bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adaptation of Akkermansia muciniphila to the Oxic-Anoxic Interface of the Mucus Layer
Authors: Ouwerkerk Janneke P. , van der Ark Kees C. H. , Davids Mark , Claassens Nico J. , Finestra Teresa Robert , de Vos Willem M. , Belzer Clara 
Published: September 2016

ABSTRACT

Akkermansia muciniphila
colonizes the mucus layer of the gastrointestinal tract, where the organism can be exposed to the oxygen that diffuses from epithelial cells. To understand how
A. muciniphila
is able to survive and grow at this oxic-anoxic interface, its oxygen tolerance and response and reduction capacities were studied.
A. muciniphila
was found to be oxygen tolerant. On top of this, under aerated conditions,
A. muciniphila
showed significant oxygen reduction capacities and its growth rate and yield were increased compared to those seen under strict anaerobic conditions. Transcriptome analysis revealed an initial oxygen stress response upon exposure to oxygen. Thereafter, genes related to respiration were expressed, including those coding for the cytochrome
bd
complex, which can function as a terminal oxidase. The functionality of
A. muciniphila
cytochrome
bd
genes was proven by successfully complementing cytochrome-deficient
Escherichia coli
strain ECOM4. We conclude that
A. muciniphila
can use oxygen when it is present at nanomolar concentrations.

IMPORTANCE
This article explains how
Akkermansia muciniphila
, previously described as a strictly anaerobic bacterium, is able to tolerate and even benefit from low levels of oxygen. Interestingly, we measured growth enhancement of
A. muciniphila
and changes in metabolism as a result of the oxygen exposure. In this article, we discuss similarities and differences of this oxygen-responsive mechanism with respect to those of other intestinal anaerobic isolates. Taken together, we think that these are valuable data that indicate how anaerobic intestinal colonizing bacteria can exploit low levels of oxygen present in the mucus layer and that our results have direct relevance for applicability, as addition of low oxygen concentrations could benefit the
in vitro
growth of certain anaerobic organisms.
BCL-2 system analysis identifies high-risk colorectal cancer patients
Authors: Lindner Andreas U , Salvucci Manuela , Morgan Clare , Monsefi Naser , Resler Alexa J , Cremona Mattia , Curry Sarah , Toomey Sinead , O'Byrne Robert , Bacon Orna , Stühler Michael , Flanagan Lorna , Wilson Richard , Johnston Patrick G , Salto-Tellez Manuel , Camilleri-Broët Sophie , McNamara Deborah A , Kay Elaine W , Hennessy Bryan T , Laurent-Puig Pierre , Van Schaeybroeck Sandra , Prehn Jochen H M 
Published: September 2016

ObjectiveThe mitochondrial apoptosis pathway is controlled by an interaction of multiple BCL-2 family proteins, and plays a key role in tumour progression and therapy responses. We assessed the prognostic potential of an experimentally validated, mathematical model of BCL-2 protein interactions (DR_MOMP) in patients with stage III colorectal cancer (CRC).DesignAbsolute protein levels of BCL-2 family proteins were determined in primary CRC tumours collected from n=128 resected and chemotherapy-treated patients with stage III CRC. We applied DR_MOMP to categorise patients as high or low risk based on model outputs, and compared model outputs with known prognostic factors (T-stage, N-stage, lymphovascular invasion). DR_MOMP signatures were validated on protein of n=156 patients with CRC from the Cancer Genome Atlas (TCGA) project.ResultsHigh-risk stage III patients identified by DR_MOMP had an approximately fivefold increased risk of death compared with patients identified as low risk (HR 5.2, 95% CI 1.4 to 17.9, p=0.02). The DR_MOMP signature ranked highest among all molecular and pathological features analysed. The prognostic signature was validated in the TCGA colon adenocarcinoma (COAD) cohort (HR 4.2, 95% CI 1.1 to 15.6, p=0.04). DR_MOMP also further stratified patients identified by supervised gene expression risk scores into low-risk and high-risk categories. BCL-2-dependent signalling critically contributed to treatment responses in consensus molecular subtypes 1 and 3, linking for the first time specific molecular subtypes to apoptosis signalling.ConclusionsDR_MOMP delivers a system-based biomarker with significant potential as a prognostic tool for stage III CRC that significantly improves established histopathological risk factors.
CT angiography-based collateral flow and time to reperfusion are strong predictors of outcome in endovascular treatment of patients with stroke
Authors: Sallustio Fabrizio , Motta Caterina , Pizzuto Silvia , Diomedi Marina , Giordano Angela , D'Agostino Vittoria Carla , Samà Domenico , Mangiafico Salvatore , Saia Valentina , Legramante Jacopo Maria , Konda Daniel , Pampana Enrico , Floris Roberto , Stanzione Paolo , Gandini Roberto , Koch Giacomo 
Published: September 2016

