Miracle-dz/UniFAR-FTUs huggingface dataset:
An overview on the use of granisetron in the treatment of emesis associated with cytostatic chemotherapy.

The clinical research programme with granisetron has involved a total of 1,229 patients, 982 receiving granisetron, 233 receiving currently available combination regimens and 14 receiving placebo. The true efficacy of granisetron was evaluated in a placebo-controlled trial with granisetron given prophylactically and being available as rescue medication in the placebo group. Granisetron produced a complete anti-emetic response in 92.9% of patients and was effective as intervention for the emesis experienced by the patients in the placebo group. Dose-finding studies have confirmed the wide therapeutic margin with four-fold increases in dose producing comparable results. In patients receiving high-dose cisplatin chemotherapy, two out of every three patients responded to a single prophylactic dose; which demonstrates granisetron's long duration of action (greater than 24 h). Additional granisetron also demonstrated benefit if the initial dose failed or delayed-onset emesis occurred. These results are also seen with other emetogenic regimens. Granisetron produces a greater degree of control than the anti-emetic combinations of metoclopramide/dexamethasone or dexamethasone/chlorpromazine. The side-effect profile in volunteers was favourable. The profile in patients is more difficult to define due to the range of potent drugs which cancer chemotherapy patients receive. Headache and constipation were the most common effects with granisetron, although the former was treatable with simple analgesics and the latter thought to be related to higher doses and subsided spontaneously. The future is promising, with the possible introduction of a fixed 3 mg i.v. dose administered over 5 min followed by oral maintenance therapy if and when required.
Teacher–student interactions and attachment states of mind as predictors of early romantic involvement and risky sexual behaviors

Adolescents’ capacities to negotiate sexual behavior in romantic relationships have important implications for their reproductive and health outcomes. This study examined adolescents’ interactions with teachers and attachment states of mind as predictors of their romantic involvement and risky sexual behavior in an economically disadvantaged sample. Negative interactions with teachers predicted increased sexual risk-taking behaviors and females’ early romantic involvement. Preoccupied states of mind increased risk for early romantic involvement and the likelihood that females would engage in risky sexual behavior. The findings demonstrate how adolescents’ school experiences contribute to adaptation in romantic relationships in mid to late adolescence above and beyond representations of parent–child attachment.
Delayed Turnover of Unphosphorylated Ssk1 during Carbon Stress Activates the Yeast Hog1 Map Kinase Pathway

In Saccharomyces cerevisiae, the Hog1 mitogen-activated protein kinase (MAPK) pathway coordinates the adaptation to osmotic stress and was recently reported to respond to acute changes in glucose levels. Similarly as in osmotic stress, glucose starvation leads to a transient accumulation of Hog1 in the nucleus. However, the kinetics and the mechanism of Hog1 activation are different for these stress conditions. During osmotic shock the activation of Hog1 can be transduced by either the Sho1 or the Sln1/Ypd1/Ssk1 branch. During glucose starvation the phosphorylation of Hog1 is slower and is completely dependent on Ssk1, but independent of Sho1. To characterize the mechanism of activation of Hog1 during carbon stress, we examined the turnover of Ssk1 protein levels upon glucose starvation in the presence of cycloheximide and monitored protein levels by western blotting. Our data demonstrate that unphosphorylated Ssk1 was quickly degraded during exponential growth and after osmotic stress but remained remarkably stable during glucose limitation. We conclude that glucose starvation induces a delay in the turnover of unphosphorylated Ssk1, which is sufficient to activate the Hog1 MAPK pathway. Although unphosphorylated Ssk1 is known to be degraded by the proteasome, its stabilization is apparently not due to changes in cellular localization or decrease in ubiquitination levels during glucose limitation.
Packet Sampling for Network Monitoring

