Miracle-dz/UniFAR-FTUs huggingface dataset:
Definition of Five New Simian Immunodeficiency Virus Cytotoxic T-Lymphocyte Epitopes and Their Restricting Major Histocompatibility Complex Class I Molecules: Evidence for an Influence on Disease Progression

ABSTRACT Simian immunodeficiency virus (SIV) infection of the rhesus macaque is currently the best animal model for AIDS vaccine development. One limitation of this model, however, has been the small number of cytotoxic T-lymphocyte (CTL) epitopes and restricting major histocompatibility complex (MHC) class I molecules available for investigating virus-specific CTL responses. To identify new MHC class I-restricted CTL epitopes, we infected five members of a family of MHC-defined rhesus macaques intravenously with SIV. Five new CTL epitopes bound by four different MHC class I molecules were defined. These included two Env epitopes bound by Mamu-A*11 and -B*03 and three Nef epitopes bound by Mamu-B*03, -B*04, and -B*17. All four restricting MHC class I molecules were encoded on only two haplotypes (b or c). Interestingly, resistance to disease progression within this family appeared to be associated with the inheritance of one or both of these MHC class I haplotypes. Two individuals that inherited haplotypes b and cseparately survived for 299 and 511 days, respectively, while another individual that inherited both haplotypes survived for 889 days. In contrast, two MHC class I-identical individuals that did not inherit either haplotype rapidly progressed to disease (survived <80 days). Since all five offspring were identical at their Mamu-DRBloci, MHC class II differences are unlikely to account for their patterns of disease progression. These results double the number of SIV CTL epitopes defined in rhesus macaques and provide evidence that allelic differences at the MHC class I loci may influence rates of disease progression among AIDS virus-infected individuals.
Both HIV-Infected and Uninfected Cells Express TRAILshort, Which Confers TRAIL Resistance upon Bystander Cells within the Microenvironment

TNF-related apoptosis-inducing ligand (TRAIL) was initially described to induce apoptosis of tumor cells and/or virally infected cells, although sparing normal cells, and has been implicated in the pathogenesis of HIV disease. We previously identified TRAILshort, a TRAIL splice variant, in HIV-infected patients and characterized it as being a dominant negative ligand to subvert TRAIL-mediated killing. Herein, using single-cell genomics we demonstrate that TRAILshort is produced by HIV-infected cells, as well as by uninfected bystander cells, and that the dominant stimulus which induces TRAILshort production are type I IFNs and TLR7, TLR8, and TLR9 agonists. TRAILshort has a short t1/2 by virtue of containing a PEST domain, which targets the protein toward the ubiquitin proteasome pathway for degradation. Further we show that TRAILshort binds preferentially to TRAIL receptors 1 and 2 with significantly reduced interaction with the decoy TRAIL receptors 3 and 4. Recombinant TRAILshort is sufficient to protect cells against TRAIL-induced killing, whereas immunodepletion of TRAILshort with a specific Ab restores TRAIL sensitivity. Importantly we show that TRAILshort is shed in microvesicles into the cellular microenvironment and therefore confers TRAIL resistance not only on the cell which produces it, but also upon neighboring bystander cells. These results establish a novel paradigm for understanding and overcoming TRAIL resistance, in particular how HIV-infected cells escape immune elimination by the TRAIL:TRAILshort receptor axis.
The Effects of Artificial Selection on the Maize Genome

Domestication promotes rapid phenotypic evolution through artificial selection. We investigated the genetic history by which the wild grass teosinte (Zea mays ssp. parviglumis) was domesticated into modern maize (Z. mays ssp. mays). Analysis of single-nucleotide polymorphisms in 774 genes indicates that 2 to 4% of these genes experienced artificial selection. The remaining genes retain evidence of a population bottleneck associated with domestication. Candidate selected genes with putative function in plant growth are clustered near quantitative trait loci that contribute to phenotypic differences between maize and teosinte. If we assume that our sample of genes is representative, ∼1200 genes throughout the maize genome have been affected by artificial selection.
Adaptation and Evaluation of Online Self-learning Modules to Teach Critical Appraisal and Evidence-Based Practice in Nursing: An International Collaboration

