Miracle-dz/UniFAR-FTUs huggingface dataset:
A Pre-Workout Supplement of Ketone Salts, Caffeine, and Amino Acids Improves High-Intensity Exercise Performance in Keto-Naïve and Keto-Adapted Individuals

Abstract Background: Acute ingestion of ketone supplements alters metabolism and potentially exercise performance. No studies to date have evaluated the impact of co-ingestion of ketone salts with caffeine and amino acids on high intensity exercise performance, and no data exists in Keto-Adapted individuals. Methods: We tested the performance and metabolic effects of a pre-workout supplement containing beta-hydroxybutyrate (BHB) salts, caffeine, and amino acids (KCA) in recreationally-active adults habitually consuming a mixed diet (Keto-Naïve; n = 12) or a ketogenic diet (Keto-Adapted; n = 12). In a randomized and balanced manner, subjects consumed either the KCA consisting of ∼7 g BHB (72% R-BHB and 28% S-BHB) with ∼100 mg of caffeine, and amino acids (leucine and taurine) or Water (control condition) 15 minutes prior to performing a staged cycle ergometer time to exhaustion test followed immediately by a 30 second Wingate test. Results: Circulating total BHB concentrations increased rapidly after KCA ingestion in KN (154 to 732 μM) and KA (848 to 1,973 μM) subjects and stayed elevated throughout recovery in both groups. Plasma S-BHB increased >20-fold 15 minutes after KCA ingestion in both groups and remained elevated throughout recovery. Compared to Water, KCA ingestion increased time to exhaustion 8.3% in Keto-Naïve and 9.8% in Keto-Adapted subjects (P < 0.001). There was no difference in power output during the Wingate test between trials. Peak lactate immediately after exercise was higher after KCA (∼14.9 vs 12.7 mM). Conclusion: These results indicate that pre-exercise ingestion of a moderate dose of R- and S-BHB salts combined with caffeine, leucine and taurine improves high-intensity exercise performance to a similar extent in both Keto-Adapted and Keto-Naïve individuals.
TGF-β and IL-15 Synergize through MAPK Pathways to Drive the Conversion of Human NK Cells to an Innate Lymphoid Cell 1–like Phenotype

Key Points TGF-β drives the conversion of human circulating NK cells to an ILC1-like phenotype. CyTOF profiling was used to elucidate heterogeneity in the stages of conversion. TGF-β–mediated conversion is driven by MAPK signaling and is enhanced by IL-15. Visual Abstract Circulating NK cells are known to convert to a type 1 innate lymphoid cell (ILC1)–like phenotype in response to TGF-β exposure. However, the precise cellular changes defining this process as well as the downstream signaling pathways guiding it remain poorly defined, particularly in humans. We used mass cytometry by time-of-flight (CyTOF) to model this phenotypic shift in vitro and identify a synergistic activity of TGF-β and IL-15 in this cellular conversion. CyTOF profiling identified substantial heterogeneity in the propensity of NK cells to adopt an ILC1-like phenotype in culture, characterized by the step-wise acquisition of various markers, including CD69, CD9, CD103, and CD49a. Activating and inhibitory receptors, including NKG2A, NKG2D, KIR2DL1, KIR3DL1, NKp30, NKp44, and NKp46, were all found to be upregulated exclusively on the cellular subsets that converted most readily in response to TGF-β. An assessment of downstream TGF-β signaling identified TAK1-mediated activation of p38 MAPK as the critical pathway driving conversion. IL-15 enhanced TGF-β–mediated conversion through Ras:RAC1 signaling as well as via the activation of MEK/ERK. Interestingly, the adoption of an ILC1-like phenotype was independent of the effect of IL-15 or TGF-β on mTOR, as the culture of NK cells in the presence of mTOR inhibitors, such as rapamycin or torin1, had minimal impact on the degree of conversion. In conclusion, we have used in vitro human culture systems and CyTOF to define the conversion of circulating NK cells to an ILC1-like phenotype and have clarified the pathways responsible for this process.
Applying RE-AIM to Evaluate the External Validity of Weight Gain Prevention Interventions in Young Adults: A Systematic Review