BackgroundCollateral flow (CF) is an effective predictor of outcome in acute ischemic stroke (AIS) with potential to sustain the ischemic penumbra. However, the clinical prognostic value of CF in patients with AIS undergoing mechanical thrombectomy has not been clearly established. We evaluated the relationship of CF with clinical outcomes in patients with large artery anterior circulation AIS treated with mechanical thrombectomy.MethodsBaseline collaterals of patients with AIS (n=135) undergoing mechanical thrombectomy were independently evaluated by CT angiography (CTA) and conventional angiography and dichotomized into poor and good CF. Multivariable analyses were performed to evaluate the predictive effect of CF on outcome and the effect of time to reperfusion on outcome based on adequacy of the collaterals.ResultsEvaluation of CF was consistent by both CTA and conventional angiography (p<0.0001). A higher rate of patients with good collaterals had good functional outcome at 3-month follow-up compared with those with poor collaterals (modified Rankin Scale (mRS) 0–2: 60% vs 10%, p=0.0001). Patients with poor collaterals had a significantly higher mortality rate (mRS 6: 45% vs 8%, p=0.0001). Multivariable analyses showed that CF was the strongest predictor of outcome. Time to reperfusion had a clear effect on favorable outcome (mRS ≤2) in patients with good collaterals; in patients with poor collaterals this effect was only seen when mRS ≤3 was considered an acceptable outcome.ConclusionsCTA is a valid tool for assessing the ability of CF to predict clinical outcome in patients with AIS treated with mechanical thrombectomy. Limiting time to reperfusion is of definite value in patients with good collaterals and also to some extent in those with poor collaterals.
MGD011, A CD19 x CD3 Dual-Affinity Retargeting Bi-specific Molecule Incorporating Extended Circulating Half-life for the Treatment of B-Cell Malignancies
Authors: Liu Liqin , Lam Chia-Ying K. , Long Vatana , Widjaja Lusiana , Yang Yinhua , Li Hua , Jin Linda , Burke Steve , Gorlatov Sergey , Brown Jennifer , Alderson Ralph , Lewis Margaret D. , Nordstrom Jeffrey L. , Koenig Scott , Moore Paul A. , Johnson Syd , Bonvini Ezio 
Published: September 2016

Abstract
Purpose: CD19, a B-cell lineage-specific marker, is highly represented in B-cell malignancies and an attractive target for therapeutic interventions. MGD011 is a CD19 x CD3 DART bispecific protein designed to redirect T lymphocytes to eliminate CD19-expressing cells. MGD011 has been engineered with a modified human Fc domain for improved pharmacokinetic (PK) properties and designed to cross-react with the corresponding antigens in cynomolgus monkeys. Here, we report on the preclinical activity, safety and PK properties of MGD011.
Experimental Design: The activity of MGD011 was evaluated in several in vitro and in vivo models. PK, safety and pharmacodynamic activity was also assessed in dose-escalation and repeat-dose studies of MGD011 administered once weekly in cynomolgus monkeys.
Results: MGD011 mediated killing of human B-cell lymphoma lines by human or cynomolgus monkey PBMCs as well as autologous B-cell depletion in PBMCs from both species. MGD011-mediated killing was accompanied by target-dependent T-cell activation and expansion, cytokine release and upregulation of perforin and granzyme B. MGD011 demonstrated antitumor activity against localized and disseminated lymphoma xenografts reconstituted with human PBMCs. In cynomolgus monkeys, MGD011 displayed a terminal half-life of 6.7 days; once weekly intravenous infusion of MGD011 at doses up to 100 μg/kg, the highest dose tested, was well tolerated and resulted in dose-dependent, durable decreases in circulating B cells accompanied by profound reductions of B lymphocytes in lymphoid organs.
Conclusions: The preclinical activity, safety and PK profile support clinical investigation of MGD011 as a therapeutic candidate for the treatment of B-cell malignancies. Clin Cancer Res; 23(6); 1506–18. ©2016 AACR.
BIRC6 Targeting as Potential Therapy for Advanced, Enzalutamide-Resistant Prostate Cancer
Authors: Luk Iris Sze Ue , Shrestha Raunak , Xue Hui , Wang Yuwei , Zhang Fang , Lin Dong , Haegert Anne , Wu Rebecca , Dong Xin , Collins Colin C. , Zoubeidi Amina , Gleave Martin E. , Gout Peter W. , Wang Yuzhuo 
Published: September 2016

