Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of amino acids essential for the antiangiogenic activity of tumstatin and its use in combination antitumor activity

Tumstatin is an angiogenesis inhibitor that binds to αvβ3 integrin and suppresses tumor growth. Previous deletion mutagenesis studies identified a 25-aa fragment of tumstatin (tumstatin peptide) with in vitro antiangiogenic activity. Here, we demonstrate that systemic administration of this tumstatin peptide inhibits tumor growth and angiogenesis. Site-directed mutagenesis identified amino acids L, V, and D as essential for the antiangiogenic activity of tumstatin. The tumstatin peptide binds to αvβ3 integrin on proliferating endothelial cells and localizes to select tumor endothelium in vivo. Using 3D molecular modeling, we identify a putative interaction interface for tumstatin peptide on αvβ3 integrin. The antitumor activity of the tumstatin peptide, in combination with bevacizumab (anti-VEGF antibody), displays significant improvement in efficacy against human renal cell carcinoma xenografts when compared with the single-agent use. Collectively, our results demonstrate that tumstatin peptide binds specifically to the tumor endothelium, and its antiangiogenic action is mediated by αvβ3 integrin, and, in combination with an anti-VEGF antibody it exhibits enhanced tumor suppression of renal cell carcinoma.
β-Citronellol, an alcoholic monoterpene with inhibitory properties on the contractility of rat trachea

β-Citronellol is an alcoholic monoterpene found in essential oils such Cymbopogon citratus (a plant with antihypertensive properties). β-Citronellol can act against pathogenic microorganisms that affect airways and, in virtue of the popular use of β-citronellol-enriched essential oils in aromatherapy, we assessed its pharmacologic effects on the contractility of rat trachea. Contractions of isolated tracheal rings were recorded isometrically through a force transducer connected to a data-acquisition device. β-Citronellol relaxed sustained contractions induced by acetylcholine or high extracellular potassium, but half-maximal inhibitory concentrations (IC50) for K+-elicited stimuli were smaller than those for cholinergic contractions. It also inhibited contractions induced by electrical field stimulation or sodium orthovanadate with pharmacologic potency equivalent to that seen against acetylcholine-induced contractions. When contractions were evoked by selective recruitment of Ca2+ from the extracellular medium, β-citronellol preferentially inhibited contractions that involved voltage-operated (but not receptor-operated) pathways. β-Citronellol (but not verapamil) inhibited contractions induced by restoration of external Ca2+ levels after depleting internal Ca2+ stores with the concomitant presence of thapsigargin and recurrent challenge with acetylcholine. Treatment of tracheal rings with L-NAME, indomethacin or tetraethylammonium did not change the relaxing effects of β-citronellol. Inhibition of transient receptor potential vanilloid subtype 1 (TRPV1) or transient receptor potential ankyrin 1 (TRPA1) receptors with selective antagonists caused no change in the effects of β-citronellol. In conclusion, β-citronellol exerted inhibitory effects on rat tracheal rings, with predominant effects on contractions that recruit Ca2+ inflow towards the cytosol by voltage-gated pathways, whereas it appears less active against contractions elicited by receptor-operated Ca2+ channels.
Deranged platelet calcium homeostasis in diabetic patients with end-stage renal failure: A possible link to increased cardiovascular mortality?

