bluuebunny/crossref_metadata_2025_split huggingface dataset:
Freezing of Gait can persist after an acute levodopa challenge in Parkinson’s disease
Authors: Lucas McKay J. , Goldstein Felicia C. , Sommerfeld Barbara , Bernhard Douglas , Perez Parra Sahyli , Factor Stewart A. 
Published: November 2019

AbstractStudy objectives included testing whether presumed levodopa-unresponsive freezing of gait (FOG) in Parkinson’s disease (PD) actually persists in the presence of adequate dopaminergic dosing and to investigate whether the presence of other parkinsonian features and their responsiveness to therapy varies across patients without FOG (NO-FOG), with levodopa-responsive FOG (OFF-FOG), and with levodopa-unresponsive FOG (ONOFF-FOG). Fifty-five PD patients completed levodopa challenges after >12-h OFF with supratherapeutic doses of dopaminergic medications. Observed responses in FOG, measured with MDS-UPDRS-III during the patient reported full “ON”, were used to classify them as NO-FOG, OFF-FOG, or ONOFF-FOG. Serum levodopa levels were measured. Only those with ≥20% improvement in MDS-UPDRS-III score were included in analyses. Levodopa challenge was sufficient to bring about a full “ON” state with ≥20% improvement in 45 patients. Levodopa-equivalent-dose utilized was 142 ± 56% of patients’ typical morning doses. Overall, 19/45 patients exhibited FOG in the full “ON” state (ONOFF-FOG), 11 were classified as OFF-FOG, and 15 NO-FOG. Linear mixed models revealed a highly significant association between serum levodopa level and total MDS-UPDRS-III score that was similar across groups. The ONOFF-FOG group exhibited significantly higher New-FOG-questionnaire and MDS-UPDRS-II scores compared to the OFF-FOG group. Among MDS-UPDRS-III subdomains significant effects of group (highest in ONOFF-FOG) were identified for other axial parkinsonian features. We found that FOG can persist in the full “ON” state brought about by ample dopaminergic dosing in PD. Other axial measures can also be levodopa-unresponsive among those with ONOFF-FOG only. These data provide evidence that ONOFF-FOG is distinct from responsive freezing.
Molecular Characterization of Auxin Efflux Carrier- ABCB1 in hexaploid wheat
Authors: Mohan Amita , Dhaliwal Amandeep K. , Nagarajan Ragupathi , Gill Kulvinder S. 
Published: November 2019

AbstractAuxin is an important phytohormone that regulates response, differentiation, and development of plant cell, tissue, and organs. Along with its local production, long-distance transport coordinated by the efflux/influx membrane transporters is instrumental in plant development and architecture. In the present study, we cloned and characterized a wheat (Triticum aestivum) auxin efflux carrier ABCB1. The TaABCB1 was physically localized to the proximal 15% of the short arm of wheat homoeologous group 7 chromosomes. Size of the Chinese spring (CS) homoeologs genomic copies ranged from 5.3–6.2 kb with the7Acopy being the largest due to novel insertions in its third intron. The three homoeologous copies share 95–97% sequence similarity at the nucleotide, 98–99% amino acid, and overall Q-score of 0.98 at 3-D structure level. Though detected in all analyzed tissues,TaABCB1predominantly expressed in the meristematic tissues likely due to the presence of meristem-specific activation regulatory element identified in the promoter region. RNAi plants ofTaABCB1gene resulted in reduced plant height and increased seed width. Promoter analysis revealed several responsive elements detected in the promoter region including that for different hormones as auxin, gibberellic acid, jasmonic acid and abscisic acid, light, and circadian regulated elements.
Elevated glucose acts directly on osteocytes to increase sclerostin expression in diabetes
Authors: Pacicca Donna M. , Brown Tammy , Watkins Dara , Kover Karen , Yan Yun , Prideaux Matthew , Bonewald Lynda 
Published: November 2019

