Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacokinetics and Safety of Two Voriconazole Formulations after Intravenous Infusion in Healthy Korean Volunteers

Background Voriconazole, a triazole antifungal agent exhibits broad-spectrum antifungal activity. It is used to treat severe, invasive fungal infections, including invasive aspergillosis and candidemia. The aim of this study was to assess the pharmacokinetic equivalence of a test formulation (Vorico® Injection) and reference formulation (Vfend® IV) of voriconazole. Materials and Methods This was a randomized, open-label, single-dose, three-group, two-treatment, two-sequence, two-period, crossover phase I trial with 7-day washout periods (ClinicalTrials.gov identifier NCT02631954). Twenty-four healthy Korean male subjects were recruited. In each group, eight subjects were randomized in a 1:1 manner to receive a single dose of 200 mg test or reference formulation intravenously over 1.5 h. Blood samples were collected over 24 h post-dose, and plasma drug concentrations were determined by liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were determined using a non-compartmental analysis, and safety was evaluated. Results Twenty-three subjects completed the study. The geometric mean ratio (90% confidence interval) of the test formulation to reference formulation was 0.9570 (0.8178 – 1.1199) for the maximum plasma concentration (Cmax) and 1.0720 (1.0262 – 1.1198) for the area under the concentration–time curve from dosing to the last quantifiable concentration (AUClast). The mean plasma concentration–time profiles, pharmacokinetic parameters, and safety were comparable between the two formulations. Conclusion Equivalent pharmacokinetic characteristics that satisfied the criteria of bioequivalence and similar safety profiles were observed for both test and reference formulations of voriconazole.
Emergency department ‘outbreak rostering’ to meet challenges of COVID-19

The COVID-19 outbreak has posed unique challenges to the emergency department rostering. Additional infection control, the possibility of quarantine of staff and minimising contact among staff have significant impact on the work of doctors in the emergency department. Infection of a single healthcare worker may require quarantine of close contacts at work. This may thus affect a potentially large number of staff. As such, we developed an Outbreak Response Roster. This Outbreak Response Roster had fixed teams of doctors working in rotation, each team that staff the emergency department in turn. Members within teams remained constant and were near equally balanced in terms of manpower and seniority of doctors. Each team worked fixed 12 hours shifts with as no overlapping of staff or staggering of shifts. Handovers between shifts were kept as brief as possible. All these were measures to limit interactions among healthcare workers. With the implementation of the roster, measures were also taken to bolster the psychological wellness of healthcare workers. With face-to-face contact limited, we also had to maintain clear, open channels for communication through technology and continue educating residents through innovative means.
Acute Portal Vein Thrombosis in SARS-CoV-2 Infection: A Case Report

INTRODUCTION Abdominal pain and hypertransaminasemia are gastrointestinal symptoms reported in approximately 10% and in more than 20% of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, respectively (1,2). SARS-CoV-2 infection has also been associated with a prothrombotic profile accounting for a high risk of deep vein thrombosis and pulmonary embolism (3,4). We present a case of acute portal vein thrombosis (PVT) in a SARSCoV-2-positive patient.
Inhibition of fibrillation of human γd-crystallin by a flavonoid morin

Abstract To inhibit the formation of amyloid fibrils by human γd-crystallin (HGD), a series of four flavonoids (quercertin, rutin, morin and hesperetin) was tested. Only morin had demonstrated significant inhibition of HGD fibrillation. Results from fluorimetric assay techniques (using thioflavin T and ANS), FTIR, circular dichroism and microscopic imaging (fluorescence microscopy and transmission electron microscopy) confirmed HGD fibrillation inhibition by morin. HGD–morin complex formation at ground state resulted tryptophan fluorescence quenching through static mechanism, which was also confirmed by determining the excited-state life time of HGD tryptophan residues. Förster resonance energy transfer occurs from HGD to morin. Synchronous, three-dimensional fluorescence, FTIR and circular dichroism results suggest that major changes in HGD conformation did not occur on binding with morin. The interactions between HGD and morin involve hydrogen bonding and/or van der Waals forces. Docking predictions also support experimental results. Communicated by Ramaswamy H. Sarma
Targeting cancer stem cells in cholangiocarcinoma (Review)

