Miracle-dz/UniFAR-FTUs huggingface dataset:
FRS2 via Fibroblast Growth Factor Receptor 1 Is Required for Platelet-derived Growth Factor Receptor β-mediated Regulation of Vascular Smooth Muscle Marker Gene Expression*

Vascular smooth muscle cells (VSMC) exhibit phenotypic plasticity and change from a quiescent contractile phenotype to a proliferative synthetic phenotype during physiological arteriogenesis and pathological conditions such as atherosclerosis and restenosis. Platelet-derived growth factor (PDGF)-BB is a potent inducer of the VSMC synthetic phenotype; however, much less is known about the role of fibroblast growth factor-2 (FGF2) in this process. Here, we show using signal transduction mutants of FGF receptor 1 (FGFR1) expressed in rat VSMC that the adaptor protein FRS2 is essential for FGFR1-mediated phenotypic modulation and down-regulation of VSMC smooth muscle α-actin (SMA) gene expression. In addition, we show that PDGF-BB and FGF2 act synergistically to induce cell proliferation and down-regulate SMA and SM22α in VSMC. Furthermore, we show that PDGF-BB induces tyrosine phosphorylation of FGFR1 and that this phosphorylation is mediated by PDGF receptor-β (PDGFRβ), but not c-Src. We demonstrate that FRS2 co-immunoprecipitates with PDGFRβ in a complex that requires FGFR1 and that both the extracellular and the intracellular domains of FGFR1 are required for association with PDGFRβ, whereas the cytoplasmic domain of FGFR1 is required for FRS2 association with the FGFR1-PDGFRβ complex. Knockdown of FRS2 in VSMC by RNA interference inhibited PDGF-BB-mediated down-regulation of SMA and SM22α without affecting PDGF-BB mediated cell proliferation or ERK activation. Together, these data support the notion that PDGFRβ down-regulates SMA and SM22α through formation of a complex that requires FGFR1 and FRS2 and prove novel insight into VSMC phenotypic plasticity.
Long-Term Consumption of Cuban Policosanol Lowers Central and Brachial Blood Pressure and Improves Lipid Profile With Enhancement of Lipoprotein Properties in Healthy Korean Participants

Metabolic syndrome is closely associated with higher risk of hypertension, cardiovascular disease (CVD), diabetes and stroke. The aim of the present study was to investigate the long-term effects of policosanol supplementation on blood pressure (BP) and the lipid profile in healthy Korean participants with pre-hypertension (systolic 120–139 mmHg, diastolic 85–89 mmHg). This randomized, double-blinded, and placebo-controlled trial included 84 healthy participants who were randomly assigned to three groups receiving 10 mg of policosanol, 20 mg of policosanol, or placebo for 24 weeks. The BP, lipid profile, and anthropometric factors were measured pre- and post-intervention and then compared. Based on an average of three measurements of brachial BP, the policosanol 20 mg group showed the most significant reduction in average systolic BP (SBP) from 138 ± 12 mmHg at week 0 to 126 ± 13 mmHg at week 24 (p < 0.0001). The policosanol 20 mg group also showed significant reductions in aortic SBP and DBP up to 9% (p = 0.00057) and 8% (p = 0.004), respectively compared with week 0. Additionally, blood renin and aldosterone levels were significantly reduced in the policosanol 20 mg group up to 63% (p < 0.01) and 42% (p < 0.05), respectively, at week 24. For the blood lipid profile, the policosanol 10 mg and 20 mg groups showed significant reductions in total cholesterol (TC) of around 8% (p = 0.029) and 13% (p = 0.0004), respectively, at week 24 compared with week 0. Serum HDL-C level significantly increased up to 16% and 12% in the policosanol 10 mg (p = 0.002) and 20 mg (p = 0.035) group, respectively. The study results suggest that long-term policosanol consumption simultaneously reduces peripheral BP as well as aortic BP accompanied by elevation of HDL-C and % HDL-C in TC in a dose-dependent manner.
Morphological, Structural, Thermal And Degradation Properties Of Polylactic Acid-Waxy Maize Starch Nanocrystals Based Nanocomposites Prepared By Melt Processing

