Miracle-dz/UniFAR-FTUs huggingface dataset:
Mitigation of Initial Cardiodynamic Effects of the S1P1 Receptor Modulator Ponesimod Using a Novel Up‐Titration Regimen

Ponesimod, a potent selective sphingosine‐1‐phosphate receptor 1 modulator, leads to a reduction in circulating total lymphocyte count and transient decreases in heart rate (HR). Based on a modeling and simulation approach, this study was conducted to investigate whether a gradual up‐titration regimen may mitigate these cardiodynamic effects. In this double‐blind, placebo‐controlled, randomized, 2‐way crossover study, 32 healthy participants (15 males) received placebo on day 1 followed by multiple‐dose administration of either ponesimod or placebo (ratio 3:1). Ponesimod was administered alternately using regimen A (incremental dose increase from 2 to 20 mg in 9 steps) or B (10 mg for 7 days followed by a single‐dose administration of 20 mg). Cardiodynamic (Holter and 12‐lead ECG), pharmacokinetic, pharmacodynamic (total lymphocyte count), and safety variables were assessed. After first‐dose ponesimod administration (day 2), a transient decrease in HR was observed (nadir 2‐3 hours postdose, back to predose values within 4‐5 hours) of approximately 6 and 12 beats/min (bpm) (mean) following regimens A and B, respectively. On day 2, occurrence of HR <45 bpm, HR decrease from baseline of over 20 bpm, PR interval ≥200 milliseconds, or PR interval increase from baseline >20 ms, was lower following regimen A than B (14 vs 43 events). During the course of the study, incidence of HR <45 bpm was lower following regimen A than B (20 vs 58 events). Fewer participants reported adverse events following regimen A than B. Pharmacokinetics and pharmacodynamics were similar between the regimens. The novel gradual up‐titration with ponesimod markedly mitigated initial cardiodynamic effects.
Biophysical insight reveals tannic acid as amyloid inducer and conformation transformer from amorphous to amyloid aggregates in Concanavalin A (ConA)

The aggregation phenomenon (amyloid and amorphous) is associated with several pathological complications in human, such as Alzheimer’s, Parkinson’s, Huntington, Cataract diseases, and Diabetes mellitus type 2. In the present study we are offering evidence and breaking the general belief with regard to the polyphenols action as protein aggregate inhibitors. Herein we confirm that tannic acid (TA) is not only an amyloid inducer, but also it switches one type of conformation, ultimately morphology, into another. We ascertain based on our findings that aggregates are not rigid structures and the stability can be challenged under certain conditions. This study also confirms that unfolded and amorphous aggregates can serve as precursors of amyloids and TA interactions with unordered aggregates (amorphous) bringing orderliness in the conformation via amyloidosis. The shifting of unordered conformation toward orderliness is governed by the modulation in surface hydrophobic patches in Concanavalin A (ConA). Hence, a degree of exposed hydrophobic cluster can be claimed as a strong parameter to detect and distinguish the native, amorphous and both types of amyloids. Turbidity and Rayleigh light scattering measurements followed similar pattern while Thioflavin T and 1-anilino-8-naphthalene sulfonate fluorescence assays of the binding with amorphous and amyloid followed an inverse relation. Electron microscopic studies revealed the morphological variation in the ConA at 65°C as amorphous while the ConA treated with TA followed by heat treatment at 65°C was defined as amyloid in nature. Interestingly for the first time we are reporting the slight agglutination activity by the ConA amyloids.
Fetoscopic laser photocoagulation in twin-to-twin transfusion syndrome: experience from a single institution.