AbstractBone quality in diabetic patients is compromised, leading to weaker bones and increased fracture risk. However, the mechanism by which this occurs in diabetic bone remains to be fully elucidated. We hypothesized that elevated glucose and glucose variation would affect the function of osteocytes, essential regulators of bone homeostasis and quality. To first test this hypothesis, we used the IDG-SW3 osteocyte-like cell line to examine the effects of glucose levels on osteocyte function and viability in vitro. We confirmed our in vitro findings using the in vivo streptozotocin-induced (STZ) diabetic rat model and ex-vivo cultured osteocytes from these rats. IDG-SW3 cells cultured under high glucose conditions displayed significantly increased Sost mRNA(100-fold) and sclerostin protein, a negative regulator of bone formation(5000-fold), compared to cells in control media. mRNA expression of osteoblast markers such as Osx, Ocn and Col1a1 was unaffected by glucose. Factors associated with osteoclast activation were affected by glucose, with Rankl being upregulated by low glucose. Opg was also transiently upregulated by high glucose in mature IDG-SW3 cells. Induction of diabetes in Sprague-Dawley rats via a single dose of STZ (70 mg/kg) resulted in elevated maximum glucose and increased variability compared to control animals (670/796 vs. 102/142 mg/dL). This was accompanied by increased Sost/sclerostin expression in the osteocytes of these animals. These results show that glucose levels directly regulate osteocyte function through sclerostin expression and suggest a potential mechanism for the negative impact of diabetes on bone quality.
Ontology-based prediction of cancer driver genes
Authors: Althubaiti Sara , Karwath Andreas , Dallol Ashraf , Noor Adeeb , Alkhayyat Shadi Salem , Alwassia Rolina , Mineta Katsuhiko , Gojobori Takashi , Beggs Andrew D. , Schofield Paul N. , Gkoutos Georgios V. , Hoehndorf Robert 
Published: November 2019

AbstractIdentifying and distinguishing cancer driver genes among thousands of candidate mutations remains a major challenge. Accurate identification of driver genes and driver mutations is critical for advancing cancer research and personalizing treatment based on accurate stratification of patients. Due to inter-tumor genetic heterogeneity many driver mutations within a gene occur at low frequencies, which make it challenging to distinguish them from non-driver mutations. We have developed a novel method for identifying cancer driver genes. Our approach utilizes multiple complementary types of information, specifically cellular phenotypes, cellular locations, functions, and whole body physiological phenotypes as features. We demonstrate that our method can accurately identify known cancer driver genes and distinguish between their role in different types of cancer. In addition to confirming known driver genes, we identify several novel candidate driver genes. We demonstrate the utility of our method by validating its predictions in nasopharyngeal cancer and colorectal cancer using whole exome and whole genome sequencing.
Southeastern China Boreal Winter Precipitation Anomalies are Dependent on Intensity of El Niño
Authors: Ke Zongjian , Jiang Xingwen , Wang Zunya 
Published: November 2019

AbstractPrevious studies reported that boreal winter precipitation in southeastern China (SEC) tends to increase during El Niño. In this study, however, we find that most weak El Niño events are accompanied by below-normal precipitation in SEC, although strong El Niño events are accompanied by above-normal precipitation in SEC for both eastern Pacific El Niño and central Pacific El Niño. Both the cold SST anomalies in the western North Pacific (WNP) and the warm SST anomalies in the central tropical Pacific are important for the formation of anomalous anticyclone over the WNP, which favors above-normal precipitation over SEC by transporting more water vapor to SEC. The cold SST anomalies in the WNP only excite a weak anomalous anticyclone locally when the weak warm SST anomalies in the central tropical Pacific are accompanied by weak enhanced convection anomalies. In such condition, El Niño does not affect precipitation in SEC apparently.
Membrane-bound Gaussia luciferase as a tool to track shedding of membrane proteins from the surface of extracellular vesicles
Authors: Zaborowski Mikołaj Piotr , Cheah Pike See , Zhang Xuan , Bushko Isabella , Lee Kyungheon , Sammarco Alessandro , Zappulli Valentina , Maas Sybren Lein Nikola , Allen Ryan M. , Rumde Purva , György Bence , Aufiero Massimo , Schweiger Markus W. , Lai Charles Pin- Kuang , Weissleder Ralph , Lee Hakho , Vickers Kasey C. , Tannous Bakhos A. , Breakefield Xandra O. 
Published: November 2019

