bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neutrophil-lymphocyte Ratio Plus Prognostic Nutritional Index Predicts the Outcomes of Patients with Unresectable Hepatocellular Carcinoma After Transarterial Chemoembolization
Authors: Liu Chang , Li Lei , Lu Wu-sheng , Du Hua , Yan Lu-nan , Yang Jia-yin , Wen Tian-fu , Zeng Guo-jun , Jiang Li , Yang Jian 
Published: October 2017

AbstractFor many malignancies, inflammation-based scores correlate with survival. The neutrophil-to-lymphocyte ratio (NLR) and prognostic nutritional index (PNI) are immunonutritional indices associated with postoperative outcomes in patients with hepatocellular carcinoma (HCC). We evaluated whether a combined preoperative NLR and PNI score was prognostically superior to either index alone in 793 patients with unresectable HCC after transarterial chemoembolization. Patient demographic, clinical, and pathological data were also collected and analysed. A receiver-operating characteristic (ROC) analysis was used to classify patients as follows: NLR-PNI 0 group (NLR ≤ 2.2 and PNI > 46), NLR-PNI 1 group (NLR > 2.2 or PNI ≤ 46) and NLR-PNI 2 group (NLR > 2.2 and PNI ≤ 46). Regarding 1-, 3-, and 5-year survival, the NLR-PNI score had superior discriminative abilities (i.e., higher area under the ROC curve), compared with either the NLR or PNI alone, and patients in the NLR-PNI 0, 1, and 2 groups had median survival times of 33 (95% confidence interval: 22.8–43.2), 14 (10.9–17.1), and 6 (9.9–14.1) months, respectively. In multivariate analyses, the Barcelona Clinic Liver Cancer, total bilirubin, vascular invasion, and NLR-PNI score adversely affected overall survival. In conclusion, the NLR-PNI score can improve the accuracy of prognoses for patients with unresectable HCC.
The liquid-glass-jamming transition in disordered ionic nanoemulsions
Authors: Braibanti Marco , Kim Ha Seong , Şenbil Nesrin , Pagenkopp Matthew J. , Mason Thomas G. , Scheffold Frank 
Published: October 2017

AbstractIn quenched disordered out-of-equilibrium many-body colloidal systems, there are important distinctions between the glass transition, which is related to the onset of nonergodicity and loss of low-frequency relaxations caused by crowding, and the jamming transition, which is related to the dramatic increase in elasticity of the system caused by the deformation of constituent objects. For softer repulsive interaction potentials, these two transitions become increasingly smeared together, so measuring a clear distinction between where the glass ends and where jamming begins becomes very difficult or even impossible. Here, we investigate droplet dynamics in concentrated silicone oil-in-water nanoemulsions using light scattering. For zero or low NaCl electrolyte concentrations, interfacial repulsions are soft and longer in range, this transition sets in at lower concentrations, and the glass and the jamming regimes are smeared. However, at higher electrolyte concentrations the interactions are stiffer, and the characteristics of the glass-jamming transition resemble more closely the situation of disordered elastic spheres having sharp interfaces, so the glass and jamming regimes can be distinguished more clearly.
Therapeutic potential of the phosphino Cu(I) complex (HydroCuP) in the treatment of solid tumors
Authors: Gandin Valentina , Ceresa Cecilia , Esposito Giovanni , Indraccolo Stefano , Porchia Marina , Tisato Francesco , Santini Carlo , Pellei Maura , Marzano Cristina 
Published: October 2017

Abstract[Cu(thp)4][PF6] (HydroCuP) is a phosphino copper(I) complex highly soluble and stable in physiological media that has been developed as a possible viable alternative to platinum-based drugs for anticancer therapy. HydroCuP potently inhibited the growth of human cancer cells derived from solid tumors by inducing endoplasmatic reticulum (ER) stress thus leading to cell death through paraptosis with a preferential efficacy against cancer rather than non-cancer cells. Aim of the present study was to assess the therapeutic potential of HydroCuPin vivo, in syngenic and xenograft murine models of solid tumors by triggering the Unfolded Protein Response (UPR) pathway. With respect to platinum drugs, HydroCuP induced a markedly higher reduction of tumor growth associated with minimal animal toxicity. In human colorectal cancer xenografts, chemotherapy with HydroCuP was extremely effective in both oxaliplatin-sensitive and resistant models. The favorablein vivotolerability of HydroCuP was also correlated to an encouraging biodistribution profile. Additionally, no signs of drug-related neurotoxicity and nephrotoxicity were observed. Altogether, these results demonstrate that HydroCuP appears worth of further investigation to evaluate its therapeutic activity towards a broad spectrum of solid malignancies.
Towards an understanding of spiral patterning in the Sargassum muticum shoot apex
Authors: Linardić Marina , Braybrook Siobhan A. 
Published: October 2017

