Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical Lipidology and the Prevention of Vascular Disease: Time for Personalized Therapy

Genetic, metabolic, and lifestyle modifications can cause elevations of lipoproteins that contribute to atherosclerotic lesions over time. In the modern world with life extension from many improvements in medicine and public health, most humans live long enough to develop atherosclerosis with concentrations of blood plasma lipoproteins that are very common. Familial abnormalities are prevalent and provide additional challenges in identifying unhealthy but treatable values of low‐density (LDL) and very low‐density lipoproteins (VLDL). Multiple community studies and clinical trials have provided guidance on selecting targets and new tools that make possible effective goals of treatment. Lipid‐lowering drugs are making it possible to achieve those goals and place responsibility on physicians to master the art of preventing atherosclerotic events. Lipoprotein management remains a very focused effort and requires an artful individualized approach for each patient. Few skills are more important for healthcare providers in primary care and cardiovascular medicine.
Recent Progress in Metal-Based Nanoparticles Mediated Photodynamic Therapy

Photodynamic therapy (PDT) is able to non-invasively treat and diagnose various cancers and nonmalignant diseases by combining light, oxygen, and photosensitizers (PSs). However, the application of PDT is hindered by poor water solubility and limited light-penetration depth of the currently available photosensitizers (PSs). Water solubility of PSs is crucial for designing pharmaceutical formulation and administration routes. Wavelength of light source at visible range normally has therapeutic depth less than 1 mm. In this review, focus is on the recent research progress of metal-based nanoparticles being applied in PDT. The potential toxicity of these nanoscales and future directions are further discussed.
Flexibility Principles in Boolean Semantics: The Interpretation of Coordination, Plurality, and Scope in Natural Language

Since the early work of Montague, Boolean semantics and its subfield of generalized quantifier theory have become the model-theoretic foundation for the study of meaning in natural languages. This book uses this framework to develop a new semantic theory of central linguistic phenomena involving coordination, plurality, and scope. The proposed theory makes use of the standard Boolean interpretation of conjunction, a choice-function account of indefinites, and a novel semantics of plurals that is not based on the distributive/collective distinction. The key to unifying these mechanisms is a version of Montagovian semantics that is augmented by flexibility principles: semantic operations that have no counterpart in phonology.This is the first book to cover these areas in a way that is both linguistically comprehensive and formally explicit. On one hand, it addresses questions of primarily linguistic concern: the semantic functions of words like and and or in different languages, the interpretation of indefinites and their scope, and the semantic typology of noun phrases and predicates. On the other hand, it addresses formal questions that are motivated by the treatment of these linguistic problems: the use of Boolean algebras in linguistics, the proper formalization of choice functions within generalized quantifier theory, and the extension of this theory to the domain of plurality. While primarily intended for readers with a background in theoretical linguistics, the book will also be of interest to researchers and advanced students in logic, computational linguistics, philosophy of language, and artificial intelligence.
Human epidermal growth factor receptor 2 neu expression in head and neck squamous cell cancers and its clinicopathological correlation: Results from an Indian cancer center

Background: Human epidermal growth factor receptor 2 (HER2)/neuprotooncogene (neu) is a proven molecular prognostic marker in breast, ovarian, gastric, and ovarian cancers. In head-and-neck cancers, varied expression is documented and therefore its prognostic role is debatable. Aim of the Study: To find the rate of overexpression of HER2/neu in head-and-neck cancers and to understand its prognostic role by evaluating its association with nodal stage and overall stage of the patient. Methodology: A total of 70 surgically resected cases of head-and-neck cancers were evaluated for expression of HER2/neu by immunohistochemistry. Scoring was done according to the American Society of Clinical Oncologists/College of American Pathologistsguidelines for Her2/neu testing in breast cancer. Results: Of the 70 cases studied, 57 were of oral cavity and 13 were laryngeal squamous cell cancers and 14 (20%) were Her2/neu positive. On correlating the expression of HER2/neu in T1/T2 (41 cases) versus T3/T4 (27 cases), the P value was found to be 0.8273 which was statistically insignificant. Furthermore, no statistically significant difference in expression of HER2/neu was found in between node negative and node positive cases (49 vs. 19 cases, respectively), with P = 0.512. Conclusion: In the current settings, HER2/neu is not found to be a prognostic marker in head-and-neck cancers. Standard immunohistochemistry staining protocols need to be established like in breast cancers to aid uniform reporting and further evaluate the role of this important protooncogene in head-and-neck cancers.
Novel Catechol Derivatives of Arylimidamides as Antileishmanial Agents

