Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical impact of the hepatitis C virus mutations in the era of directly acting antivirals

Introduced in 2013–2014, the second‐ and third‐wave directly acting antivirals (DAAs) have strongly enhanced the efficacy and tolerability of anti‐HCV treatment, with a sustained virological response (SVR) in 90–95% of cases treated. The majority of patients who did not achieve an SVR were found to be infected with HCV strains with a reduced susceptibility to these drugs. Indeed, the high error rate of the viral polymerase and a fast virion production (100‐fold higher than the human immunodeficiency virus) result in a mixture of viral genetic populations (quasi‐species) pre‐existing treatment initiation. These mutants occur frequently in the NS5A region, with a moderate frequency in the NS3/4A region and rarely in the NS5B region. Treatment‐induced resistant mutants to NS5A DAAs persist for years after treatment discontinuation, whereas those resistant to the NS3 DAAs have a shorter duration. This review focuses on the type and prevalence of viral strains with a reduced sensitivity to DAAs, their clinical impact and influence on the response to treatment and, consequently, on treatment choice for DAA‐experienced patients. J. Med. Virol. 88:1659–1671, 2016. © 2016 Wiley Periodicals, Inc.
Conversion from dopamine agonists to pramipexole. An open-label trial in 227 patients with advanced Parkinson's disease.

BACKGROUND Pramipexole is a nonergoline dopamine agonist with D2 and preferential D3 dopamine receptor activity. This selective activity may result in clinically different effects. Small clinical trials indicate that overnight switching from one agonist to another can be performed safely. Objective To determine safety and efficacy of overnight switching from dopamine agonists to pramipexole in patients with advanced Parkinson's disease (PD). OBJECTIVE To determine safety and efficacy of overnight switching from dopamine agonists to pramipexole in patients with advanced Parkinson's disease (PD). METHODS Patients with advanced PD and motor complications not optimally controlled by levodopa and a stable dose of bromocriptine, pergolide or ropinirole were converted to pramipexole overnight. Clinical assessments were performed just prior to conversion and after 2, 6 and 12 weeks of treatment, when an optimal dose of pramipexole was achieved. RESULTS Two hundred and seventeen patients were included in the trial. One hundred and twenty five were converted from pergolide to pramipexole, 58 from bromocriptine and 34 from ropinirole. After 12 weeks, the average dose of pramipexole was 2.8, 2.9 and 3.4 mg/d in patients converted from bromocriptine, pergolide, and ropinirole, respectively. UPDRS II, III and IV scores were reduced by 26-30% in all patients (p<0.0001). Mean levodopa dose was slightly reduced in all groups (p: NS). No serious or unexpected side effects were reported. The dose equivalences calculated from this trial were: bromocriptine:pramipexole 6.9:1, pergolide:pramipexole 0.9:1, ropinirole:pramipexole 1.5:1. CONCLUSION Switching from bromocriptine, pergolide or ropinirole to pramipexole in an overnight schedule is safe. The observed clinical improvement may be related to a placebo effect, to the use of low doses of dopamine agonists or to a direct effect of pramipexole.
Saving lives, maintaining safety, and science‐based policy: qualitative interview findings from the Blood Donation Rules Opinion Study (Blood DROPS)

Indefinite deferral from donation for any man who discloses having had sex with another man even once since 1977 (MSM77) is the US FDA's standing policy. This qualitative component of the Blood Donation Rules and Opinion Study was designed to provide insight into the perceptions and practices of current or previous donors with MSM history.
Measurement and statistical analysis of spectrum occupancy

In this paper, we discuss two definitions of spectrum occupancy in land-mobile radiocommunication, actual occupancy and mean occupancy. We argue that for most monitoring purposes, the mean occupancy is the more relevant notion. We propose measurement procedures for spectrum occupancy, based on discrete observations of the channel, and investigate their properties. For the estimation of the mean occupancy, we provide confidence intervals, both for long as well as for short sampling intervals. For short sampling intervals, dependence of the observations is of crucial importance. We analyse the dependence for an alternating renewal model with Erlang(2)-distributed renewals, which is better supported by the data than the exponential distribution used in past models. For the estimation of the actual spectrum occupancy, we propose a new random sampling scheme and investigate its properties. Copyright © 2004 AEI.
Porcine Pluripotent Stem Cells Derived from IVF Embryos Contribute to Chimeric Development In Vivo