Currently used petroleum-based polymers have adversely affected the environment in various ways, mainly due to their non-biodegradability. This undesirable aspect of commercial polymers led to increased interest in the research area of biodegradable polymer nanocomposites. Polylactic acid (PLA) based nanocomposites, with three different loadings of waxy maize starch nanocrystals (WSNC) as nanofiller (1, 3 and 5 wt%), were melt-blended in a Haake Rheomix. The morphological, structural, thermal and abiotic degradation characteristics of the prepared PLA WSNC nanocomposites were studied to determine the effects of adding WSNC at different loadings in PLA. The results indicated that WSNC were dispersed uniformly at lower loadings (0-3 wt%) and agglomerated at higher loadings (5 wt%) within the PLA matrix. All PLA-WSNC nanocomposites were found to be stable over the processing temperature range of 25-220 oC. In addition, there was no considerable change in the glass transition temperature and the melting point of the nanocomposites. Though, the cold crystallization temperature was reduced with the increase of WSNC loadings. The abiotic degradation studies, used as an initial screening tool, indicated that WSNC can accelerate the degradation process of PLA. As a result, the degradation rate was improved for all the PLA-WSNC nanocomposites. The PLA-WSNC-3 wt% was found to be the optimum concentration to enhance the crystallinity and morphological property of PLA, and beyond that the properties were affected by agglomeration.
Viruses Infecting Reptiles

A large number of viruses have been described in many different reptiles. These viruses include arboviruses that primarily infect mammals or birds as well as viruses that are specific for reptiles. Interest in arboviruses infecting reptiles has mainly focused on the role reptiles may play in the epidemiology of these viruses, especially over winter. Interest in reptile specific viruses has concentrated on both their importance for reptile medicine as well as virus taxonomy and evolution. The impact of many viral infections on reptile health is not known. Koch’s postulates have only been fulfilled for a limited number of reptilian viruses. As diagnostic testing becomes more sensitive, multiple infections with various viruses and other infectious agents are also being detected. In most cases the interactions between these different agents are not known. This review provides an update on viruses described in reptiles, the animal species in which they have been detected, and what is known about their taxonomic positions.
The dysexecutive syndrome of Alzheimer's disease: the GREFEX study.

BACKGROUND Dysexecutive disorders are common in early-stage Alzheimer's disease (AD) but have yet to be characterized in detail. OBJECTIVE The objectives of the present study based on validated diagnostic criteria were to determine the frequency and characterize the profile of behavioral and cognitive dysexecutive disorders in AD. METHODS 102 patients with AD (mild: n = 92; moderate: n = 10; mean MMSE score: 23.2) were examined with the GREFEX battery. Neuropsychological data were interpreted within a validated framework based on the performance levels of 780 control participants from the GREFEX study. RESULTS Dysexecutive syndrome was observed in 87.5% (95%CI: 79-96) of the AD patients (p = 0.0001). The dysexecutive disorder profile was characterized by prominent impairments of planning, inhibition flexibility and generation in the cognitive domain (p = 0.0001 as compared to controls for all) and global hypoactivity in the behavioral domain (p = 0.0001 as compared to controls). CONCLUSIONS Dysexecutive syndrome is observed in over 80% of AD patients and has a distinct profile.
Cesarean delivery and risk of inflammatory bowel disease: a systematic review and meta-analysis

Abstract Objective. It has been considered that cesarean delivery is a risk factor for the two subtypes of inflammatory bowel diseases (IBDs): Crohn’s disease (CD) and ulcerative colitis (UC). The aim of this meta-analysis was to examine the relationship between cesarean delivery and the development of IBD. Material and methods. We searched the articles retrieved by PubMed, MEDLINE and EMBASE databases to identify observational studies regarding the relationship between cesarean section and the development of CD and/or UC. Pooled odds ratios were calculated for each relationship. Results. Nine studies evaluated the potential association between cesarean delivery and the development of IBD and met all of our inclusion criteria. The pooled data from six included studies indicated cesarean delivery was a risk factor for CD (95% confidence interval [CI]: 1.12–1.70; p = 0.003). Likewise, we observed a positive association between cesarean delivery and pediatric CD (95% CI: 1.06–1.35; p = 0.005). However, results from the four included studies for UC indicated the rate of cesarean section in UC patients was not higher than that of control subjects (95% CI: 0.87–1.32; p = 0.54). Overall, we did not observe a positive relationship between cesarean delivery and IBD (95% CI: 0.99–1.30; p = 0.08). Conclusion. Results of this meta-analysis support the hypothesis that cesarean delivery was associated with the risk of CD but not of UC. The total rate of cesarean delivery of IBD patients was similar with that of control subjects.
Long-Term Monitoring of Field Trial Sites with Genetically Modified Oilseed Rape (Brassica napus L.) in Saxony-Anhalt, Germany. Fifteen Years Persistence to Date but No Spatial Dispersion

