Miracle-dz/UniFAR-FTUs huggingface dataset:
Photodynamic therapy – hypericin tetraether liposome conjugates and their antitumor and antiangiogenic activity

Abstract Photodynamic therapy (PDT) is an established noninvasive tumor treatment. The hydrophobic natural occurring pigment hypericin shows a lot of attractive properties for the application in PDT. Hence, the administration to biological systems or patients requires the formulation in drug carriers enabling sufficient bioavailability. Therefore, free hypericin was encapsulated by the thin film hydration method or a hypericin-hydroxypropyl-β-cyclodextrin inclusion complex (Hyp-HPβCD) was incorporated by dehydration-rehydration vesicle method in either conventional or ultra-stable tetraether lipid (TEL) liposomes. The hydrodynamic diameter of the prepared nanoformulations ranged between 127 and 212 nm. These results were confirmed by atomic force microscopy. All liposomes showed a good stability under physiological conditions. TEL liposomes which tend to build more rigid bilayers, generate higher encapsulation efficiencies than their conventional counterparts. Furthermore, the suitability for intravenous application was confirmed by hemocompatibility studies resulting in a hemolytic potential less than 20% and a coagulation time less than 50 sec. The uptake of liposomal hypericin into human ovarian carcinoma cells (SK-OV-3) was confirmed using confocal microscopy and further characterized by pathway studies. It was demonstrated that the lipid composition and intraliposomal hypericin localization influenced the anti-vascular effect in the chorioallantoic membrane (CAM). While hypericin TEL liposomes exhibit substantial destruction of the microvasculature drug-in-cyclodextrin TEL liposomes showed no effect. Nevertheless, both formulations yielded severe photocytotoxicity in SK-OV-3 cells in a therapeutic dosage range. Conclusively, hypericin TEL liposomes would be perfectly suited for anti-vascular targeting while Hyp-HPβCD TEL liposomes could deliver the photosensitizer to the tumor site in a more protected manner.
An evaluation of metabolite profiling of six drugs using dried blood spot

Abstract Dry blood spot (DBS) analysis has been extensively used for the quantitative analysis of drugs by mass spectrometry; however, utilization of DBS for qualitative metabolite profiling has been very limited. In the present study, we investigated the use of DBS for metabolite profiling of genistein, carbamazepine, losartan, sunitinib, sildenafil and zoniporide representing a range of Phase I and Phase II biotransformations following oral and intravenous dosing to rats. Plasma and DBS were collected for PK and metabolite profiling. Analyte extraction recovery from DBS was optimized using the parent compound and metabolite standard. Rat DBS metabolite profiles from all six compounds were similar to plasma metabolite profiles, however Phase II metabolites appeared to be extracted less efficiently from DBS compared to plasma, and compounds that were unstable in blood showed different metabolite profiles. In summary, this study showed that in addition to PK bioanalytical analysis, DBS samples may also be utilized for metabolite profiling and a comparison of plasma and DBS metabolite profiling can also provide partitioning/association of major circulating metabolites compared to the parent drug even in the absence of a metabolite standard.
Sex Differences in Cardiovascular Risk Profile From Childhood to Midlife Between Individuals Who Did and Did Not Develop Diabetes at Follow-up: The Bogalusa Heart Study

OBJECTIVE Childhood and young adulthood may represent time periods in which cardiovascular risk factors (CVRFs) and their cumulative exposure lay the foundation for future risk of chronic diseases. We examined the longitudinal burden of CVRFs since childhood in men and women in whom diabetes did and did not develop at follow-up. RESEARCH DESIGN AND METHODS We included 1,530 participants (mean [SD] follow-up time 33.1 [8.2] years), who participated in the Bogalusa Heart Study and had been examined at least four times starting in childhood (mean age [SD] at first examination 9.4 [3.1] years). The area under the growth curve was used as a measure of cumulative exposure to CVRFs since childhood. RESULTS In childhood, boys and girls in whom diabetes did and did not develop at follow-up had similar CVRFs. Yet, over time, women during the transition from normoglycemia to diabetes experienced greater adverse changes in total cholesterol (TC), LDL cholesterol, and fasting plasma glucose (FPG) (noted as early as 23.5 years old and persisting across adulthood up to the age of the diagnosis of diabetes); a higher burden of exposure to BMI, TC, LDL cholesterol, and FPG from childhood to midlife; and a greater change in rates of BMI, TC, LDL cholesterol, and FPG since childhood than men during the same transition (interaction P values <0.05). CONCLUSIONS The greater exposure of women to and burden of CVRFs associated with diagnosis of diabetes may help to explain the stronger impact of diabetes as a major risk factor for cardiovascular events in women compared with men.
Association Among County-Level Economic Factors, Clinician Supply, Metropolitan or Rural Location, and Neonatal Abstinence Syndrome

