Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacokinetics and Immunological Effects of Romidepsin in Rhesus Macaques

HIV/SIV persistence in latent reservoirs requires lifelong antiretroviral treatment and calls for effective cure strategies. Romidepsin (RMD), a histone deacetylase inhibitor, was reported to reactivate HIV/SIV from reservoirs in virus-suppressed individuals. We characterized in detail the pharmacokinetics and safety profile of RMD in three SIV-naïve rhesus macaques which received two rounds of treatment. In plasma, RMD mean terminal half-life was 15.3 h. In comparison, RMD mean terminal half-life was much longer in tissues: 110 h in the lymph nodes (LNs) and 28 h in gastrointestinal tract. RMD administration was accompanied by transient liver and systemic toxicity. Isoflurane anesthesia induced near-immediate transient lymphopenia, which was further exacerbated and extended with the extensive immune modifications by RMD. The effect of RMD on circulating immune cells was complex: (i) slight increase in lymphocyte death rates; (ii) transient, robust increase in neutrophils; (iii) massive downregulation of lymphocyte surface markers; (iv) important migration of CD3+ T cells to the gut and LNs; and (v) hindrance to CD8+ T cell functionality, yet without reaching significance. Our results show that, in contrast to transient plasma concentrations, RMD has a long-term presence in tissues, with multiple immunomodulatory effects and minimal to moderate kidney, liver, and lymphocyte toxicities. As such, we concluded that RMD can be used for “shock and kill” approaches, preferentially in combination with other latency reversal agents or cytotoxic T lymphocyte boosting strategies with consideration taken for adverse effects.
Comparison of Short-Term Outcomes Between Endovenous 1,940-nm Laser Ablation and Radiofrequency Ablation for Incompetent Saphenous Veins

Background: Radiofrequency ablation (RFA) has shown faster recovery and lower pain scores compared to Endovenous laser ablation (EVLA) for treatment of varicose veins. However, a comparison of 1,940-nm EVLA and RFA has not been reported. This study compared short-term outcomes using 1,940-nm EVLA and RFA for varicose veins. Methods: Between April 2018 and June 2018, 43 patients (83 incompetent saphenous veins) were treated with 1,940-nm EVLA and 37 patients (64 incompetent saphenous veins) with RFA. Follow-up duplex was checked at 1 month and 3 months. Results: Baseline characteristics showed no significant differences between both groups except for age. Pain scores at 6 h, and at 1, 10, and 30 days after treatment showed no differences. Complications and time to return to normal activity showed no differences. The 100% closure rate was checked in both groups at 1 month and 3 months follow-up. Conclusion: Short-term outcomes showed no significant differences between 1,940-nm EVLA and RFA treatment.
TSPO Ligands PK11195 and Midazolam Reduce NLRP3 Inflammasome Activation and Proinflammatory Cytokine Release in BV-2 Cells

Neuroinflammation related to microglial activation plays an important role in neurodegenerative diseases. Translocator protein 18 kDa (TSPO), a biomarker of reactive gliosis, its ligands can reduce neuroinflammation and can be used to treat neurodegenerative diseases. Therefore, we explored whether TSPO ligands exert an anti-inflammatory effect by affecting the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome, thereby inhibiting the release of inflammatory cytokines in microglial cells. In the present study, BV-2 cells were exposed to lipopolysaccharide (LPS) for 6 h to induce an inflammatory response. We found that the levels of reactive oxygen species (ROS), NLRP3 inflammasome, interleukin-1β (IL-1β), and interleukin-18 (IL-18) were significantly increased. However, pretreatment with TSPO ligands inhibited BV-2 microglial and NLRP3 inflammasome activation and significantly reduced the levels of ROS, IL-1β, and IL-18. Furthermore, a combination of LPS and ATP was used to activate the NLRP3 inflammasome. Both pretreatment and post-treatment with TSPO ligand can downregulate the activation of NLRP3 inflammasome and IL-1β expression. Finally, we found that TSPO was involved in the regulation of NLRP3 inflammasome with TSPO ligands treatment in TSPO knockdown BV2 cells. Collectively, these results indicate that TSPO ligands are promising targets to control microglial reactivity and neuroinflammatory diseases.
Developing Abstract Representations of Passives: Evidence From Bilingual Children’s Interpretation of Passive Constructions

