Miracle-dz/UniFAR-FTUs huggingface dataset:
Metabolic regulation of hepatic immunopathology by myeloid-derived suppressor cells

The liver provides a highly immunotolerant environment, that is exploited by hepatotropic viruses such as Hepatitis B virus (HBV), which establishes persistent infection in more than 350 million people worldwide. In this thesis the potential for myeloid-derived suppressor cells (MDSC) to exert metabolic regulation in this setting has been investigated. We found a mean approximate 9-fold expansion of granulocytic MDSC (gMDSC) in patients with chronic HBV infection (CHB) compared to uninfected, healthy controls (p<0.001). The most striking increases were seen in patients replicating HBV in the absence of immunopathology (p<0.01). gMDSC expressed high levels of the chemokine receptor, CXCR1, providing the potential for them to be chemoattracted by liver-derived interleukin-8 (IL-8); consistent with this, they were further enriched in the intrahepatic compartment. gMDSC from patients with CHB expressed increased amounts of arginase I, correlating with an increase in serum levels of this enzyme (p<0.01). Arginase I metabolises the conditionally essential amino acid L-arginine that is required for proliferating T cells; in line with this was an observed decrease in circulating L-arginine, particularly in those patients without liver inflammation. Liver pathology in CHB is ampli ed by the recruitment and activation of bystander (non-HBV-speci c) T cells; therefore the potential of gMDSC to down-regulate such responses was explored. Puri ed gMDSC from patients with CHB potently inhibit the expansion of bystander T cells capable of producing pro-inflammatory cytokines or mediating cytotoxicity. This inhibition was blocked using an arginase I-specific inhibitor, N-hydroxy-nor-arginine (nor-NOHA). Taken together, these data demonstrate the capacity for expanded arginase I expressing gMDSC to regulate liver immunopathology in CHB by depriving T cells of L-arginine.
Longitudinal Morphological and Functional Assessment of RGC Neurodegeneration After Optic Nerve Crush in Mouse

The mouse optic nerve crush (ONC) model has been widely used to study optic neuropathies and central nervous system (CNS) axon injury and repair. Previous histological studies of retinal ganglion cell (RGC) somata in retina and axons in ON demonstrate significant neurodegeneration after ONC, but longitudinal morphological and functional assessment of RGCs in living animals is lacking. It is essential to establish these assays to provide more clinically relevant information for early detection and monitoring the progression of CNS neurodegeneration. Here, we present in vivo data gathered by scanning laser ophthalmoscopy (SLO), optical coherence tomography (OCT), and pattern electroretinogram (PERG) at different time points after ONC in mouse eyes and corresponding histological quantification of the RGC somata and axons. Not surprisingly, direct visualization of RGCs by SLO fundus imaging correlated best with histological quantification of RGC somata and axons. Unexpectedly, OCT did not detect obvious retinal thinning until late time points (14 and 28-days post ONC) and instead detected significant retinal swelling at early time points (1–5 days post-ONC), indicating a characteristic initial retinal response to ON injury. PERG also demonstrated an early RGC functional deficit in response to ONC, before significant RGC death, suggesting that it is highly sensitive to ONC. However, the limited progression of PERG deficits diminished its usefulness as a reliable indicator of RGC degeneration.
A High-Resolution Global Dataset of Extreme Sea Levels, Tides, and Storm Surges, Including Future Projections

The world’s coastal areas are increasingly at risk of coastal flooding due to sea-level rise (SLR). We present a novel global dataset of extreme sea levels, the Coastal Dataset for the Evaluation of Climate Impact (CoDEC), which can be used to accurately map the impact of climate change on coastal regions around the world. The third generation Global Tide and Surge Model (GTSM), with a coastal resolution of 2.5 km (1.25 km in Europe), was used to simulate extreme sea levels for the ERA5 climate reanalysis from 1979 to 2017, as well as for future climate scenarios from 2040 to 2100. The validation against observed sea levels demonstrated a good performance, and the annual maxima had a mean bias (MB) of -0.04 m, which is 50% lower than the MB of the previous GTSR dataset. By the end of the century (2071–2100), it is projected that the 1 in 10-year water levels will have increased 0.34 m on average for RCP4.5, while some locations may experience increases of up to 0.5 m. The change in return levels is largely driven by SLR, although at some locations changes in storms surges and interaction with tides amplify the impact of SLR with changes up to 0.2 m. By presenting an application of the CoDEC dataset to the city of Copenhagen, we demonstrate how climate impact indicators derived from simulation can contribute to an understanding of climate impact on a local scale. Moreover, the CoDEC output locations are designed to be used as boundary conditions for regional models, and we envisage that they will be used for dynamic downscaling.
Noise Helps Optimization Escape From Saddle Points in the Synaptic Plasticity

