Miracle-dz/UniFAR-FTUs huggingface dataset:
Pretreatment Prevotella-to-Bacteroides ratio and salivary amylase gene copy number as prognostic markers for dietary weight loss.

BACKGROUND The inconsistent link observed between salivary amylase gene copy number (AMY1 CN) and weight management is likely modified by diet and microbiome. OBJECTIVE Based on analysis of a previously published study, we investigated the hypothesis that interaction between diet, Prevotella-to-Bacteriodes ratio (P/B ratio), and AMY1 CN influence weight change. METHODS Sixty-two people with increased waist circumference were randomly assigned to receive an ad libitum New Nordic Diet (NND) high in dietary fiber, whole grain, intrinsic sugars, and starch or an Average Danish (Western) Diet (ADD) for 26 weeks. All foods were provided free of charge. Before subjects were randomly assigned to receive the NND or ADD diet, blood and fecal samples were collected, from which AMY1 CN and P/B ratio, respectively, were determined. Body weight change was described by using linear mixed models, including biomarker [log10(P/B ratio) and/or AMY1 CN] diet-group interactions. RESULTS Baseline means ± SDs of log10(P/B ratio) and AMY1 CN were -2.1 ± 1.8 and 6.6 ± 2.4, respectively. Baseline P/B ratio predicted a 0.99-kg/unit (95% CI: 0.40, 1.57; n = 54; P < 0.001) higher weight loss for those subjects on the NND compared with those on the ADD diet, whereas AMY1 CN was not found to predict weight loss differences between the NND and ADD groups [0.05 kg/CN (95% CI: -0.40, 0.51; n = 54; P = 0.83)]. However, among subjects with low AMY1 CN (<6.5 copies), baseline P/B ratio predicted a 2.12-kg/unit (95% CI: 1.37, 2.88; n = 30; P < 0.001) higher weight loss for the NND group than the ADD group. No such differences in weight loss were found among subjects in both groups with high AMY1 CN [-0.17 kg/unit (95% CI: -1.01, 0.66; n = 24; P = 0.68)]. CONCLUSIONS The combined use of low AMY1 CN and pretreatment P/B ratio for weight loss prediction led to highly individualized weight loss results with the introduction of more fiber, whole grain, intrinsic sugars, and starch in the diet. These preliminary observations suggest that more undigested starch reaches the colon in individuals with low AMY1 CN, and that the fate of this starch depends on the gut microbiota composition. This trial was registered at clinicaltrials.gov as NCT01195610.
Therapist Driven Rehabilitation Protocol for Patients with Chronic Heart and Lung Diseases: A Real-Life Study

Therapist driven protocols may help to tailor rehabilitation programs to individual patients. We aimed to test the feasibility, safety, and clinical usefulness of a therapist driven protocol for rehabilitation including exercise training of patients with heart or lung diseases. An internal audit elaborated the Cardio-Respiratory Exercise Maugeri Algorithm (CREMA) based on: (a) standardized baseline assessments, (b) decision-making pathways, and (c) frequency/intensity/time/type (FITT) of prescription for each exercise. Outpatients (n = 620) with chronic heart disease (CHD), recent myocardial revascularization (REVASC), chronic airway (Obstructive), and restrictive lung (Restrictive) diseases underwent exercise training according to CREMA during 4 years. Peripheral muscle strengthening was the most prescribed exercise (83.6%), while arm endurance training was the least frequently (0.75%). Exercise prescription varied widely among the disease groups (interval training 19–47%, balance 35–49%, lower limb muscle training 6–15%). After training, REVASC patients were the best improvers in the 6 min walking distance (+48.7 (56.1) m), maximal inspiratory pressure (+9.6 (15.4) cmH2O), and daily steps (+1087.2 (3297.1) n/day). Quadriceps and biceps strength, maximal expiratory pressure, and balance improved in all groups, without significant differences. Minor side effects were observed in 11.2% of the patients. The CREMA therapist driven protocol was feasible, safe, and useful for prescribing tailored training programs. Exercise prescriptions and training response differed among diseases.
The Impact of Surgical Margins and Adjuvant Radiotherapy in Patients with Undifferentiated Pleomorphic Sarcomas of the Extremities: A Single-Institutional Analysis of 192 Patients