In this paper, the emphasis is placed on various packet sampling methods and their application to network monitoring. We present the motivations for packet sampling on high-speed network links. We give an overview of all known packet sampling techniques, point out their strengths and weaknesses in terms of reliability and accuracy in the estimation in different network traffic parameters. We also provide more details about the adaptive packet sampling, as a way to increase this accuracy. One of the key objectives of our study is to gain some insight about the feasibility of the packet sampling in context of network anomaly detection. It was proven that packet sampling provides reliable estimates in traffic monitoring applications. However there is not much research on whether packet sampling provides sufficient amount of information for the anomaly detection.
A micromorphometry‐based concept for routine classification of sentinel lymph node metastases and its clinical relevance for patients with melanoma

The sentinel lymph nodes (SLNs) as the primary targets for lymphatic metastases can be removed selectively by γ probe‐guided sentinel lymph nodectomy (SLNE) in nearly all patients with cutaneous melanoma. Correspondingly high standards in terms of specificity, sensitivity, and microstaging are required for the evaluation of SLNs.
Quantitative analysis of multi-agent formations: Theory and applications

Zhu, Guangwei Ph.D., Purdue University, May 2013. Quantitative Analysis of MultiAgent Formations: Theory and Applications. Major Professor: Jianghai Hu. In this thesis, formations of multi-agent systems, including multi-vehicle systems and sensor networks, are studied from a quantitative perspective. First, matrix and scalar valued quantities related to multi-agent system formations are proposed. These quantities are useful in characterizing the robustness, collaborative performance and manipulability of multi-agent systems, are intuitively associated with physical analogies of formations. Their practical value in the analysis of formation control and localization systems is also demonstrated through application examples. With these quantitative characterizations of formations, several optimization problems can be formulated, which are helpful in designing efficient formations for improving the performance of multi-agent systems in various aspects. Finally, based on the concept of stiffness matrix, distributed algorithms are designed to localize agents in the network using angle-of-arrival information. The stability and performance analysis as well as optimization techniques regarding such algorithms are studied using the quantitative framework developed above.
Leptin Regulation of Gonadotrope Gonadotropin-Releasing Hormone Receptors As a Metabolic Checkpoint and Gateway to Reproductive Competence

The adipokine leptin signals the body’s nutritional status to the brain, and particularly, the hypothalamus. However, leptin receptors (LEPRs) can be found all throughout the body and brain, including the pituitary. It is known that leptin is permissive for reproduction, and mice that cannot produce leptin (Lep/Lep) are infertile. Many studies have pinpointed leptin’s regulation of reproduction to the hypothalamus. However, LEPRs exist at all levels of the hypothalamic–pituitary–gonadal axis. We have previously shown that deleting the signaling portion of the LEPR specifically in gonadotropes impairs fertility in female mice. Our recent studies have targeted this regulation to the control of gonadotropin releasing hormone receptor (GnRHR) expression. The hypotheses presented here are twofold: (1) cyclic regulation of pituitary GnRHR levels sets up a target metabolic checkpoint for control of the reproductive axis and (2) multiple checkpoints are required for the metabolic signaling that regulates the reproductive axis. Here, we emphasize and explore the relationship between the hypothalamus and the pituitary with regard to the regulation of GnRHR. The original data we present strengthen these hypotheses and build on our previous studies. We show that we can cause infertility in 70% of female mice by deleting all isoforms of LEPR specifically in gonadotropes. Our findings implicate activin subunit (InhBa) mRNA as a potential leptin target in gonadotropes. We further show gonadotrope-specific upregulation of GnRHR protein (but not mRNA levels) following leptin stimulation. In order to try and understand this post-transcriptional regulation, we tested candidate miRNAs (identified with in silico analysis) that may be binding the Gnrhr mRNA. We show significant upregulation of one of these miRNAs in our gonadotrope-Lepr-null females. The evidence provided here, combined with our previous work, lay the foundation for metabolically regulated post-transcriptional control of the gonadotrope. We discuss possible mechanisms, including miRNA regulation and the involvement of the RNA binding protein, Musashi. We also demonstrate how this regulation may be vital for the dynamic remodeling of gonadotropes in the cycling female. Finally, we propose that the leptin receptivity of both the hypothalamus and the pituitary are vital for the body’s ability to delay or slow reproduction during periods of low nutrition.
Understanding lupus nephritis: diagnosis, management, and treatment options

