Miracle-dz/UniFAR-FTUs huggingface dataset:
Biomarkers of environmental manganese exposure

Abstract We conducted a critical review on biomarkers of environmental manganese (Mn) exposure to answer the following questions: 1) are there reliable biomarkers of internal Mn exposure (Mn in biological matrices) associated with external metrics of Mn exposure (Mn in environmental media)? and 2) are there accurate reference values (RVs) for Mn in biological matrices? Three bibliographic databases were searched for relevant references and identified references were screened by two independent reviewers. Of the 6342 unique references identified, 86 articles were retained for data abstraction. Our analysis of currently available evidence suggests that Mn levels in blood and urine are not useful biomarkers of Mn exposure in non-occupational settings. The strength of the association between Mn in environmental media and saliva was variable. Findings regarding the utility of hair Mn as a biomarker of environmental Mn exposure are inconsistent. Measurements of Mn in teeth are technically challenging and findings on Mn in tooth components are scarce. In non-occupationally exposed individuals, bone Mn measurements using in vivo neutron activation analysis (IVNAA) are associated with large uncertainties. Findings suggest that Mn in nails may reflect Mn in environmental media and discriminate between groups of individuals exposed to different environmental Mn levels, although more research is needed. Currently, there is no strong evidence for any biological matrix as a valid biomarker of Mn exposure in non-occupational settings. Because of methodological limitations in studies aimed at derivation of RVs for Mn in biological materials, accurate RVs are scarce.
Optimization of Biocomposite Film Based on Whey Protein Isolate and Nanocrystalline Cellulose from Pineapple Crown Leaf Using Response Surface Methodology

This study employed response surface methodology to optimize the preparation of biocomposites based on whey protein isolate, glycerol, and nanocrystalline cellulose from pineapple crown leaf. The effects of different concentrations of nanocrystalline cellulose as a filler and glycerol as a plasticizer on the thickness, the tensile strength, and the elongation at break on the resulting biocomposite films were investigated. The central composite design was used to determine the optimum preparation conditions for biocomposite films with optimum properties. The regression of a second-order polynomial model resulted in an optimum composition consisting of 4% glycerol and 3.5% nanocrystalline cellulose concentrations, which showed a desirability of 92.7%. The prediction of the regression model was validated by characterizing the biocomposite film prepared based on the optimum composition, at which the thickness, tensile strength, and elongation at break of the biocomposite film were 0.13 mm, 7.16 MPa, and 39.10%, respectively. This optimum composition can be obtained in range concentrations of glycerol (4–8%) and nanocrystalline cellulose (3–7%). Scanning electron microscope images showed that nanocrystalline cellulose dispersed well in the pure whey protein isolate, and the films had a relatively smooth surface. In comparison, a rough and uneven surface results in more porous biocomposite films. Fourier transform infrared spectroscopy revealed that nanocrystalline cellulose and glycerol showed good compatibility with WPI film by forming hydrogen bonds. The addition of nanocrystalline cellulose as a filler also decreased the transparency, solubility, and water vapor permeability and increased the crystallinity index of the resulting biocomposite film.
Can calcitonin gene-related peptide (CGRP) and pentraxin-3 (PTX-3) be useful in diagnosing acute migraine attack?

Abstract Purpose Even if migraine is not fatal, it is a common and challenging disease with adverse effects on individuals' lives. The lack of objective diagnostic tools causes delays in diagnosis and treatment initiation. The primary aim of this study is to reveal the diagnostic value of Calcitonin Gene-Related Peptide (CGRP) and Pentraxin-3 (PTX-3) in acute migraine. To this aim, we compared the serum CGRP and PTX-3 levels of migraine patients with acute attacks to those in healthy individuals. Material and method A total of 135 individuals (85 patients with migraine attacks with or without aura and 50 healthy controls) participated in the study. Serum CGRP and PTX-3 levels were measured with ELISA analysis. A p value less than 0.05 was considered significant. Results Serum CGRP [146.70 (21.52–413.67) vs. 65.90 (3.80–256.60) pg/mL] and PTX-3 levels [12.71 (0.62–33.97) vs. 1.01 (0.06–9.48) ng/mL] were higher in patients with migraine attack than the control group (p < 0.01 and p < 0.01, respectively). ROC analysis showed that the cutoff value for serum CGRP was 121.39 pg/mL (AUC: 0.751, Sen:%61, Spe:%64) whereas the cutoff value for PTX-3 was 4,06 ng/mL (AUC:0.876, Sen:%73, Spe:%76). Serum CGRP levels were positively correlated with pain intensity. Serum CGRP and PTX-3 levels did not differ across gender groups and presence of aura in subgroup analysis. Conclusion Patients with acute migraine attacks have higher serum CGRP and PTX-3 levels than controls. Both biomarkers show high potential for the diagnosis of a migraine attack.
Fortification of Pectin/Blackberry Hydrogels with Apple Fibers: Effect on Phenolics, Antioxidant Activity and Inhibition of α-Glucosidase

