Miracle-dz/UniFAR-FTUs huggingface dataset:
Risk of Death from Prostate Cancer with and without Definitive Local Therapy when Gleason Pattern 5 is Present: A Surveillance, Epidemiology, and End Results Analysis

Purpose The purpose is to evaluate the patterns of care and comparative effectiveness for cause-specific and overall survival of definitive local treatments versus conservatively managed men with a primary or secondary Gleason pattern of 5. Methods and materials Patients diagnosed from 2004 to 2012 with a primary or secondary Gleason pattern of 5 N0M0 prostate cancer were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier and Cox regression analyses were used to estimate the survival. Results We identified 20,560 men. Median age and follow-up were 68 years and 4.33 years, respectively. At eight years, cause-specific survival (CSS) was 86.6% and 57.4% of those receiving and not receiving definitive local treatments, respectively. For CSS multivariate analysis, the following were significant: age, race, insurance status, total Gleason Score, T-stage, and type or omission of definitive local treatments. Compared to prostatectomy alone, men not undergoing definitive local treatments had the highest risk of death (HR: 6.07; 95% CI: 5.19-7.10). Those undergoing external beam radiotherapy alone (HR: 2.11; 95% CI: 1.80-2.48) were also at elevated risk of death. The number needed to treat (NNT) to prevent a prostate cancer death at eight years was three persons. Conclusions Death from prostate cancer with a primary or secondary Gleason pattern of 5 histology without definitive local treatment is high. In this hypothesis-generating study, we found that men with a limited life expectancy (less than eight years) and non-metastatic Gleason pattern of 5 disease may benefit from definitive local treatments. Given the high mortality in men with a Gleason pattern of 5, combined modality local therapies and consideration of chemotherapies may be warranted.
Noninvasive Quantification of the Contractile Reserve of Stunned Myocardium by Ultrasonic Strain Rate and Strain

Background—We sought to investigate ultrasonic strain rate and strain as new indices to quantify the contractile reserve of stunned myocardium during dobutamine infusion. Methods and Results—Stunning of the left ventricular posterior wall was induced in 9 closed-chest pigs after 30 minutes of severe hypoperfusion followed by 60 minutes of reperfusion of the left circumflex coronary artery territory. A second group of 7 animals had no coronary occlusion and served as normal controls. An incremental dobutamine infusion protocol was used in both groups. Changes in regional radial function were monitored by use of ultrasound-derived maximal systolic radial strain rate (SR) and systolic strain (&egr;). In the control group, dobutamine induced an increase in both SR and maximal dP/dt, which correlated linearly (r =0.85). Conversely, &egr; values increased at low doses of dobutamine (2.5 to 5 &mgr;g · kg−1 · min−1) but decreased during higher infusion rates (10 to 20 &mgr;g · kg−1 · min−1). During circumflex hypoperfusion, SR and &egr; of the posterior wall decreased from 5.0±0.3 s−1 and 63±6% to 2.9±0.3 s−1 and 27±4%, respectively (P <0.01). After 60 minutes of reperfusion, SR and &egr; failed to fully resume because of stunning, averaging 3.6±0.2 s−1 and 35±3%, respectively (P =0.12 versus ischemia, P <0.05 versus baseline). During dobutamine infusion, SR increased at 5 &mgr;g · kg−1 · min−1 and exceeded baseline values at 20 &mgr;g · kg−1 · min−1 (P <0.05), whereas &egr; increased only at high doses and remained below baseline levels (P <0.05). Conclusions—The changes in regional function of stunned myocardium during inotropic stimulation could be characterized by use of ultrasonic deformation parameters. During dobutamine infusion, strain-rate values quantified the contractile reserve better than strain values.
Engaging Engineering Students with Gamification An empirical study

