bluuebunny/crossref_metadata_2025 huggingface dataset:
Abalone Muscle Texture Evaluation and Prediction Based on TPA Experiment
Authors: Dong Jiaxu , Fang Xiaoyan , Wang Huihui , Zhang Xu , Tao Xueheng
Published: September 2017

The effects of different heat treatments on abalones’ texture properties and sensory characteristics were studied. Thermal processing of abalone muscle was analyzed to determine the optimal heat treatment condition based on fuzzy evaluation. The results showed that heat treatment at 85°C for 1 hour had certain desirable effects on the properties of the abalone meat. Specifically, a back propagation (BP) neural network was introduced to predict the equations of statistically significant sensory hardness, springiness, and smell using the texture data gained through TPA (texture profile analysis) experiments as input and sensory evaluation data as the desired output. The final outcome was that the predictability was proved to be satisfactory, with an average error of 6.93%.
Effectiveness of Therapeutic Exercise in Fibromyalgia Syndrome: A Systematic Review and Meta-Analysis of Randomized Clinical Trials
Authors: Sosa-Reina M. Dolores , Nunez-Nagy Susana , Gallego-Izquierdo Tomás , Pecos-Martín Daniel , Monserrat Jorge , Álvarez-Mon Melchor
Published: September 2017

Objective. The aim of this study was to summarize evidence on the effectiveness of therapeutic exercise in Fibromyalgia Syndrome. Design. Studies retrieved from the Cochrane Plus, PEDro, and Pubmed databases were systematically reviewed. Randomized controlled trials and meta-analyses involving adults with fibromyalgia were included. The primary outcomes considered in this systematic review were pain, global well-being, symptoms of depression, and health-related quality of life. Results. Effects were summarized using standardized mean differences with 95% confidence intervals using a random effects model. This study provides strong evidence that physical exercise reduces pain (−1.11 [95% CI] −1.52; −0.71; overall effect p<0.001), global well-being (−0.67 [95% CI] −0.89, −0.45; p<0.001), and symptoms of depression (−0.40 [95% CI] −0.55, −0.24; p<0.001) and that it improves both components of health-related quality of life (physical: 0.77 [95% CI] 0.47; 1.08; p<0.001; mental: 0.49 [95% CI] 0.27; 0.71; p<0.001). Conclusions. This study concludes that aerobic and muscle strengthening exercises are the most effective way of reducing pain and improving global well-being in people with fibromyalgia and that stretching and aerobic exercises increase health-related quality of life. In addition, combined exercise produces the biggest beneficial effect on symptoms of depression.
Biotransformation of Dioscorea nipponica by Rat Intestinal Microflora and Cardioprotective Effects of Diosgenin
Authors: Feng Jia-Fu , Tang Yi-Na , Ji Hong , Xiao Zhan-Gang , Zhu Lin , Yi Tao
Published: September 2017

Studying the biotransformation of natural products by intestinal microflora is an important approach to understanding how and why some medicines—particularly natural medicines—work. In many cases, the active components are generated by metabolic activation. This is critical for drug research and development. As a means to explore the therapeutic mechanism of Dioscorea nipponica (DN), a medicinal plant used to treat myocardial ischemia (MI), metabolites generated by intestinal microflora from DN were identified, and the cardioprotective efficacy of these metabolites was evaluated. Our results demonstrate that diosgenin is the main metabolite produced by rat intestinal microflora from DN. Further, our results show that diosgenin protects the myocardium against ischemic insult through increasing enzymatic and nonenzymatic antioxidant levels in vivo and by decreasing oxidative stress damage. These mechanisms explain the clinical efficacy of DN as an anti‐MI drug.
Andrographolide Promotes Neural Differentiation of Rat Adipose Tissue-Derived Stromal Cells through Wnt/β-Catenin Signaling Pathway
Authors: Liang Yan , Li Miao , Lu Tao , Peng Wang , Wu Jian-Huang
Published: September 2017

Adipose tissue-derived stromal cells (ADSCs) are a high-yield source of pluripotent stem cells for use in cell-based therapies. We explored the effect of andrographolide (ANDRO, one of the ingredients of the medicinal herb extract) on the neural differentiation of rat ADSCs and associated molecular mechanisms. We observed that rat ADSCs were small and spindle-shaped and expressed multiple stem cell markers including nestin. They were multipotent as evidenced by adipogenic, osteogenic, chondrogenic, and neural differentiation under appropriate conditions. The proportion of cells exhibiting neural-like morphology was higher, and neurites developed faster in the ANDRO group than in the control group in the same neural differentiation medium. Expression levels of the neural lineage markers MAP2, tau, GFAP, and β-tubulin III were higher in the ANDRO group. ANDRO induced a concentration-dependent increase in Wnt/β-catenin signaling as evidenced by the enhanced expression of nuclear β-catenin and the inhibited form of GSK-3β (pSer9). Thus, this study shows for the first time how by enhancing the neural differentiation of ADSCs we expect that ANDRO pretreatment may increase the efficacy of adult stem cell transplantation in nervous system diseases, but more exploration is needed.
Semiautomatic Epicardial Fat Segmentation Based on Fuzzy c-Means Clustering and Geometric Ellipse Fitting
Authors: Zlokolica Vladimir , Krstanović Lidija , Velicki Lazar , Popović Branislav , Janev Marko , Obradović Ratko , Ralević Nebojsa M. , Jovanov Ljubomir , Babin Danilo
Published: September 2017