AbstractIn plants and parenchymatous brown algae the body arises through the activity of an apical meristem (a niche of cells or a single cell). The meristem produces lateral organs in specific patterns, referred to as phyllotaxis. In plants, two different control mechanisms have been proposed: one is position-dependent and relies on morphogen accumulation at future organ sites; the other is a lineage-based system which links phyllotaxis to the apical cell division pattern. Here we examine the apical patterning of the brown alga, Sargassum muticum, which exhibits spiral phyllotaxis (137.5° angle) and an unlinked apical cell division pattern. The Sargassum apex presents characteristics of a self-organising system, similar to plant meristems. In contrast to complex plant meristems, we were unable to correlate the plant morphogen auxin with bud positioning in Sargassum, nor could we predict cell wall softening at new bud sites. Our data suggests that in Sargassum muticum there is no connection between phyllotaxis and the apical cell division pattern indicating a position-dependent patterning mechanism may be in place. The underlying mechanisms behind the phyllotactic patterning appear to be distinct from those seen in plants.
Cytoplasmic cyclin D1 controls the migration and invasiveness of mantle lymphoma cells
Authors: Body Simon , Esteve-Arenys Anna , Miloudi Hadjer , Recasens-Zorzo Clara , Tchakarska Guergana , Moros Alexandra , Bustany Sophie , Vidal-Crespo Anna , Rodriguez Vanina , Lavigne Régis , Com Emmanuelle , Casanova Isolda , Mangues Ramón , Weigert Oliver , Sanjuan-Pla Alejandra , Menéndez Pablo , Marcq Bénédicte , Picquenot Jean-Michel , Pérez-Galán Patricia , Jardin Fabrice , Roué Gaël , Sola Brigitte 
Published: October 2017

AbstractMantle cell lymphoma (MCL) is a hematologic neoplasm characterised by the t(11;14)(q13;q32) translocation leading to aberrant cyclin D1 expression. The cell functions of cyclin D1 depend on its partners and/or subcellular distribution, resulting in different oncogenic properties. We observed the accumulation of cyclin D1 in the cytoplasm of a subset of MCL cell lines and primary cells. In primary cells, this cytoplasmic distribution was correlated with a more frequent blastoid phenotype. We performed immunoprecipitation assays and mass spectrometry on enriched cytosolic fractions from two cell lines. The cyclin D1 interactome was found to include several factors involved in adhesion, migration and invasion. We found that the accumulation of cyclin D1 in the cytoplasm was associated with higher levels of migration and invasiveness. We also showed that MCL cells with high cytoplasmic levels of cyclin D1 engrafted more rapidly into the bone marrow, spleen, and brain in immunodeficient mice. Both migration and invasion processes, both in vivo and in vitro, were counteracted by the exportin 1 inhibitor KPT-330, which retains cyclin D1 in the nucleus. Our data reveal a role of cytoplasmic cyclin D1 in the control of MCL cell migration and invasion, and as a true operator of MCL pathogenesis.
Obstetric outcomes in pregnant women with and without depression: population-based comparison
Authors: Huang Hui-Chun , Sung Fung-Chang , Chen Pei-Chun , Chang Cherry Yin-Yi , Muo Chih-Hsin , Shiue Huei-Sheng , Huang Jian-Pei , Li Tsai-Chung , Tzeng Ya-Ling , Wu Shu-I 
Published: October 2017