Numerous experimental studies suggest that noise is inherent in the human brain. However, the functional importance of noise remains unknown. n particular, from a computational perspective, such stochasticity is potentially harmful to brain function. In machine learning, a large number of saddle points are surrounded by high error plateaus and give the illusion of the existence of local minimum. As a result, being trapped in the saddle points can dramatically impair learning and adding noise will attack such saddle point problems in high-dimensional optimization, especially under the strict saddle condition. Motivated by these arguments, we propose one biologically plausible noise structure and demonstrate that noise can efficiently improve the optimization performance of spiking neural networks based on stochastic gradient descent. The strict saddle condition for synaptic plasticity is deduced, and under such conditions, noise can help optimization escape from saddle points on high dimensional domains. The theoretical results explain the stochasticity of synapses and guide us on how to make use of noise. In addition, we provide biological interpretations of proposed noise structures from two points: one based on the free energy principle in neuroscience and another based on observations of in vivo experiments. Our simulation results manifest that in the learning and test phase, the accuracy of synaptic sampling with noise is almost 20% higher than that without noise for synthesis dataset, and the gain in accuracy with/without noise is at least 10% for the MNIST and CIFAR-10 dataset. Our study provides a new learning framework for the brain and sheds new light on deep noisy spiking neural networks.
The Effects of Whole-Body Photobiomodulation Light-Bed Therapy on Creatine Kinase and Salivary Interleukin-6 in a Sample of Trained Males: A Randomized, Crossover Study

Photobiomodulation therapy (PBMT) can be applied to the whole body as compared to the application of using single hand-held devices that isolate a smaller muscle area. The purpose of this study was to examine the effects of an acute dose of whole-body PBMT pre- and post-high-intensity resistance training on creatine kinase (CK) and salivary interleukin-6 (IL-6) in a sample of trained males. Twelve males (31 ± 8.3 years, 177.2 ± 5.4 cm, and 86.0 ± 7.5 kg) were part of a randomized, counterbalanced, cross-over design, whereby each participant performed a high-intensity resistance training session that consisted of the bench press, chin-up, and repeated sprints on two separate occasions. Each participant was assigned to either the PBMT or control condition on two separate weeks, with a 10-days washout period between the weeks. Creatine kinase was measured at baseline, 24, 48, and 72 h post-exercise. Salivary IL-6 was measured at baseline, 60, 90, and 120 min. A paired t-test showed no significant difference (p = 0.669) in the area under the curve (AUC) for CK during the PBMT (191.7 ± 48.3) and control conditions (200.2 ± 68.0). A Wilcoxon signed-rank test also showed no significant median difference (p = 0.155) in the AUC for salivary IL-6 during the PBMT (Mdn = 347.7) and control conditions (Mdn = 305.8). An additional Wilcoxon signed-rank test for CK percentage change from 24 to 72 h showed the PBMT condition (Mdn = −45%) to have a −18% median difference as compared to the control condition (Mdn = −41%). As such, whole-body PBMT does not significantly reduce the activity of salivary IL-6 or CK concentration during the 24 to 72-h recovery post-high-intensity resistance training.
Body Movement Synchrony Predicts Degrees of Information Exchange in a Natural Conversation