Automatic segmentation of particular heart parts plays an important role in recognition tasks, which is utilized for diagnosis and treatment. One particularly important application is segmentation of epicardial fat (surrounds the heart), which is shown by various studies to indicate risk level for developing various cardiovascular diseases as well as to predict progression of certain diseases. Quantification of epicardial fat from CT images requires advance image segmentation methods. The problem of the state-of-the-art methods for epicardial fat segmentation is their high dependency on user interaction, resulting in low reproducibility of studies and time-consuming analysis. We propose in this paper a novel semiautomatic approach for segmentation and quantification of epicardial fat from 3D CT images. Our method is a semisupervised slice-by-slice segmentation approach based on local adaptive morphology and fuzzy c-means clustering. Additionally, we use a geometric ellipse prior to filter out undesired parts of the target cluster. The validation of the proposed methodology shows good correspondence between the segmentation results and the manual segmentation performed by physicians.
Metallothionein in Brain Disorders
Authors: Juárez-Rebollar Daniel , Rios Camilo , Nava-Ruíz Concepción , Méndez-Armenta Marisela
Published: September 2017

Metallothioneins are a family of proteins which are able to bind metals intracellularly, so their main function is to regulate the cellular metabolism of essential metals. There are 4 major isoforms of MTs (I–IV), three of which have been localized in the central nervous system. MT‐I and MT‐II have been localized in the spinal cord and brain, mainly in astrocytes, whereas MT‐III has been found mainly in neurons. MT‐I and MT‐II have been considered polyvalent proteins whose main function is to maintain cellular homeostasis of essential metals such as zinc and copper, but other functions have also been considered: detoxification of heavy metals, regulation of gene expression, processes of inflammation, and protection against free radicals generated by oxidative stress. On the other hand, the MT‐III has been related in events of pathogenesis of neurodegenerative diseases such as Parkinson and Alzheimer. Likewise, the participation of MTs in other neurological disorders has also been reported. This review shows recent evidence about the role of MT in the central nervous system and its possible role in neurodegenerative diseases as well as in brain disorders.
The Rainfall Intensity Effects on 1–13 GHz UWB-Based 5G System for Outdoor Applications
Authors: Suryana Joko
Published: September 2017

This paper reports a research contribution on tropical outdoor channel characterization in 1–13 GHz band for 5G systems. This 1–13 GHz ultra-wideband (UWB) channel characterization is formulated with rain intensity as the most important variable, from 20 mm/h to 200 mm/h. Tropical rain will cause pulse broadening and distorts the transmitted symbols, so the probability of symbol errors will increase. In this research, the bit error rate (BER) performance evaluation is done using both matched filtering or correlator-based receivers. At no rain conditions, BER 10−6 will be attained at signal to noise ratio (SNR) 5 dB, but at rainfall intensity 200 mm/h, the BER will fall to 10−2 for matched filter and 5×10-2 for correlator-based receivers. For improving the BER performance, an adaptive nonlinear phase equalizer is proposed which adopts multiple allpass biquad infinite impulse response (IIR) filters combined with low-order finite impulse response (FIR) filter to mitigate the nonlinearity phase and differential attenuation of magnitude responses due to antenna and tropical outdoor UWB channel effects. Our simulation results show that the proposed equalizer has worked successfully with BER 10−6 on the rain rate that is exceeded for 0.01% of the time (R0.01) rain intensity or 99.99% availability. In addition, at rainfall rate 120 mm/h, the proposed nonlinear phase equalizer can give 9 dB signal improvement.
MMP‐Inhibitory Effects of Flavonoid Glycosides from Edible Medicinal Halophyte Limonium tetragonum
Authors: Bae Min Joo , Karadeniz Fatih , Oh Jung Hwan , Yu Ga Hyun , Jang Mi-Soon , Nam Ki-Ho , Seo Youngwan , Kong Chang-Suk
Published: September 2017

Limonium tetragonum has been well‐known for its antioxidative properties as a halophyte. This study investigated the antimetastasis effect of solvent‐partitioned L. tetragonum extracts (LTEs) and isolated compounds on HT1080 mouse melanoma cell model with a focus on matrix metalloproteinase (MMP) activity and TIMP and MAPK pathways. Upregulation and stimulation of MMPs result in elevated degradation of extracellular matrix which is part of several complications such as metastasis, cirrhosis, and arthritis. The anti‐MMP capacity of LTEs was confirmed by their MMP‐inhibitory effects, regulation of MMP and TIMP expression, and suppression of MAPK pathway. Among all tested LTEs, 85% aq. MeOH and n‐BuOH were found to be most active fractions which later yielded two known flavonoid glycosides, myricetin 3‐galactoside and quercetin 3‐o‐beta‐galactopyranoside. Anti‐MMP potential of the compounds was confirmed by their ability to regulate MMP expression through inhibited MAPK pathway activation. These results suggested that L. tetragonum might serve as a potential source of bioactive substances with effective anti‐MMP properties.
Osteopontin Augments M2 Microglia Response and Separates M1- and M2-Polarized Microglial Activation in Permanent Focal Cerebral Ischemia
Authors: Ladwig Anne , Walter Helene Luise , Hucklenbroich Jörg , Willuweit Antje , Langen Karl-Josef , Fink Gereon Rudolph , Rueger Maria Adele , Schroeter Michael
Published: September 2017

