bluuebunny/crossref_metadata_2025_split huggingface dataset:
MUC1-C Represses the Crumbs Complex Polarity Factor CRB3 and Downregulates the Hippo Pathway
Authors: Alam Maroof , Bouillez Audrey , Tagde Ashujit , Ahmad Rehan , Rajabi Hasan , Maeda Takahiro , Hiraki Masayuki , Suzuki Yozo , Kufe Donald 
Published: September 2016

Abstract
Apical–basal polarity and epithelial integrity are maintained in part by the Crumbs (CRB) complex. The C--terminal subunit of MUC1 (MUC1-C) is a transmembrane protein that is expressed at the apical border of normal epithelial cells and aberrantly at high levels over the entire surface of their transformed counterparts. However, it is not known whether MUC1-C contributes to this loss of polarity that is characteristic of carcinoma cells. Here it is demonstrated that MUC1-C downregulates expression of the Crumbs complex CRB3 protein in triple-negative breast cancer (TNBC) cells. MUC1-C associates with ZEB1 on the CRB3 promoter and represses CRB3 transcription. Notably, CRB3 activates the core kinase cassette of the Hippo pathway, which includes LATS1 and LATS2. In this context, targeting MUC1-C was associated with increased phosphorylation of LATS1, consistent with activation of the Hippo pathway, which is critical for regulating cell contact, tissue repair, proliferation, and apoptosis. Also shown is that MUC1-C--mediated suppression of CRB3 and the Hippo pathway is associated with dephosphorylation and activation of the oncogenic YAP protein. In turn, MUC1-C interacts with YAP, promotes formation of YAP/β-catenin complexes, and induces the WNT target gene MYC. These data support a previously unrecognized pathway in which targeting MUC1-C in TNBC cells (i) induces CRB3 expression, (ii) activates the CRB3-driven Hippo pathway, (iii) inactivates YAP, and thereby (iv) suppresses YAP/β-catenin–mediated induction of MYC expression.
Implications: These findings demonstrate a previously unrecognized role for the MUC1-C oncoprotein in the regulation of polarity and the Hippo pathway in breast cancer. Mol Cancer Res; 14(12); 1266–76. ©2016 AACR.
Clinical picture of heparin-induced thrombocytopenia (HIT) and its differentiation from non-HIT thrombocytopenia
Authors: Warkentin Theodore E. 
Published: September 2016

SummaryHIT is an acquired antibody-mediated disorder strongly associated with thrombosis, including microthrombosis secondary to disseminated intravascular dissemination (DIC). The clinical features of HIT are reviewed from the perspective of the 4Ts scoring system for HIT, which emphasises its characteristic timing of onset of thrombocytopenia. HIT antibodies recognize multimolecular complexes of platelet factor 4 (PF4)/heparin. However, a subset of HIT sera recognise PF4 bound to platelet chondroitin sulfate; these antibodies activate platelets in vitro and in vivo even in the absence of heparin, thus explaining: delayed-onset HIT (where HIT begins or worsens after stopping heparin); persisting HIT (where HIT takes several weeks to recover); spontaneous HIT syndrome (a disorder clinically and serologically resembling HIT but without proximate heparin exposure); and fondaparinux-associated HIT (four distinct syndromes featuring thrombocytopenia that begins or worsens during treatment with fondaparinux), with a new patient case presented with ongoing thrombocytopenia (and fatal haemorrhage) during treatment of HIT with fondaparinux, with fondaparinux-dependent platelet activation induced by patient serum (“fondaparinux cross-reactivity”). Ironically, despite existence of fondaparinux-associated HIT, this pentasaccharide anticoagulant is a frequent treatment for HIT (including one used by the author). HIT can be confused with other disorders, including those with a) timing similar to HIT (e. g. abciximab-associated thrombocytopenia of delayed-onset); b) combined thrombocytopenia/thrombosis (e. g. symmetrical peripheral gangrene secondary to acute DIC and shock liver); and c) both timing of onset and thrombosis (e. g. warfarin-associated venous limb gangrene complicating cancer-associated DIC). By understanding clinical and pathophysiological similarities and differences between HIT and non-HIT mimicking disorders, the clinician is better able to make the correct diagnosis.
Prangos multicostata (Apiaceae), a new species from eastern Kazakhstan
Authors: LYSKOV DMITRY F. , KLJUYKOV EUGENE V. , SAMIGULLIN TAHIR H. , UKRAINSKAJA ULIANA A. , KHRUSTALEVA IRINA A. 
Published: September 2016

