Miracle-dz/UniFAR-FTUs huggingface dataset:
Autoimmune thyroid disease: further developments in our understanding.

The revolution in molecular techniques has allowed dissection of the autoimmune response in a way impossible to imagine 10 yr ago. There have been spectacular advances in our understanding of self-tolerance mechanisms and how these may fail, combined with a detailed comprehension of antigen presentation, functional T cell subsets, and TCR utilization in autoimmunity, albeit usually in animal models that resemble, but do not exactly duplicate, human diseases. More gradually, these findings are being translated to thyroid autoimmunity, where the major achievement of the last decade has been the molecular characterization of the three main thyroid autoantigens. This in turn has allowed epitope identification, although again the only clear data so far have come from animal models of EAT. Another advance has been the recognition that the thyrocyte is not a helpless target of autoaggression, being capable of expressing a wide array of immunologically active molecules, which may exacerbate or diminish the autoimmune response. In 1983, there was considerable excitement at the discovery of the first of these phenomena, namely MHC class II expression, but its possible role in autoantigen presentation remains to be defined. By analogy with pancreatic beta-cells, and based on our own data, we believe that class II-expressing thyrocytes have little, if any, such role and suspect that instead this may be a mechanism for inducing peripheral tolerance. Defining the contribution of thyrocytes to the intrathyroidal autoimmune response, whether from released cytokines or surface-bound molecules, will be crucial to our future understanding, as well as holding the promise that these thyroid-derived products might be therapeutic targets. Despite molecular developments in HLA analysis, there have been no really major improvements in our understanding of the immunogenetics of thyroid autoimmunity, equivalent to those made in type 1 diabetes mellitus. The available data suggest strongly that non-MHC genes play an important role in susceptibility, and novel approaches will be required to identify these. On the other hand, we know more about the importance of environmental and endogenous (most probably hormonal) factors in thyroid autoimmunity. Understanding the basic immunological changes in the postpartum period is still poor, however, as most studies to date have concentrated on epidemiology and clinical delineation. As PPTD undergoes spontaneous remission, elucidation of these mechanisms has clear implications for treatment. (ABSTRACT TRUNCATED AT 400 WORDS)
Subcutaneous administration of rhIGF-I post irradiation exposure enhances hematopoietic recovery and survival in BALB/c mice

It is unclear how to effectively mitigate against irradiation injury. In this study, we studied the capacity of recombinant human insulin-like growth factor-I (rhIGF-I) on hematologic recovery in irradiated BALB/c mice and its possible mechanism. BALB/c mice were injected with rhIGF-I subcutaneously at a dose of 100 μg/kg twice daily for 7 days after total body irradiation. Compared with a saline control group, treatment with rhIGF-I significantly improved the survival of mice after lethal irradiation (7.5 Gy). It was found that treatment with rhIGF-I not only could increase the frequency of Sca-1+ cells in bone marrow harvested at Day 14 after irradiation, but also it could decrease the apoptosis of mononuclear cells induced by irradiation as measured by flow cytometry, suggesting that rhIGF-I may mediate its effects primarily through promoting hematopoietic stem cell/progenitor survival and protecting mononuclear cells from apoptosis after irradiation exposure. Moreover, we have found that rhIGF-I might facilitate thrombopoiesis in an indirect way. Our data demonstrated that rhIGF-I could promote overall hematopoietic recovery after ionizing radiation and reduce the mortality when administered immediately post lethal irradiation exposure.
Using Both Sides of the Brain: Experiences that Integrate Art and Talk Therapy Through Scribble Drawings

Neuroscience researchers identify a cerebral cortex with two functioning hemispheres: a left hemisphere associated with language and speech and a right hemisphere associated with visual-motor activities. Additionally, neuroscientists argue that contemporary lifestyles favor the verbal, logical left brain and often ignore the truths that present in the right brain. Psychotherapy techniques range in their use of left-brain verbal discourse and right-brain nonverbal discourse. In a case study, the author describes experiences integrating both verbal and nonverbal therapy with a client with severe anxiety and depression. Nonverbal therapy involved annotated scribble drawings. Images in the drawings became the stimuli for verbal discourse with the client. Other client responses to the annotated scribble drawings are described.
Two-compartment comparison of gentamicin and tobramycin in normal volunteers

