Miracle-dz/UniFAR-FTUs huggingface dataset:
Are VEGFR-TKIs effective or safe for patients with advanced non-small cell lung cancer?

Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) might be new therapeutic strategies for advanced non-small cell lung cancer (NSCLC). Here a total of 12,520 patients from 23 randomized controlled trials (RCTs) were enrolled to evaluate the efficacy and safety of VEGFR-TKIs quantitatively in advanced NSCLC. Compared with non-VEGFR-TKIs, VEGFR-TKIs regimen significantly improved progression-free survival (PFS) [hazard ratio (HR): 0.839, 95% confidence interval (CI): 0.805-0.874, P < 0.001], objective response rates (ORR) [relative risk (RR): 1.374, 95% CI: 1.193-1.583, P < 0.001] and disease control rates (DCR) (RR: 1.113, 95% CI: 1.027-1.206, P = 0.009), but not overall survival (OS) (HR: 0.960, 95% CI: 0.921-1.002, P = 0.060) for NSCLC patients. The RR of all-grade neutropenia, thrombocytopenia, hypertension, hemorrhage, fatigue, anorexia, stomatitis, diarrhea, rash, hand-foot skin reaction (HFSR) were increased in patients received VEGFR-TKIs. As for high-grade (≥ 3) adverse events (AEs), VEGFR-TKIs were associated with higher RR of neutropenia, thrombocytopenia, hypertension, fatigue, stomatitis, diarrhea, rash and HFSR. This study demonstrates VEGFR-TKIs improve PFS, ORR and DCR, but not OS in advanced NSCLC patients. VEGFR-TKIs induce more frequent and serious AEs compared with control therapies.
A Systematic Review and Narrative Synthesis of Interventions for Parental Human Immunodeficiency Virus Disclosure

Introduction Disclosure of parental human immunodeficiency virus (HIV) infection to their children remains a difficult process for parents living with HIV (PLWH). In order to identify the best strategies to facilitate parental HIV disclosure, it is necessary to examine the efficacy of existing interventions designed to help PLWH parents with the disclosure process to their children. Objectives To systematically review the efficacy of interventions designed to assist PLWH disclose their HIV status to their children. Methods We conducted a systematic review and narrative synthesis of interventions designed to assist PLWH disclose their HIV status to their children. MEDLINE/PubMed, PsycINFO, Embase, Global Health, and Web of Science were searched. Results Studies were eligible for inclusion if they evaluated an intervention for parental HIV disclosure. Five studies published between 2001 and 2015 met the inclusion criteria. The interventions were conducted in South Africa, China, and the United States. Three of the studies used two-arm randomized controlled trials, in which the intervention group was given enhanced care while the control group received standard care. Four of the five studies included a theoretically informed intervention and three were limited to mothers. Results showed that four of the interventions increased parental HIV disclosure. Conclusion The findings suggest that parental HIV disclosure interventions are successful in assisting parents with the disclosure process and can be adapted in different cultural context. Future parental HIV disclosure interventions should include fathers in order to assist men with parental HIV disclosure.
Edinburgh Research Explorer Differential gene expression and alternative splicing in insect immune specificity

Background: Ecological studies routinely show genotype-genotype interactions between insects and their parasites. The mechanisms behind these interactions are not clearly understood. Using the bumblebee Bombus terrestris /trypanosome Crithidia bombi model system (two bumblebee colonies by two Crithidia strains), we have carried out a transcriptome-wide analysis of gene expression and alternative splicing in bees during C. bombi infection. We have performed four analyses, 1) comparing gene expression in infected and non-infected bees 24 hours after infection by Crithidia bombi , 2) comparing expression at 24 and 48 hours after C. bombi infection, 3) determining the differential gene expression associated with the bumblebee-Crithidia genotype-genotype interaction at 24 hours after infection and 4) determining the alternative splicing associated with the bumblebee-Crithidia genotype-genotype interaction at 24 hours post infection. Results: We found a large number of genes differentially regulated related to numerous canonical immune pathways. These genes include receptors, signaling pathways and effectors. We discovered a possible interaction between the peritrophic membrane and the insect immune system in defense against Crithidia . Most interestingly, we found differential expression and alternative splicing of immunoglobulin related genes ( Dscam and Twitchin ) are associated with the genotype-genotype interactions of the given bumblebee colony and Crithidia strain. Conclusions: In this paper we have shown that the expression and alternative splicing of immune genes is associated with specific interactions between different host and parasite genotypes in this bumblebee/trypanosome model.
Modelling peculiar velocities of dark matter haloes

