bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular pathogenesis of human prostate basal cell hyperplasia
Authors: Henry Gervaise , Malewska Alicia , Mauck Ryan , Gahan Jeffrey , Hutchinson Ryan , Torrealba Jose , Francis Franto , Roehrborn Claus , Strand Douglas 
Published: August 2017

BackgroundUnderstanding the molecular pathogenesis of distinct phenotypes in human benign prostatic hyperplasia (BPH) is essential to improving therapeutic intervention. Current therapies target smooth muscle and luminal epithelia for relief of lower urinary tract symptoms (LUTS) due to BPH, but basal cell hyperplasia (BCH) remains untargeted. The incidence of has been reported at 8‐10%, but a molecular and cellular characterization has not been performed on this phenotype.MethodsUsing freshly digested tissue from surgical specimens, we performed RNA‐seq analysis of flow cytometry‐purified basal epithelia from 3 patients with and 4 patients without a majority BCH phenotype. qPCR was performed on 28 genes identified as significant from 13 non‐BCH and 7 BCH specimens to confirm transcriptomic analysis. IHC was performed on several non‐BCH and BCH specimens for 3 proteins identified as significant by transcriptomic analysis.ResultsA total of 141 human BPH specimens were analyzed for the presence of BCH. Clinical characteristics of non‐BCH and BCH cohorts revealed no significant differences in age, PSA, prostate volume, medical treatment, or comorbidities. Quantitation of cellular subsets by flow cytometry in 11 BCH patients vs. 11 non‐BCH patients demonstrated a significant increase in the ratio of basal to luminal epithelia in patients with BCH (P <0.05), but no significant differences in the total number of leukocytes. RNA‐seq data from flow cytometry isolated basal epithelia from patients with and without BCH were subjected to gene set enrichment analysis of differentially expressed genes, which revealed increased expression of members of the epidermal differentiation complex. Transcriptomic data were complemented by immunohistochemistry for members of the epidermal differentiation complex, revealing a morphological similarity to other stratified squamous epithelial layers.ConclusionsIncreased expression of epidermal differentiation complex members and altered epithelial stratification resembles the progression of other metaplastic diseases. These data provide insight into the plasticity of the human prostate epithelium and suggest a classification of basal cell hyperplasia as a metaplasia.
Exploring the Impacts of Mining on Tourism Growth and Local Sustainability: The Case of Mapungubwe Heritage Site, Limpopo, South Africa
Authors: Leonard Llewellyn , Lebogang Thema 
Published: August 2017

AbstractMining licenses in post‐apartheid South Africa are being granted by the ruling government in sensitive areas that are important tourism hubs and employment generators. Limited research has been conducted to understand mining impacts on protected environments and tourism sites. This paper will focus on the Mapungubwe World Heritage Site as a tourist attraction in Limpopo to shed light on how mining is impacting on the area and on tourism development and local sustainability. This paper examines the difficulties that have been encountered by the tourism destination and surrounding communities due to the mining licences granted. Semi‐structured interviews were conducted with key informants (communities, an employee at the heritage site and a government official) and are reported in this paper. We conclude that mining should not be allowed, with the need to rather safeguard the environment for cultural and environmental purposes. Stakeholder participation needs to be taken seriously by both the mining company and the government. Copyright © 2017 John Wiley & Sons, Ltd and ERP Environment
Bleeding Recurrence and Mortality Following Interventional Management of Spontaneous HCC Rupture: Results of a Multicenter European Study
Authors: Schwarz Lilian , Bubenheim Michael , Zemour Johanna , Herrero Astrid , Muscari Fabrice , Ayav Ahmet , Riboud Romain , Ducerf Christian , Regimbeau J‐Marc , Tranchart Hadrien , Lermite Emilie , Petrovai Gheorghe , Suhol Amal , Doussot Alexandre , Capussotti Lorenzo , Tuech Jean Jacques , Le Treut Yves Patrice ,   the FRENCH association
Published: August 2017