Abstract
Purpose: Enzalutamide resistance has emerged as a major problem in the management of castration-resistant prostate cancer (CRPC). Research on therapy resistance of CRPCs has primarily focused on the androgen receptor pathway. In contrast, there is limited information on antiapoptotic mechanisms that may facilitate the treatment resistance. The inhibitor of apoptosis proteins (IAP) family is well recognized for its role in promoting treatment resistance of cancers by inhibiting drug-induced apoptosis. Here, we examined whether BIRC6, an IAP family member, has a role in enzalutamide resistance of CRPCs and could provide a therapeutic target for enzalutamide-resistant CRPC.
Experimental Design: Use of enzalutamide-resistant CRPC models: (i) the transplantable, first high-fidelity LTL-313BR patient-derived enzalutamide-resistant CRPC tissue xenograft line showing primary enzalutamide resistance, (ii) MR42D and MR49F CRPC cells/xenografts showing acquired enzalutamide resistance. Specific BIRC6 downregulation in these models was produced using a BIRC6-targeting antisense oligonucleotide (ASO-6w2). Gene expression was determined by qRT-PCR and gene expression profiling. Molecular pathways associated with growth inhibition were assessed via gene enrichment analysis.
Results: Of eight IAPs examined, BIRC6 was the only one showing elevated expression in both enzalutamide-resistant CRPC models. Treatment with ASO-6w2 markedly suppressed growth of LTL-313BR xenografts and increased tumor apoptosis without inducing major host toxicity. Pathway enrichment analysis indicated that GPCR and matrisome signaling were the most significantly altered pathways. Furthermore, ASO-6w2 inhibited expression of prosurvival genes that were upregulated in the LTL-313BR line.
Conclusions: BIRC6 targeting inhibited the growth of enzalutamide-resistant CRPC models and may represent a new option for clinical treatment of advanced, enzalutamide-resistant prostate cancer. Clin Cancer Res; 23(6); 1542–51. ©2016 AACR.
Identification of Keratin 19–Positive Cancer Stem Cells Associating Human Hepatocellular Carcinoma Using 18F-Fluorodeoxyglucose Positron Emission Tomography
Authors: Kawai Takayuki , Yasuchika Kentaro , Seo Satoru , Higashi Tatsuya , Ishii Takamichi , Miyauchi Yuya , Kojima Hidenobu , Yamaoka Ryoya , Katayama Hokahiro , Yoshitoshi Elena Yukie , Ogiso Satoshi , Kita Sadahiko , Yasuda Katsutaro , Fukumitsu Ken , Nakamoto Yuji , Hatano Etsuro , Uemoto Shinji 
Published: September 2016

Abstract
Purpose: The current lack of tools for easy assessment of cancer stem cells (CSC) prevents the development of therapeutic strategies for hepatocellular carcinoma (HCC). We previously reported that keratin 19 (K19) is a novel HCC-CSC marker and that PET with 18F-fluorodeoxyglucose (18F-FDG) is an effective method for predicting postoperative outcome in hepatocellular carcinoma. Herein, we examined whether K19+ HCC-CSCs can be tracked using 18F-FDG-PET.
Experimental Design: K19 and glucose transporter-1 (GLUT1) expression was evaluated by IHC in 98 hepatocellular carcinoma patients who underwent 18F-FDG-PET scans before primary tumor resection. Standardized uptake values (SUV) for primary tumors and tumor-to-nontumor SUV ratios (TNR) were calculated using FDG accumulation levels, and values were compared among K19+/K19− patients. Using hepatocellular carcinoma cell lines encoding with a K19 promoter–driven enhanced GFP, 18F-FDG uptake and GLUT1 expression were examined in FACS-isolated K19+/K19− cells.
Results: In hepatocellular carcinoma patients, K19 expression was significantly correlated with GLUT1 expression and FDG accumulation. ROC analyses revealed that among preoperative clinical factors, TNR was the most sensitive indicator of K19 expression in hepatocellular carcinoma tumors. In hepatocellular carcinoma cells, FACS-isolated K19+ cells displayed significantly higher 18F-FDG uptake than K19− cells. Moreover, gain/loss-of-function experiments confirmed that K19 regulates 18F-FDG uptake through TGFβ/Smad signaling, including Sp1 and its downstream target GLUT1.
Conclusions: 18F-FDG-PET can be used to predict K19 expression in hepatocellular carcinoma and should thereby aid in the development of novel therapeutic strategies targeting K19+ HCC-CSCs. Clin Cancer Res; 23(6); 1450–60. ©2016 AACR.
Corpo mal-dito: considerações à margem da obra de Qorpo-Santo
Authors: Finazzi-Agrò Ettore 
Published: September 2016

