Miracle-dz/UniFAR-FTUs huggingface dataset:
How to optimize HCV therapy in genotype 2 patients

Hepatitis C Virus (HCV) Genotype 2 accounts for 10% of the patients with chronic HCV worldwide. The current standard of care (SOC) in these patients is 24 weeks of Pegylated Interferon (PEG‐IFN) plus Ribavirin (RBV), with sustained virological response rates (SVR) of 80–90%. However, there are subgroups of patients with HCV‐2, such as those with advanced fibrosis/cirrhosis, in whom SVR rates are still suboptimal, and highly responsive groups in whom SVR rates reach 95%. Treatment optimization is necessary to maximize efficacy in the former group and reduce treatment‐related side effects in the latter. Unfortunately, any attempt to modify the duration or dosing of the SOC according to baseline factors has been disappointing and should not be continued at present. On the other hand on‐treatment HCV RNA kinetics are fundamental for individualized treatment regimens because achieving negative HCV RNA at week 4 (rapid virological response, RVR) is the key factor when the duration of PEG‐IFN/RBV is tailored in HCV‐2 patients. Several studies have shown that treatment can be shortened to 16 weeks in HCV‐2 patients with a RVR, without increasing the risk of post‐treatment relapse, thus increasing tolerance to treatment while reducing healthcare costs. On the other hand, patients who do not achieve a RVR correspond to a population of difficult‐to‐cure HCV‐2 patients who need alternative treatment strategies which are not yet available.
Essential Role of CD8 Palmitoylation in CD8 Coreceptor Function1

To investigate the molecular basis that makes heterodimeric CD8αβ a more efficient coreceptor than homodimeric CD8αα, we used various CD8 transfectants of T1.4 T cell hybridomas, which are specific for H-2Kd, and a photoreactive derivative of the Plasmodium berghei circumsporozoite peptide PbCS 252–260 (SYIPSAEKI). We demonstrate that CD8 is palmitoylated at the cytoplasmic tail of CD8β and that this allows partitioning of CD8αβ, but not of CD8αα, in lipid rafts. Localization of CD8 in rafts is crucial for its coreceptor function. First, association of CD8 with the src kinase p56lck takes place nearly exclusively in rafts, mainly due to increased concentration of both components in this compartment. Deletion of the cytoplasmic domain of CD8β abrogated localization of CD8 in rafts and association with p56lck. Second, CD8-mediated cross-linking of p56lck by multimeric Kd-peptide complexes or by anti-CD8 Ab results in p56lck activation in rafts, from which the abundant phosphatase CD45 is excluded. Third, CD8-associated activated p56lck phosphorylates CD3ζ in rafts and hence induces TCR signaling and T cell activation. This study shows that palmitoylation of CD8β is required for efficient CD8 coreceptor function, mainly because it dramatically increases CD8 association with p56lck and CD8-mediated activation of p56lck in lipid rafts.
Quantitative imaging of endosome acidification and single retrovirus fusion with distinct pools of early endosomes

Diverse enveloped viruses enter host cells through endocytosis and fuse with endosomal membranes upon encountering acidic pH. Currently, the pH dynamics in virus-carrying endosomes and the relationship between acidification and viral fusion are poorly characterized. Here, we examined the entry of avian retrovirus that requires two sequential stimuli—binding to a cognate receptor and low pH—to undergo fusion. A genetically encoded sensor incorporated into the viral membrane was used to measure the pH in virus-carrying endosomes. Acid-induced virus fusion was visualized as the release of a fluorescent viral content marker into the cytosol. The pH values in early acidic endosomes transporting the virus ranged from 5.6 to 6.5 but were relatively stable over time for a given vesicle. Analysis of viral motility and luminal pH showed that cells expressing the transmembrane isoform of the receptor (TVA950) preferentially sorted the virus into slowly trafficking, less acidic endosomes. In contrast, viruses internalized by cells expressing the GPI-anchored isoform (TVA800) were uniformly distributed between stationary and mobile compartments. We found that the lag times between acidification and fusion were significantly shorter and fusion pores were larger in dynamic endosomes than in more stationary compartments. Despite the same average pH within mobile compartments of cells expressing alternative receptor isoforms, TVA950 supported faster fusion than TVA800 receptor. Collectively, our results suggest that fusion steps downstream of the low-pH trigger are modulated by properties of intracellular compartments harboring the virus.
Influence of a traction battery's input impedance on conducted emissions of an automotive HV inverter

