Miracle-dz/UniFAR-FTUs huggingface dataset:
Cardiovascular and Neural Adjustments to Exercise in Chronic Disease States Stimulation of spinal (cid:2) -opioid receptors attenuates the exercise pressor reﬂex in decerebrate rats

Kaufman MP. Stimulation of spinal (cid:2) -opioid receptors attenuates the exercise pressor reﬂex in decerebrate rats. Am J Physiol Regul Integr Comp Physiol 316: R727–R734, 2019. reﬂex arising from contracting hindlimb muscle is responsible in part for the increases in arterial pressure and heart rate evoked by exercise. The afferent arm of this reﬂex comprises group III and IV afferents. (cid:2) -Opioid receptors are expressed predominately on the spinal endings of group III afferents, whereas (cid:3) -opioid receptors are expressed predominately on the spinal endings of group IV afferents. Using stimuli that activated group III afferents, namely static contraction, calcaneal tendon stretch, and lactic acid injection into the superﬁcial epigastric artery, we tested the hypothesis that, in rats with either patent or ligated femoral arteries, activation of pre- and postsynaptic (cid:2) -opioid receptors in the dorsal horn attenuated pressor reﬂex responses to these stimuli. In rats with patent arteries or ligated femoral arteries, [ D -Pen 2,5 ]enkephalin (DPDPE), a (cid:2) -opioid agonist injected intrathecally (10 (cid:3) g in 10 (cid:3) l), signiﬁcantly attenuated the pressor responses to contraction, stretch, and lactic acid (all P (cid:4) 0.05). Naltrindole, a (cid:2) -opioid receptor antagonist, prevented the attenuation. In contrast, DPDPE did not attenuate the pressor response to capsaicin injection into the superﬁcial epigastric artery in either group of rats (both P (cid:5) 0.05). Intrathecal injection of saline (10 (cid:3) l), the vehicle for DPDPE, had no effect on the pressor responses in either group of rats. We conclude that activation of spinal (cid:2) -opioid receptors attenuates reﬂexes evoked by group III afferents in both freely perfused and ligated rats.
Racial Disparities in Sleep: Associations With Discrimination Among Ethnic/Racial Minority Adolescents.

This study investigates the same-day associations between discrimination and sleep among 350 adolescents ages 13-15 (M = 14.29, SD = 0.65; Asian = 41%, Black = 22%, Latinx = 37%). Assessing sleep duration, sleep onset latency, and wake minutes after sleep onset using wrist actigraphy, Black adolescents slept 35 min less than Asian and 36 min less than Latinx youth. Black adolescents suffered the most wake minutes after sleep onset, followed by Latinx and Asian youth. Latinx youth reported the highest levels of sleep disturbance, whereas Asian youth reported the highest levels of daytime dysfunction. Daily discrimination was associated with lower levels of same-night sleep onset latency, more sleep disturbance, more next-day daytime dysfunction, and higher next-day daytime sleepiness.
Altered Bacterial-Fungal Interkingdom Networks in the Guts of Ankylosing Spondylitis Patients

