EAT were increased in the CHF patients. CTRP1 is involved in the pathogenesis of CHF by modulating IL-6 levels and aldosterone release.
Determinants of inter-firm and inter-regional employment mobility in the formal sector in Brazil
Authors: Mendes Philipe Scherrer , Gonçalves Eduardo , Freguglia Ricardo
Published: August 2017

O objetivo deste artigo é analisar os determinantes da mobilidade laboral, diferenciando possíveis opções de mudança de emprego entre firmas de uma mesma cidade e entre firmas de diferentes localidades. Usando microdados da RAIS-Migra, propõe-se verificar os determinantes dessa mobilidade laboral no Brasil, controlando por características dos trabalhadores e fazendo uma distinção setorial por intensidades tecnoló- gicas. A partir de modelos de regressão logística multinomial com interceptos aleatórios (GLLAMM), os principais resultados obtidos evidenciam que a mobilidade é positivamente relacionada com o salário para as mudanças interfirmas e entre municípios (localizados em um mesmo Estado). Por outro lado, todos esses resultados podem diferir significativamente em relação à extensão territorial da mobilidade.
Smoking and wage penalty in the Brazilian labor market
Authors: Almeida Aléssio Tony Cavalcanti de , Araújo Júnior Ignácio Tavares de
Published: August 2017

Esse artigo investiga a heterogeneidade da repercussão de hábitos pessoais não saudáveis, expressa pelo o uso do cigarro, sobre a produtividade do trabalho no Brasil. Baseado na Pesquisa Especial de Tabagismo integrante da Pesquisa Nacional por Amostra de Domicílios 2008, os principais modelos empíricos são desenvolvidos por meio de regressão quantílica com variáveis instrumentais. Os resultados encontrados explicitam que fumantes, independentemente dos modelos condicionados para a mé- dia ou por quantil com e sem variáveis instrumentais, apresentam menor rendimento do trabalho. Assim, a penalização salarial para fumantes com controle para endogeneidade varia de 15,2% a 36,5% ao longo da distribuição condicional dos rendimentos individuais.