Human interaction has two principle functions: building and maintaining relationships with others and exchanging information. The function of building and maintaining relationships with others relates to interpersonal coordination; this behavior pattern is expected to predict the outcome of social relationships, such as between therapists and patients. It is unclear, however, whether the exchange of information is associated with interpersonal coordination. In the present study, we tested a hypothesis of whether body movement synchrony occurs in a natural conversation and whether this synchrony has a positive correlation with the degree of information exchange. Fifty participants were engaged in a conversation task; each had different roles in the conversation. We measured their body movements during this conversation using an optical motion capture system. Similar to methods that can be found in previous research, we calculated body movements and quantified their synchrony applying the methods previously reported that automatically quantified their body movements. Moreover, we determined the participants’ degree of information exchange concerning the conversation using a questionnaire. We observed that the body movement synchrony of pairs who talked with each other was significantly higher than that of pairs who did not talk with each other, and that this synchrony was positively associated with the degree of information exchange. These results suggest that body movement synchrony predicted information exchange.
Targeting Ubiquitin-Proteasome Pathway by Natural Products: Novel Therapeutic Strategy for Treatment of Neurodegenerative Diseases

Misfolded proteins are the main common feature of neurodegenerative diseases, thereby, normal proteostasis is an important mechanism to regulate the neural survival and the central nervous system functionality. The ubiquitin-proteasome system (UPS) is a non-lysosomal proteolytic pathway involved in numerous normal functions of the nervous system, modulation of neurotransmitter release, synaptic plasticity, and recycling of membrane receptors or degradation of damaged and regulatory intracellular proteins. Aberrant accumulation of intracellular ubiquitin-positive inclusions has been implicated to a variety of neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington disease (HD), Amyotrophic Lateral Sclerosis (ALS), and Multiple Myeloma (MM). Genetic mutation in deubiquitinating enzyme could disrupt UPS and results in destructive effects on neuron survival. To date, various agents were characterized with proteasome-inhibitory potential. Proteins of the ubiquitin-proteasome system, and in particular, E3 ubiquitin ligases, may be promising molecular targets for neurodegenerative drug discovery. Phytochemicals, specifically polyphenols (PPs), were reported to act as proteasome-inhibitors or may modulate the proteasome activity. PPs modify the UPS by means of accumulation of ubiquitinated proteins, suppression of neuronal apoptosis, reduction of neurotoxicity, and improvement of synaptic plasticity and transmission. This is the first comprehensive review on the effect of PPs on UPS. Here, we review the recent findings describing various aspects of UPS dysregulation in neurodegenerative disorders. This review attempts to summarize the latest reports on the neuroprotective properties involved in the proper functioning of natural polyphenolic compounds with implication for targeting ubiquitin-proteasome pathway in the neurodegenerative diseases. We highlight the evidence suggesting that polyphenolic compounds have a dose and disorder dependent effects in improving neurological dysfunctions, and so their mechanism of action could stimulate the UPS, induce the protein degradation or inhibit UPS and reduce protein degradation. Future studies should focus on molecular mechanisms by which PPs can interfere this complex regulatory system at specific stages of the disease development and progression.
The Mediating Role of Stress in the Relationship Between Attention to Threat Bias and Psychotic-Like Experiences Depends on Coping Strategies

Aim Recent studies have provided evidence that enhanced stress level is associated with the increase of psychotic symptoms in both clinical and non-clinical populations. It has also been demonstrated that cognitive biases contribute to psychotic experiences. However, it remains unclear whether the effect of cognitive biases and perceived stress on psychotic-like experiences (PLEs) is influenced by coping methods. In the present study we examined whether the relationship linking cognitive biases with PLEs is mediated by the level of stress and whether particular coping methods modify the relationship between stress and PLEs. Methods The study sample consisted of 290 non-clinical subjects; study variables were assessed by questionnaires. Moderated mediation analyses were conducted. Results Perceived stress was found to serve as a partial mediator in the relationship linking attention to threat (ATB) and external attribution biases (ETB) with psychotic-like experiences. Also, moderated mediation analysis revealed that the indirect effect of attention to threat bias on positive and depressive symptoms of psychotic-like experiences via perceived stress was stronger at higher levels of distraction seeking coping. Moreover, the indirect effect of ATB on depressive symptoms was moderated by task-oriented coping and emotion-oriented coping. Task-oriented coping also moderated the indirect effect of ETB on depression. Conclusion The findings imply that both perceived stress and coping styles are important factors affecting the association between cognitive biases and psychotic-like experiences.
Population Pharmacokinetics and Pharmacodynamics Modeling of Torasemide and Furosemide After Oral Repeated Administration in Healthy Dogs