Oilseed rape is known to persist in arable fields because of its ability to develop secondary seed dormancy in certain agronomic and environmental conditions. If conditions change, rapeseeds are able to germinate up to 10 years later to build volunteers in ensuing crops. Extrapolations of experimental data acted on the assumption of persistence periods for more than 20 years after last harvest of rapeseed. Genetically-modified oilseed rape—cultivated widely in Northern America since 1996—is assumed not to differ from its conventional form in this property. Here, experimental data are reported from official monitoring activities that verify these assumptions. At two former field trial sites in Saxony-Anhalt genetically-modified herbicide-resistant oilseed rape volunteers are found up to fifteen years after harvest. Nevertheless, spatial dispersion or establishment of GM plants outside of the field sites was not observed within this period.
Sentences in the Brain: Event-Related Potentials as Real-Time Reflections of Sentence Comprehension and Language Learning

From the perspective of a person trying to understand a sentence, language is a continuous flow of information distributed over time. Somehow, the listener translates this stream of information into discrete and rapidly sequenced units of sound, meaning, and structure, and does so in real time, that is, nearly instantaneously. The results of these complex analyses are then integrated into a single coherent interpretation, even in the presence of considerable ambiguity. The challenge facing us is to account for how people accomplish this. Asking the listener or reader for an answer to this question provides little useful information; the relevant processes are not generally available to conscious reflection. We must therefore rely on other methods of investigation. One might surmise that the ideal method would mirror the properties of comprehension itself (Osterhout, McLaughlin, & Bersick, 1997). The ideal method should provide continuous measurement throughout the process of understanding a sentence, have a temporal resolution exceeding that of the relevant processes, and be differentially sensitive to events occurring at different levels of analysis (phonological, syntactic, semantic, etc.). Furthermore, language comprehension is clearly a function of the human brain. Theoretical accounts of some of the most fundamental questions about human language (e.g., the ability of children to acquire language, and the effects of age on language-learning ability) rely explicitly on biological explanations. Compelling tests of these hypotheses necessarily require biological measurement. For these and other reasons, the ideal method should also provide a means for relating the obtained data to brain function.
Crosstalk between Bile Acids and Gut Microbiota and Its Impact on Farnesoid X Receptor Signalling

Background: The gut microbiota has a substantial impact on health and disease. The human gut microbiota influences the development and progression of metabolic diseases; however, the underlying mechanisms are not fully understood. The nuclear farnesoid X receptor (FXR), which regulates bile acid homeostasis and glucose and lipid metabolism, is activated by primary human and murine bile acids, chenodeoxycholic acid and cholic acid, while rodent specific primary bile acids tauromuricholic acids antagonise FXR activation. The gut microbiota deconjugates and subsequently metabolises primary bile acids into secondary bile acids in the gut and thereby changes FXR activation and signalling. Key Message: Mouse models have been used to study the crosstalk between bile acids and the gut microbiota, but the substantial differences in bile acid composition between humans and mice need to be considered when interpreting data from such studies and for the development of so-called humanised mouse models. Conclusion: It is of special importance to elucidate how a human gut microbiota influences bile acid composition and FXR signalling in colonised mice.
Institutional-based tumor registry of hematopoietic malignancies: A 4 years' preliminary report from Karachi