Lendo os textos de José Joaquim de Campos Leão, duas instâncias se apresentam como predominantes na sua escrita: por um lado, a urgência do testemunho e, pelo outro, a vontade de transgressão de qualquer gramática da representação. Balançando entre esses dois polos, Qorpo-Santo chega a nos dizer muito mais de que qualquer tratado histórico ou estudo sociológico sobre a sua condição de intelectual marginal e marginalizado e, mais em geral, sobre a situação cultural e humana vigente num Brasil periférico na segunda metade do século XIX.
Extreme Precipitation Indices over China in CMIP5 Models. Part II: Probabilistic Projection
Authors: Li Wei , Jiang Zhihong , Xu Jianjun , Li Laurent 
Published: September 2016

Abstract
The present article is the second part of a study on the extreme precipitation indices over China in CMIP5 models that perform a probabilistic projection of future precipitation indices with reference to the period 1986–2005. This is realized with a rank-based weighting method. The ranking of the 25 models is done according to their performance in simulating rainfall indices in present-day climate. Such weights are used to form a weighted ensemble for future climate projection. Results show that, compared to the unweighted raw ensemble, the projection with the weighted scheme is more credible, as the signal-to-noise ratio (SNR) of indices is larger from the weighted ensemble. From the beginning of the mid-twenty-first century, changes of wet indices with probability &gt;0.5 increase significantly, especially over western China and the Yellow–Huai River basin, where the changes of all wet indices are in excess of 10%, the increase of total precipitation (PRCPTOT) can reach up to 20% over western China at the end of twenty-first century, and the SNR of PRCPTOT and precipitation intensity (SDII) is the highest at those two regions. This indicates that the precipitation in those regions has a high reliability to become more extreme. The maximum consecutive dry days (CDD) decreases throughout the north of 30°N, which shows that drought conditions in northern China would be reduced, and they are more likely to increase in southern China. However, the SNR for projection of CDD is less than 1.0 almost everywhere. Such a situation seems related to a strengthening of the East Asian summer monsoon and the associated northward shift of the monsoon front.
Experiences of healthcare professionals as caregivers of a dying family member: an exploratory study
Authors: Fouto Ana Luísa Roque , Partington Lynne 
Published: September 2016

Background: Many health-care professionals also take on a caregiver role at home, usually by caring for a dying relative. Very little is known about the perceptions, experiences and needs of this specific group of carers. Objective: To understand the perceptions and experiences of healthcare professionals as caregivers and identify their needs. Methods: Health-care professionals working at one health unit in Portugal participated in a semi-structured interview (n=9). Data were analysed and organised thematically. Results: Four key themes emerged from the analysis: (i) the perception of the caregiver role, (ii) the difficulties experienced in the caregiver role, (iii) the rewards obtained by carrying out the caregiver role and (iv) the healthcare professional's needs as a caregiver. Conclusion: Healthcare professionals' needs as caregivers are not assessed and addressed holistically, creating room for improvement. Participants felt emotionally pressured by their families to get answers and find solutions during caregiving. Despite it being a complex and painful process, participants still gave examples of rewards experienced during caregiving.
La evaluación de la investigación en las universidades privadas: Presente y horizonte según el discurso de CONEAU
Authors: Bustamante Laura Andrea 
Published: September 2016

En el presente trabajo analizaremos cómo es evaluada la investigación en las instituciones privadas de educación superior. Entendiéndola como producción de conocimiento científico, asumimos que la política de evaluación institucional, puesta en práctica por la Comisión Nacional de Evaluación y Acreditación Universitaria (CONEAU), ha incidido en la forma de percibir la investigación al interior de las universidades. En este marco es pertinente preguntarse ¿Cuál es el estado de la investigación en las universidades privadas argentinas? ¿Cómo es evaluada externamente? ¿Qué perspectivas podemos estimar acerca de la investigación en las universidades privadas? Para esta investigación hemos planteado un diseño cualitativo, realizando un análisis de contenido de evaluaciones publicadas por CONEAU. Hemos seleccionado un corpus de 12 informes: 6 pertenecen a instituciones fundadas durante el primer período desarrollado (entre el 55 y el 66), 3 de este grupo son Universidades Católicas; y 6 a universidades que fueron fundadas en la década del 90. La sostenida recomendación de CONEAU en sus informes es incrementar la investigación, apuntando para ello al financiamiento privado. Los resultados parecen indicar que la supervisión de CONEAU genera un movimiento al interior de las universidades que perciben la presión del sistema y generan estrategias de adaptación al mismo. En este sentido, la evaluación parecería haber funcionado como una herramienta de adoctrinamiento y homogeneización, ante lo cual cabe la pregunta de cuán sostenible será dicho proceso en el tiempo.
Millenaristic Equity. Theological Order and Legal Faith
Authors: Costantini Cristina 
Published: September 2016