Background: Undifferentiated pleomorphic sarcomas are a frequent subtype within the heterogeneous group of soft tissue sarcomas. As the attainment of negative margins can be complicated at the extremities, we determined the prognostic significance of surgical margins in our patient population. Methods: We retrospectively determined the relationship between local recurrence-free survival (LRFS), overall survival (OS), and potential prognostic factors in 192 patients with UPS of the extremities who were suitable for surgical treatment in curative intent. The median follow-up time was 5.1 years. Results: The rates of LRFS and OS after 2 years were 75.7% and 87.2% in patients with R0-resected primary tumors and 49.1% and 81.8% in patients with R1/R2-status (LRFS: p = 0.013; OS: p = 0.001). Adjuvant radiotherapy significantly improved LRFS (5-year: 67.6% vs. 48.4%; p < 0.001) and OS (5-year: 82.8 vs. 61.8; p = 0.016). Both, negative margins and adjuvant radiotherapy were found to be independent prognostic factors in multivariate analysis. Conclusions: The data from this study could underscore the beneficial prognostic impact of negative margins on LRFS and OS. However, the width of negative margins seemed to be not relevant. Notably, adjuvant radiotherapy was not only able to decrease the risk of local failure but also improved OS in a significant manner.
Comprehensive Investigation of Moringa oleifera from Different Regions by Simultaneous Determination of 11 Polyphenols Using UPLC-ESI-MS/MS

In this study, we develop and validate a simultaneous quantification of polyphenols method based on an ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) to adequately understand how different habitats influence the quality and profile of Moringa oleifera polyphenol. Furthermore, principal component analysis (PCA) and hierarchical cluster analysis (HCA) were used to compare and discriminate 25 samples collected from different areas. A significant correlation was found between the polyphenol profile and the collection area. Significant differences in the polyphenol content of Moringa oleifera from different regions indicate that the genetic diversity of Moringa oleifera was relatively rich, possibly due to differences in cultivation conditions, climate, or soil environment resulting in the accumulation of different polyphenols. These observations provide a theoretical basis for subsequent Moringa oleifera germplasm selection and development research. Furthermore, the quantitative analysis methodology used to characterize the polyphenols may be used toward developing quality assessment and future pharmacodynamic investigations of Moringa oleifera.
A Novel Eye Drop Candidate for Age-Related Macular Degeneration Treatment: Studies on its Pharmacokinetics and Distribution in Rats and Rabbits

Age-related macular degeneration (AMD) is wearing down of macula of retina, causing a blur or loss of vision in the center of the visual field. It can be categorized into dry or wet AMD. Until now, medical treatments for dry AMD have not been developed yet. The aim of this study was to evaluate pharmacokinetics (PKs) and tissue distribution of CK41016, a novel candidate for dry AMD, after intravenous (IV) or eye drop administration in rats and rabbits. In addition, a simple and sensitive bioanalytical method for CK41016 using ultra performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS) was developed. PK parameters were estimated by compartmental analysis using a WinNonlin® software version 8.1 (a Certara™ company). A PK model of CK41016 was well-described by the two-compartment model. The tissue-to-plasma partition coefficient (Kp) of CK41016 was the highest in the vitreous humor of rats and the cornea of rabbits after eye drop administration. In addition, the Caco-2 cell transporter assay confirmed that CK41016 was not an active substrate for the efflux transporter. In summary, the PKs and tissue distribution of CK41016 were successfully evaluated and investigated whether this drug was a substrate of efflux transporters.
Tricyclic Nucleobase Analogs and Their Ribosides as Substrates and Inhibitors of Purine-Nucleoside Phosphorylases III. Aminopurine Derivatives

Etheno-derivatives of 2-aminopurine, 2-aminopurine riboside, and 7-deazaadenosine (tubercidine) were prepared and purified using standard methods. 2-Aminopurine reacted with aqueous chloroacetaldehyde to give two products, both exhibiting substrate activity towards bacterial (E. coli) purine-nucleoside phosphorylase (PNP) in the reverse (synthetic) pathway. The major product of the chemical synthesis, identified as 1,N2-etheno-2-aminopurine, reacted slowly, while the second, minor, but highly fluorescent product, reacted rapidly. NMR analysis allowed identification of the minor product as N2,3-etheno-2-aminopurine, and its ribosylation product as N2,3-etheno-2-aminopurine-N2-β-d-riboside. Ribosylation of 1,N2-etheno-2-aminopurine led to analogous N2-β-d-riboside of this base. Both enzymatically produced ribosides were readily phosphorolysed by bacterial PNP to the respective bases. The reaction of 2-aminopurine-N9-β -d-riboside with chloroacetaldehyde gave one major product, clearly distinct from that obtained from the enzymatic synthesis, which was not a substrate for PNP. A tri-cyclic 7-deazaadenosine (tubercidine) derivative was prepared in an analogous way and shown to be an effective inhibitor of the E. coli, but not of the mammalian enzyme. Fluorescent complexes of amino-purine analogs with E. coli PNP were observed.
Plasma disposition of gabapentin after the intragastric administration of escalating doses to adult horses