The human gut is colonized by diverse fungi (mycobiota), and fungi have long been suspected in the pathogenesis of SpA. Our study unraveled a disease-specific interkingdom network alteration in AS, suggesting that fungi, or the interkingdom interactions between bacteria and fungi, may play an essential role in AS development. However, our study is limited by sample size, and in-depth mechanism studies and additional large-scale investigations characterizing the gut mycobiome in AS patients are needed to form a foundation for research into the relationship between mycobiota dysbiosis and AS development. ABSTRACT Intestinal bacterial dysbiosis has been increasingly linked to ankylosing spondylitis (AS), which is a prototypic and best studied subtype of spondyloarthritis (SpA). Fungi and bacteria coexist in the human gut and interact with each other. Although they have been shown to contribute actively to health or disease, no studies have investigated whether the fungal microbiota in AS patients is perturbed. In this study, fecal samples from 22 AS patients, with clinical and radiographic assessments, and 16 healthy controls (HCs) were collected to systematically characterize the gut microbiota and mycobiota in AS patients by 16S rRNA gene- and ITS2-based DNA sequencing. Our results showed that the microbiota of AS patients was characterized by increased abundance of Proteobacteria and decreased Bacteroidetes, which was contributed by enrichment of Escherichia-Shigella, Veillonella, Lachnospiraceae NK4A136 group, and reduction of Prevotella strain 9, Megamona, and Fusobacterium. The gut mycobiota of AS patients was characterized by higher levels of Ascomycota, especially the class of Dothideomycetes, and decreased abundance of Basidiomycota, which was mainly contributed by the decease of Agaricales. Compared to HCs, decreased ITS2/16S biodiversity ratios and altered bacterial-fungal interkingdom networks were observed in AS patients. Compared with nonsteroidal anti-inflammatory drugs (NSAIDs), treating AS patients with biological agents induced obvious changes in the gut mycobiota, and this result was highly associated with disease activity indexes, including AS disease activity index (ASDAS) C-reactive protein (asCRP), erythrocyte sedimentation rate (ESR), and Bath AS disease activity index (BASDAI). In addition, altered mycobiota in AS patients was also found associated with the degree of radiographic damage. IMPORTANCE The human gut is colonized by diverse fungi (mycobiota), and fungi have long been suspected in the pathogenesis of SpA. Our study unraveled a disease-specific interkingdom network alteration in AS, suggesting that fungi, or the interkingdom interactions between bacteria and fungi, may play an essential role in AS development. However, our study is limited by sample size, and in-depth mechanism studies and additional large-scale investigations characterizing the gut mycobiome in AS patients are needed to form a foundation for research into the relationship between mycobiota dysbiosis and AS development.
Circulating Tumor Cells Identify Patients with Super-High-Risk Non-Muscle-Invasive Bladder Cancer: Updated Outcome Analysis of a Prospective Single-Center Trial.

BACKGROUND Clinical behavior of non-muscle-invasive bladder cancer (NMIBC) is largely unpredictable, and even patients treated according to European Association of Urology recommendations have a heterogeneous prognosis. High-grade T1 (HGT1) bladder cancer is the highest-risk subtype of NMIBC, with an almost 40% rate of recurrence and 20% of progression at 5 years. Nomograms predicting risk of recurrence, progression, and cancer-specific survival (CSS) are not available specifically within HGT1 bladder cancer, and the identification of robust prognostic biomarkers to better guide therapeutic strategies in this subgroup of patients is of paramount importance. Strategies to identify putative biomarkers in liquid biopsies from blood and urine collected from patients with bladder cancer have been intensively studied in the last few years. SUBJECTS, MATERIALS, AND METHODS We here report the final analysis of a single-center prospective study aimed to investigate the impact of circulating tumor cells (CTCs) on CSS and overall survival (OS) in 102 patients with HGT1 bladder cancer, in a median follow-up of 63 months. RESULTS We here demonstrate that the presence of even a single CTC is predictive of shorter CSS and OS, as compared with the standard predictive variables. Points of attention in this multivariable analysis are the long-term follow-up and the adequate number of outcome events. CONCLUSION The accurate risk stratification provided by CTCs might be essential for determining the best surveillance strategy for patients after diagnosis. A closer follow-up, an early radical surgery, or even a systemic treatment might be recommended in patients with super-high-risk non-muscle-invasive bladder cancer. IMPLICATIONS FOR PRACTICE Circulating tumor cells identify patients with super-high-risk non-muscle-invasive bladder cancer who require closer monitoring for local recurrence and/or progression of disease. This super-high-risk subgroup of patients might also require more aggressive treatment interventions, which should be evaluated in large prospective cohorts.
Nivolumab versus everolimus in advanced renal cell carcinoma: Japanese subgroup 3-year follow-up analysis from the Phase III CheckMate 025 study.

