Miracle-dz/UniFAR-FTUs huggingface dataset:
Zoledronic Acid Abrogates Restraint Stress-Induced Macrophage Infiltration, PDGF-AA Expression, and Ovarian Cancer Growth

Simple Summary Biobehavioral disorders can negatively impact patients with ovarian cancer. Growing evidence suggests that chronic stress can promote tumor progression, the release of inflammatory mediators, and macrophage infiltration into the tumor. However, the role of stress hormones in regulating cancer cell/macrophage crosstalk remains unclear. This study aimed to assess the role of stress hormone-stimulated macrophages in modulating inflammatory networks and ovarian cancer biology. Our data show that stress hormones induced secretion of inflammatory proteins in ovarian cancer cell/macrophage co-cultures. Furthermore, we show that restraint stress leads to cancer growth, macrophage infiltration, and PDGF-AA protein expression in animal models of ovarian cancer. Conversely, zoledronic acid was able to prevent the effects of restraint stress on ovarian cancer growth. Overall, our data suggest a role for stress hormone-stimulated macrophages in ovarian cancer progression and suggest the involvement of PDGF-AA as a key mediator of this process. Abstract Multiple studies suggest that chronic stress accelerates the growth of existing tumors by activating the sympathetic nervous system. Data suggest that sustained adrenergic signaling can induce tumor growth, secretion of pro-inflammatory cytokines, and macrophage infiltration. Our goal was to study the role of adrenergic-stimulated macrophages in ovarian cancer biology. Cytokine arrays were used to assess the effect of adrenergic stimulation in pro-tumoral cytokine networks. An orthotopic model of ovarian cancer was used to assess the in vivo effect of daily restraint stress on tumor growth and adrenergic-induced macrophages. Cytokine analyses showed that adrenergic stimulation modulated pro-inflammatory cytokine secretion in a SKOV3ip1 ovarian cancer cell/U937 macrophage co-culture system. Among these, platelet-derived growth factor AA (PDGF-AA), epithelial cell-derived neutrophil-activating peptide (ENA-78), Angiogenin, vascular endothelial growth factor (VEGF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-5 (IL-5), Lipocalin-2, macrophage migration inhibitory factor (MIF), and transferrin receptor (TfR) were upregulated. Enriched biological processes included cytokine-mediated signaling pathways and positive regulation of cell proliferation. In addition, daily restraint stress increased ovarian cancer growth, infiltration of CD68+ macrophages, and expression of PDGF-AA in orthotopic models of ovarian cancer (SKOV3ip1 and HeyT30), while zoledronic acid, a macrophage-depleting agent, abrogated this effect. Furthermore, in ovarian cancer patients, high PDGFA expression correlated with worse outcomes. Here, it is shown that the adrenergic regulation of macrophages and PDGFA might play a role in ovarian cancer progression.
Impact of Proton Beam Irradiation on the Growth and Biochemical Indexes of Barley (Hordeum vulgare L.) Seedlings Grown under Salt Stress

The present paper examines the effects of salt stress on the growth, pigments, lipid peroxidation and antioxidant ability of barley (Hordeum vulgare L.) seedlings raised from proton beam irradiated caryopses. In order to assess the effects of radiation on the early stages of plant growth and analyze its possible influence on the alleviation of salinity, 3 and 5 Gy doses were used on dried barley seeds and germination occurred in the presence/absence of NaCl (100 mM and 200 mM). After treatment, photosynthetic pigments increased in the 5 Gy variant, which registered a higher value than the control. Among the antioxidant enzymes studied (SOD, CAT, and POD) only CAT activity increased in proton beam irradiated seeds germinated under salinity conditions, which indicates the activation of antioxidant defense. The malondialdehyde (MDA) content declined with the increase of irradiation doses on seeds germinated at 200 mM NaCl. On the other hand, the concentration of 200 mM NaCl applied alone or combined with radiation revealed an increase in soluble protein content. The growth rate suggests that 3 Gy proton beam irradiation of barley seeds can alleviate the harmful effects of 100 mM NaCl salinity, given that seedlings’ growth rate increased by 1.95% compared to the control.
Impact of Different Stoppers on the Composition of Red and Rosé Lagrein, Schiava (Vernatsch) and Merlot Wines Stored in Bottle