AbstractThis study used insurance claims data to evaluate obstetric outcomes in pregnant women with and without depression because population study for Asian women on the issue is limited. We identified 5,064 women with depression at pregnancy in 2005–2013, and 20,024 pregnant women without depression, frequency matched by age, pregnant year and parity. Obstetric events during pregnancy and deliveries were evaluated. The depression group had more events than comparisons for hyperemesis (39.3 vs. 35.5%), abortion (3.3 vs. 2.6%), malpresentation (12.3 vs. 10.3%), C-section (40.2 vs. 34.6%) and intrauterine fetal demise (0.7 vs. 0.4%); risks of these events were significant for childbearing depressed women, not for the 35+ years subgroup. These incidences were higher in depressed women taking antidepressant than those without the medication, but were significant in childbearing depressed subgroup for hyperemesis and C-section with odds ratios of 1.18 (95% confidence intervals (CI), 1.02–1.36) and 1.29 (95% CI, 1.11–1.49), respectively. Incident preterm and low birth weight births were also higher in the depression group than in comparisons, but weren’t significant. In conclusion, women with depression during pregnancy may develop more adverse events than comparisons and are more likely to have a C-section delivery.
ALK and IGF-1R as independent targets in crizotinib resistant lung cancer
Authors: Wilson Christabel , Nimick Mhairi , Nehoff Hayley , Ashton John C. 
Published: October 2017

AbstractALK positive non-small cell lung cancer is highly responsive to ALK inhibitors such as crizotinib, but drug resistance typically develops within a year of treatment. In this study we investigated whether IGF-1R is an independent druggable target in ALK-positive lung cancer cells. We confirmed that combination ALK and IGF-1R inhibitor treatment is synergistically cytotoxic to ALK-positive lung cancer cells and that this remains the case for at least 12 days after initial exposure to crizotinib. ALK-positive cells with acquired resistance to crizotinib did not acquire cross-resistance to IGF-1R inhibition, though combination treatment in the resistant cells gave additive rather than synergistic cytotoxicity. We concluded that IGF-1R is an independent druggable target in ALK-positive lung cancer and support the trial of combination treatment.
Specific neurophysiological mechanisms underlie cognitive inflexibility in inflammatory bowel disease
Authors: Petruo Vanessa A , Zeißig Sebastian , Schmelz Renate , Hampe Jochen , Beste Christian 
Published: October 2017

AbstractInflammatory bowel disease (IBD) is highly prevalent. While the pathophysiological mechanisms of IBD are increasingly understood, there is a lack of knowledge concerning cognitive dysfunctions in IBD. This is all the more the case concerning the underlying neurophysiological mechanisms. In the current study we focus on possible dysfunctions of cognitive flexibility (task switching) processes in IBD patients using a system neurophysiological approach combining event-related potential (ERP) recordings with source localization analyses. We show that there are task switching deficits (i.e. increased switch costs) in IBD patients. The neurophysiological data show that even though the pathophysiology of IBD is diverse and wide-spread, only specific cognitive subprocesses are altered: There was a selective dysfunction at the response selection level (N2 ERP) associated with functional alterations in the anterior cingulate cortex and the right inferior frontal gyrus. Attentional selection processes (N1 ERP), perceptual categorization processes (P1 ERP), or mechanisms related to the flexible implementation of task sets and related working memory processes (P3 ERP) do not contribute to cognitive inflexibility in IBD patients and were unchanged. It seems that pathophysiological processes in IBD strongly compromise cognitive-neurophysiological subprocesses related to fronto-striatal networks. These circuits may become overstrained in IBD when cognitive flexibility is required.
4-Hydroxybenzaldehyde accelerates acute wound healing through activation of focal adhesion signalling in keratinocytes
Authors: Kang Chan Woo , Han Ye Eon , Kim Jean , Oh Joo Heon , Cho Yoon Hee , Lee Eun Jig 
Published: October 2017

Abstract4-Hydroxybenzaldehyde (4-HBA) is a naturally occurring benzaldehyde and the major active constituent of Gastrodia elata. While recent studies have demonstrated metabolic effects of 4-HBA, little is known about the physiological role of 4-HBA in acute wound healing. Here, we investigated the effects and mechanisms of 4-HBA on acute wound healing. Using an in vitro approach, we found that 4-HBA significantly promoted keratinocyte cell migration and invasion by increasing focal adhesion kinase and Src activity. In addition, 4-HBA treatment also promoted wound healing and re-epithelialization in an in vivo excision wound animal model. Combination treatment with 4-HBA and platelet-derived growth factor subunit B homodimer showed synergistic effects in promoting wound healing. Taken together, our results demonstrated that treatment with 4-HBA promoted keratinocyte migration and wound healing in mouse skin through the Src/mitogen-activated protein kinase pathway. Therefore, 4-HBA could be a candidate therapeutic agent with the potential to promote acute wound healing.
Genomic predictive model for recurrence and metastasis development in head and neck squamous cell carcinoma patients
Authors: Ribeiro Ilda Patrícia , Caramelo Francisco , Esteves Luísa , Menoita Joana , Marques Francisco , Barroso Leonor , Miguéis Jorge , Melo Joana Barbosa , Carreira Isabel Marques 
Published: October 2017