Healthcare professionals need to update their knowledge and acquire skills to continually inform their practice based on scientific evidence. This study was designed to evaluate online self-learning modules on critical appraisal skills to promote the use of research in clinical practice among nurses from Quebec (Canada) and the Basque Country (Spain). The teaching material was developed in Quebec and adapted to the Basque Country as part of an international collaboration project. A prospective pre-post study was conducted with 36 nurses from Quebec and 47 from the Basque Country. Assessment comprised the administration of questionnaires before and after the course in order to explore the main intervention outcomes: knowledge acquisition and self-learning readiness. Satisfaction was also measured at the end of the course. Two of the three research hypotheses were confirmed: (1) participants significantly improved their overall knowledge score after the educational intervention; and (2) they were, in general, satisfied with the course, giving it a rating of seven out of 10. Participants also reported a greater readiness for self-directed learning after the course, but this result was not significant in Quebec. The study provides unique knowledge on the cultural adaptation of online self-learning modules for teaching nurses about critical appraisal skills and evidence-based practice.
Audiological findings in Williams syndrome: A study of 69 patients

The aim of this study was to investigate, in a clinical setting, the auditory function of a group of individuals affected by Williams syndrome (WS). Sixty‐nine patients with WS, aged 2–30, underwent comprehensive audiological testing including air/bone conduction behavioral audiometry, speech audiometry, tympanometry and measurement of the acoustic reflex, transient evoked otoacoustic emissions and brainstem auditory evoked responses. Hearing loss, defined by a pure‐tone average above 15 dB HL, affected 22.6% of the patients studied with traditional audiometry and was mostly slight in severity. Hearing loss was conductive in 9.4% of patients, mainly children with otitis media with effusion, and sensorineural in 13.2% of patients. However, 30% of the ears studied had a hearing impairment in the high frequency range (high‐frequency pure‐tone audiometry above 15 dB HL), higher in participants above 15 years (46.15%) than in the younger ones (23.45%). Contralateral stapedial reflexes were present in all patients with A‐type tympanograms. Transient otoacoustic emissions were absent in 44% of the ears of patients with normal hearing. Brainstem auditory evoked responses fell within normal ranges thus confirming the absence of retrocochlear dysfunction. Although hearing loss does not seem to be frequent, a cochlear fragility, especially in the high frequency range, related to outer hair cells is characteristic of WS. Therefore we strongly recommend monitoring patients affected by WS using annual audiometric tests and performing otoacoustic emissions in order to identify a subclinical cochlear dysfunction which might benefit from an audiological follow up before the possible onset of hearing loss. © 2012 Wiley Periodicals, Inc.
Spiritual care in Christian parish nursing.

AIM This paper reports the development of a substantive theory to explain the process parish nurses use to provide spiritual care to parishioners in Christian churches in a context where patients and nurses share a common set of values. BACKGROUND Despite a surge of interest in spirituality and spiritual care in nursing, consensus is lacking on how care should be conceptualized and provided. METHOD Grounded theory method was used to explore and describe the processes 10 American parish nurses experienced and used as they gave spiritual care. Data were collected between 1998 and 2001. Participants were interviewed and audiotapes transcribed verbatim. Constant comparative methods were used to analyse more than 50 separate incidents reported by the nurses. FINDINGS From its initial emergence as the core category, 'Bringing God Near' became a Basic Social Process theory of giving spiritual care for these parish nurses. This Basic Social Process became a theory through writing theoretical memos that described how the 'main concern' of the nurses to give spiritual care was resolved. Phases within the process include: trusting God, forming relationships with the patient/family, opening to God, activating/nurturing faith and recognizing spiritual renewal or growth. The essence is bringing God near to people as they face health challenges. Findings from the study and spiritual care literature are integrated in the discussion. CONCLUSION The parish nurses' spiritual challenge is to respond to what God is directing the nurse to be and do to strengthen people spiritually. This spiritual care can help restore the patient's sense of well-being, and encourage growth in faith. Those interested in providing and teaching spiritual care in the church context will find this theory useful as a conceptual guide.
Six‐minute walk test is reliable and valid in spinal muscular atrophy