INTRODUCTION Twin-to-twin transfusion syndrome (TTTS) is the most common serious complication of monochorionic (MC) twin pregnancies, with perinatal mortality rates of up to 90% if untreated. This study aimed to review the perinatal and perioperative outcomes of MC twin pregnancies treated for TTTS by fetoscopic laser photocoagulation (FLP) since its introduction at KK Women's and Children's Hospital (KKH), Singapore, in 2011. METHODS This was a retrospective review of five consecutive patients who underwent FLP of placental anastomoses for TTTS at KKH from June 2011 to March 2014. FLP was offered to patients who were diagnosed with TTTS of at least Quintero Stage II before 26 weeks of gestation. The main outcome measures were perioperative complications and perinatal survival rates. RESULTS Five sets of MC twin pregnancies underwent FLP during the study period - three pregnancies were diagnosed with Stage III TTTS and two pregnancies with Stage II TTTS. Median gestational ages at initial presentation, laser photocoagulation and delivery were 19 (range 17-20) weeks, 20 (range 19-23) weeks and 29 (range 28-34) weeks, respectively. One patient had bleeding into the amniotic cavity intraprocedurally. Overall, the perinatal survival rate, double-infant survival rate and survival rate for at least one twin were 60% (6/10 fetuses), 40% (2/5 twins) and 80% (4/5 twins), respectively. CONCLUSION FLP is a feasible treatment for TTTS, with minimal maternal complications. Perinatal survival rates of this patient group that was managed at our centre were comparable to those of international centres.
Ticagrelor vs prasugrel one-month maintenance therapy: Impact on platelet reactivity and bleeding events

Summary Platelet reactivity (PR) and bleeding events following therapy with ticagrelor vs prasugrel have not been adequately studied. We aimed to compare PR and bleeding events in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) while on ticagrelor vs prasugrel for one month. Consecutive patients who were discharged either on ticagrelor 90 mg bid maintenance dose (MD) or prasugrel 10 mg MD were invited for PR assessment (VerifyNow, in PRU) at one month. High PR (HPR) was defined as >208 PRU. Bleeding events [Bleeding Academic Research Consortium (BARC) classification] were monitored. Out of 937 screened patients, 512 were analysed, 278 under ticagrelor MD and 234 under prasugrel MD. PR at 30 days (C-statistic of the propensity score model 0.63, 0.58–0.67 95% CI, p<0.001) was lower when on ticagrelor compared with prasugrel (33.3, 95% CI 29.3–37.3 vs 84.6, 95% CI 73.6–95.6, p<0.001). In the analysed population more BARC type 1 bleeding events were observed with ticagrelor compared to prasugrel (36.7% vs 28.2%, p=0.047). In 221 propensity score matched pairs, BARC type 1 bleeding rate was marginally higher in ticagrelor vs prasugrel treated patients (35.7% vs 27.1%, p=0.05). BARC type ≥2 events did not differ between groups 5 (2.3%) vs 5 (2.3%). HPR rate was higher for prasugrel-treated patients (5.4% vs 0%, p<0.001). In conclusion, in patients with ACS undergoing PCI, ticagrelor MD produces a significantly higher platelet inhibition compared to prasugrel MD. This pharmacodynamic difference might be associated with more nuisance bleeding events with ticagrelor use. Clinical Trial Registration ClinicalTrials.gov Identifier: NCT01774955.
Advising Consumption of Green Vegetables, Beef, and Full-Fat Dairy Products Has No Adverse Effects on the Lipid Profiles in Children

In children, little is known about lipid profiles and the influence of dietary habits. In the past, we developed a dietary advice for optimizing the immune system, which comprised green vegetables, beef, whole milk, and full-fat butter. However, there are concerns about a possible negative influence of the full-fat dairy products of the diet on the lipid profile. We investigated the effect of the developed dietary advice on the lipid profile and BMI (body mass index)/BMI-z-score of children. In this retrospective cohort study, we included children aged 1–16 years, of whom a lipid profile was determined in the period between June 2011 and November 2013 in our hospital. Children who adhered to the dietary advice were assigned to the exposed group and the remaining children were assigned to the unexposed group. After following the dietary advice for at least three months, there was a statistically significant reduction in the cholesterol/HDL (high-density lipoproteins) ratio (p < 0.001) and non-HDL-cholesterol (p = 0.044) and a statistically significant increase in the HDL-cholesterol (p = 0.009) in the exposed group, while there was no difference in the BMI and BMI z-scores. The dietary advice has no adverse effect on the lipid profile, BMI, and BMI z-scores in children, but has a significant beneficial effect on the cholesterol/HDL ratio, non-HDL-cholesterol, and the HDL-cholesterol.
Measuring Short Text Reuse for the Urdu Language