Torasemide is a loop diuretic licensed in dogs for cardiogenic pulmonary oedema. The aim of this pharmacokinetic-pharmacodynamic (PK/PD) study was to define an optimally effective dosage regimen based on preclinical data. In a first study, 5 dogs received once-daily oral torasemide (0, 0.1, 0.2, 0.4, 0.8 mg/kg/day) for 14 days. A second study compared once-daily oral torasemide (0, 0.1, 0.2, 0.3, 0.4 mg/kg/day) to twice-daily furosemide (1, 2, 4, 8 mg/kg/day). For all doses of the second study, 11 dogs received a first day of treatment, followed by a 3 day washout and resumed daily treatment for 10 days (until Day 14). Blood and urine were collected to measure urinary torasemide excretion and plasma torasemide concentrations and daily diuresis and natriuresis. Torasemide PK was linear. After rapid absorption (Tmax 0.5–1 h), 61% of the bioavailable torasemide was eliminated unchanged in urine. Diuresis and natriuresis observed with torasemide were similar to the ones obtained after furosemide (daily dose-ratios: 1/20 to 1/10). The average diuresis increased from baseline (220 ± 53 mL/day for 10 kg dogs) to 730 ±120 mL after the first torasemide administration and up to 1150 ± 252 mL after 10 administrations at the highest dose. At higher doses (≥0.3 mg/kg/day), daily diureses after 10 diuretic treatment-days were higher than Day 1 and variable between dogs; in contrast, diureses remained constant over time and less variable for doses up to 0.2 mg/kg/day. Natriuresis peaked after the first day and decreased dramatically after the 2nd treatment-day then stabilized to a value close to baseline, except for 0.4 mg/kg/day. Urinary torasemide excretion predicted pharmacodynamics better than plasma concentrations. The decrease in natriuresis observed was successfully modeled using a resistance mechanism; this is likely due to a reabsorption of sodium which did not seem however to affect the volume of urine excreted. For a daily target diuresis of 460 mL/dog/day in severe pulmonary oedema (net fluid loss 240 mL/dog/day), a computed dose of 0.26 mg/kg/day (3.5 mg/kg/day furosemide-equivalent) was selected for clinical studies. Due to high inter-individual variability in diureses at doses ≥0.3 mg/kg, higher doses should be limited to 3–5 days to avoid supra-clinical effects in high responders.
The Effect of Side of Implantation on the Cortical Processing of Frequency Changes in Adult Cochlear Implant Users

Cochlear implants (CI) are widely used in children and adults to restore hearing function. However, CI outcomes are vary widely. The affected factors have not been well understood. It is well known that the right and left hemispheres play different roles in auditory perception in adult normal hearing listeners. It is unknown how the implantation side may affect the outcomes of CIs. In this study, the effect of the implantation side on how the brain processes frequency changes within a sound was examined in 12 right-handed adult CI users. The outcomes of CIs were assessed with behaviorally measured frequency change detection threshold (FCDT), which has been reported to significantly affect CI speech performance. The brain activation and regions were also examined using acoustic change complex (ACC, a type of cortical potential evoked by acoustic changes within a stimulus), on which the waveform analysis and the standardized low-resolution brain electromagnetic tomography (sLORETA) were performed. CI users showed activation in the temporal lobe and non-temporal areas, such as the frontal lobe. Right-ear CIs could more efficiently activate the contralateral hemisphere compared to left-ear CIs. For right-ear CIs, the increased activation in the contralateral temporal lobe together with the decreased activation in the contralateral frontal lobe was correlated with good performance of frequency change detection (lower FCDTs). Such a trend was not found in left-ear CIs. These results suggest that the implantation side may significantly affect neuroplasticity patterns in adults.
ANÁLISIS FUNCIONAL DE PROTEÍNAS CODIFICADAS POR EL VIRUS DE LA ROTURA DEL COLOR DE LA FLOR DEL PELARGONIUM