Two novel bis‐arylimidamide derivatives with terminal catechol moieties (9a and 10a) and two parent compounds with terminal phenyl groups (DB613 and DB884) were synthesized as dihydrobromide salts (9b and 10b). The designed compounds were hybrid molecules consisting of a catechol functionality embedded in an arylimidamide moiety. All compounds were examined for in vitro antiparasitic activity upon promastigotes of Leishmania major and L. infantum as well as axenic amastigotes of L. major. It was shown that conversion of terminal phenyl groups into catechol moieties resulted in more than 10‐fold improvement in potency, coupled with lower cytotoxicity against fibroblast cells, compared to the corresponding parent compounds. The furan‐containing analog 9a exhibited the highest activity with submicromolar IC50 values, ranging from 0.29 to 0.36 μm, which is comparable in efficacy to the reference drug amphotericin B (IC50 0.28 – 0.33 μm). The results justify further study of this class of compounds. It seems that the combination of catechol chelating groups with potent antiparasitic agents could improve the efficacy by presenting novel hybrid compounds.
Biomonitoring of Urinary Benzene Metabolite SPMA in the General Population in Central Italy

Background: Benzene is an important component of cigarette smoke and car exhaust. Products containing benzene in concentrations greater than 0.1% are prohibited in Europe, but 1% of benzene is still allowed in gasoline. The purpose of the study was to assess the levels of urine benzene biomarkers in a sample of the general population not occupationally exposed to benzene, resident in the period 2013–2014 in Central Italy, compared to other groups. Methods: The urinary levels of the benzene metabolites S-phenyl-mercapturic acid (SPMA) and cotinine (nicotine metabolite) were determined by means of HPLC with mass spectrometric detection in 1076 subjects. Results: The median SPMA value in smokers was 1.132 µg/g of creatinine while in non-smokers it was 0.097 µg/g of creatinine, and the 95th percentile results were seven times higher. Conclusion: The main source of benzene exposure in the studied population was active smoking, however, non-smokers were also exposed to airborne benzene concentrations. The concentration ranges found in this study can be used as a background reference for occupational exposure assessment to benzene by means of SPMA biomonitoring.
[Exogenous agmatine inhibits lipopolysaccharide-induced activation and dysfunction of human umbilical vein endothelial cells].

OBJECTIVE To investigate whether exogenous agmatine inhibits lipopolysaccharide (LPS)-induced activation and dysfunction of human umbilical vein endothelial cells (HUVECs) by modulating nuclear factor-κB (NF-κB) and MAPK signal pathways and the production of reactive oxygen species (ROS). METHODS Cultured HUVECs were treated with agmatine at the optimized concentration of 1.0 mmolγL, LPS (10 µgγmL), and LPS + agmatine, with or without pretreatment with the inhibitors of NF-κB (PDTC), p38 (SB203580), and ERK (PD98059) for 1 h. The levels of soluble vascular cell adhesion molecule 1 (VCAM-1), soluble intercellular adhesion molecule 1 (sICAM-1), soluble E-selectin and monocyte chemoattractant protein 1 (MCP-1) in the supernatant were determined using ELISA, and their mRNA expressions, along with heme oxygenase-1 (HO-1), and NAD(P)H: quinone oxidoreductase 1 (NQO-1), were assessed using real-time PCR. ROS production in the cells was determined using 2, 7-dichlorofluoresce in diacetate (DCFH-DA) as the fluorescence probe. The protein expressions of VCAM-1, ICAM-1, p65, phospho-p65 (p-p65), IκBα, p-IκBα, ERK, p-ERK, p38, p-p38, JNK, and p-JNK were detected using Western blotting. RESULTS LPS stimulation for 6 and 24 h significantly increased the levels of sVCAM-1, sICAM-1, sE-selectin and MCP-1 in the supernatant, intracellular ROS production, and the mRNA expressions of these molecules (P<0.05). Intervention with 1 mmolγL agmatine, similar with pretreatment with p38, ERK and NF-κB inhibitors, obviously inhibited such effects of LPS in HUVECs (P<0.05). Agmatine significantly up-regulated the mRNA expression of HO-1 (P<0.05), inhibited LPS-induced phosphorylation of p38, ERK, nuclear p65 and cytoplasmic IκBα, and up-regulated the protein expression of cytoplasmic IκBα. CONCLUSION Agmatine inhibits LPS-induced activation and dysfunction of HUVECs by modulating NF-κB and MAPK signal pathways to down-regulate the expressions of adhesion molecules and chemokines and by up-regulating the expression of HO-1 to reduce ROS production.
The Effect of Low Ionic Strength on Diffusion and Viscosity of Monoclonal Antibodies.