Abstract Background In humans, gabapentin an analgesic, undergoes non‐proportional pharmacokinetics which can alter efficacy. No information exists on the pharmacokinetics of dosages >20 mg/kg, escalating dosages or dose proportionality of gabapentin in horses. Hypothesis and Objectives Gabapentin exposure in plasma would not increase proportionally relative to the dose in horses receiving dosages ≥20 mg/kg. To assess the plasma pharmacokinetics of gabapentin after nasogastric administration of gabapentin at dosages of 10 to 160 mg/kg in adult horses. Animals Nine clinically healthy adult Arabian and Quarter Horses. Methods In a randomized blinded trial, gabapentin was administered by nasogastric intubation to horses at 10, 20 mg/kg (n = 3) and 60, 80, 120, 160 mg/kg (n = 6). Plasma was collected before and at regular times over 64 hours after administration of gabapentin. Gabapentin was quantified using a validated chromatographic method. Dose proportionality was estimated using a power model. Pharmacokinetic parameters were estimated using compartmental pharmacokinetic analysis. Results Plasma pharmacokinetics parameters of gabapentin were estimated after nasogastric administration at dosages of 10 to 160 mg/kg. Gabapentin plasma concentration increased with dose increments. However, the area under the concentration curve from zero to infinity and maximal plasma concentration did not increase proportionally relative to the dose in horses. Conclusions and Clinical Importance Gabapentin exposure in plasma is not proportional relative to the dose in horses receiving nasogastric dosages of 10 to 160 mg/kg.
Variable Strength in Thoron Interference for a Diffusion-Type Radon Monitor Depending on Ventilation of the Outer Air

Thoron interference in radon measurements using passive diffusion radon detectors/monitors is a crucial problem when it comes to assessing the internal exposure to radon precisely. The present study reported, as one of the potential factors, the effects of air flow conditions on changes in thoron interference. Rates of thoron infiltration (as thoron interference) into the diffusion chamber of the monitor were evaluated. The temporal variation was obtained based on measurements of the underfloor space of a Japanese wooden dwelling using a diffusion-type radon monitor, a reference radon monitor which was not affected by thoron interference, and a thoron monitor. The thoron infiltration rate for the diffusion-type monitor varied from 0% to 20%. In particular, it appeared to increase when ventilation of the underfloor space air was forced. The variable thoron infiltration rate, with respect to ventilation strength, implied that not only a diffusive process, but also an advective process, played a major role in air exchange between the diffusion chamber of the monitor and the outer air. When an exposure room is characterized by the frequent variation in air ventilation, a variable thoron response is considered to occur in radon–thoron discriminative detectors, in which only diffusive entry is employed as a mechanism for the discrimination of radon and thoron.
Domain Shuffling between Vip3Aa and Vip3Ca: Chimera Stability and Insecticidal Activity against European, American, African, and Asian Pests

The bacterium Bacillus thuringiensis produces insecticidal Vip3 proteins during the vegetative growth phase with activity against several lepidopteran pests. To date, three different Vip3 protein families have been identified based on sequence identity: Vip3A, Vip3B, and Vip3C. In this study, we report the construction of chimeras by exchanging domains between Vip3Aa and Vip3Ca, two proteins with marked specificity differences against lepidopteran pests. We found that some domain combinations made proteins insoluble or prone to degradation by trypsin as most abundant insect gut protease. The soluble and trypsin-stable chimeras, along with the parental proteins Vip3Aa and Vip3Ca, were tested against lepidopteran pests from different continents: Spodoptera exigua, Spodoptera littoralis, Spodoptera frugiperda, Helicoverpa armigera, Mamestra brassicae, Anticarsia gemmatalis, and Ostrinia furnacalis. The exchange of the Nt domain (188 N-terminal amino acids) had little effect on the stability and toxicity (equal or slightly lower) of the resulting chimeric protein against all insects except for S. frugiperda, for which the chimera with the Nt domain from Vip3Aa and the rest of the protein from Vip3Ca showed a significant increase in toxicity compared to the parental Vip3Ca. Chimeras with the C-terminal domain from Vip3Aa (from amino acid 510 of Vip3Aa to the Ct) with the central domain of Vip3Ca (amino acids 189–509 based on the Vip3Aa sequence) made proteins that could not be solubilized. Finally, the chimera including the Ct domain of Vip3Ca and the Nt and central domain from Vip3Aa was unstable. Importantly, an insect species tolerant to Vip3Aa but susceptible to Vip3Ca, such as Ostrinia furnacalis, was also susceptible to chimeras maintaining the Ct domain from Vip3Ca, in agreement with the hypothesis that the Ct region of the protein is the one conferring specificity to Vip3 proteins.
Gliadin Nanoparticles Induce Immune Tolerance to Gliadin in Mouse Models of Celiac Disease.