The objective of this study was to determine whether differences in tissue accumulation observed upon multiple dosing of aminoglycosides in hospitalized patients could be identified in appropriate single-dose studies in normal volunteers. Ten volunteers received single intravenous doses of 1.0 mg of gentamicin and tobramycin per kg of body weight in randomized crossover fashion. Multiple serum and urine samples were collected during the next 30 days. Serum aminoglycoside concentrations and urinary excretion rates were fitted to a two-compartment pharmacokinetic model, and parameters were derived. Tobramycin exhibited a higher clearance (P less than 0.08) and a lower volume of distribution at steady state (P less than 0.1), neither of which was significant. Tobramycin also showed a significantly lower predicted amount of drug in the body at steady state (P less than 0.05). These differences are consistent with observations made in patients receiving multiple doses. Single-dose studies appear to be capable of discriminating pharmacokinetic characteristics relevant to the comparative nephrotoxic potential of these two aminoglycosides.
Aldehyde dehydrogenase activation prevents reperfusion arrhythmias by inhibiting local renin release from cardiac mast cells.

BACKGROUND Renin released by ischemia/reperfusion from cardiac mast cells activates a local renin-angiotensin system (RAS). This exacerbates norepinephrine release and reperfusion arrhythmias (ventricular tachycardia and fibrillation), making RAS a new therapeutic target in myocardial ischemia. METHODS AND RESULTS We investigated whether ischemic preconditioning (IPC) prevents cardiac RAS activation in guinea pig hearts ex vivo. When ischemia/reperfusion (20 minutes of ischemia/30 minutes of reperfusion) was preceded by IPC (two 5-minute ischemia/reperfusion cycles), renin and norepinephrine release and ventricular tachycardia and fibrillation duration were markedly decreased, a cardioprotective anti-RAS effect. Activation and blockade of adenosine A(2b)/A(3) receptors and activation and inhibition of protein kinase Cepsilon (PKCepsilon) mimicked and prevented, respectively, the anti-RAS effects of IPC. Moreover, activation of A(2b)/A(3) receptors or activation of PKCepsilon prevented degranulation and renin release elicited by peroxide in cultured mast cells (HMC-1). Activation and inhibition of mitochondrial aldehyde dehydrogenase type-2 (ALDH2) also mimicked and prevented, respectively, the cardioprotective anti-RAS effects of IPC. Furthermore, ALDH2 activation inhibited degranulation and renin release by reactive aldehydes in HMC-1. Notably, PKCepsilon and ALDH2 were both activated by A(2b)/A(3) receptor stimulation in HMC-1, and PKCepsilon inhibition prevented ALDH2 activation. CONCLUSIONS The results uncover a signaling cascade initiated by A(2b)/A(3) receptors, which triggers PKCepsilon-mediated ALDH2 activation in cardiac mast cells, contributing to IPC-induced cardioprotection by preventing mast cell renin release and the dysfunctional consequences of local RAS activation. Thus, unlike classic IPC in which cardiac myocytes are the main target, cardiac mast cells are the critical site at which the cardioprotective anti-RAS effects of IPC develop.
A HoloLens Application to Aid People who are Visually Impaired in A HoloLens Application to Aid People who are Visually Impaired in Navigation Tasks Navigation Tasks