Introduction: The Six‐Minute Walk Test (6MWT) was adopted as a clinical outcome measure for ambulatory spinal muscular atrophy (SMA). However, a systematic review of measurement properties reported significant variation among chronic pediatric conditions. Our purpose was to assess the reliability/validity of the 6MWT in SMA. Methods: Thirty participants performed assessments, including the 6MWT, strength, and function. Reproducibility was evaluated by intraclass correlation coefficients. Criterion/convergent validity were determined using Pearson correlation coefficients. Results: Test–retest reliability was excellent. The 6MWT was associated positively with peak oxygen uptake, Hammersmith Functional Motor Scale Expanded (HFMSE), lower extremity manual muscle testing, knee flexion hand‐held dynamometry, and inversely with 10‐m walk/run. The 6MWT discriminates between disease severity, unlike the HFMSE. Conclusions: This study documents measurement properties of reproducibility, positive criterion validity, and convergent validity with established clinical assessments and reaffirms the value of the 6MWT as a pivotal outcome measure in SMA clinical trials. Muscle Nerve 54: 836–842, 2016
Endogenous brain oscillations and related networks detected by surface EEG‐combined fMRI

It is difficult to study the brain “at rest” with an approach generally pursued in science when external manipulation (independent variable) is used to obtain informative measurements (dependent variable) about the object of interest. External manipulation in its classic sense may suspend the resting state, and hence the object of interest will evade. Naturally, unless in a final and irreversible state, biological rest will always be an endogenously dynamic process. Combining two modalities, electroencephalography (EEG) and functional magnetic resonance imaging (fMRI), to simultaneously measure the brain's activity from two angles, one can be chosen to be interpreted as the independent variable and the other as the dependent variable, and without external manipulation the brain's spontaneous dynamics can be studied. The EEG, for example, observes endogenous modulations of vigilance and detects spontaneous events such as sleep spindles or epileptic discharges and can be used as the independent variable, i.e., to form a regressor to interrogate the fMRI data (dependent variable). The opposite is possible as well, and data fusion attempts try using all data both as dependent and independent variables at the same time. This review limits itself to an exemplary discussion of simultaneous EEG/fMRI studies in humans, and among a variety of proposed resting state networks only discusses a few, especially those for which non‐resting state literature has proposed a functional meaning: the “default mode” network and an attentional network. It will be shown that one EEG feature can correlate with different fMRI activation maps and that a single resting state network may be associated with a variety of EEG patterns giving insight into the function of different resting states and the relationship between the two modalities in themselves. Hum Brain Mapp 2008. © 2008 Wiley‐Liss, Inc.
Lyme Neuroborreliosis in Children: A Prospective Study of Clinical features, Prognosis, and Outcome

Background: Evaluation of children with clinically suspected neuroborreliosis (NB) is difficult. With a prospective study design we wanted to characterize children with signs and symptoms indicative for NB, investigate clinical outcome and, if possible, identify factors of importance for recovery. Material/Methods: Children being evaluated for NB (n = 177) in southeast Sweden were categorized into 3 groups: “confirmed neuroborreliosis” (41%) with Borrelia antibodies in the cerebrospinal fluid, “possible neuroborreliosis” (26%) with pleocytosis but no Borrelia antibodies in the cerebrospinal fluid, and “not determined” (33%) with no pleocytosis and no Borrelia antibodies in the cerebrospinal fluid. Antibiotic treatment was given to 69% of children. Patients were followed during 6 months and compared with a matched control group (n = 174). Results: Clinical recovery at the 6-month follow-up (n = 177) was generally good and no patient was found to have recurrent or progressive neurologic symptoms. However, persistent facial nerve palsy caused dysfunctional and cosmetic problems in 11% of patients. Persistent nonspecific symptoms, such as headache and fatigue, were not more frequently reported in patients than in controls. Influence on daily life was reported to the same extent in patients and controls. Consequently, persistent headache and fatigue at follow-up should not be considered as attributable to NB. No prognostic factors could be identified. Conclusions: Clinical recovery was satisfactory in children being evaluated for NB although persistent symptoms from facial nerve palsy occurred. Persistent nonspecific symptoms, such as headache and fatigue, were not more frequently reported in patients than in controls.
Embedded-atom method potential for modeling hydrogen and hydrogen-defect interaction in tungsten