AbstractBackgroundThe incidence of spontaneous rupture of hepatocellular carcinoma (HCC) is low in Europe, at less than 3%. HCC rupture remains a life‐threatening complication, with mortality reported between 16 and 30%. The risk of bleeding recurrence has never been clearly evaluated in such clinical situation. The objectives of this study were to evaluate the current risk of mortality related to HCC rupture and to focus on the risk of bleeding recurrence following interventional management.MethodsAll patients admitted to 14 French–Italian surgical centers for spontaneous rupture of HCC between May 2000 and May 2012 were retrospectively included. Clinical data, imaging features, relevant laboratory data, treatment strategies, and prognoses were analyzed.ResultsOverall, 58 of the 138 included patients (42%) had cirrhosis. Thirty‐five patients (25%) presented with hemorrhagic shock, and 19% with organ(s) dysfunction. Bleeding control was obtained by interventional hemostasis, emergency liver resection, and conservative medical management in 86 (62%), 24 (18%), and 21 (15%) patients, respectively. Best supportive care was chosen for 7 (5%) patients. The mortality rate following rupture was 24%. The bleeding recurrence rate was 22% with related mortality of 52%. In multivariate analysis, a bilirubin level >17 micromol/L (HR 3.768; p = 0.006), bleeding recurrence (HR 5.400; p < 0.0001), and ICU admission after initial management (HR 8.199; p < 0.0001) were associated with in‐hospital mortality.ConclusionThis European, multicenter, large‐cohort study confirmed that the prognosis of ruptured HCC is poor with an overall mortality rate of 24%, despite important advances in endovascular techniques. Overall, the rate of bleeding recurrence was more than 20%, with a related high risk of mortality.
The Psychosocial Impact of Carrying a Debated Variant in the GLA Gene
Authors: Macklin Sarah , Laney Dawn , Lisi Emily , Atherton Andrea , Smith Elizabeth 
Published: August 2017

AbstractThe clinical significance of the c.427G>A (p.A143T) variant in GLA is a topic of debate within the lysosomal storage disease community. A review of the literature and published case reports found the clinical impact of the variant to range from classic Fabry symptoms to healthy unaffected males with normal alpha‐ galactosidase enzyme levels, leaving clinicians unsure of how to manage these individuals. As the number of states testing for Fabry disease on their newborn screening panel has increased, more people with this variant are being identified. The goal of this project was to learn how the uncertainty surrounding the clinical significance of the p.A143T variant affects those with this change. A self‐response questionnaire was developed to explore this topic. In addition to evaluating participant feelings, the questionnaire explored individuals’ beliefs regarding the pathogenicity of the variant. Results suggest that people have diverse feelings regarding reclassification of the p.A143T variant. Around half of those surveyed reported feeling frustrated by the lack of clear information. Despite the ambiguity regarding the health consequences of this variant, many participants felt that knowing this result helps guide medical management.
A Micellar Liquid Chromatographic Method for the Determination of Azosemide in Solubilized System
Authors: Malvia Hitesh , Sharma Ashok , Sharma Pratibha , Mishra Ritesh 
Published: August 2017

AbstractA simple micellar liquid chromatographic method was developed and validated for the determination of azosemide (AZS). The method incorporates surfactant media beyond the critical micellar concentration level for the study of AZS in bulk and pharmaceutical dosage forms. Quantitation was achieved through UV detection. An interpretive optimization procedure was used to ascertain the optimum conditions based on the accurate description of the retention and shape of the chromatographic peak for quantification of AZS, viz., selection of surfactants, pH of buffer solution, concentration of surfactant and selection of solvent etc. The method was successfully validated as per the requirements of the international Council for Harmonisation (ICH) guidelines and showed excellent linearity within the limits of detection and limit of quantitation. The method was linear over the concentration range 0.001–0.2 mg ml−1 with regression coefficient (r2) 0.999. The proposed method was successfully applied for ascertaining the stability and determination of AZS under different stressed conditions viz., basic, acidic, oxidative, photolytic, and thermal degradation. The method elicited good selectivity, repeatability, linearity and sensitivity of the validated parameters. Recoveries obtained were in a range of 98.90–99.58%. The method allows accurate and reliable determination of AZS for drug stability assays in pharmaceutical investigations using environmentally friendly materials.
Rethink space: (Re)designing a workspace using human-centered design to support flexibility, collaboration, and engagement among clinical and translational research support services
Authors: Doshi Aalap , Clay Christina 
Published: August 2017

