Miracle-dz/UniFAR-FTUs huggingface dataset:
Genotoxicity of Marijuana in Mono-Users

Marijuana (Cannabis sp.) is among the most recurred controlled substances in the world, and there is a growing tendency to legalize its possession and use; however, the genotoxic effects of marijuana remain under debate. A clear definition of marijuana's genotoxic effects remains obscure by the simultaneous consumption of tobacco and other recreational substances. In order to assess the genotoxic effects of marijuana and to prevent the bias caused by the use of substances other than cannabis, we recruited marijuana users that were sub-divided into three categories: (1) users of marijuana-only (M), (2) users of marijuana and tobacco (M+T), and (3) users of marijuana plus other recreative substances or illicit drugs (M+O), all the groups were compared against a non-user control group. We quantified DNA damage by detection of γH2AX levels and quantification of micronuclei (MN), one of the best-established methods for measuring chromosomal DNA damage. We found increased levels of γH2AX in peripheral blood lymphocytes from the M and M+T groups, and increased levels of MNs in cultures from M+T group. Our results suggest a DNA damage increment for M and M+T groups but the extent of chromosomal damage (revealed here by the presence of MNs and NBuds) might be related to the compounds found in tobacco. We also observed an elevated nuclear division index in all marijuana users in comparison to the control group suggesting a cytostatic dysregulation caused by cannabis use. Our study is the first in Mexico to assess the genotoxicity of marijuana in mono-users and in combination with other illicit drugs.
Bioaccumulation of PCBs, OCPs and PBDEs in Marine Mammals From West Antarctica

To understand the bioaccumulation and food web dynamics of persistent organic pollutants (POPs) as a function of species, age and sex in Antarctic mammals, blubber samples of 3 killer whales (Type C) and 77 pinnipeds (Weddell, Ross and crabeater seals) were collected from the Southern Ocean, Antarctica. They were analyzed for polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs) and polybrominated diphenyl ethers (PBDEs). ΣDDTs, Σ29PCBs and chlordanes (12 – 4,600, 13 – 1,600, and < 1.5 – 1,700 ng/g lipid, respectively) were the most abundant POPs. Killer whales typically displayed several times greater concentrations of POPs compared to seals, except for PBDEs. PCBs and PBDEs were consistently higher in adult crabeater and Weddell seal males, and in adult female Ross seals than in other sex and age groups reflecting an age accumulation and possible influence of segregated diet, foraging areas, and metabolic transformation rates. POPs concentrations significantly correlated with gene transcription of nuclear receptors involved in detoxification of contaminants and immune relevant cell mediators in the crabeater seals, indicating possible immunotoxic and deleterious health effects. This represents one of the largest studies on POPs in Antarctic marine predators and highlights the complexity of POPs bioaccumulation. Graphical Abstract POPs in Antarctic Mammals.
Antibiotic Stewardship Initiatives as Part of the UK 5-Year Antimicrobial Resistance Strategy

Antibiotic use is a major driver for the emergence and spread of antibiotic resistance. Antimicrobial stewardship programmes aim to improve antibiotic prescribing with the objectives of optimizing clinical outcomes while at the same time minimizing unintended consequences such as adverse effects and the selection of antibiotic resistance. In 2013, a five-year national strategy for tackling antimicrobial resistance was published in the UK. The overarching goal of the strategy is to slow the development and spread of resistance and to this end it has three strategic aims, namely to improve knowledge and understanding of resistance, to conserve and steward the effectiveness of existing treatments and to stimulate the development of new antibiotics, diagnostics and novel therapies. This article reviews the antimicrobial stewardship activities included in the strategy and describes their implementation and evaluation.
Store Brands and Retail Grocery Competition

Grocery retailers rank store brands as the most important factor that differentiates them from their competitors. Retailer competition should have a stronger impact on the more substitutable national brands than the more differentiated store brands. However, the literature has not studied the impacts empirically. In this paper, I quantify the different impacts of retailer competition on national brands and store brands using the scanner data of a U.S. chain retailer. I estimate a structural demand and supply model that incorporates the differentiation effect and retailer competition. The results show that national brand consumers are more likely to switch stores than store brands consumers. By analyzing two counterfactual cases, I find that 1) if the retailer did not sell store brands, its profit would decrease, and the loss would be greater in markets with more competitors; and 2) if the retailer competition had increased, then the national brands' retail prices would decrease more than the store brands' prices.
Electrical penetration graph studies to investigate the effects of cyantraniliprole on feeding behavior of Myzus persicae (Hemiptera: Aphididae) on Capsicum annuum.