According to usage-based theories, children initially acquire surface-level constructions and then abstract representations. If so, bilingual children might show lags relative to monolingual children early in acquisition, but not later on, once they rely on abstract representations. We tested this prediction with comprehension of passives in 3- to 6-year-old children: French–English bilinguals and English monolinguals. As predicted, younger bilingual children tended to be less accurate than monolingual children. In contrast, the older bilingual children scored equivalently to monolinguals, despite less exposure to English. When the children made errors, the bilingual children were more likely to interpret the subject as the agent of the action than the monolingual children. These results are consistent with the argument that children develop increasingly abstract representations of linguistic constructions with usage. They further suggest that bilingual children might catch up with monolingual through use of selective attention and/or a semantic bias.
Inhibition of p38 MAPK Mitigates Lung Ischemia Reperfusion Injury by Reducing Blood–Air Barrier Hyperpermeability

Background: Lung ischemia reperfusion injury (LIRI) is a complex pathophysiological process activated by lung transplantation and acute lung injury. The p38 mitogen-activated protein kinase (MAPK) is involved in breakdown of the endothelial barrier during LIRI, but the mechanism is still unclear. Therefore, we investigated the function of p38 MAPK in LIRI in vivo and in vitro. Methods: Sprague–Dawley rats were subjected to ischemia reperfusion with or without pretreatment with a p38 MAPK inhibitor. Lung injury was assessed using hematoxylin and eosin staining, and pulmonary blood–air barrier permeability was evaluated using Evans blue staining. A rat pulmonary microvascular endothelial cell line was infected with lentiviral expressing short hairpin (sh)RNA targeting p38 MAPK and then cells were subjected to oxygen/glucose deprivation and reoxygenation (OGD/R). Markers of endothelial destruction were measured by western blot and immunofluorescence. Results: In vivo LIRI models showed structural changes indicative of lung injury and hyperpermeability of the blood–air barrier. Inhibiting p38 MAPK mitigated these effects. Oxygen/glucose deprivation and reoxygenation promoted hyperpermeability of the endothelial barrier in vitro, but knockdown of p38 MAPK attenuated cell injury; maintained endothelial barrier integrity; and partially reversed injury-induced downregulation of permeability protein AQP1, endothelial protective protein eNOS, and junction proteins ZO-1 and VE-cadherin while downregulating ICAM-1, a protein involved in destroying the endothelial barrier, and ET-1, a protein involved in endothelial dysfunction. Conclusion: Inhibition of p38 MAPK alleviates LIRI by decreasing blood–air hyperpermeability. Blocking p38 MAPK may be an effective treatment against acute lung injury.
Applying the Theory of Motivated Information Management to the Context of Conflicting Online Health Information: Implications for Childhood Vaccination Communication with Parents

ABSTRACT This study investigates how parents manage conflicting online information, which may affect their information-seeking behavior and decision-making about childhood vaccination, by applying the Theory of Motivated Information Management in online communication contexts. Although an extensive body of literature has demonstrated the effectiveness of TMIM in predicting how individuals manage health uncertainty and information in the interpersonal communication contexts, the present study goes beyond and applies the theoretical framework in the online communication contexts. Our findings of a survey with 439 parents in the United States are in conjunction with previous applications of TMIM, which show that individuals adopt a similar process to deal with uncertainty resulting from conflicting information in the online environment. Although further research must be conducted to change perceptions, attitudes, and vaccine-related behaviors, this study may help communication practitioners, vaccination advocates, and related nonprofit organizations to eliminate misconceptions about immunization among parents.
Multi-Slice Radiomic Analysis of Apparent Diffusion Coefficient Metrics Improves Evaluation of Brain Alterations in Neonates With Congenital Heart Diseases