Prangos multicostata (Apiaceae) is described and illustrated as a new species from the Western Tarbagatai Mts. in Eastern Kazakhstan. The species is related to P. ledebourii, P. dzhungarica and P. herderi, but differs from the aforementioned taxa in the length of its leaflets, the absence of bracts and bracteoles, and the appearance of secondary ribs on the mericarps.
Sensitivity of Supercell Simulations to Initial-Condition Resolution
Authors: Potvin Corey K. , Murillo Elisa M. , Flora Montgomery L. , Wheatley Dustan M. 
Published: September 2016

Abstract
Observational and model resolution limitations currently preclude analysis of the smallest scales important to numerical prediction of convective storms. These missing scales can be recovered if the forecast model is integrated on a sufficiently fine grid, but not before errors are introduced that subsequently grow in scale and magnitude. This study is the first to systematically evaluate the impact of these initial-condition (IC) resolution errors on high-resolution forecasts of organized convection. This is done by comparing high-resolution supercell simulations generated using identical model settings but successively coarsened ICs. Consistent with the Warn-on-Forecast paradigm, the simulations are initialized with ongoing storms and integrated for 2 h. Both idealized and full-physics experiments are performed in order to examine how more realistic model settings modulate the error evolution.
In all experiments, scales removed from the IC (wavelengths &lt; 2, 4, 8, or 16 km) regenerate within 10–20 min of model integration. While the forecast errors arising from the initial absence of these scales become quantitatively large in many instances, the qualitative storm evolution is relatively insensitive to the IC resolution. It therefore appears that adopting much finer forecast (e.g., 250 m) than analysis (e.g., 3 km) grids for data assimilation and prediction would improve supercell forecasts given limited computational resources. This motivates continued development of mixed-resolution systems. The relative insensitivity to IC resolution further suggests that convective forecasting can be more readily advanced by improving model physics and numerics and expanding extrastorm observational coverage than by increasing intrastorm observational density.
Retrofitting building fire service water tanks as chilled water storage for power demand limiting
Authors: Yan Chengchu , Wang Shengwei , Fan Cheng , Xiao Fu 
Published: September 2016

Peak demand cost usually contributes a large proportion of the total electricity bills in buildings. Using existing building facilities for power demand limiting has been verified as effective measures to reduce monthly peak demands and associated costs. Fire service water tanks exist in most commercial buildings. This paper presents a comprehensive study on how to effectively retrofit existing building fire service water tanks as chilled water storage for power demand limiting. Important technical and economic factors that may affect the implementation of the proposed retrofitting are addressed. Two retrofitting schemes, i.e. a small ΔT (storage temperature difference) scheme and a large ΔT scheme are proposed for integrating the chilled water storage system into an existing all-air system and an existing air-water air conditioning system, respectively. Two optimal demand limiting control strategies, i.e. time-based control and demand-based control, are proposed for maximizing the monthly peak demand reduction of buildings with regular and variable peak occurring time, respectively. The cost-effectiveness of different retrofitting schemes in three real buildings in Hong Kong is analysed. Results show that substantial cost savings can be achieved with short payback periods (0.7–2.6 years) for the retrofits in these three buildings. Practical application: This paper presents a techno-economic analysis on retrofitting existing building fire service water tanks as chilled water storage for power demand limiting and operational cost saving. The proposed retrofitting schemes and demand limiting control strategies enable chilled water storage systems to be readily applied to most existing buildings. Building owners can benefit from the peak demand cost saving as the monthly peak demand can be significantly reduced by using chilled water storage. The extra costs involved in tank retrofits and system integrations can be paid back within three years.
Glycemic Control Indices and Their Aggregation in the Prediction of Nocturnal Hypoglycemia From Intermittent Blood Glucose Measurements
Authors: Sampath Sivananthan , Tkachenko Pavlo , Renard Eric , Pereverzev Sergei V. 
Published: September 2016

