Miracle-dz/UniFAR-FTUs huggingface dataset:
KIT (CD117): A Review on Expression in Normal and Neoplastic Tissues, and Mutations and Their Clinicopathologic Correlation

CD117 (KIT) is a type III receptor tyrosine kinase operating in cell signal transduction in several cell types. Normally KIT is activated (phosphorylated) by binding of its ligand, the stem cell factor. This leads to a phosphorylation cascade ultimately activating various transcription factors in different cell types. Such activation regulates apoptosis, cell differentiation, proliferation, chemotaxis, and cell adhesion. KIT-dependent cell types include mast cells, some hematopoietic stem cells, germ cells, melanocytes, and Cajal cells of the gastrointestinal tract, and neoplasms of these cells are examples of KIT-positive tumors. Other KIT-positive normal cells include epithelial cells in skin adnexa, breast, and subsets of cerebellar neurons. KIT positivity has been variably reported in sarcomas such as angiosarcoma, Ewing sarcoma, synovial sarcoma, leiomyosarcoma, and MFH; results of the last three are controversial. The variations in published data may result from incomplete specificity of some polyclonal antibodies, possibly contributed by too high dilutions. Also, KIT is expressed in pulmonary and other small cell carcinomas, adenoid cystic carcinoma, renal chromophobe carcinoma, thymic, and some ovarian and few breast carcinomas. A good KIT antibody reacts with known KIT positive cells, and smooth muscle cells and fibroblasts are negative. KIT deficiency due to hereditary nonsense/missense mutations leads to disruption of KIT-dependent functions such as erythropoiesis, skin pigmentation, fertility, and gastrointestinal motility. Conversely, pathologic activation of KIT through gain-of-function mutations leads to neoplasia of KIT-dependent and KIT-positive cell types at least in three different systems: mast cells/myeloid cells-mastocytosis/acute myeloid leukemia, germ cells-seminoma, and Cajal cells-gastrointestinal stromal tumors (GISTs). KIT tyrosine kinase inhibitors such as imatinib mesylate are the generally accepted treatment of metastatic GISTs, and their availability has prompted an active search for other treatment targets among KIT-positive tumors such as myeloid leukemias and small cell carcinoma of the lung, with variable and often nonconvincing results.
FIGalpha, a germ cell-specific transcription factor required for ovarian follicle formation.

Primordial follicles are formed perinatally in mammalian ovaries and at birth represent the lifetime complement of germ cells. With cyclic periodicity, cohorts enter into a growth phase that culminates in ovulation of mature eggs, but little is known about the regulatory cascades that govern these events. FIGalpha, a transcription factor implicated in postnatal oocyte-specific gene expression, is detected as early as embryonic day 13. Mouse lines lacking FIGalpha were established by targeted mutagenesis in embryonic stem cells. Although embryonic gonadogenesis appeared normal, primordial follicles were not formed at birth, and massive depletion of oocytes resulted in shrunken ovaries and female sterility. Fig(&agr;) (the gene for FIGalpha null males have normal fertility. The additional observation that null females do not express Zp1, Zp2 or Zp3 indicates that FIGalpha plays a key regulatory role in the expression of multiple oocyte-specific genes, including those that initiate folliculogenesis and those that encode the zona pellucida required for fertilization and early embryonic survival. The persistence of FIGalpha in adult females suggests that it may regulate additional pathways that are essential for normal ovarian development.
New Directions in Antiplatelet Therapy