Supplemental Digital Content is Available in the Text. Objectives: The purpose of this review was to use RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) to assess the extent to which weight gain prevention studies targeting young adults reported on elements of external validity. Design: Systematic review. Eligibility Criteria: Articles of interest included a lifestyle/behavioral intervention targeting weight gain prevention. Eligibility criteria included the following: study design of randomized controlled trials, quasi-randomized control trials, or natural experiments; average participant age between 18 and 35 years; study duration of at least 12 months; and published in English between January 2008 and May 2018. Studies had to report weight or body mass index as a measured outcome and were excluded if they were paired with smoking cessation programs, were conducted in specific groups (ie, pregnant women, breast cancer survivors), or were follow-ups to weight loss studies. Study Selection: After removing duplicates, the search yielded 11426 articles. Titles and abstracts were screened by 1 reviewer; 144 articles were assessed in a full-text review by 2 reviewers. Discrepancies were resolved by consensus. Nine studies (13 articles) were included in the review. Main Outcomes Measure(s): Reported elements of the RE-AIM framework. Results: A total of 9 studies met the selection criteria. All studies lacked full reporting on external validity elements. Of the total of 60 RE-AIM reporting criteria, 8 were reported by all 9 studies, 26 criteria were reported by fewer than 4 studies, and 22 criteria were not reported by any of the studies. Discussion: There remains inadequate reporting of elements of external validity and generalizability in weight gain prevention studies. This is a significant scientific constraint that limits the information required to disseminate and implement prevention of weight gain interventions for population impact. Standardized reporting may be needed to ensure results that demonstrate not only internal validity but also external validity and generalizability are needed to promote public health impact.
RIG-I-like receptor activation drives type I IFN and antiviral signaling to limit Hantaan orthohantavirus replication

Pathogenic hantaviruses, genus Orthohantaviridae, are maintained in rodent reservoirs with zoonotic transmission to humans occurring through inhalation of rodent excreta. Hantavirus disease in humans is characterized by localized vascular leakage and elevated levels of circulating proinflammatory cytokines. Despite the constant potential for deadly zoonotic transmission to humans, specific virus-host interactions of hantaviruses that lead to innate immune activation, and how these processes impart disease, remain unclear. In this study, we examined the mechanisms of viral recognition and innate immune activation of Hantaan orthohantavirus (HTNV) infection. We identified the RIG-I-like receptor (RLR) pathway as essential for innate immune activation, interferon (IFN) production, and interferon stimulated gene (ISG) expression in response to HTNV infection in human endothelial cells, and in murine cells representative of a non-reservoir host. Our results demonstrate that innate immune activation and signaling through the RLR pathway depends on viral replication wherein the host response can significantly restrict replication in target cells in a manner dependent on the type 1 interferon receptor (IFNAR). Importantly, following HTNV infection of a non-reservoir host murine model, IFNAR-deficient mice had higher viral loads, increased persistence, and greater viral dissemination to lung, spleen, and kidney compared to wild-type animals. Surprisingly, this response was MAVS independent in vivo. Innate immune profiling in these tissues demonstrates that HTNV infection triggers expression of IFN-regulated cytokines early during infection. We conclude that the RLR pathway is essential for recognition of HTNV infection to direct innate immune activation and control of viral replication in vitro, and that additional virus sensing and innate immune response pathways of IFN and cytokine regulation contribute to control of HTNV in vivo. These results reveal a critical role for innate immune regulation in driving divergent outcomes of HTNV infection, and serve to inform studies to identify therapeutic targets to alleviate human hantavirus disease.
Higher Gene Expression Related to Wound Healing by Fibroblasts on Silk Fibroin Biomaterial than on Collagen

Silk fibroin (SF), which offers the benefits of biosafety, biocompatibility, and mechanical strength, has potential for use as a good biomedical material, especially in the tissue engineering field. This study investigated the use of SF biomaterials as a wound dressing compared to commercially available collagen materials. After human fibroblasts (WI-38) were cultured on both films and sponges, their cell motilities and gene expressions related to wound repair and tissue reconstruction were evaluated. Compared to the collagen film (Col film), the SF film induced higher cell motility; higher expressions of genes were observed on the SF film. Extracellular matrix production-related genes were up-regulated in WI-38 fibroblasts cultured on the SF sponges. These results suggest that SF-based biomaterials can accelerate wound healing and tissue reconstruction. They can be useful biomaterials for functional wound dressings.
Genome-Wide DNA Methylation and RNA Analysis Reveal Potential Mechanism of Resistance to Streptococcus agalactiae in GIFT Strain of Nile Tilapia (Oreochromis niloticus)

