Miracle-dz/UniFAR-FTUs huggingface dataset:
Plasma Markers for Identifying Patients with Metastatic Melanoma

Purpose: With the rising incidence of melanoma, more patients are undergoing surveillance for disease recurrence. Our purpose was to study levels of proteins that might be secreted in the blood of patients with metastatic melanoma that can be used for monitoring these individuals. Methods: Genome-wide gene expression data were used to identify abundantly expressed genes in melanoma cells that encode for proteins likely to be present in the blood of cancer patients, based on high expression levels in tumors. ELISA assays were employed to measure proteins in plasma of 216 individuals; 108 metastatic melanoma patients and 108 age- and gender-matched patients with resected stage I/II disease split into equal-sized training and test cohorts. Results: Levels of seven markers, CEACAM (carcinoembryonic antigen–related cell adhesion molecule), ICAM-1 (intercellular adhesion molecule 1), osteopontin, MIA (melanoma inhibitory activity), GDF-15 (growth differentiation factor 15), TIMP-1 (tissue inhibitor of metalloproteinase 1), and S100B, were higher in patients with unresected stage IV disease than in patients with resected stage I/II disease. About 81% of the stage I/II patients in the training set had no marker elevation, whereas 69% of the stage IV patients had elevation of at least one marker (P < 0.0001). Receiver operating characteristic curves for the markers in combination in these two patient populations had an area under curve (AUC) of 0.79 in the training set and 0.8 in the test set. A CART (Classification and Regression Trees) model developed in the training set further improved the AUC in the test set to 0.898. Conclusions: Plasma markers, particularly when assessed in combination, can be used to monitor patients for disease recurrence and can compliment currently used lactate dehydrogenase and imaging studies; prospective validation is warranted. Clin Cancer Res; 17(8); 2417–25. ©2011 AACR.
Erythropoietin protects against acute kidney injury and failure

Erythropoietin (EPO) has traditionally been viewed as a hormone dedicated to the regulation of erythropoiesis. More recently, the EPO receptor (EPOR) has been found to be expressed in a large variety of non-haematopoietic tissues suggesting that EPO might have important actions beyond erythrocyte production. Over the last five years, short-term, high dose administration of EPO has been shown to ameliorate acute kidney injury (AKI), as evidenced by suppressed tubular epithelial apoptosis, enhanced tubular epithelial proliferation, and hastened functional recovery. This renoprotective effect is still apparent when administration is delayed up to 6 hours after the onset of injury and has been demonstrated in a variety of animals (mouse, rat, dog, pig) in response to a variety of renal insults (ischaemia-reperfusion injury, cisplatin, ureteral obstruction, cyclosporine, radiographic contrast, endotoxaemia, heat-shock, and aristolochic acid). Based on these highly encouraging results, several large randomised controlled trials of EPO therapy in ischaemic or toxic AKI are currently underway. The purpose of this article is to review the experimental and clinical evidence for a renoprotective benefit of EPO in acute kidney injury (AKI), the potential mechanisms underpinning these renoprotective actions and possible future directions for research in this important area.
THE RELATIONSHIP BETWEEN PERCEPTUAL AND PHYSICAL SPACE OF FRICATIVES

This study investigates the correlations between perceptual and other process is involved, for example; the distance metric may be physical spaces of voiceless English fricatives /f 6 s 5 h/, using Multidimensional scaling (MDS) technique. The spatial representations were constructed from perceptual similarity judgments and various spectral distance measures [1]. The results show that physical configuration based on Euclidean distance metric produces best prediction of the perceptual data. In both spaces, 2-dimensional solutions adequately accounted for the data and fricatives in the map were clearly organised in terms of their ‘place’ and ‘sibilance’ properties. The two dimensions were also closely correlated to the frequency of the main spectral peak and the ‘peakiness’ of spectra in their acoustic characterisation. The close correlation between linguistic characterisations of fricatives and their perceptual and physical configurations supports a model of speech perception based mainly on the general physical characteristics of speech.
Optimizing the reading of electronic text using rapid serial visual presentation

