Miracle-dz/UniFAR-FTUs huggingface dataset:
Superior Effects of High-Intensity Interval vs. Moderate-Intensity Continuous Training on Endothelial Function and Cardiorespiratory Fitness in Patients With Type 1 Diabetes: A Randomized Controlled Trial

This study aimed to compare the effect of high-intensity interval training (HIIT) with moderate-intensity continuous training (MCT) on endothelial function, oxidative stress and clinical fitness in patients with type 1 diabetes. Thirty-six type 1 diabetic patients (mean age 23.5 ± 6 years) were randomized into 3 groups: HIIT, MCT, and a non-exercising group (CON). Exercise was performed in a stationary cycle ergometers during 40 min, 3 times/week, for 8 weeks at 50–85% maximal heart rate (HRmax) in HIIT and 50% HRmax in MCT. Endothelial function was measured by flow-mediated dilation (FMD) [endothelium-dependent vasodilation (EDVD)], and smooth-muscle function by nitroglycerin-mediated dilation [endothelium-independent vasodilation (EIVD)]. Peak oxygen consumption (VO2peak) and oxidative stress markers were determined before and after training. Endothelial dysfunction was defined as an increase < 8% in vascular diameter after cuff release. The trial is registered at ClinicalTrials.gov, identifier: NCT03451201. Twenty-seven patients completed the 8-week protocol, 9 in each group (3 random dropouts per group). Mean baseline EDVD was similar in all groups. After training, mean absolute EDVD response improved from baseline in HIIT: + 5.5 ± 5.4%, (P = 0.0059), but remained unchanged in MCT: 0.2 ± 4.1% (P = 0.8593) and in CON: −2.6 ± 6.4% (P = 0.2635). EDVD increase was greater in HIIT vs. MCT (P = 0.0074) and CON (P = 0.0042) (ANOVA with Bonferroni). Baseline VO2peak was similar in all groups (P = 0.96). VO2peak increased 17.6% from baseline after HIIT (P = 0.0001), but only 3% after MCT (P = 0.055); no change was detected in CON (P = 0.63). EIVD was unchanged in all groups (P = 0.18). Glycemic control was similar in all groups. In patients with type 1 diabetes without microvascular complications, 8-week HIIT produced greater improvement in endothelial function and physical fitness than MCT at a similar glycemic control.
Tomato SlWRKY3 acts as a positive regulator for resistance against the root-knot nematode Meloidogyne javanica by activating lipids and hormone-mediated defense-signaling pathways

ABSTRACT Diseases caused by plant-parasitic nematodes in vegetables, among them Meloidogyne spp. root-knot nematodes (RKNs), lead to extensive yield decline. A molecular understanding of the mechanisms underlying plants’ innate resistance may enable developing safe alternatives to harmful chemical nematicides in controlling RKNs. A tight relationship has been revealed between the WRKY transcription factors and RKN parasitism on tomato roots. We investigated the function role of tomato SlWRK3 and SlWRKY35 in regulating nematode disease development. Using promoter–GUS reporter gene fusions, we show that both SlWRKY3 and SlWRKY35 are induced within 5 days of infection and through feeding-site development and gall maturation, with a much stronger response of the former vs. the latter to nematode infection. Histological analysis of nematode-feeding sites indicated a high expression of SlWRKY3 in developing and mature feeding cells and associated vasculature cells, whereas SlWRKY35 expression was only observed in mature feeding sites. Both SlWRKY3 and SlWRKY35 promoters were induced by the defense phytohormones salicylic acid and indole-3-butyric acid, with no response to either jasmonic acid or methyl jasmonate. SlWRKY3 overexpression resulted in lower infection of the RKN Meloidogyne javanica, whereas knocking down SlWRKY3 resulted in increased infection. Phytohormone and oxylipin profiles determined by LC–MS/MS showed that the enhanced resistance in the former is coupled with an increased accumulation of defense molecules from the shikimate and oxylipin pathways. Our results pinpoint SlWRKY3 as a positive regulator of induced resistance in response to nematode invasion and infection, mostly during the early stages of nematode infection.
Whole genome bisulfite sequencing of Down syndrome brain reveals regional DNA hypermethylation and novel disorder insights