OBJECTIVE Platelet hyperfunction is a typical feature of the prothrombotic state that frequently complicates the natural history of diabetes. In uremia, a bleeding diathesis is present, which principally involves the primary phase of hemostasis. Thus, in patients with uremia of diabetic origin, the infrequent coexistence of two opposite alterations of hemostasis takes place. In patients with uremia, an increased incidence of cardiovascular events and related mortality is observed. This phenomenon is greatly amplified in uremia of diabetic origin. Calcium homeostasis is a critical aspect of platelet function, which has recently become available in human diseases. The aim of this study was to evaluate calcium homeostasis in platelets from patients with uremia of diabetic and nondiabetic origin. RESEARCH DESIGN AND METHODS We evaluated, by means of Fura 2, the intracellular concentration of ionized calcium ([Ca2+]i) in platelets from 18 patients with uremia of diabetic origin, 12 patients with uremia of nondiabetic origin and 16 healthy control subjects [Ca2+]i was evaluated in resting conditions and after stimulation with 0.05, 0.1, 0.5 U/ml thrombin. RESULTS Platelets from uremic patients with diabetes had higher resting [Ca2+]i than both control subjects (P = 0.01) and uremic patients without diabetes (P = 0.001). Similarly, after stimulation with thrombin, the absolute increase of [Ca2+]i was higher (P < 0.05) in platelets from uremic patients with diabetes compared with both control subjects and uremic patients without diabetes. The relative increase of [Ca2+]i was higher (P < 0.05) than normal in platelets from uremic patients after weak or intermediate strength thrombin. No correlation were present between [Ca2+]i values and other clinical and laboratory variables potentially associated with platelet hyperfunction. CONCLUSIONS Diabetes and uremia in combination further deteriorate the abnormal platelet calcium homeostasis observed in uremia.
Postoperative Interleukin-6 Level and Early Detection of Complications After Elective Major Abdominal Surgery

Objective:To assess the association of systemic inflammation and outcome after major abdominal surgery. Background:Major abdominal surgery carries a high postoperative morbidity and mortality rate. Studies suggest that inflammation is associated with unfavorable outcome. Methods:Levels of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-&agr; and the systemic inflammatory response syndrome (SIRS) were assessed in 137 patients undergoing major abdominal surgery. Blood samples were drawn on days 0, 1, 3, and 7, and SIRS was scored during 48 hours after surgery. Primary outcome was a composite of mortality, pneumonia, sepsis, anastomotic dehiscence, wound infection, noncardiac respiratory failure, atrial fibrillation, congestive heart failure, myocardial infarction, and reoperation within 30 days of surgery. Results:An IL-6 level more than 432 pg/mL on day 1 was associated with an increased risk of complications (adjusted odds ratio: 3.3; 95% confidence interval [CI]: 1.3–8.5) and a longer median length of hospital stay (7 vs 12 days, P < 0.001). As a single test, an IL-6 cut-off level of 432 pg/mL on day 1 yielded a specificity of 70% and a sensitivity of 64% for the prediction of complications (area under the curve: 0.67; 95% CI: 0.56–0.77). Levels of CRP started to discriminate from day 3 onward with a specificity of 87% and a sensitivity of 58% for a cut-off level of 203 mg/L (AUC: 0.73; 95% CI: 0.63–0.83). Conclusions:A high IL-6 level on day 1 is associated with postoperative complications. Levels of IL-6 help distinguish between patients at low and high risk for complications before changes in levels of CRP.
Synergistic Effect of Bolus Exposure to Zinc Oxide Nanoparticles on Bleomycin-Induced Secretion of Pro-Fibrotic Cytokines without Lasting Fibrotic Changes in Murine Lungs

Zinc oxide (ZnO) nanoparticles are widely used in various products, and the safety evaluation of this manufactured material is important. The present study investigated the inflammatory and fibrotic effects of pulmonary exposure to ZnO nanoparticles in a mouse model of pulmonary fibrosis. Pulmonary fibrosis was induced by constant subcutaneous infusion of bleomycin (BLM). Female C57BL/6Jcl mice were divided into BLM-treated and non-treated groups. In each treatment group, 0, 10, 20 or 30 µg of ZnO nanoparticles were delivered into the lungs through pharyngeal aspiration. Bronchoalveolar lavage fluid (BALF) and the lungs were sampled at Day 10 or 14 after administration. Pulmonary exposure by a single bolus of ZnO nanoparticles resulted in severe, but transient inflammatory infiltration and thickening of the alveolar septa in the lungs, along with the increase of total and differential cell counts in BLAF. The BALF level of interleukin (IL)-1β and transforming growth factor (TGF)-β was increased at Day 10 and 14, respectively. At Day 10, the synergistic effect of BLM and ZnO exposure was detected on IL-1β and monocyte chemotactic protein (MCP)-1 in BALF. The present study demonstrated the synergistic effect of pulmonary exposure to ZnO nanoparticles and subcutaneous infusion of BLM on the secretion of pro-fibrotic cytokines in the lungs.
Programmed death-ligand-1 expression in advanced gastric cancer detected with RNA in situ hybridization and its clinical significance