The focus on communications technology in recent years has led to the question of how to best display electronic text onto small-screened devices. Past studies have shown that the compact method of rapid serial visual presentation (RSVP) is efficient but not well liked. Two experiments were conducted to explore ways of improving the preference for and feasibility of RSVP. In experiment 1, the effects of a completion meter, punctuation pauses, and variable word duration were studied. Although the sentence-by-sentence and normal page formats were still superior, post-experiment ratings indicated that punctuation pauses improved user preference for RSVP, and its preference increased in general with practice. In experiment 2, a modified RSVP condition included a completion meter, punctuation pauses, interruption pauses and pauses at clause boundaries. This condition was significantly preferred to a normal RSVP condition. The present enhancements may increase the feasibility of using RSVP with small displays.
Ocular manifestations of graft-versus-host disease: 10 years’ experience

Purpose To evaluate the ocular presentation, treatment, and clinical course of graft-versus-host disease (GVHD). Design Retrospective case series. Participants Two hundred and forty-nine patients with systemic GVHD were included in the study. Methods Ocular and systemic data were collected from 2003 to 2013. Main outcome measures Mortality, visual acuity, and response of ocular symptoms. Results Sixty-four patients had ocular manifestations (25.7%). At presentation, the mean age was 44.5 years and mean latency was 16.4 months. The most common presentations were keratoconjunctivitis sicca, cataract, blepharitis, ocular hypertension, and filamentary keratitis. Visual acuity at presentation was 20/49; at the worst point in the disease was 20/115; and at most recent visit was 20/63. When topical anti-inflammatory drops were used in addition to tears, 54.3% of patients’ ocular symptoms stabilized. When autologous serum was used in addition, 80% stabilized. The overall 10-year mortality of GVHD was 29.7%. For those with ocular involvement, it was 21.9%. Conclusion Systemic GVHD has a high mortality rate, but ocular involvement does not suggest a worse prognosis. The main ocular presentations were keratoconjunctivitis sicca, cataracts, and ocular hypertension. Dry eyes in this population were very severe with overall worsening in visual acuity. However, with a step-wise approach involving topical anti-inflammatory medications and autologous serum tears, ocular symptoms do improve. It is important to monitor these patients closely, as they are prone to serious ocular complications such as corneal perforation and endophthalmitis.
Prevalence of restless legs syndrome among men aged 18 to 64 years: An association with somatic disease and neuropsychiatric symptoms

Standardized diagnostic criteria determined by the International Restless Legs Syndrome Study Group were used to investigate the current prevalence of restless legs syndrome (RLS). Possible associations between RLS and neuropsychiatric and somatic complaints were also investigated. A random sample of 4,000 men living in central Sweden were sent a questionnaire that included questions about sleep habits, symptoms of sleepiness, and somatic and neuropsychiatric complaints. Four symptom questions accepted as minimal diagnostic criteria for RLS were also included. Odds (OR) ratios and 95% confidence interval (CI) for different variables were calculated by means of multivariate logistic regression; 5.8% of the men suffered from RLS. The prevalence of RLS increased with age. Sleep‐related complaints were more frequent among the RLS sufferers. Complaints of headache at awakening and daytime headache were reported three to five times more frequently among RLS sufferers and there was a tendency toward reported social isolation related to RLS. Subjects with RLS more frequently reported depressed mood (OR, 2.6; 95% CI, 1.8–3.8), and complained more often of reduced libido (OR, 2.2; 95% CI, 1.4–3.3). RLS sufferers more frequently reported hypertension (OR, 1.5; 95% CI, 0.9–2.4) and heart problems (OR, 2.5; 95% CI, 1.4–4.3). Results show that restless legs syndrome is common among men. It is hypothesized that RLS may be associated with several somatic and neuropsychiatric symptoms. © 2001 Movement Disorder Society.
Relationship Between Cancer and Cardiovascular Outcomes Following Percutaneous Coronary Intervention