Day-to-day activities such as navigation and reading can be particularly challenging for people with visual impairments. Reading text on signs may be especially difﬁcult for people who are visually impaired because signs have variable color, contrast, and size. Indoors, signage may include ofﬁce, classroom, restroom, and ﬁre evacuation signs. Outdoors, they may include street signs, bus numbers, and store signs. Depending on the level of visual impairment, just identifying where signs exist can be a challenge. Using Microsoft’s HoloLens, an augmented reality device, I designed and implemented the TextSpotting application that helps those with low vision identify and read indoor signs so that they can navigate text-heavy environments. The application can provide both visual information and auditory information. In addition to developing the application, I conducted a user study to test its effectiveness. Participants were asked to ﬁnd a room in an unfamiliar hallway. Those that used the TextSpotting application completed the task less quickly yet reported higher levels of ease, comfort, and conﬁdence, indicating the application’s limitations and potential in providing an effective means to navigate unknown environments via signage.
Generalized Algebraic Deadlock Avoidance Policies for Sequential Resource Allocation Systems

Currently, one of the most actively researched approaches regarding the design of deadlock avoidance policies for sequential resource allocation systems is based on concepts and techniques provided by the, so called, theory of regions, that addresses the broader problem of synthesizing PN models with pre-specified behaviors. However, one limitation of the theory of regions and its aforementioned derivatives is that they cannot be applied when the target behavior has a non-convex representation in the underlying state space. In this paper, we show how this problem can be circumvented by appropriately generalizing the employed class of the candidate policies.
Commercial Breaks and Ongoing Emotions: Effects of Program Arousal and Valence on Emotions, Memory and Evaluation of Commercials

While effects of program context on commercials have been investigated exhaustively, most of these studies investigated a limited number of independent and dependent variables. Conversely, the present study examined the effects of program elicited arousal (medium and high) and valence (positive and negative) on subjects’ emotions, memory as well as evaluation of neutral commercials. Moreover, the pod position (first, third and fifth) of the target commercial has been examined in conjunction with the abovementioned variables. Results show that program arousal affects cued recall, commercial evaluation and arousal during the commercials negatively, indicating that commercials are better recalled and evaluated more favorably in a medium arousal program context than in a high arousal program context. Also program valence affects commercial evaluation and emotional valence during the commercial negatively. Commercials are better liked and subjects feel more positive during commercials shown in a negative program context compared to commercials shown in a positive program context. Effects of pod position are found as well. Results show that program context effects gradually disappear after the end of the program. Cued recall and evaluation of the commercial are only significantly affected by program context for the first pod position. However, the effect of program arousal on arousal during the commercial remains the whole commercial break.
M2e-Based Universal Influenza A Vaccines

The successful isolation of a human influenza virus in 1933 was soon followed by the first attempts to develop an influenza vaccine. Nowadays, vaccination is still the most effective method to prevent human influenza disease. However, licensed influenza vaccines offer protection against antigenically matching viruses, and the composition of these vaccines needs to be updated nearly every year. Vaccines that target conserved epitopes of influenza viruses would in principle not require such updating and would probably have a considerable positive impact on global human health in case of a pandemic outbreak. The extracellular domain of Matrix 2 (M2e) protein is an evolutionarily conserved region in influenza A viruses and a promising epitope for designing a universal influenza vaccine. Here we review the seminal and recent studies that focused on M2e as a vaccine antigen. We address the mechanism of action and the clinical development of M2e-vaccines. Finally, we try to foresee how M2e-based vaccines could be implemented clinically in the future.
Confronting a solar irradiance reconstruction with solar and stellar data

Context. A recent paper by Shapiro and colleagues (2011, A&A, 529, A67) reconstructs spectral and total irradiance variations of the Sun during the holocene. Aims. In this note, we comment on why their methodology leads to large (0.5%) variations in the solar TSI on century-long time scales, in stark contrast to other reconstructions which have 22 yr) components of the irradiance reconstructions with secular changes in stellar photometric data that span 20 years or less, and find that the Sun, if varying with such large amplitudes, would still lie within the distribution of stellar photometric variations measured over a 10−20 year period. However, the stellar time series are individually too short to see if the reconstructed variations will remain consistent with stellar variations when observed for several decades more. Conclusions. By adopting model A, Shapiro et al. have over-estimated quiet-Sun irradiance variations by about a factor of two, based upon a re-analysis of sub-mm data from the James Clerk Maxwell telescope. But both estimates are within bounds set by current stellar data. It is therefore vital to continue accurate photometry of solar-like stars for at least another decade, to reveal secular and cyclic variations on multi-decadal time scales of direct interest to the Sun.
Likelihood of changes in forest species suitability, distribution, and diversity under future climate: The case of Southern Europe

