Miracle-dz/UniFAR-FTUs huggingface dataset:
Dual Pharmacological Targeting of HDACs and PDE5 Inhibits Liver Disease Progression in a Mouse Model of Biliary Inflammation and Fibrosis

Simple Summary Chronic liver injury and inflammation leads to excessive deposition of extracellular matrix, known as liver fibrosis, and the distortion of the hepatic parenchyma. Liver fibrosis may progress to cirrhosis, a condition in which hepatic function is impaired and most cases of liver tumors occur. Currently, there are no effective therapies to inhibit and reverse the progression of liver fibrosis, and therefore, chronic liver disease remains a global health problem. In this study we have tested the efficacy of a new class of molecules that simultaneously target two molecular pathways known to be involved in the pathogenesis of hepatic fibrosis. In a clinically relevant mouse model of liver injury and inflammation we show that the combined inhibition of histones deacetylases and the cyclic guanosine monophosphate (cGMP) phosphodiesterase phosphodiesterase 5 (PDE5) results in potent anti-inflammatory and anti-fibrotic effects. Our findings open new avenues for the treatment of liver fibrosis and therefore, the prevention of hepatic carcinogenesis. Abstract Liver fibrosis, a common hallmark of chronic liver disease (CLD), is characterized by the accumulation of extracellular matrix secreted by activated hepatic fibroblasts and stellate cells (HSC). Fibrogenesis involves multiple cellular and molecular processes and is intimately linked to chronic hepatic inflammation. Importantly, it has been shown to promote the loss of liver function and liver carcinogenesis. No effective therapies for liver fibrosis are currently available. We examined the anti-fibrogenic potential of a new drug (CM414) that simultaneously inhibits histone deacetylases (HDACs), more precisely HDAC1, 2, and 3 (Class I) and HDAC6 (Class II) and stimulates the cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) pathway activity through phosphodiesterase 5 (PDE5) inhibition, two mechanisms independently involved in liver fibrosis. To this end, we treated Mdr2-KO mice, a clinically relevant model of liver inflammation and fibrosis, with our dual HDAC/PDE5 inhibitor CM414. We observed a decrease in the expression of fibrogenic markers and collagen deposition, together with a marked reduction in inflammation. No signs of hepatic or systemic toxicity were recorded. Mechanistic studies in cultured human HSC and cholangiocytes (LX2 and H69 cell lines, respectively) demonstrated that CM414 inhibited pro-fibrogenic and inflammatory responses, including those triggered by transforming growth factor β (TGFβ). Our study supports the notion that simultaneous targeting of pro-inflammatory and fibrogenic mechanisms controlled by HDACs and PDE5 with a single molecule, such as CM414, can be a new disease-modifying strategy.
Vowel variability and contrast in Childhood Apraxia of Speech: acoustics and articulation

ABSTRACT Phoneme production may be affected by limited speech motor control in Childhood Apraxia of Speech (CAS), with a general instability of acoustic targets across multiple repetitions of speech stimuli. This acoustic and Ultrasound Tongue Imaging (UTI) study shows that increased variability and reduction of contrast in vowel production is found in native Italian speakers with CAS, particularly as far as the height dimension is concerned. The data suggest that vowel production should play a major role in CAS diagnosis and treatment. Moreover, this study shows that a combined acoustic and articulatory approach allows direct observation of lingual dynamics together with an estimation of changes in the acoustic dimension. The two dimensions are shown not to correspond in a straightforward way in the speech of children with CAS, and encourage consideration of articulatory compensation strategies aimed at saving the acoustic identity of vowels.
A Francisella tularensis Chitinase Contributes to Bacterial Persistence and Replication in Two Major U.S. Tick Vectors