Systemic lupus erythematosus (SLE) predominantly affects women in their reproductive years. Renal disease (glomerulonephritis) is one of the most frequent and serious manifestations of SLE. Of the various histological types of lupus glomerulonephritis, diffuse proliferative nephritis carries the worst prognosis. Combined with high-dose prednisone, mycophenolate mofetil (MMF) has emerged as a first-line immunosuppressive treatment, although data regarding the efficacy of MMF on the long-term preservation of renal function are forthcoming. Cyclophosphamide is reserved for more severe forms of lupus nephritis, such as crescentic glomerulonephritis with rapidly deteriorating renal function, patients with significant renal function impairment at presentation, and refractory renal disease. Evidence for the calcineurin inhibitors in the treatment of lupus nephritis is weaker, and it concerns patients who are intolerant or recalcitrant to other agents. While further controlled trials are mandatory, B cell modulation therapies, such as rituximab, belimumab and epratuzumab are confined to refractory disease. Non-immunosuppressive measures, such as angiotensin-converting enzyme inhibitors, vigorous blood pressure control, prevention and treatment of hyperlipidemia and osteoporosis, are equally important.
Substituting depth for intensity and real-time phosphene rendering: Visual navigation under low vision conditions

Navigation and way finding including obstacle avoidance is difficult when visual perception is limited to low resolution, such as is currently available on a bionic eye. Depth visualisation may be a suitable alternative. Such an approach can be evaluated using simulated phosphenes with a wearable mobile virtual reality kit. In this paper, we present two novel approaches: (i) an implementation of depth visualisation; and, (ii) novel methods for rapid rendering of simulated phosphenes with an empirical comparison between them. Our new software-based method for simulated phosphene rendering shows large speed improvements, facilitating the display in real-time of a large number of phosphenes with size and brightness dependent on pixel intensity, and with customised output dynamic range. Further, we describe the protocol, navigation environment and system used for visual navigation experiments to evaluate the use of depth on low resolution simulations of a bionic eye perceptual experience. Results for these experiments show that a depth-based representation is effective for navigation, and shows significant advantages over intensity-based approaches when overhanging obstacles are present. The results of the experiments were reported in [1], [2].
Treatment of neuropsychiatric conditions associated with multiple sclerosis

This article reviews the treatment of behavioral disturbances associated with multiple sclerosis. Pharmacological and psychotherapeutic treatment data, when available, are presented for five discrete conditions: major depression, bipolar affective disorder, anxiety, psychosis, pseudobulbar affect and cognitive dysfunction. Despite the paucity of empirical treatment data that characterizes all of these conditions, with the exception of pseudobulbar affect, the message from open-label trials and anecdotal experience is that therapy is often successful, leading to improvements in quality of life for patients. Thus, all health professionals involved in the care of multiple sclerosis patients should have a good working knowledge of the neurotherapeutics of multiple sclerosis-related behavioral disorders.
A prion reduction filter does not completely remove endogenous prion infectivity from sheep blood

Variant Creutzfeldt‐Jakob disease (vCJD) is a transmissible spongiform encephalopathy affecting humans, acquired initially through infection with bovine spongiform encephalopathy (BSE). A small number of vCJD cases have been acquired through the transfusion of blood from asymptomatic donors who subsequently developed vCJD. Filter devices that selectively bind the infectious agent associated with prion disease have been developed for removal of infection from blood. This study independently assessed one such filter, the P‐CAPT filter, for efficacy in removing infectivity associated with the BSE agent in sheep blood. The sheep BSE model has previously been used to evaluate the distribution of infectivity in clinically relevant blood components. This is the first study to assess the ability of the P‐CAPT filter to remove endogenous infectivity associated with blood components prepared from a large animal model.
EspM inhibits pedestal formation by enterohaemorrhagic Escherichia coli and enteropathogenic E. coli and disrupts the architecture of a polarized epithelial monolayer