AbstractThe head and neck squamous cell carcinoma (HNSCC) population consists mainly of high-risk for recurrence and locally advanced stage patients. Increased knowledge of the HNSCC genomic profile can improve early diagnosis and treatment outcomes. The development of models to identify consistent genomic patterns that distinguish HNSCC patients that will recur and/or develop metastasis after treatment is of utmost importance to decrease mortality and improve survival rates. In this study, we used array comparative genomic hybridization data from HNSCC patients to implement a robust model to predict HNSCC recurrence/metastasis. This predictive model showed a good accuracy (>80%) and was validated in an independent population from TCGA data portal. This predictive genomic model comprises chromosomal regions from 5p, 6p, 8p, 9p, 11q, 12q, 15q and 17p, where several upstream and downstream members of signaling pathways that lead to an increase in cell proliferation and invasion are mapped. The introduction of genomic predictive models in clinical practice might contribute to a more individualized clinical management of the HNSCC patients, reducing recurrences and improving patients’ quality of life. The power of this genomic model to predict the recurrence and metastases development should be evaluated in other HNSCC populations.
Disulfide cross-linked multimers of TDP-43 and spinal motoneuron loss in a TDP-43A315T ALS/FTD mouse model
Authors: Bargsted Leslie , Medinas Danilo B. , Martínez Traub Francisca , Rozas Pablo , Muñoz Natalia , Nassif Melissa , Jerez Carolina , Catenaccio Alejandra , Court Felipe A. , Hetz Claudio , Matus Soledad 
Published: October 2017

AbstractTar DNA binding protein 43 (TDP-43) is the principal component of ubiquitinated protein inclusions present in nervous tissue of most cases of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Previous studies described a TDP-43A315T transgenic mouse model that develops progressive motor dysfunction in the absence of protein aggregation or significant motoneuron loss, questioning its validity to study ALS. Here we have further characterized the course of the disease in TDP-43A315T mice using a battery of tests and biochemical approaches. We confirmed that TDP-43 mutant mice develop impaired motor performance, accompanied by progressive body weight loss. Significant differences were observed in life span between genders, where females survived longer than males. Histopathological analysis of the spinal cord demonstrated a significant motoneurons loss, accompanied by axonal degeneration, astrogliosis and microglial activation. Importantly, histopathological alterations observed in TDP-43 mutant mice were similar to some characteristic changes observed in mutant SOD1 mice. Unexpectedly, we identified the presence of different species of disulfide-dependent TDP-43 aggregates in cortex and spinal cord tissue. Overall, this study indicates that TDP-43A315T transgenic mice develop key features resembling key aspects of ALS, highlighting its relevance to study disease pathogenesis.
Interaction Between the Trace Amine-Associated Receptor 1 and the Dopamine D2 Receptor Controls Cocaine’s Neurochemical Actions
Authors: Asif-Malik Aman , Hoener Marius C. , Canales Juan J. 
Published: October 2017

AbstractRecent evidence suggests that the trace amine-associated receptor 1 (TAAR1) plays a pivotal role in the regulation of dopamine (DA) transmission and cocaine’s actions. However, the underlying mechanisms through which TAAR1 activation mediates these effects have not yet been elucidated. Here, we used fast-scan cyclic voltammetry to measure DA dynamics and explore such mechanisms. We show, first, that the full TAAR1 agonist, RO5256390, dose-dependently blocked cocaine-induced inhibition of DA clearance in slices of the nucleus accumbens. Second, subthreshold inhibition of PKA or PKC phosphorylation did not prevent TAAR1 suppression of cocaine effects whereas subeffective doses of the DA D2 receptor antagonist, L-741,626, rescued cocaine’s ability to produce changes in DA uptake in the presence of full TAAR1 activation, thus indicating that TAAR1 modulation of cocaine effects requires simultaneous DA D2 receptor activation. Predictably, inhibition of glycogen synthase kinase-3 (GSK-3), which results from activation of D2/TAAR1 heterodimers, fully reproduced the inhibitory effects of TAAR1 activation on cocaine-induced changes in DA transmission. Collectively, the present observations reveal that the ability of TAAR1 to regulate cocaine effects is linked to cooperative interactions with D2 autoreceptors and associated downstream molecular targets converging on GSK-3 and suggest a new mechanism to disrupt cocaine neurochemical actions.
Identification of MST1 as a potential early detection biomarker for colorectal cancer through a proteomic approach
Authors: Yu Jiekai , Zhai Xiaohui , Li Xiaofen , Zhong Chenhan , Guo Cheng , Yang Fuquan , Yuan Ying , Zheng Shu 
Published: October 2017