Well-designed games are good motivators by nature, as they imbue players with clear goals and a sense of reward and fulfillment, thus encouraging them to persist and endure in their quests. Recently, this motivational power has started to be applied to non-game contexts, a practice known as Gamification. This adds gaming elements to non-game processes, motivating users to adopt new behaviors, such as improving their physical condition, working more, or learning something new. This paper describes an experiment in which game-like elements were used to improve the delivery of a Master’s level College course, including scoring, levels, leaderboards, challenges and badges. To assess how gamification impacted the learning experience, we compare the gamified course to its non-gamified version from the previous year, using different performance measures. We also assessed student satisfaction as compared to other regular courses in the same academic context. Results were very encouraging, showing significant increases ranging from lecture attendance to online participation, proactive behaviors and perusing the course reference materials. Moreover, students considered the gamified instance to be more motivating, interesting and easier to learn as compared to other courses. We finalize by discussing the implications of these results on the design of future gamified learning experiences. Keywords—Gamification; Education; Student participation; Classroom learning; Evaluation
Treatment Target in Polycythemia Vera

studies). Chance effects cannot be ruled out as a potential explanation for the higher incidence of sudden death, unstable angina, arrhythmia, and acute renal failure observed with peginesatide relative to darbepoetin in the PEARL studies. However, the hypothesis that an intrinsic prop-erty of peginesatide contributed to these findings is unsubstantiated, given that in the EMERALD studies, higher rates of death and cardiovascular events were not observed with peginesatide as compared with epoetin. Patients receiving hemo-dialysis are at high risk for cardiovascular events,
High Prevalence of Celiac Disease in Patients with Lactose Intolerance

Background/Aims: Acquired lactase deficiency is a common cause of gastrointestinal symptoms but its etiology remains unclear. Celiac disease could lead to lactase deficiency and is much more common than previously suspected. Several studies have highlighted the prevalence of lactose intolerance in celiac disease, but studies assessing the prevalence of celiac disease in lactose intolerance are lacking. We evaluated the prevalence of celiac disease in patients with a positive H2-lactose breath test compared to a control group. Methods: This retrospective study included 54 patients (15 males/39 females; mean age 37.8 ± 7 years) from southern Italy, referred to the Gastroenterology Unit for bloating and diarrhea after the introduction of milk or dietary lactose. They had a positive H2-lactose breath test and a negative H2-glucose breath test. 50 blood donors were drawn from a similar population, matched for sex and age, and enrolled as a control group. All patients were screened for possible celiac disease by measuring the serum level of IgA antibodies to endomysium, anti-transglutaminase and total IgA. Patients positive for at least one of these markers were submitted to upper gastrointestinal endoscopy. Results: None of the patients had a IgA deficiency. 24% of the patients showed positivity of celiac disease antibodies compared to 2% in the control group (p < 0.001). Histologic samples of these patients showed villous atrophy (53.8% Marsh type IIIa, 38.4% Marsh IIIb, and 7.6% with Marsh type IIIc) confirming the celiac disease, while in the control subjects duodenal biopsies were normal. Conclusions: A high prevalence of celiac disease was observed in patients with a positive H2-lactose breath test compared to healthy controls. In these subjects lactase deficiency seems to be the only manifestation of celiac disease. We suggest serologic screening for celiac disease in all patients with a positive H2-lactose breath test before beginning a milk-exclusion diet.
Towards Structural Determination of the Water-splitting Enzyme

A photosystem II preparation from the thermophilic cyanobacterium Synechococcus elongatus, which is especially suitable for three-dimensional crystallization in a fully active form was developed. The efficient purification method applied here yielded 10 mg of protein of a homogenous dimeric complex of about 500 kDa within 2 days. Detailed characterization of the preparation demonstrated a fully active electron transport chain from the manganese cluster to plastoquinone in the QB binding site. The oxygen-evolving activity, 5000–6000 μmol of O2/(h·mg of chlorophyll), was the highest so far reported and is maintained even at temperatures as high as 50 °C. The crystals obtained by the vapor diffusion method diffracted to a resolution of 4.3 Å. The space group was determined to be P212121 with four photosystem II dimers per unit cell. Analysis of the redissolved crystals revealed that activity, supramolecular organization, and subunit composition were maintained during crystallization.
Genetic counselling in ALS: facts, uncertainties and clinical suggestions