Nearly 100 years after the first report of tick-borne tularemia, questions remain about the tick vector(s) that pose the greatest risk for transmitting Francisella tularensis (Ft), the causative agent of tularemia. Additionally, few studies have identified genes/proteins required for Ft to infect, persist, and replicate in ticks. To answer questions about vector competence and Ft transmission by ticks, we infected Dermacentor variabilis (Dv), Amblyomma americanum (Aa), and Haemaphysalis longicornis (Hl; invasive species from Asia) ticks with Ft, finding that although Aa ticks initially become infected with 1 order of magnitude higher Ft, Ft replicated more robustly in Dv ticks, and did not persist in Hl ticks. In transmission studies, both Dv and Aa ticks efficiently transmitted Ft to naïve mice, causing disease in 57% and 46% of mice, respectively. Of four putative Ft chitinases, FTL1793 is the most conserved among Francisella sp. We generated a ΔFTL1793 mutant and found that ΔFTL1793 was deficient for infection, persistence, and replication in ticks. Recombinant FTL1793 exhibited chitinase activity in vitro, suggesting that FTL1793 may provide an alternative energy source for Ft in ticks. Taken together, Dv ticks appear to pose a greater risk for harboring and transmitting tularemia and FTL1793 plays a major role in promoting tick infections by Ft.
Cardiorespiratory fitness, hippocampal subfield volumes, and mnemonic discrimination task performance in aging

Aging and exercise have opposing effects on mnemonic discrimination task performance, which putatively taxes pattern separation mechanisms reliant on the dentate gyrus (DG) subfield of the hippocampus. In young adults, increasing cardiorespiratory fitness (CRF) has been shown to improve mnemonic discrimination task performance and increase left anterior DG/CA3 volume. It is unknown how these variables interact in cognitive aging, yet this knowledge is critical, given the established effects of aging on hippocampal plasticity. To investigate these relationships, 65 older adults (aged 55–85 years) completed a submaximal treadmill test to estimate CRF, a mnemonic discrimination task, and a high‐resolution MRI scan to determine hippocampal subfield volumes. Our older adult sample demonstrated the lowest task accuracy in the condition with the greatest stimuli similarity and left DG/CA3 body volume significantly predicted accuracy in this condition. Our results did not provide support for relationships between CRF and task accuracy or CRF and DG/CA3 volume as evidenced in studies of young adults. Instead, CRF predicted bilateral subiculum volume in older adult women, not men. Altogether, these findings provide further support for a role of the DG in behavioral pattern separation in humans and suggest that CRF may have differential effects on hippocampal subfield integrity in older adult men and women. ClinicalTrials.gov identifiers: (a) Neuroimaging Study of Exercise and Memory Function, NCT02057354; (b) The Entorhinal Cortex and Aerobic Exercise in Aging, NCT02775760; (c) Physical Activity and Cognition Study, NCT02773121.
Tuning the Magnetism in Boron-Doped Strontium Titanate

The magnetic and electronic properties of boron-doped SrTiO3 have been studied by first-principles calculations. We found that the magnetic ground states of B-doped SrTiO3 strongly depended on the dopant-dopant separation distance. As the dopant–dopant distance varied, the magnetic ground states of B-doped SrTiO3 can have nonmagnetic, ferromagnetic or antiferromagnetic alignment. The structure with the smallest dopant-dopant separation exhibited the lowest total energy among all configurations considered and was characterized by dimer pairs due to strong attraction. Ferromagnetic coupling was observed to be stronger when the two adjacent B atoms aligned linearly along the B-Ti-B axis, which could be associated with their local bonding structures. Therefore, the symmetry of the local structure made an important contribution to the generation of a magnetic moment. Our study also demonstrated that the O-Ti-O unit was easier than the Ti-B-Ti unit to deform. The electronic properties of boron-doped SrTiO3 tended to show semiconducting or insulating features when the dopant–dopant distance was less than 5 Å, which changed to metallic properties when the dopant–dopant distance was beyond 5 Å. Our calculated results indicated that it is possible to manipulate the magnetism and band gap via different dopant–dopant separations.
Optimization of Visual Stimulus Sequence in a Brain-Computer Interface Based on Code Modulated Visual Evoked Potentials