Apparent diffusion coefficients (ADC) can provide phenotypic information of brain lesions, which can aid the diagnosis of brain alterations in neonates with congenital heart diseases (CHDs). However, the corresponding clinical significance of quantitative descriptors of brain tissue remains to be elucidated. By using ADC metrics and texture features, this study aimed to investigate the diagnostic value of single-slice and multi-slice measurements for assessing brain alterations in neonates with CHDs. ADC images were acquired from 60 neonates with echocardiographically confirmed non-cyanotic CHDs and 22 healthy controls (HCs) treated at Children's Hospital of Nanjing Medical University from 2012 to 2016. ADC metrics and texture features for both single and multiple slices of the whole brain were extracted and analyzed to the gestational age. The diagnostic performance of ADC metrics for CHDs was evaluated by using analysis of covariance and receiver operating characteristic. For both the CHD and HC groups, ADC metrics were inversely correlated with the gestational age in single and multi-slice measurements (P < 0.05). Histogram metrics were significant for identifying CHDs (P < 0.05), while textural features were insignificant. Multi-slice ADC (P < 0.01) exhibited greater diagnostic performance for CHDs than single-slice ADC (P < 0.05). These findings indicate that radiomic analysis based on ADC metrics can objectively provide more quantitative information regarding brain development in neonates with CHDs. ADC metrics for the whole brain may be more clinically significant in identifying atypical brain development in these patients. Of note, these results suggest that multi-slice ADC can achieve better diagnostic performance for CHD than single-slice.
On the Electron Affinities of Atomic Fluorine, Oxygen and Lithium

The Ritz variational method in conjunction with an extrapolation procedure has been employed to calculate the electron affinities of atomic fluorine, oxygen and lithium, the values obtained being 3.05, 1.12 and 0.74 eV respectively. In the case of fluorine the accord with the value 3.57 eV found by using the Born-Haber cycle is reasonable. The electron affinity of oxygen obtained from collision experiments is 2.2±0.2 eV, which is considerably larger than the value calculated in this paper. No comparison data are available for lithium.
Physical, Chemical, and Sensory Properties of Bologna Sausage Made with Ostrich Meat

: Three formulations of bologna were prepared, differing only by the lean meat used: (1) ostrich meat from Iliofibularis muscle (fan thigh), (2) ostrich meat from Femorotibialis medius muscle (tip thigh), and (3) beef meat from Subscapularis muscle (shoulder). Physical, chemical, and sensory analyses were made. The final products formulated with ostrich meat, although having a dark appearance, were acceptable in chemical composition and other sensory characteristics. The low fat and high protein content for ostrich bolognas will help to ensure that, if marketed in sufficient quantities, ostrich meat can successfully compete with other healthy meat products. The ostrich meat (Iliofibularis muscle) formula reached the highest general quality scores in the sensory evaluation.
Long Term Comparison of Talc- and Peat-Based Phytobeneficial Pseudomonas fluorescens and Pseudomonas synxantha Bioformulations for Promoting Plant Growth