An embedded-atom method potential has been developed for modeling hydrogen in body-centered-cubic (bcc) tungsten by fitting to an extensive database of density functional theory (DFT) calculations. Comprehensive evaluations of the new potential are conducted by comparing various hydrogen properties with DFT calculations and available experimental data, as well as all the other tungsten–hydrogen potentials. The new potential accurately reproduces the point defect properties of hydrogen, the interaction among hydrogen atoms, the interplay between hydrogen and a monovacancy, and the thermal diffusion of hydrogen in tungsten. The successful validation of the new potential confirms its good reliability and transferability, which enables large-scale atomistic simulations of tungsten–hydrogen system. The new potential is afterward employed to investigate the interplay between hydrogen and other defects, including [1 1 1] self-interstitial atoms (SIAs) and vacancy clusters in tungsten. It is found that both the [1 1 1] SIAs and the vacancy clusters exhibit considerable attraction for hydrogen. Hydrogen solution and diffusion in strained tungsten are also studied using the present potential, which demonstrates that tensile (compressive) stress facilitates (impedes) hydrogen solution, and isotropic tensile (compressive) stress impedes (facilitates) hydrogen diffusion while anisotropic tensile (compressive) stress facilitates (impedes) hydrogen diffusion.
Evidence for Two Distinct Binding Sites for Lipoprotein Lipase on Glycosylphosphatidylinositol-anchored High Density Lipoprotein-binding Protein 1 (GPIHBP1)*

Background: GPIHBP1 is crucial for the transport and localization of lipoprotein lipase (LPL) at the vascular endothelium. Results: The N-terminal and Ly6 domains of GPIHBP1 interact with LPL independently and with different kinetics. Conclusion: The domains of GPIHBP1 act as two independent binding sites for LPL. Significance: The partition of LPL between the binding sites on GPIHBP1 may influence its function in lipoprotein metabolism. GPIHBP1 is an endothelial membrane protein that transports lipoprotein lipase (LPL) from the subendothelial space to the luminal side of the capillary endothelium. Here, we provide evidence that two regions of GPIHBP1, the acidic N-terminal domain and the central Ly6 domain, interact with LPL as two distinct binding sites. This conclusion is based on comparative binding studies performed with a peptide corresponding to the N-terminal domain of GPIHBP1, the Ly6 domain of GPIHBP1, wild type GPIHBP1, and the Ly6 domain mutant GPIHBP1 Q114P. Although LPL and the N-terminal domain formed a tight but short lived complex, characterized by fast on- and off-rates, the complex between LPL and the Ly6 domain formed more slowly and persisted for a longer time. Unlike the interaction of LPL with the Ly6 domain, the interaction of LPL with the N-terminal domain was significantly weakened by salt. The Q114P mutant bound LPL similarly to the N-terminal domain of GPIHBP1. Heparin dissociated LPL from the N-terminal domain, and partially from wild type GPIHBP1, but was unable to elute the enzyme from the Ly6 domain. When LPL was in complex with the acidic peptide corresponding to the N-terminal domain of GPIHBP1, the enzyme retained its affinity for the Ly6 domain. Furthermore, LPL that was bound to the N-terminal domain interacted with lipoproteins, whereas LPL bound to the Ly6 domain did not. In summary, our data suggest that the two domains of GPIHBP1 interact independently with LPL and that the functionality of LPL depends on its localization on GPIHBP1.
Early Exercise Test in Acute Myocardial Infarction Treated with Intravenous Streptokinase