Background.Focal cerebral ischemia induces distinct neuroinflammatory processes. We recently reported the extracellular phosphor-glyco-protein osteopontin (OPN) to directly affect primary microgliain vitro, promoting survival while shifting their inflammatory profile towards a more neutral phenotype. We here assessed the effects of OPN on microglia after strokein vivo, with focus on infarct demarcation.Methods.Animals underwent focal photothrombotic stroke and were injected intracerebroventricularly with 500 μg OPN or vehicle. Immunohistochemistry assessed neuronal damage and infarct volume, neovascularisation, glial scar formation, microglial activation, and M1 and M2 polarisation.Results.After photothrombotic stroke, areas covered by M1 and M2 microglia substantially overlapped. OPN treatment reduced that overlap, with microglia appearing more spread out and additionally covering the infarct core. OPN additionally modulated the quantity of microglia subpopulations, reducing iNOS+ M1 cells while increasing M2 microglia, shifting the M1/M2 balance towards an M2 phenotype. Moreover, OPN polarized astrocytes towards the infarct.Conclusion.Microglial activation and M1 and M2 polarization have distinct but overlapping spatial patterns in permanent focal ischemia. Data suggest that OPN is involved in separating M1 and M2 subpopulations, as well as in shifting microglia polarization towards the M2 phenotype modulating beneficially inflammatory responses after focal infarction.
Morinda Officinalis Polysaccharides Stimulate Hypothalamic GnRH Secretion in Varicocele Progression
Authors: Zhu Zhu , Huang Feng , Wang Feng , Zhang Yonghong , Zhao Xiaozhen , Wang Wei
Published: September 2017

Varicoceles (VCs) are the predominant cause of male infertility and are a risk factor for chronic venous disease. Morinda officinalis (M. officinalis) is a traditional Chinese medicine used to tonify the kidney and strengthen yang. In this study, we evaluated the effects of water‐soluble polysaccharides extracted from M. officinalis (MOPs) on gonadotropin‐release hormone (GnRH) secretion in a classic experimental left VC (ELV) rat model. Intragastric administration of MOPs at a dose ranging from 50 mg kg−1 to 100 mg kg−1 facilitated improvements in sperm parameters and seminiferous epithelial structures, modulated serum hormone profiles, and stimulated GnRH synthesis and release in the hypothalamus. MOPs also promoted spinogenesis and functional spine maturation in the arcuate nuclei (Arc), wherein they acted mainly on Kiss1 and GnRH neurons. Moreover, MOP‐mediated Kisspeptin‐GPR54 pathway upregulation and MAPK phosphorylation activation may have been responsible for increases in GnRH synthesis and release. Collectively, the findings of this study indicate that MOPs were effective in stimulating GnRH secretion, possibly by upregulating the Kiss1/GPR54 pathway and enhancing synaptic plasticity, and that MOPs can serve as a therapy for early VCs.
Landslide Monitoring Network Establishment within Unified Datum and Stability Analysis in the Three Gorges Reservoir Area
Authors: Huang Shengxiang , Li Chenfeng , Luo Li
Published: September 2017

A landslide monitoring network construction within unified datum which combined fiducial points, working reference points, and monitoring points was intensively studied in the Three Gorges Reservoir area. With special long and narrow geographical location in the area, designing and building monitoring network was vital to the realization of landslide monitoring. To build such a network with high precision, this paper mainly focused on the following four aspects: (1) method of using multiple GPS reference stations to build a unified datum network and subnet adjustment, (2) GPS data processing algorithm with millimeter level, (3) analysis of influence on the adjustment resulting from systematic error of time evolution datum from different GPS observations, and (4) establishment and stability analysis of unified datum. Then, using global test and trial-and-error method to analyze the datum based on the GPS observations (2008~2011) of landslide monitoring network in the area, we concluded that there were moved reference points during the three years of high water impoundment, and the horizontal displacement of moved reference points was more than 4 cm, even up to 79.4 cm. The displacement direction of unstable reference points was inspected with geographical environment at sites, which revealed congruency between them.
New Advances and Challenges of Targeting Cancer Stem Cells
Authors: Dashzeveg Nurmaa K. , Taftaf Rokana , Ramos Erika K. , Torre-Healy Luke , Chumakova Anastasia , Silver Daniel J. , Alban Tyler J. , Sinyuk Maksim , Thiagarajan Praveena S. , Jarrar Awad M. , Turaga Soumya M. , Saygin Caner , Mulkearns-Hubert Erin , Hitomi Masahiro , Rich Jeremy N. , Gerson Stanton L. , Lathia Justin D. , Liu Huiping
Published: September 2017

The second International Cancer Stem Cell Conference in Cleveland, Ohio, on September 20–23, 2016, convened 330 attendees from academic, industrial, and clinical organizations. It featured a debate on the concepts and challenges of the cancer stem cells (CSC) as well as CSC-centered scientific sessions on clinical trials, genetics and epigenetics, tumor microenvironment, immune suppression, metastasis, therapeutic resistance, and emerging novel concepts. The conference hosted 35 renowned speakers, 100 posters, 20 short talks, and a preconference workshop. The reported advances of CSC research and therapies fostered new collaborations across national and international borders, and inspired the next generation's young scientists. Cancer Res; 77(19); 5222–7. ©2017 AACR.
Roles for Innate Immunity in Combination Immunotherapies
Authors: Moynihan Kelly D. , Irvine Darrell J.
Published: September 2017