Importance Neonatal abstinence syndrome (NAS) has increased over the last 2 decades, but limited data exist on its association with economic conditions or clinician supply. Objective To determine the association among long-term unemployment, clinician supply (as assessed by primary care and mental health clinician shortage areas), and rates of NAS and evaluate how associations differ based on rurality. Design, Setting, and Participants Ecological time-series analysis of a retrospective, repeated cross-sectional study using outcome data from all 580 counties in Florida, Kentucky, Massachusetts, Michigan, New York, North Carolina, Tennessee, and Washington from 2009 to 2015 and economic data from 2000 to 2015. Negative binomial models were used with year and county-level fixed effects. Interactions were tested and stratified analyses were conducted by metropolitan counties, rural counties adjacent to metropolitan counties, and rural remote counties. Exposures County-level 10-year unemployment rate and mental health and primary care clinician supply obtained from the Health Resources and Services Administration Area Health Resources Files. Main Outcomes and Measure Rates of NAS, excluding iatrogenic withdrawal, obtained from state inpatient databases. Results The sample included observations from 580 counties over 7 years (1803 county-years from metropolitan counties, 1268 county-years from rural counties adjacent to metropolitan counties, and 927 county-years from rural remote counties). During the study period, there were 6 302 497 births and 47 224 diagnoses of NAS. The median rate of NAS was 7.1 per 1000 hospital births (interquartile range [IQR], 2.2-15.8), the 10-year unemployment rate was 7.6% (IQR, 6.4%-9.0%), and 83.9% of county-years were partial or complete mental health shortage areas. In the adjusted analyses, mental health shortage areas had higher NAS rates (unadjusted rate in shortage areas of 14.0 per 1000 births vs unadjusted rate in nonshortage areas of 10.6 per 1000 births; adjusted incidence rate ratio [IRR], 1.17 [95% CI, 1.07-1.27]), occurring primarily in metropolitan counties (adjusted IRR, 1.28 [95% CI, 1.16-1.40]; P = .02 for test of equivalence between metropolitan counties and rural counties adjacent to metropolitan counties). There was no significant association between primary care shortage areas and rates of NAS. The 10-year unemployment rate was associated with higher rates of NAS (unadjusted rate in highest unemployment quartile of 20.1 per 1000 births vs 7.8 per 1000 births in lowest unemployment quartile; adjusted IRR, 1.11 [95% CI, 1.00-1.23]) occurring primarily in rural remote counties (adjusted IRR, 1.34 [95% CI, 1.05-1.70]; P = .04 for test of equivalence between metropolitan counties and rural remote counties). Conclusions and Relevance In this ecological analysis of counties in 8 US states, there was a significant association among higher long-term unemployment, higher mental health clinician shortage areas, and higher county-level rates of neonatal abstinence syndrome.
Data Analysis and Visualization of Newspaper Articles on Thirdhand Smoke: A Topic Modeling Approach

Background Thirdhand smoke has been a growing topic for years in China. Thirdhand smoke (THS) consists of residual tobacco smoke pollutants that remain on surfaces and in dust. These pollutants are re-emitted as a gas or react with oxidants and other compounds in the environment to yield secondary pollutants. Objective Collecting media reports on THS from major media outlets and analyzing this subject using topic modeling can facilitate a better understanding of the role that the media plays in communicating this health issue to the public. Methods The data were retrieved from the Wiser and Factiva news databases. A preliminary investigation focused on articles dated between January 1, 2013, and December 31, 2017. Use of Latent Dirichlet Allocation yielded the top 10 topics about THS. The use of the modified LDAvis tool enabled an overall view of the topic model, which visualizes different topics as circles. Multidimensional scaling was used to represent the intertopic distances on a two-dimensional plane. Results We found 745 articles dated between January 1, 2013, and December 31, 2017. The United States ranked first in terms of publications (152 articles on THS from 2013-2017). We found 279 news reports about THS from the Chinese media over the same period and 363 news reports from the United States. Given our analysis of the percentage of news related to THS in China, Topic 1 (Cancer) was the most popular among the topics and was mentioned in 31.9% of all news stories. Topic 2 (Control of quitting smoking) was related to roughly 15% of news items on THS. Conclusions Data analysis and the visualization of news articles can generate useful information. Our study shows that topic modeling can offer insights into understanding news reports related to THS. This analysis of media trends indicated that related diseases, air and particulate matter (PM2.5), and control and restrictions are the major concerns of the Chinese media reporting on THS. The Chinese press still needs to consider fuller reports on THS based on scientific evidence and with less focus on sensational headlines. We recommend that additional studies be conducted related to sentiment analysis of news data to verify and measure the influence of THS-related topics.
Tail Wags the Dog? Functional Gene Classes Driving Genome-Wide GC Content in Plasmodium spp.