We present a simple model that accurately describes various statistical properties of peculiar velocities of dark matter haloes. We pay particular attention to the following two effects. First, the evolution of the halo peculiar velocity depends on the local matter density, instead of the global density. Secondly, dark matter haloes are biased tracers of the underlying mass distribution, thus haloes tend to be located preferentially at high density regions. For the former, we develop an empirical model calibrated with N -body simulations while, for the latter, we use a conventional halo bias model based on the extended Press-Schechter model combined with an empirical lognormal probability distribution function of the mass density distribution. We find that, compared with linear theory, the present model significantly improves the accuracy of predictions of statistical properties of the halo peculiar velocity field including the velocity dispersion, the probability distribution function, and the pairwise velocity dispersion at large separations. Thus, our model predictions may be useful in analysing future observations of the peculiar velocities of galaxy clusters.
Energy Absorption Performance of Meso-Scale Discontinuous Carbon Fibre Composites

Discontinuous carbon fiber composites are increasingly being considered for use in automotive crash energy management structures. Discontinuous fibers represent a route to high speed, low cost automated manufacture, either in the form of moulding compound, advanced moulding compound, or directed fiber preforming approaches. In this research, 40 discontinuous 6K high strength carbon/epoxy tubes have been preformed and manufactured for testing. Variables were fiber length (30mm, 60mm, and 90mm), specimen shape (circular or square), and thickness (2.54mm and 5.08mm). Mouldings were cut into 4 specimens and tested both quasi-statically at 1.6e-4m/s and dynamically at 5m/s. Average specific energy absorption (SEA) was 62.5kJ/kg for static and 43kJ/kg for dynamic. The optimum fiber architecture was a circular tube profile with 30mm long fibers and 5mm wall thickness which gave SEA values of 80.2kJ/kg and 48.4kJ/kg. In-plane mechanical testing was also performed on planar versions of the same fiber architectures to determine whether mesoscopic homogeneity effects which dominate tensile testing affect the energy absorption levels, but poor correlation was observed between tensile and energy absorption results.
Adoptive transfer of anti-CD3-activated CD4+ T cells plus cyclophosphamide and liposome-encapsulated interleukin-2 cure murine MC-38 and 3LL tumors and establish tumor-specific immunity.

The infusion of anti-CD3-activated murine T cells plus interleukin-2 (IL-2) exerts antitumor effects against several tumors in murine immunotherapy models. This study compares the therapeutic efficacy of anti-CD3-activated CD4+ or CD8+ T-cell subsets, when given with cyclophosphamide (Cy) and liposome-encapsulated IL-2 (L-IL2) in a murine model. C57BL/6 mice bearing subcutaneous (S.C.) MC-38 colon adenocarcinoma, 3LL Lewis lung carcinoma, or 38C13 lymphoma for 7 to 14 days were pretreated with low-dose intraperitoneal (I.P.) Cy before intravenous (I.V.) injection of anti-CD3-activated T cells or T-cell subsets. Cell administration was followed by I.P. administration of L-IL2 for 5 days. Mice receiving activated CD4+ T cells showed significantly reduced tumor growth or complete remissions with prolonged disease-free survival in MC-38, 3LL, and 38C13. The timing of Cy doses in relation to adoptive transfer was critical in obtaining the optimal antitumor effect by CD4+ cells. Injecting Cy 4 days before the infusion of CD4+ cells greatly enhanced the antitumor effect of the CD4+ cells and improved survival of the mice compared with other Cy regimens. C57BL/6 mice cured of MC-38 after treatment with CD4+ T cells developed tumor-type immunologic memory as demonstrated by their ability to reject rechallenges with MC-38, but not 3LL. Similarly, mice cured of 3LL tumors rejected rechallenges of 3LL, but not MC-38. The immunologic memory could be transferred with an I.V. injection of splenocytes from mice cured of MC-38 or 3LL. No cytotoxic T-lymphocyte activity was detected in T cells or T-cell subsets from mice cured of MC-38 or 3LL. Increased IL-2 and interferon-gamma (IFN-gamma) production was observed from CD4+ subsets in cured animals when stimulated in vitro with the original tumor, but not with an unrelated syngeneic tumor. These results suggest that tumor-specific immunity can be achieved in vivo with anti-CD3-stimulated CD4+ T cells in this cellular therapy model.
The effect of a preliminary programming and problem solving course on performance in a traditional programming course for computer science majors