Text reuse occurs when one borrows the text (either verbatim or paraphrased) from an earlier written text. A large and increasing amount of digital text is easily and readily available, making it simpler to reuse but difficult to detect. As a result, automatic detection of text reuse has attracted the attention of the research community due to the wide variety of applications associated with it. To develop and evaluate automatic methods for text reuse detection, standard evaluation resources are required. In this paper, we propose one such resource for a significantly under-resourced language—Urdu, which is widely used in day to day communication and has a large digital footprint particularly in the Indian subcontinent. Our proposed Urdu short text reuse corpus contains 2684 short Urdu text pairs, manually labeled as verbatim (496), paraphrased (1329), and independently written (859). In addition, we describe an evaluation of the corpus using various state-of-the-art text reuse detection methods with binary and multi-classification settings and a set of four classifiers. Output results show that character n-gram overlap using J48 classifier outperform other methods for the Urdu short text reuse detection task.
Aging-related gains and losses associated with word production in connected speech

ABSTRACT Older adults have been observed to use more nonnormative, or atypical, words than younger adults in connected speech. We examined whether aging-related losses in word-finding abilities or gains in language expertise underlie these age differences. Sixty younger and 60 older adults described two neutral photographs. These descriptions were processed into word types, and textual analysis was used to identify interrupted speech (e.g., pauses), reflecting word-finding difficulty. Word types were assessed for normativeness, with nonnormative word types defined as those used by six (5%) or fewer participants to describe a particular picture. Accuracy and precision ratings were provided by another sample of 48 high-vocabulary younger and older adults. Older adults produced more interrupted and, as predicted, nonnormative words than younger adults. Older adults were more likely than younger adults to use nonnormative language via interrupted speech, suggesting a compensatory process. However, older adults’ nonnormative words were more precise and trended for having higher accuracy, reflecting expertise. In tasks offering response flexibility, like connected speech, older adults may be able to offset instances of aging-related deficits by maximizing their expertise in other instances.
CNN oriented fast PU mode decision for HEVC hardwired intra encoder

The number of intra prediction modes in High Efficiency Video Coding (HEVC) has been increased up to 35. To the end of alleviating the complexity of intra coding, we bring in the convolution neural network (CNN) to obtain the candidate modes of current PU and adopt the corner detection algorithm to further reduce the candidate modes. The virtues of proposed algorithm include: Firstly, our algorithm skip the rough PU mode decision (RMD) process and get the candidate list from CNN directly. In other words, the computations are relaxed in our algorithm. Secondly, the inputs of CNN in proposed algorithm merely contain the source image pixels and quantization parameter (QP), this feature makes it friendly to high parallel hardwired encoder. As compared with HM-15.0, experiments show that our algorithm decreases the intra coding time by 27.92% while the corresponding BDBR augment is 1.15%. At last but not least, our algorithm possesses a stable coding performance. In specific, for the most sensitive sequence (Class F), our algorithm could save 27.10% intra coding time with 2.01% BDBR increase.
Depressive Symptoms and Perceived Burdensomeness Mediate the Association between Anxiety and Suicidal Ideation in Adolescents

A relationship between anxiety disorders and suicide-related behaviors has been demonstrated in adolescents, with a paucity of research examining mediators of this association. The present study hypothesized that anxiety would be associated with suicidal ideation via a serial mediation pathway through depressive symptoms and perceived burdensomeness and/or thwarted belongingness. A sample of 80 adolescents (68.8% female, 65.8% Hispanic), 13–19 years of age (mean = 16.93, SD = 1.66), completed 3 interviews as part of a randomized controlled trial. Results indicated a significant serial mediation from anxiety to suicidal ideation via depressive symptoms and perceived burdensomeness, but not thwarted belongingness. Clinicians and mental health service providers working with adolescents experiencing elevated anxiety should regularly assess for perceived burdensomeness and suicidal ideation.
Comparing Pixel- and Object-Based Approaches in Effectively Classifying Wetland-Dominated Landscapes