BACKGROUND Nivolumab treatment resulted in superior efficacy and safety versus everolimus treatment in the 2-year follow-up of the CheckMate 025 Phase III study, with consistent results in the global population and the Japanese population. Here, we report the 3-year follow-up in both groups. METHODS Patients were randomized 1:1 to nivolumab 3 mg/kg intravenously every 2 weeks or everolimus 10 mg orally once daily until progression/intolerable toxicity. The primary endpoint was overall survival (OS). Key secondary endpoints included objective response rate, progression-free survival, safety and patient-reported quality of life. RESULTS Of 410 and 411 patients randomized to nivolumab and everolimus, 37 and 26 were Japanese, respectively. The median OS for the global population was 25.8 months with nivolumab and 19.7 months with everolimus (hazard ratio 0.74; 95.5% confidence interval [CI]: 0.63-0.88; P = 0.0005); in the Japanese population, median OS was 45.9 months and not reached (hazard ratio 1.08; 95% CI: 0.50-2.34; P = 0.85), respectively. The investigator-assessed objective response rate was 26% versus 5% with nivolumab versus everolimus (odds ratio [OR] 6.19; 95% CI: 3.82-10.06) in the global population and 43% versus 8% in the Japanese population (OR 6.80; 95% CI: 1.60-28.91; P = 0.0035), respectively. The incidence of any-grade treatment-related adverse events was lower with nivolumab versus everolimus in both the global patient population (80% versus 89%) and the Japanese population (81% versus 100%). CONCLUSIONS At the 3-year follow-up, the efficacy and safety results of CheckMate 025 are generally consistent in the global and the Japanese populations.
Analysis of the reaction and behavior of nurses after training on young child feeding.

OBJECTIVE to assess the reaction and behavior of nurses after training on the use of educational tool to promote heathy nutrition to children. METHOD pilot assessment study, of descriptive and quantitative approach, carried out in 2014 with eight nurses from the rural area of Ceará, Brazil, by observing a training workshop on the use of the serial album "Alimentos regionais: promovendo a segurança alimentar na promoção da alimentação infantil saudável" [Regional food: promoting food safety through child healthy feeding]. RESULTS the analysis of the reaction of nurses to the workshop showed that all of them (100%) were satisfied with the training. In behavior analysis, more than a half of the nurses have achieved the expected performance when implementing the illustrations of the serial album, seven of them (87.5%) being considered able to use the serial album. CONCLUSION the training was considered effective, as all the participant nurses were satisfied and most of them considered capable of using the educational tool in promoting child healthy feeding.
Indoxyl Sulfate and p-Cresyl Sulfate Promote Vascular Calcification and Associate with Glucose Intolerance.

BACKGROUND Protein-bound uremic toxins indoxyl sulfate (IS) and p-cresyl sulfate (PCS) have been associated with cardiovascular morbidity and mortality in patients with CKD. However, direct evidence for a role of these toxins in CKD-related vascular calcification has not been reported. METHODS To study early and late vascular alterations by toxin exposure, we exposed CKD rats to vehicle, IS (150 mg/kg per day), or PCS (150 mg/kg per day) for either 4 days (short-term exposure) or 7 weeks (long-term exposure). We also performed unbiased proteomic analyses of arterial samples coupled to functional bioinformatic annotation analyses to investigate molecular signaling events associated with toxin-mediated arterial calcification. RESULTS Long-term exposure to either toxin at serum levels similar to those experienced by patients with CKD significantly increased calcification in the aorta and peripheral arteries. Our analyses revealed an association between calcification events, acute-phase response signaling, and coagulation and glucometabolic signaling pathways, whereas escape from toxin-induced calcification was linked with liver X receptors and farnesoid X/liver X receptor signaling pathways. Additional metabolic linkage to these pathways revealed that IS and PCS exposure engendered a prodiabetic state evidenced by elevated resting glucose and reduced GLUT1 expression. Short-term exposure to IS and PCS (before calcification had been established) showed activation of inflammation and coagulation signaling pathways in the aorta, demonstrating that these signaling pathways are causally implicated in toxin-induced arterial calcification. CONCLUSIONS In CKD, both IS and PCS directly promote vascular calcification via activation of inflammation and coagulation pathways and were strongly associated with impaired glucose homeostasis.
T cell and antibody functional correlates of severe COVID-19