IntroductionSpace matters. We read space like we read people’s faces. Space is an instrument of collaboration and innovation. At the University of Michigan’s Institute for Clinical and Health Research (MICHR), a team was created to creatively and economically enhance our operating space into a flexible workspace that supports privacy, innovation, creativity, and most important, a culture of collaboration.MethodsThe team used a human-centered design process to creatively engage the staff at large into analyzing our existing space, identifying latent needs, proposing solutions, generating feedback, and economically building the rethought process.ResultsThe redesigned workspace embraces the differences among MICHR’s teams while encouraging collaboration and teamwork and keeping costs at a minimum. It has resulted in a flexible space that includes co-located teams, spaces dedicated to different work goals, an open area for collaboration, quiet zones for focused work, and better wayfinding.ConclusionsThrough our Rethink Space project, we hope to have demonstrated that, by initiating the project internally and by engaging the users of the space themselves in an empathetic, visual, and human-centered way, a space redesign can be undertaken economically while also leading to improved levels of employee and team satisfaction.
Internal shear layers from librating objects
Authors: Le Dizès Stéphane , Le Bars Michael 
Published: August 2017

In this work, we analyse the internal shear layer structures generated by the libration of an axisymmetric object in an unbounded fluid rotating at a rotation rate $\unicode[STIX]{x1D6FA}^{\ast }$ using direct numerical simulation and small Ekman number asymptotic analysis. We consider weak libration amplitude and libration frequency $\unicode[STIX]{x1D714}^{\ast }$ within the inertial wave interval $(0,2\unicode[STIX]{x1D6FA}^{\ast })$ such that the fluid dynamics is mainly described by a linear axisymmetric harmonic solution. The internal shear layer structures appear along the characteristic cones of angle $\unicode[STIX]{x1D703}_{c}=\text{acos}(\unicode[STIX]{x1D714}^{\ast }/(2\unicode[STIX]{x1D6FA}^{\ast }))$ which are tangent to the librating object at so-called critical latitudes. These layers correspond to thin viscous regions where the singularities of the inviscid solution are smoothed. We assume that the velocity field in these layers is described by the class of similarity solutions introduced by Moore & Saffman (Phil. Trans. R. Soc. Lond. A, vol. 264, 1969, pp. 597–634). These solutions are characterized by two parameters only: a real parameter $m$, which measures the strength of the underlying singularity, and a complex amplitude coefficient $C_{0}$. We first analyse the case of a disk for which a general asymptotic solution for small Ekman numbers is known when the disk is in a solid plane. We demonstrate that the numerical solutions obtained for a free disk and for a disk in a solid plane are both well described by the asymptotic solution and by its similarity form within the internal shear layers. For the disk, we obtain a parameter $m=1$ corresponding to a Dirac source at the edge of the disk and a coefficient $C_{0}\propto E^{1/6}$ where $E$ is the Ekman number. The case of a smoothed librating object such as a spheroid is found to be different. By asymptotically matching the boundary layer solution to similarity solutions close to a critical latitude on the surface, we show that the adequate parameter $m$ for the similarity solution is $m=5/4$, leading to a coefficient $C_{0}\propto E^{1/12}$, that is larger than for the case of a disk for small Ekman numbers. A simple general expression for $C_{0}$ valid for any axisymmetric object is obtained as a function of the local curvature radius at the critical latitude in agreement with this change of scaling. This result is tested and validated against direct numerical simulations.
HOW TO SABOTAGE A SECRET SOCIETY: THE DEMISE OF CARL FRIEDRICH BAHRDT'S GERMAN UNION IN 1789
Authors: MCKENZIE-MCHARG ANDREW 
Published: August 2017