PURPOSE To determine the effect of solution conditions, especially low ionic strength, on the dynamics of molecular diffusion and protein-protein interactions in monoclonal antibody solutions. METHODS The interaction parameter, kD, was calculated from diffusion data obtained from dynamic light scattering (DLS) measurements performed using a Zetasizer. Theoretical considerations were utilized to evaluate the hard sphere and electrostatic contribution to molecular interactions. RESULTS At low ionic strengths, repulsions were the dominant forces governing the behavior of both mAbs. As ionic strength increased, attractions contributed to the behavior of mAb1, while repulsions remained the dominant factor affecting mAb3 behavior. Repulsions alone were not sufficient to affect mAb3 viscosity in water, while the presence of repulsions as well as specific attractions was suggested to cause an increase in the viscosity of mAb1 in water compared to 15 mM ionic strength. CONCLUSIONS Solution physical properties varied for the mAbs investigated. Our findings highlighted the importance of developing a fundamental understanding of interplay of forces governing solution properties of each individual mAb under low ionic strength conditions. Such understanding is critical in enabling successful development of self-buffered formulations.
Selfie posting and self-esteem among young adult women: A mediation model of positive feedback and body satisfaction

This study examined whether selfie-posting was positively associated with women’s self-esteem and whether this association was mediated by positive feedback and body satisfaction. A sample of 442 Chinese young adult women completed questionnaires on selfie-posting, positive feedback, body satisfaction, and self-esteem. Results indicated that selfie-posting was significantly and positively related to women’s self-esteem. In addition, positive feedback mediated the relation between selfie-posting and women’s self-esteem. Furthermore, the association between selfie-posting and self-esteem was sequentially mediated through positive feedback and body satisfaction. Findings from this study provide new insights into the relation between selfie-posting and self-esteem.
Match Running Performance of Elite Soccer Players: V[Combining Dot Above]O2max and Players Position Influences.

Metaxas, TI. Match running performance of elite soccer players: V[Combining Dot Above]O2max and players position influences. J Strength Cond Res XX(X): 000-000, 2018-The aims of this study were (a) to assess the relationship between laboratory-measured V[Combining Dot Above]O2max with total distance covered in a soccer match, (b) to assess the relationship between laboratory-measured V[Combining Dot Above]O2max with the distance covered at a different running intensity in a soccer match, (c) to quantify different intensity running in various playing positions, and (d) to determine the differences of running performance between halves. Analyzed match running performance of the Greek elite (n = 14) soccer players using a global positioning system within the second division professional league. No correlation was found between V[Combining Dot Above]O2max and match running performance at any velocity. The players covered greater distances in the first half at all speed levels except walking. In the first half, they covered a greater distance than in the second half (1,533 vs. 1,297 m, p < 0.001; 879 vs. 708 m, p < 0.001; 433 vs. 359 m, p < 001; 185 vs. 152 m, p < 0.01; 81.4 vs. 65.5 m, p < 0.001) when jogging, running, high-intensity running, fast running, sprint and total, respectively. Wide players covered greater distances at fast running (p < 0.001) and sprint zone than the players who played at the axon of the field (348 vs. 297 and 186 vs. 113 m, respectively). In addition, midfielders covered a greater distance at high-intensity running zone and at fast running zone than the defenders and forwards (1,768 vs. 1,372 m, p < 0.01 and 1,768 vs. 1,361 m, p < 0.01; 686 vs. 878 m, p < 0.01 and 709 vs. 878 m, p < 0.05, respectively). The results demonstrate that match running performance and the distance covered depends on the tactical role of each player in the team. These data provide valuable information for coaches regarding the running profile of the Greek elite soccer players that could be used to design a more effective training program.
People with intellectual disabilities’ experiences of psychological therapy: A systematic review and meta-ethnography