Immunity to infectious agents involves a coordinated response of innate and adaptive immune cells working in concert, with many feed-forward and regulatory interactions between both arms of the immune system. In contrast, many therapeutic strategies to augment immunity against tumors have focused predominantly on stimulation of adaptive immunity. However, a growing appreciation of the potential contributions of innate immune effectors to antitumor immunity, especially in the context of combination immunotherapy, is leading to novel strategies to elicit a more integrated immune response against cancer. Here we review antitumor activities of innate immune cells, mechanisms of their synergy with adaptive immune responses against tumors, and discuss recent studies highlighting the potential of combination therapies recruiting both innate and adaptive immune effectors to eradicate established tumors. Cancer Res; 77(19); 5215–21. ©2017 AACR.
High BCR–ABL/GUSIS Levels at Diagnosis of Chronic Phase CML Are Associated with Unfavorable Responses to Standard-Dose Imatinib
Authors: Vigneri Paolo , Stagno Fabio , Stella Stefania , Cupri Alessandra , Forte Stefano , Massimino Michele , Antolino Agostino , Siragusa Sergio , Mannina Donato , Impera Stefana Stella , Musolino Caterina , Malato Alessandra , Mineo Giuseppe , Tomaselli Carmela , Murgano Pamela , Musso Maurizio , Morabito Fortunato , Molica Stefano , Martino Bruno , Manzella Livia , Müller Martin C. , Hochhaus Andreas , Raimondo Francesco Di
Published: September 2017

Purpose: The approval of second-generation tyrosine kinase inhibitors (TKIs) for the first-line treatment of chronic myeloid leukemia (CML) has generated an unmet need for baseline molecular parameters associated with inadequate imatinib responses.

Experimental Design: We correlated BCR–ABL/GUSIS and BCR–ABL/ABL transcripts at diagnosis with the outcome—defined by the 2013 European LeukemiaNet recommendations—of 272 patients newly diagnosed with CML receiving imatinib 400 mg/daily. Applying receiver-operating characteristic curves, we defined BCR–ABL/GUSIS and BCR–ABL/ABL levels associated with lower probabilities of optimal response, failure-free (FFS), event-free (EFS), transformation-free (TFS), and overall survival (OS).

Results: With a median follow-up of 60 months, 65.4% of patients achieved an optimal response (OR), 5.6% were classified as “warnings,” 22.4% failed imatinib, and 6.6% switched to a different TKI because of drug intolerance. We recorded 19 deaths (6.9%), seven (2.5%) attributable to disease progression. We found that higher BCR–ABL/GUSIS levels at diagnosis were associated with inferior rates of OR (P < 0.001), FFS (P < 0.001), and EFS (P < 0.001). Elevated BCR–ABL/GUSIS levels were also associated with lower rates of TFS (P = 0.029) but not with OS (P = 0.132). Similarly, high BCR–ABL/ABL levels at diagnosis were associated with inferior rates of OR (P = 0.03), FFS (P = 0.001), and EFS (P = 0.005), but not with TFS (P = 0.167) or OS (P = 0.052). However, in internal validation experiments, GUS outperformed ABL in samples collected at diagnosis as the latter produced 80% misclassification rates.

Conclusions: Our data suggest that high BCR–ABL transcripts at diagnosis measured using GUS as a reference gene identify patients with CML unlikely to benefit from standard-dose imatinib. Clin Cancer Res; 23(23); 7189–98. ©2017 AACR.
Quantitative and Mechanistic Understanding of AZD1775 Penetration across Human Blood–Brain Barrier in Glioblastoma Patients Using an IVIVE–PBPK Modeling Approach
Authors: Li Jing , Wu Jianmei , Bao Xun , Honea Norissa , Xie Youming , Kim Seongho , Sparreboom Alex , Sanai Nader
Published: September 2017

Purpose: AZD1775, a first-in-class, small-molecule inhibitor of the Wee1 tyrosine kinase, is under evaluation as a potential chemo- and radiosensitizer for treating glioblastoma. This study was to prospectively, quantitatively, and mechanistically investigate the penetration of AZD1775 across the human blood–brain barrier (BBB).

Experimental Design: AZD1775 plasma and tumor pharmacokinetics were evaluated in 20 patients with glioblastoma. The drug metabolism, transcellular passive permeability, and interactions with efflux and uptake transporters were determined using human derived in vitro systems. A whole-body physiologically based pharmacokinetic (PBPK) model integrated with a four-compartment permeability-limited brain model was developed for predicting the kinetics of AZD1775 BBB penetration and assessing the factors modulating this process.

Results: AZD1775 exhibited good tumor penetration in patients with glioblastoma, with the unbound tumor-to-plasma concentration ratio ranging from 1.3 to 24.4 (median, 3.2). It was a substrate for ABCB1, ABCG2, and OATP1A2, but not for OATP2B1 or OAT3. AZD1775 transcellular passive permeability and active efflux clearance across MDCKII–ABCB1 or MDCKII–ABCG2 cell monolayers were dependent on the basolateral pH. The PBPK model well predicted observed drug plasma and tumor concentrations in patients. The extent and rate of drug BBB penetration were influenced by BBB integrity, efflux and uptake active transporter activity, and drug binding to brain tissue.

Conclusions: In the relatively acidic tumor microenvironment where ABCB1/ABCG2 transporter-mediated efflux clearance is reduced, OATP1A2-mediated active uptake becomes dominant, driving AZD1775 penetration into brain tumor. Variations in the brain tumor regional pH, transporter expression/activity, and BBB integrity collectively contribute to the heterogeneity of AZD1775 penetration into brain tumors. Clin Cancer Res; 23(24); 7454–66. ©2017 AACR.

See related commentary by Peer et al., p. 7437
BMP4 Induces M2 Macrophage Polarization and Favors Tumor Progression in Bladder Cancer
Authors: Martínez Víctor G. , Rubio Carolina , Martínez-Fernández Mónica , Segovia Cristina , López-Calderón Fernando , Garín Marina I. , Teijeira Alicia , Munera-Maravilla Ester , Varas Alberto , Sacedón Rosa , Guerrero Félix , Villacampa Felipe , de la Rosa Federico , Castellano Daniel , López-Collazo Eduardo , Paramio Jesús M. , Vicente Ángeles , Dueñas Marta
Published: September 2017

Purpose: Bladder cancer is a current clinical and social problem. At diagnosis, most patients present with nonmuscle-invasive tumors, characterized by a high recurrence rate, which could progress to muscle-invasive disease and metastasis. Bone morphogenetic protein (BMP)–dependent signaling arising from stromal bladder tissue mediates urothelial homeostasis by promoting urothelial cell differentiation. However, the possible role of BMP ligands in bladder cancer is still unclear.