Abstract Plasmodium parasites are valuable models to understand how nucleotide composition affects mutation, diversification, and adaptation. No other observed eukaryotes have undergone such large changes in genomic Guanine–Cytosine (GC) content as seen in the genus Plasmodium (∼30% within 35–40 Myr). Although mutational biases are known to influence GC content in the human-infective Plasmodium vivax and Plasmodium falciparum; no study has addressed how different gene functional classes contribute to genus-wide compositional changes, or if Plasmodium GC content variation is driven by natural selection. Here, we tested the hypothesis that certain gene processes and functions drive variation in global GC content between Plasmodium species. We performed a large-scale comparative genomic analysis using the genomes and predicted genes of 17 Plasmodium species encompassing a wide genomic GC content range. Genic GC content was sorted and divided into ten equally sized quantiles that were then assessed for functional enrichment classes. In agreement that selection on gene classes may drive genomic GC content, trans-membrane proteins were enriched within extreme GC content quantiles (Q1 and Q10). Specifically, variant surface antigens, which primarily interact with vertebrate immune systems, showed skewed GC content distributions compared with other trans-membrane proteins. Although a definitive causation linking GC content, expression, and positive selection within variant surface antigens from Plasmodium vivax, Plasmodium berghei, and Plasmodium falciparum could not be established, we found that regardless of genomic nucleotide composition, genic GC content and expression were positively correlated during trophozoite stages. Overall, these data suggest that, alongside mutational biases, functional protein classes drive Plasmodium GC content change.
Validation of Selected Non-Destructive Methods for Determining the Compressive Strength of Masonry Units Made of Autoclaved Aerated Concrete

Minor-destructive (MDT) and non-destructive (NDT) techniques are not commonly used for masonry as they are complex and difficult to perform. This paper describes validation of the following methods: semi-non-destructive, non-destructive, and ultrasonic technique for autoclaved aerated concrete (AAC). The subject of this study covers the compressive strength of AAC test elements with declared various density classes of: 400, 500, 600, and 700 (kg/m3), at various moisture levels. Empirical data including the shape and size of specimens, were established from tests on 494 cylindrical and cuboid specimens, and standard cube specimens 100 mm × 100 mm × 100 mm using the general relationship for ordinary concrete (Neville’s curve). The effect of moisture on AAC was taken into account while determining the strength fBw for 127 standard specimens tested at different levels of water content (w = 100%, 67%, 33%, 23%, and 10%). Defined empirical relations were suitable to correct the compressive strength of dry specimens. For 91 specimens 100 mm × 100 mm × 100 mm, the P-wave velocity cp was tested with the transmission method using the ultrasonic pulse velocity method with exponential transducers. The curve (fBw–cp) for determining the compressive strength of AAC elements with any moisture level (fBw) was established. The developed methods turned out to be statistically significant and can be successfully applied during in-situ tests. Semi-non-destructive testing can be used independently, whereas the non-destructive technique can be only applied when the developed curve fbw–cp is scaled.
Predictors of psychotic symptoms among young people with special educational needs

Background Psychotic symptoms and psychotic disorders occur at increased rates in adults with intellectual disability, including borderline intellectual functioning, compared with the general population. Little is known about the development of such symptoms in this population. Aims To examine whether clinical factors predictive of psychotic disorder in a familial study of schizophrenia also apply to those with intellectual disability. Method Adolescents with special educational needs (SEN) were assessed with the Structured Interview for Schizotypy (SIS) and Childhood Behavioural Checklist (CBCL). These scores were used to prospectively divide participants based on their anticipated risk for psychotic disorder. A subsample were reassessed three times over 6 years, using the Positive and Negative Syndrome Scale (PANSS). Results The SEN group were more symptomatic than controls throughout (Cohen's d range for PANSS subscale scores: 0.54–1.4, all P < 0.007). Over 6 years of follow-up, those above the SIS and CBCL cut-off values at baseline were more likely than those below to display morbid positive psychotic symptoms (odds ratio, 3.5; 95% CI 1.3–9.0) and develop psychotic disorder (odds ratio, 11.4; 95% CI 2.6–50.1). Baseline SIS and CBCL cut-off values predicted psychotic disorder with sensitivity of 0.67, specificity of 0.85, positive predictive value of 0.26 and negative predictive value of 0.97. Conclusions Adolescents with SEN have increased psychotic and non-psychotic symptoms. The personality and behavioural features associated with later psychotic disorder in this group are similar to those in people with familial loading. Relatively simple screening measures may help identify those in this vulnerable group who do and do not require monitoring for psychotic symptoms. Declaration of interest None.
Anticipatory Neural Activity Improves the Decoding Accuracy for Dynamic Head-Direction Signals

