bluuebunny/crossref_metadata_2025_split huggingface dataset:
Racial and Ethnic Variation in Health-Related Quality of Life Scores Prior to Prostate Cancer Treatment
Authors: Reading Stephanie R. , Porter Kimberly R. , Slezak Jeffrey M. , Harrison Teresa N. , Gelfond Joy S. , Chien Gary W. , Jacobsen Steven J. 
Published: August 2017

Abstract

Introduction
Many men diagnosed with prostate cancer are concerned with how the disease and its course of treatment could affect their health-related quality of life (HRQOL). To aid in the decision-making process on a course of treatment and to better understand how these treatments can affect HRQOL, knowledge of pretreatment HRQOL is essential.

Aims
To assess the racial and ethnic variations in HRQOL scores in men newly diagnosed with prostate cancer before electing a course of treatment.

Methods
Male members of the Kaiser Permanente of Southern California health plan who were newly diagnosed with prostate cancer completed the five-domain specific Expanded Prostate Index Composite–26 (EPIC-26) HRQOL questionnaire from March 1, 2011 through August 31, 2013 (N = 2,579). Domain scores were compared across racial and ethnic subgroups and multiple logistic regression analyses were used to assess the association after adjusting for sociodemographic and clinical characteristics.

Main Outcome Measures
The five EPIC-26 domain scores (sexual, bowel, hormonal, urinary incontinence, and urinary irritation and obstruction).

Results
Results from the fully adjusted analyses indicated that non-Hispanic black men were more likely to be above the sample median on the sexual (odds ratio [OR] = 1.43, 95% CI = 1.09–1.88), hormonal (OR = 1.35, 95% CI = 1.03–1.77), and urinary irritation and obstruction (OR = 1.34, 95% CI = 1.03–1.74) domains compared with non-Hispanic white men. The Asian or Pacific Islander men were less likely to be above the sample median on the sexual domain (OR = 0.60, 95% CI = 0.44–0.83) compared with non-Hispanic white men. No additional statistically significant differences were identified.

Conclusions
Within an integrated health care organization, we found minimal racial and ethnic differences, aside from sexual function, in pretreatment HRQOL in men newly diagnosed with prostate cancer. These findings provide important insight with which to interpret HRQOL changes in men newly diagnosed with prostate cancer during and after prostate cancer treatment.
Apoptotic resistance of human skin mast cells is mediated by Mcl-1
Authors: Hazzan Tarek , Eberle Jürgen , Worm Margitta , Babina Magda 
Published: August 2017

AbstractMast cells (MCs) are major effector cells of allergic reactions and contribute to multiple other pathophysiological processes. MCs are long-lived in the tissue microenvironment, in which they matured, but it remains ill-defined how longevity is established by the natural habitat, as research on human MCs chiefly employs cells generated and expanded in culture. In this study, we report that naturally differentiated skin MCs exhibit substantial resilience to cell death with considerable portions surviving up to 3 days in the complete absence of growth factors (GF). This was evidenced by kinetic resolution of membrane alterations (Annexin-V, YoPro), DNA degradation (propidium iodide), mitochondrial membrane disruption (Depsipher), and Caspase-3 activity. Because of the high basal survival, further protection by SCF was modest. Conversely, survival was severely compromised by staurosporine, implying functional caspase machinery. Contrary to the resistance of freshly purified MCs, their culture-expanded counterpart readily underwent cell death upon GF deprivation. Searching for the molecular underpinnings explaining the difference, we identified Mcl-1 as a critical protector. In fact, silencing Mcl-1 by RNAi led to impaired survival in skin MCs ex vivo, but not their cultured equivalent. Therefore, MCs matured in the skin have not only higher expression of Mcl-1 than proliferating MCs, but also greater reliance on Mcl-1 for their survival. Collectively, we report that human skin MCs display low susceptibility to cell death through vast expression of Mcl-1, which protects from mortality and may contribute to MC longevity in the tissue.
Enriched housing promotes post-stroke functional recovery through astrocytic HMGB1-IL-6-mediated angiogenesis
Authors: Chen Jia-Yi , Yu Yuan , Yuan Yin , Zhang Yu-Jing , Fan Xue-Peng , Yuan Shi-Ying , Zhang Jian-Cheng , Yao Shang-Long 
Published: August 2017