AbstractIn 1789 in Leipzig, a slim pamphlet of 128 pages appeared that sent shock waves through the German republic of letters. The pamphlet, bearing the title Mehr Noten als Text (More notes than text), was an ‘exposure’ whose most sensational element was a list naming numerous members of the North German intelligentsia as initiates of a secret society. This secret society, known as the German Union, aimed to push back against anti-Enlightenment tendencies most obviously manifest in the policies promulgated under the new Prussian king Frederick William II. The German Union was the brainchild of the notorious theologian Carl Friedrich Bahrdt (1741–92). But who was responsible for the ‘exposure’? Using material culled from several archives, this article pieces together for the first time the back story to Mehr Noten als Text and in doing so uncovers a surprisingly heterogeneous network of Freemasons, publishers, and state officials. The findings prompt us to reconsider general questions about the relationship of state and society in the late Enlightenment, the interplay of the public and the arcane spheres and the status of religious heterodoxy at this time.
A stretched conformation of DNA with a biological role?
Authors: Bosaeus Niklas , Reymer Anna , Beke-Somfai Tamás , Brown Tom , Takahashi Masayuki , Wittung-Stafshede Pernilla , Rocha Sandra , Nordén Bengt 
Published: August 2017

AbstractWe have discovered a well-defined extended conformation of double-stranded DNA, which we call Σ-DNA, using laser-tweezers force-spectroscopy experiments. At a transition force corresponding to free energy change ΔG = 1·57 ± 0·12 kcal (mol base pair)−1 60 or 122 base-pair long synthetic GC-rich sequences, when pulled by the 3′−3′ strands, undergo a sharp transition to the 1·52 ± 0·04 times longer Σ-DNA. Intriguingly, the same degree of extension is also found in DNA complexes with recombinase proteins, such as bacterial RecA and eukaryotic Rad51. Despite vital importance to all biological organisms for survival, genome maintenance and evolution, the recombination reaction is not yet understood at atomic level. We here propose that the structural distortion represented by Σ-DNA, which is thus physically inherent to the nucleic acid, is related to how recombination proteins mediate recognition of sequence homology and execute strand exchange. Our hypothesis is that a homogeneously stretched DNA undergoes a ‘disproportionation’ into an inhomogeneous Σ-form consisting of triplets of locally B-like perpendicularly stacked bases. This structure may ensure improved fidelity of base-pair recognition and promote rejection in case of mismatch during homologous recombination reaction. Because a triplet is the length of a gene codon, we speculate that the structural physics of nucleic acids may have biased the evolution of recombinase proteins to exploit triplet base stacks and also the genetic code.
Differential spatial expression of peripheral olfactory neuron-derived BACE1 induces olfactory impairment by region-specific accumulation of β-amyloid oligomer
Authors: Yoo Seung-Jun , Lee Ji-Hye , Kim So Yeun , Son Gowoon , Kim Jae Yeon , Cho Bongki , Yu Seong-Woon , Chang Keun-A , Suh Yoo-Hun , Moon Cheil 
Published: August 2017

AbstractOlfactory dysfunction is a common symptom associated with neurodegenerative diseases including Alzheimer’s disease (AD). Although evidence exists to suggest that peripheral olfactory organs are involved in the olfactory dysfunction that accompanies AD pathology, the underlying mechanisms are not fully understood. As confirmed using behavioral tests, transgenic mice overexpressing a Swedish mutant form of human amyloid precursor proteins exhibited olfactory impairments prior to evidence of cognitive impairment. By measuring the expression of tyrosine hydroxylase, we observed that specific regions of the olfactory bulb (OB) in Tg2576 mice, specifically the ventral portion exhibited significant decreases in the number of dopaminergic neurons in the periglomerular regions from the early stage of AD. To confirm the direct linkage between these olfactory impairments and AD-related pathology, β-site amyloid precursor protein cleaving enzyme 1 (BACE1)—the initiating enzyme in Aβ genesis—and β-amyloid peptide (Aβ), hallmarks of AD were analyzed. We found that an increase in BACE1 expression coincided with an elevation of amyloid-β (Aβ) oligomers in the ventral region of OB. Moreover, olfactory epithelium (OE), in particular the ectoturbinate in which axons of olfactory sensory neurons (OSNs) have direct connections with the dendrites of mitral/tufted cells in the ventral part of OB, exhibited significant decreases in both thickness and cell number even at early stages. This result suggests that Aβ oligomer toxicity in the OE may have induced a decline in the number of OSNs and functional impairment of the olfactory system. We first demonstrated that disproportionate levels of regional damage in the peripheral olfactory system may be a specific symptom of AD with Aβ oligomer accumulation occurring prior to damage within the CNS. This regional damage in the olfactory system early in the progression of AD may be closely related to AD-related pathological abnormality and olfactory dysfunction found in AD patients.
MUC1 induces acquired chemoresistance by upregulating ABCB1 in EGFR-dependent manner
Authors: Jin Wei , Liao Xiaodong , Lv Yaping , Pang Zhi , Wang Yuming , Li Quanfu , Liao Yahui , Ye Qing , Chen Guoqiang , Zhao Kewen , Huang Lei 
Published: August 2017