AbstractThe essay aims to prospect an original understanding of Equity Jurisdiction at the intersection of Law, Literature and Theology, theoretically based on a critical reassessment of E. Kantorowicz’s and E.L. Santner’s arguments. In this perspective, the Author uncovers the tensional metamorphoses, which ontologically affected and transmuted Equity from Medieval foundations to Renaissance reformed settlement, in order to fulfil a process of mystical secularization. Moving from a deeper appreciation of Chancellor’s figure and institutional role, the new intellectual vision here proposed brings to the light the historical and symbolical relevance of the Chancellor’s two bodies, which mimically reflected the dualities embedded in the normative figure of the King. The main purpose is to demonstrate how Equity Jurisdiction was charged with an eschatological significance and was attracted into millenaristic visions and narratives. Equity definitely constituted the salvific seam between Theological Order and Legal Faith. Meaningful arguments, in order to support the main thesis, comes from Medieval Literature, and especially from the spectacularized allegorical representation enacted by verses of Piers Plowman, where the contending claims of Common Law and Equity are christologically reinterpreted. Other foundative elements emerge from the valorization of the connection between Equity’s strategies and Elizabethan Apocalypticism. The Equity jurisdiction was a powerful device in order to gives voice and expression to the
Muscle-Specific Effective Mechanical Advantage and Joint Impulse in Weightlifting
Authors: Kipp Kristof , Harris Chad 
Published: September 2016

Abstract
Kipp, K, and Harris, C. Muscle-specific effective mechanical advantage and joint impulse in weightlifting. J Strength Cond Res 31(7): 1905–1910, 2017—Lifting greater loads during weightlifting exercises may theoretically be achieved through increasing the magnitudes of net joint impulses or manipulating the joints' effective mechanical advantage (EMA). The purpose of this study was to investigate muscle-specific EMA and joint impulse as well as impulse–momentum characteristics of the lifter-barbell system across a range of external loads during the execution of the clean. Collegiate-level weightlifters performed submaximal cleans at 65, 75, and 85% of their 1-repetition maximum (1-RM), whereas data from a motion analysis system and a force plate were used to calculate lifter-barbell system impulse and velocity, as well as net extensor impulse generated at the hip, knee, and ankle joints and the EMA of the gluteus maximus, hamstrings, quadriceps, and triceps surae muscles. The results indicated that the lifter-barbell system impulse did not change as load increased, whereas the velocity of the lifter-barbell system decreased with greater load. In addition, the net extensor impulse at all joints increased as load increased. The EMA of all muscles did not, however, change as load increased. The load-dependent effects on the impulse–velocity characteristics of the lifter-barbell system may reflect musculoskeletal force–velocity behaviors, and may further indicate that the weightlifting performance is limited by the magnitude of ground reaction force impulse. In turn, the load-dependent effects observed at the joint level indicated that lifting greater loads were due to greater net extensor impulses generated at the joints of the lower extremity and not greater EMAs of the respective extensor muscles. In combination, these results suggest that lifting greater external loads during the clean is due to the ability to generate large extensor joint impulses, rather than manipulate EMA.
What Is a Ballad? Reading for Genre, Format, and Medium
Authors: McGill Meredith L. 
Published: September 2016

Meredith L. McGill, “What Is a Ballad? Reading for Genre, Format, and Medium” (pp. 156–175)
In this essay I show how definitions of the ballad shift as critics take into account not only the place of ballads within the genre system but also the mediation of nineteenth-century ballads across the full range of popular and elite print formats. Arguing that the ballad is a genre that flourishes with the rise of print, I show how Henry Wadsworth Longfellow’s “The Wreck of the Hesperus” (1840) exploits the ballad’s multimedia appeal, forgoing the fiction of folk origins and oral transmission to explore the terms of a sensationalist mass culture.