AbstractEnriched environment (EE) is shown to promote angiogenesis, neurogenesis and functional recovery after ischemic stroke. However, the underlying mechanisms remain unclear. C57BL/6 mice underwent middle cerebral artery occlusion (60 min) followed by reperfusion, after which mice were housed in either standard environment (SE) or EE. Here we found that post-ischemic EE exhibited decreased depression and anxiety-like behavior, and promoted angiogenesis and functional recovery compared to SE mice. EE mice treated with high-mobility group box-1 (HMGB1) inhibitor glycyrrhizin had an increased post-stroke depression and anxiety-like behavior, and the angiogenesis and functional recovery were decreased. HMGB1 and interleukin-6 (IL-6) expression in astrocyte were increased in EE mice. EE mice treated with glycyrrhizin decreased, whereas EE mice treated with recombinant HMGB1 (rHMGB1) increased the levels of IL-6 and p-AKT. Blockade of IL-6 with anti-IL-6-neutralizing antibody in EE mice attenuated EE-mediated angiogenesis and functional recovery. Furthermore, our in vitro data revealed that in primary astrocyte cultures rHMGB1 promoted the expression of IL-6 in activated astrocytes. PI3K/AKT signaling pathway was involved in HMGB1-mediated expression of astrocytic IL-6. Thus, our results reveal a previously uncharacterized property of HMGB1/IL-6 signaling pathway in EE-mediated angiogenesis and functional recovery after ischemic stroke.
Dimerization in tailoring uptake efficacy of the HSV-1 derived membranotropic peptide gH625
Authors: Falanga Annarita , Valiante Salvatore , Galdiero Emilia , Franci Gianluigi , Scudiero Olga , Morelli Giancarlo , Galdiero Stefania 
Published: August 2017

AbstractgH625 constitutes a promising delivery vehicle for the transport of therapeutic biomacromolecules across membrane barriers. We report an application of multivalency to create a complex nanosystem for delivery and to elucidate the mechanism of peptide-lipid bilayer interactions. Multivalency may offer a route to enhance gH625 cellular uptake as demonstrated by results obtained on dimers of gH625 by fluorescence spectroscopy, circular dichroism, and surface plasmon resonance. Moreover, using both phase contrast and light sheet fluorescence microscopy we were able to characterize and visualize for the first time the fusion of giant unilamellar vesicles caused by a membranotropic peptide.
Cancer-targeted Nucleic Acid Delivery and Quantum Dot Imaging Using EGF Receptor Aptamer-conjugated Lipid Nanoparticles
Authors: Kim Min Woo , Jeong Hwa Yeon , Kang Seong Jae , Choi Moon Jung , You Young Myoung , Im Chan Su , Lee Tae Sup , Song In Ho , Lee Chang Gun , Rhee Ki-Jong , Lee Yeon Kyung , Park Yong Serk 
Published: August 2017

AbstractCo-application of fluorescent quantum dot nanocrystals and therapeutics has recently become a promising theranostic methodology for cancer treatment. We developed a tumor-targeted lipid nanocarrier that demonstrates notable efficacy in gene delivery as well as tumor bio-imaging. Coupling of aptamer molecules against the EGF receptor (EGFR) to the distal termini of lipid nanoparticles provided the carrier with tumor-specific recognition capability. The cationic lipid component, referred to as O,O’-dimyristyl-N-lysyl glutamate (DMKE), was able to effectively complex with anionic small-interfering RNA (siRNA). The hydrophobic quantum dots (Q-dots) were effectively incorporated in hydrophobic lipid bilayers at an appropriate Q-dot to lipid ratio. In this study, we optimized the liposomal formula of aptamer-conjugated liposomes containing Q-dots and siRNA molecules (Apt-QLs). The anti-EGFR Apt-QLs exhibited remarkable EGFR-dependent siRNA delivery as well as fluorescence imaging, which were analyzed in cultured cancer cells and tumor xenografts in mice. These results imply that the formulation of Apt-QLs could be widely utilized as a carrier for tumor-directed gene delivery and bio-imaging.
Optimal Translation Along a Circular mRNA
Authors: Zarai Yoram , Ovseevich Alexander , Margaliot Michael 
Published: August 2017