Background: Despite the risk associated with nocturnal hypoglycemia (NH) there are only a few methods aiming at the prediction of such events based on intermittent blood glucose monitoring data. One of the first methods that potentially can be used for NH prediction is based on the low blood glucose index (LBGI) and suggested, for example, in Accu-Chek® Connect as a hypoglycemia risk indicator. On the other hand, nowadays there are other glucose control indices (GCI), which could be used for NH prediction in the same spirit as LBGI. In the present study we propose a general approach of combining NH predictors constructed from different GCI. Methods: The approach is based on a recently developed strategy for aggregating ranking algorithms in machine learning. NH predictors have been calibrated and tested on data extracted from clinical trials, performed in EU FP7-funded project DIAdvisor. Then, to show a portability of the method we have tested it on another dataset that was received from EU Horizon 2020-funded project AMMODIT. Results: We exemplify the proposed approach by aggregating NH predictors that have been constructed based on 4 GCI associated with hypoglycemia. Even though these predictors have been preliminary optimized to exhibit better performance on the considered dataset, our aggregation approach allows a further performance improvement. On the dataset, where a portability of the proposed approach has been demonstrated, the aggregating predictor has exhibited the following performance: sensitivity 77%, specificity 83.4%, positive predictive value 80.2%, negative predictive value 80.6%, which is higher than conventionally considered as acceptable. Conclusion: The proposed approach shows potential to be used in telemedicine systems for NH prediction.
rapidGSEA: Speeding up gene set enrichment analysis on multi-core CPUs and CUDA-enabled GPUs
Authors: Hundt Christian , Hildebrandt Andreas , Schmidt Bertil 
Published: September 2016

Abstract
Background
Gene Set Enrichment Analysis (GSEA) is a popular method to reveal significant dependencies between predefined sets of gene symbols and observed phenotypes by evaluating the deviation of gene expression values between cases and controls. An established measure of inter-class deviation, the enrichment score, is usually computed using a weighted running sum statistic over the whole set of gene symbols. Due to the lack of analytic expressions the significance of enrichment scores is determined using a non-parametric estimation of their null distribution by permuting the phenotype labels of the probed patients. Accordingly, GSEA is a time-consuming task due to the large number of required permutations to accurately estimate the nominal p-value – a circumstance that is even more pronounced during multiple hypothesis testing since its estimate is lower-bounded by the inverse number of samples in permutation space.

Results
We present rapidGSEA – a software suite consisting of two tools for facilitating permutation-based GSEA: cudaGSEA and ompGSEA. cudaGSEA is a CUDA-accelerated tool using fine-grained parallelization schemes on massively parallel architectures while ompGSEA is a coarse-grained multi-threaded tool for multi-core CPUs. Nominal p-value estimation of 4,725 gene sets on a data set consisting of 20,639 unique gene symbols and 200 patients (183 cases + 17 controls) each probing one million permutations takes 19 hours on a Xeon CPU and less than one hour on a GeForce Titan X GPU while the established GSEA tool from the Broad Institute (broadGSEA) takes roughly 13 days.

Conclusion
cudaGSEA outperforms broadGSEA by around two orders-of-magnitude on a single Tesla K40c or GeForce Titan X GPU. ompGSEA provides around one order-of-magnitude speedup to broadGSEA on a standard Xeon CPU. The rapidGSEA suite is open-source software and can be downloaded at https://github.com/gravitino/cudaGSEAas standalone application or package for the R framework.
Combinatorial identification of DNA methylation patterns over age in the human brain
Authors: Torabi Moghadam Behrooz , Dabrowski Michal , Kaminska Bozena , Grabherr Manfred G. , Komorowski Jan 
Published: September 2016

Abstract
Background
DNA methylation plays a key role in developmental processes, which is reflected in changing methylation patterns at specific CpG sites over the lifetime of an individual. The underlying mechanisms are complex and possibly affect multiple genes or entire pathways.

Results
We applied a multivariate approach to identify combinations of CpG sites that undergo modifications when transitioning between developmental stages. Monte Carlo feature selection produced a list of ranked and statistically significant CpG sites, while rule-based models allowed for identifying particular methylation changes in these sites.
Our rule-based classifier reports combinations of CpG sites, together with changes in their methylation status in the form of easy-to-read IF-THEN rules, which allows for identification of the genes associated with the underlying sites.