The objective of this study was to prepare hydrogels based on pectin and blackberry juice and additionally to fortify those hydrogels with apple fiber. For that purpose, two types of pectin (low methoxylated and high methoxylated) were used, and fortification was conducted with the addition of 10% of apple fiber. The hydrogels were evaluated for phenolic compounds, antioxidant activity and inhibition of α-glucosidase. In addition, the stability of these parameters after 8 months of storage was evaluated. Pectin type and addition of apple fiber had an impact on investigated parameters. Low methoxylated pectin hydrogels had a higher concentration of anthocyanins than high methoxylated pectin hydrogels, while the addition of apple fibers caused a decrease in anthocyanin content. However, fortified hydrogels had higher antioxidant activity due to the presence of phenolics from apple fibers. The results showed that anthocyanins were more favorable in inhibiting α-glucosidase because samples with higher anthocyanins concentration had lower IC50 values. Obtained hydrogels can be used as intermediate products or ingredients (like fruit fillings or spreads) for the improvement or development of novel food products to increase their fiber content and antioxidant potential.
Association of Renin Angiotensin Aldosterone System Inhibitors and Outcomes of Hospitalized Patients With COVID-19

OBJECTIVES: To determine the association of prior use of renin-angiotensin-aldosterone system inhibitors (RAASIs) with mortality and outcomes in hospitalized patients with COVID-19. DESIGN: Retrospective observational study. SETTING: Multicenter, international COVID-19 registry. Subjects: Adult hospitalized COVID-19 patients on antihypertensive agents (AHAs) prior to admission, admitted from March 31, 2020, to March 10, 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data were compared between three groups: patients on RAASIs only, other AHAs only, and those on both medications. Multivariable logistic and linear regressions were performed after controlling for prehospitalization characteristics to estimate the effect of RAASIs on mortality and other outcomes during hospitalization. Of 26,652 patients, 7,975 patients were on AHAs prior to hospitalization. Of these, 1,542 patients (19.3%) were on RAASIs only, 3,765 patients (47.2%) were on other AHAs only, and 2,668 (33.5%) patients were on both medications. Compared with those taking other AHAs only, patients on RAASIs only were younger (mean age 63.3 vs 66.9 yr; p < 0.0001), more often male (58.2% vs 52.4%; p = 0.0001) and more often White (55.1% vs 47.2%; p < 0.0001). After adjusting for age, gender, race, location, and comorbidities, patients on combination of RAASIs and other AHAs had higher in-hospital mortality than those on RAASIs only (odds ratio [OR] = 1.28; 95% CI [1.19–1.38]; p < 0.0001) and higher mortality than those on other AHAs only (OR = 1.09; 95% CI [1.03–1.15]; p = 0.0017). Patients on RAASIs only had lower mortality than those on other AHAs only (OR = 0.87; 95% CI [0.81–0.94]; p = 0.0003). Patients on ACEIs only had higher mortality compared with those on ARBs only (OR = 1.37; 95% CI [1.20–1.56]; p < 0.0001). CONCLUSIONS: Among patients hospitalized for COVID-19 who were taking AHAs, prior use of a combination of RAASIs and other AHAs was associated with higher in-hospital mortality than the use of RAASIs alone. When compared with ARBs, ACEIs were associated with significantly higher mortality in hospitalized COVID-19 patients.
The Composites of Polyamide 12 and Metal Oxides with High Antimicrobial Activity