ABSTRACT Down Syndrome (DS) is the most common genetic cause of intellectual disability, in which an extra copy of human chromosome 21 (HSA21) affects regional DNA methylation profiles across the genome. Although DNA methylation has been previously examined at select regulatory regions across the genome in a variety of DS tissues and cells, differentially methylated regions (DMRs) have yet to be examined in an unbiased sequencing-based approach. Here, we present the first analysis of DMRs from whole genome bisulfite sequencing (WGBS) data of human DS and matched control brain, specifically frontal cortex. While no global differences in DNA methylation were observed, we identified 3,152 DS-DMRs across the entire genome, the majority of which were hypermethylated in DS. DS-DMRs were significantly enriched at CpG islands and de-enriched at specific gene body and regulatory regions. Functionally, the hypermethylated DS-DMRs were enriched for one-carbon metabolism, membrane transport, and glutamatergic synaptic signalling, while the hypomethylated DMRs were enriched for proline isomerization, glial immune response, and apoptosis. Furthermore, in a cross-tissue comparison to previous studies of DNA methylation from diverse DS tissues and reference epigenomes, hypermethylated DS-DMRs showed a strong cross-tissue concordance, while a more tissue-specific pattern was observed for the hypomethylated DS-DMRs. Overall, this approach highlights that low-coverage WGBS of clinical samples can identify epigenetic alterations to known biological pathways, which are potentially relevant to therapeutic treatments and include metabolic pathways. These results also provide new insights into the genome-wide effects of genetic alterations on DNA methylation profiles indicative of altered neurodevelopment and brain function.
Pre-transplant hypomethylating agents do not influence post-transplant survival in myelodysplastic syndrome

Abstract Information on the use of hypomethylating agents (HMAs) as a pre-transplant cytoreductive therapy in MDS is limited. We retrospectively evaluated outcomes of 172 adult MDS patients, who underwent allogeneic hematopoietic stem cell transplantation between January 2000 and December 2016. Patients were divided into three groups: group 1 – pre-transplant blasts <5% with HMA (n = 42), group 2 – pre-transplant blasts ≥5% with HMA (n = 38), group 3 – no HMA (n = 92). With a median follow up of 4.08 years, 1-year survival and relapse rates for groups 1, 2, and 3 were 75%, 40.2%, and 60.71%, respectively; and 17.6%, 26.6%, and 9.8%, respectively. Multivariate analysis revealed adverse relapse (HR 3.54; p = .03) in group 2 compared to groups 1 and 3, while no difference in overall survival was noticed. Our study shows no survival association with pre-transplant HMA; although, higher relapse rate was observed in the non-responding patients indicating possible chemotherapy resistant disease.
RGS1 silencing inhibits the inflammatory response and angiogenesis in rheumatoid arthritis rats through the inactivation of Toll‐like receptor signaling pathway

Emerging evidence shows that rheumatoid arthritis (RA) progression can be induced by the activation of Toll‐like receptor (TLR) signaling pathway. Regulator of G‐protein signaling 1 (RGS1) is observed to be a candidate biomarker for arthritis. Accordingly, the present study aims to determine the potential effects of RGS1 mediating TLR on RA. A rat model of collagen‐induced arthritis (CIA) was established to mimic the features of RA by injection of bovine type II collagen. The rats with CIA were treated with short hairpin RNA (shRNA) against RGS1 or TLR pathway activator Poly I:C to elucidate the role of RGS1 in RA progression. The inflammatory factors were measured, and the thoracic gland and spleen indexes as well as the vascular density were determined. The expression levels of RGS1, TLR3, vascular endothelial growth factor (VEGF), metalloproteinase‐2 (MMP‐2), MMP‐9, and interleukin 1 receptor‐associated kinase‐4 (IRAK4) were determined. RGS1 was robustly increased in RA. The TLR signaling pathway was suppressed by RGS1 silencing. shRNA‐mediated depletion of RGS1 was shown to significantly enhance thoracic gland index and inhibit the serum levels of TNF‐α, IL‐1β, and IL‐17, spleen index, vascular density, and the expression levels of TLR3, VEGF, MMP‐2, MMP‐9, and IRAK4. However, when the rats with CIA were treated with Poly I:C, the trend of effects was opposite. These findings highlight that functional suppression of RGS1 inhibits the inflammatory response and angiogenesis by inactivating the TLR signaling pathway in rats with CIA, thereby providing a novel therapeutic target for RA treatment.
Modeling of Transient Trapping of Fatty Acid Tails in Phospholipids