Atherosclerosis is a chronic inflammatory process that is known to be the underlying cause of coronary artery disease (CAD). 1 In addition to being the first step of primary hemostasis, platelets play a pivotal role in the thrombotic process that follows rupture, fissure, or erosion of an atherosclerotic plaque.2 Because atherothrombotic events are essentially platelet-driven processes, this underscores the importance of antiplatelet agents, which represent the cornerstone of treatment, particularly in the settings of patients with acute coronary syndromes (ACS) and undergoing percutaneous coronary intervention (PCI). Currently, there are 3 different classes of antiplatelet drugs that are approved for clinical use and recommended per guidelines for the treatment and prevention of ischemic events in the settings of ACS and PCI: (1) cycloxigenase-1 (COX-1) inhibitor: aspirin, (2) adenosine diphosphate (ADP) P2Y12 receptor antagonists: ticlopidine, clopidogrel, prasugrel, and ticagrelor, and (3) glycoprotein IIb/IIIa inhibitors (GPI): abciximab, eptifibatide, and tirofiban.3–6 GPIs currently are available only for parenteral administration, and therefore their use is limited only to the acute phase of treatment of ACS patients undergoing PCI. Oral antiplatelet agents, namely aspirin and P2Y12 receptor inhibitors, are recommended for prevention of ischemic events in both the acute and long-term phases of treatment. For over a decade, dual antiplatelet therapy (DAPT) with aspirin and clopidogrel has been considered the standard of care in the setting of ACS and PCI. However, a considerable number of adverse ischemic events continue to occur with this DAPT regimen, which has led to the development of newer and more potent antiplatelet agents. The objective of the present manuscript is to provide an overview on the most recent advances of currently approved antiplatelet agents in the setting of ACS and PCI, as well as on emerging agents that are in clinical development (Figure 1). Other …
The Decision to Intensify Therapy in Patients with Type 2 Diabetes: Results from an Experiment Using a Clinical Case Vignette

Purpose: Lack of medication intensification is a widely recognized but poorly understood barrier to effective diabetes care. We used a video case vignette to assess whether patient or physician demographic variables influence the decision to intensify therapy. Methods: One hundred ninety-two US primary care physicians each viewed one case vignette of an actor portraying a patient who had type 2 diabetes and borderline indications for medication intensification. Case vignettes were clinically identical and differed only by patient age (35 or 65 years old); sex; race/ethnicity (white, Hispanic, or black); and socioeconomic status (occupation of lawyer or janitor). After viewing the vignette and indicating their management plans, physicians were also asked to discuss the challenges related to managing such a patient. Results: Just over half (53%) of physicians indicated that they would recommend a medication prescription for the vignette patient. Demographic characteristics (of the patient, physician, or practice) did not significantly influence this decision (P > .1 for all comparisons). Compared with physicians who did not recommend a diabetic-related prescription, physicians recommending therapy more often identified patient medication costs (74% vs 43% of physicians who would not increase therapy); medication adherence (63% vs 49%); and subsequent complications (34% vs 22%) as important clinical issues in managing diabetes. Physicians not intensifying therapy more often indicated that they needed more clinical information (16% vs 9%). Conclusions: Using an experimental design we found that differences in the decision to intensify therapy were not significantly explained by patient, physician, or practice demographic variables. Physicians who intensified therapy were more likely to consider issues such as medication costs, patient adherence, and downstream complications.
Smyd1b_tv1, a Key Regulator of Sarcomere Assembly, Is Localized on the M-Line of Skeletal Muscle Fibers

Background Smyd1b is a member of the Smyd family that plays a key role in sarcomere assembly during myofibrillogenesis. Smyd1b encodes two alternatively spliced isoforms, smyd1b_tv1 and smyd1b_tv2, that are expressed in skeletal and cardiac muscles and play a vital role in myofibrillogenesis in skeletal muscles of zebrafish embryos. Methodology/Principal Findings To better understand Smyd1b function in myofibrillogenesis, we analyzed the subcellular localization of Smyd1b_tv1 and Smyd1b_tv2 in transgenic zebrafish expressing a myc-tagged Smyd1b_tv1 or Smyd1b_tv2. The results showed a dynamic change of their subcellular localization during muscle cell differentiation. Smyd1b_tv1 and Smyd1b_tv2 were primarily localized in the cytosol of myoblasts and myotubes at early stage zebrafish embryos. However, in mature myofibers, Smyd1b_tv1, and to a small degree of Smyd1b_tv2, exhibited a sarcomeric localization. Double staining with sarcomeric markers revealed that Smyd1b_tv1was localized on the M-lines. The sarcomeric localization was confirmed in zebrafish embryos expressing the Smyd1b_tv1-GFP or Smyd1b_tv2-GFP fusion proteins. Compared with Smyd1b_tv1, Smyd1b_tv2, however, showed a weak sarcomeric localization. Smyd1b_tv1 differs from Smyd1b_tv2 by a 13 amino acid insertion encoded by exon 5, suggesting that some residues within the 13 aa insertion may be critical for the strong sarcomeric localization of Smyd1b_tv1. Sequence comparison with Smyd1b_tv1 orthologs from other vertebrates revealed several highly conserved residues (Phe223, His224 and Gln226) and two potential phosphorylation sites (Thr221 and Ser225) within the 13 aa insertion. To determine whether these residues are involved in the increased sarcomeric localization of Smyd1b_tv1, we mutated these residues into alanine. Substitution of Phe223 or Ser225 with alanine significantly reduced the sarcomeric localization of Smyd1b_tv1. In contrast, other substitutions had no effect. Moreover, replacing Ser225 with threonine (S225T) retained the strong sarcomeric localization of Smyd1b_tv1. Conclusion/Significance Together, these data indicate that Phe223 and Ser225 are required for the M-line localization of Smyd1b_tv1.
Quantitation of neuropeptides in Cpe(fat)/Cpe(fat) mice using differential isotopic tags and mass spectrometry.