Different technical cork stoppers (blend of natural cork microgranules, one-piece natural cork, agglomerated natural cork, technical cork 1+1) were compared to evaluate the effects on the phenolic, volatile profiles and dissolved oxygen in three red (Merlot, Lagrein red, St. Magdalener) and one rosé (Lagrein rosé) wines, which were stored in bottles for 12 months. Gallic acid, caffeic acid, p-coumaric acid, trans-resveratrol, glutahionyl caftaric acid and protocatechuic acid did not vary remarkably during the first three months, whereas at six months a net increase was reported, followed by a clear decrease at 12 months. The same trend was observed in Lagrein rosé, but only for gallic acid. The total anthocyanins content decreased during the storage period in the four wines. Isopentyl acetate, 1-hexanol, ethyl hexanoate, 2-phenylethyl alcohol, diethyl succinate, ethyl octanoate and ethyl decanoate were the main volatile compounds. The sum of alcohols decreased in all four of the wines. The esters decreased in Merlot; however, they increased in Lagrein rosé, Lagrein red and St. Magdalener during the storage. Univariate and multivariate statistics and a sensory discriminant triangle test displayed similar influences of the different stoppers on the phenolic and volatile compounds during the whole storage duration. The changes detected in the phenolic and volatile concentrations were presumably due to the non-oxygen-mediated reactions occurring during 12 months of storage in bottle.
Test-retest reliability of spatial navigation in adults at-risk of Alzheimer’s disease

The Virtual Supermarket Task (VST) and Sea Hero Quest detect high-genetic-risk Alzheimer`s disease (AD). We aimed to determine their test-retest reliability in a preclinical AD population. Over two time points, separated by an 18-month period, 59 cognitively healthy individuals underwent a neuropsychological and spatial navigation assessment. At baseline, participants were classified as low-genetic-risk of AD or high-genetic-risk of AD. We calculated two-way mixed effects intraclass correlation coefficients (ICC) for task parameters and used repeated measures ANOVAS to determine whether genetic risk or sex contributed to test-retest variability. The egocentric parameter of the VST measure showed the highest test–retest reliability (ICC = .72), followed by the SHQ distance travelled parameter (ICC = .50). Post hoc longitudinal analysis showed that boundary-based navigation predicts worsening episodic memory concerns in high-risk (F = 5.01, P = 0.03), but in not low-risk, AD candidates. The VST and the Sea Hero Quest produced parameters with acceptable test-retest reliability. Further research in larger sample sizes is desirable.
Methrotexate Treatment Inmunomodulates Abnormal Cytokine Expression by T CD4 Lymphocytes Present in DMARD-Naïve Rheumatoid Arthritis Patients

CD4+T-lymphocytes are relevant in the pathogenesis of rheumatoid arthritis (RA), however, their potential involvement in early RA remains elusive. Methotrexate (MTX) is a commonly used disease-modifying antirheumatic drug (DMARD), but its mechanism has not been fully established. In 47 new-onset DMARD-naïve RA patients, we investigated the pattern of IFNγ, IL-4 and IL-17A expression by naïve (TN), central (TCM), effector memory (TEM) and effector (TE) CD4+ subsets; their STAT-1, STAT-6 and STAT-3 transcription factors phosphorylation, and the circulating levels of IFNγ, IL-4 and IL-17. We also studied the RA patients after 3 and 6 months of MTX treatment and according their clinical response. CD4+T-lymphocyte subsets and cytokine expression were measured using flow cytometry. New-onset DMARD-naïve RA patients showed a significant expansion of IL-17A+, IFNγ+ and IL-17A+IFNγ+ CD4+T-lymphocyte subsets and increased intracellular STAT-1 and STAT-3 phosphorylation. Under basal conditions, nonresponder patients showed increased numbers of circulating IL-17A producing TN and TMC CD4+T-lymphocytes and IFNγ producing TN, TCM, TEM CD4+T-lymphocytes with respect to responders. After 6 months, the numbers of CD4+IL-17A+TN remained significantly increased in nonresponders. In conclusion, CD4+T-lymphocytes in new-onset DMARD-naïve RA patients show IL-17A and IFNγ abnormalities in TN, indicating their relevant role in early disease pathogenesis. Different patterns of CD4+ modulation are identified in MTX responders and nonresponders.
Antioxidants in Sport Sarcopenia