Conducted emissions of automotive high voltage (HV) components recently are measured according to CIPSR 25. If the tested device conforms to specific limits on component level (set by customer and supplier agreements) it is inserted into the automotive system. Thus, the EMC performance of the investigated device has to be independent of the test level, e.g. on component or vehicle level. Comparing the standardized test setup with an automotive HV system, the main difference consists in the termination of the cable harness. In a component level EMC test setup the HV harness is terminated with line impedance stabilization networks (LISNs), whereas implemented in a vehicle the cables are connected to a traction battery. This contribution investigates the difference in the conducted emissions of an automotive power inverter, when it is introduced into an electromagnetic environment that is similar to vehicle level. Therefore, the input impedances of a HV battery are characterized and modeled. This battery emulation is introduced into the component level test setup and the deviations in the conducted emissions of a traction inverter are determined.
Controller design with a evolutionary multi-objective optimization approach

Controller design is performed to meet some performance criteria. Some of them are the gain and phase margins, control effort, settling time, overshoot, amongst other indexes. Obtaining a controller or compensator that fits all these criteria (or some of them) for a closed loop control is done in both empirical and analytical procedures. The most of these procedures assumes the plant to be controlled could be modelled as first or second-order system. This paper aims to show a way to find the controller parameters based on the multi-objective optimization with a evolutionary approach. The systems to be controlled must be the type SISO (Single Input Single Output) whose transfer functions may have order higher than second order.
An A, B-Polar Approach for Multimode Polarization Analysis in Satellite Communications

This paper describes a convenient method of polarization analysis for a circular multimode aperture antenna by decomposing the field distribution into two components called A,B -polar. The new idea in this technique is the separation of the A,B -polar for field expression into a rotationally symmetric magnitude function and an orientation function independent of the antenna off-axis. This leads to easily sketched figures of the multimode polarization patterns which give a clear physical picture on their effects and applications. Several examples are done in the context of the frequency reuse capabilities of earth-station antennas.
Clinical pharmacology and efficacy of sugammadex in the reversal of neuromuscular blockade

ABSTRACT Introduction: Sugammadex is the first clinical representative of a class of drugs called steroidal muscle relaxant encapsulators. Due to its 1:1 binding of rocuronium or vecuronium, sugammadex can reverse any depth of neuromuscular block and has therefore revolutionized the way anesthetists think about drug reversal. Areas covered: This review gives an overview of the clinical pharmacology and efficacy of sugammadex in healthy patients as well as in patients with pre-existing diseases. Expert opinion: After approval in Europe in 2008 and Asia in 2010, sugammadex has recently been approved in the USA and Canada. This will open the field for further research especially for the use in special patient populations and specific diseases. Due to its pharmacodynamic profile, sugammadex in combination with rocuronium might have the potential to displace succinylcholine as the gold standard muscle relaxant for rapid sequence inductions. The use of rocuronium or vecuronium with the potential to reverse its action with sugammadex seems to be safe in patients with impaired neuromuscular transmission, i.e. (neuro)muscular diseases including myasthenia gravis. Data from long-term use of sugammadex is not yet available. Evidence towards an economic advantage of using sugammadex, justifying the relatively high costs for an anesthesia-related drug, is missing.
Sensitivity to the rewarding effects of food and exercise in the eating disorders.