Use of plant growth promoting rhizobacteria (PGPR) is an important strategy in sustainable agriculture. Among PGPR, many Pseudomonas strains are of great interest due to their abilities to colonize and thrive in the rhizosphere, in addition to displaying mechanisms in plant growth promotion and biocontrol activities. However, as Pseudomonas strains are non-spore forming micro-organisms, their development into stable bioformulations for commercial applications can be difficult. This study examined over a long term period the effect of two different carriers, peat and talc, to prepare bioformulations using phytobeneficial Pseudomonas strains belonging to two taxonomical groups of interest: P. fluorescens and P. synxantha. Each strain has previously demonstrated plant growth promotion activity when inoculated in the rhizosphere. Each bioformulation was stored at ambient temperature and their viability was measured up to 180 days. In parallel, every 30 days (up to 180 days) each bioformulation was also applied in the rhizosphere of plantlets to validate their plant growth promotion activity, and their establishment in the rhizosphere was quantified by using strain-specific quantitative polymerase chain reaction assays. The viability of both Pseudomonas strains in the bioformulations was found to decrease after the first 15 days and remained relatively stable for up to 180 days. When applying the bioformulations to Buglossoides arvensis plantlets, the expected plant growth promotion was observed when using up to 180 day-old formulations of P. fluorescens and up to 120 day-old formulations of P. synxantha, with similar results for both carriers. Establishment of both Pseudomonas strains in the rhizosphere inoculated with the peat-based carrier bioformulations stored for up to 180 days was found to be stable. While a lower establishment of P. fluorecens in the rhizosphere was observed when talc-based bioformulations were stored for 90 days or more, rhizosphere colonization by P. synxantha talc-based bioformulations remained stable for up to 180 days. In conclusion, both peat and talc appear to be suitable carriers for Pseudomonas bioformulations, however strain-specific variability exists and therefore the viability of each Pseudomonas strain and its capacity to maintain its plant growth promotion activity should be validated in different substrates before determining which formulation to use.
Study on anomalous n-type conduction of P-doped ZnO using P2O5 dopant source

The unexpected n-type conduction observed in P-doped ZnO thin films fabricated from rf magnetron sputtering, was studied systematically through a combined approach of experiment and computer modeling. The carrier stability was predicted from first-principles density functional theory and chemical thermodynamic calculations. It demonstrated that, under oxygen-poor growth condition and low temperature, the stable doping defect PO−1 may have negative effect on n-type conduction and, under oxygen-poor growth condition and high temperature, the stable doping defect may contribute significantly to the n-type conduction. Furthermore, under oxygen-rich growth condition, the stable doping defect PZn1 may help to maintain the n-type conduction at high oxygen partial pressures. Our model predictions are in good agreement with experimental observations in anomalous conduction of P2O5-doped ZnO thin films and provide scientific explanation. This research not only revealed increased fundamental understanding on electro.
SARS-CoV-2: Immune Response Elicited by Infection and Development of Vaccines and Treatments

The World Health Organization (WHO) announced in March a pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). This new infectious disease was named Coronavirus Disease 19 (COVID-19), and at October 2020, more than 39,000,000 cases of SARS-CoV-2 have been detected worldwide leading to near 1,100,000 deaths. Clinically, COVID-19 is characterized by clinical manifestations, such as fever, dry cough, headache, and in more severe cases, respiratory distress. Moreover, neurological-, cardiac-, and renal-related symptoms have also been described. Clinical evidence suggests that migration of immune cells to the affected organs can produce an exacerbated release of proinflammatory mediators that contribute to disease and render the immune response as a major player during the development of the COVID-19 disease. Due to the current sanitary situation, the development of vaccines is imperative. Up to the date, 42 prototypes are being tested in humans in different clinical stages, with 10 vaccine candidates undergoing evaluation in phase III clinical trials. In the same way, the search for an effective treatment to approach the most severe cases is also in constant advancement. Several potential therapies have been tested since COVID-19 was described, including antivirals, antiparasitic and immune modulators. Recently, clinical trials with hydroxychloroquine—a promising drug in the beginning—were suspended. In addition, the Food and Drug Administration (FDA) approved convalescent serum administration as a treatment for SARS-CoV-2 patients. Moreover, monoclonal antibody therapy is also under development to neutralize the virus and prevent infection. In this article, we describe the clinical manifestations and the immunological information available about COVID-19 disease. Furthermore, we discuss current therapies under study and the development of vaccines to prevent this disease.
Case Report: Management of Cholestasis Associated With Congenital Syphilis