Abstract Forest conservation strategies and plans can be unsuccessful if the new habitat conditions determined by climate change are not considered. Our work aims at investigating the likelihood of future suitability, distribution and diversity for some common European forest species under the projected changes in climate, focusing on Southern Europe. We combine an Ensemble Platform for Species Distribution Models (SDMs) to five Global Circulation Models (GCMs) driven by two Representative Concentration Pathways (RCPs), to produce maps of future climate‐driven habitat suitability for ten categories of forest species and two time horizons. For each forest category and time horizon, ten maps of future distribution (5 GCMs by 2 RCPs) are thus combined in a single suitability map supplied with information about the “likelihood” adopting the IPCC terminology based on consensus among projections. Then, the statistical significance of spatially aggregated changes in forest composition at local and regional level is analyzed. Finally, we discuss the importance, among SDMs, that environmental predictors seem to have in influencing forest distribution. Future impacts of climate change appear to be diversified across forest categories. A strong change in forest regional distribution and local diversity is projected to take place, as some forest categories will find more suitable conditions in previously unsuitable locations, while for other categories the same new conditions will become less suited. A decrease in species diversity is projected in most of the area, with Alpine region showing the potentiality to become a refuge for species migration.
Critical Appraisal of Bivalirudin versus Heparin for Percutaneous Coronary Intervention: A Meta-Analysis of Randomized Trials

Percutaneous coronary intervention with bivalirudin plus bail-out glycoprotein IIb/IIIa inhibitors has been shown to be as effective as unfractionated heparin plus routine glycoprotein IIb/IIIa inhibitors in preventing cardiac ischemic events, but with a lower bleeding risk. It is unknown whether bivalirudin would have the same beneficial effects if compared with heparin when the use of glycoprotein IIb/IIIa inhibitors was similar between treatment arms. We searched the MEDLINE, Web of Science, and Cochrane databases from inception until March 2015 for randomized trials that compared bivalirudin to heparin in patients undergoing percutaneous coronary intervention. We required that the intended use of glycoprotein IIb/IIIa inhibitors was similar between the study groups. Summary estimates were principally constructed by the Peto method. Fifteen trials met our inclusion criteria, which yielded 25,824 patients. Bivalirudin versus heparin was associated with an increased hazard of stent thrombosis (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.15-1.92, P = .002, I2 = 16.9%), with a similar hazard of myocardial infarction (OR 1.09, 95% CI 0.98-1.22, P = .11, I2 = 35.8%), all-cause mortality (OR 0.88, 95% CI 0.72-1.08, P = .21, I2 = 31.5%) and major adverse cardiac events (OR 1.04, 95% CI 0.94-1.14, P = .46, I2 = 53.9%). Bivalirudin was associated with a reduced hazard of major bleeding (OR 0.80, 95% CI 0.70-0.92, P = .001, I2 = 63.5%). The dose of heparin in the control arm modified this association; when the dose of unfractionated heparin in the control arm was ≥ 100 units/kg, bivalirudin was associated with a reduction in major bleeding (OR 0.55, 95% CI 0.45-0.68, P < .0001), but when the dose of unfractionated heparin was ≤ 75 units/kg, bivalirudin was not associated with reduction in bleeding (OR 1.09, 95% CI 0.91-1.31, P = .36). Among patients undergoing PCI, bivalirudin was associated with an increased hazard of stent thrombosis. Bivalirudin may be associated with a reduced hazard of major bleeding; however, this benefit was no longer apparent when compared with a dose of unfractionated heparin ≤ 75 units/kg.
Modeling of Oil Mist and Oil Vapor Concentration in the Shale Shaker Area on Offshore Drilling Installations