Enterohaemorrhagic Escherichia coli and enteropathogenic E. coli are enteropathogens characterized by their ability to induce the host cell to form actin‐rich structures, termed pedestals. A type III secretion system, through which the pathogens deliver effector proteins into infected host cells, is essential for their virulence and pedestal formation. Enterohaemorrhagic E. coli encodes two similar effectors, EspM1 and EspM2, which activate the RhoA signalling pathway and induce the formation of stress fibres upon infection of host cells. We confirm these observations and in addition show that EspM inhibits the formation of actin pedestals. Moreover, we show that translocation of EspM into polarized epithelial cells induces dramatic changes in the tight junction localization and in the morphology and architecture of infected polarized monolayers. These changes are manifested by altered localization of the tight junctions and ‘bulging out’ morphology of the cells. Surprisingly, despite the dramatic changes in their architecture, the cells remain alive and the epithelial monolayer maintains a normal barrier function. Taken together, our results show that the EspM effectors inhibit pedestal formation and induce tight junction mislocalization as well as dramatic changes in the architecture of the polarized monolayer.
Phagocytosis, peritoneal influx, and enzyme activities in peritoneal macrophages from germfree, conventional, and ex-germfree mice

Peritoneal macrophages from germfree mice showed a higher basic activity of lysosomal enzymes than did macrophages from conventional mice, whereas oil-induced peritoneal influx, induction of lysosomal enzymes, and phagocytosis via the C3b receptor after endotoxin stimulation were reduced or absent. After germfree mice had been housed with conventional mice for 1 week, peritoneal influx and C3b receptor-mediated phagocytosis reached normal levels; after 4 weeks, enzyme activities also reached normal levels.
Molecular mechanisms and pathways in bladder cancer development and progression.

BACKGROUND The basis for bladder cancer development and progression is complex and involves genetic abnormalities. These abnormalities yield phenotypic changes that allow normal transitional cells to become cancerous and finally acquire the "malignant phenotype. " METHODS The authors review the most common genetic alterations in bladder cancer and the molecular mechanisms and pathways involved in the conversion of normal transitional cell into malignant transitional cancer cells. RESULTS There are several potential genetic changes of the urothelium that eventually cause bladder cancer initiation and tumor progression. Some of these alterations are also found in other malignancies suggesting that key common pathways exist in the development of cancer. CONCLUSIONS As the roles of certain genes or proteins are further elucidated, a better understanding of cancer development can aid in the prevention, diagnosis, and treatment of bladder cancer.
The Significance of Deaf Identity for Psychological Well-Being.

Research has paid attention to how deaf identity affects life outcomes such as psychological well-being. However, studies are often carried out with small samples and without including other variables. This study examined how different forms of identity – deaf, hearing, bicultural (deaf and hearing), and marginal (neither deaf nor hearing) – were associated with levels of psychological well-being, including a number of other variables. The sample was 742 adults with hearing loss in Denmark. The study found that identifying as deaf, hearing, and bicultural was associated with better psychological well-being compared to those with a marginal identity. Further, it found that additional disability, educational level, and feeling discriminated against because of hearing loss significantly explained the degree of psychological well-being. Results are discussed here with respect to social identity theory and current deaf identity themes.
Firefighting on Trees Beyond Integrality Gaps

The Firefighter problem and a variant of it, known as Resource Minimization for Fire Containment (RMFC), are natural models for optimal inhibition of harmful spreading processes. Despite considerable progress on several fronts, the approximability of these problems is still badly understood. This is the case even when the underlying graph is a tree, which is one of the most-studied graph structures in this context and the focus of this article. In their simplest version, a fire spreads from one fixed vertex step by step from burning to adjacent non-burning vertices, and at each time step B many non-burning vertices can be protected from catching fire. The Firefighter problem asks, for a given B, to maximize the number of vertices that will not catch fire, whereas RMFC (on a tree) asks to find the smallest B that allows for saving all leaves of the tree. Prior to this work, the best known approximation ratios were an O(1)-approximation for the Firefighter problem and an O(log* n)-approximation for RMFC, both being LP-based and essentially matching the integrality gaps of two natural LP relaxations. We improve on both approximations by presenting a PTAS for the Firefighter problem and an O(1)-approximation for RMFC, both qualitatively matching the known hardness results. Our results are obtained through a combination of the known LPs with several new techniques, which allow for efficiently enumerating over super-constant size sets of constraints to strengthen the natural LPs.
Decoding Binary Node Labels from Censored Edge Measurements: Phase Transition and Efficient Recovery