We explore the dynamics of the bilayer in liposomes in relationship to the motion of individual lipid molecules. Monitoring the dynamics at the length-scale of single lipids is important because it may relate to cellular signaling and regulatory processes. Our experiments prove a very localized relaxation, which we experimentally confirmed as a trapped motion of the fatty acid tails in a very crowded environment, by analyzing results from neutron spin echo spectroscopy on fully and partially deuterated lipids. This motion is visible over several orders of magnitude in time- and length-scale and a comprehensive scientific study require several neutron spectroscopic techniques. Analyzing experiments on protonated and partially deuterated lipids indicate the statistical independence of tail-motion and height-height correlation of the membrane. This permits to deduct a theoretical model that describes neutron spectroscopy data of liposomes. Our results are best compatible with lipid tails relaxing in potential with cylindrical symmetry. Our modeling approach satisfactorily describes the dynamics of different phospholipids, including mixtures of different lipids, and partially deuterated systems. Despite substantial differences in the chemistry of the fatty acid tails, the observed motion seems to behave rather universal. The existence of the fast-localized tail motion and the slow translational diffusion of liposomes limit the time range in which the height-height correlation function can be monitored and analyzed. Taking into account these time constraints, we determined bending moduli between 8 kBT (SoyPC) to 22 kBT (DSPC). These values are slightly lesser than determined in the earlier literature, i.e., without including explicitly lipid tail motion. Thus, the new analysis shows that these membranes are a bit more elastic than observed before.
Acute Effects of Single Doses of Bonito Fish Peptides and Vitamin D on Whole Blood Gene Expression Levels: A Randomized Controlled Trial

Fish contains high quality proteins and essential nutrients including 25-hydroxyvitamin D (25(OH)D). Fish peptide consumption can lower cardiovascular disease (CVD) risk factors, and studies have shown an association between 25(OH)D deficiency, CVD and CVD risk factors, such as diabetes. This study investigated acute effects of a single dose of cholecalciferol (VitD3), bonito fish peptide hydrolysate (BPH), or a combination of both on CVD risk factors and whole blood gene expression levels. A randomized, crossover, placebo controlled trial was conducted in 22 adults. They ingested, in random order and at 7-day intervals, 1000 IU of VitD3, 3 g of BPH, a combination of both, or a placebo. A 180 min oral glucose tolerance test was performed. Differences in whole-genome expression levels after versus before each supplementation were computed for 18 subjects. We observed that 16, 1 and 5 transcripts were differentially expressed post- vs. pre-ingestion for VitD3, BPH or VitD3 + BPH treatments, respectively. VitD3-containing treatments affected the expression of the solute carrier family 25 member 20 (SLC25A20) gene involved in fatty acid oxidation, various transcription factors and genes related to glucose metabolism. These results suggest that VitD3 rapidly modulates genes related to CVD risk factors in blood while BPH seems to moderately modulate gene expression levels.
Eu3+, Tb3+- and Er3+, Yb3+-Doped α-MoO3 Nanosheets for Optical Luminescent Thermometry

Here we report a novel synthesis approach for the preparation of α-MoO3:Ln3+ materials employing a two-step synthesis. Additionally, in this work the α-MoO3:Ln3+ materials are reported as potential optical thermometers for the first time. In this synthesis approach, first MoS2 2D nanosheets were prepared, which were further heat treated to obtain α-MoO3. These materials were fully characterized by powder X-ray diffraction (XRD), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), X-ray fluorescence (XRF), thermogravimetry (TG) and differential thermal analysis (DTA), transmission electron microscopy (TEM), and luminescence spectroscopy. Temperature-dependent luminescence measurements were carried out to determine the optical thermometric properties of two different types of α-MoO3:Ln3+ materials (Eu3+/Tb3+ downshifting and Er3+/Yb3+ upconversion luminescence systems). We demonstrate in this study that this class of material could be a potential candidate for temperature-sensing applications.
The Patient with Difficult Cancer Pain