PD-L1 expression may be a predictive marker for anti-PD-1 therapeutic efficacy. No standard detection method of PD-L1 expression was available for advanced gastric cancer (AGC), which would be investigated in this study using RNA in situ hybridization and immunohistochemistry. Patients (N = 165) with AGC treated at Peking University Cancer Hospital from October 2008 to February 2013 were retrospectively studied. Tissue samples prior to chemotherapy were assessed for PD-L1 expression using RNA in situ hybridization (an RNAscope assay) and immunohistochemistry (IHC). The correlations of PD-L1 expression to patient characteristics and clinical outcomes were statistically analyzed. PD-L1 mRNA signals were located in tumor compartments or the mesenchyme in a brown dotted or clustered pattern, and PD-L1 mRNA expression in gastric cancer was heterogeneous. PD-L1-positive expressions were observed in 33.9% (56/165) and 35.1% (46/131) patients in mRNA level and protein level, respectively. A positive relationship was found between PD-L1 mRNA and PD-L1 protein, and compared to IHC, RNAscope assay could provide an intuitional and quantitative data with potential clinical application. No statistically significant differences occurred between PD-L1 expression and clinical response to chemotherapy, or survival. However, we found that PD-L1 expression was higher in intestinal type than in diffuse type. These findings suggested that the RNAscope assay may be a promising method for patient assessment in gastric cancer clinical trials, which would be illustrated in further study.
Predicting the optical performance of eyes implanted with IOLs to correct spherical aberration.

PURPOSE To use powerful modeling techniques for predicting the optical performance of eyes implanted with different types of intraocular lenses (IOLs). This approach will allow performance of "virtual cataract surgery," with different IOL designs that can be used and physical parameters that may occur during actual surgery-in particular, in IOLs that correct spherical aberration. METHODS A computer model was developed to predict the optical performance of individual eyes after IOL implantation. The approach was validated in a group of patients with eyes implanted with different IOLs. In these patients, corneal wavefront aberrations were calculated from elevations provided by videokeratography. Ocular aberrations were measured with a high-dynamic range Hartmann-Shack wavefront sensor. Misalignments (IOL tilt and decentration) were estimated with a new instrument, based on recording Purkinje images. This model of particular corneal aberrations and IOL parameters (intrinsic optical design details plus geometric location data) was used to estimate the total ocular aberrations after surgery and to compared them with actual aberrations measured directly with the wavefront sensor. RESULTS The aberrations of implanted eyes predicted by the individualized optical models were well correlated with the actual aberration measured in each subject. This result indicates that the approach is adequate in evaluating the actual optical performance of different types of lenses. The model allows a large number of "virtual" surgeries to be performed, to test the performance of current or future IOL designs. CONCLUSIONS A "virtual surgery" approach was designed to predict the optical performance in pseudophakic eyes. In each subject, it was possible to obtain the eye's optical performance with a particular IOL and biometric data after surgery. Specifically, this modeling can be used to evaluate the tolerances to misalignments and depth of focus of IOLs correcting spherical aberration in actual eyes. This approach is quite powerful and is especially applicable to the study of current and future aberration-correction IOL designs.
The Random Projection Method for Stiff Detonation Waves

In this paper we present a simple and robust random projection method for underresolved numerical simulation of stii detonation waves in chemically reacting ows. This method is based on the random projection method proposed by the authors for general hyperbolic systems with stii reaction terms 1], where the ignition temperature is randomized in a suitable domain. It is simpliied using the equations of instantaneous reaction, and then extended to handle the interactions of detonations. Extensive numerical experiments, including interaction of detonation waves, and in two dimensions, demonstrate the reliability and robustness of this novel method.
AIDR: artificial intelligence for disaster response