AbstractExtracellular vesicles (EVs) released by cells play a role in intercellular communication. Reporter and targeting proteins can be modified and exposed on the surface of EVs to investigate their half-life and biodistribution. A characterization of membrane-bound Gaussia luciferase (mbGluc) revealed that its signal was detected also in a form smaller than common EVs (<70 nm). We demonstrated that mbGluc initially exposed on the surface of EVs, likely undergoes proteolytic cleavage and processed fragments of the protein are released into the extracellular space in active form. Based on this observation, we developed a new assay to quantitatively track shedding of membrane proteins from the surface of EVs. We used this assay to show that ectodomain shedding in EVs is continuous and is mediated by specific proteases, e.g. metalloproteinases. Here, we present a novel tool to study membrane protein cleavage and release using both in vitro and in vivo models.
Recent Increase in Winter Hazy Days over Central India and the Arabian Sea
Authors: Thomas Abin , Sarangi Chandan , Kanawade Vijay P. 
Published: November 2019

AbstractIndian subcontinent is greatly vulnerable to air pollution, especially during the winter season. Here, we use 15 years (2003–2017) of satellite and model reanalysis datasets over India and adjoining Seas to estimate the trend in hazy days (i.e. days with high aerosol loading) during the dry winter season (November to February). The number of hazy days is increasing at the rate of ~2.6 days per year over Central India. Interestingly, this is higher than over the Indo-Gangetic Plain (~1.7 days/year), a well known global hotspot of particulate pollution. Consistent increasing trends in absorbing aerosols are also visible in the recent years. As a result, the estimated atmospheric warming trends over Central India are two-fold higher than that over Indo-Gangetic Plain. This anomalous increment in hazy days over Central India is associated with the relatively higher increase in biomass burning over the region. Moreover, the trend in aerosol loading over the Arabian Sea, which is located downwind to Central India, is also higher than that over the Bay of Bengal during the dry winter season. Our findings not only draw attention to the rapid deteriorating air quality over Central India, but also underline the significance of increasing biomass burning under the recent climate change.
Risk of Venous Thromboembolism after New Onset Heart Failure
Authors: Smilowitz Nathaniel R. , Zhao Qi , Wang Li , Shrestha Sulena , Baser Onur , Berger Jeffrey S. 
Published: November 2019

AbstractNew-onset heart failure (HF) is associated with cardiovascular morbidity and mortality. It is uncertain to what extent HF confers an increased risk of venous thromboembolism (VTE). Adults ≥65 years old hospitalized with a new diagnosis of HF were identified from Medicare claims from 2007–2013. We identified the incidence, predictors and outcomes of VTE in HF. We compared VTE incidence during follow-up after HF hospitalization with a corresponding period 1-year prior to the HF diagnosis. Among 207,535 patients with a new HF diagnosis, the cumulative incidence of VTE was 1.4%, 2.5%, and 10.5% at 30 days, 1 year, and 5 years, respectively. The odds of VTE were greatest immediately after new-onset HF and steadily declined over time (OR 2.2 [95% CI 2.0–2.3], OR 1.5 [1.4–1.7], and OR 1.2 [1.2–1.3] at 0–30 days, 4–6 months, and 7–9 months, respectively). Over 26-month follow-up, patients with HF were at two-fold higher risk of VTE than patients without HF (adjusted HR 2.31 [2.18–2.45]). VTE during follow-up was associated with long-term mortality (adjusted HR 1.60, 95% CI 1.56–1.64). In conclusion, patients with HF are at increased risk of VTE early after a new HF diagnosis. VTE in patients with HF is associated with long-term mortality.
Engineering dual-glycan responsive expression systems for tunable production of heterologous proteins in Bacteroides thetaiotaomicron
Authors: Jones Darryl R. , Smith Marshall B. , McLean Richard , Grondin Julie M. , Amundsen Carolyn R. , Inglis G. Douglas , Selinger Brent , Abbott D. Wade 
Published: November 2019

AbstractGenetically engineering intestinal bacteria, such as Bacteroides thetaiotaomicron (B. theta), holds potential for creating new classes of biological devices, such as diagnostics or therapeutic delivery systems. Here, we have developed a series of B. theta strains that produce functional transgenic enzymes in response to dextran and arabinogalactan, two chemically distinct glycans. Expression systems for single glycan induction, and a novel “dual-glycan” expression system, requiring the presence of both dextran and arabinogalactan, have been developed. In addition, we have created two different chromosomal integration systems and one episomal vector system, compatible with engineered recipient strains, to improve the throughput and flexibility of gene cloning, integration, and expression in B. theta. To monitor activity, we have demonstrated the functionality of two different transgenic enzymes: NanoLuc, a luciferase, and BuGH16C, an agarase from the human intestinal bacterium, Bacteroides uniforms NP1. Together this expression platform provides a new collection of glycan-responsive tools to improve the strength and fidelity of transgene expression in B. theta and provides proof-of-concept for engineering more complex multi-glycan expression systems.
Microvolt T-wave alternans at the end of surgery is associated with postoperative mortality in cardiac surgery patients
Authors: Koo Chang-Hoon , Lee Hyung-Chul , Kim Tae Kyong , Cho Youn Joung , Nam Karam , Choi Eue-Keun , Choi Sheung-Nyoung , Yoon Sehee , Jeon Yunseok 
Published: November 2019