BACKGROUND The anthranilic diamide insecticide cyantraniliprole has been shown to suppress aphid and whitefly populations as well as reduce transmission of plant viruses by thrips and whiteflies when taken up systemically by the plant. In this study, electrical penetration graphing (EPG) was used to compare effects of cyantraniliprole on feeding behavior of Myzus persicae with those of the neonicotinoid insecticide imidacloprid applied as a soil drench to pepper plants two-, six-, and ten-days post-treatment. RESULTS Significant reductions in the total amount of time spent probing, mean number of phloem feeding events, and mean number of intracellular punctures were observed on both cyantraniliprole- and imidacloprid-treated plants, compared to aphids that fed on plants treated only with water. Imidacloprid treatment also caused a significant reduction in the total number of probes relative to the water treated control. The effects of cyantraniliprole were statistically significant only in assays conducted at ten-days post-treatment, whereas the effects of imidacloprid on aphid feeding were significant in assays conducted at two-, six-, and ten-days post-treatment. CONCLUSION These findings document significant effects of cyantraniliprole on feeding by Myzus persicae.
Gelatin/Polycaprolactone Electrospun Nanofibrous Membranes: The Effect of Composition and Physicochemical Properties on Postoperative Cardiac Adhesion

Cardiovascular diseases have become a major threat to human health. The adhesion formation is an inevitable pathophysiological event after cardiac surgery. We have previously shown that gelatin/polycaprolactone (GT/PCL, mass ratio 50:50) electrospun nanofibrous membranes have high potential in preventing postoperative cardiac adhesion, but the effect of GT:PCL composition on anti-adhesion efficacy was not investigated. Herein, nanofibrous membranes with different GT:PCL mass ratios of 0:100, 30:70, 50:50, and 70:30 were prepared via electrospinning. The 70:30 membrane failed to prevent postoperative cardiac adhesion, overly high GT contents significantly deteriorated the mechanical properties, which complicated the suturing during surgery and hardly maintained the structural integrity after implantation. Unexpectedly, the 0:100 membrane (no gelatin contained) could not effectively prevent either, since its large pore size allowed the penetration of numerous inflammatory cells to elicit a severe inflammatory response. Only the GT:PCL 50:50 membrane exhibited excellent mechanical properties, good biocompatibility and effective anti-cell penetration ability, which could serve as a physical barrier to prevent postoperative cardiac adhesion and might be suitable for other biomedical applications such as wound healing, guided tissue or bone regeneration.
Assessment of cell viability, early apoptosis, and hematopoietic potential in umbilical cord blood units after storage

Successful hematopoietic stem cell transplantation using stored umbilical cord blood (CB) largely depends on cell dose and quality of CB units. The aim of this study was to assess the degree of early apoptosis, in addition to cell viability and hematopoietic potential, in umbilical CB units after storage.
Socioeconomic differences in smoking cessation: the role of social participation

Objectives: The aim of this study was to investigate whether psychosocial resources explain socioeconomic differences in smoking cessation and its maintenance. Methods: A subpopulation of 11,837 individuals from the Malmö Diet and Cancer Study interviewed in 1992-94, age range 45-64 years, was investigated in this cross-sectional study. A multivariate logistic regression model was used to assess relative risks of having stopped smoking, adjusting for age, country of origin, previous/ current diseases, and marital status. Results: An odds ratio of 1.9 (1.4-2.5; 95% CI) for men and 2.0 (1.4-2.7; 95% CI) for women of having stopped smoking was found for higher non-manual employees when compared with unskilled manual workers. A decrease in these odds ratios was found when social participation was introduced into the model. The other three social network and social support variables were non-significant. Conclusion: High social participation is a predictor of maintenance of smoking cessation. It seems possible to interpret parts of the socioeconomic differences in smoking cessation and its maintenance as a consequence of differing social network resources and social capital between socioeconomic groups.
Population-Based Case-Control Study of Renin-Angiotensin System Genes Polymorphisms and Hypertension among Hispanics