The lack of resistance of plastic objects to various pathogens and their increasing activity in our daily life have made researchers develop polymeric materials with biocidal properties. Hence, this paper describes the thermoplastic composites of Polyamide 12 mixed with 1–5 wt % of the nanoparticles of zinc, copper, and titanium oxides prepared by a twin-screw extrusion process and injection moulding. A satisfactory biocidal activity of polyamide 12 nanocomposites was obtained thanks to homogenously dispersed metal oxides in the polymer matrix and the wettability of the metal oxides by PA12. At 4 wt % of the metal oxides, the contact angles were the lowest and it resulted in obtaining the highest reduction rate of the Escherichia coli (87%), Candida albicans (53%), and Herpes simplex 1 (90%). The interactions of the nanocomposites with the fibroblasts show early apoptosis (11.85–27.79%), late apoptosis (0.81–5.04%), and necrosis (0.18–0.31%), which confirms the lack of toxicity of used metal oxides. Moreover, the used oxides affect slightly the thermal and rheological properties of PA12, which was determined by oscillatory rheology, thermogravimetric analysis, and differential scanning calorimetry.
A Randomized Phase II Study of S-1 Adjuvant Chemotherapy With or Without Hochu-ekki-to, a Japanese Herbal Medicine, for Stage II/III Gastric Cancer: The KUGC07 (SHOT) Trial

Objectives: A multicenter randomized phase II study was conducted to evaluate the effects of Hochu-ekki-to (TJ-41) for reducing adverse reactions and increasing compliance with S-1 adjuvant therapy for advanced gastric cancer. Methods: The eligibility criteria were pathological stage II/III after R0 resection. Patients received adjuvant therapy with S-1 alone (group S) or S-1 with TJ-41 (group ST) for 1 year. The primary endpoint was the completion rate of S-1. Secondary endpoints were adverse events, relative dose intensity, relapse-free survival (RFS), and overall survival (OS). Results: We randomly assigned 56 patients to group ST and 57 patients to group S. The completion rates of S-1 were 54.5 and 50.9%, the median relative dose intensities were 89.2 and 71.9%, and adverse events of grade 3 or 4 occurred in 45.5 and 54.5% in groups ST and S, respectively. There was no significant difference in 3-year OS or RFS between the two groups. Conclusions: TJ-41 does not increase relative dose and completion rate of S-1 significantly. J-41 may reduce toxic effects, but our findings do not support routine use of TJ-41 after gastrectomy.
Serum Vitamin D Concentrations, Time to Pregnancy, and Pregnancy Outcomes among Preconception Couples: A Cohort Study in Shanghai, China

Background: The role of vitamin D in reproductive health is still unclear. This study aimed to assess the effect of serum 25-hydroxyvitamin D (25(OH)D), among preconception couples, on fecundity, and the associations between 25(OH)D concentrations before and during pregnancy, and pregnancy outcomes. Methods: 200 preconception couples attempting to conceive were recruited and were followed-up until childbirth. Time to pregnancy was collected via telephone every two months or obtained via a questionnaire during pregnancy. Blood samples were collected to measure serum 25(OH)D levels from both partners at enrollment and from women during the second and third trimester of pregnancy. Results: Couples had higher conception rates within six months (adjusted odds ratio (aOR): 3.72, 95% CI: 1.16, 11.9) and reduced time to pregnancy (adjusted fecundability ratio (aFR): 1.50, 95% CI: 1.01, 2.23) if male partners had sufficient 25(OH)D compared with insufficient 25(OH)D. Compared to pregnant women with insufficient 25(OH)D in the third trimester of pregnancy, sufficient 25(OH)D was associated with reduced odds of anemia (OR: 0.22, 95% CI: 0.06, 0.82), longer gestational age (β: 0.53, 95% CI: 0.04, 1.01) and newborns’ higher ponderal index (β: 0.10, 95% CI: 0.01, 0.19). Conclusions: Sufficient serum 25(OH)D levels among preconception men or during pregnancy were associated with better reproductive health.
Factors Associated with Outpatient Satisfaction in Provincial Tertiary Hospitals in Nanchang, China: A Structural Equation Modeling Approach

Outpatient satisfaction is important in evaluating the performance of tertiary public hospitals in China. However, only a few studies have examined the interaction between outpatient satisfaction and its related factors. This study aimed to explore the relationship between patient satisfaction and its related factors in provincial tertiary hospitals. Six hundred outpatients in three provincial tertiary hospitals in Nanchang, China, were randomly selected. Structural equation modeling was used to analyze the relationship of the factors associated with outpatient satisfaction. The conceptual model fitted the data well (χ2/df = 4.367, CFI = 0.951, TLI = 0.937, SRMR = 0.055, RMSEA = 0.075), with all the path coefficients being statistically significant (p < 0.001). The environment and facilities showed the most significant influence on outpatient satisfaction (standardized total effect = 0.389), followed by the quality of diagnosis and treatment (standardized total effect = 0.235). The waiting time for medical services showed a partial mediation effect of 0.077 between the environment and facilities and outpatient satisfaction. The study indicates that targeted measures should be taken to improve the amenities of hospitals and shorten the waiting time for medical services, thus further improving outpatients’ medical experience.
Alcohol norms and alcohol intake among high school students