Experimental Design: Tumor and normal tissue from 68 patients with urothelial cancer were prospectively collected and analyzed for expression of BMP and macrophage markers. The mechanism of action was assessed in vitro by experiments with bladder cancer cell lines and peripheral blood monocyte–derived macrophages.

Results: We observed BMP4 expression is associated and favored type II macrophage differentiation. In vitro experiments showed that both recombinant BMP4 and BMP4-containing conditioned media from bladder cancer cell lines favored monocyte/macrophage polarization toward M2 phenotype macrophages, as shown by the expression and secretion of IL10. Using a series of human bladder cancer patient samples, we also observed increased expression of BMP4 in advanced and undifferentiated tumors in close correlation with epithelial–mesenchymal transition (EMT). However, the p-Smad 1,5,8 staining in tumors showing EMT signs was reduced, due to the increased miR-21 expression leading to reduced BMPR2 expression.

Conclusions: These findings suggest that BMP4 secretion by bladder cancer cells provides the M2 signal necessary for a protumoral immune environment. In addition, the repression of BMPR2 by miR-21 makes the tumor cells refractory to the prodifferentiating actions mediated by BMP ligands, favoring tumor growth. Clin Cancer Res; 23(23); 7388–99. ©2017 AACR.
Dementia-Predicting Cognitive Risk Score and Its Correlation with Cortical Thickness in Parkinson Disease
Authors: Ye Byoung Seok , Jeon Seun , Ham Jee Hyun , Lee Jae Jung , Lee Jong Min , Lee Hye Sun , Lee Phil Hyu , Sohn Young H.
Published: September 2017

Background: We developed a risk score system to predict risks of developing dementia in individual Parkinson disease (PD) patients using baseline neuropsychological tests. Methods: A total of 216 nondemented PD patients underwent a baseline neuropsychological evaluation and were followed up for a mean of 2.7 (±1.1) years. Univariate Cox regression models controlled for age, gender, and education selected neuropsychological tests individually predicting dementia risk. Then, a multivariate Cox regression model combined them into a cognitive risk score system. Cortical areas correlating with cognitive risk score were investigated using a separate MRI data set from 207 nondemented PD patients. Results: Fifty-two patients (23.9%) developed dementia. The univariate Cox regression analyses identified the confrontational naming and semantic fluency tests, frontal/executive function tests, immediate verbal memory test, and visuospatial function test as predicting dementia risk. The calculated cognitive risk score (range 53-188) predicted future dementia with moderate accuracy (integrated area under the curve = 0.79; 95% CI: 0.73-0.85). A higher cognitive risk score correlated with cortical thinning in the right anteromedial temporal cortex, bilateral posterior cingulate cortex, right anterior cingulate cortex, left parahippocampal gyrus, and right superior frontal cortex in a separate MRI data set. Conclusion: The cognitive risk score system is a useful approach to predict the dementia risk among PD patients.
Treatment of Leptomeningeal Metastases in a Patient with Non-Small Cell Lung Cancer Harboring EGFR T790M Mutation
Authors: Niu Hardy , Zhou Junle , Maan Harvinder , Markman Maurie , Niu Jiaxin
Published: September 2017

Background: Leptomeningeal metastasis (LM) is an uncommon complication in patients with solid tumors, associated with poor survival. However, LM appears to be more frequent in lung cancer patients with EGFR mutations, posing a unique clinical challenge to treating physicians. Case Presentation: We report the case of a 68-year-old Asian man with metastatic lung adenocarcinoma harboring an EGFR L858R mutation, which was initially treated with gefitinib. He developed disease progression 1 year later. Re-biopsy of the right lower lobe primary lesion revealed only an EGFR L858R mutation in the absence of a T790M mutation. The patient also experienced persistent confusion and generalized fatigue, and magnetic resonance imaging (MRI) of the brain demonstrated extensive LM. At this time, a liquid biopsy revealed an EGFR T790M mutation. Following initiation of treatment with osimertinib, the patient exhibited a rapid response with MRI of the brain showing substantial improvement of the LM after 6 months. Unfortunately, the LM recurred after 1 year at which time the patient declined further systemic chemotherapy. Conclusion: To our knowledge, this is the second reported case of LM in a patient with lung cancer harboring an EGFR T790M mutation that was successfully treated with osimertinib.
Simvastatin, a Novel Stimulator of Eryptosis, the Suicidal Erythrocyte Death
Authors: Al Mamun Bhuyan Abdulla Al Mamun , Nüßle Sigrid , Cao Hang , Zhang Shaqiu , Lang Florian
Published: September 2017