The clinical approach to patients with amyotrophic lateral sclerosis (ALS) has been largely modified by the identification of novel genes, the detection of gene mutations in apparently sporadic patients, and the discovery of the strict genetic and clinical relation between ALS and frontotemporal dementia (FTD). As a consequence, clinicians are increasingly facing the dilemma on how to handle genetic counselling and testing both for ALS patients and their relatives. On the basis of existing literature on genetics of ALS and of other late-onset life-threatening disorders, we propose clinical suggestions to enable neurologists to provide optimal clinical and genetic counselling to patients and families. Genetic testing should be offered to ALS patients who have a first-degree or second-degree relative with ALS, FTD or both, and should be discussed with, but not offered to, all other ALS patients, with special emphasis on its major uncertainties. Presently, genetic testing should not be proposed to asymptomatic at-risk subjects, unless they request it or are enrolled in research programmes. Genetic counselling in ALS should take into account the uncertainties about the pathogenicity and penetrance of some genetic mutations; the possible presence of mutations of different genes in the same individual; the poor genotypic/phenotypic correlation in most ALS genes; and the phenotypic pleiotropy of some genes. Though psychological, social and ethical implications of genetic testing are still relatively unexplored in ALS, we recommend multidisciplinary counselling that addresses all relevant issues, including disclosure of tests results to family members and the risk for genetic discrimination.
Measuring marine self-potential using an autonomous underwater vehicle

S U M M A R Y The marine self-potential (SP) method is used to explore for hydrothermal venting and associated seafloor mineralization. Measurements are commonly made in deep water using instruments towed close to the seafloor, which requires dedicated ship time, is limited to slow speeds, and is subject to navigation errors. Instead, we mounted a three-axis electric field receiver on an autonomous underwater vehicle (AUV), and tested the method with data collected in the Iheya area of the Okinawa Trough, off Japan. Parts of this prospect have documented hydrothermal venting and seafloor massive sulfide (SMS) deposits. An International Submarine Engineering Limited explorer-class AUV was fitted with a controlled-source electromagnetic (CSEM) amplifier and logging system, modified to collect DC SP data using silver chloride electrodes on approximately 1 m dipoles. A 1 km × 1 km area was surveyed with a flight pattern of six lines, collected three times to assess repeatability and noise levels. The entire data set was collected in a single day on station with a 10 hr AUV deployment. Flying height was 70 m, navigation errors were less than 3 m, collection speed was 1.1 m s−1 and electric field noise levels were less than 5 μV m−1. Localized anomalies of 0.3 mV m−1 were observed, from which potentials were estimated using regularized inversion, yielding negative SP anomalies of 15–25 mV. Modelling electric field data as dipoles shows that the negative poles causing the anomalies are localized near the seafloor with a diffuse return current deeper than 1000 m below seafloor. Apparent conductivities as high as 30 S m−1 were derived from CSEM data collected during the same deployment, which strongly suggests that SMS mineralization is associated with one of the SP anomalies, although the localization near the seafloor and the lack of a dipolar signal suggest that the causative mechanism for the SP anomalies is due to hydrothermal venting. In either case, we have demonstrated that AUV-mounted instrument systems are an efficient, effective and low noise means of collecting marine SP data.
Amifostine Inhibits Angiogenesis in Vivo

Amifostine (WR-2721) is an inorganic thiophosphate-cytoprotective agent developed to selectively protect normal tissues against the toxicity of chemotherapy and radiation. We have previously shown that amifostine protects both chicken embryo chorioallantoic membrane (CAM) vessels and cells from the effects of X-rays. In the present work, we studied the effect of amifostine on angiogenesis in vivo, using the CAM model. Amifostine decreased the number of CAM vessels in a dose-dependent manner, without being toxic for the tissue. It also decreased the mRNA levels of both vascular endothelial growth factor (VEGF) isoforms VEGF165 and VEGF190, 6 and up to 48 h after its application onto the CAM. Similarly, it decreased the mRNA levels of inducible nitric-oxide synthase, 24 and 48 h after drug application. Furthermore, amifostine decreased the deposited amounts of laminin and collagen I 24 h after its application, without affecting the expression of the corresponding genes. The protein amounts and activity of matrix metalloproteinase-2 were not affected, whereas the expression of the corresponding gene was decreased up to 48 h after drug application. Finally, the activity of plasmin was increased 6 h after amifostine application and remained increased at later time points. These findings suggest that amifostine alters the expression of several molecules implicated in the angiogenesis process and affects the composition of the extracellular matrix in a way that leads to inhibition of angiogenesis. Such an antiangiogenic action of amifostine, together with its radioprotective effects, further supports its use in combination with radiotherapy for increased therapeutic efficacy.
Boosting Information Extraction Systems with Character-level Neural Networks and Free Noisy Supervision