BACKGROUND & AIMS Celiac disease could be treated, and potentially cured, by restoring T-cell tolerance to gliadin. We investigated the safety and efficacy of negatively charged, 500 nm, poly(lactide-co-glycolide) nanoparticles encapsulating gliadin protein (TIMP-GLIA) in 3 mouse models of celiac disease. Uptake of these nanoparticles by antigen-presenting cells was shown to induce immune tolerance in other animal models of autoimmune disease. METHODS We performed studies with C57BL/6, RAG1-/- (C57BL/6), and HLA-DQ8, huCD4 transgenic Ab0 NOD mice. Mice were given 1 or 2 tail-vein injections of TIMP-GLIA or control nanoparticles. Some mice were given intradermal injections of gliadin in complete Freund's adjuvant (immunization), or of soluble gliadin or ovalbumin (ear challenge). RAG-/- mice were given intraperitoneal injections of CD4+CD62L-CD44hi T cells from gliadin-immunized C57BL/6 mice, and were fed with AIN-76A-based diet containing wheat gluten (oral challenge), or without gluten. Spleen or lymph node cells were analyzed in proliferation and cytokine secretion assays, or by flow cytometry, RNA sequencing or real-time quantitative PCR. Serum samples were analyzed by gliadin antibody ELISA, and intestinal tissues were analyzed by histology. Human PBMC, or immature dendritic cells derived from human PBMC, were cultured in medium containing TIMP-GLIA, anti-CD3 antibody, or LPS (controls) and analyzed in proliferation and cytokine secretion assays or by flow cytometry. Whole blood or plasma from healthy volunteers was incubated with TIMP-GLIA, and hemolysis, platelet activation and aggregation, and complement activation or coagulation were analyzed. RESULTS TIMP-GLIA did not increase markers of maturation on cultured human dendritic cells or induce activation of T cells from patients with active or treated celiac disease. In the delayed-type hypersensitivity (model 1), the HLA-DQ8 transgenic (model 2), and the gliadin memory T cell enteropathy (model 3) models of celiac disease, intravenous injections of TIMP-GLIA significantly decreased gliadin-specific T cell proliferation (in models 1 and 2), inflammatory cytokine secretion (in models 1, 2, and 3), circulating gliadin-specific IgG/IgG2c (in models 1 and 2), ear swelling (in model 1), gluten-dependent enteropathy (in model 3), and body weight loss (in model 3). In model 1, the effects were shown to be dose dependent. Splenocytes from HLA-DQ8 transgenic mice given TIMP-GLIA nanoparticles, but not control nanoparticles, had increased levels of FOXP3, and gene expression signatures associated with tolerance induction. CONCLUSIONS In mice with gliadin sensitivity, injection of TIMP-GLIA nanoparticles induced unresponsiveness to gliadin, and reduced markers of inflammation and enteropathy. This strategy might be developed for treatment of celiac disease.
Safety and Design Aspects of Powered Toothbrush—A Narrative Review

The powered toothbrush has become a modern dental tool that is available in the supermarket. Indeed, the design of the powered toothbrush, e.g., mechanical and electrical, would affect not only the efficacy but also the safety of the products. This narrative review attempted to view the powered toothbrush from design, safety, and application points with respect to tufts, filaments, handles, mechanics, motions, and materials interactions from various available sources. Different brands and models of powered toothbrushes have their own designs that might affect the clinical outcome. The rotational design was advocated to be clinically more effective than the manual one, some modern models might be designed with vibrational or oscillation (or mixed) tufts head that might be useful in patients with specific needs, such as having xerostomia or for the elderly. To conclude, tuft retention design is important in the powered toothbrush as it contributes significantly to safety as the fallen off tufts, filaments and metal parts might cause injury. Tests revealing the retention force of brush head plates and brush head bristles will be significant references for consumers to determine which design of powered toothbrushes is relatively safer.
Differential contributions of fatigue‐induced strength loss and slowing of angular velocity to power loss following repeated maximal shortening contractions