The effect of polymorphisms of the RAS genes on the incidence of hypertension seems to be population-dependent. We studied the effects of the angiotensinogen T174M and M235T, angiotensin converting enzyme insertion/deletion (ACE I/D), and angiotensin II receptor 1 (AT1R) A1166C gene polymorphisms on the risk of hypertension among Hispanics. We selected all cases (n=256) and 257 age and sex group-matched controls from a random sample of free living Colombians (n=2,989). Logistic regression was used to estimate the independent effect of each polymorphism. All polymorphisms were in Hardy-Weinberg equilibrium in controls, with the exception of M235T, which showed a small excess of heterozygotes (p=0.005; disequilibrium coefficient, D=−0.0264). After adjustment for age, sex, body mass index, race, physical activity, family history of hypertension and cardiovascular disease, and other polymorphisms, subjects with the ACE DD genotype were 1.56 times (95% confidence interval [CI]: 1.05, 2.33) more likely to be hypertensive than carriers of the I allele (p=0.03). Also, adjusted systolic and diastolic blood pressure were 4.58 (95% CI: −0.39, 9.56) and 3.32 (95% CI: 0.78, 5.86) mmHg higher in DD homozygous individuals than in carriers of the I allele, respectively. Approximately 15% of the cases of hypertension in this population could be attributed to carriage of the DD genotype. None of the other polymorphisms was associated with either hypertension or blood pressure level. In conclusion, the ACE DD genotype appears to be an independent risk factor for development of hypertension and may explain a significant fraction of incident cases among Hispanics.
Response to temperature shifts of expression of the amp gene on pBR322 in Escherichia coli K-12

Synthesis of beta-lactamase, the product of the amp gene on pBR322, in Escherichia coli K-12 was reversibly repressed with a shift-up of the growth temperature from 30 to 42 degrees C. The temperature shift, however, did not affect the level of mRNA encoding beta-lactamase, which suggested the involvement of translational control.
Demand Shock, Speculative Beta, and Asset Prices: Evidence from the Shanghai-Hong Kong Stock Connect Program

Upon the announcement of the Shanghai-Hong Kong Stock Connect program, connected stocks in the Shanghai Stock Exchange experience significant value appreciation of 1.8% over a seven-day announcement window and significant increases in turnover and volatility compared with unconnected stocks with similar firm characteristics, especially for stocks with higher market beta. The beta effect on stock prices is stronger for stocks with higher beta-to-idiosyncratic variance ratios and is reversed within three months. The results support the speculative nature of beta and the multiplier effect of speculation on demand shocks as predicted by Hong, Scheinkman, and Xiong (2006) and Hong and Sraer (2016). The announcement of the Shenzhen-Hong Kong Stock Connect program serves as an out-of-sample test and confirms our findings.
Further evidence for a synergistic association between APOE epsilon4 and BCHE-K in confirmed Alzheimer's disease.

Recent reports on a potential association between the K-variant of the gene for butyrylcholinesterase (BCHE-K) and Alzheimer's disease (AD) are discordant. An initial finding of association through a synergistic enhancement of risk of APOE epsilon4 with late-onset AD has not been confirmed by others. We have conducted a case-control study of histopathologically confirmed AD (n=135) and non-AD (n=70) cases (age of death > or =60 years), in which we have genotyped for APOE epsilon4, BCHE-K, and BCHE-A1914G, a silent polymorphism 299 bp downstream of the BCHE-K mutation. The allelic frequency of BCHE-K was 0.13 in the controls and 0.23 in the AD cases, giving a carrier odds ratio (OR(c)) of 2.1 (95% C.I. 1.1-4.1) for BCHE-K in confirmed AD. The allelic frequency for the BCHE-1914G variant was 0.19 and 0.33 in controls and AD cases, respectively (OR(c)=2.4; 95% C.I. 1.3-4.5). In an older sub-sample of 27/70 controls and 89/135 AD patients with ages of death > or =75 years, the OR(c) was increased to 4.5 (95% C.I. 1.4-15) for BCHE-K and 2.7 (95% C.I. 1.0-7.2) for BCHE-1914G carriers. The BCHE-K association with AD became even stronger in carriers of at least one APOE epsilon4 allele. Only three out of 19 controls compared with 39/81 AD cases carried BCHE-K in addition to APOE epsilon4, giving an odds ratio of confirmed AD of 5.0 (95% C.I. 1.3-19) for BCHE-K carriers within APOE epsilon4 carriers. Five out of 19 controls and 52/81 AD cases carried BCHE-1914G, giving the same odds ratio of confirmed AD of 5.0 (95% C.I. 1.6-16) for BCHE-1914G carriers within APOE epsilon4 carriers. In addition, our results suggest strong linkage disequilibrium between BCHE-K and BCHE-1914G but no major association of the sole BCHE-1914G chromosome with AD. We conclude that BCHE through its K-variant, rather than a nearby marker, is a susceptibility factor for AD and enhances the AD risk defined by APOE epsilon4 alone in an age-dependent manner.
Heterogeneity in the Epigenetic Landscape of Murine Testis-Specific Histone Variants TH2A and TH2B Sharing the Same Bi-Directional Promoter