Aims: To analyse whether parental alcohol norms were associated with the alcohol intake of high school students and whether this association persisted across different levels of alcohol intake in school and trustful communication with parents. Methods: This was a cross-sectional study among 70,544 high school students (mean age 18 years) participating in the Danish National Youth Study 2014. We examined the associations between parental alcohol norms and individual alcohol intake as the number of drinks at the most recent school party and the frequency of binge drinking in the last 30 days using negative binomial regression. We then performed joint analyses of parental alcohol norms and alcohol intake at school level, and parental alcohol norms and trustful communication with parents. Results: The mean intake of alcohol at the most recent school party was 9.9 units of alcohol for boys and 7.6 units of alcohol for girls. A total of 36.2% of boys and 24.7% of girls were binge drinking frequently (more than four occasions in the last month). Lenient parental alcohol norms and a low level of trustful communication with parents were associated with a higher intake at the most recent school party and with the frequency of binge drinking. Joint analyses showed that these associations persisted across different levels of school level alcohol intake and levels of trustful communication with parents. Conclusions: Among high school students, parental alcohol norms were strongly associated with alcohol intake and consistently so across different levels of school level alcohol intake and level of trustful communication with parents. This indicates that the role of parents in preventing excessive drinking is important, even in older adolescents.
SARS-CoV-2 infection threatening intestinal health: A review of potential mechanisms and treatment strategies

Abstract The outbreak of the COVID-19 pandemic has brought great problems to mankind, including economic recession and poor health. COVID-19 patients are frequently reported with gastrointestinal symptoms such as diarrhea and vomiting in clinical diagnosis. Maintaining intestinal health is the key guarantee to maintain the normal function of multiple organs, otherwise it will be a disaster. Therefore, the purpose of this review was deeply understanded the potential mechanism of SARS-CoV-2 infection threatening intestinal health and put forward reasonable treatment strategies. Combined with the existing researches, we summarized the mechanism of SARS-CoV-2 infection threatening intestinal health, including intestinal microbiome disruption, intestinal barrier dysfunction, intestinal oxidative stress and intestinal cytokine storm. These adverse intestinal events may affect other organs through the circulatory system or aggravate the course of the disease. Typically, intestinal disadvantage may promote the progression of SARS-CoV-2 through the gut-lung axis and increase the disease degree of COVID-19 patients. In view of the lack of specific drugs to inhibit SARS-CoV-2 replication, the current review described new strategies of probiotics, prebiotics, postbiotics and nutrients to combat SARS-CoV-2 infection and maintain intestinal health. To provide new insights for the prevention and treatment of gastrointestinal symptoms and pneumonia in patients with COVID-19.
Clinical Perspectives and Management of Edema in Chronic Venous Disease—What about Ruscus?

Background: Edema is highly prevalent in patients with cardiovascular disease and is associated with various underlying pathologic conditions, making it challenging for physicians to diagnose and manage. Methods: We report on presentations from a virtual symposium at the Annual Meeting of the European Venous Forum (25 June 2021), which examined edema classification within clinical practice, provided guidance on making differential diagnoses and reviewed evidence for the use of the treatment combination of Ruscus extract, hesperidin methyl chalcone and vitamin C. Results: The understanding of the pathophysiologic mechanisms underlying fluid build-up in chronic venous disease (CVD) is limited. Despite amendments to the classic Starling Principle, discrepancies exist between the theories proposed and real-world evidence. Given the varied disease presentations seen in edema patients, thorough clinical examinations are recommended in order to make a differential diagnosis. The recent CEAP classification update states that edema should be considered a sign of CVD. The combination of Ruscus extract, hesperidin methyl chalcone and vitamin C improves venous tone and lymph contractility and reduces macromolecule permeability and inflammation. Conclusions: Data from randomized controlled trials support guideline recommendations for the use of Ruscus extract, hesperidin methyl chalcone and vitamin C to relieve major CVD-related symptoms and edema.
Intravenously Injected Mesenchymal Stem Cells Penetrate the Brain and Treat Inflammation-Induced Brain Damage and Memory Impairment in Mice