AbstractThe ribosome flow model on a ring (RFMR) is a deterministic model for ribosome flow along a circularized mRNA. We derive a new spectral representation for the optimal steady-state production rate and the corresponding optimal steady-state ribosomal density in the RFMR. This representation has several important advantages. First, it provides a simple and numerically stable algorithm for determining the optimal values even in very long rings. Second, it enables efficient computation of the sensitivity of the optimal production rate to small changes in the transition rates along the mRNA. Third, it implies that the optimal steady-state production rate is a strictly concave function of the transition rates. Maximizing the optimal steady-state production rate with respect to the rates under an affine constraint on the rates thus becomes a convex optimization problem that admits a unique solution. This solution can be determined numerically using highly efficient algorithms. This optimization problem is important, for example, when re-engineering heterologous genes in a host organism. We describe the implications of our results to this and other aspects of translation.
A neuropeptide, Substance-P, directly induces tissue-repairing M2 like macrophages by activating the PI3K/Akt/mTOR pathway even in the presence of IFNγ
Authors: Lim Ji Eun , Chung Eunkyung , Son Youngsook 
Published: August 2017

AbstractMacrophage polarization plays an important role in tissue damage and repair. In this study, we show that Substance-P (SP) can directly induce M2 polarization of inflammatory macrophages. SP induced the differentiation of GM-CSF-differentiated pro-inflammatory macrophages into alternatively activated phagocytic M2 like macrophages (M2SP) through direct activation of the PI3K/Akt/mTOR/S6kinase pathway and induction of Arginase-1, CD163, and CD206, all of which were nullified by pretreatment with the neurokinin-1 receptor (NK-1R) antagonist RP67580 and specific signaling pathway inhibitors. M2SP were distinct from IL-4/IL-13-induced M2a and IL-10-induced M2c subtypes; they did not show STAT activation and exhibited high phagocytic and endothelial adhesive activity. Furthermore, SP had a dominant effect on M2 polarization over Interferon gamma (IFNγ), a potent M1-skewing cytokine, and effectively induced the M2 phenotype in monocytes and the human THP-1 cell line. Finally, adoptively transferred M2SP migrated to a spinal cord injury (SCI) lesion site and improved functional recovery. Collectively, our findings show that SP, a neuropeptide, plays a role as a novel cytokine by inducing tissue-repairing M2SP macrophages and thus may be developed for pharmacological intervention in diseases involving chronic inflammation and acute injury.
An informatics guided classification of miscible and immiscible binary alloy systems
Authors: Zhang R. F. , Kong X. F. , Wang H. T. , Zhang S. H. , Legut D. , Sheng S. H. , Srinivasan S. , Rajan K. , Germann T. C. 
Published: August 2017

AbstractThe classification of miscible and immiscible systems of binary alloys plays a critical role in the design of multicomponent alloys. By mining data from hundreds of experimental phase diagrams, and thousands of thermodynamic data sets from experiments and high-throughput first-principles (HTFP) calculations, we have obtained a comprehensive classification of alloying behavior for 813 binary alloy systems consisting of transition and lanthanide metals. Among several physics-based descriptors, the slightly modified Pettifor chemical scale provides a unique two-dimensional map that divides the miscible and immiscible systems into distinctly clustered regions. Based on an artificial neural network algorithm and elemental similarity, the miscibility of the unknown systems is further predicted and a complete miscibility map is thus obtained. Impressively, the classification by the miscibility map yields a robust validation on the capability of the well-known Miedema’s theory (95% agreement) and shows good agreement with the HTFP method (90% agreement). Our results demonstrate that a state-of-the-art physics-guided data mining can provide an efficient pathway for knowledge discovery in the next generation of materials design.
Solvent Assisted Tuning of Morphology of a Peptide-Perylenediimide Conjugate: Helical Fibers to Nano-Rings and their Differential Semiconductivity
Authors: Ahmed Sahnawaz , Pramanik Bapan , Sankar K. N. Amba , Srivastava Abhinav , Singha Nilotpal , Dowari Payel , Srivastava Arpita , Mohanta Kallol , Debnath Ananya , Das Debapratim 
Published: August 2017

AbstractUnderstanding the regulatory factors of self-assembly processes is a necessity in order to modulate the nano-structures and their properties. Here, the self-assembly mechanism of a peptide-perylenediimide (P-1) conjugate in mixed solvent systems of THF/water is studied and the semiconducting properties are correlated with the morphology. In THF, right handed helical fibers are formed while in 10% THF-water, the morphology changes to nano-rings along with a switch in the helicity to left-handed orientation. Experimental results combined with DFT calculations reveal the critical role of thermodynamic and kinetic factors to control these differential self-assembly processes. In THF, P-1 forms right handed helical fibers in a kinetically controlled fashion. In case of 10% THF-water, the initial nucleation of the aggregate is controlled kinetically. Due to differential solubility of the molecule in these two solvents, elongation of the nuclei into fibers is restricted after a critical length leading to the formation of nano-rings which is governed by the thermodynamics. The helical fibers show superior semi-conducting property to the nano-rings as confirmed by conducting-AFM and conventional I-V characteristics.
Retinal cell death dependent reactive proliferative gliosis in the mouse retina
Authors: Sardar Pasha Sheik Pran Babu , Münch Robert , Schäfer Patrick , Oertel Peter , Sykes Alex M. , Zhu Yiqing , Karl Mike O. 
Published: August 2017