We present an architecture to boost the precision of existing information extraction systems. This is achieved by augmenting the existing parser, which may be constraint-based or hybrid statistical, with a character-level neural network. Our architecture combines the ability of constraint-based or hybrid extraction systems to easily incorporate domain knowledge with the ability of deep neural networks to leverage large amounts of data to learn complex features. The network is trained using a measure of consistency between extracted data and existing databases as a form of cheap, noisy supervision. Our architecture does not require large scale manual annotation or a system rewrite. It has led to large precision improvements over an existing, highly-tuned production information extraction system used at Bloomberg LP for financial language text.
An Alternative Splice Form of Mdm2 Induces p53-independent Cell Growth and Tumorigenesis*

The Mdm2 gene is amplified in approximately one-third of human sarcomas and overexpressed in a variety of other human cancers. Mdm2 functions as an oncoprotein, in part, by acting as a negative regulator of the p53 tumor suppressor protein. Multiple spliced forms of Mdm2 transcripts have been observed in human tumors; however, the contribution of these variant transcripts to tumorigenesis is unknown. In this report, we isolate alternative splice forms of Mdm2 transcripts from sarcomas that spontaneously arise in Mdm2-overexpressing mice, including Mdm2-b, the splice form most commonly observed in human cancers. Transduction of Mdm2-b into a variety of cell types reveals that Mdm2-b promotes p53-independent cell growth, inhibits apoptosis, and up-regulates the RelA subunit of NFκB. Furthermore, expression of Mdm2-b induces tumor formation in transgenic mice. These results identify a p53-independent role for Mdm2 and determine that an alternate spliced form of Mdm2 can contribute to formation of cancer via a p53-independent mechanism. These findings also provide a rationale for the poorer prognosis of those patients presenting with tumors harboring multiple Mdm2 transcripts.
Trauma-induced plasmalemma disruptions in three-dimensional neural cultures are dependent on strain modality and rate.

Traumatic brain injury (TBI) results from cell dysfunction or death following supra-threshold physical loading. Neural plasmalemma compromise has been observed following traumatic neural insults; however, the biomechanical thresholds and time-course of such disruptions remain poorly understood. In order to investigate trauma-induced membrane disruptions, we induced dynamic strain fields (0.50 shear or compressive strain at 1, 10, or 30? sec(? 1) strain rate) in 3-D neuronal-astrocytic co-cultures (>500? m thick). Impermeant dyes were present during mechanical loading and entered cells in a strain rate-dependent manner for both shear and compression. Real-time imaging revealed increased membrane permeability in a sub-population of cells immediately upon deformation. Alterations in cell membrane permeability, however, were transient and biphasic over the ensuing hour post-insult, suggesting initial membrane damage and rapid repair, followed by a phase of secondary membrane degradation. At 48? h post-insult, cell death increased significantly in the high-strain-rate group, but not after quasi-static loading, suggesting that cell survival relates to the initial extent of transient structural compromise. Cells were more sensitive to bulk shear deformation than compression with respect to acute permeability changes and subsequent cell survival. These results provide insight into the temporally varying alterations in membrane stability following traumatic loading and provide a basis for elucidating physical cellular tolerances.
Requirements for Brome Mosaic Virus Subgenomic RNA Synthesis In Vivo and Replicase-Core Promoter Interactions In Vitro