We consider the problem of clustering a graph G into two communities by observing a subset of the vertex correlations. Specifically, we consider the inverse problem with observed variables Y = B<sub>G</sub>x ⊕ Z, where B<sub>G</sub> is the incidence matrix of a graph G, x is the vector of unknown vertex variables (with a uniform prior), and Z is a noise vector with Bernoulli (ε) i.i. d. entries. All variables and operations are Boolean. This model is motivated by coding, synchronization, and community detection problems. In particular, it corresponds to a stochastic block model or a correlation clustering problem with two communities and censored edges. Without noise, exact recovery (up to global flip) of x is possible if and only the graph G is connected, with a sharp threshold at the edge probability log (n)/n for Erdos-Renyi random graphs. The first goal of this paper is to determine how the edge probabilityp needs to scale to allow exact recovery in the presence of noise. Defining the degree rate of the graph by α = np/log(n), it is shown that exact recovery is possible if and only if α > 2/(1 - 2ε)<sup>2</sup> + o(1/(1 - 2ε)<sup>2</sup>). In other words, 2/(1 - 2ε)<sup>2</sup> is the information theoretic threshold for exact recovery at low-SNR. In addition, an efficient recovery algorithm based on semidefinite programming is proposed and shown to succeed in the threshold regime up to twice the optimal rate. For a deterministic graph G, defining the degree rate as α = d/log(n), where d is the minimum degree of the graph, it is shown that the proposed method achieves the rate α > 4((1 + λ)/(1 - λ)<sup>2</sup>/(1 - 2ε)<sup>2</sup> + o(1/(1 - 2ε)<sup>2</sup>), where 1-λ is the spectral gap of the graph G.
Physical work capacity after 7 wk of wheelchair training: effect of intensity in able-bodied subjects.

PURPOSE The purpose of this study was to study the effects of a 7-wk wheelchair training program on physical work capacity in able-bodied subjects. Effects of training intensities of 50 and 70% heart rate (HR) reserve (HRR) were studied for different subject groups. METHODS Twenty-seven able-bodied male subjects participated in this study. They were randomly divided into a control group (N = 8), a 50%-intensity group (N = 9), and a 70%-intensity group (N = 10). The 50%- and the 70%-intensity groups received a 7-wk wheelchair training program: three times a week, one-half hour wheelchair exercise on a motor driven treadmill at an average intensity of 50 and 70% of the HRR, respectively. Before and after the training period, parameters for physical work capacity (maximal isometric strength (Fiso), sprint power (P30), maximal power output (POmax) and peak oxygen uptake (VO2peak)), and submaximal performance (mechanical efficiency, HR) at 20 and 40% of the estimated POmax (ME20, ME40; HR20, HR40) were obtained during tests on a stationary wheelchair ergometer. RESULTS A two-factor ANOVA for repeated measures on the within-subjects factor "pre-post tests," the between-subject factor training (50% and 70% training vs control) and the interaction term showed that the 50%-intensity group significantly increased on P30 and POmax compared with the control group. The 70% intensity group significantly increased on P30, POmax and VO2peak compared with the control group (P < 0.05). The 70% group did not show significantly higher increases in P30 and POmax over training than the 50% intensity. No significant effects were found for the Fiso and the parameters at submaximal PO. CONCLUSIONS The wheelchair training at both intensities can have favorable effects on maximal physical work capacity in able-bodied subjects, and possibly also on mechanical efficiency at submaximal power output. Effects are seen in parameters for both aerobic and anaerobic work capacities. Although training at 70% intensity was more effective than the 50% intensity, training at 50% HRR may initially be more appropriate in untrained individuals, such as novice wheelchair users at the start of their rehabilitation, to prevent fatigue and enhance motivation.