AbstractNeurodegeneration is a common starting point of reactive gliosis, which may have beneficial and detrimental consequences. It remains incompletely understood how distinctive pathologies and cell death processes differentially regulate glial responses. Müller glia (MG) in the retina are a prime model: Neurons are regenerated in some species, but in mammals there may be proliferative disorders and scarring. Here, we investigated the relationship between retinal damage and MG proliferation, which are both induced in a reproducible and temporal order in organotypic culture of EGF-treated mouse retina: Hypothermia pretreatment during eye dissection reduced neuronal cell death and MG proliferation; stab wounds increased both. Combined (but not separate) application of defined cell death signaling pathway inhibitors diminished neuronal cell death and maintained MG mitotically quiescent. The level of neuronal cell death determined MG activity, indicated by extracellular signal-regulated kinase (ERK) phosphorylation, and proliferation, both of which were abolished by EGFR inhibition. Our data suggest that retinal cell death, possibly either by programmed apoptosis or necrosis, primes MG to be able to transduce the EGFR–ERK activity required for cell proliferation. These results imply that cell death signaling pathways are potential targets for future therapies to prevent the proliferative gliosis frequently associated with certain neurodegenerative conditions.
Intrinsic brain connectivity after partial sleep deprivation in young and older adults: results from the Stockholm Sleepy Brain study
Authors: Nilsonne Gustav , Tamm Sandra , Schwarz Johanna , Almeida Rita , Fischer Håkan , Kecklund Göran , Lekander Mats , Fransson Peter , Åkerstedt Torbjörn 
Published: August 2017

AbstractSleep deprivation has been reported to affect intrinsic brain connectivity, notably reducing connectivity in the default mode network. Studies to date have however shown inconsistent effects, in many cases lacked monitoring of wakefulness, and largely included young participants. We investigated effects of sleep deprivation on intrinsic brain connectivity in young and older participants. Participants aged 20–30 (final n = 30) and 65–75 (final n = 23) years underwent partial sleep deprivation (3 h sleep) in a cross-over design, with two 8-minutes eyes-open resting state functional magnetic resonance imaging (fMRI) runs in each session, monitored by eye-tracking. We assessed intrinsic brain connectivity using independent components analysis (ICA) as well as seed-region analyses of functional connectivity, and also analysed global signal variability, regional homogeneity, and the amplitude of low-frequency fluctuations. Sleep deprivation caused increased global signal variability. Changes in investigated resting state networks and in regional homogeneity were not statistically significant. Younger participants had higher connectivity in most examined networks, as well as higher regional homogeneity in areas including anterior and posterior cingulate cortex. In conclusion, we found that sleep deprivation caused increased global signal variability, and we speculate that this may be caused by wake-state instability.
Virtual histological assessment of the prenatal life history and age at death of the Upper Paleolithic fetus from Ostuni (Italy)
Authors: Nava Alessia , Coppa Alfredo , Coppola Donato , Mancini Lucia , Dreossi Diego , Zanini Franco , Bernardini Federico , Tuniz Claudio , Bondioli Luca 
Published: August 2017

AbstractThe fetal remains from the Ostuni 1 burial (Italy, ca 27 ka) represent a unique opportunity to explore the prenatal biological parameters, and to reconstruct the possible patho-biography, of a fetus (and its mother) in an Upper Paleolithic context. Phase-contrast synchrotron X-ray microtomography imaging of two deciduous tooth crowns and microfocus CT measurements of the right hemimandible of the Ostuni 1b fetus were performed at the SYRMEP beamline and at the TomoLab station of the Elettra - Sincrotrone laboratory (Trieste, Italy) in order to refine age at death and to report the enamel developmental history and dental tissue volumes for this fetal individual. The virtual histology allowed to estimate the age at death of the fetus at 31–33 gestational weeks. Three severe physiological stress episodes were also identified in the prenatal enamel. These stress episodes occurred during the last two months and half of pregnancy and may relate to the death of both individuals. Compared with modern prenatal standards, Os1b’s skeletal development was advanced. This cautions against the use of modern skeletal and dental references for archaeological finds and emphasizes the need for more studies on prenatal archaeological skeletal samples.
Altered expression of Tumor Necrosis Factor Alpha -Induced Protein 3 correlates with disease severity in Ulcerative Colitis
Authors: Majumdar Ishani , Ahuja Vineet , Paul Jaishree 
Published: August 2017