The incidence of cholangiocarcinoma has been increasing steadily over the past 50 years, but the survival rates remained low due to the disease being highly resistant to non-surgical treatment interventions. Cancer stem cell markers are expressed in cholangiocarcinoma, suggesting that they serve a significant role in the physiology of the disease. Cancer stem cells are frequently implicated in tumor relapse and acquired resistance to a number of therapeutic strategies, including chemotherapy, radiation and immune checkpoint inhibitors. Novel targeted therapies to eradicate cancer stem cells may assist in overcoming treatment resistance in cholangiocarcinoma and reduce the rates of relapse and recurrence. Several signaling pathways have been previously documented to regulate the development and survival of cancer stem cells, including Notch, janus kinase/STAT, Hippo/yes-associated protein 1 (YAP1), Wnt and Hedgehog signaling. Although pharmacological agents have been developed to target these pathways, only modest effects were reported in clinical trials. The Hippo/YAP1 signaling pathway has come to the forefront in the field of cancer stem cell research due to its reported involvement in epithelium-mesenchymal transition, cell adhesion, organogenesis and tumorigenesis. In the present article, recent findings in terms of cancer stem cell research in cholangiocarcinoma were reviewed, where the potential therapeutic targeting of cancer stem cells in this disease was discussed.
Inadequate Knowledge, Attitude and Practices about Second-Hand Smoke among Non-Smoking Pregnant Women in Urban Vietnam: The Need for Health Literacy Reinforcement

The rate of exposure to second-hand smoke (SHS) is relatively high in several countries, including Vietnam, and health issues related to SHS have worsened in recent years, especially for pregnant women and their infants. Enhancement of knowledge, attitude, and practice (KAP) scores of pregnant women in Vietnam could raise practical interventions to protect their health and reduce complications of SHS. A cross-sectional study of 432 pregnant women who came to the Obstetrics Department of Bach Mai Hospital, Hanoi, Vietnam for antenatal care was conducted in 2016 to collect information about their KAP related to SHS. Composite mean scores from survey questions assessing their KAP were calculated on a 10-point scale, finding mean scores of 4.19, 7.45, and 4.30, respectively. Higher scores indicated better knowledge, attitude, and practice. Generalized linear models identified that age, occupation, living place, and sources of information were associated with SHS-related KAP. Findings from this study indicate that suitable programs related to SHS should be implemented to improve and reinforce health literacy to both mothers and smokers to reduce the harmfulness of smoking on women and their infants’ health.
A New IL6 Isoform in Chinese Soft-Shelled Turtle (Pelodiscus sinesis) Discovered: Its Regulation during Cold Stress and Infection

The Chinese soft-shelled turtle (Pelodiscus sinesis) is a widely cultured commercial species in East and Southeast Asian countries. The turtles frequently suffer from acute cold stress during farming in China. Stress-induced factor such as Interleukin-6 (IL6) is a multifunctional molecule that plays important roles in innate and adaptive immune response. In the present study, we found that the turtle possessed two IL6 transcripts, where one IL6 transcript contained a signal peptide sequence (psIL6), while the other IL6 transcript (psIL6ns) possessed no such signal peptide gene. To test any differential expression of the two isoforms during temperature and microbial stress, turtles were adapted to optimal environmental water temperature (25 °C), stressed by acute cooling for 24 h, followed with the challenge of Aeromonas hydrophila (1.8 × 108 CFU) or Staphylococcus aureus (5.8 × 108 CFU). Gene characterization revealed that psIL6ns, a splicer without codons encoding a signal peptide and identical to the one predicted from genomic sequence, and psIL6, a splicer with codons encoding a signal peptide, were both present. Inducible expression was documented in primary spleen cells stimulated with ConA and poly I: C. The splenic and intestinal expression of psIL6ns and psIL6 was increased in response to temperature stress and bacterial infection.
Effect of differentiated nitrogen fertilisation on the yield and quality of leaf lettuce