AbstractMicrovolt T-wave alternans (MTWA), which reflects electrical dispersion of repolarization, is known to be associated with arrhythmia or sudden cardiac death in high risk patients. In this study we investigated the relationship between MTWA and postoperative mortality in 330 cardiac surgery patients. Electrocardiogram, official national data and electric chart were analysed to provide in-hospital and mid-term outcome. MTWA at the end of surgery was significantly associated with in-hospital mortality in both univariate analysis (OR = 27.378, 95% CI 5.616–133.466, p < 0.001) and multivariate analysis (OR = 59.225, 95% CI 6.061–578.748, p < 0.001). Cox proportional hazards model revealed MTWA at the end of surgery was independently associated with mid-term mortality (HR = 4.337, 95% CI 1.594–11.795). The area under the curve of the model evaluating MTWA at the end of surgery was 0.764 (95% CI, 0.715–0.809) and it increased to 0.929 (95% CI, 0.896–0.954) when combined with the EuroSCORE II. MTWA positive at the end of surgery had a 60-fold increase in in-hospital mortality and a 4-fold increase in mid-term mortality. Moreover, MTWA at the end of surgery could predict in-hospital mortality and this predictability is more robust when combined with the EuroSCORE II.
Preoperative CT texture features predict prognosis after curative resection in pancreatic cancer
Authors: Kim Hyung Sun , Kim Young Jae , Kim Kwang Gi , Park Joon Seong 
Published: November 2019

AbstractPancreatic cancer is a lethal disease, and resistance to chemotherapy is a critical factor influencing the postoperative prognosis. Tumour heterogeneity is an important indicator of chemoresistance. Therefore, we analysed tumour heterogeneity in preoperative computed tomography scans by performing texture analysis using the grey-level run-length matrix and analysed the correlation of survival with the value obtained in these analyses. We analysed 116 consecutive patients who underwent curative resection and had preoperative contrast-enhanced computed tomography data available for analysis. A region of interest was drawn on all slices with a visible tumour and normal pancreas on the arterial phase computed tomography scans; the correlation of pathological characteristics with grey-level run-length matrix features was analysed. We then performed Kaplan–Meier survival curve analysis among pancreatic cancer patients. The grey-level non-uniformity values in grey-level run-length matrix features for tumours were higher than those for normal pancreas. High grey-level non-uniformity values represent a non-uniform texture, i.e., heterogeneity. Grey-level run-length matrix features showed that recurrence-free survival was shorter in the group with high grey-level non-uniformity 135 values (p = 0.025). Our analyses of the correlation between pathological outcomes and grey-level run-length matrix features in pancreatic cancer patients showed that grey-level non-uniformity values were powerful prognostic indicators.
A new model isolates glioblastoma clonal interactions and reveals unexpected modes for regulating motility, proliferation, and drug resistance
Authors: Davis Justin B , Krishna Sreshta S , Abi Jomaa Ryan , Duong Cindy T. , Espina Virginia , Liotta Lance A , Mueller Claudius 
Published: November 2019

AbstractTumor clonal heterogeneity drives treatment resistance. But robust models are lacking that permit eavesdropping on the basic interaction network of tumor clones. We developed an in vitro, functional model of clonal cooperation using U87MG glioblastoma cells, which isolates fundamental clonal interactions. In this model pre-labeled clones are co-cultured to track changes in their individual motility, growth, and drug resistance behavior while mixed. This highly reproducible system allowed us to address a new class of fundamental questions about clonal interactions. We demonstrate that (i) a single clone can switch off the motility of the entire multiclonal U87MG cell line in 3D culture, (ii) maintenance of clonal heterogeneity is an intrinsic and influential cancer cell property, where clones coordinate growth rates to protect slow growing clones, and (iii) two drug sensitive clones can develop resistance de novo when cooperating. Furthermore, clonal communication for these specific types of interaction did not require diffusible factors, but appears to depend on cell-cell contact. This model constitutes a straightforward but highly reliable tool for isolating the complex clonal interactions that make up the fundamental “hive mind” of the tumor. It uniquely exposes clonal interactions for future pharmacological and biochemical studies.
Low-frequency oscillations in coupled phase oscillators with inertia
Authors: Song Huihui , Zhang Xuewei , Wu Jinjie , Qu Yanbin 
Published: November 2019