Neuroendocrine peptides play important roles as intercellular messengers. We previously developed a technique to isolate and identify a large number of neuroendocrine peptides from Cpe(fat)/Cpe(fat) mice (Che, F.; et al. Proc. Natl. Acad. Sci. U.S.A. 2001, 98, 9971-6); these mice lack carboxypeptidase E activity and this defect causes an accumulation of neuropeptide intermediates that contain C-terminal Lys or Arg residues (Naggert, J. K.; et al. Nat. Genet. 1995, 10, 135-42). In the present study, we have developed a differential isotopic-labeling technique that can be used to quantitate changes in neuropeptide levels in Cpe(fat)/Cpe(fat) mouse tissues. Samples are treated with either the H6 or the D6 form of acetic anhydride, peptides that contain C-terminal basic amino acids are isolated by affinity chromatography on anhydrotrypsin agarose, and the isolated peptides are analyzed by mass spectrometry. Measurement of the regulation of pituitary peptides in response to dehydration showed a decrease in vasopressin. The general method described in this report should be widely applicable to a large number of neuroendocrine peptides, known and novel, in a variety of regulatory paradigms.
Adaptive Hypergraph Learning for Unsupervised Feature Selection

In this paper, we propose a new unsupervised feature selection method to jointly learn the similarity matrix and conduct both subspace learning (via learning a dynamic hypergraph) and feature selection (via a sparsity constraint). As a result, we reduce the feature dimensions using different methods (i.e., subspace learning and feature selection) from different feature spaces, and thus makes our method select the informative features effectively and robustly. Experimental results show that our proposed method outperforms all the comparison methods in terms of clustering tasks.
Multi-Formalism Modelling and Model Execution

Abstract Modelling complex software systems requires multiple modelling formalisms adapted to the nature of each part of the system (control, signal processing, etc.), to the aspect on which the model focuses (functionality, time, fault tolerance, etc.) and to the level of abstraction at which the system, or one of its parts, is studied. The use of different modelling formalisms during the development cycle is therefore both unavoidable and essential. As a consequence, system designers deal with a large variety of models that relate to a given system but do not form a global model of this system. A major difficulty is then to answer questions about properties of the whole system, and in particular about its behaviour. Multi-Formalism Modelling allows the joint use of different modelling formalisms in a given model to overcome issues related to the integration of heterogeneous models. It applies to different tasks of the development cycle such as simulation, verification or testing.1 We propose an approach to multi-formalism modelling, called ModHel’X, which is based on the concept of Model of Computation and focuses on the simulation of models. Our approach addresses two important issues in this particular field: (a) providing support for the specification of the execution semantics of a modelling formalism, and (b) allowing the specification of the interactions between parts of a model described using different modelling formalisms.
Public knowledge and attitudes towards antibiotic usage: a cross-sectional study among the general public in the state of Penang, Malaysia.