The decline of skeletal muscle mass and strength that leads to sarcopenia is a pathology that might represent an emergency healthcare issue in future years. Decreased muscle mass is also a condition that mainly affects master athletes involved in endurance physical activities. Skeletal muscles respond to exercise by reshaping the biochemical, morphological, and physiological state of myofibrils. Adaptive responses involve the activation of intracellular signaling pathways and genetic reprogramming, causing alterations in contractile properties, metabolic status, and muscle mass. One of the mechanisms leading to sarcopenia is an increase in reactive oxygen and nitrogen species levels and a reduction in enzymatic antioxidant protection. The present review shows the recent experimental models of sarcopenia that explore molecular mechanisms. Furthermore, the clinical aspect of sport sarcopenia will be highlighted, and new strategies based on nutritional supplements, which may contribute to reducing indices of oxidative stress by reinforcing natural endogenous protection, will be suggested.
Higher infiltration of intratumoral CD25+ FOXP3+ lymphocytes correlates with a favorable prognosis in patients with diffuse large B-cell lymphoma

Abstract Regulatory T-cells (Tregs) play an important role in cancer immunity but their prognostic impact is controversial in diffuse large B-cell lymphoma (DLBCL). Intratumoral Tregs in DLBCL (n = 70) were evaluated by double-stained CD25 and FOXP3 lymphocytes in formalin-fixed paraffin-embedded tissues, and correlated with clinicopathologic features. We found that increased numbers of intratumoral FOXP3+ lymphocytes (>2.4/HPF) and CD25 + FOXP3+ lymphocytes (>0.8/HPF) are favorable prognosticators (p = .004 and p < .001, respectively) in DLBCL patients, along with age <70 years, stage I–II disease, normal serum LDH level and low IPI scores (p < .001, .002, .002, and <.001, respectively). On multivariate analyses, a higher number of CD25 + FOXP3+ lymphocytes retained prognostic significance (p = .040). Interestingly, higher Treg infiltration correlated with increased infiltration by cytotoxic T-lymphocytes (γ = 0.294, p = .038) and nodal location (γ = 0.390, p = .004), but not with infiltration by CD123+ plasmacytoid dendritic cells, which were reported to induce Tregs with immune tolerance. Therefore, congruent with literature meta-analyses, higher intratumoral CD25 + FOXP3+ lymphocytes have a beneficial impact on DLBCL.
Absence of norovirus contamination in shellfish harvested and commercialized in the Northeast coast of Brazil

Norovirus (NoV) is the main cause of gastroenteritis outbreaks worldwide. Although NoV spreads mainly from person to person, it is estimated that a large proportion of NoV outbreaks are caused by foodborne transmission. Bivalve mollusks are one of the most important foods involved in NoV transmission to humans. Little is known about NoV prevalence in shellfish harvested and commercialized in Brazil. The aim of this study was to map, for the first time, the distribution of NoV contamination in oysters and mussels harvested and commercialized in the coast of Pernambuco state, northeast Brazil. A total of 380 mollusks (260 oysters and 120 mussels) were collected between February and August 2017 either directly from harvesting areas or obtained from beach vendors at 17 sites in Pernambuco. Samples were processed and tested for NoV contamination using a SYBR Green real-time PCR assay. All samples were negative for NoV GI or GII contamination, suggesting a low risk of NoV contamination from this food source during the study period. Additional surveys in different areas of the Brazilian coast are warranted to monitor the risk of NoV infection upon seafood consumption.
Comparison of Two Assessment Tools for Hospitalized Subjects With Asthma