ABSTRACT BACKGROUND: Pakistan has a population of over 198 million making it the world’s sixth populous country. However, operational population-based cancer registries in Pakistan are lacking. Limited data are available based on institutional or Karachi Cancer Registry from Karachi; however, no exclusive registry for hematological malignancies is established till date. Hence, we decided to conduct a database analysis to determine the frequencies of various hematological cancers in our tertiary care center in Karachi. PATIENTS AND METHODS: Retrospective assessment of 366 patients presented to Hematology Department, Liaquat National Hospital and Medical College from May 2012 to May 2016 with confirmed diagnosis of hematological cancers was performed. Data were retrieved from hospital-based tumor registry. All pro forma was filled by qualified medical research officer, which included demographic data as age, gender, history, disease type, and its stage at presentation. RESULTS: Male gender was predominant and accounted for 69.9% (n = 256) and female accounted for 30.0% (n = 110) of the total cases with the male-to-female ratio of ~2:1. The mean ages of female and male patients were 42.9 ± 20.7 and 49.7 ± 18.1 years with the median age of 45 and 51.5 years, respectively. In males, the three most frequent malignancies were chronic myeloid leukemia (CML) (16%), acute lymphoblastic leukemia (ALL), and acute myeloid leukemia (AML) (12.8% of each). In females, AML was the most common cancer accounting for 21.8% followed by CML (18.1%) and ALL (10%). CONCLUSIONS: Our institution-based tumor registry indicates CML and AML were the most common cancers in males and females, respectively, followed by ALL. Chronic lymphoid leukemia, unlike in the West, is seen infrequently in our population. National and provisional hematological tumor registry will be beneficial for future health planning and research.
Approximation Vector Machines for Large-scale Online Learning

One of the most challenging problems in kernel online learning is to bound the model size and to promote the model sparsity. Sparse models not only improve computation and memory usage, but also enhance the generalization capacity, a principle that concurs with the law of parsimony. However, inappropriate sparsity modeling may also significantly degrade the performance. In this paper, we propose Approximation Vector Machine (AVM), a model that can simultaneously encourage the sparsity and safeguard its risk in compromising the performance. When an incoming instance arrives, we approximate this instance by one of its neighbors whose distance to it is less than a predefined threshold. Our key intuition is that since the newly seen instance is expressed by its nearby neighbor the optimal performance can be analytically formulated and maintained. We develop theoretical foundations to support this intuition and further establish an analysis to characterize the gap between the approximation and optimal solutions. This gap crucially depends on the frequency of approximation and the predefined threshold. We perform the convergence analysis for a wide spectrum of loss functions including Hinge, smooth Hinge, and Logistic for classification task, and $l_1$, $l_2$, and $\epsilon$-insensitive for regression task. We conducted extensive experiments for classification task in batch and online modes, and regression task in online mode over several benchmark datasets. The results show that our proposed AVM achieved a comparable predictive performance with current state-of-the-art methods while simultaneously achieving significant computational speed-up due to the ability of the proposed AVM in maintaining the model size.
Targeting GLI Transcription Factors in Cancer

Aberrant activation of hedgehog (Hh) signaling has been observed in a wide variety of tumors and accounts for more than 25% of human cancer deaths. Inhibitors targeting the Hh signal transducer Smoothened (SMO) are widely used and display a good initial efficacy in patients suffering from basal cell carcinoma (BCC); however, a large number of patients relapse. Though SMO mutations may explain acquired therapy resistance, a growing body of evidence suggests that the non-canonical, SMO-independent activation of the Hh pathway in BCC patients can also account for this adverse effect. In this review, we highlight the importance of glioma-associated oncogene (GLI) transcription factors (the main downstream effectors of the canonical and the non-canonical Hh cascade) and their putative role in the regulation of multiple oncogenic signaling pathways. Moreover, we discuss the contribution of the Hh signaling to malignant transformation and propose GLIs as central hubs in tumor signaling networks and thus attractive molecular targets in anti-cancer therapies.
Chemical Imaging of Poplar Wood Cell Walls by Confocal Raman Microscopy