Abstract Two field experiments with leaf lettuce were conducted in 2006-2008. The first factor tested was the diversified contents of mineral nitrogen in the soil, amounting to 50, 100 and 150 mg N dm-3 before lettuce cultivation. The second factor tested four nitrogen fertilisers differing in chemical composition and in nitrogen form introduced into the soil: ammonium nitrate 34% N - (NH4NO3), calcium nitrate 15.5% N - (Ca(NO3)2 × H2O + NH4NO3), ammonium sulfate 20.0% N - ((NH4)2SO4), and ENTEC 26% N - (NH4NO3 + (NH4)2SO4 + 0.8% DNPP). Two cultivars of leaf lettuce were used: green leaf ‘Casabella’ (Lollo Bionda type) and red leaf ‘Klausia’ (Lollo Rosa type). The best source of nitrogen for ‘Casabella’ cultivar lettuce was ENTEC 26 fertiliser and calcium nitrate, which resulted in significantly higher yields as compared to ammonium sulfate, yet did not differ from the yields comprising plants fertilised with ammonium nitrate. In the case of the ‘Klausia’ cultivar, ENTEC 26 fertiliser and ammonium nitrate generated the best production results. Regardless the type of nitrogen fertiliser used, the increase in concentration of this element in soil from 50 mg N dm-3 to 150 mg N dm-3 resulted in a considerable increase in marketable yield of both cultivars with simultaneously higher nitrate accumulation and decreased dry matter in the ‘Klausia’ cultivar. Lettuce fertilised with ammonium sulfate as well as with ENTEC 26 presented significantly lower average nitrate content in leaves before harvesting than after application of ammonium and calcium nitrate as a source of nitrogen for the plants. Introduction of ammonium nitrate and calcium nitrate in the dose of 150 mg N dm-3 contributed to nitrate accumulation in the amounts exceeding permissible by legal regulations regarding the content of this element in lettuce, while application of ENTEC 26 allowed us to obtain a high yield size of both lettuce cultivars without risk of exceeding permissible nitrate content.
Plant Viruses Infecting Solanaceae Family Members in the Cultivated and Wild Environments: A Review

Plant viruses infecting crop species are causing long-lasting economic losses and are endangering food security worldwide. Ongoing events, such as climate change, changes in agricultural practices, globalization of markets or changes in plant virus vector populations, are affecting plant virus life cycles. Because farmer’s fields are part of the larger environment, the role of wild plant species in plant virus life cycles can provide information about underlying processes during virus transmission and spread. This review focuses on the Solanaceae family, which contains thousands of species growing all around the world, including crop species, wild flora and model plants for genetic research. In a first part, we analyze various viruses infecting Solanaceae plants across the agro-ecological interface, emphasizing the important role of virus interactions between the cultivated and wild zones as global changes affect these environments on both local and global scales. To cope with these changes, it is necessary to adjust prophylactic protection measures and diagnostic methods. As illustrated in the second part, a complex virus research at the landscape level is necessary to obtain relevant data, which could be overwhelming. Based on evidence from previous studies we conclude that Solanaceae plant communities can be targeted to address complete life cycles of viruses with different life strategies within the agro-ecological interface. Data obtained from such research could then be used to improve plant protection methods by taking into consideration environmental factors that are impacting the life cycles of plant viruses.
Impact of UK Tobacco Control Policies on Inequalities in Youth Smoking Uptake: A Natural Experiment Study