BACKGROUND: Pediatric Asthma Assessment tools used to guide the weaning of inhaled therapies during inpatient hospitalization require further evaluation and validation. This study aimed to compare 2 asthma assessment tools: an asthma scale versus an asthma score. METHODS: A prospective, physician-blinded, comparison study was conducted in 2 separate 6-week phases of patients > 2 y old admitted to a tertiary care children's hospital with status asthmaticus between July and November 2014. The asthma scale categorized 5 components (oxygen, auscultation, dyspnea, breathing frequency, and pulse oximetry) into 1 of 3 respiratory assessments: mild, moderate, or severe. The asthma score used a sum of the components, resulting in a score of 1–15. Study tool predictability was measured using a metric based on hours on continuous albuterol, with area under the curve ≥ 0.8 indicating good predictability. Agreement between clinicians was measured using the Cohen kappa statistic. Study tool clinical correlation was measured using Spearman coefficient. Usability was evaluated using web-based surveys. RESULTS: Phase 1 included 1,971 assessments (97 unique subjects), whereas phase 2 included 607 assessments (69 unique subjects). Using the continuous albuterol metric, predictability of the asthma scale had an area under the curve of 0.62 versus the asthma score area under the curve of 0.80. Agreement early in hospitalization for the asthma scale was kappa = 0.34 (95% CI 0.18–0.5; n = 84) versus kappa = 0.55 (95% CI 0.35–0.76; n = 44) for the asthma score. Agreement late in hospitalization for the asthma scale was kappa = 0.38 (95% CI 0.17–0.59; n = 66) versus kappa = 0.41 (95% CI 0.13–0.69; n = 33) for the asthma score. Clinical correlation for the asthma scale (no. = 1,908) was r = 0.57 (P < .001) versus r = 0.80 (P < .001) for the asthma score (no. = 558). Mean asthma scale usability was 3.38 versus 3.68 for the asthma score. CONCLUSIONS: The asthma score showed better clinical predictability and clinical correlation compared to the asthma scale. Numerical scores provided more objective assessments compared to categorical scores. Validated scoring tools such as the asthma score are crucial to the success of management of inpatient asthma care.
Characterization of a New Set of Microsatellite Markers Suggests Polygyny and Polyandry in Atta cephalotes (Hymenoptera: Formicidae)

Abstract The leaf-cutting ant, Atta cephalotes L. (1758), is a major herbivore with great economic impact in the Neotropics. Because of its broad range and human-mediated dissemination, the ecology of this ant has received considerable attention; however, questions concerning its population genetics, dispersal, and social structure remain unexplored. Here, we aimed to identify and provide information on molecular and statistical performance of a suite of polymorphic microsatellite markers for A. cephalotes while demonstrating their utility for further genetic studies.We designed primer sequences targeting thousands of microsatellite loci and then screened 30 of these for amplification and polymorphism. Fifteen of these loci were selected and used to evaluate their polymorphism using 74 ants sampled from 15 different nests of the same location. This set of 15 loci exhibited variation of 2–20 alleles, with a mean heterozygosity of 0.57. All loci followed Hardy–Weinberg expectations with no evidence of linkage disequilibrium, while two loci showed evidence of null alleles. Our preliminary analysis suggested substantial nest differentiation with no population viscosity within the sampled location, as well as colonies with multiple queens (polygyny) and paternity (polyandry). Our newly identified microsatellites have proven to be highly informative to investigate gene flow, social structure and reproduction of this key agricultural pest.
Antigen-Specific Cytokine and Chemokine Gene Expression for Diagnosing Latent and Active Tuberculosis

Tuberculosis infection exhibits different forms, namely, pulmonary, extrapulmonary, and latent. Here, diagnostic markers based on the gene expression of cytokines and chemokines for differentiating between tuberculosis infection state(s) were identified. Gene expression of seven cytokines (Interferon gamma (IFN-γ), Interferon gamma-induced protein 10 (IP-10), Interleukin-2 receptor (IL-2R), C-X-C Motif Chemokine Ligand 9 (CXCL-9), Interleukin 10 (IL-10), Interleukin 4 (IL-4), and Tumor Necrosis Factor alpha (TNF-α)) in response to tuberculosis antigen was analyzed using real-time polymerase reaction. The sensitivity and specificity of relative quantification (2^-ΔΔCt) of mRNA expression were analyzed by constructing receiver operating characteristic curves and measuring the area under the curve (AUC) values. Combinations of cytokines were analyzed using the R statistical software package. IFN-γ, IP-10, IL2R, and CXCL-9 showed high expression in latent and active tuberculosis patients (p = 0.001), with a decrease in IL10 expression, and no statistical difference in IL-4 levels among all the groups (p = 0.999). IL-10 differentiated pulmonary tuberculosis patients from latent cases with an AUC of 0.731. IL10 combined with CXCL-9 distinguished pulmonary tuberculosis patients from extrapulmonary cases with a sensitivity, specificity, and accuracy of 85.7%, 73.9%, and 81.0%, respectively. IL-10 together with IP-10 and IL-4 differentiated pulmonary tuberculosis from latent cases with a sensitivity and specificity of 77.1% and 88.1%, respectively. Decision tree analysis demonstrated that IFN-γ IL-2R, and IL-4 can diagnose tuberculosis infection with a sensitivity, specificity, and accuracy of 89.7%, 96.1%, and 92.7%, respectively. A combination of gene expression of cytokines and chemokines might serve as an effective marker to differentiate tuberculosis infection state(s).
Micronutrient Fertilization of Greenhouse Cucumbers Mitigates Pirimicarb Resistance in Aphis gossypii (Hemiptera: Aphididae)