The aim of this study was to assess the value of the early exercise test (ET) in patients with acute myocardial infarction (AMI) treated with IV streptokinase (SK). The authors studied 70 patients with first AMI; 31 were treated with SK and 39 were not. Before discharge everyone was given early exercise up to 5-6 METs and catheterized within 22.9 ± 7.2 days. There was no significant difference in the number of positive ETs between the two groups (11/31 and 14/39 respectively). There was significant difference in favor of: (1) the recanalization of the infarct-related artery in the SK group, (2) the negative ET in patients with recanalized vessels in both groups, (3) the positive ET in patients with multi-vessel coronary disease. It is concluded that the results of early ET in patients with AMI are related to the recanalization of the infarct-related artery and the coexistence of multi-vessel coronary artery disease, regardless of SK treatment. Patients with successful thrombolysis have negative ET more frequently.
Genotypic Survey of Recent β-Lactam-Resistant Pneumococcal Nasopharyngeal Isolates from Asymptomatic Children in Chile

ABSTRACT To assess pneumococcal strain variability among young asymptomatic carriers in Chile, we used serotyping, antibiotic susceptibility testing, and genotyping to analyze 68 multidrug-resistant pneumococcal isolates recovered from 54 asymptomatic children 6 to 48 months of age. The isolates represented capsular serotypes 19F (43 isolates), 14 (14 isolates), 23F (7 isolates), 6B (3 isolates), and 6A (1 isolate). Genotypic analysis, which included pulsed-field gel electrophoresis (PFGE) of chromosomal digests, penicillin binding protein (PBP) gene fingerprinting, and dhf gene fingerprinting, revealed that the isolates represented six different genetic lineages. Clear circumstantial evidence of capsular switching was seen within each of four of the genetically related sets. The majority of the isolates, consisting of the 43 19F isolates and 2 type 6B isolates, appeared to represent a genetically highly related set distinct from previously characterized pneumococcal strains. Each of three other genetically defined lineages was closely related to one of the previously characterized clones Spain6B-2, France9V-3, or Spain23F-1. A fifth lineage was comprised of four type 23F isolates that, by the techniques used for this study, were genetically indistinguishable from three recent type 19F sterile-site isolates from the United States. Finally, a sixth lineage was represented by a single type 23F isolate which had a unique PFGE type and unique PBP anddhf gene fingerprints.
Characterization of axonal transport defects in Drosophila Huntingtin mutants

Abstract Polyglutamine (polyQ) expansion within Huntingtin (Htt) causes the fatal neurodegenerative disorder Huntington’s Disease (HD). Although Htt is ubiquitously expressed and conserved from Drosophila to humans, its normal biological function is still being elucidated. Here we characterize a role for the Drosophila Htt homolog (dHtt) in fast axonal transport (FAT). Generation and expression of transgenic dHtt-mRFP and human Htt-mRFP fusion proteins in Drosophila revealed co-localization with mitochondria and synaptic vesicles undergoing FAT. However, Htt was not ubiquitously associated with the transport machinery, as it was excluded from dense-core vesicles and APLIP1 containing vesicles. Quantification of cargo movement in dHtt deficient axons revealed that mitochondria and synaptic vesicles show a decrease in the distance and duration of transport, and an increase in the number of pauses. In addition, the ratio of retrograde to anterograde flux was increased in mutant animals. Dense-core vesicles did not display similar defects in processivity, but did show altered retrograde to anterograde flux along axons. Given the co-localization with mitochondria and synaptic vesicles, but not dense-core vesicles, the data suggest dHtt likely acts locally at cargo interaction sites to regulate processivity. An increase in dynein heavy chain expression was also observed in dHtt mutants, suggesting that the altered flux observed for all cargo may represent secondary transport changes occurring independent of dHtt’s primary function. Expression of dHtt in a milton (HAP1) mutant background revealed that the protein does not require mitochondria or HAP1 to localize along axons, suggesting Htt has an independent mechanism for coupling with motors to regulate their processivity during axonal transport.
A Simple Theoretical Explanation of the Forecast Combination Puzzle

This paper offers a theoretical explanation why forecast combination with the estimated optimal weights has often poor performance in applications. The explanation is simple. The properties of the combination are often derived under the assumption that the weights are fixed while in practice they have to be estimated. If the weight estimation is taken into account during the optimality derivation, the combination might be biased (even if the original forecasts are unbiased) and its variance is larger and no longer guaranteed to be an improvement upon the original forecasts. If normality does not hold, then the optimal weights can be different from the weights derived without taking the estimation step into account.