Background/Aims: The 3-hydroxy-3-methyl-glutaryl-Coenzyme A (HMG-CoA) reductase inhibitor simvastatin has been shown to trigger apoptosis of several cell types. The substance has thus been proposed as an additional treatment of malignancy. Similar to apoptosis of nucleated cells, erythrocytes may enter eryptosis, the suicidal erythrocyte death. Hallmarks of eryptosis include cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the extracellular face of the erythrocyte cell membrane. Signaling contributing to stimulation of eryptosis include increase of cytosolic Ca2+ activity ([Ca2+]i), induction of oxidative stress, increase of ceramide abundance, and activation of SB203580-sensitive p38 kinase. The present study explored, whether simvastatin induces eryptosis and aimed to shed light on cellular mechanisms involved. Methods: Flow cytometry was employed to quantify phosphatidylserine exposure at the cell surface from annexin-V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, reactive oxygen species (ROS) abundance from DCFDA dependent fluorescence, and ceramide abundance utilizing specific antibodies. Hemolysis was estimated from hemoglobin concentration in the supernatant. Results: A 48 h exposure of human erythrocytes to simvastatin (1 µg/ml) significantly decreased the forward scatter, significantly augmented the percentage of annexin-V-binding cells, significantly increased Fluo3-fluorescence, and significantly enhanced DCFDA fluorescence. Simvastatin tended to increase ceramide abundance, an effect, however, escaping statistical significance. The effect of simvastatin on annexin-V-binding was significantly blunted by removal of extracellular Ca2+ and by addition of SB203580 (2 µM). Conclusions: Simvastatin stimulates eryptosis, an effect at least in part due to Ca2+ entry, oxidative stress, and p38 kinase.
Vascular Access Placement Order and Outcomes in Hemodialysis Patients: A Longitudinal Study
Authors: Murea Mariana , Brown W. Mark , Divers Jasmin , Moossavi Shahriar , Robinson Todd W. , Bagwell Benjamin , Burkart John M. , Freedman Barry I.
Published: September 2017

Background: Arteriovenous accesses (AVA) in patients performing hemodialysis (HD) are labeled “permanent” for AV fistulas (AVF) or grafts (AVG) and “temporary” for tunneled central venous catheters (TCVC). Durability and outcomes of permanent vascular accesses based on the sequence in which they were placed or used receives little attention. This study analyzed longitudinal transitions between TCVC-based and AVA-based HD outcomes according to the order of placement. Methods: All 391 patients initiating chronic HD via a TCVC between 2012 and 2013 at 12 outpatient academic dialysis units were included in this study. Chronological distributions of HD vascular accesses were recorded over a mean (SD) of 2.8 (0.9) years and sequentially grouped into periods for TCVC-delivered and AVA-delivered (AVF or AVG) HD. Primary AVA failure and cumulative access survival were evaluated based on access placement sequence and type, adjusting for age. Results: In total, 92.3% (361/391) of patients underwent 497 AVA placement surgeries. Analyzing the initial 3 surgeries, primary AVF failure rates increased with each successive fistula placement (p = 0.008). Among the 82.9% (324/391) of TCVC patients successfully converted to an AVA, 30.9% returned to a TCVC, followed by a 58.0% conversion rate to another AVA. Annual per-patient vascular access transition rates were 2.02 (0.09) HD periods using a TCVC and 0.54 (0.03) HD periods using an AVA. Comparing the first AVA used with the second, cumulative access survivals were 701.0 (370.0) vs. 426.5 (275.0) days, respectively. Excluding those never converting to an AVF or AVG, 169 (52.2%) subsequently converted from a TCVC to a permanent access and received HD via AVA for ≥80% of treatments. Conclusions: HD vascular access outcomes differ based on the sequence of placement. In spite of frequent AVA placements, only half of patients effectively achieved a “permanent” vascular access and used an AVA for the majority of HD treatments.
PDK4 Inhibits Cardiac Pyruvate Oxidation in Late Pregnancy
Authors: Liu Laura X. , Rowe Glenn C. , Yang Steven , Li Jian , Damilano Federico , Chan Mun Chun , Lu Wenyun , Jang Cholsoon , Wada Shogo , Morley Michael , Hesse Michael , Fleischmann Bernd K. , Rabinowitz Joshua D. , Das Saumya , Rosenzweig Anthony , Arany Zoltan
Published: September 2017

Rationale:

Pregnancy profoundly alters maternal physiology. The heart hypertrophies during pregnancy, but its metabolic adaptations, are not well understood.

Objective:

To determine the mechanisms underlying cardiac substrate use during pregnancy.

Methods and Results:

We use here
13
C glucose,
13
C lactate, and
13
C fatty acid tracing analyses to show that hearts in late pregnant mice increase fatty acid uptake and oxidation into the tricarboxylic acid cycle, while reducing glucose and lactate oxidation. Mitochondrial quantity, morphology, and function do not seem altered. Insulin signaling seems intact, and the abundance and localization of the major fatty acid and glucose transporters, CD36 (cluster of differentiation 36) and GLUT4 (glucose transporter type 4), are also unchanged. Rather, we find that the pregnancy hormone progesterone induces PDK4 (pyruvate dehydrogenase kinase 4) in cardiomyocytes and that elevated PDK4 levels in late pregnancy lead to inhibition of PDH (pyruvate dehydrogenase) and pyruvate flux into the tricarboxylic acid cycle. Blocking PDK4 reverses the metabolic changes seen in hearts in late pregnancy.

Conclusions:

Taken together, these data indicate that the hormonal environment of late pregnancy promotes metabolic remodeling in the heart at the level of PDH, rather than at the level of insulin signaling.
Alteration of Cholinergic Anti‐Inflammatory Pathway in Rat With Ischemic Cardiomyopathy–Modified Electrophysiological Function of Heart
Authors: Wu Shu‐Jie , Li Yue‐Chun , Shi Zhe‐Wei , Lin Zhong‐Hao , Rao Zhi‐Heng , Tai Si‐Chao , Chu Mao‐Ping , Li Lei , Lin Jia‐Feng
Published: September 2017

Background

With chronic ischemia after myocardial infarction, the resulting scar tissue result in electrical and structural remodeling vulnerable to an arrhythmogenic substrate. The cholinergic anti‐inflammatory pathway elicited by vagal nerve via α7 nicotinic acetylcholine receptors (α7‐n
AC
hR) can modulate local and systemic inflammatory responses. Here, we aimed to clarify a novel mechanism for the antiarrhythmogenic properties of vagal nerve during the ischemic cardiomyopathy (
ICM
).