INTRODUCTION Public knowledge and attitudes towards antibiotics play a vital role in the success of the treatment process. This study aimed to assess public knowledge and attitudes toward antibiotic usage which could serve as baseline data for future studies within a government hospital setting in Malaysia. METHODOLOGY A self-administered cross-sectional survey involving 408 respondents was conducted using a validated questionnaire at an outpatient pharmacy department in Penang Hospital, Malaysia, from February to March 2009. RESULTS Nearly 55% of the respondents had a moderate level of knowledge. Three quarters of the respondents (76.7%) could correctly identify that antibiotics are indicated for the treatment of bacterial infections. However, 67.2% incorrectly thought that antibiotics are also used to treat viral infections. About 59.1% of the respondents were aware of antibiotic resistance phenomena in relation to overuse of antibiotics. With regard to attitudes, 38% believed that taking antibiotics when having cold symptoms could help them to recover faster, while 47.3% expected antibiotics to be prescribed for common cold symptoms. Age, race and educational level were among the demographic characteristics significantly associated with knowledge and attitudes toward antibiotic use. Poor level of knowledge was found in less than one-third of the respondents whereas more than one-third of the respondents wrongly self-medicate themselves with antibiotics once they have a cold. CONCLUSION Educational interventions are needed to promote prudent use of antibiotics among the public.
Recollection of the early years of the research on cytochrome P450

Since the publication of the first paper on “cytochrome P450” in 1962, the biochemical research on this novel hemoprotein expanded rapidly in the 1960s and the 1970s as its principal roles in various important metabolic processes including steroid hormone biosynthesis in the steroidogenic organs and drug metabolism in the liver were elucidated. Establishment of the purification procedures of microsomal and mitochondrial P450s in the middle of the 1970s together with the introduction of molecular biological techniques accelerated the remarkable expansion of the research on P450 in the following years. This review paper summarizes the important developments in the research on P450 in the early years, for about two decades from the beginning, together with my personal recollections.
Deceleration Trauma to the Heart and Great Vessels after Road-traffic Accidents

Four young men involved in high-speed car crashes developed cardiovascular trauma. Two patients had aortic aneurysms, one rupture of the mitral valve, and one ventricular septal defect; successful surgical correction was undertaken in all. The importance of considering the possibility of cardiovascular trauma in these circumstances is emphasized, and x-ray films (repeated if necessary) should be taken even when there are no external signs of trauma.
Non-parametric learning for natural plan generation

We present a novel way to learn sampling distributions for sampling-based motion planners by making use of expert data. We learn an estimate (in a non-parametric setting) of sample densities around semantic regions of interest, and incorporate these learned distributions into a sampling-based planner to produce natural plans. Our motivation is that certain aspects of the workspace have a local influence on planning strategies, which is dependent both on where, and what, they are. In the event that learning the density estimate of the training data is impractical in the original feature space, we utilize a non-linear dimensionality-reduction technique and perform density estimation on a lower-dimensional embedding. Samples are then lifted from this embedded density into the original feature space, producing samples that still well approximate the original distribution. A goal of this work is to learn how various features in the environment influence the behavior of experts - for example, how pedestrian crossings, traffic signals and so on affect drivers. We show that learning sampling distributions from expert trajectory data around these semantic regions leads to more natural paths that are measurably closer to those of an expert. We demonstrate the feasibility of the technique in various scenarios for a virtual car-like robotic vehicle and a simple manipulator, contrasting the differences in planned trajectories of the semantically-biased distributions with conventional techniques.
CHANGES IN SECONDARY METABOLITES PROFILES AND BIOLOGICAL ACTIVITY OF THE FRESH FRUITING BODIES OF Stereum hirsutum EXPOSED TO HIGH-DOSE UV-B RADIATION