The diminished capacity to experience pleasure or reward ("anhedonia") has its biological underpinnings in the mesolimbic dopamine system and is strongly implicated in risk for a variety of addictive behaviors. The present study tested the prediction that patients with anorexia nervosa (AN) would be more anhedonic than those with bulimia nervosa (BN)-a factor that could contribute to their respective avoidance and approach relationship to food. We also tested the idea that anhedonia would be correlated with high-level exercising from the viewpoint that the latter serves as a compensatory behavior for a blunted affect. AN patients of the restrictor subtype (n = 78) and BN patients with no history of AN (n = 76) were included in the regression analyses. Patients were also classified as excessive exercisers or moderate/nonexercisers according to information gathered during a structured clinical interview. Findings were largely supportive of our predictions. AN patients were highly anhedonic compared to BN patients, and excessive exercisers tended to be more anhedonic than those who did not exercise. We discuss the AN-BN differences in capacity for reward/pleasure in the context of the common psychobiological links between the eating disorders and drug and alcohol addiction, and speculate on how these differences might relate to the etiology and pathophysiology of both AN and BN.
Meshed vs. radial MV distribution network in presence of large amount of DG

Until now, distribution networks are regarded as a passive termination of the transmission network, with a radial structure, unidirectional power flows, and a simple and efficient protection scheme. In presence of a large amount of distributed generation (DG), distribution networks will gradually, but ineluctably, change towards a new kind of active networks. The most revolutionary change, needed to efficiently allocate so much DG, could be represented by the adoption of a meshed network architecture. For this reason, in the paper new possible arrangements for distribution networks have been deeply investigated and compared with the radial scheme. Steady state and dynamic simulations have been performed, considering a portion of the real Italian distribution network, and voltage profile, power losses, short circuit currents and grid reliability have been analyzed.
Bilateral robot therapy based on haptics and reinforcement learning: Feasibility study of a new concept for treatment of patients after stroke.

OBJECTIVE To carry out a preliminary feasibility study of a new concept of robot therapy for severely impaired patients after stroke. DESIGN A haptic manipulandum connected to a bar that can rotate freely while providing a measure of the rotation angle. The controller combines a bilateral reaching task with the task of balancing the action of the 2 arms. Reinforcement is given to the subject in 2 forms: audio-visual and haptic by means of adaptable force fields. PATIENTS Four highly paretic patients with chronic stroke (Fugl-Meyer score less than 15). METHODS The training cycle consisted of 5 sessions over a period of 2 weeks. Each session (45 min) was divided in blocks of 10 pairs of forward/backward movements. Performance was determined by evaluating the number of successful movements per session, the session-by-session decrease in the assistive field, the mean reaching time, and the mean stopping field. RESULTS All subjects could understand the task, appreciated it and improved their performance during training. The reaching movements became smoother and quicker; balance errors and the magnitude of the resisting field were consistently reduced. CONCLUSION Bilateral robot therapy is a promising technique, provided that it self-adapts to the patient's performance. Formal clinical trials should address this point.
Use of Intensive Care Services for Medicare Beneficiaries Undergoing Major Surgical Procedures

Background:Use of intensive care after major surgical procedures and whether routinely admitting patients to intensive care units (ICUs) improve outcomes or increase costs is unknown. Methods:The authors examined frequency of admission to an ICU during the hospital stay for Medicare beneficiaries undergoing selected major surgical procedures: elective endovascular abdominal aortic aneurysm (AAA) repair, cystectomy, pancreaticoduodenectomy, esophagectomy, and elective open AAA repair. The authors compared hospital mortality, length of stay, and Medicare payments for patients receiving each procedure in hospitals admitting patients to the ICU less than 50% of the time (low use), 50 to 89% (moderate use), and 90% or greater (high use), adjusting for patient and hospital factors. Results:The cohort ranged from 7,878 patients in 162 hospitals for esophagectomies to 69,989 patients in 866 hospitals for endovascular AAA. Overall admission to ICU ranged from 35.6% (endovascular AAA) to 71.3% (open AAA). Admission to ICU across hospitals ranged from less than 5% to 100% of patients for each surgical procedure. There was no association between hospital use of intensive care and mortality for any of the five surgical procedures. There was a consistent association between high use of intensive care with longer length of hospital stay and higher Medicare payments only for endovascular AAA. Conclusions:There is little consensus regarding the need for intensive care for patients undergoing major surgical procedures and no relationship between a hospital’s use of intensive care and hospital mortality. There is also no consistent relationship across surgical procedures between use of intensive care and either length of hospital stay or payments for care.
Prevalence of metabolic syndrome by the Adult Treatment Panel III, International Diabetes Federation, and World Health Organization definitions and their association with coronary heart disease in an elderly Iranian population.