The effectiveness of a range of psychological models adapted for use with people with intellectual disabilities has been well documented. A number of studies have used qualitative methods to examine people with intellectual disabilities’ experiences of these adapted interventions. Such research is important for identifying service users’ views on the helpful and challenging aspects of psychological interventions to ensure that they meet the needs of people with intellectual disabilities. To consolidate this research, a systematic review using a meta-ethnographic approach was undertaken. A systematic search identified 16 relevant studies. These studies were reviewed, critically appraised and key themes were extracted. Five key concepts were identified: adapting to therapy, the therapeutic environment, group dynamics, the therapeutic relationship and the impact of therapy on life. The need for further consideration of power differentials within the therapeutic relationship and further adaptations to ensure accessibility of therapy for people with intellectual disabilities is discussed.
Partially Hydrolyzed Whey Infant Formula: Literature Review on Effects on Growth and the Risk of Developing Atopic Dermatitis in Infants from the General Population

Limited evidence is available regarding the effect of partially hydrolyzed whey-based formula (pHF-W) on growth and atopic dermatitis (AD) risk reduction in infants within the general infant population, and without a familial history of allergy as an inclusion or exclusion criterion. We reviewed the current evidence available from studies using pHF-W in the general population and summarized the data on safety (growth) and efficacy outcomes (reduction of AD), comparing the studies side by side. A total of 8 clinical trials were identified from the literature search, 7 of which used the same pHF-W. Six out of 8 studies indicated a reduction of atopic manifestations using a specific pHF-W versus cow’s milk formula (CMF) in the first years of life. Data were summarized and compared side by side for growth (3 studies) and efficacy (5 studies). In these diverse general populations, the results on growth and AD were consistent with the previous findings reported on infants with a family history of allergy, but numerous limitations to these studies were identified. This literature review confirms that pHF-W supports normal growth in infants, and suggests that the risk of AD may be reduced in not-fully breastfed infants from the general population when supplemented with a specific pHF-W when compared to CMF during the first 4–6 months of life. Further studies are warranted to confirm these results.
Antibodies to periodontogenic bacteria are associated with higher disease activity in lupus patients.

OBJECTIVES Microbial infections and mucosal dysbiosis influence morbidity in patients with systemic lupus erythematosus (SLE). In the oral cavity, periodontal bacteria and subgingival plaque dysbiosis provide persistent inflammatory stimuli at the mucosal surface. This study was undertaken to evaluate whether exposure to periodontal bacteria influences disease parameters in SLE patients. METHODS Circulating antibodies to specific periodontal bacteria have been used as surrogate markers to determine an ongoing bacterial burden, or as indicators of past exposure to the bacteria. Banked serum samples from SLE patients in the Oklahoma Lupus Cohort were used to measure antibody titres against periodontal pathogens (Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Treponema denticola) and commensals (Capnocytophaga ochracea, and Streptococcus gordonii) by ELISA. Correlations between anti-bacterial antibodies and different clinicalparameters of SLE including, autoantibodies (anti-dsDNA, anti-SmRNP, anti-SSA/Ro and anti-SSB/La), complement, and disease activity (SLEDAI and BILAG) were studied. RESULTS SLE patients had varying amounts of antibodies to different oral bacteria. The antibody titres against A. actinomycetemcomitans, P. gingivalis, T. denticola, and C. ochracea were higher in patients positive for anti-dsDNA antibodies, and they showed significant correlations with anti-dsDNA titres and reduced levels of complement. Among the periodontal pathogens, only antibodies to A. actinomycetemcomitans were associated with higher disease activity. CONCLUSIONS Our results suggest that exposure to specific pathogenic periodontal bacteria influences disease activity in SLE patients. These findings provide a rationale for assessing and improving periodontal health in SLE patients, as an adjunct to lupus therapies.
TGFβ1 regulates HGF‐induced cell migration and hepatocyte growth factor receptor MET expression via C‐ets‐1 and miR‐128‐3p in basal‐like breast cancer