AbstractColorectal cancer (CRC) is a common malignant neoplasm worldwide. It is important to identify new biomarkers for the early detection of CRC. In this study, magnetic beads and the Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) platform were used to analyse CRC and healthy control (HC) serum samples. The CRC diagnosis pattern was established to have a specificity of 94.7% and sensitivity of 92.3% in a blind test. The candidate biomarker serine/threonine kinase 4 (STK4, also known as MST1) was identified by Tandem mass spectrometry (MS/MS) and verified with western blotting and enzyme-linked immunosorbent assay (ELISA). The results indicated that there was a higher concentration of MST1 in HC subjects than stage I CRC patients for the early detection of CRC and a lower concentration in stage IV patients than in other CRC patients. The sensitivity and specificity of MST1 combined with carcinoembryonic antigen (CEA) and faecal occult blood test (FOBT) in diagnosis of colorectal cancer were 92.3% and 100%, respectively. Additionally, low MST1 expression was associated with the poor prognosis. These results illustrate that MST1 is a potential biomarker for early detection, prognosis and prediction of distant metastasis of CRC.
Ocular antigen does not cause disease unless presented in the context of inflammation
Authors: Voigt Valentina , Wikstrom Matthew E. , Kezic Jelena M. , Schuster Iona S. , Fleming Peter , Makinen Kimmo , Daley Stephen R. , Andoniou Christopher E. , Degli-Esposti Mariapia A. , Forrester John V. 
Published: October 2017

AbstractOcular antigens are sequestered behind the blood-retina barrier and the ocular environment protects ocular tissues from autoimmune attack. The signals required to activate autoreactive T cells and allow them to cause disease in the eye remain in part unclear. In particular, the consequences of peripheral presentation of ocular antigens are not fully understood. We examined peripheral expression and presentation of ocular neo-self-antigen in transgenic mice expressing hen egg lysozyme (HEL) under a retina-specific promoter. High levels of HEL were expressed in the eye compared to low expression throughout the lymphoid system. Adoptively transferred naïve HEL-specific CD4+T cells proliferated in the eye draining lymph nodes, but did not induce uveitis. By contrast, systemic infection with a murine cytomegalovirus (MCMV) engineered to express HEL induced extensive proliferation of transferred naïve CD4+T cells, and significant uveoretinitis. In this model, wild-type MCMV, lacking HEL, did not induce overt uveitis, suggesting that disease is mediated by antigen-specific peripherally activated CD4+T cells that infiltrate the retina. Our results demonstrate that retinal antigen is presented to T cells in the periphery under physiological conditions. However, when the same antigen is presented during viral infection, antigen-specific T cells access the retina and autoimmune uveitis ensues.
Lateral Boundary of Cirrus Cloud from CALIPSO Observations
Authors: Fu Yunfei , Chen Yilun , Li Rui , Qin Fang , Xian Tao , Yu Lu , Zhang Aoqi , Liu Guosheng , Zhang Xiangdong 
Published: October 2017

AbsractDue to the thinness and small scale of cirrus clouds, its lateral boundary may be missed by conventional passive remote-sensing techniques and climate models. Here, using satellite observations in June–August from 2006 to 2011, a global dataset for the cirrus cloud lateral boundary (CCLB) was established. The results indicate that the optical properties, such as the lidar backscatter, the depolarization ratio and the optical depth, sharply decrease from cloudy regions to clear-sky regions. There are significant regional differences in optical properties and height and thickness of the CCLB. Based on a quantitative estimation, the strongest longwave warming effects (>0.3 W m−2) are found near the Equator and over tropical continents. The global average longwave warming effect of the CCLB is at least 0.07 W m−2, which is much larger than some of the radiative forcings considered in the Intergovernmental Panel on Climate Change (IPCC) reports. Specifically, the CCLB in traditional “clear-sky” region may be totally missed by current models and IPCC reports, which contributes 28.25% (~0.02 W m−2) of the whole CCLB radiative effect, twice greater than contrail effect. It is recommended that the CCLB effect should be taken account in future climate models and the next IPCC reports.