Methods and Results

Left anterior descending artery of adult male Sprague‐Dawley rats was ligated for 4 weeks to develop
ICM
. Western blot revealed that eliciting the cholinergic anti‐inflammatory pathway by nicotine treatment showed a significant reduction in the amounts of collagens, cytokines, and other inflammatory mediators in the left ventricular infarcted border zone via inhibited
NF
‐
κB
activation, whereas it increased the phosphorylated connexin 43. Vagotomy inhibited the anti‐inflammatory, anti‐fibrosis, and anti‐arrhythmogenic effect of nicotine administration. And immunohistochemistry confirmed that the nicotine administration‐induced increase of connexin 43 was located in intercellular junctions. Furthermore nicotine treatment suppressed
NF
‐κB activation in lipopolysaccharide‐stimulated
RAW
264.7 cells, and α‐bungarotoxin (an α7‐n
AC
hR selective antagonist) partly inhibited the nicotine‐treatment effect. In addition, 4‐week nicotine administration slightly improved the cardiac function, increased cardiac parasympathetic tone, decreased the prolonged
QT
c, and decreased the arrhythmia score of programmed electric stimulation‐induced ventricular arrhythmia.

Conclusions

Eliciting the cholinergic anti‐inflammatory pathway exerts anti‐arrhythmogenic effects against
ICM
‐induced ventricular arrhythmia accompanied by downregulation of cytokines, downgenerating of collagens, decrease in sympathetic/parasympathetic ratio, and prevention of the loss of phosphorylated connexin 43 during
ICM
. Our findings may suggest a promising therapy for the generation of
ICM
‐induced ventricular arrhythmia by eliciting the cholinergic anti‐inflammatory pathway.
From Sidi to Ene
Authors: Adeleke E.B.
Published: September 2017

To say that African women have come a long way is to state the obvious. In economic, spiritual, political, and educational terms, African women have made significant contributions to Africa’s development. In literature generally, but especially in drama, the phases of the African woman are easily traceable. The maxim used to be ‘the place of a woman is in the kitchen’ or ‘women are to be seen and not heard’. Accordingly, African women were depicted in early modern African plays as docile, submissive, cooperative, and obedient. However, contemporary African drama shows that African women can no longer be tagged in this way. Therefore, in this essay, exploring various shades of feminism, we trace the evolutionary phases of African women from Wole Soyinka’s Sidi in The Lion and the Jewel to Tracy Utoh-Ezeajugh’s Ene in Our Wives Have Gone Mad Again, to show that African women have developed from the docile to the rebellious and even ruthless. We shall draw our illustrations from plays across Africa.
The Poet as Town-Crier
Authors: Bello Idaevbor
Published: September 2017

This essay proceeds from the consideration of literature as a medium of disseminating information to society at large, and argues that poetry, being a branch of literature, lends its resources and compact form to this function of information dissemination. It goes further to argue that Niyi Osundare in Village Voices, like the town-crier in our traditional societies, clearly brings to the attention of the leaders and the led important developments within society. However, he does not stop at informing society of those developments, especially the negative conduct of its leaders, but goes further to warn the latter of the consequences of persisting in their negative ways, and, addressing the mass of the people, calls for the necessary action that would extricate and free them from their bad leaders.
The Triple Play of Violence in Ismael R. Mbise’s Blood on Our Land
Authors: Mustafa Fawzia
Published: September 2017

Ismael R. Mbise’s novel Blood on Our Land (1974) re-creates the events known as the Meru Land Case, when in 1951 a group of Wameru from northern Tanganyika petitioned the UN to prevent the British authorities from evicting them from their land. The petition drew international attention to the area for a fleeting moment and, though unsuccessful, it has since entered the national imaginary as an original gesture of peaceful resistance to colonial control. Mbise’s re-creation has also been read as a critical allegory of the implementation of villagization associated with the policies of Ujamaa. The novel does this and more in its brilliant comparative analysis of the vectors of violence within the politics of language, history, and representation, the practices of Indirect Rule and its force of law, and development and its mechanics of ‘modernization’: a triple play.
And then there were six: a revision of the genus Phanolinopsis Scheerpeltz (Coleoptera: Staphylinidae: Staphylininae)
Authors: CHATZIMANOLIS STYLIANOS
Published: September 2017

The previously monotypic genus Phanolinopsis Scheerpeltz is revised and four species are described as new: Phanolinopsis erythros sp. n. from Guatemala and Panama, Phanolinopsis goniakos sp. n. from Costa Rica, Phanolinopsis metaksenios sp. n. from Costa Rica and Panama, and Phanolinopsis norahae sp. n. from Colombia and Ecuador. Torobus fassli (Bernhauer) is transferred to Phanolinopsis as Phanolinopsis fassli comb. n. Detailed morphological illustrations and a key is provided for the identification of the species.
A re-description of Longicyatholaimus maldivarum Gerlach, 1964 (Nematoda, Cyatholamidae) with an emended identification key of the genus
Authors: SEMPRUCCI FEDERICA , BURATTINI SABRINA , FALCIERI ELISABETTA , BALSAMO MARIA
Published: September 2017