Conclusion
We utilized machine learning and statistical methods to discretize decision class (age) values to get a general pattern of methylation changes over the lifespan. The CpG sites present in the significant rules were annotated to genes involved in brain formation, general development, as well as genes linked to cancer and Alzheimer’s disease.
Noninvasive in-vivo tracing and imaging of transplanted stem cells for liver regeneration
Authors: Cen Panpan , Chen Jiajia , Hu Chenxia , Fan Linxiao , Wang Jie , Li Lanjuan 
Published: September 2016

AbstractTerminal liver disease is a major cause of death globally. The only ultimate therapeutic approach is orthotopic liver transplant. Because of the innate defects of organ transplantation, stem cell-based therapy has emerged as an effective alternative, based on the capacity of stem cells for multilineage differentiation and their homing to injured sites. However, the disease etiology, cell type, timing of cellular graft, therapeutic dose, delivery route, and choice of endpoints have varied between studies, leading to different, even divergent, results. In-vivo cell imaging could therefore help us better understand the fate and behaviors of stem cells to optimize cell-based therapy for liver regeneration. The primary imaging techniques in preclinical or clinical studies have consisted of optical imaging, magnetic resonance imaging, radionuclide imaging, reporter gene imaging, and Y chromosome-based fluorescence in-situ hybridization imaging. More attention has been focused on developing new or modified imaging methods for longitudinal and high-efficiency tracing. Herein, we provide a descriptive overview of imaging modalities and discuss recent advances in the field of molecular imaging of intrahepatic stem cell grafts.
Association of anticholinergic burden with adverse effects in older people with intellectual disabilities: an observational cross-sectional study
Authors: O'Dwyer Máire , Maidment Ian D. , Bennett Kathleen , Peklar Jure , Mulryan Niamh , McCallion Philip , McCarron Mary , Henman Martin C. 
Published: September 2016

BackgroundNo studies to date have investigated cumulative anticholinergic exposure and its effects in adults with intellectual disabilities.AimsTo determine the cumulative exposure to anticholinergics and the factors associated with high exposure.MethodA modified Anticholinergic Cognitive Burden (ACB) scale score was calculated for a representative cohort of 736 people over 40 years old with intellectual disabilities, and associations with demographic and clinical factors assessed.ResultsAge over 65 years was associated with higher exposure (ACB 1–4 odds ratio (OR) = 3.28, 95% CI 1.49–7.28, ACB 5+ OR = 3.08, 95% CI 1.20–7.63), as was a mental health condition (ACB 1–4 OR = 9.79, 95% CI 5.63–17.02, ACB 5+ OR = 23.74, 95% CI 12.29–45.83). Daytime drowsiness was associated with higher ACB (P<0.001) and chronic constipation reported more frequently (26.6% ACB 5+v.7.5% ACB 0,P<0.001).ConclusionsOlder people with intellectual disabilities and with mental health conditions were exposed to high anticholinergic burden. This was associated with daytime dozing and constipation.
An in vitro model of murine middle ear epithelium
Authors: Mulay Apoorva , Akram Khondoker M. , Williams Debbie , Armes Hannah , Russell Catherine , Hood Derek , Armstrong Stuart , Stewart James P. , Brown Steve D. M. , Bingle Lynne , Bingle Colin D. 
Published: September 2016

ABSTRACT
Otitis media (OM), or middle ear inflammation, is the most common paediatric disease and leads to significant morbidity. Although understanding of underlying disease mechanisms is hampered by complex pathophysiology it is clear that epithelial abnormalities underpin the disease. There is currently a lack of a well-characterised in vitro model of the middle ear (ME) epithelium that replicates the complex cellular composition of the middle ear. Here, we report the development of a novel in vitro model of mouse middle ear epithelial cells (mMECs) at an air–liquid interface (ALI) that recapitulates the characteristics of the native murine ME epithelium. We demonstrate that mMECs undergo differentiation into the varied cell populations seen within the native middle ear. Proteomic analysis confirmed that the cultures secrete a multitude of innate defence proteins from their apical surface. We showed that the mMECs supported the growth of the otopathogen, nontypeable Haemophilus influenzae (NTHi), suggesting that the model can be successfully utilised to study host–pathogen interactions in the middle ear. Overall, our mMEC culture system can help to better understand the cell biology of the middle ear and improve our understanding of the pathophysiology of OM. The model also has the potential to serve as a platform for validation of treatments designed to reverse aspects of epithelial remodelling that underpin OM development.
Evaluation of the relationship between cognitive functioning in patients with borderline personality disorder and their general functioning
Authors: Mosiołek Anna , Gierus Jacek , Koweszko Tytus , Szulc Agata 
Published: September 2016