INTRODUCTION To determine the prevalence of the metabolic syndrome (MS) in an Iranian elderly population and show its association with coronary heart disease (CHD). MATERIALS AND METHODS This is a cross-sectional study on 720 Iranian men and women aged > or = 65 years who participated in the Tehran Lipid and Glucose Study (TLGS). Logistic regression analysis was used to estimate the odds ratio (OR) of developing CHD in model 1, an age-adjusted model; model 2, adjusted for age, smoking status, premature history of CHD and low-density lipoprotein (LDL) cholesterol; and model 3, adjusted for mentioned variables plus the MS components. RESULTS The prevalence of MS was 50.8%, 41.8% and 41.9% based on the Adult Treatment Panel (ATPIII), the World Health Organisation (WHO), and the International Diabetes Federation (IDF) definitions, respectively. The IDF definition showed high agreement with the ATPIII definition. Age-adjusted OR (95% CI) of the MS for CHD was 1.6 (1.2 to 2.2) by both the ATPIII and WHO definitions and 1.4 (1.0 to 1.9) by the IDF definition. IDF-defined MS lost its association with CHD in model 2. In model 3, obesity (WHO definition) and high blood pressure (ATPIII and WHO definitions) were associated with CHD. CONCLUSIONS In an elderly Iranian population MS is highly prevalent. ATPIII and WHO definitions seem to be more pertinent than IDF for screening CHD risk. None of these definitions showed association with CHD when considering their components.
Comparative study of dihydroartemisinin and artesunate safety in healthy Thai volunteers.

OBJECTIVE As part of new drug development initiatives in Thailand, a new tablet formulation of dihydroartemisinin (DHA, an antimalarial drug) has been developed. Our previous bioequivalence study indicated that the new and reference DHA formulations were well tolerated; however, a significant decrease in hemoglobin was detected after a single 200-mg oral dose. To explore further, a clinical study with an emphasis on hematological parameters was conducted. METHODS A single-center, randomized, single-blind, cross-over clinical study was conducted in 18 healthy volunteers with a dosage of 300 mg daily for 2 days. Artesunate was used as a comparator. Adverse events were monitored and laboratory parameters on study Days 0, 2, 5, and 7 post drug administrations were analyzed. RESULTS Eighteen volunteers completed both rounds of the study. Both drugs were well tolerated. All adverse events were mild. Significant decrease in hemoglobin compared to baseline was detected for both drugs 7 days after administration (DHA: 0.48 g/dl, p = 0.007; artesunate 0.38 g/dl, p = 0.001). Transient bone marrow suppression was evidenced by reduction of reticulocytes with a lowest number on study Day 5 (artesunate 75% reduction in reticulocyte count; DHA 47%, p < 0.001 for both drugs compared to baseline). CONCLUSION The present study confirmed our previous finding on significant decrease in hemoglobin. Artesunate appeared to have more negative effects on the numbers of reticulocytes and white blood cells than DHA. Systemic laboratory and toxicity profiles presented in this study may be used as a framework for future clinical studies of artemisinin and its derivatives.
The ABO blood group gene: a locus of considerable genetic diversity.