Although the pig is considered an important model of human disease and an ideal animal for the preclinical testing of cell transplantation, the utility of this model has been hampered by a lack of genuine porcine embryonic stem cells. Here, we derived a porcine pluripotent stem cell (pPSC) line from day 5.5 blastocysts in a newly developed culture system based on MXV medium and a 5% oxygen atmosphere. The pPSCs had been passaged more than 75 times over two years, and the morphology of the colony was similar to that of human embryonic stem cells. Characterization and assessment showed that the pPSCs were alkaline phosphatase (AKP) positive, possessed normal karyotypes and expressed classic pluripotent markers, including OCT4, SOX2 and NANOG. In vitro differentiation through embryonic body formation and in vivo differentiation via teratoma formation in nude mice demonstrated that the pPSCs could differentiate into cells of the three germ layers. The pPSCs transfected with fuw-DsRed (pPSC-FDs) could be passaged with a stable expression of both DsRed and pluripotent markers. Notably, when pPSC-FDs were used as donor cells for somatic nuclear transfer, 11.52% of the reconstructed embryos developed into blastocysts, which was not significantly different from that of the reconstructed embryos derived from porcine embryonic fibroblasts. When pPSC-FDs were injected into day 4.5 blastocysts, they became involved in the in vitro embryonic development and contributed to the viscera of foetuses at day 50 of pregnancy as well as the developed placenta after the chimeric blastocysts were transferred into recipients. These findings indicated that the pPSCs were porcine pluripotent cells; that this would be a useful cell line for porcine genetic engineering and a valuable cell line for clarifying the molecular mechanism of pluripotency regulation in pigs.
6 Ikaros in T-Cell Leukemia

Although extensive clinical data have established that the loss of Ikaros tumor suppressor activity via genetic inactivation is a major contributor to leukemogenesis leading to B-cell ALL, less is known about the role of Ikaros in T-cell leukemia. The T-cell malignancies observed in Ikaros-deficient mice suggest that Ikaros is likely to function as a tumor suppressor in T-cells. In human, multiple studies have identified genetic inactivation of Ikaros (deletion or mutation) to be associated with ~5% of T-ALL cases. Additional studies provide evidence that the functional inactivation of Ikaros due to defects in signal pathways that normally regulate Ikaros activity is likely to be a critical factor in the development of Tcell malignancies. These studies provide a rationale for new chemotherapeutic strategies in the treatment of T-cell leukemia. In this chapter, we summarize the newest advances that shed light on the role of Ikaros in T-cell leukemia.
Beer binging and mortality: results from the kuopio ischaemic heart disease risk factor study, a prospective population based study

Abstract Objective: To examine the association between beer binging (regular sessions of heavy beer drinking) and mortality. Design: Prospective population based study with the baseline assessment of level of alcohol intake (dose), by type of drink and drinking pattern, previous and existing diseases, socioeconomic background, occupational status, involvement in organisations during leisure time, physical activity in leisure time, body mass index, blood pressure, serum lipids and plasma fibrinogen concentration, during an average of 7.7 years' follow up of mortality. Setting: Finland. Subjects: A population sample of 1641 men who consumed beer who were aged 42, 48, 54, or 60 years at baseline. Main outcome measures: All cause mortality, cardiovascular mortality, death due to external causes, fatal myocardial infarctions. Results: The risk of death was substantially increased in men whose usual dose of beer was 6 or more bottles per session compared with men who usually consumed less than 3 bottles, after adjustment for age and total alcohol consumption (relative risk 3.01 (95% confidence interval 1.54 to 5.90) for all deaths; 7.10 (2.01 to 25.12) for external deaths; and 6.50 (2.05 to 20.61) for fatal myocardial infarction). The association changed only slightly when smoking, occupational status, previous diseases, systolic blood pressure, low density lipoprotein and high density lipoprotein cholesterol concentration, plasma fibrinogen concentration, body mass index, marital status, leisure time physical activity, and involvement in organisations were controlled for. Conclusion: The pattern of beer binging is associated with increased risk of death, independently of the total average consumption of alcoholic drinks. The relation is not explained by known behavioural, psychosocial, or biological risk factors. Death due to injuries and other external causes is overrepresented among beer bingers, but a strong association with fatal myocardial infarction suggests that the pathway may also involve other acute triggers of severe health events. Key messages The effects of drinking pattern on mortality and morbidity are less well known than the effects of total alcohol consumption The binging style of drinking beer was associated with the risk of death from any cause and from cardiovascular and external causes and with fatal myocardial infarctions in middle aged men in Finland The association was not explained by the total amount of alcohol consumption, and it remained after adjustments for several potential confounders Strong association of beer binging with deaths from external causes and fatal myocardial infarction suggests that this type of drinking pattern may involve triggers of severe acute events
smARTLab @ work Team Description Paper 2016

With this paper, we apply for the RoboCup@Work competition with the smARTLab@work team that has won the 2014 RoboCup@Work competition. smARTLab (swarms, multi-agent, and robot technologies and learning lab) is a robotics research lab that is part of the Agent ART group at the computer science department of the University of Liverpool. This team has won the competition for the second year in a row. The various techniques that have been combined to win the competition come from different computer science domains, entailing machine learning, (simultaneous) localization and mapping, navigation, object recognition and object manipulation. While the RoboCup@Work league is not a standard platform league, all participants use a (customized) Kuka youBot. The stock youBot is a ground based platform, capable of omnidirectional movement and equipped with a five degree of freedom arm featuring a parallel gripper. We present our adaptations to the robot, in which the replacement of the gripper was the most important upgrade comparing to the version of the robot that was used last year.
Relationship of canine bispectral index to multiples of sevoflurane minimal alveolar concentration, using patch or subdermal electrodes.