Background Cardiovascular disease and cancer increasingly coexist, yet relationships between cancer and long-term cardiovascular outcomes post–percutaneous coronary intervention (PCI) are not well studied. Methods and Results We examined stented PCI patients at Duke (1996–2010) using linked data from the Duke Information Systems for Cardiovascular Care and the Duke Tumor Registry (a cancer treatment registry). Our primary outcome was cardiovascular mortality. Secondary outcomes included composite cardiovascular mortality, myocardial infarction, or repeat revascularization and all-cause mortality. We used adjusted cause-specific hazard models to examine outcomes among cancer patients (cancer treatment pre-PCI) versus controls (no cancer treatment pre-PCI). Cardiovascular mortality was explored in a cancer subgroup with recent (within 1 year pre-PCI) cancer and in post-PCI cancer patients using post-PCI cancer as a time-dependent variable. Among 15 008 patients, 3.3% (n=496) were cancer patients. Observed rates of 14-year cardiovascular mortality (31.4% versus 27.7%, P=0.31) and composite cardiovascular death, myocardial infarction, or revascularization (51.1% versus 55.8%, P=0.37) were similar for cancer versus control groups; all-cause mortality rates were higher (79.7% versus 49.3%, P<0.01). Adjusted risk of cardiovascular mortality was similar for cancer patients versus controls (hazard ratio 0.95; 95% CI 0.76 to 1.20) and for patients with versus without recent cancer (hazard ratio 1.46; 95% CI 0.92 to 2.33). Post-PCI cancer, present in 4.3% (n=647) of patients, was associated with cardiovascular mortality (adjusted hazard ratio 1.51; 95% CI 1.11 to 2.03). Conclusions Cancer history was present in a minority of PCI patients but was not associated with worse long-term cardiovascular outcomes. Further investigation into PCI outcomes in this population is warranted.
A Simple End-to-End Throughput Model for 802.11 Multi-Radio Multi-Rate Wireless Mesh Networks

We address the problem of estimating the end-to-end throughput of UDP flows in a multi-radio, multi-channel, and multi-rate 802.11 wireless mesh network (WMN). Estimates of the end-to-end throughput of flows in a WMN can facilitate the design of traffic-aware routing and channel assignment algorithms. We introduce a simple and intuitive model that captures key features of 802.11 WMNs such as contention, interference, and performance degradation due to links with low transmission rates. We use simulation to validate the accuracy of the proposed model in various scenarios for a network topology containing multiple transmitters and wired gateways.
Vedolizumab exposure in pregnancy: outcomes from clinical studies in inflammatory bowel disease

Vedolizumab is a gut‐selective immunoglobulin G1 monoclonal antibody to α4β7 integrin for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). Prospective clinical studies of vedolizumab in pregnancy have not been conducted; therefore, existing safety data of vedolizumab in pregnancy were examined.
Myristoleic acid, a cytotoxic component in the extract from Serenoa repens, induces apoptosis and necrosis in human prostatic LNCaP cells

Prostatic tumors are well known to progress to hormonal therapy‐resistant terminal states. At this stage, there are no chemotherapeutic agents to affect clinical outcome. An effective cell death inducer for these prostate cells may be a candidate as an attractive antitumor agent. The extracts from S. repens have been used to improve the state of prostatic diseases and we have attempted to identify the effective component from the extract.
Homologous recombination and non‐homologous end‐joining pathways of DNA double‐strand break repair have overlapping roles in the maintenance of chromosomal integrity in vertebrate cells

Eukaryotic cells repair DNA double‐strand breaks (DSBs) by at least two pathways, homologous recombination (HR) and non‐homologous end‐joining (NHEJ). Rad54 participates in the first recombinational repair pathway while Ku proteins are involved in NHEJ. To investigate the distinctive as well as redundant roles of these two repair pathways, we analyzed the mutants RAD54−/−, KU70−/− and RAD54−/−/KU70−/−, generated from the chicken B‐cell line DT40. We found that the NHEJ pathway plays a dominant role in repairing γ‐radiation‐induced DSBs during G1–early S phase while recombinational repair is preferentially used in late S–G2 phase. RAD54−/−/KU70−/− cells were profoundly more sensitive to γ‐rays than either single mutant, indicating that the two repair pathways are complementary. Spontaneous chromosomal aberrations and cell death were observed in both RAD54−/− and RAD54−/−/KU70−/− cells, with RAD54−/−/KU70−/− cells exhibiting significantly higher levels of chromosomal aberrations than RAD54−/− cells. These observations provide the first genetic evidence that both repair pathways play a role in maintaining chromosomal DNA during the cell cycle.
Passage of chromium-mordanted and rare earth-labeled fiber: time of dosing kinetics.