Abstract The nutritional status of host plants can have direct impacts on herbivore physiology and insect–plant interactions. We investigated the effect of micronutrients, including manganese, iron, zinc, and copper, on cucumber plant physiology, and on the biology and physiology of a strain of Aphis gossypii Glover selected over 12 generations to be resistant to pirimicarb. The micronutrient treatment increased the activity of superoxide dismutase, ascorbate peroxidase, guaiacol peroxidase, polyphenol oxidase, and phenylalanine ammonia-lyase in cucumber plants, and also increased levels of total phenolics, hydrogen peroxide, salicylic acid, and total chlorophyl, whereas malondialdehyde levels were unaffected. Pirimicarb-resistant cotton aphids that fed on micronutritient-amended cucumber plants expressed significantly decreased levels of acetylcholinesterase and detoxifying enzymes, specifically glutathione S-transferase, and carboxylesterase. Analysis of energy reserves in resistant A. gossypii fed on micronutritient-amended plants revealed decreases in the lipid and protein contents of aphids, whereas glycogen and carbohydrate contents showed no response. Resistant cotton aphids fed on micronutritient-amended plants showed significantly reduced fecundity, longevity, and reproductive periods, and a 1.7-fold reduction in pirimicarb LC50 compared with those fed on control plants. We conclude that micronutrient amendment negatively impacts the biological performance of insecticide-resistant cotton aphids, and diminishes their resistance to pirimicarb. Both direct effects on plant health, such as enhanced inducible defenses, and indirect effects on aphid fitness, such as reduced biological performance and detoxification abilities, were implicated. Therefore, optimization of micronutrient amendments could be a useful complement to other tactics for managing insecticide-resistant A. gossypii on cucumbers, and warrants exploration in other contexts.
Gamma radiation LD 50 determination in Heliconia bihai (Heliconiaceae) explants

SUMMARY The high economic importance of ornamental plants represents a stimulus for breeders in the research for new cultivars. Among the several employed techniques, gamma radiation induced mutation can bring promising results in Heliconia species. The 50 % lethal dose (LD 50) determination, in in vitro Heliconia bihai cultivation, is the initial step for utilization of that breeding method. The doses: 0; 10; 20; 30; 40 and 50 Gy gamma ray in 25 shoot apexes were tested. The results indicated that LD 50, for this in vitro culture, ranges between 30 and 40 Gy.
Genomics and Pharmacogenomics Knowledge, Attitude and Practice of Pharmacists Working in United Arab Emirates: Findings from Focus Group Discussions—A Qualitative Study

(1) Background: Genomics and pharmacogenomics are relatively new fields in medicine in the United Arab Emirates (UAE). Understanding the knowledge, attitudes and current practices among pharmacists is an important pillar to establish the roadmap for implementing genomic medicine and pharmacogenomics; (2) Methods: A qualitative method was used, with focus group discussions (FGDs) being conducted among pharmacists working in public and private hospitals in Abu Dhabi Emirate. Snowball sampling was used. Thematic inductive analysis was performed by two researchers independently. NVIVO software was used to establish the themes; (3) Results: Lack of knowledge of genomics and pharmacogenomics among pharmacists was one of the most prominent findings. Therefore, the role of pharmacist in making the right decisions was highlighted to be a barrier for pharmacogenomics implementation in the UAE. Pharmacists have a positive attitude toward pharmacogenomics, but they are preoccupied with concern of confidentiality. In addition, religion and culture shadowed their attitudes toward genetic testing; (4) Conclusions: It is highly recommended to introduce new courses and training workshops for healthcare providers to improve the opportunities for genomics and pharmacogenomics application in the UAE. Pharmacists agreed that the health authorities should take the lead for improving trust and confidence in the system for a better future in the era of genomics and pharmacogenomics.