Neuroinflammation is regarded as one of the pathogenic factors of Alzheimer disease (AD). Previously, we showed that mice regularly injected with bacterial lipopolysaccharide (LPS) possessed the AD-like symptoms like episodic memory decline, elevated amounts of amyloid beta (Aβ) peptide (1–42), and decreased levels of nicotinic acetylcholine receptors (nAChRs) in the brain. The use of mesenchymal stem cells (MSCs), which can differentiate into multiple cell types, including neurons, is an attractive idea of regenerative medicine, in particular, for neurodegenerative disorders like AD. In the present study, we aimed to investigate whether pathogenic effect of LPS on the brain and behavior of mice can be prevented or treated by injection of MSCs or MSC-produced soluble factors. Fluorescently-labeled MSCs, injected intravenously, were found in the brain blood vessels of LPS-treated mice. Mice co-injected with LPS and MSCs did not demonstrate episodic memory impairment, Aβ (1–42) accumulation, and nAChR decrease in the brain and brain mitochondria. Their mitochondria released less cytochrome c under the effect of Ca2+ compared to mitochondria of LPS-only-treated mice. Moreover, MSCs could reverse the pathogenic symptoms developed 3 weeks after LPS injection. Cultured MSCs produced IL-6 in response to LPS and MSCs effect in vivo was accompanied by additional stimulation of both micro- and macroglia. Xenogeneic (human) MSCs were almost as efficient as allogeneic (mouse) ones and regular injections of human MSC-conditioned medium also produced positive effect. These data allow suggesting MSCs as a potential therapeutic tool to cure neuroinflammation-related cognitive pathology.
Fear in the Theater of the Mind: Differential Fear Conditioning With Imagined Stimuli

Many symptoms of anxiety and posttraumatic stress disorder are elicited by fearful mental imagery. Yet little is known about how visual imagery of conditioned stimuli (CSs) affects the acquisition of differential fear conditioning. Across three experiments with younger human adults (Experiment 1: n = 33, Experiment 2: n = 27, Experiment 3: n = 26), we observed that participants acquired differential fear conditioning to both viewed and imagined percepts serving as the CSs, as measured via self-reported fear and skin conductance responses. Additionally, this differential conditioning generalized across CS-percept modalities such that differential conditioning acquired in response to visual percepts generalized to the corresponding imagined percepts and vice versa. This is novel evidence that perceived and imagined stimuli engage learning processes in very similar ways and is consistent with the theory that mental imagery is depictive and recruits neural resources shared with visual perception. Our findings also provide new insight into the mechanisms of anxiety and related disorders.
Muscone and (+)-Borneol Cooperatively Strengthen CREB Induction of Claudin 5 in IL-1β-Induced Endothelium Injury

Claudin 5 is one of the major proteins of tight junctions and is responsible for cerebrovascular integrity and BBB function. Muscone and (+)-borneol is the major ingredient of moschus and borneolum, respectively, with antioxidative and anti-inflammatory activities. This study investigated whether muscone and (+)-borneol combination protected claudin 5 by targeting ROS-mediated IL-1β accumulation. Muscone and (+)-borneol reduced cerebral infarct volume and cerebrovascular leakage with claudin 5 protection in mice after stroke, largely due to inhibiting ROS accumulation and inflammatory infiltrate of microglia. Muscone reduced ROS and then blocked the CaN/Erk1/2 pathway to decrease IL-1β release, while (+)-borneol removed mitochondrial ROS and attenuated the SDH/Hif-1α pathway to inhibit IL-1β transcription, thereby jointly reducing IL-1β production. Accumulated IL-1β disrupted cAMP/CREB activation and attenuated transcriptional regulation of claudin 5. Muscone and (+)-borneol combination cooperatively protected BBB function by blocking IL-1β-mediated cAMP/CREB/claudin 5 cascades. Mutation of Ser133 site of CREB or knockdown of claudin 5 weakened the effects of muscone and (+)-borneol on upregulation of TEER value and downregulation of FITC-dextran permeability, suggesting that targeting CREB/claudin 5 was an important strategy to protect vascular integrity. This study provided ideas for the studies of synergistic protection against ischemic brain injury about the active ingredients of traditional Chinese medicines (TCMs).