We present AIDR (Artificial Intelligence for Disaster Response), a platform designed to perform automatic classification of crisis-related microblog communications. AIDR enables humans and machines to work together to apply human intelligence to large-scale data at high speed. The objective of AIDR is to classify messages that people post during disasters into a set of user-defined categories of information (e.g., "needs", "damage", etc.) For this purpose, the system continuously ingests data from Twitter, processes it (i.e., using machine learning classification techniques) and leverages human-participation (through crowdsourcing) in real-time. AIDR has been successfully tested to classify informative vs. non-informative tweets posted during the 2013 Pakistan Earthquake. Overall, we achieved a classification quality (measured using AUC) of 80%. AIDR is available at http://aidr.qcri. org/.
Hostility and the progression of carotid atherosclerosis.

&NA; We studied prospectively the association of hostility and anger suppression by the use of ultrasonographically assessed 2‐year progression of carotid atherosclerosis (PCA) in a sample of 119 middle‐aged men from eastern Finland. Based on measures of cynical distrust, impatience‐irritability, anger‐in, and anger‐control, four variants of hostility‐by‐anger suppression model were tested with multiple regression analysis. In addition to the previously established risk factors (i.e., serum low‐density lipoprotein cholesterol concentration, smoking, and old age), cynical distrust and anger‐control significantly predicted PCA. There was about a two‐fold accelerated PCA in the group with high cynical distrust and high anger‐control even after we controlled for the established biological risk factors and possible confounding background variables. The impact of the independent variables on PCA seemed to be additive rather than synergistic. These results, based on a relatively small, but nonselected population sample, extend previous results of angiographic studies.
Longest cycles in sparse random digraphs

Long paths and cycles in sparse random graphs and digraphs were studied intensively in the 1980's. It was finally shown by Frieze in 1986 that the random graph \documentclass{article}\usepackage{mathrsfs, amsmath, amssymb}\pagestyle{empty}\begin{document}${\mathcal{G}}(n,p)$\end{document} with p = c/n has a cycle on at all but at most (1 + ε)ce−cn vertices with high probability, where ε = ε (c) → 0 as c → ∞. This estimate on the number of uncovered vertices is essentially tight due to vertices of degree 1. However, for the random digraph \documentclass{article}\usepackage{mathrsfs, amsmath, amssymb}\pagestyle{empty}\begin{document}${\mathcal{D}}(n,p)$\end{document} no tight result was known and the best estimate was a factor of c/2 away from the corresponding lower bound. In this work we close this gap and show that the random digraph \documentclass{article}\usepackage{mathrsfs, amsmath, amssymb}\pagestyle{empty}\begin{document}${\mathcal{D}}(n,p)$\end{document} with p = c/n has a cycle containing all but (2 + ε)e−cn vertices w.h. p., where ε = ε (c) → 0 as c → ∞. This is essentially tight since w.h. p. such a random digraph contains (2e−c − o(1))n vertices with zero in‐degree or out‐degree. © 2012 Wiley Periodicals, Inc. Random Struct. Alg. , 2013
Pooling of Urine Samples for Screening for Neisseria gonorrhoeae by Ligase Chain Reaction: Accuracy and Application

ABSTRACT The accuracy of detection of genital Neisseria gonorrhoeae infection in pooled urine samples by ligase chain reaction (LCR) was examined in three populations. Firstly, urine specimens from 300 female military recruits (FMR) were tested by LCR individually and in pools of four and six. Secondly, 300 urine specimens from middle-school students (MSS) were tested individually by LCR, and then the processed specimens were stored frozen for subsequent testing in pools of 4 and 10. Thirdly, 600 frozen urine specimens from high-school students (HSS) were tested by using the LCR pooling algorithm, i.e., testing processed specimens in pools of four in one test unit dose, and retesting individual specimens from positive pools. Finally, the pooling algorithm results were compared to culture results for a subset of 344 students from the original 600 HSS from whom cervical or urethral samples were taken at the discretion of the school nurse practitioners. Compared to individual testing of specimens by LCR in the FMR population, the pooling-by-four algorithm was 100% sensitive (5 of 5) and 100% pool specific (70 of 70), and the pool-by-six algorithm was 100% sensitive (5 of 5) and 100% pool specific (45 of 45). In the MSS population, the pool-by-4 algorithm was 95.8% sensitive (23 of 24) and 100% (52 of 52) pool specific, and the pool-by-10 algorithm was 95.8% sensitive (23 of 24) and 100% (17 of 17) pool specific. In the subset of 344 HSS from whom endocervical or urethral specimens were collected for culture, 31 were positive by LCR in urine and 26 were positive by culture. After results discrepant between culture and LCR were adjudicated by a confirmatory LCR test, the pooling algorithm was 93.8% (30 of 32) sensitive and 99.7% (311 of 312) specific. Culture from these 344 HSS was 81.3% (26 of 32) sensitive. The pooling algorithm reduced the cost of the N. gonorrhoeae LCR assay by 60% compared to individual testing of the HSS specimens and was both sensitive and specific.
Smoking habits among medical students in Western Saudi Arabia.