Key Points Whole-genome bisulfite sequencing distinguishes between resistant and susceptible O. niloticus. Promoter methylation regulates gene expression in immune-related genes. Streptococcus agalactiae is an important pathogenic bacterium causing great economic loss in Nile tilapia (Oreochromis niloticus) culture. Resistant and susceptible groups sharing the same genome showed significantly different resistance to S. agalactiae in the genetically improved farmed tilapia strain of Nile tilapia. The resistance mechanism is unclear. We determined genome-wide DNA methylation profiles in spleen of resistant and susceptible O. niloticus at 5 h postinfection with S. agalactiae using whole-genome bisulfite sequencing. The methylation status was higher in the spleen samples from resistant fish than in the susceptible group. A total of 10,177 differentially methylated regions were identified in the two groups, including 3725 differentially methylated genes (DMGs) (3129 hyper-DMGs and 596 hypo-DMGs). The RNA sequencing showed 2374 differentially expressed genes (DEGs), including 1483 upregulated and 891 downregulated. Integrated analysis showed 337 overlapping DEGs and DMGs and 82 overlapping DEGs and differentially methylated region promoters. By integrating promoter DNA methylation with gene expression, we revealed four immune-related genes (Arnt2, Nhr38, Pcdh10, and Ccdc158) as key factors in epigenetic mechanisms contributing to pathogen resistance. Our study provided systematic methylome maps to explore the epigenetic mechanism and reveal the methylation loci of pathogen resistance and identified methylation-regulated genes that are potentially involved in defense against pathogens.
Mycetoma epidemiology, diagnosis management, and outcome in three hospital centres in Senegal from 2008 to 2018

Mycetoma is a neglected tropical disease caused by various actinomycetes or fungi. The disease is characterized by the formation of tumor like-swellings and grains. Senegal is an endemic country where mycetoma cases are under-or misdiagnosed due to the lack of capacities and knowledge among health workers and the community; and where the management of eumycetoma, burdened by a high amputation rate, is currently inadequate. This study aimed to update data on the epidemiology of mycetoma cases diagnosed in three hospital centres in Senegal over a 10 years-period. A total of 193 patients, diagnosed from 2008 to 2018, were included in the study. The most frequent presentation was eumycetoma (47.2%); followed by actinomycetoma (36.8%); it remained undetermined in 16.1% of the patients. The mean age was 38.3 years (68.4% of the patients were between 15 and 45 years-old); the male: female ratio was a 2.94; and most were farmers. One hundred fifty-six (80.8%) patients had used phytotherapy before attending the hospital. Mycetoma was mainly located to the lower limbs (91.2%). Grains were observed in 85% of the patients; including white (25.6%) and yellow (4.3%) grains. The etiological diagnosis was complex, resulting in negative direct microscopy, culture and/or histopathology findings, which explains that 16.1% remained uncharacterized. In most of cases, actinomycetoma were treated with a combination of cotrimoxazole, amoxicillin/clavulanic acid, and streptomycin; whereas eumycetoma cases were treated with terbinafine. The surgery was done in 100 (51.8%) of the patients including 9 in actinomycetoma, 78 in eumycetoma and 13 in undetermined form. The high number of uncharacterized mycetoma in this study, the delay in attending a qualified health-care facility, and the lack of available adequate antifungal drug, point out the need to strengthen mycetoma management capacities in Senegal.
DFT Study of Molecular and Electronic Structure of Ca(II) and Zn(II) Complexes with Porphyrazine and tetrakis(1,2,5-thiadiazole)porphyrazine