Wetland ecosystems straddle both terrestrial and aquatic habitats, performing many ecological functions directly and indirectly benefitting humans. However, global wetland losses are substantial. Satellite remote sensing and classification informs wise wetland management and monitoring. Both pixel- and object-based classification approaches using parametric and non-parametric algorithms may be effectively used in describing wetland structure and habitat, but which approach should one select? We conducted both pixel- and object-based image analyses (OBIA) using parametric (Iterative Self-Organizing Data Analysis Technique, ISODATA, and maximum likelihood, ML) and non-parametric (random forest, RF) approaches in the Barguzin Valley, a large wetland (~500 km2) in the Lake Baikal, Russia, drainage basin. Four Quickbird multispectral bands plus various spatial and spectral metrics (e.g., texture, Non-Differentiated Vegetation Index, slope, aspect, etc.) were analyzed using field-based regions of interest sampled to characterize an initial 18 ISODATA-based classes. Parsimoniously using a three-layer stack (Quickbird band 3, water ratio index (WRI), and mean texture) in the analyses resulted in the highest accuracy, 87.9% with pixel-based RF, followed by OBIA RF (segmentation scale 5, 84.6% overall accuracy), followed by pixel-based ML (83.9% overall accuracy). Increasing the predictors from three to five by adding Quickbird bands 2 and 4 decreased the pixel-based overall accuracy while increasing the OBIA RF accuracy to 90.4%. However, McNemar’s chi-square test confirmed no statistically significant difference in overall accuracy among the classifiers (pixel-based ML, RF, or object-based RF) for either the three- or five-layer analyses. Although potentially useful in some circumstances, the OBIA approach requires substantial resources and user input (such as segmentation scale selection—which was found to substantially affect overall accuracy). Hence, we conclude that pixel-based RF approaches are likely satisfactory for classifying wetland-dominated landscapes.
FTY720 (Fingolimod) Inhibits HIF1 and HIF2 Signaling, Promotes Vascular Remodeling, and Chemosensitizes in Renal Cell Carcinoma Animal Model

Clear cell renal cell carcinoma (ccRCC) is characterized by intratumoral hypoxia and chemoresistance. The hypoxia-inducible factors HIF1α and HIF2α play a crucial role in ccRCC initiation and progression. We previously identified the sphingosine kinase 1/sphingosine 1-phosphate (SphK1/S1P) pathway as a new modulator of HIF1α and HIF2α under hypoxia in various cancer cell models. Here, we report that FTY720, an inhibitor of the S1P signaling pathway, inhibits both HIF1α and HIF2α accumulation in several human cancer cell lines. In a ccRCC heterotopic xenograft model, we show that FTY720 transiently decreases HIF1α and HIF2α intratumoral level and modifies tumor vessel architecture within 5 days of treatment, suggesting a vascular normalization. In mice bearing subcutaneous ccRCC tumor, FTY720 and a gemcitabine-based chemotherapy alone display a limited effect, whereas, in combination, there is a significant effect on tumor size without toxicity. Noteworthy, administration of FTY720 for 5 days before chemotherapy is not associated with a more effective tumor control, suggesting a mode of action mainly independent of the vascular remodeling. In conclusion, these findings demonstrate that FTY720 could successfully sensitize ccRCC to chemotherapy and establish this molecule as a potent therapeutic agent for ccRCC treatment, independently of drug scheduling. Mol Cancer Ther; 15(10); 2465–74. ©2016 AACR.
Effect of solvents on forming poly(butyl-2-cyanoacrylate) encapsulated paeonol nanocapsules