Testis-specific histone variants are crucial to promote open chromatin structure to enable nucleosome disassembly in the final stages of spermiogenesis. However, even after histone replacement, mature sperm retain a proportion of these variants, the function of which is unknown. The present study aimed to understand the functional relevance of the retained H2B and H2A variants, TH2B and TH2A. While no literature is available on the phenotype of TH2A knockouts, TH2B/TH2A double knockout male mice are reported to be infertile. In this study, ChIP-seq analysis was done for TH2B and TH2A to understand the epigenomics of the retained TH2B and TH2A, using murine caudal sperm. Distribution across genomic partitions revealed ∼35% of the TH2B peaks within ±5 kb of TSS whereas TH2A peaks distribution was sparse at TSS. Gene Ontology revealed embryo development as the most significant term associated with TH2B. Also, based on genomic regions, TH2B was observed to be associated with spindle assembly and various meiosis-specific genes, which is an important finding as TH2A/TH2B DKO mice have been reported to have defective cohesin release. A comparison of mouse and human TH2B-linked chromatin revealed 26% overlap between murine and human TH2B-associated genes. This overlap included genes crucial for embryogenesis. Most importantly, heterogeneity in the epigenetic landscape of TH2A and TH2B was seen, which is intriguing as TH2B and TH2A are well reported to be present in the same nucleosomes to promote open chromatin. Additionally, unlike TH2B, TH2A was enriched on the mitochondrial chromosome. TH2A was found to be associated with Nuclear insertion of Mitochondrial DNA sequences (NUMTs) in sperm. A comprehensive analysis of these observations indicates novel functions for the sperm-retained TH2B and TH2A.
Moderate and Deep Hypothermic Circulatory Arrest Have Comparable Effects on Severe Systemic Inflammatory Response Syndrome After Total Aortic Arch Replacement in Patients With Type A Aortic Dissection

Background: The objective of this study was to compare the incidence of severe systemic inflammatory response syndrome (sSIRS) after total aortic arch replacement between patients who underwent moderate hypothermic circulatory arrest (MHCA) and those who underwent deep hypothermic circulatory arrest (DHCA). Methods: At Fuwai Hospital, 600 patients who underwent total aortic arch replacement with MHCA or DHCA from January 2013 to December 2016 were consecutively enrolled and divided into DHCA (14.1–20.0°C) and MHCA (20.1–28.0°C) groups. Preliminary statistical analysis revealed that some baseline indicators differed between the two groups; therefore, propensity score matching (PSM) was used to balance the covariates. Post-operative sSIRS as the primary outcome was compared between the groups both before and after PSM. Results: A total of 275 (45.8%) patients underwent MHCA, and 325 (54.2%) patients underwent DHCA. After PSM analysis, a total of 191 matched pairs were obtained. The overall incidence of sSIRS was 27.3%. There was no significant difference in post-operative sSIRS between the MHCA group and the DHCA group in either the overall cohort or the PSM cohort (no-PSM: P = 0.188; PSM: P = 0.416); however, post-operative sSIRS was increased by ~4% in the DHCA group compared with the MHCA group in both the no-PSM and PSM cohorts (no-PSM: 29.5 vs. 24.7%; PSM: 29.3 vs. 25.1%). Both before and after PSM, the rates of gastrointestinal hemorrhage and pulmonary infection and post-operative length of stay were significantly increased in the DHCA group compared with the MHCA group (P < 0.05), and the remaining secondary outcomes were not significantly different between the groups. Conclusions: MHCA and DHCA are associated with comparable incidences of sSIRS in patients following total aortic arch replacement for type A aortic dissection. However, the MHCA group had a shorter cardiopulmonary bypass time, a shorter post-operative length of stay and lower pulmonary infection and gastrointestinal hemorrhage rates than the DHCA group. We cautiously recommend the use of MHCA for most total arch replacements in patients with type A aortic dissection.
Reproductive and behavioral responses of earthworms exposed to nano‐sized titanium dioxide in soil