Electronic and geometric structures of Ca(II) and Zn(II) complexes with porphyrazine (Pz) and tetrakis(1,2,5-thiadiazole)porphyrazine (TTDPz) were investigated by density functional theory (DFT) calculations and compared. The perimeter of the coordination cavity was found to be practically independent on the nature of a metal and a ligand. According to the results of the natural bond orbital (NBO) analysis and quantum theory of atoms in molecules (QTAIM) calculations, Ca–N bonds possess larger ionic contributions as compared to Zn–N. The model electronic absorption spectra obtained with the use of time-dependent density functional theory (TDDFT) calculations indicate a strong bathochromic shift (~70 nm) of the Q-band with a change of Pz ligand by TTDPz for both Ca and Zn complexes. Additionally, CaTTDPz was synthesized and its electronic absorption spectrum was recorded in pyridine and acetone.
Aesculus hippocastanum L. Extract Does Not Induce Fibroblast to Myofibroblast Conversion but Increases Extracellular Matrix Production In Vitro Leading to Increased Wound Tensile Strength in Rats

The ability of horse chestnut extract (HCE) to induce contraction force in fibroblasts, a process with remarkable significance in skin repair, motivated us to evaluate its wound healing potential in a series of experiments. In the in vitro study of the ability of human dermal fibroblasts to form myofibroblast-like cells was evaluated at the protein level (Western blot and immunofluorescence). The in vivo study was conducted on male Sprague-Dawley rats with inflicted wounds (one open circular and one sutured incision) on their backs. Rats were topically treated with two tested HCE concentrations (0.1% and 1%) or sterile water. The control group remained untreated. The incisions were processed for wound tensile strength (TS) measurement whereas the open wounds were subjected to histological examination. On the in vitro level the HCE extract induced fibronectin-rich extracellular matrix formation, but did not induced α-smooth muscle actin (SMA) expression in dermal fibroblasts. The animal study revealed that HCE increased wound TS and improved collagen organization. In conclusion, the direct comparison of both basic wound models demonstrated that the healing was significantly increased following HCE, thus this extract may be found useful to improve healing of acute wounds. Nevertheless, the use of an experimental rat model warrants a direct extrapolation to the human clinical situation.
Vitamin D Supplementation and Blood Pressure in Children and Adolescents: A Systematic Review and Meta-Analysis

Suboptimal vitamin D status is associated with elevated blood pressure (BP) in children and adolescents. Whether vitamin D supplementation reduces BP remains unclear. To systematically review whether vitamin D supplementation reduces BP in children and adolescents, we conducted a literature review according to the PRISMA statement. We included vitamin-D supplementation human interventions studies that reported on BP as an outcome. We searched PUBMED, MEDLINE, CINAHL, EMBASE, the Cochrane Library, and the clinical trials website. We also hand searched the references of the included articles and previous reviews of vitamin D therapy. No language or time restrictions were applied. We extracted data on population characteristics, baseline and endline vitamin D and BP values, and assessed the risk of bias of the included studies. We performed a narrative review of the findings, conducted a meta-analysis when possible, and performed sensitivity analyses to test the robustness of our results. We assessed the overall quality of the evidence produced in the meta-analysis. We included eight studies in our review and five studies in the meta-analysis, none of which included hypertensive only participants. The risk of bias was variable. In non-randomized studies, no effect of vitamin D supplementation was seen on systolic BP (SBP) (mean difference: 0.39 (95% confidence interval (CI): −0.9; 1.68) mmHg; p = 0.55; I2 = 0%). Only a significant decrease in diastolic BP (DBP) (mean difference: −1.87 (95% CI: −3.02; −0.72) mmHg; p = 0.001; I2 = 0%) was noted. Both analyses had a low quality of evidence. In randomized controlled trials (RCTs), no effect was noted on SBP (mean difference: −2.04 (95% CI: −5.12; 1.04) mmHg; p = 0.19; I2 = 71%) nor DBP (mean difference: 0.01 (95% CI: −1.09; 1.12) mmHg; p = 0.98; I2 = 0%). The final quality of evidence ranged between low and moderate. Sensitivity analyses did not affect the results. Vitamin D supplementation was found to be ineffective in lowering SBP and DBP in children and adolescents.
Comparison of multi-parallel qPCR and double-slide Kato-Katz for detection of soil-transmitted helminth infection among children in rural Bangladesh