PURPOSE The purpose of the study reported here was to determine the relationship of bispectral index (BIS) to multiples of sevoflurane minimal alveolar concentration (MAC), using proprietary patch or subdermal needle electrodes in dogs. METHODS Eight English Pointers (4 males, 4 females; mean +/- SD age and body weight of 3.9+/-2.2 years and 20.7+/-4.1 kg, respectively) were studied. Sevoflurane MAC was determined in each dog, using the standard tail clamp technique. One week later, BIS was determined in each dog at 0.8, 1.0, 1.5, and 2.0 MAC multiples of sevoflurane, using proprietary patch electrodes and 29-gauge platinum needle electrodes applied in randomized order. Ventilation was controlled, and atracurium (0.2 mg/kg of body weight, followed by 6 microg/kg/min, i.v.) was administered to eliminate the electromyographic artifact from the electroencephalogram. The BIS was determined, using an A-2000 BIS monitor connected to a computer for data logging at five-second intervals. After a 15-min equilibration period at each sevoflurane MAC-multiple, BIS data were collected for five minutes, and median BIS values were calculated. Heart rate, direct mean arterial blood pressure, esophageal temperature, and arterial pH and blood gas tensions were measured immediately after each BIS collection period. End-tidal CO2 and sevoflurane concentrations were continuously monitored, using an infrared gas analyzer. Data were analyzed, using one-way repeated measures analysis of variance (P < 0.05). Agreement of BIS values from each electrode type was determined. RESULTS Mean +/- SD sevoflurane MAC was 2.1 +/- 0.3%. Mean +/- SD BIS values at 0.8, 1.0, 1.5, and 2.0 MAC were 77 +/- 3, 73 +/- 5, 57 +/- 7, and 53 +/- 7, respectively, for patch electrodes and 80 +/- 6, 72 +/- 7, 56 +/- 4, and 50 +/- 5, respectively, for subdermal needle electrodes. At 2 MAC, BIS could not be determined in six dogs due to presence of burst suppression in the EEG. The regression equation comparing electrodes was: BIS (subdermal) = -5.5 + (1.1 x BIS [patch]); R2= 0.846; bias = -0.192, with a 95% confidence interval of -9.96 to 9.56. Of the other measured variables, none were significantly different between electrode types. Within each group of electrode type, MAP was significantly different among MAC multiples. Within the patch electrode group, PaO2, bicarbonate concentration, and base excess were significantly different among MAC multiples. CONCLUSIONS Bispectral index significantly decreased with increasing sevoflurane MAC multiples over the range of 0.8 to 2.0 MAC, using patch or subdermal electrodes in dogs. Use of subdermal needle electrodes is a reliable and practical alternative to use of patch electrodes for measurement of BIS in dogs.
Toxicity and carcinogenicity of Cr(VI) in animal models and humans.

The toxicity and carcinogenicity of hexavalent chromium (Cr) in animal and human models are reviewed. The focus of this review is not on the well-established fact that hexavalent Cr compounds of low and high water solubility can induce respiratory cancers, but rather this review addresses other types of cancers induced by exposure to hexavalent Cr compounds. Additionally, non-cancer endpoints are also discussed with documentation of human and animal studies showing non-cancer health effects of hexavalent Cr exposure on the respiratory system, GI system, immune system, liver, and kidney. There is an emerging understanding that because hexavalent chromate is isostructural with phosphate and sulfate, it is readily taken up by the G.I. tract and penetrates to many tissues and organs throughout the body. This is supported by animal studies and experiments using human volunteers. From the epidemiological studies, there is suggestive evidence that hexavalent Cr causes increased risk of bone, prostate, lymphomas, Hodgkins, leukemia, stomach, genital, renal, and bladder cancer, reflecting the ability of hexavalent chromate to penetrate all tissues in the body. A high accumulation of Cr(III) in all tissues and organs is a strong indication of the wide toxic potential of exposure to soluble hexavalent Cr in the drinking water and in the ambient environment.
Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade

The cellular ancestry of tumor antigens One contributing factor in antitumor immunity is the repertoire of neoantigens created by genetic mutations within tumor cells. Like the corresponding mutations, these neoantigens show intratumoral heterogeneity. Some are present in all tumor cells (clonal), and others are present in only a fraction of cells (subclonal). In a study of lung cancer and melanoma, McGranahan et al. found that a high burden of clonal tumor neoantigens correlated with improved patient survival, an increased presence of tumor-infiltrating lymphocytes, and a durable response to immunotherapy. Science, this issue p. 1463 Analysis of the cellular ancestry of tumor neoantigens can predict which are most likely to induce an immune response. As tumors grow, they acquire mutations, some of which create neoantigens that influence the response of patients to immune checkpoint inhibitors. We explored the impact of neoantigen intratumor heterogeneity (ITH) on antitumor immunity. Through integrated analysis of ITH and neoantigen burden, we demonstrate a relationship between clonal neoantigen burden and overall survival in primary lung adenocarcinomas. CD8+ tumor-infiltrating lymphocytes reactive to clonal neoantigens were identified in early-stage non–small cell lung cancer and expressed high levels of PD-1. Sensitivity to PD-1 and CTLA-4 blockade in patients with advanced NSCLC and melanoma was enhanced in tumors enriched for clonal neoantigens. T cells recognizing clonal neoantigens were detectable in patients with durable clinical benefit. Cytotoxic chemotherapy–induced subclonal neoantigens, contributing to an increased mutational load, were enriched in certain poor responders. These data suggest that neoantigen heterogeneity may influence immune surveillance and support therapeutic developments targeting clonal neoantigens.
Human body sensing: A pervasive approach by implanted RFID tags

Starting from the physical evidence that passive RFID systems may be used as self-sensing devices, the feasibility of human monitoring by means of implanted tags is here investigated. The key parameters to master with the purpose to enhance the sensitivity of the implanted radiosensor have been theoretically analyzed and numerically applied to a specific medical problem, i.e. the continuous monitoring of liver cancer evolution. Preliminary experimental results with simplified phantoms corroborate the analysis.
Deal or No Deal: Hormones and the Mergers and Acquisitions Game

Young male CEOs appear to be combative: they are 4% more likely to be acquisitive and, having initiated an acquisition, they are over 20% more likely to withdraw an offer. Furthermore, a young target male CEO is 2% more likely to force a bidder to resort to a tender offer. We argue that this combative nature is a result of testosterone levels that are higher in young males. Testosterone, a hormone associated with male dominance seeking, has been shown to influence prospects for a cooperative outcome of the ultimatum game. Specifically, high-testosterone responders tend to reject low offers even though this is against their interest. It has been argued that this is consistent with a low offer being seen as dominance seeking. The acts of attempting or resisting an acquisition can be viewed as striving to achieve dominance. We argue that the evidence reported in this paper is consistent with the presence of a significant hormone effect in mergers and acquisitions.
On a more realistic lock contention model and its analysis

Most performance modeling studies of lock contention in transaction processing systems are deficient in that they postulate a homogeneous database access model. The non-homogeneous database access model described in this paper allows multiple transaction classes with different access patterns to the database regions. The performance of the system from the viewpoint of lock contention is analyzed in the context of the standard two-phase locking concurrency control method with the general waiting policy. The approximate analysis is based on mean values of parameters and derives expressions for the probability of lock conflict (usually leading to transaction blocking) and the mean blocking time. The latter requires estimating the distribution of the effective wait-depth encountered by blocked transactions and the mean waiting time associated with different blocking levels. The accuracy of the analysis is validated against simulation results and also shown to be more accurate than analytic solutions considering only two levels of transaction blocking. Previously proposed metrics for load control have limited applicability for the model under consideration. <<ETX>>
Immediate coronary angiography in survivors of out-of-hospital cardiac arrest.

BACKGROUND The incidence of acute coronary-artery occlusion among patients with sudden cardiac arrest outside of the hospital is unknown, and the role of reperfusion therapy has not been determined. We therefore performed immediate coronary angiography and angioplasty when indicated in survivors of out-of-hospital cardiac arrest. METHODS Between September 1994 and August 1996, coronary angiography was performed in 84 consecutive patients between the ages of 30 and 75 years who had no obvious noncardiac cause of cardiac arrest. RESULTS Sixty of the 84 patients had clinically significant coronary disease on angiography, 40 of whom had coronary-artery occlusion (48 percent). Angioplasty was attempted in 37 patients and was technically successful in 28. Clinical and electrocardiographic findings, such as the occurrence of chest pain and the presence of ST-segment elevation, were poor predictors of acute coronary-artery occlusion. The in-hospital survival rate was 38 percent. Multivariate logistic-regression analysis revealed that successful angioplasty was an independent predictor of survival (odds ratio, 5.2; 95 percent confidence interval, 1.1 to 24.5; P=0.04). CONCLUSIONS Acute coronary-artery occlusion is frequent in survivors of out-of-hospital cardiac arrest and is predicted poorly by clinical and electrocardiographic findings. Accurate diagnosis by immediate coronary angiography can be followed in suitable candidates by coronary angioplasty, which seems to improve survival.