AbstractUlcerative colitis (UC), an inflammatory disorder of the colon arises from dysregulated immune response towards gut microbes. Transcription factor NFκB is a major regulatory component influencing mucosal inflammation. We evaluated expression of Tumor Necrosis Factor Alpha Induced Protein3 (TNFAIP3), the inhibitor of NFκB activation and its associated partners ITCH, RNF11 and Tax1BP1 in inflamed mucosa of UC patients. We found highly significant up-regulated mRNA expression of TNFAIP3 that negatively correlated with disease activity in UC. mRNA levels of ITCH, RNF11 and Tax1BP1 were significantly down-regulated. Significant positive correlation with disease activity was noted for Tax1BP1. All four genes showed significant down-regulation at protein level. mRNA levels of inducers of TNFAIP3 expression, NFκB p65 subunit and MAST3 was determined. There was significant increase in p65 mRNA expression and down-regulated MAST3 expression. This suggested that increase in NFκB expression regulates TNFAIP3 levels. Deficiency of TNFAIP3 expression resulted in significant up-regulation of NFκB p65 sub-unit as well as its downstream genes such as iNOS, an inflammatory marker, inhibitors of apoptosis like cIAP2 and XIAP and mediators of anti-apoptotic signals TRAF1 and TRAF2. Taken together, decreased expression of TNFAIP3 and its partners contribute to inflammation and up-regulation of apoptosis inhibitors that may create microenvironment for colorectal cancer.
A preclinical model for identifying rats at risk of alcohol use disorder
Authors: Jadhav Kshitij S. , Magistretti Pierre J. , Halfon Olivier , Augsburger Marc , Boutrel Benjamin 
Published: August 2017

AbstractAlcohol use is one of the world’s leading causes of death and disease, although only a small proportion of individuals develop persistent alcohol use disorder (AUD). The identification of vulnerable individuals prior to their chronic intoxication remains of highest importance. We propose here to adapt current methodologies for identifying rats at risk of losing control over alcohol intake by modeling diagnostic criteria for AUD: inability to abstain during a signaled period of reward unavailability, increased motivation assessed in a progressive effortful task and persistent alcohol intake despite aversive foot shocks. Factor analysis showed that these three addiction criteria loaded on one underlying construct indicating that they represent a latent construct of addiction trait. Further, not only vulnerable rats displayed higher ethanol consumption, and higher preference for ethanol over sweetened solutions, but they also exhibited pre-existing higher anxiety as compared to resilient rats. In conclusion, the present preclinical model confirms that development of an addiction trait not only requires prolonged exposure to alcohol, but also depends on endophenotype like anxiety that predispose a minority of individuals to lose control over alcohol consumption.
A Model of Exposure to Extreme Environmental Heat Uncovers the Human Transcriptome to Heat Stress
Authors: Bouchama Abderrezak , Aziz Mohammad Azhar , Mahri Saeed Al , Gabere Musa Nur , Dlamy Meshan Al , Mohammad Sameer , Abbad Mashael Al , Hussein Mohamed 
Published: August 2017

AbstractThe molecular mechanisms by which individuals subjected to environmental heat stress either recover or develop heat-related complications are not well understood. We analysed the changes in blood mononuclear gene expression patterns in human volunteers exposed to extreme heat in a sauna (temperature of 75.7 ± 0.86 °C). Our analysis reveals that expression changes occur rapidly with no significant increase in core temperature and continue to amplify one hour after the end of heat stress. The reprogramed transcriptome was predominantly inhibitory, as more than two-thirds of the expressed genes were suppressed. The differentially expressed genes encoded proteins that function in stress-associated pathways; including proteostasis, energy metabolism, cell growth and proliferation, and cell death, and survival. The transcriptome also included mitochondrial dysfunction, altered protein synthesis, and reduced expression of genes -related to immune function. The findings reveal the human transcriptomic response to heat and highlight changes that might underlie the health outcomes observed during heat waves.