Cel pracyCelem pracy było badanie zależności pomiędzy funkcjonowaniem poznawczym osób z osobowością chwiejną emocjonalnie typ borderline, a ich ogólnym poziomem funkcjonowania oraz nasileniem psychopatologii swoistej dla tego typu zaburzeń osobowości.MetodaPrzebadano 64 osoby w wieku 18-55 lat (M=30,09) z zaburzeniem osobowości chwiejnej emocjonalnie typ borderline wg. ICD-10. W badaniu korzystano z: kwestionariusza demograficzno - opisowego, ustrukturalizowanego wywiadu SCID-II, skali Borderline Symptom Checklist-23 oraz skali GAF. Oceny poznawczej dokonywano przy pomocy Testu 15 Słów Reya, Testu Figury Złożonej Reya, TMT A, TMT B, testu fluencji słownej, testu Stroopa oraz Frontal Assessment Battery.WynikiŚredni wskaźnik GAF w badanej próbie wyniósł M=43,65. Wykryto istotne różnice pomiędzy wymienionymi grupami pod względem wskaźnika GAF (U Mann-Whitney=300,500, p=0,008) oraz szereg istotnych (p<0.05) związków korelacyjnych pomiędzy poziomem funkcji poznawczych, a funkcjonowaniem w grupie osób bez współzachorowalności.WnioskiW grupie badanych osób z osobowością chwiejną emocjonalnie typ borderline utrzymywały się znaczące klinicznie zaburzenia w funkcjonowaniu ogólnym i społecznym. Uzyskane dane wydają się sugerować, że funkcje poznawcze wpływają na ogólne funkcjonowanie jedynie u osób ze współzachorowalnością psychiatryczną. U osób bez współzachorowalności psychiatrycznej wykazują powiązania jedynie z niektórymi aspektami swoistej dla BPD psychopatologii.
The efficacy of statins in preventing glucocorticoid-related osteonecrosis in animal models
Authors: Yang Z. , Liu H. , Li D. , Xie X. , Qin T. , Ma J. , Kang P. 
Published: September 2016

Objectives The primary purpose of this meta-analysis was to determine whether statin usage could reduce the risk of glucocorticoid-related osteonecrosis in animal models. Methods A systematic literature search up to May 2015 was carried out using the PubMed, Ovid, EBM reviews, ISI Web of Science, EBSCO, CBM, CNKI databases with the term and boolean operators: statins and osteonecrosis in all fields. Risk ratio (RR), as the risk estimate of specific outcome, was calculated along with 95% confidence intervals (CI). The methodological quality of individual studies was assessed using a quantitative tool based on the updated Stroke Therapy Academic Industry Roundtable (STAIR) recommendations. Results A total of 11 eligible studies were included according to predetermined criteria. The pooled data demonstrated that animals with statin usage, either alone or combined with other treatments, were at a decreased risk of developing glucocorticoid-related osteonecrosis (RR = 2.06, 95% confidence interval (CI) 1.71 to 2.50). Moreover, subgroup analysis revealed that compared with statins alone, statins combined with other treatments significantly decreased the risk of osteonecrosis (RR = 1.23, 95% CI 1.02 to 1.47). However, we could find no significant risk difference for different gender, or for different time points. Conclusions The present study suggests that statins combined with other treatments are efficient in preventing the development of glucocorticoid-related osteonecrosis in animals. These results might shed light on clinical practice when glucocorticoids are prescribed, and could be further investigated in high-quality clinical trials. Cite this article: Z. Yang, H. Liu, D. Li, X. Xie, T. Qin, J. Ma, P. Kang. The efficacy of statins in preventing glucocorticoid-related osteonecrosis in animal models: A meta-analysis. Bone Joint Res 2016;5:393–402. DOI: 10.1302/2046-3758.59.2000500.