Breast cancer is the most common cancer in women worldwide. The tumor microenvironment contributes to tumor progression by inducing cell dissemination from the primary tumor and metastasis. TGFβ signaling is involved in breast cancer progression and is specifically elevated during metastatic transformation in aggressive breast cancer. In this study, we performed genomewide correlation analysis of TGFBR2 expression in a panel of 51 breast cancer cell lines and identified that MET is coregulated with TGFBR2. This correlation was confirmed at the protein level in breast cancer cell lines and human tumor tissues. Flow cytometric analysis of luminal and basal‐like breast cancer cell lines and examination of 801 tumor specimens from a prospective cohort of breast cancer patients using reverse phase protein arrays revealed that expression of TGFBR2 and MET is increased in basal‐like breast cancer cell lines, as well as in triple‐negative breast cancer tumor tissues, compared to other subtypes. Using real‐time cell analysis technology, we demonstrated that TGFβ1 triggered hepatocyte growth factor (HGF)‐induced and MET‐dependent migration in vitro. Bioinformatic analysis predicted that TGFβ1 induces expression of C‐ets‐1 as a candidate transcription factor regulating MET expression. Indeed, TGFβ1‐induced expression of ETS1 and breast cancer cell migration was blocked by knockdown of ETS1. Further, we identified that MET is a direct target of miR‐128‐3p and that this miRNA is negatively regulated by TGFβ1. Overexpression of miR‐128‐3p reduced MET expression and abrogated HGF‐induced cell migration of invasive breast cancer cells. In conclusion, we have identified that TGFβ1 regulates HGF‐induced and MET‐mediated cell migration, through positive regulation of C‐ets‐1 and negative regulation of miR‐128‐3p expression in basal‐like breast cancer cell lines and in triple‐negative breast cancer tissue.
Assessment of Lung Cancer Risk on the Basis of a Biomarker Panel of Circulating Proteins

Importance There is an urgent need to improve lung cancer risk assessment because current screening criteria miss a large proportion of cases. Objective To investigate whether a lung cancer risk prediction model based on a panel of selected circulating protein biomarkers can outperform a traditional risk prediction model and current US screening criteria. Design, Setting, and Participants Prediagnostic samples from 108 ever-smoking patients with lung cancer diagnosed within 1 year after blood collection and samples from 216 smoking-matched controls from the Carotene and Retinol Efficacy Trial (CARET) cohort were used to develop a biomarker risk score based on 4 proteins (cancer antigen 125 [CA125], carcinoembryonic antigen [CEA], cytokeratin-19 fragment [CYFRA 21-1], and the precursor form of surfactant protein B [Pro-SFTPB]). The biomarker score was subsequently validated blindly using absolute risk estimates among 63 ever-smoking patients with lung cancer diagnosed within 1 year after blood collection and 90 matched controls from 2 large European population-based cohorts, the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Northern Sweden Health and Disease Study (NSHDS). Main Outcomes and Measures Model validity in discriminating between future lung cancer cases and controls. Discrimination estimates were weighted to reflect the background populations of EPIC and NSHDS validation studies (area under the receiver-operating characteristics curve [AUC], sensitivity, and specificity). Results In the validation study of 63 ever-smoking patients with lung cancer and 90 matched controls (mean [SD] age, 57.7 [8.7] years; 68.6% men) from EPIC and NSHDS, an integrated risk prediction model that combined smoking exposure with the biomarker score yielded an AUC of 0.83 (95% CI, 0.76-0.90) compared with 0.73 (95% CI, 0.64-0.82) for a model based on smoking exposure alone (P = .003 for difference in AUC). At an overall specificity of 0.83, based on the US Preventive Services Task Force screening criteria, the sensitivity of the integrated risk prediction (biomarker) model was 0.63 compared with 0.43 for the smoking model. Conversely, at an overall sensitivity of 0.42, based on the US Preventive Services Task Force screening criteria, the integrated risk prediction model yielded a specificity of 0.95 compared with 0.86 for the smoking model. Conclusions and Relevance This study provided a proof of principle in showing that a panel of circulating protein biomarkers may improve lung cancer risk assessment and may be used to define eligibility for computed tomography screening.