Comorbid medical illnesses, such as obesity and diabetes, are associated with more severe COVID-19, hospitalization, and death. However, the role of the immune system in mediating these clinical outcomes has not been determined. We used multi-parameter flow cytometry and systems serology to comprehensively profile the functions of T cells and antibodies targeting spike, nucleocapsid, and envelope proteins in a convalescent cohort of COVID-19 subjects who were either hospitalized (n=20) or not hospitalized (n=40). To avoid confounding, subjects were matched by age, sex, ethnicity, and date of symptom onset. Surprisingly, we found that the magnitude and functional breadth of virus-specific CD4 T cell and antibody responses were consistently higher among hospitalized subjects, particularly those with medical comorbidities. However, an integrated analysis identified more coordination between polyfunctional CD4 T-cells and antibodies targeting the S1 domain of spike among subjects that were not hospitalized. These data reveal a functionally diverse and coordinated response between T cells and antibodies targeting SARS-CoV-2 which is reduced in the presence of comorbid illnesses that are known risk factors for severe COVID-19. Our data suggest that isolated measurements of the magnitudes of spike-specific immune responses are likely insufficient to anticipate vaccine efficacy in high-risk populations.
Sensitivity analysis of FDA´s benchmark nozzle regarding in vitro imperfections - Do we need asymmetric CFD benchmarks?

Abstract Modern technologies and methods such as computer simulation, so-called in silico methods, foster the development of medical devices. For accelerating the uptake of computer simulations and to increase credibility and reliability the U.S. Food and Drug Administration organized an inter-laboratory round robin study of a generic nozzle geometry. In preparation of own bench testing experiment using Particle Image Velocimetry, a custom made silicone nozzle was manufactured. By using in silico computational fluid dynamics method the influence of in vitro imperfections, such as inflow variations and geometrical deviations, on the flow field were evaluated. Based on literature the throat Reynolds number was varied Rethroat = 500 ± 50. It could be shown that the flow field errors resulted from variations of inlet conditions can be largely eliminated by normalizing if the Reynolds number is known. Furthermore, a symmetric imperfection of the silicone model within manufacturing tolerance does not affect the flow as much as an asymmetric failure such as an unintended curvature of the nozzle. In brief, we can conclude that geometrical imperfection of the reference experiment should be considered accordingly to in silico modelling. The question arises, if an asymmetric benchmark for biofluid analysis needs to be established. An eccentric nozzle benchmark could be a suitable case and will be further investigated.
Ginsenoside Rg5 induces apoptosis in human esophageal cancer cells through the phosphoinositide-3 kinase/protein kinase B signaling pathway

The role of ginsenoside in the prevention of cancer has been well established. Ginsenoside Rg5 is one of the main components isolated from red ginseng, which has been demonstrated to have anti-tumor effects by inhibiting cell proliferation and causing DNA damage. However, the role of ginsenoside Rg5 and its molecular mechanisms remain unclear in human esophageal cancer. In the present study, Rg5 was investigated as a novel drug for the chemotherapy of esophageal cancer in in vitro experiments. Esophageal cancer Eca109 cells were exposed to various concentrations of ginsenoside Rg5 (0–32 µΜ) for 24 h. Subsequent cell proliferation assays demonstrated that treatment with ginsenoside Rg5 resulted in the dose-dependent inhibition of proliferation, while a significant increase in apoptotic rate and increased activities of caspase-3, −8 and −9 were observed. In addition, the mitochondrial membrane potential was decreased and the cytoplasmic free calcium level increased following treatment with ginsenoside Rg5. Furthermore, the expression of B-cell lymphoma 2 and phosphorylated-protein kinase B (p-Akt) decreased. The specific phosphoinositide-3 kinase (PI3K) inhibitor LY294002 promoted this effect, while insulin-like growth factor-1, a specific PI3K activator, inhibited this action. Taken together, the results suggested that ginsenoside Rg5 may have a tumor-suppressive effect on esophageal cancer by promoting apoptosis and may be associated with the downregulation of the PI3K/Akt signaling pathway.
Phenotypic Heterogeneity in Tumor Progression, and Its Possible Role in the Onset of Cancer

Heterogeneity among isogenic cells/individuals has been known for at least 150 years. Even Mendel, working on pea plants, realized that not all tall plants were identical. However, Mendel was more interested in the discontinuous variation between genetically distinct individuals. The concept of environment dictating distinct phenotypes among isogenic individuals has since been shown to impact the evolution of populations in numerous examples at different scales of life. In this review, we discuss how phenotypic heterogeneity and its evolutionary implications exist at all levels of life, from viruses to mammals. In particular, we discuss how a particular disease condition (cancer) is impacted by heterogeneity among isogenic cells, and propose a potential role that phenotypic heterogeneity might play toward the onset of the disease.
Bioactive Components and Radical Scavenging Activity in Selected Advance Lines of Salt-Tolerant Vegetable Amaranth