Nanometer‐sized titanium dioxide (nano‐TiO2) is found in a number of commercial products; however, its effects on soil biota are largely unknown. In the present study, earthworms (Eisenia andrei and Eisenia fetida) were exposed to three types of commercially available, uncoated TiO2 nanomaterials with nominal diameters of 5, 10, and 21 nm. Nanomaterials were characterized for particle size, agglomeration, surface charge, chemical composition, and purity. Standard lethality, reproduction, and avoidance tests, as well as a juvenile growth test, were conducted in artificial soil or field soil amended with nano‐TiO2 by two methods, liquid dispersion and dry powder mixing. All studies included a micrometer‐sized TiO2 control. Exposure to field and artificial soil containing between 200 and 10,000 mg nano‐TiO2 per kilogram of dry soil (mg/kg) had no significant effect (p > 0.05) on juvenile survival and growth, adult earthworm survival, cocoon production, cocoon viability, or total number of juveniles hatched from these cocoons. However, earthworms avoided artificial soils amended with nano‐TiO2. The lowest concentration at which avoidance was observed was between 1,000 and 5,000 mg nano‐TiO2 per kilogram of soil, depending on the TiO2 nanomaterial applied. Furthermore, earthworms differentiated between soils amended with 10,000 mg/kg nano‐TiO2 and micrometer‐sized TiO2. A positive relationship between earthworm avoidance and TiO2 specific surface area was observed, but the relationship between avoidance and primary particle size was not determined because of the agglomeration and aggregation of nano‐TiO2 materials. Biological mechanisms that may explain earthworm avoidance of nano‐TiO2 are discussed. Results of the present study indicate that earthworms can detect nano‐TiO2 in soil, although exposure has no apparent effect on survival or standard reproductive parameters. Environ. Toxicol. Chem. 2012;31:184–193. © 2011 SETAC
Hormonal Regulation of the MHC Class I Gene in Thyroid Cells: Role of the Promoter “Tissue-Specific” Region

In previous studies we have demonstrated that the expression of the Major Histocompatibility Complex (MHC) class I gene in thyrocytes is controlled by several hormones, growth factors, and drugs. These substances mainly act on two regions of the MHC class I promoter a “tissue-specific” region (−800 to −676 bp) and a “hormone/cytokines-sensitive” region (−500 to −68 bp). In a previous study, we have shown that the role of the “tissue-specific” region in the MHC class I gene expression is dominant compared to that of the “hormone/cytokines-sensitive” region. In the present report we further investigate the dominant role of the “tissue-specific” region evaluating the effect of thyroid stimulating hormone (TSH), methimazole (MMI), phenylmethimazole (C10), glucose and thymosin-α1. By performing experiments of electrophoretic mobility shift assays (EMSAs) we show that TSH, MMI and C10, which inhibit MHC class I expression, act on the “tissue-specific” region increasing the formation of a silencer complex. Glucose and thymosin-α1, which stimulate MHC class I expression, act decreasing the formation of this complex. We further show that the silencer complex is formed by two distinct members of the transcription factors families activator protein-1 (AP-1) and nuclear factor-kB (NF-kB), c-jun and p65, respectively. These observations are important in order to understand the regulation of MHC class I gene expression in thyroid cells and its involvement in the development of thyroid autoimmunity.