ABSTRACT Based solely on in vitro results, two contrasting models have been proposed for the recognition of the brome mosaic virus (BMV) subgenomic core promoter by the replicase. The first posits that the replicase recognizes at least four key nucleotides in the core promoter, followed by an induced fit, wherein some of the nucleotides base pair prior to the initiation of RNA synthesis (S. Adkins and C. C. Kao, Virology 252:1-8, 1998). The second model posits that a short RNA hairpin in the core promoter serves as a landing pad for the replicase and that at least some of the key nucleotides help form a stable hairpin (P. C. J. Haasnoot, F. Brederode, R. C. L. Olsthoorn, and J. Bol, RNA 6:708-716, 2000; P. C. J. Haasnoot, R. C. L. Olsthoorn, and J. Bol, RNA 8:110-122, 2002). We used transfected barley protoplasts to examine the recognition of the subgenomic core promoter by the BMV replicase. Key nucleotides required for subgenomic initiation in vitro were found to be important for RNA4 levels in protoplasts. In addition, additional residues not required in vitro and the formation of an RNA hairpin within the core promoter were correlated with wild-type RNA4 levels in cells. Using a template competition assay, the core promoter of ca. 20 nucleotides was found to be sufficient for replicase binding. Mutations of the key residues in the core promoter reduced replicase binding, but deletions that disrupt the predicted base pairing in the proposed stem retained binding at wild-type levels. Together, these results indicate that key nucleotides in the BMV subgenomic core promoter direct replicase recognition but that the formation of a stem-loop is required at a step after binding. Additional functional characterization of the subgenomic core promoter was performed. A portion of the promoter for BMV minus-strand RNA synthesis could substitute for the subgenomic core promoter in transfected cells. The comparable sequence from Cowpea Chlorotic Mottle Virus (CCMV) could also substitute for the BMV subgenomic core promoter. However, nucleotides in the CCMV core required for RNA synthesis are not identical to those in BMV, suggesting that the subgenomic core promoter can induce the BMV replicase in interactions needed for subgenomic RNA transcription in vivo.
An Experimental Comparison of Range Image Segmentation Algorithms

A methodology for evaluating range image segmentation algorithms is proposed. This methodology involves (1) a common set of 40 laser range finder images and 40 structured light scanner images that have manually specified ground truth and (2) a set of defined performance metrics for instances of correctly segmented, missed, and noise regions, over- and under-segmentation, and accuracy of the recovered geometry. A tool is used to objectively compare a machine generated segmentation against the specified ground truth. Four research groups have contributed to evaluate their own algorithm for segmenting a range image into planar patches.
Lentiviral Vpx Accessory Factor Targets VprBP/DCAF1 Substrate Adaptor for Cullin 4 E3 Ubiquitin Ligase to Enable Macrophage Infection

Vpx is a small virion-associated adaptor protein encoded by viruses of the HIV-2/SIVsm lineage of primate lentiviruses that enables these viruses to transduce monocyte-derived cells. This probably reflects the ability of Vpx to overcome an as yet uncharacterized block to an early event in the virus life cycle in these cells, but the underlying mechanism has remained elusive. Using biochemical and proteomic approaches, we have found that Vpx protein of the pathogenic SIVmac 239 strain associates with a ternary protein complex comprising DDB1 and VprBP subunits of Cullin 4–based E3 ubiquitin ligase, and DDA1, which has been implicated in the regulation of E3 catalytic activity, and that Vpx participates in the Cullin 4 E3 complex comprising VprBP. We further demonstrate that the ability of SIVmac as well as HIV-2 Vpx to interact with VprBP and its associated Cullin 4 complex is required for efficient reverse transcription of SIVmac RNA genome in primary macrophages. Strikingly, macrophages in which VprBP levels are depleted by RNA interference resist SIVmac infection. Thus, our observations reveal that Vpx interacts with both catalytic and regulatory components of the ubiquitin proteasome system and demonstrate that these interactions are critical for Vpx ability to enable efficient SIVmac replication in primary macrophages. Furthermore, they identify VprBP/DCAF1 substrate receptor for Cullin 4 E3 ubiquitin ligase and its associated protein complex as immediate downstream effector of Vpx for this function. Together, our findings suggest a model in which Vpx usurps VprBP-associated Cullin 4 ubiquitin ligase to enable efficient reverse transcription and thereby overcome a block to lentivirus replication in monocyte-derived cells, and thus provide novel insights into the underlying molecular mechanism.