AbstractChemoresistance contributes to cancer relapse and increased mortality in a variety of cancer types, raising a pressing need to better understand the underlying mechanism. MUC1 is abnormally overexpressed in numerous carcinomas and associated with poor prognosis. However, the functional significance of MUC1 in chemoresistance has not been fully elucidated. Here, we showed that MUC1 expression was considerably induced in cells that had acquired chemoresistance at both transcriptional and post-translational levels. Using gain- and loss-of function approaches, we demonstrated a critical role of MUC1 in induction of drug resistance. Through stimulation of EGFR activation and nuclear translocation, MUC1 increased the expression of ATP-binding cassette transporter B1 (ABCB1). Remarkably, targeted suppression of EGFR or ABCB1 by both shRNAs and inhibitors effectively reversed chemoresistance. Moreover, co-administration of the inhibitors of MUC1–EGFR–ABCB1 with paclitaxel significantly blocked not only tumor growth but also relapse in xenograft mouse model. Our data collectively support a model in which MUC1 induces acquired chemotherapy resistance by upregulating ABCB1 in an EGFR-dependent manner, providing a novel molecular basis of using the EGFR inhibitor in MUC1-positive cancers to prevent chemotherapy resistance.
Upregulation of DACT2 suppresses proliferation and enhances apoptosis of glioma cell via inactivation of YAP signaling pathway
Authors: Tan Ying , Li Qiu-Meng , Huang Ning , Cheng Si , Zhao Guan-Jian , Chen Hong , Chen Song , Tang Zhao-Hua , Zhang Wen-Qian , Huang Qin , Cheng Yuan 
Published: August 2017

AbstractDACT2, one of the Dact gene family members, was shown to function as a tumor suppressor. However, its function in gliomas remains largely unknown. In this study, we investigated the role of DACT2, underlying molecular mechanisms and its clinical significance in glioma patients. Downexpression of DACT2 in gliomas compared with adjacent normal brain tissues was correlated with glioma grade and poor survival. Cox regression analysis revealed that the DACT2 is an independent prognostic indicator for glioma patients. Overexpression of DACT2 in glioma cells inhibited proliferation, cell cycle and enhanced apoptosis, sensitivity to temozolomide in vitro and suppressed tumor growth in vivo. Whereas knockdown of DACT2 induce opposite reaction. Mechanistically, overexpression of DACT2 resulted in upregulation of important signaling molecules such as p-YAP and p-β-catenin, and prevent YAP translocating into nucleus and sequestering in the cytoplasm to degrade. The study further proved that DACT2 can suppress YAP through Wnt/β-catenin signaling pathway. Collectively, these data indicate that DACT2 has a tumor suppressor function via inactivation of YAP pathway, providing a promising target for the treatment of gliomas.
Long-term consistency in chimpanzee consolation behaviour reflects empathetic personalities
Authors: Webb Christine E. , Romero Teresa , Franks Becca , de Waal Frans B. M. 
Published: August 2017

AbstractIn contrast to a wealth of human studies, little is known about the ontogeny and consistency of empathy-related capacities in other species. Consolation—post-conflict affiliation from uninvolved bystanders to distressed others—is a suggested marker of empathetic concern in non-human animals. Using longitudinal data comprising nearly a decade of observations on over 3000 conflict interactions in 44 chimpanzees (Pan troglodytes), we provide evidence for relatively stable individual differences in consolation behaviour. Across development, individuals consistently differ from one another in this trait, with higher consolatory tendencies predicting better social integration, a sign of social competence. Further, similar to recent results in other ape species, but in contrast to many human self-reported findings, older chimpanzees are less likely to console than are younger individuals. Overall, given the link between consolation and empathy, these findings help elucidate the development of individual socio-cognitive and -emotional abilities in one of our closest relatives.