Coastal bermudagrass hay was labeled with Cr by the Cr-mordant procedure and with 177Lu applied to the same fiber. Neutral detergent fiber prepared from the same Coastal bermudagrass hay was labeled with Yb, 169Yb, Tb and 160Tb by soaking overnight following by thorough washing and drying. Wood chips were similarly labeled with Sm or La, and Solka Floc was labeled with 147Nd and 141Ce. The carriers, labels and times of administration to cattle were: bermudagrass fiber with both Cr and 177Lu, bermudagrass fiber with 169Yb and Solka Floc labeled with 147Nd at 0 h; bermudagrass fiber with Yb, Solka Floc with 141Ce and wood chips with Sm at 24 h; wood chips with La at 48 h; and bermudagrass fiber labeled with 160Tb at the beginning and labeled with Tb at the end of a meal. Fecal collection followed and passage characteristics were determined with a two-compartment, age-dependent model. Markers labeling the different fiber sources had different (P less than .01) passage rates (Solka Floc greater than Coastal bermudagrass greater than wood chips), but there was no difference within fiber source for rare earth passage. There also was no difference between the passage characteristics of Cr-mordant and 177Lu. However, passage rate of particles administered at the beginning of the meal (160Tb) was 42% higher than for particles at the end of the meal (Tb). (ABSTRACT TRUNCATED AT 250 WORDS)
Buffer-based smooth rate adaptation for dynamic HTTP streaming

Recently, Dynamic Streaming over HTTP (DASH) has been widely deployed in the Internet. However, it is still a challenge to play back video smoothly with high quality in the time-varying Internet. In this paper, we propose a buffer based rate adaptation scheme, which is able to smooth bandwidth variations and provide a continuous video playback. Through analysis, we show that simply preventing buffer underflow/overflow in the greedy rate adaptation method may incur serious rate oscillations, which is poor quality-of-experience for users. To improve it, we present a novel control-theoretic approach to control buffering size and rate adaptation. We modify the buffered video time model by adding two thresholds: an overflow threshold and an underflow threshold, to filter the effect of short-term network bandwidth variations while keeping playback smooth. However, the modified rate adaptation system is nonlinear. By choosing operating point properly, we linearize the rate control system. By a Proportional-Derivative (PD) controller, we are able to adapt video rate with high responsiveness and stability. We carefully design the parameters for the PD controller. Moreover, we show that reserving a small positive/negative bandwidth margin can greatly decrease the opportunities of buffer underflow/overflow incurred by the bandwidth prediction error. At last, we demonstrate that our proposed control-theoretic approach are highly efficient through real network trace.
Drosophila Mon2 couples Oskar-induced endocytosis with actin remodeling for cortical anchorage of the germ plasm

Drosophila pole (germ) plasm contains germline and abdominal determinants. Its assembly begins with the localization and translation of oskar (osk) RNA at the oocyte posterior, to which the pole plasm must be restricted for proper embryonic development. Osk stimulates endocytosis, which in turn promotes actin remodeling to form long F-actin projections at the oocyte posterior pole. Although the endocytosis-coupled actin remodeling appears to be crucial for the pole plasm anchoring, the mechanism linking Osk-induced endocytic activity and actin remodeling is unknown. Here, we report that a Golgi-endosomal protein, Mon2, acts downstream of Osk to remodel cortical actin and to anchor the pole plasm. Mon2 interacts with two actin nucleators known to be involved in osk RNA localization in the oocyte, Cappuccino (Capu) and Spire (Spir), and promotes the accumulation of the small GTPase Rho1 at the oocyte posterior. We also found that these actin regulators are required for Osk-dependent formation of long F-actin projections and cortical anchoring of pole plasm components. We propose that, in response to the Osk-mediated endocytic activation, vesicle-localized Mon2 acts as a scaffold that instructs the actin-remodeling complex to form long F-actin projections. This Mon2-mediated coupling event is crucial to restrict the pole plasm to the oocyte posterior cortex.
Genome-Wide Functional Profiling Identifies Genes and Processes Important for Zinc-Limited Growth of Saccharomyces cerevisiae