Interes del estudio: El virus de la rotura del color de la flor del Pelargonium (Pelargonium flower break virus, PFBV) (genero Carmovirus, familia Tombusviridae) constituye uno de patogenos virales mas frecuentes en geranio, una planta ornamental de gran interes para la industria floral. En los ultimos anos se ha registrado un aumento progresivo de las infecciones causadas por este patogeno, con un porcentaje de incidencia superior al 80% en regiones de Europa occidental y en algunas areas de Espana. La informacion acerca de las relaciones estructura-funcion en las proteinas de este virus era practicamente inexistente al inicio de este trabajo y bastante limitada para las proteinas equivalentes de muchos virus relacionados, de modo que la aportacion de datos adicionales en este campo puede ser de gran utilidad para entender mejor el establecimiento de la infeccion y los mecanismos de interaccion con el huesped de este virus y de otros equivalentes. Objetivos: Durante el desarrollo de esta Tesis Doctoral se han llevado a cabo analisis de las relaciones estructura-funcion de las proteinas que codifica el PFBV, centrandonos en aquellos productos virales con caracteristicas atipicas o cuya funcion no esta del todo clara dentro del grupo al cual pertenece el virus. Con ello se ha pretendido aportar nuevos datos al conocimiento del patogeno y, en general, del grupo al que pertenece. Elementos de la metodologia a destacar: La realizacion de esta Tesis ha permitido la publicacion de varios articulos de divulgacion cientifica, aprobados por comites que han avalado convenientemente el uso de las metodologias empleadas. Resultados logrados: Con este trabajo se ha establecido la etapa del ciclo infeccioso en la que se encuentran involucradas las distintas proteinas del PFBV y se han analizado relaciones estructura-funcion en dichos productos. Asimismo, se han determinado algunas propiedades relevantes de proteinas implicadas en la replicacion, asi como de aquellas que asisten
Determination of Fatty Acid Composition and Total Trans Fatty Acids in Meat Products

In this research, fatty acid composition and trans fatty acids of 22 selected meat products produced by Turkish companies were analyzed by capillary gas liquid chromatography (GLC). Total fat contents of the meat products ranged from 11.60-42.50%. Salami had the lowest fat content 11.60% and sucuk (soudjuk) the highest 42.50%. Major fatty acids were C 16:0 , C 18:0 , trans C 18:1 , cis C 18:1 , and C 18:2 in the samples. Total unsaturated fatty acid contents have changed from 38.73 to 70.71% of total fatty acids, and sausage had the highest percentage among the samples. The majority of samples contain trans fatty acids and the level ranged from 2.28 to 7.95% of the total fatty acids. The highest amount of total trans fatty acids was determined in kavurma (Cavurmas) (7.95%), and total trans fatty acids of meat products such as pastrami contained more than 5% of the total fatty acids.
Compassion Satisfaction and Fatigue in Cardiovascular Nurses: A Cross-sectional Descriptive Study

Background: Cardiovascular nurses play a key role in improving the treatment outcomes in patients. Compassion satisfaction and fatigue influence the quality of nursing care. Thus, it is important to examine the levels of compassion satisfaction and fatigue in cardiovascular nurses. This study was performed to determine compassion satisfaction and fatigue in cardiovascular nurses. Materials and Methods: This cross-sectional, descriptive study was conducted with a single-stage design on 200 cardiovascular nurses who were randomly selected from among nurses working in four educational hospitals in Isfahan, Iran, in July–October 2018. Data collection was conducted using the Professional Quality Of Life Scale (version 5) (ProQOL- version 5) with 30 items in the three subscales of compassion satisfaction, burnout, and Secondary Traumatic Stress (STS). The results were analyzed using descriptive and inferential statistics in SPSS software. Results: The results indicated the high mean (SD) score of 41.39 (5.54) for compassion satisfaction and the moderate mean (SD) scores of 26.93 (4.62) and 26.69 (5.90) for burnout and STS, respectively, in more than two-thirds of the nurses. Pearson correlation coefficient showed no significant relationship between the nurses' age, level of education, work experience, and monthly working hours and scores of compassion satisfaction, burnout, and STS, and total compassion fatigue score (p > 0.05). Work experience was directly related to STS score (r = 0.18,p = 0.01). However, it had no significant relationship with compassion satisfaction and burnout (p > 0.05). Conclusions: The results showed that the score of compassion satisfaction was high and fatigue was moderate in the cardiovascular nurses. Further research seems necessary to enhance compassion satisfaction and reduce fatigue in nurses.