Most patients with cancer pain can be managed with relatively simple methods using oral analgesics at relatively low doses, even for prolonged periods of time. However, in some clinical conditions pain may be more difficult to manage. Various factors can interfere with a desirable and favorable analgesic response. Data from several studies assessing factors of negative pain prognosis have indicated that neuropathic pain, incident pain, psychological distress, opioid addiction, and baseline pain intensity were associated with more difficult pain control. In this narrative review, the main factors that make the therapeutic response to opioids difficult are examined.
High Prevalence of Diabetes in Patients With Primary Aldosteronism (PA) Associated With Subclinical Hypercortisolism and Prediabetes More Prevalent in Bilateral Than Unilateral PA: A Large, Multicenter Cohort Study in Japan

OBJECTIVE To investigate the prevalence and causes of diabetes in patients with primary aldosteronism (PA) in a multi-institutional cohort study in Japan. RESEARCH DESIGN AND METHODS The prevalence of diabetes was determined in 2,210 patients with PA (diagnosed or glycated hemoglobin [HbA1c] ≥6.5% [≥48 mmol/mol]; NGSP) and compared with that of the Japanese general population according to age and sex. In 1,386 patients with PA and clear laterality (unilateral or bilateral), the effects of plasma aldosterone concentration (PAC), hypokalemia (<3.5 mEq/L), suspected subclinical hypercortisolism (SH; serum cortisol ≥1.8 µg/dL after 1-mg dexamethasone suppression test), and PA laterality on the prevalence of diabetes or prediabetes (5.7% ≤ HbA1c <6.5% [39 mmol/mol ≤ HbA1c <48 mmol/mol]) were examined. RESULTS Of the 2,210 patients with PA, 477 (21.6%) had diabetes. This prevalence is higher than that in the general population (12.1%) or in 10-year cohorts aged 30–69 years. Logistic regression or χ2 test revealed a significant contribution of suspected SH to diabetes. Despite more active PA profiles (e.g., higher PAC and lower potassium concentrations) in unilateral than bilateral PA, BMI and HbA1c values were significantly higher in bilateral PA. PA laterality had no effect on the prevalence of diabetes; however, the prevalence of prediabetes was significantly higher in bilateral than unilateral PA. CONCLUSIONS Individuals with PA have a high prevalence of diabetes, which is associated mainly with SH. The prevalence of prediabetes is greater for bilateral than unilateral PA, suggesting a unique metabolic cause of bilateral PA.
Can platelet-rich plasma be an alternative to surgery for resistant chronic patellar tendinopathy in sportive people? Poor clinical results at 1-year follow-up

Introduction and purpose: Patellar tendinopathy is a disease affecting particularly athletes. Platelet-rich plasma (PRP) injections have gained increasing interest for their potential benefits. Anyway, a tendon disease longer than 6 months should be considered as an indication for surgery. The aim of our study was to evaluate the efficacy of PRP in athletes with a severe chronic patellar tendinopathy longer than 6 months when surgery should be chosen. Methods: We enrolled 17 sport practitioners (19 patellar tendons) who did not want to undergo surgery and who are nonresponders to other conservative treatments. We treated them with PRP and calculated the results using the visual analog scale (VAS), the Victorian Institute of Sport Assessment-Patellar (VISA-P) score, and Tegner Activity Scale. Every test has been conducted at T0, T1 (4 months), and T2 (12 months). Results: We found a poor improvement at T1 and a clinical worsening at T2 through VAS. VISA-P showed a medium improvement both at T1 and T2. Tegner scale did not show improvements. Conclusions: Our study was not able to remove the doubts about the benefits of PRP in patellar tendinopathy, confirming ambiguous certainties. Further investigations are needed to assess its effectiveness.
The Combination Rifampin-Nitazoxanide, but Not Rifampin-Isoniazid-Pyrazinamide-Ethambutol, Kills Dormant Mycobacterium tuberculosis in Hypoxia at Neutral pH