The purpose of this study was to investigate the relationship between fatigue‐induced reductions in isometric torque and isotonic power and to quantify the extent to which the decreases in angular velocity and dynamic torque can explain the power loss immediately following an isotonic fatiguing task and throughout recovery in seven young males and six young females. All measurements were performed with both legs. For dorsiflexion, fatigue‐related time‐course changes in isometric maximal voluntary contraction (MVC) torque, angular velocity, dynamic torque, and power production following repeated maximal isotonic contractions (load: 20% MVC) were investigated before, immediately after, and 1, 2, 5 and 10 min after a fatiguing task. There were no relationships between the fatigue‐related reductions in isometric MVC torque and peak power at any timepoint, suggesting that fatigue‐induced reductions in isometric MVC torque does not entirely reflect fatigue‐induced changes in dynamic performance. The relative contribution of fatigue‐related reduction in dynamic torque on power loss was greater immediately following the task, and lower throughout recovery than the corresponding decrease in angular velocity. Thus, power loss immediately following the task was more strongly related to the decline in dynamic torque; however, this relationship shifted throughout recovery to a greater dependence on slowing of angular velocity for power loss.
Circulatory miR-133b and miR-21 as Novel Biomarkers in Early Prediction and Diagnosis of Coronary Artery Disease

While coronary artery disease (CAD) has become a major threat worldwide, the timely biomarker-based early diagnosis of CAD remains a major unmet clinical challenge. We aimed towards assessing the level of circulatory microRNAs as candidates of novel biomarkers in patients with CAD. A total of 147 subjects were recruited which includes 78 subjects with angiographically proven CAD, 15 pre-atherosclerotic normal coronary artery (NCA) subjects and 54 healthy individuals. Quantitative real-time PCR assays were performed. MiR-133b was downregulated by 4.6 fold (p < 0.0001) whereas miR-21 was upregulated by ~2 fold (p < 0.0001) in plasma samples of CAD patients. Importantly, both the miRNAs showed association with disease severity as miR-133b was downregulated by 8.45 fold in acute coronary syndrome (ACS), 3.38 fold in Stable angina (SA) and 2.08 fold in NCA. MiR-21 was upregulated by 2.46 fold in ACS, 1.90 fold in SA and 1.12 fold in NCA. Moreover, miR-133b could significantly differentiate subjects with ST-elevation myocardial infarction (STEMI) from Non-STEMI. Area under the curve (AUC) for miR-133b was 0.80 with >75.6% sensitivity and specificity, AUC for miR-21 was 0.79 with >69.4% sensitivity and specificity. Our results suggest that miR-133b and miR-21 could be possible candidates of novel biomarkers in early prediction of CAD.
Airway Epithelial cGAS Is Critical for Induction of Experimental Allergic Airway Inflammation

Key Points Airway epithelial cGAS plays a key role in asthma pathogenesis. cGAS may be a promising target against allergic airway inflammation. DNA damage could lead to the accumulation of cytosolic DNA, and the cytosolic DNA–sensing pathway has been implicated in multiple inflammatory diseases. However, the role of cytosolic DNA–sensing pathway in asthma pathogenesis is still unclear. This article explored the role of airway epithelial cyclic GMP-AMP synthase (cGAS), the major sensor of cytosolic dsDNA, in asthma pathogenesis. Cytosolic dsDNA accumulation in airway epithelial cells (ECs) was detected in the setting of allergic inflammation both in vitro and in vivo. Mice with cGAS deletion in airway ECs were used for OVA- or house dust mite (HDM)–induced allergic airway inflammation. Additionally, the effects of cGAS knockdown on IL-33–induced GM-CSF production and the mechanisms by which IL-33 induced cytosolic dsDNA accumulation in human bronchial epithelial (HBE) cells were explored. Increased accumulation of cytosolic dsDNA was observed in airway epithelium of OVA- or HDM-challenged mice and in HBE cells treated with IL-33. Deletion of cGAS in the airway ECs of mice significantly attenuated the allergic airway inflammation induced by OVA or HDM. Mechanistically, cGAS participates in promoting TH2 immunity likely via regulating the production of airway epithelial GM-CSF. Furthermore, Mito-TEMPO could reduce IL-33–induced cytoplasmic dsDNA accumulation in HBE cells possibly through suppressing the release of mitochondrial DNA into the cytosol. In conclusion, airway epithelial cGAS plays an important role via sensing the cytosolic dsDNA in asthma pathogenesis and could serve as a promising therapeutic target against allergic airway inflammation.