The objective of this study was to develop regression models to predict concentrations of oil mist and oil vapor in the workplace atmosphere in the shale shaker area of offshore drilling installations. Collection of monitoring reports of oil mist and oil vapor in the mud handling areas of offshore drilling installations was done during visits to eight oil companies and five drilling contractors. A questionnaire was sent to the rig owners requesting information about technical design of the shaker area. Linear mixed-effects models were developed using concentration of oil mist or oil vapor measured by stationary sampling as dependent variables, drilling installation as random effect, and potential determinants related to process technical parameters and technical design of the shale shaker area as fixed effects. The dataset comprised stationary measurements of oil mist (n = 464) and oil vapor (n = 462) from the period 1998 to 2004. The arithmetic mean concentrations of oil mist and oil vapor were 3.89 mg/m 3 and 39.7 mg/m 3 , respectively. The air concentration models including significant determinants such as viscosity of base oil, mud temperature, well section, type of rig, localization of shaker, mechanical air supply, air grids in outer wall, air curtain in front of shakers, and season explained 35% and 17% of the total variance in oil vapor and oil mist, respectively. The developed models could be used to indicate what impact differences in technical design and changes in process parameters have on air concentrations of oil mist and oil vapor. Thus, the models will be helpful in planning control measures to reduce the potential for occupational exposure.
Frailty in Older Adults Using Pre-hospital Care and the Emergency Department: A Narrative Review

Background Older adults use more health-care services per capita than younger age groups and the older adult population varies greatly in its needs. Evidence suggests that there is a critical distinction between relative frailty and fitness in older adults. Here, we review how frailty is described in the pre-hospital literature and in the broader emergency medicine literature. Methods PubMed was used as the primary database, but was augmented by searches of CINAHL and EMBASE. Articles were included if they focused on patients 60 years and older and implemented a definition of frailty or risk screening tool in the Emergency Medical Services (EMS) or Emergency Department setting. Results In the broad clinical literature, three types of measures can be identified: frailty index measures, frailty scales, and a phenotypic definition. Each offers advantages and disadvantages for the EMS stakeholder. We identified no EMS literature on frailty conceptualization or management, although some risk measures from emergency medicine use terms that overlap with the frailty literature. Conclusions There is a paucity of research on frailty in the Emergency Medical Services literature. No research was identified that specifically addressed frailty conceptualization or management in EMS patients. There is a compelling need for further research in this area.
Molecular basis for an attenuated mitochondrial adaptive plasticity in aged skeletal muscle

Our intent was to investigate the mechanisms driving the adaptive potential of subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria in young (6 mo) and senescent (36 mo) animals in response to a potent stimulus for organelle biogenesis. We employed chronic electrical stimulation (10 Hz, 3 h/day, 7 days) to induce contractile activity of skeletal muscle in 6 and 36 mo F344XBN rats. Subsequent to chronic activity, acute stimulation (1 Hz, 5 min) in situ revealed greater fatigue resistance in both age groups. However, the improvement in endurance was significantly greater in the young, compared to the old animals. Chronic muscle use also augmented SS and IMF mitochondrial volume to a greater extent in young muscle. The molecular basis for the diminished organelle expansion in aged muscle was due, in part, to the collective attenuation of the chronic stimulation-evoked increase in regulatory proteins involved in mediating mitochondrial protein import and biogenesis. Furthermore, adaptations in mitochondrial function were also blunted in old animals. However, chronic contractile activity evoked greater reductions in mitochondrially-mediated proapoptotic signaling in aged muscle. Thus, mitochondrial plasticity is retained in aged animals, however the magnitude of the changes are less compared to young animals due to attenuated molecular processes regulating organelle biogenesis.