Brain-computer interfaces based on code-modulated visual evoked potentials provide high information transfer rates, which make them promising alternative communication tools. Circular shifts of a binary sequence are used as the flickering pattern of several visual stimuli, where the minimum correlation between them is critical for recognizing the target by analyzing the EEG signal. Implemented sequences have been borrowed from communication theory without considering visual system physiology and related ergonomics. Here, an approach is proposed to design optimum stimulus sequences considering physiological factors, and their superior performance was demonstrated for a 6-target c-VEP BCI system. This was achieved by defining a time-factor index on the frequency response of the sequence, while the autocorrelation index ensured a low correlation between circular shifts. A modified version of the non-dominated sorting genetic algorithm II (NSGAII) multi-objective optimization technique was implemented to find, for the first time, 63-bit sequences with simultaneously optimized autocorrelation and time-factor indexes. The selected optimum sequences for general (TFO) and 6-target (6TO) BCI systems, were then compared with m-sequence by conducting experiments on 16 participants. Friedman tests showed a significant difference in perceived eye irritation between TFO and m-sequence (p = 0.024). Generalized estimating equations (GEE) statistical test showed significantly higher accuracy for 6TO compared to m-sequence (p = 0.006). Evaluation of EEG responses showed enhanced SNR for the new sequences compared to m-sequence, confirming the proposed approach for optimizing the stimulus sequence. Incorporating physiological factors to select sequence(s) used for c-VEP BCI systems improves their performance and applicability.
Mode Analysis of Pt/LGS Surface Acoustic Wave Devices

Platinum (Pt) gratings on langasite (LGS) substrates are a widely used structures in high temperature surface acoustic wave (SAW) devices. Multiple modes can be excited in Pt/LGS SAW devices owing to the heavy weight of the Pt electrode and leaky waves in the LGS substrate. In this work, we report on a detailed mode analysis of Pt/LGS SAW devices, where three commonly used LGS cuts are considered. A three-dimensional (3D) finite element method (FEM) numerical model was developed, and the simulation and experiment results were compared. The experiment and simulation results showed that there are two modes excited in the Pt/LGS SAW devices with Euler angle (0°, 138.5°, 27°) and (0°, 138.5°, 117°), which are Rayleigh-type SAW and SH-type leaky wave, respectively. Only the Rayleigh-type mode was observed in the Pt/LGS SAW devices with Euler angle (0°, 138.5°, 72°). It was found that the acoustic velocities are dependent on the wavelength, which is attributed to the change of wave penetration depth in interdigital transducers (IDTs) and the velocity dispersion can be modulated by the thickness of the Pt electrode. We also demonstrated that addition of an Al2O3 passivation layer has no effect on the wave modes, but can increase the resonant frequencies. This paper provides a better understanding of the acoustic modes of Pt/LGS SAW devices, as well as useful guidance for device design. It is believed that the Rayleigh-type SAW and SH-type leaky waves are potentially useful for dual-mode sensing applications in harsh environments, to achieve multi-parameter monitoring or temperature-compensation on a single chip.
Perceived Healthiness of Sweeteners among Young Adults in Canada.

Purpose: To compare the perceived healthiness of different sweeteners relative to table sugar and examine efforts to consume less sugars and sweeteners.Methods: As part of the 2017 Canada Food Study online survey, 1000 youth and young adults were randomized to rate the healthiness of 1 of 6 sweeteners (aspartame, sucralose, stevia, agave, high-fructose corn syrup, "raw" sugar) or 1 sweetener brand name (Splenda) compared with "table sugar". Results: Perceptions of sweeteners varied widely. For example, the majority of respondents perceived high-fructose corn syrup (63.9%) and aspartame (52.4%) as less healthy than table sugar, whereas almost half (47.8%) perceived raw sugar as being healthier than table sugar. No assessed socio-demographic variables were significantly associated with perceived healthiness of sweeteners compared with table sugar (P ≥ 0.05). More consumers had attempted to consume less sugar (65.4%) compared with less "artificial" (31.2%) or "natural" (24.0%) low-calorie sweeteners.Conclusions: Perceptions of sweetener healthiness may be related to sweeteners' perceived level of "naturalness" rather than energy content. This has important implications for understanding consumer preferences, particularly given greater use of low-calorie sweeteners in the food supply and policy developments such as sugar taxes and enhanced sugar labelling.
Methiocarb Degradation by Electro-Fenton: Ecotoxicological Evaluation