There is growing interest in local elimination of soil-transmitted helminth (STH) infection in endemic settings. In such settings, highly sensitive diagnostics are needed to detect STH infection. We compared double-slide Kato-Katz, the most commonly used copromicroscopic detection method, to multi-parallel quantitative polymerase chain reaction (qPCR) in 2,799 stool samples from children aged 2–12 years in a setting in rural Bangladesh with predominantly low STH infection intensity. We estimated the sensitivity and specificity of each diagnostic using Bayesian latent class analysis. Compared to double-slide Kato-Katz, STH prevalence using qPCR was almost 3-fold higher for hookworm species and nearly 2-fold higher for Trichuris trichiura. Ascaris lumbricoides prevalence was lower using qPCR, and 26% of samples classified as A. lumbricoides positive by Kato-Katz were negative by qPCR. Amplicon sequencing of the 18S rDNA from 10 samples confirmed that A. lumbricoides was absent in samples classified as positive by Kato-Katz and negative by qPCR. The sensitivity of Kato-Katz was 49% for A. lumbricoides, 32% for hookworm, and 52% for T. trichiura; the sensitivity of qPCR was 79% for A. lumbricoides, 93% for hookworm, and 90% for T. trichiura. Specificity was ≥ 97% for both tests for all STH except for Kato-Katz for A. lumbricoides (specificity = 68%). There were moderate negative, monotonic correlations between qPCR cycle quantification values and eggs per gram quantified by Kato-Katz. While it is widely assumed that double-slide Kato-Katz has few false positives, our results indicate otherwise and highlight inherent limitations of the Kato-Katz technique. qPCR had higher sensitivity than Kato-Katz in this low intensity infection setting.
Multiple Stressor Effects of Radon and Phthalates in Children: Background Information and Future Research

The present paper reviews available background information for studying multiple stressor effects of radon (222Rn) and phthalates in children and provides insights on future directions. In realistic situations, living organisms are collectively subjected to many environmental stressors, with the resultant effects being referred to as multiple stressor effects. Radon is a naturally occurring radioactive gas that can lead to lung cancers. On the other hand, phthalates are semi-volatile organic compounds widely applied as plasticizers to provide flexibility to plastic in consumer products. Links of phthalates to various health effects have been reported, including allergy and asthma. In the present review, the focus on indoor contaminants was due to their higher concentrations and to the higher indoor occupancy factor, while the focus on the pediatric population was due to their inherent sensitivity and their spending more time close to the floor. Two main future directions in studying multiple stressor effects of radon and phthalates in children were proposed. The first one was on computational modeling and micro-dosimetric studies, and the second one was on biological studies. In particular, dose-response relationship and effect-specific models for combined exposures to radon and phthalates would be necessary. The ideas and methodology behind such proposed research work are also applicable to studies on multiple stressor effects of collective exposures to other significant airborne contaminants, and to population groups other than children.
Biomechanical stimulation effects on the metabolism of adipocyte

Adipose tissue plays a leading role in obesity, which, in turn, can lead to Type 2 diabetes. Adipocytes (AD) respond to the biomechanical stimulation experienced in fat tissue under static stretch during prolonged sitting or lying. To investigate the effect of such chronic stimulation on adipocyte cell metabolism, we used an in vitro system to mimic the static stretch conditions. Under in vitro culture stretching, cells were analyzed at the single‐cell level and we measured an increase in the projected area of the AD and higher content of lipid droplets. A decrease in the projected area of these cells’ nucleus is associated with peroxisome proliferator‐activated receptor‐gamma expression and heterochromatin. This is the first study to reveal proteins that were altered under static stretch following a mass spectrometry analysis and main pathways that affect cell fate and metabolism. Bioinformatics analysis of the proteins indicated an increase in mitochondrial activity and associated pathways under static stretch stimulation. Quantification of the mitochondrial activity by 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyl tetrazolium bromide (MTT) assay and the ATPase related proteins specifically measured ATP5B indicated an increase in adipogenesis which points to a higher rate of cell metabolism under static stretch. In summary, our results elaborate on the metabolism of AD exposed to biomechanical stimulation, that is, associated with altered cellular protein profile and thereby influenced cell fate. The static stretch stimulation accelerated adipocyte differentiation through increased mitochondrial activity. Hence, in this study, we introduce a new perspective in understanding the molecular regulation of mechano‐transduction in adipogenesis.