Longicyatholaimus maldivarum was a species erected by Gerlach in 1964 from specimens found in the Maldivian archipelago. Due to the finding of additional representatives of this species, L. maldivarum is re-described with the addition of new morphological details mainly about males, because the information about female in the original description are very scarce. The newly found specimens showed a total body length higher than in the type specimens (1936–2063 µm vs. 1330 µm long) as well as the ratio of the total body length divided by maximum body diameter (22–28 vs. 27). The multispiral amphideal fovea showed 5 turns vs. 4 turns and Gerlach did not notice the presence of sub-ventral teeth that were clearly observed in the present specimens. The copulatory apparatus that perfectly matched the Gerlach description showed a central lamella mainly visible under confocal microscopy. A slightly lower ratio of the spicule length divided by anal body diameter (1 vs. 1.4) and longer gubernaculum (25–32 vs. 25 µm long) were noticed as well. Pre-cloacal supplements appeared very interesting for the presence of stout and conical setae protruding from cup-shaped structures. Supplements were more than in type species (8–9 vs. 7). Also the tail revealed some differences with a lower ratio of its total length divided by anal body diameter 6 vs. 7–8. The current list of 15 valid species of the genus was reduced to 10 species. In detail, we considered Longicyatholaimus heterurus and Longicyatholaimus sp. 3 species inquirendae for the absence of male specimens in the original description. We also excluded L. filicaudatus and L. tenuicaudatus because they were considered species inquirendae by Wieser & Hopper (1967) and L. zosterae because it was transferred by Lorenzen (1972) to the genus Paralongicyatholaimus. The new morphological details observed for Longicyatholaimus maldivarum and the modified number of valid species of the genus required also a revision of the identification key.
A new species of the endemic South African spider genus Austrachelas (Araneae: Gallieniellidae) and first description of the male of A. bergi
Authors: HADDAD CHARLES R. , MBO ZINGISILE
Published: September 2017

The Gallieniellidae is a small family of ground-dwelling gnaphosoid spiders with a Gondwanan distribution, currently including 10 genera and 55 species (World Spider Catalog 2017). The composition of the group remains unresolved, as different phylogenies have either supported (Platnick 2002; Haddad et al. 2009) or disputed (Ramírez 2014; Wheeler et al. in press) its monophyly.
Status Spillovers: The Effect of Status-conferring Prizes on the Allocation of Attention
Authors: Reschke Brian P. , Azoulay Pierre , Stuart Toby E.
Published: September 2017

We investigate the effect of a status-enhancing prize on the attention that a recipient’s “neighbors” subsequently receive. Do neighbors—individuals who work in economic, intellectual, or artistic domains that are proximate to prize winners—bask in the reflected glory of the ascendant actor and therefore gain as well? Or does competition for attention ensue, attenuating the recognition neighbors would otherwise have garnered? We study the spillover effects of status shocks using life sciences research articles published from 1984 through 2003. Exploiting expert-assigned article keywords, we identify papers that are topically related to publications of future appointees to the prestigious Howard Hughes Medical Institute (HHMI). In difference-in-difference specifications, we find that these scientific neighbor articles experience substantial declines in citation rates after HHMI appointments are announced. That is, neighboring articles attract less attention when authors of papers near them receive a prestigious prize. This pattern reflects more than the trivial transfer of attention from non-winners to winners: once prizes are announced, actors cede scientific territory to prize winners and pursue other opportunities. These negative spillover effects are moderated or even reversed by scientists’ social connections and by the novelty and stature of scientific domains.
The Identity of University Social Responsibility on the Websites of the Universities of the Autonomous Region of Madrid (Spain) and the State of Puebla (Mexico), As a Tool of Grassroots Public Diplomacy
Authors: Arceo Alfredo
Published: September 2017

The identity of the universities is one more piece to consider inside the puzzle of the grassroots public diplomacy. University social responsibility is not well exploited on university websites. This is the main conclusion we have reached following a comparative study of the websites of the universities of the Autonomous Region of Madrid (Spain) and those of the universities of the State of Puebla, including public, private, and Catholic Church institutions. All the universities of the Madrid region and 92.5% of those consulted in the State of Puebla have a website, but none of them gives an explicit reference on its homepage that operations are performed within all occupational aspects in accordance with the realm of university social responsibility. It would therefore be fair to say that there is no evidence of optimal exploitation of university social responsibility on the websites. When this must be considered as one element that it is necessary to include in the communicative frame of reference to obtain mutual understanding, stable, and beneficial relations for all the parts.
A Review of Calibration Transfer Practices and Instrument Differences in Spectroscopy
Authors: Workman Jerome J.
Published: September 2017

Calibration transfer for use with spectroscopic instruments, particularly for near-infrared, infrared, and Raman analysis, has been the subject of multiple articles, research papers, book chapters, and technical reviews. There has been a myriad of approaches published and claims made for resolving the problems associated with transferring calibrations; however, the capability of attaining identical results over time from two or more instruments using an identical calibration still eludes technologists. Calibration transfer, in a precise definition, refers to a series of analytical approaches or chemometric techniques used to attempt to apply a single spectral database, and the calibration model developed using that database, for two or more instruments, with statistically retained accuracy and precision. Ideally, one would develop a single calibration for any particular application, and move it indiscriminately across instruments and achieve identical analysis or prediction results. There are many technical aspects involved in such precision calibration transfer, related to the measuring instrument reproducibility and repeatability, the reference chemical values used for the calibration, the multivariate mathematics used for calibration, and sample presentation repeatability and reproducibility. Ideally, a multivariate model developed on a single instrument would provide a statistically identical analysis when used on other instruments following transfer. This paper reviews common calibration transfer techniques, mostly related to instrument differences, and the mathematics of the uncertainty between instruments when making spectroscopic measurements of identical samples. It does not specifically address calibration maintenance or reference laboratory differences.