This paper studies the degradation of methiocarb, a highly hazardous pesticide found in waters and wastewaters, through an electro-Fenton process, using a boron-doped diamond anode and a carbon felt cathode; and evaluates its potential to reduce toxicity towards the model organism Daphnia magna. The influence of applied current density and type and concentration of added iron source, Fe2(SO4)3·5H2O or FeCl3·6H2O, is assessed in the degradation experiments of methiocarb aqueous solutions. The experimental results show that electro-Fenton can be successfully used to degrade methiocarb and to reduce its high toxicity towards D. magna. Total methiocarb removal is achieved at the applied electric charge of 90 C, and a 450× reduction in the acute toxicity towards D. magna, on average, from approximately 900 toxic units to 2 toxic units, is observed at the end of the experiments. No significant differences are found between the two iron sources studied. At the lowest applied anodic current density, 12.5 A m−2, an increase in iron concentration led to lower methiocarb removal rates, but the opposite is found at the highest applied current densities. The highest organic carbon removal is obtained at the lowest applied current density and added iron concentration.
The Interplay of WNT and PPARγ Signaling in Vascular Calcification

Vascular calcification (VC), the ectopic deposition of calcium phosphate crystals in the vessel wall, is one of the primary contributors to cardiovascular death. The pathology of VC is determined by vascular topography, pre-existing diseases, and our genetic heritage. VC evolves from inflammation, mediated by macrophages, and from the osteochondrogenic transition of vascular smooth muscle cells (VSMC) in the atherosclerotic plaque. This pathologic transition partly resembles endochondral ossification, involving the chronologically ordered activation of the β-catenin-independent and -dependent Wingless and Int-1 (WNT) pathways and the termination of peroxisome proliferator-activated receptor γ (PPARγ) signal transduction. Several atherosclerotic plaque studies confirmed the differential activity of PPARγ and the WNT signaling pathways in VC. Notably, the actively regulated β-catenin-dependent and -independent WNT signals increase the osteochondrogenic transformation of VSMC through the up-regulation of the osteochondrogenic transcription factors SRY-box transcription factor 9 (SOX9) and runt-related transcription factor 2 (RUNX2). In addition, we have reported studies showing that WNT signaling pathways may be antagonized by PPARγ activation via the expression of different families of WNT inhibitors and through its direct interaction with β-catenin. In this review, we summarize the existing knowledge on WNT and PPARγ signaling and their interplay during the osteochondrogenic differentiation of VSMC in VC. Finally, we discuss knowledge gaps on this interplay and its possible clinical impact.
Incidence and risk factors for feline lymphoma in UK primary‐care practice

Objectives The study aimed to estimate the incidence and prevalence of feline lymphoma in cats attending primary‐care practices across the UK and to identify patient‐based and environmental (radon and pesticide exposure) risk factors. Materials and Methods Case records from the VetCompass programme from primary‐care veterinary practices in the UK were searched for a diagnosis of lymphoma in cats in 2016. Cases were required to have had an external laboratory confirmed diagnosis based on cytology and/or histopathology. A nested case–control study design was used to identify risk factors for lymphoma using multivariable logistic regression. Results From a cohort of 562,446 cats under veterinary care at VetCompass participating practices in 2016, a total of 271 lymphoma cases were identified (prevalence: 48/100,000, 95% confidence interval (CI) 44 to 56/100,000; incidence 32/100,000, 95% CI 26 to 35/100,000). There were 180 incident lymphoma cases and 803 controls, all aged 2 years and older. Male (odds ratio (OR) 1.7, 95% CI 1.2 to 2.4), insured (OR 3.6, 95% CI 2.3 to 5.6) and older cats (compared to cats 2 to <5 years, OR 5.0, 95% CI 2.8 to 8.8) were associated with increased odds of lymphoma diagnosis. Vaccinated cats were associated with decreased odds (OR 0.7, 95% CI 0.5 to 1.0) compared to unvaccinated cats, although the type of vaccination received was not statistically significant. Breed and environmental factors studied were not associated with a diagnosis of lymphoma. Clinical Significance This is the first study to estimate the frequency and report risk factors for lymphoma in cats attending UK primary‐care practice.
Motivations and Barriers for the Use of Face Coverings during the COVID-19 Pandemic: Messaging Insights from Focus Groups