Cholestasis is a rare but life-threatening complication of congenital syphilis. However, standard management methods for this disease have not been established. Here, we report a case of congenital syphilis presenting with progressively worsening cholestasis, and we review the clinical features and management practices. In these cases, differentiation from other diseases presenting with cholestasis during the neonatal period, such as biliary atresia, is critical. In this regard, operative cholangiogram and histopathological analysis of the liver are required. Moreover, comprehensive genetic analysis can be useful. Although there is no specific treatment for cholestasis associated with congenital syphilis, appropriate nutritional management and supplementation with fat-soluble vitamins, especially vitamin K, should be provided. The severity of liver fibrosis may affect the prognosis of cholestasis associated with congenital syphilis. Therefore, attention should be paid to liver fibrosis in these patients.
Insights Into the Proteomic Profiling of Extracellular Vesicles for the Identification of Early Biomarkers of Neurodegeneration

Extracellular vesicles (EVs) are involved in the development and progression of neurodegenerative diseases, including Alzheimer's and Parkinson's disease. Moreover, EVs have the capacity to modify the physiology of neuronal circuits by transferring proteins, RNA, lipids, and metabolites. The proteomic characterization of EVs (exosomes and microvesicles) from preclinical models and patient samples has the potential to reveal new proteins and molecular networks that affect the normal physiology prior to the appearance of traditional biomarkers of neurodegeneration. Noteworthy, many of the genetic risks associated to the development of Alzheimer's and Parkinson's disease affect the crosstalk between mitochondria, endosomes, and lysosomes. Recent research has focused on determining the role of endolysosomal trafficking in the onset of neurodegenerative diseases. Proteomic studies indicate an alteration of biogenesis and molecular content of EVs as a result of endolysosomal and autophagic dysfunction. In this review, we discuss the status of EV proteomic characterization and their usefulness in discovering new biomarkers for the differential diagnosis of neurodegenerative diseases. Despite the challenges related to the failure to follow a standard isolation protocol and their implementation for a clinical setting, the analysis of EV proteomes has revealed the presence of key proteins with post-translational modifications that can be measured in peripheral fluids.
Changes in Electroencephalography and Cardiac Autonomic Function During Craft Activities: Experimental Evidence for the Effectiveness of Occupational Therapy

Occupational therapy often uses craft activities as therapeutic tools, but their therapeutic effectiveness has not yet been adequately demonstrated. The aim of this study was to examine changes in frontal midline theta rhythm (Fmθ) and autonomic nervous responses during craft activities, and to explore the physiological mechanisms underlying the therapeutic effectiveness of occupational therapy. To achieve this, we employed a simple craft activity as a task to induce Fmθ and performed simultaneous EEG and ECG recordings. For participants in which Fmθ activities were provoked, parasympathetic and sympathetic activities were evaluated during the appearance of Fmθ and rest periods using the Lorenz plot analysis. Both parasympathetic and sympathetic indices increased with the appearance of Fmθ compared to during resting periods. This suggests that a relaxed-concentration state is achieved by concentrating on craft activities. Furthermore, the appearance of Fmθ positively correlated with parasympathetic activity, and theta band activity in the frontal area were associated with sympathetic activity. This suggests that there is a close relationship between cardiac autonomic function and Fmθ activity.
Stress, Emotional Intelligence and the Intention to Use Cannabis in Spanish Adolescents: Influence of COVID-19 Confinement

The disease brought about by the SARS-CoV-2, COVID-19 coronavirus has had an unprecedented global impact. Confinement to control the outbreak may have mental health consequences for the most vulnerable in the population, including adolescents. This study aims to describe and analyze the relationships between the stress variables, Emotional Intelligence and the intention to use cannabis in healthy adolescents, before and after the end of the COVID-19 pandemic containment stage. A comparative correlational study was carried out with validated self-completed questionnaires through an online platform. The sample is made up of adolescents (n = 300) aged 13–17 from two different schools in Ponferrada (León, Spain). The analysis of correlation and differences between the groups indicate that confinement has had effects on the mental health of the adolescents, specifically on the emotional manifestations of stress. Furthermore, significant gender differences were found for stress values and Emotional Intelligence. However, no differences have been found for cannabis use intention.