The present study aims to investigate the effects of ultraviolet radiation (type B) on the steroid and fatty acids content, phenolic compounds and biological activities of Stereum hirsutum wild fruiting bodies, which has been used by both Chinese and Korean folk medicine to treat cancer and recently as functional food. From another perspective, the distribution of steroid derivatives as well as fatty acids underwent significant changes after UV exposure over time. In our model of study UV-B radiation induced a decrease in the relative abundance of ergosterol derivatives while squalene increased. We also detected that UVB radiation (1.2 W m-2) enhanced the antioxidant activity of Stereum hirsutum , with the acetonic extract after 48 hours of radiation the most efficient with a half-maximal inhibitory concentration (IC50) of 339.9 μg/mL. Gas-mass chromatography (GC-MS) analysis at this 48 hours stage revealed a high content of phenolic compounds (70%). We observed a decrease in the antibacterial activity against Escherichia coli , Salmonella typhi and Salmonella typhimurium compared to their respective controls. The study concludes that UV-B influences the pathway of secondary metabolites to induce changes metabolic in the composition of sterols and fatty acids and increasing the abundance of antioxidant compounds in S. hirsutum.
The protective role of adenosine in inducing nitric oxide synthesis in rat liver ischemia preconditioning is mediated by activation of adenosine A2 receptors

This study aims to determine if the protective role of adenosine in liver ischemic preconditioning is mediated by the activation of adenosine receptors and to ascertain which of these receptors is implicated in the process. Administration of adenosine A1 and A2 receptor antagonists to preconditioned animals indicates that hepatic preconditioning is mediated by the activation of adenosine A2 receptors. Propentofylline (an inhibitor of adenosine transport into cells) in the preconditioned group, subjected to previous administration of an adenosine A2 receptor antagonist, prevented the negative effect of the latter on the protection offered by preconditioning. An increase of NO production was detected just immediately after hepatic preconditioning, and the administration of an adenosine A2 receptor antagonist to the preconditioning group prevented this increase, thus abolishing the protective effect of preconditioning. However, the administration of a NO donor to the preconditioned group subjected to previous administration of the adenosine A2 receptor antagonist was able to maintain the preconditioning effects. In conclusion, these results indicate that, in preconditioning, the protective effect of adenosine could be a result of an increase in extracellular adenosine. This in turn would induce the activation of adenosine A2 receptors, which, by eliciting an increase in NO generation, would protect against the injury associated with hepatic ischemia‐reperfusion.
Therapy of Ischemic Cardiomyopathy With the Immunomodulating Agent Pentoxifylline: Results of a Randomized Study

Background—Inflammatory immune activation commonly occurs in heart failure and may perpetuate this syndrome. We sought to determine whether the immunomodulating agent pentoxifylline enhances left ventricular function in patients with ischemic cardiomyopathy. We also investigated the effect of therapy on levels of brain natriuretic peptide (NT-pro BNP), C-reactive protein (CRP), tumor necrosis factor-&agr; (TNF-&agr;), and the marker of apoptosis, Fas/Apo-1. Methods and Results—In a single-center, prospective, randomized, double-blind, placebo-controlled study, 38 patients with ischemic cardiomyopathy received pentoxifylline 400 mg TID or placebo in addition to standard therapy. Clinical assessment, radionuclide ventriculography, echocardiography, and blood analyses were performed at baseline and after 6 months. There were no differences in baseline characteristics between the groups. Five patients died (4 in the placebo group). Pentoxifylline treatment resulted in an improvement in functional class (P <0.005) and an increase in systolic blood pressure (P <0.05) and left ventricular radionuclide ejection fraction (P <0.05) compared with the placebo-treated group. There were reductions in plasma concentrations of CRP, NT-pro BNP, TNF-&agr;, and Fas/Apo-1 in the pentoxifylline compared with the placebo-treated group. Conclusions—In patients with heart failure due to ischemic left ventricular dysfunction, the addition of pentoxifylline to standard therapy results in improvements in clinical status and radionuclide ejection fraction, which are accompanied by reductions in plasma markers of inflammation, prognosis, and apoptosis.
Term Distribution Visualizations with a Focus + Context Model

Many text searches are meant to identify one particular fact or one particular section of a document. Unfortunately, predominant search paradigms focus mostly on identifying relevant documents and leave the burden of within-document searching on the user. This research explores term distribution visualizations as a means to more clearly identify both the relevance of documents and the location of specific information within them. We present a set of term distribution visualizations and introduce a Focus+Context model for within-document search and navigation.