A preliminary PASCAL course which emphasized problem solving was designed for incoming computer science majors who were identified as being at risk. In addition, students in the required PASCAL course could transfer back to the preliminary course prior to the administration of the first examination. Students in the preliminary course were paired with comparable freshman majors from the preceeding academic year. Paired t-tests revealed significantly higher grades in the required course for those students who had previously completed the preliminary course. The preliminary course also served as a filter; approximately 43% of the students did not subsequently attempt the required course. Sex differences in persistence were also noted.
Direct and indirect effects of H-NS and Fis on global gene expression control in Escherichia coli

Nucleoid-associated proteins (NAPs) are global regulators of gene expression in Escherichia coli, which affect DNA conformation by bending, wrapping and bridging the DNA. Two of these—H-NS and Fis—bind to specific DNA sequences and structures. Because of their importance to global gene expression, the binding of these NAPs to the DNA was previously investigated on a genome-wide scale using ChIP-chip. However, variation in their binding profiles across the growth phase and the genome-scale nature of their impact on gene expression remain poorly understood. Here, we present a genome-scale investigation of H-NS and Fis binding to the E. coli chromosome using chromatin immunoprecipitation combined with high-throughput sequencing (ChIP-seq). By performing our experiments under multiple time-points during growth in rich media, we show that the binding regions of the two proteins are mutually exclusive under our experimental conditions. H-NS binds to significantly longer tracts of DNA than Fis, consistent with the linear spread of H-NS binding from high- to surrounding lower-affinity sites; the length of binding regions is associated with the degree of transcriptional repression imposed by H-NS. For Fis, a majority of binding events do not lead to differential expression of the proximal gene; however, it has a significant indirect effect on gene expression partly through its effects on the expression of other transcription factors. We propose that direct transcriptional regulation by Fis is associated with the interaction of tandem arrays of Fis molecules to the DNA and possible DNA bending, particularly at operon-upstream regions. Our study serves as a proof-of-principle for the use of ChIP-seq for global DNA-binding proteins in bacteria, which should become significantly more economical and feasible with the development of multiplexing techniques.
Cutaneous collision tumour (melanocytic naevus, basal cell carcinoma, seborrhoeic keratosis): a clinical, dermoscopic and pathological case report

The association of contiguous or ‘collision’ tumours in the same biopsy specimen is not uncommon and is often reported in the literature. The most common association, basal cell carcinoma (BCC) and naevus, is very difficult to diagnose clinically. We describe a 38‐year‐old woman with a previous history of melanoma, who presented with a modified pigmented lesion of the hip that had begun to change 6 months earlier. Histologically, the lesion was a melanocytic compound naevus and a BCC with a seborrhoeic keratosis. The case was investigated clinically and by focusing on the dermoscopic features and their pathological correlates. Cutaneous collision tumours are extremely difficult to diagnose preoperatively, even with the help of dermoscopy, in particular when one of the lesions is melanocytic.
Event-Separation Properties of Event-Triggered Control Systems