The blood group ABO gene shows considerable polymorphism in most of the 7 exons. Introns examined so far have also shown blood group-related polymorphisms, as has an upstream enhancer region. Several polymorphisms affect the specificity of the gene product (glycosyltransferase) and explain the occurrence of blood group A and B. Various lethal mutations result in blood group O. Other mutations are presumed to alter the activity rather than the specificity of the enzyme and result in weaker A and B blood group phenotypes. In total, 27 A alleles, 15 B alleles, 26 O alleles, and 4 AB hybrid alleles are described and surely more will surface in the near future. Variation in geographic/ethnic distribution of allele frequencies is discussed, along with the confusing nomenclatures currently in use.
Depression in Vascular Dementia Is Quantitatively and Qualitatively Different from Depression in Alzheimer’s Disease

Background/Aims: To compare the prevalence and characteristics of depression in vascular dementia (VaD) and Alzheimer’s disease (AD) after adjusting for dementia severity and gender. Methods: One hundred and eight pairs of VaD and AD patients matched for dementia severity and gender were assessed. Results: Major depressive disorder (MDD) was more prevalent in the VaD group than in the AD group (20.4% in VaD, 10.2% in AD, p = 0.04, Cochran-Mantel-Haenszel, CMH, test) regardless of the dementia severity and gender. The odds ratio for developing MDD in the VaD group versus the AD group was estimated to be 2.20 (95% confidence interval = 1.02–4.74). Neurovegetative symptoms such as ‘felt tired and weak all the time’ (30.6% in VaD, 13.9% in AD, p = 0.003, CMH test) and ‘changed weight without trying’ (16.7% in VaD, 6.5% in AD, p = 0.02, CMH test) were more prevalent in the VaD group than in the AD group. Conclusion: Depression in VaD was quantitatively and qualitatively different from that in AD regardless of the severity of dementia and gender; depression was more prevalent, severer and more retarded and vegetative in VaD than in AD.
Adherence to asthma treatments: ‘we know, we intend, we advocate’

Purpose of reviewTo highlight the state of the art and the current outlook on the adherence to treatment in asthma, starting from the ‘Manifesto on Adherence to asthma treatment in respiratory allergy’ endorsed by the World Allergy Organization, Allergic Rhinitis and Its Impact on Asthma and Global Allergy, Asthma European Network, and Interasma. Recent findingsAdherence to the pharmacological treatments of asthma is known to be low: about 50% of those who had been prescribed long-term treatment are nonadherent, at least part of the time. Nonadherence is associated with lack of asthma control, poor health outcomes, and increased costs. The reasons for suboptimal adherence are multifaceted and may be related to the patients, the treatment and asthma features, the physician–patient relationship, and the healthcare resources and facilities. SummaryTaking into account the multidimensional nature of adherence, no single intervention or strategy is per se able to enhance it, but all players involved in the process (government authorities, patient organizations, scientific societies, stakeholders, and others) are called to work together to develop a combined action plan based on the patient's complexity.
Foundations for a theory of mind for a humanoid robot

Human social dynamics rely upon the ability to correctly attribute beliefs, goals, and percepts to other people. The set of abilities that allow an individual to infer these hidden mental states based on observed actions and behavior has been called a “theory of mind” (Premack & Woodruff, 1978). Existing models of theory of mind have sought to identify a developmental progression of social skills that serve as the basis for more complex cognitive abilities. These skills include detecting eye contact, identifying self-propelled stimuli, and attributing intent to moving objects. If we are to build machines that interact naturally with people, our machines must both interpret the behavior of others according to these social rules and display the social cues that will allow people to naturally interpret the machine's behavior. Drawing from the models of Baron-Cohen (1995) and Leslie (1994), a novel architecture called embodied theory of mind was developed to link high-level cognitive skills to the low-level perceptual abilities of a humanoid robot. The implemented system determines visual saliency based on inherent object attributes, high-level task constraints, and the attentional states of others. Objects of interest are tracked in real-time to produce motion trajectories which are analyzed by a set of naive physical laws designed to discriminate animate from inanimate movement. Animate objects can be the source of attentional states (detected by finding faces and head orientation) as well as intentional states (determined by motion trajectories between objects). Individual components are evaluated by comparisons to human performance on similar tasks, and the complete system is evaluated in the context of a basic social learning mechanism that allows the robot to mimic observed movements. (Copies available exclusively from MIT Libraries, Rm. 14-0551, Cambridge, MA 02139-4307. Ph. 617-253-5668; Fax 617-253-1690.)