Abstract Introduction UK countries implemented smoke-free public places legislation and increased the legal age for tobacco purchase from 16 to 18 years between 2006 and 2008. We evaluated the immediate and long-term impacts of these UK policy changes on youth smoking uptake and inequalities therein. Aims and Methods We studied 74 960 person-years of longitudinal data from 14 992 youths (aged 11–15 years) in annual UK household surveys between 1994 and 2016. Discrete-time event history analyses examined whether changes in rates of youth smoking transitions (initiation, experimentation, and escalation to daily smoking or quitting) or their inequalities (by parental education) were associated with policy implementation. Parallel analyses examined smoke-free legislation and the change in legal age. We interpret the results as a combined effect of the two pieces of legislation as their implementation dates were too close to identify separate effects. Models were adjusted for sex, age, UK country, historical year, tobacco taxation, and e-cigarette prevalence, with multiple imputation for missing data. Results For both policies, smoking initiation reduced following implementation (change in legal age odds ratio [OR]: 0.67; 95% confidence interval [CI]: 0.55 to 0.81; smoke-free legislation OR: 0.68; 95% CI: 0.56 to 0.82), while inequalities in initiation narrowed over subsequent years. The legal age change was associated with annual increases in progression from initiation to occasional smoking (OR: 1.26; 95% CI: 1.07 to 1.50) and a reduction in quitting following implementation (OR: 0.57; 95% CI: 0.35 to 0.94). Similar effects were observed for smoke-free legislation but CIs overlapped the null. Conclusions Policies such as these may be highly effective in preventing and reducing socioeconomic inequalities in youth smoking initiation. Implications UK implementation of smoke-free legislation and an increase in the legal age for tobacco purchase from 16 to 18 years were associated with an immediate reduction in smoking initiation and a narrowing of inequalities in initiation over subsequent years. While the policies were associated with reductions in the initiation, progression to occasional smoking increased and quitting decreased following the legislation.
Effects of Aloe arborescens Whole Plant Homogenate on Lipid Metabolism, Inflammatory Conditions and Liver Function of Dairy Cows during the Transition Period

Simple Summary This study highlights the positive effect of an Aloe arborescens Mill. whole plant homogenate on the liver and renal function of dairy cows during the peripartum period. Such positive effects could depend on both anti-hyperlipidemic and anti-inflammatory effects of Aloe that could have mitigated hepatic stresses that typically occur in early lactation. Our findings suggest Aloe arborescens supplementation to be an effective strategy to ameliorate adverse metabolic conditions in transition cows, indicating it as a preventive nutraceutical strategy against metabolic disorders. Abstract The anti-hyperlipidemic and anti-inflammatory effects exerted by Aloe on monogastric mammals suggest it as a potential strategy to address the tremendous metabolic alterations that affect dairy cows during their transition to calving. A group of 20 multiparous Italian Holstein dairy cows were housed in freestalls and allocated into two homogeneous groups to receive either 200 g/d of water (CTR) or 200 g/day of Aloe arborescens Mill. whole plant homogenate through a rumen tube (AAM) between −14 and 14 days from calving (DFC). From −14 to 35 DFC, the BCS, and milk yield were measured, and blood samples were collected to assess the hematochemical profile. Data underwent ANOVA testing using a mixed model for repeated measurements, including the treatment and time and their interactions as fixed effects. Compared to CTR cows, AAM cows had a less pronounced BCS loss in early lactation (p < 0.01), indicating less mobilization of body reserves. Compared to CTR cows, AAM cows had a lower plasma concentration of nonesterified fatty acids and beta hydroxybutyrate (p < 0.01 and = 0.01 respectively) that, paired with the lower butterfat content and fat/protein ratio in their milk (p = 0.03 and < 0.01 respectively), indicates that Aloe reduced the mobilization of body fats. AAM cows had a reduced concentration of myeloperoxidase in plasma and a lower SCC in milk compared to CTR cows (p = 0.02 for both), indicating an anti-inflammatory effect of Aloe. Furthermore, AAM cows had a lower plasma concentration of ceruloplasmin (p < 0.05) and higher plasma concentration of cholesterol, retinol, and paraoxonase compared to CTR cows (p < 0.01, < 0.01 and < 0.05 respectively), indicating Aloe was effective in mitigating the acute phase response in early lactation. Finally, AAM cows had lower plasma creatinine concentrations around calving (p < 0.05), a lower concentration of plasma bilirubin, and a higher concentration of plasma tocopherol compared to CTR cows (p = 0.01 for both). These data suggest Aloe has anti-hyperlipidemic and anti-inflammatory effects on transition dairy cows that could have ameliorated liver and kidney function disruption and increased the availability of body antioxidants in early lactation.
Risk Factors for Depressive Symptoms in Long-Haul Truck Drivers