In this paper, we study fundamental properties of minimum inter-event times for several event-triggered control architectures, both in the absence and presence of external disturbances and/or measurement noise. This analysis reveals, amongst others, that for several popular event-triggering mechanisms no positive minimum inter-event time can be guaranteed in the presence of arbitrary small external disturbances or measurement noise. This clearly shows that it is essential to include the effects of external disturbances and measurement noise in the analysis of the computation/communication properties of event-triggered control systems. In fact, this paper also identifies event-triggering mechanisms that do exhibit these important event-separation properties.
Esaim: Control, Optimisation and Calculus of Variations Regularity and Variationality of Solutions to Hamilton-jacobi Equations. Part I: Regularity (2nd Edition) *

We formulate an Hamilton–Jacobi partial differential equation H(x, Du(x)) = 0 on a n dimensional manifold M , with assumptions of convexity of H(x, ·) and regularity of H (locally in a neighborhood of {H = 0} in T * M); we define the " min solution " u, a generalized solution; to this end, we view T * M as a symplectic manifold. The definition of " min solution " is suited to proving regularity results about u; in particular, we prove in the first part that the closure of the set where u is not regular may be covered by a countable number of n − 1 dimensional manifolds, but for a H n−1 negligeable subset. These results can be applied to the cutlocus of a C 2 submanifold of a Finsler manifold. The dates will be set by the publisher.
Combined dexamethasone/corticotropin-releasing factor test in chronic fatigue syndrome

Background Studies of hypothalamic–pituitary–adrenal (HPA) axis function in chronic fatigue syndrome (CFS) point to hypofunction, although there are negative reports. Suggested mechanisms include a reduced hypothalamic or supra-hypothalamic stimulus to the HPA axis and enhanced sensitivity to the negative feedback of glucocorticoids. The aim of the current study was to investigate HPA axis function in CFS with the dexamethasone/corticotropin-releasing factor (Dex/CRF) test, in analogy with research in affective disorders. Method Thirty-four well-characterized female CFS patients and 25 healthy control subjects participated in the low-dose Dex/CRF test. Current major depressive episode was an exclusion criterion. History of early-life stress (ELS) was assessed with the Structured Trauma Interview. Results Salivary cortisol responses after 0.5 mg Dex were lower in CFS patients than in controls (before 100 μg CRF, p=0.038; after 100 μg CRF, p=0.015). A secondary analysis revealed an influence of early-life stress and of oestrogen intake. After removal of the 10 participants who were taking an oral oestrogen, patients without a history of ELS showed lower cortisol responses than patients with ELS and controls (before CRF, p=0.005; after CRF, p=0.008). Conclusions CFS is globally associated with reduced cortisol responses in the combined low-dose Dex/CRF test, but this effect is only clearly present in CFS patients without a history of ELS. This study provides further support for an enhanced glucocorticoid negative feedback and/or a reduced central HPA axis drive in CFS. Furthermore, it demonstrates that ELS is an important variable to consider in CFS research.
Characterization of stable kinetic equilibria of rigid, dipolar rod ensembles for coupled dipole–dipole and Maier–Saupe potentials

We study equilibria of the Smoluchowski equation for rigid, dipolar rod ensembles where the intermolecular potential couples the dipole–dipole interaction and the Maier–Saupe interaction. We thereby extend previous analytical results for the decoupled case of the dipolar potential only (Fatkullin and Slastikov 2005 Nonlinearity 18 2565–80; Ji et al Phys. Fluids at press; Wang et al 2005 Commun. Math. Sci. 3 605–20) or the Maier–Saupe potential only (Constantin et al 2004 Arch. Ration. Mech. Anal. 174 365–84; Constantin et al 2004 Discrete Contin. Dyn. Syst. 11 101–12; Constantin and Vukadinovic 2005 Nonlinearity 18 441–3; Constantin 2005 Commun. Math. Sci. 3 531–44; Fatkullin and Slastikov 2005 Commun. Math. Sci. 3 21–6; Liu et al 2005 Commun. Math. Sci. 3 201–18; Luo et al 2005 Nonlinearity 18 379–89; Zhou et al 2005 Nonlinearity 18 2815–25; Zhou and Wang Commun. Math. Sci. at press), and prove certain numerical observations for equilibria of coupled potentials (Ji et al Phys. Fluids at press). We first derive stability conditions, on the magnitude of the polarity vector (the first moment of the orientational probability distribution function) and on the direction of the polarity. We then prove that all stable equilibria of rigid, dipolar rod dispersions are either isotropic or prolate uniaxial. In particular, all stable anisotropic equilibrium distributions admit the following remarkable symmetry: the peak axis of orientation is aligned with both the polarity vector (first moment) and the distinguished director of the uniaxial second moment tensor. The stability is essential in establishing the axisymmetry. To demonstrate that the stability is indeed required, we show that there exist unstable non-axisymmetric equilibria.
Effect of annealing time of an ice crystal on the activity of type III antifreeze protein