I read with interest the article by Wali on smoking habits (SH) among medical students in Western Saudi Arabia.1 Smoking habits among medical students, and hence, future physicians yields deep concern as smoking physicians could adversely impact interactions with patients on smoking, and they are less likely to initiate cessation interventions.2 Various anecdotal studies have shown that SH is generally prevailing among Saudi medical students. It is worthy to mention that over the past few years there was nearly a 3-fold increase in the prevalence SH among Saudi female medical students from 2.4% in 20063 to 9.1% in 2009-2010.1 It is expected that the prevalence is on the rise in the forthcoming future. Although SH among elderly woman is socially accepted in many Arabian conservative communities, it is still socially disapproved among young women. Increased social acceptance of women’s smoking is a part of general liberalization of norms concerning women’s behavior, reflecting increasing equality between genders.4 Factors significantly contributing to increase motives towards smoking among women, including medical students, have been recently elucidated. They were found to involve curiosity, decreases boredom, tension, and helps one to relax. Also, women had the misconception that smoking helps to reduce weight.5,6 I do agree with Wali1 that education and anti-smoking campaigns are the key toward successfully containing the foreseeable burden of SH. However, special emphasis is needed to be focused on women not because of the close association of smoking with certain health hazards among them, but also because women could play as influential role models within families to strongly discourage family members, including children and adolescents from smoking.
The Regulation of Amylin and Insulin Gene Expression and Secretion

Amylin and insulin are cosecreted by beta cells in the islets of the pancreas. Insulin is required for glucose homeostasis; however, the physiology of amylin and its metabolic importance are not well understood. Dysregulation of insulin and peripheral insulin resistance of skeletal muscle are the major factors responsible for diabetes. Amylin may contribute to the development of diabetes by inhibiting insulin release from the beta cells and promoting beta cell death through apoptosis. Other pathologic conditions such as pancreatic cancer and obesity are associated with elevated amylin levels and hypoglycemia. Although insulin secretion and gene expression are well understood, new factors have been discovered that affect both pathways. The regulation of amylin secretion and gene expression is less clear, but recent studies have demonstrated the complexity of amylin regulation, both in concert with insulin and in a nonparallel fashion. This review describes the current thinking behind amylin and insulin regulation by beta cells under normal physiologic conditions and during pathologic states. Insulin secretion is a complex phenomenon that is triggered by circulating metabolites and hormones as well as neural factors. Circulating glucose levels play a central role in the control of insulin secretion. However, under normal circumstances, glucose concentrations in the bloodstream do not change by more than 20% with feeding. The regulation between the gastrointestinal tract and insulin secretion is known as the enteroinsular axis. The signals of the enteroinsular axis are dependent on a small increase in circulating glucose, a process that has evolved to prevent inappropriate hypoglycemia following nutrient ingestion. The major endocrine mediators of the enteroinsular axis (incretins) are glucosedependent insulinotropic peptide (GIP) and glucagon-like peptide 1 (GLP-1). Both of these incretins activate insulin and amylin secretion through interactions with 7 transmembrane serpentine receptors that are coupled to G proteins and the cAMP second messenger system.