The activities of rifampin, nitazoxanide, PA-824, and sutezolid were tested against dormant Mycobacterium tuberculosis under conditions mimicking caseous granulomas (hypoxia at pH 7.3) in comparison with those of the combination rifampin-isoniazid-pyrazinamide-ethambutol (R-I-Z-E), which is used for human therapy. Mycobacterial viability was monitored by CFU and regrowth in MGIT 960. ABSTRACT The activities of rifampin, nitazoxanide, PA-824, and sutezolid were tested against dormant Mycobacterium tuberculosis under conditions mimicking caseous granulomas (hypoxia at pH 7.3) in comparison with those of the combination rifampin-isoniazid-pyrazinamide-ethambutol (R-I-Z-E), which is used for human therapy. Mycobacterial viability was monitored by CFU and regrowth in MGIT 960. As shown by lack of regrowth in MGIT, rifampin-nitazoxanide-containing combinations, but not R-I-Z-E, killed dormant cells in 28 to 35 days. These observations might be important in designing new tuberculosis therapies.
The Effects of Choline and Magnesium Co-Supplementation on Metabolic Parameters, Inflammation, and Endothelial Dysfunction in Patients With Type 2 Diabetes Mellitus: A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract Objective: To our knowledge, no study has investigated the effects of choline and magnesium co-supplementation on metabolic parameters, inflammation, and endothelial dysfunction in patients with type 2 diabetes mellitus (T2DM). The aim of this study was investigation of the effects of the choline and magnesium co-supplementation on metabolic parameters, inflammation, and endothelial dysfunction in patients with T2DM. Methods: A randomized double-blind placebo-controlled parallel clinical trial was carried out among 96 diabetic patients. Ninety-six patients were randomly assigned to either choline, magnesium, choline-magnesium, or placebo for 2 months. Anthropometric measurement; metabolic, inflammatory, and endothelial markers; dietary intake; and physical activity were assessed at baseline and after treatment. Results: There was a significant change in serum magnesium in both magnesium and choline-magnesium groups (p < 0.05). Also, significant changes were observed in interleukin (IL)-6 levels in magnesium and choline-magnesium groups (p < 0.05). Moreover, vascular cell adhesion molecule-1 (VCAM-1) levels decreased in choline and choline-magnesium groups (p < 0.05). When adjusted for potential confounders, inflammation and endothelial factors (IL-6 and VCAM-1) decreased significantly in the choline-magnesium group as compared to other groups (p < 0.05). Compared to baseline values there were no significant differences in all anthropometric measurements and metabolic factors among four groups (p > 0.05). Conclusions: Choline and magnesium co-supplementation was more effective in improving inflammation and endothelial dysfunction than supplementation with choline or magnesium alone.
Foliar water uptake in Amazonian trees: Evidence and consequences

The absorption of atmospheric water directly into leaves enables plants to alleviate the water stress caused by low soil moisture, hydraulic resistance in the xylem and the effect of gravity on the water column, while enabling plants to scavenge small inputs of water from leaf‐wetting events. By increasing the availability of water, and supplying it from the top of the canopy (in a direction facilitated by gravity), foliar uptake (FU) may be a significant process in determining how forests interact with climate, and could alter our interpretation of current metrics for hydraulic stress and sensitivity. FU has not been reported for lowland tropical rainforests; we test whether FU occurs in six common Amazonian tree genera in lowland Amazônia, and make a first estimation of its contribution to canopy–atmosphere water exchange. We demonstrate that FU occurs in all six genera and that dew‐derived water may therefore be used to “pay” for some morning transpiration in the dry season. Using meteorological and canopy wetness data, coupled with empirically derived estimates of leaf conductance to FU (kfu), we estimate that the contribution by FU to annual transpiration at this site has a median value of 8.2% (103 mm/year) and an interquartile range of 3.4%–15.3%, with the biggest sources of uncertainty being kfu and the proportion of time the canopy is wet. Our results indicate that FU is likely to be a common strategy and may have significant implications for the Amazon carbon budget. The process of foliar water uptake may also have a profound impact on the drought tolerance of individual Amazonian trees and tree species, and on the cycling of water and carbon, regionally and globally.