Work-related stress is a salient risk factor for depression. While long-haul truck drivers (LHTDs) face a myriad of occupational pressures and demands, little research has examined predictors of depressive symptoms in this occupational group. The purpose of this study was to identify predictors of depressive symptoms in LHTDs. A cross-sectional study was used to examine depressive symptoms, health and working conditions in a sample of 107 LHTDs (mean age of 50.7 ± 12.3; 95.6% were men) at truck stops from five Western Canadian cities. The findings show that 44% of LHTDs reported symptoms of depression in the past 12 months. Severe work-related stress, the use of psychiatric medications and broken sleep were significant predictors of depressive symptomology accounting for 41% of the variance. The findings suggest that LHTDs experience a host of occupational stressors that are embedded within the transportation industry that may increase the risk for depressive symptoms. Mental health promotion efforts that improve sleep quality, decrease work-related demands and pressures, and increase the use of psychiatric medication may reduce rates of depressive symptoms among LHTDs.
PLCγ signaling underlies BDNF potentiation of Purkinje cell responses to GABA

Brain‐derived neurotrophic factor (BDNF) regulates neuronal survival, neurite outgrowth, and excitatory synaptic transmission. We reported recently that acute BDNF exposure decreased γ‐aminobutyric acid (GABA) responses in cultured mouse cerebellar granule cells through tyrosine receptor kinase B (TrkB) receptor‐mediated signaling. In the present study, we extend this work to investigate BDNF‐induced modulation of GABA responses and GABAA receptor‐mediated synaptic events in cerebellar slices. Thin (200 μm) parasagittal slices of cerebellum were prepared from postnatal Day 7 and 14 mice. Purkinje cells and granule cells, both of which express TrkB‐like immunoreactivity, were identified for whole‐cell recording. BDNF promptly enhanced GABA responses in Purkinje cells but, consistent with our previous finding in culture, attenuated those recorded in granule cells. In Purkinje cells, BDNF exposure shifted rightward the cumulative peak amplitude distribution for miniature inhibitory postsynaptic currents (mIPSCs) without changing the mIPSC frequency. BDNF‐induced potentiation of Purkinje cell responses to GABA was blocked by TrkB‐Fc (receptor body that sequesters BDNF), K252a (inhibitor of TrkB receptor autophosphorylation), U73122 (inhibitor of phospholipase‐Cγ [PLCγ]), KN62 (specific inhibitor of calcium/calmodulin‐dependent kinase), KT5720 (specific cyclic AMP‐dependent kinase inhibitor), and by intracellular dialysis of Rp‐cyclic AMP or BAPTA (1,2‐bis(o‐aminophenoxy)ethane‐N,N, N′,N′‐tetraacetic acid). Overall, our results indicate that BDNF acutely potentiates GABAA receptor function in cerebellar Purkinje cells via the TrkB receptor‐PLCγ signal transduction cascade. In addition, we propose that cyclic AMP‐mediated intracellular signaling mechanisms may facilitate manifestation of the BDNF‐induced modulatory outcome. © 2005 Wiley‐Liss, Inc.
Is Academic Achievement Related to Mediterranean Diet, Substance Use and Social-Cognitive Factors: Findings from Lebanese Adolescents

There is substantial evidence that good academic performance significantly enhances the prospects of success for adolescents in terms of employment, social status, quality of life and health. Identifying which factors are correlated to good academic achievement and which factors may need to be addressed by policies is crucial. Despite its importance, there is insufficient data concerning factors associated with academic achievement in the Middle East, particularly Lebanon. This study assessed the association of lifestyle, socio-demographics and motivational factors with academic achievement of Lebanese adolescents. Grade 10 and 11 Lebanese adolescents aged 15 to 18 years (n = 600), from private and public schools in Beirut and the Mount Lebanon area, completed a multi-component questionnaire assessing health behaviors, socio-demographic characteristics and motivational factors. Height and weight were physically measured and, subsequently, Body Mass Index was calculated. Academic achievement was assessed using self-reported grades and was categorized into high and low. Associations between all factors and academic achievement were tested using logistic regression models. Adherence to the Mediterranean diet, high self-efficacy and intention were positively associated with academic achievement, whereas smoking was associated with poor achievement. Our findings support the need for targeting adolescents with an unhealthier lifestyle and focusing on socio-cognitive determinants interventions aimed at enhancing academic achievement.