Antifreeze proteins (AFPs) possess a unique ability to bind to a seed ice crystal to inhibit its growth. The strength of this binding has been evaluated by thermal hysteresis (TH). In this study, we examined the dependence of TH on experimental parameters, including cooling rate, annealing time, annealing temperature and the size of the seed ice crystal for an isoform of type III AFP from notched‐fin eelpout (nfeAFP8). TH of nfeAFP8 dramatically decreased when using a fast cooling rate (0.20 °C·min−1). It also decreased with increasing seed crystal size under a slow cooling rate (0.01 °C·min−1), but such dependence was not detected under the fast cooling rate. TH was enhanced 1.4‐ and 2.5‐fold when ice crystals were annealed for 3 h at 0.05 and 0.25 °C below Tm, respectively. After annealing for 2 h at 0.25 °C below Tm, TH activity showed marked dependence on the size of ice crystals. These results suggest that annealing of an ice crystal for 2–3 h significantly increased the TH value of type III AFP. Based on a proposed adsorption–inhibition model, we assume that type III AFP undergoes additional ice binding to the convex ice front over a 2–3 h time scale, which results in the TH dependence on the annealing time.
Hepatitis B Virus Revaccination With Standard Versus Pre-S Vaccine in Previously Immunized Patients With Celiac Disease

Objective: Previous studies have suggested that hepatitis B virus (HBV) vaccines may be less immunogenic in individuals with celiac disease (CD). A pre-S vaccine (Sci-B-Vac) has demonstrated superior immunogenicity compared with standard HBV vaccines in several diseases. We compared the short-term immunogenicity of a pre-S vaccine with a HBV vaccine (Engerix B) for repeat vaccination of seronegative, previously immunized patients with CD. Methods: Participants were 1 to 18-year-old children with CD who despite standard HBV vaccines in infancy had nonprotective hepatitis B surface antibody (HBs-Ab) concentrations (⩽10 mIU/mL). Patients were randomized to receive either Engerix B or pre-S vaccine. HBs-Ab concentrations were measured 1 month after the first dose. For those who had not responded after 1 dose, measurement was repeated after the third dose. Results: Children (n = 82) were analyzed (42 pre-S vaccine and 40 Engerix B). Baseline characteristics were similar for both groups, including gluten-free diet status. Both arms showed high response rates following the first injection: 41 (98%) versus 35 (87%) for pre-S vaccine and Engerix B recipients, respectively (P = 0.08). All other patients responded when measured after dose 3. HBs-Ab concentrations (mIU/mL) were higher in the pre-S vaccine group (median 925, interquartile range [IQR] 424–1000) than the Engerix B group (median 363, IQR 106–996, P = 0.005). Twenty (48%) of the pre-S vaccine recipients were “high responders” (>1000 mIU/mL) versus 10 (25%) in Engerix B recipients (P = 0.008). Conclusions: Both vaccines elicited adequate booster responses in most previously vaccinated patients with CD with nonprotective HBs-Ab concentrations. Pre-S vaccine administration resulted in higher Hbs-Ab concentrations. Our data suggest that a single dose of either vaccine is sufficient to raise titers to protective levels in most patients with CD.