Four selected advance lines of salt-tolerant vegetable amaranth were evaluated for proximate, nutraceuticals, pigments, phytochemicals, and antioxidants components antioxidants activity in completely randomized block design (RCBD) design in three replicates. Salt-tolerant vegetable amaranth contained adequate carbohydrates, protein, moisture, and dietary fiber. The remarkable contents of iron, manganese, copper, zinc, sodium, molybdenum, boron, potassium, calcium, magnesium, phosphorus, sulfur, betacyanins, betalains, betaxanthins, chlorophylls, ascorbic acid, polyphenols, flavonoids, and antioxidant potentiality were found in salt-tolerant vegetable amaranth. The genotypes LS7 and LS9 had abundant proximate, nutraceuticals, pigments, phytochemicals, and antioxidants compared to the genotypes LS3 and LS5. Salt-tolerant vegetable amaranth demonstrated high content of flavonoid compounds including flavonols such as rutin, kaempferol, isoquercetin, myricetin, hyperoside, and quercetin; flavanol, such as catechin; flavone such as apigenin; and flavanone, such as naringenin. For the first time, we identified one flavonol such as myricetin; one flavanol, such as catechin; one flavone such as apigenin; and one flavanone, such as naringenin in salt-tolerant vegetable amaranth. Across six flavonols, rutin and quercetin were identified as the most prominent compounds followed by isoquercetin and myricetin in selected salt-tolerant vegetable amaranths. Across the genotypes, LS7 exhibited the highest flavonols such as rutin, kaempferol, isoquercetin, myricetin, hyperoside, and quercetin as well as the highest flavanols, such as catechin; flavones such as apigenin; and flavanones, such as naringenin. It revealed from the correlation study that antioxidant components of salt-tolerant vegetable amaranth genotypes exhibited good radical quenching capacity of 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) and 2,2-diphenyl-1-picrylhydrazyl equivalent to Trolox. The two genotypes LS7 and LS9 of vegetable amaranth containing excellent sources of proximate, nutraceuticals, pigments, phytochemicals, and antioxidants components could be used as potent antioxidants to attaining nutrients and antioxidant sufficiency in the saline prone area of the globe. We can extract colorful juice from the genotypes LS7 and LS9 as drink purposes for consuming the nutraceuticals and antioxidant deficient community in the saline prone area around the world. However, further detail experimentation is required to confirm the standardization and stabilization of functional components of vegetable amaranth for extraction of juice as drinks.
First report and phylogenetic analysis of porcine deltacoronavirus in Mexico

Abstract Porcine deltacoronavirus has caused great economic losses in the swine industry worldwide. In this study, we carried out the first detection, sequencing and characterization of this virus in Mexico. We analysed 885 rectal samples by multiplex RT‐PCR to determine coinfections. In addition, the Spike gene was amplified, sequenced and analysed phylogenetically. We found 85 positive samples for porcine deltacoronavirus, representing 9.6% of the total samples, and we determined that the most frequent coinfection was with porcine epidemic diarrhoea virus (54.1%). Four sequences of Mexican isolates were most closely related to those of the United States. The antigenic regions and the glycosylation site of the strains obtained coincide with those previously reported. This relationship is probably related to the commercial exchange of pigs between the US and Mexico and the geographical proximity of these two countries.
Hikes and Levadas in Madeira: Characterizing Visitors and their experience

Abstract Recent research indicates that more and more often tourists use the Madeira Natural Park (MNP) area to develop their physical activity, through mountain hiking and Levada walks. This study aims at identifying tourists’ characteristics and to understand how visitors live their experience. A survey was carried out at the end of two different activities and the sample was divided into two groups (G1: Levada Walks in the Laurissilva; G2: Walks outside the Laurissilva). The data was collected immediately after the activity ended (total: 293; male: 124; female: 169) and people were asked about: 1. Information available at the start of the activity; 2. Interaction and attention demand; 3. Natural area visited. The data indicates that the Madeira tourists have higher education, many are students and teachers, the majority being European. Our tourists are well informed about the natural environment and more than 90% agreed that it was ideal for aesthetic enjoyment and inspiring exploration. Our findings can help the tourist agents to improve their products, encourage the agencies to attract new markets outside Europe and can work as a basis for providing more guidance in the MNP, promoting a higher ‘flow experience’.