Insects and vertebrates harbor specific neurons that encode the animal's head direction (HD) and provide an internal compass for spatial navigation. Each HD cell fires most strongly in one preferred direction. As the animal turns its head, however, HD cells in rat anterodorsal thalamic nucleus (ADN) and other brain areas fire already before their preferred direction is reached, as if the neurons anticipated the future HD. This phenomenon has been explained at a mechanistic level, but a functional interpretation is still missing. To close this gap, we use a computational approach based on the movement statistics of male rats and a simple model for the neural responses within the ADN HD network. Network activity is read out using population vectors in a biologically plausible manner, so that only past spikes are taken into account. We find that anticipatory firing improves the representation of the present HD by reducing the motion-induced temporal bias inherent in causal decoding. The amount of anticipation observed in ADN enhances the precision of the HD compass read-out by up to 40%. More generally, our theoretical framework predicts that neural integration times not only reflect biophysical constraints, but also the statistics of behaviorally relevant stimuli; in particular, anticipatory tuning should be found wherever neurons encode sensory signals that change gradually in time. SIGNIFICANCE STATEMENT Across different brain regions, populations of noisy neurons encode dynamically changing stimuli. Decoding a time-varying stimulus from the population response involves a trade-off: For short read-out times, stimulus estimates are unreliable as the number of stochastic spikes is small; for long read-outs, estimates are biased because they lag behind the true stimulus. We show that optimal decoding of temporally correlated stimuli not only relies on finding the right read-out time window but requires neurons to anticipate future stimulus values. We apply this general framework to the rodent head-direction system and show that the experimentally observed anticipation of future head directions can be explained at a quantitative level from the neuronal tuning properties, network size, and the animal's head-movement statistics.
[High-performance liquid chromatography-mass spectrometry-based serum metabolic profiling in patients with HBV-related hepatocellular carcinoma].

OBJECTIVE To explore the diagnostic value of the serum metabolites identified by high-performance liquid chromatography-mass spectrometry (HPLC/MS) for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODS A total of 126 patients admitted to Tianjin Third Central Hospital were enrolled, including 27 patients with HBV-related hepatitis with negative viral DNA (DNA-N), 24 with HBV-related hepatitis with positive viral DNA, 24 with HBV-related liver cirrhosis, 27 with HBV-related HCC undergoing surgeries or radiofrequency ablation, and 24 with HBV-related HCC receiving interventional therapy, with 25 healthy volunteers as the normal control group. Serum samples were collected from all the subjects for HPLC/MS analysis, and the data were pretreated to establish an orthogonal partial least- squares discriminant analysis (OPLS-DA) model. The differential serum metabolites were preliminarily screened by comparisons between the HBV groups and the control group, and the characteristic metabolites were identified according to the results of non-parametric test. The potential clinical values of these characteristic metabolites were evaluated using receiver operator characteristic curve (ROC) analysis. RESULTS A total of 25 characteristic metabolites were identified in the HBV- infected patients, including 9 lysophosphatidylcholines, 2 fatty acids, 17α-estradiol, sphinganine, 5-methylcytidine, vitamin K2, lysophosphatidic acid, glycocholic acid and 8 metabolites with few reports. The patients with HBV- related HCC showed 22 differential serum metabolites compared with the control group, 4 differential metabolites compared with patients with HBV-related liver cirrhosis; 10 differential metabolites were identified in patients with HBV-related HCC receiving interventional therapy compared with those receiving surgical resection or radiofrequency ablation. From the normal control group to HBV-related HCC treated by interventional therapy, many metabolites underwent variations following a similar pattern. CONCLUSIONS We identified 25 characteristic metabolites in patients with HBV-related HCC, and these metabolites may have potential clinical values in the diagnosis of HBV-related HCC. The continuous change of some of these metabolites may indicate the possibility of tumorigenesis, and some may also have indications for the choice of surgical approach.
The Factors Affecting Older Adults’ Intention toward Ongoing Participation in Virtual Reality Leisure Activities

Due to the aging of organs, older adults may have limited physical strength for participating in outdoor activities. Therefore, indoor activities offer an alternative for maintaining the health of older adults. Following advances in technology, individuals can use virtual reality to exercise in their homes and are no longer subject to the constraints of the outdoor environment or weather conditions. In addition, these activities are easier to participate in when compared to real-world leisure activities. The present research included 294 older adults as its research subjects. They were given firsthand experience of Wii games for 10 weeks, in order to examine the ongoing participation intention of older adults following an experience with virtual reality leisure activities. The study found that experience attributes, experience consequences, and experience values were important factors in determining ongoing participation intention and can effectively predict ongoing participation intention. Four experience attributes—ease of use, usefulness, safety and flexibility, and fun—significantly influenced the experience value and experience consequences of older adults’ participants. Experience values also influenced ongoing participation intention.