AbstractThis work considers a second-order Kuramoto oscillator network periodically driven at one node to model low-frequency forced oscillations in power grids. The phase fluctuation magnitude at each node and the disturbance propagation in the network are numerically analyzed. The coupling strengths in this work are sufficiently large to ensure the stability of equilibria in the unforced system. It is found that the phase fluctuation is primarily determined by the network structural properties and forcing parameters, not the parameters specific to individual nodes such as power and damping. A new “resonance” phenomenon is observed in which the phase fluctuation magnitudes peak at certain critical coupling strength in the forced system. In the cases of long chain and ring-shaped networks, the Kuramoto model yields an important but somehow counter-intuitive result that the fluctuation magnitude distribution does not necessarily follow a simple attenuating trend along the propagation path and the fluctuation at nodes far from the disturbance source could be stronger than that at the source. These findings are relevant to low-frequency forced oscillations in power grids and will help advance the understanding of their dynamics and mechanisms and improve the detection and mitigation techniques.
When and where mortality occurs throughout the annual cycle changes with age in a migratory bird: individual vs population implications
Authors: Sergio Fabrizio , Tavecchia Giacomo , Tanferna Alessandro , Blas Julio , Blanco Guillermo , Hiraldo Fernando 
Published: November 2019

AbstractThe annual cycle of most animals is structured into discrete stages, such as breeding, migration and dispersal. While there is growing appreciation of the importance of different stages of an organism’s annual cycle for its fitness and population dynamics, almost nothing is known about if and how such seasonal effects can change through a species lifespan. Here, we take advantage of the opportunity offered by a long-term satellite/GPS-tracking study and a reliable method of remote death-detection to show that certain stages of both the annual and life cycle of a migratory long-lived raptor, the Black kite Milvus migrans, may represent sensitive bottlenecks for survival. In particular, migratory journeys caused bursts of concentrated-mortality throughout life, but the relative importance of stage-specific survival changed with age. On the other hand, the balance between short-stages of high mortality and long-stages of low mortality made population-growth similarly dependent on all portions of the annual cycle. Our results illustrate how the population dynamics of migratory organisms can be inextricably linked to ecological pressures balanced over multiple stages of the annual cycle and thus multiple areas of the globe, suggesting the frequent need for challenging conservation strategies targeting all portions of a species year-round range.
Transcriptome analysis of differential gene expression in the longissimus dorsi muscle from Debao and landrace pigs based on RNA-sequencing
Authors: Song Shang-Qiao , Ma Wei-wei , Zeng Su-Xian , Zhang Chao-Long , Yan Jin , Sun Cui-Cui , Li Xin , Wang Rui-Min , Li Zong-Qiang 
Published: November 2019

Abstract
RNA-seq analysis was used to identify differentially expressed genes (DEGs) at the genetic level in the longissimus dorsi muscle from two pigs to investigate the genetic mechanisms underlying the difference in meat quality between Debao pigs and Landrace pigs. Then, these DEGs underwent functional annotation, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and protein–protein interaction (PPI) analyses. Finally, the expression levels of specific DEGs were assessed using qRT-PCR. The reference genome showed gene dosage detection of all samples which showed that the total reference genome comprised 22342 coding genes, including 14743 known and 190 unknown genes. For detection of the Debao pig genome, we obtained 14168 genes, including 13994 known and 174 unknown genes. For detection of the Landrace pig genome, we obtained 14404 genes, including 14223 known and 181 unknown genes. GO analysis and KEGG signaling pathway analysis show that DEGs are significantly related to metabolic regulation, amino acid metabolism, muscular tissue, muscle structure development etc. We identified key genes in these processes, such as FOS, EGR2, and IL6, by PPI network analysis. qRT-PCR confirmed the differential expression of six selected DEGs in both pig breeds. In conclusion, the present study revealed key genes and related signaling pathways that influence the difference in pork quality between these breeds and could provide a theoretical basis for improving pork quality in future genetic thremmatology.