Zinc is an essential nutrient because it is a required cofactor for many enzymes and transcription factors. To discover genes and processes in yeast that are required for growth when zinc is limiting, we used genome-wide functional profiling. Mixed pools of ∼4,600 deletion mutants were inoculated into zinc-replete and zinc-limiting media. These cells were grown for several generations, and the prevalence of each mutant in the pool was then determined by microarray analysis. As a result, we identified more than 400 different genes required for optimal growth under zinc-limiting conditions. Among these were several targets of the Zap1 zinc-responsive transcription factor. Their importance is consistent with their up-regulation by Zap1 in low zinc. We also identified genes that implicate Zap1-independent processes as important. These include endoplasmic reticulum function, oxidative stress resistance, vesicular trafficking, peroxisome biogenesis, and chromatin modification. Our studies also indicated the critical role of macroautophagy in low zinc growth. Finally, as a result of our analysis, we discovered a previously unknown role for the ICE2 gene in maintaining ER zinc homeostasis. Thus, functional profiling has provided many new insights into genes and processes that are needed for cells to thrive under the stress of zinc deficiency.
Percutaneous Implantation of the CoreValve Self-Expanding Valve Prosthesis in High-Risk Patients With Aortic Valve Disease: The Siegburg First-in-Man Study

Background— The morbidity and mortality of surgical aortic valve replacement are increased in elderly patients with multiple high-risk comorbid conditions. Therefore, a prospective, single-center, nonrandomized study was performed in high-risk patients with aortic valve disease to evaluate the feasibility and safety of percutaneous implantation of a novel self-expanding aortic valve bioprosthesis (CoreValve). Methods and Results— Symptomatic high-risk patients with an aortic valve area <1 cm2 were considered for enrollment. CoreValve implantation was performed under general anesthesia with extracorporeal support using the retrograde approach. Clinical follow-up and transthoracic echocardiography were performed after the procedure and at days 15 and 30 after device implantation to evaluate short-term patient and device outcomes. A total of 25 patients with symptomatic aortic valve stenosis (mean gradient before implantation, 44.2±10.8 mm Hg) and multiple comorbidities (median logistic EuroScore, 11.0%) were enrolled. Device success and procedural success were achieved in 22 (88%) and 21 (84%) patients, respectively. Successful device implantation resulted in a marked reduction in the aortic valve gradients (mean gradient after implantation, 12.4±3.0 mm Hg; P<0.0001). The mean aortic regurgitation grade was unchanged. Major in-hospital cardiovascular and cerebral events occurred in 8 patients (32%), including mortality in 5 patients (20%). Among 18 patients with device success surviving to discharge, no adverse events occurred within 30 days after leaving the hospital. Conclusions— Percutaneous implantation of the self-expanding CoreValve aortic valve prosthesis in high-risk patients with aortic stenosis with or without aortic regurgitation is feasible and, when successful, results in marked hemodynamic and clinical improvement.
The Coiled-Coil and Nucleotide Binding Domains of the Potato Rx Disease Resistance Protein Function in Pathogen Recognition and Signaling[W][OA]

Plant genomes encode large numbers of nucleotide binding and leucine-rich repeat (NB-LRR) proteins, some of which mediate the recognition of pathogen-encoded proteins. Following recognition, the initiation of a resistance response is thought to be mediated by the domains present at the N termini of NB-LRR proteins, either a Toll and Interleukin-1 Receptor or a coiled-coil (CC) domain. In order to understand the role of the CC domain in NB-LRR function, we have undertaken a systematic structure–function analysis of the CC domain of the potato (Solanum tuberosum) CC-NB-LRR protein Rx, which confers resistance to Potato virus X. We show that the highly conserved EDVID motif of the CC domain mediates an intramolecular interaction that is dependent on several domains within the rest of the Rx protein, including the NB and LRR domains. Other conserved and nonconserved regions of the CC domain mediate the interaction with the Ran GTPase–activating protein, RanGAP2, a protein required for Rx function. Furthermore, we show that the Rx NB domain is sufficient for inducing cell death typical of hypersensitive plant resistance responses. We describe a model of CC-NB-LRR function wherein the LRR and CC domains coregulate the signaling activity of the NB domain in a recognition-specific manner.