Widespread use of face coverings is a key public health strategy to prevent the spread of COVID-19. However, few studies have examined why Americans use or do not use face coverings, and little is known about the most effective messaging strategies. This study explored perceptions of face coverings, including motivations and barriers for use, and examined reactions to messaging promoting the use of face coverings. Six virtual focus groups were conducted with 34 North Carolina residents in July 2020. Participants reported high compliance with face covering recommendations but often did not wear them around family, friends, and colleagues. The most prevalent motivation for the use of face coverings was to protect or respect other people, including high-risk populations and individuals. Other motivators were self-protection, responsibility, desire for control, requirements, and expert advice. Barriers included physical and social discomfort, confusion or misinformation, low perceived susceptibility to COVID-19, and perceptions of identity and autonomy. Even among individuals who frequently wear face coverings, there are opportunities to improve compliance. Messaging should highlight how face coverings protect the wearer and others around them, normalize the use of face coverings in social settings, and emphasize requirements. Positive messages that focus on unity, personal experiences and the rationale for face coverings are recommended.
Assessing the Prevalence and Association of Pulp Stones with Cardiovascular Diseases and Diabetes Mellitus in the Saudi Arabian Population—A CBCT Based Study

The detection of pulp stone in a patient suffering from undiagnosed systemic diseases can be an early diagnostic indicator. Thus, the aim of the study was to assess the prevalence of pulp stones in the Saudi Arabian population with cardiovascular diseases and diabetes mellitus. In a retrospective study, we included cone-beam computed tomography (CBCT) scans of 73 patients with cardiovascular disease and 76 patients with diabetes mellitus as group I and II, respectively. Group III comprised of CBCT scan of 80 healthy controls. From a total of 229 scans, 4807 teeth were screened for pulp stones throughout the arches. A chi-square test was used for comparing the prevalence of pulp stones among the groups. Univariable and multivariable analysis was done to evaluate the independent risk indicators for pulp stones. The tooth-wise prevalence of pulp stones in group I, II, and III was found to be 16.65%, 9.01%, and 3.86%, respectively. Patient-wise (p < 0.01) and tooth-wise (p < 0.01) prevalence was recorded significantly highest in the cardiovascular group followed by the diabetic group. The control group had the least prevalence. Significantly (p < 0.01) higher number of pulp stones were found in cardiovascular patients with age > 50 years compared to other groups. Similarly, a significantly increased number of pulp stones were seen in the 1st molar (p < 0.05) and the maxillary jaw (p < 0.05) of patients with cardiovascular diseases. Subjects with cardiovascular disease and diabetes were found to have 2.94 times (p < 0.001; CI 1.54–3.10) and 1.81 times (p < 0.01; CI 0.48–2.06) higher risk of having pulp stones in comparison to healthy subjects. The first molar has 2.20 times (p < 0.001; CI 0.84–2.45) increased the risk of having pulp stones compared to other tooth types. Systemic disease such as cardiovascular disease and diabetes mellitus poses a higher risk for the development of pulp stones. Among the systemic disease group, patients in the cardiovascular group showed a higher risk for pulp stones and also reported the maximum number of pulp stones compared to the diabetic and healthy subjects.
Growth and structural characterization of YMnO3 thin films grown by pulsed liquid injection MOCVD on Si and SrTiO3 substrates

Optimum parameters for the growing of YMnO3 films by pulsed liquid injection metalorganic chemical vapor deposition have been studied. Si substrates were used for the optimization of the deposition process. X-ray diffraction (XRD) and transmission electron microscopy (TEM) results show that polycrystalline single phase YMnO3 films can be obtained for an optimal ratio of Y and Mn on the injected solution and either amorphous, metastable orthorhombic, and/or hexagonal YMnO3 phases can be obtained depending on the deposition temperature and precursors ratio. In a second stage, YMnO3 films were grown on SrTiO3 substrates. Pure epitaxial orthorhombic YMnO3 phase was confirmed by XRD. The films microstructure, characterized by scanning electron microscopy and TEM, shows a columnar growth. Each columnar grain grows epitaxially with three possible orientations.