Confocal Raman microscopy was used to illustrate changes of molecular composition in secondary plant cell wall tissues of poplar (Populus nigra × Populus deltoids) wood. Two-dimensional spectral maps were acquired and chemical images calculated by integrating the intensity of characteristic spectral bands. This enabled direct visualization of the spatial variation of the lignin content without any chemical treatment or staining of the cell wall. A small (0.5 μm) lignified border toward the lumen was observed in the gelatinous layer of poplar tension wood. The variable orientation of the cellulose was also characterized, leading to visualization of the S1 layer with dimensions smaller than 0.5 μm. Scanning Raman microscopy was thus shown to be a powerful, nondestructive tool for imaging changes in molecular cell wall organization with high spatial resolution.
Improved Volitional Recall of Motor-Imagery-Related Brain Activation Patterns Using Real-Time Functional MRI-Based Neurofeedback

Motor imagery (MI), a covert cognitive process where an action is mentally simulated but not actually performed, could be used as an effective neurorehabilitation tool for motor function improvement or recovery. Recent approaches employing brain–computer/brain–machine interfaces to provide online feedback of the MI during rehabilitation training have promising rehabilitation outcomes. In this study, we examined whether participants could volitionally recall MI-related brain activation patterns when guided using neurofeedback (NF) during training. The participants’ performance was compared to that without NF. We hypothesized that participants would be able to consistently generate the relevant activation pattern associated with the MI task during training with NF compared to that without NF. To assess activation consistency, we used the performance of classifiers trained to discriminate MI-related brain activation patterns. Our results showed significantly higher predictive values of MI-related activation patterns during training with NF. Additionally, this improvement in the classification performance tends to be associated with the activation of middle temporal gyrus/inferior occipital gyrus, a region associated with visual motion processing, suggesting the importance of performance monitoring during MI task training. Taken together, these findings suggest that the efficacy of MI training, in terms of generating consistent brain activation patterns relevant to the task, can be enhanced by using NF as a mechanism to enable participants to volitionally recall task-related brain activation patterns.
Problematic Social Support From Patients’ Perspective: The Case of Systemic Lupus Erythematosus

Several studies demonstrated the importance of psychosocial factors, like social support, for understanding the experience of people with Systemic Lupus Erythematosus (SLE). Less information is available on “problematic support”; that is, instances of support that are perceived as non-supportive, even though the provider’s actions may be well intended. Aim of this qualitative study was to explore the experiences of problematic support from SLE patients’ perspective. Nine women with SLE were interviewed and transcripts were analyzed through qualitative content analysis. Three main types of problematic social support were indentified. Oppressive support describes social support offers characterized by excessive worries and unwanted advices. Support denying the illness is characterized by a neglect of the disease or of its consequences. Support based on divergent illness representations is perceived as not punctual and not in line with patients’ actual clinical condition. This study confirms the complexity of providing useful support to SLE patients and suggest that also people living close to patients should represent a target of interventions.
EB1 promotes Aurora-B kinase activity through blocking its inactivation by protein phosphatase 2A

EB1 (end-binding protein 1) is a key player in the regulation of microtubule dynamics. In concert with its binding partners, adenomatous polyposis coli and p150glued, EB1 plays a crucial role in a variety of microtubule-based cellular processes. In this study we have identified in a yeast two-hybrid screen the mitotic kinase and chromosome passenger protein Aurora-B as a binding partner of EB1. GST pull-down and immunoprecipitation experiments reveal a specific interaction between Aurora-B and EB1 both in cells and in vitro. Immunofluorescence microscopy shows that these two proteins colocalize on the central spindle in anaphase and in the midbody during cytokinesis. Kinase assays using both immunoprecipitated and purified Aurora-B demonstrate that EB1 is not a substrate of Aurora-B. Rather, EB1 positively regulates Aurora-B kinase activity. EB1 overexpression remarkably enhances Aurora-B activity and knockdown of its expression impairs Aurora-B activity. Our data further show that EB1 is able to protect Aurora-B from dephosphorylation/inactivation by protein phosphatase 2A (PP2A) by blocking PP2A binding to Aurora-B. These findings establish Aurora-B as an EB1-interacting protein and suggest that EB1 stimulates Aurora-B activity through antagonizing its dephosphorylation/inactivation by PP2A.