Abstract The effect of ethanol or acetone, as oil phase solvents, upon the form of paeonol-loaded poly(butyl-2-cyanoacrylate) encapsulated nanocapsules (Pae@PNCs) by interfacial spontaneously polymerization were investigated. Pae@PNCs characterizations including morphology, radius distribution, polydispersity index (PDI), particle size, zeta potential, entrapment efficiency (EE%), drug loading (DL%) and in vitro paeonol release kinetics were evaluated. Results show that 100% acetone have a significant effect on forming nanocapsules, which showed the smaller size (168.3 ± 6.76 nm) under scanning electron microscopy (SEM) and one radius distribution by the particle size analyser. The data showed that using 100% acetone to prepare Pae@PNCs was leading to smaller particle size and lower polydispersity index (PDI), higher zeta potential, better EE (%) and perfect DL (%), which is linear decrease in radius (r2 = 0.939) and PDI (r2 = 0.974) and linear increase EE% (r2 = 0.9879) and DL% (r2 = 0.9892) with the acetone concentration (range 10–100% v/v). Paeonol encapsulated into and adhered on PNCs were confirmed by UV–Visible spectra (UV–Vis), Fourier transform infrared spectroscopy (FTIR) and Differential scanning calorimetry (DSC). Drug release behavior in vitro showed that 100% acetone as solvents on developing Pae@PNCs have greater advantages in controlling and prolonging paeonol release. Results demonstrated that solvents have a significant influence on forming Pae@PNCs.
Exact recovery of sparse signals from binary measurements

In this paper we propose a new fast single-pass algorithm for sparse signal recovery by using binary measurement matrices that achieves exact recovery of sparse vectors. This algorithm is therefore superior to algorithms based on ℓ1-norm minimization, and methods based on expander graphs (which require multiple iterations and have lower accuracy). Our method is able to exactly recover a sparse signal from a few measurements and the number of measurements is the lowest amongst all methods that use binary measurement matrices.
A distance-based approach for testing the mediation effect of the human microbiome

Motivation Recent studies have revealed a complex interplay between environment, the human microbiome and health and disease. Mediation analysis of the human microbiome in these complex relationships could potentially provide insights into the role of the microbiome in the etiology of disease and, more importantly, lead to novel clinical interventions by modulating the microbiome. However, due to the high dimensionality, sparsity, non-normality and phylogenetic structure of microbiome data, none of the existing methods are suitable for testing such clinically important mediation effect. Results We propose a distance-based approach for testing the mediation effect of the human microbiome. In the framework, the nonlinear relationship between the human microbiome and independent/dependent variables is captured implicitly through the use of sample-wise ecological distances, and the phylogenetic tree information is conveniently incorporated by using phylogeny-based distance metrics. Multiple distance metrics are utilized to maximize the power to detect various types of mediation effect. Simulation studies demonstrate that our method has correct Type I error control, and is robust and powerful under various mediation models. Application to a real gut microbiome dataset revealed that the association between the dietary fiber intake and body mass index was mediated by the gut microbiome. Availability and implementation An R package 'MedTest' is freely available at https://github.com/jchen1981/MedTest. Contact zhiwei@njit.edu or chen.jun2@mayo.edu. Supplementary information Supplementary data are available at Bioinformatics online.
Contrasting Genetic Structure in Two Co-Distributed Species of Old World Fruit Bat

The fulvous fruit bat (Rousettus leschenaulti) and the greater short-nosed fruit bat (Cynopterus sphinx) are two abundant and widely co-distributed Old World fruit bats in Southeast and East Asia. The former species forms large colonies in caves while the latter roots in small groups in trees. To test whether these differences in social organization and roosting ecology are associated with contrasting patterns of gene flow, we used mtDNA and nuclear loci to characterize population genetic subdivision and phylogeographic histories in both species sampled from China, Vietnam and India. Our analyses from R. leschenaulti using both types of marker revealed little evidence of genetic structure across the study region. On the other hand, C. sphinx showed significant genetic mtDNA differentiation between the samples from India compared with China and Vietnam, as well as greater structuring of microsatellite genotypes within China. Demographic analyses indicated signatures of past rapid population expansion in both taxa, with more recent demographic growth in C. sphinx. Therefore, the relative genetic homogeneity in R. leschenaulti is unlikely to reflect past events. Instead we suggest that the absence of substructure in R. leschenaulti is a consequence of higher levels of gene flow among colonies, and that greater vagility in this species is an adaptation associated with cave roosting.