Miracle-dz/UniFAR-FTUs huggingface dataset:
Associations of plasma trimethylamine N-oxide, choline, carnitine, and betaine with inflammatory and cardiometabolic risk biomarkers and the fecal microbiome in the Multiethnic Cohort Adiposity Phenotype Study.

BACKGROUND Trimethylamine N-oxide (TMAO), a compound derived from diet and metabolism by the gut microbiome, has been associated with several chronic diseases, although the mechanisms of action are not well understood and few human studies have investigated microbes involved in its production. OBJECTIVES Our study aims were 1) to investigate associations of TMAO and its precursors (choline, carnitine, and betaine) with inflammatory and cardiometabolic risk biomarkers; and 2) to identify fecal microbiome profiles associated with TMAO. METHODS We conducted a cross-sectional analysis using data collected from 1653 participants (826 men and 827 women, aged 60-77 y) in the Multiethnic Cohort Study. Plasma concentrations of TMAO and its precursors were measured by LC-tandem MS. We also analyzed fasting blood for markers of inflammation, glucose and insulin, cholesterol, and triglycerides (TGs), and further measured blood pressure. Fecal microbiome composition was evaluated by sequencing the 16S ribosomal RNA gene V1-V3 region. Associations of TMAO and its precursors with disease risk biomarkers were assessed by multivariable linear regression, whereas associations between TMAO and the fecal microbiome were assessed by permutational multivariate ANOVA and hurdle regression models using the negative binomial distribution. RESULTS Median (IQR) concentration of plasma TMAO was 3.05 μmol/L (2.10-4.60 μmol/L). Higher concentrations of TMAO and carnitine, and lower concentrations of betaine, were associated with greater insulin resistance (all P < 0.02). Choline was associated with higher systolic blood pressure, TGs, lipopolysaccharide-binding protein, and lower HDL cholesterol (P ranging from <0.001 to 0.03), reflecting an adverse cardiometabolic risk profile. TMAO was associated with abundance of 13 genera (false discovery rate < 0.05), including Prevotella, Mitsuokella, Fusobacterium, Desulfovibrio, and bacteria belonging to the families Ruminococcaceae and Lachnospiraceae, as well as the methanogen Methanobrevibacter smithii. CONCLUSIONS Plasma TMAO concentrations were associated with a number of trimethylamine-producing bacterial taxa, and, along with its precursors, may contribute to inflammatory and cardiometabolic risk pathways.
MicroRNA‐34a causes ceramide accumulation and effects insulin signaling pathway by targeting ceramide kinase (CERK) in aging skeletal muscle

Aging skeletal muscle shows perturbations in metabolic functions. MicroRNAs have been shown to play a critical role in aging and metabolic functions of skeletal muscle. MicroRNA‐34a (miR‐34a) is implicated in the brain and cardiac aging, however, its role in aging muscle is unclear. We analyzed levels of miR‐34a, ceramide kinase (CERK) and other insulin signaling molecules in skeletal muscle from old mice. In addition to in vivo model, levels of these molecules were also analyzed in myoblast derived from insulin resistant (IR) humans and C2C12 myoblasts overexpressing mir‐34a. Our results show that miR‐34a is elevated in the muscles of 2‐year‐old mice and in the myoblasts of IR humans. Overexpression of miR‐34a in C2C12 myoblasts leads to alterations in the insulin signaling pathway, which were rescued by its antagonism. Our analyses revealed that miR‐34a targets CERK resulting in ceramide accumulation, activation of PP2A and the pJNK pathway in muscle and C2C12 myoblasts. Also, myostatin (Mstn) levels were increased in 2‐year‐old mouse muscle and Mstn treatment upregulated miR‐34a in C2C12 myoblasts. In addition, miR‐34a expression and ceramide levels did not increase during aging in Mstn−/− mice muscle. In summary, we, therefore, propose that Mstn levels increase in aging muscle and upregulate miR‐34a, which inhibits CERK resulting in increased ceramide levels. This ceramide accumulation activates PP2A and pJNK causing hypophosphorylation of AKT and hyperphosphorylation of IRS1 (Ser307), respectively, impairing insulin signaling pathway and eventually inhibiting the sarcolemma localization of GLUT4. These changes would result in reduced glucose uptake and insulin resistance. This study is the first to explain the phenomenon of ceramide accrual and impairment of insulin signaling pathway in aging muscle through a miR‐34a based mechanism. In conclusion, our results suggest that Mstn and miR‐34a antagonism can help ameliorate ceramide accumulation and loss of insulin sensitivity in aging skeletal muscle.
A systematic review of cross-sectional studies on the association of sedentary behavior with cardiometabolic diseases and related biomarkers in South American adults.

INTRODUCTION sedentary behavior (SB) has been independently associated with detrimental health outcomes in different regions worldwide. The aim of this systematic review was to examine whether domain-specific SB is associated with cardiometabolic diseases (CMD) and related biomarkers in South American adults. METHODS nine electronic databases were searched to identify all studies that analyzed the association between SB and CMD-e.g. obesity, diabetes, hypertension, metabolic syndrome (MetS) and clustering of chronic diseases (CCD)-and related biomarkers in South American adults. Two independent reviewers performed the necessary abstract/full-text screening, data abstraction, and quality assessments. The review protocol was registered in the PROSPERO database (CRD42018099319). RESULTS from the 1,262 articles identified in the search 262 were reviewed in full and 20 were used in the analysis in accordance to the inclusion criteria. High SB (mainly sitting and TV time) was associated with an increased likelihood of obesity (n = 8), diabetes (n = 6), and CCD (n = 3), as well as high values of BMI (n = 8), WC (n = 7), % BF (n = 4), plasma lipids (n = 4), and glycemia (n = 5). Eleven out of 20 studies were of higher quality. CONCLUSION long time spent in SB, mainly sitting and TV time, was positively associated with the occurrence of CMD and related biomarkers in South American adults.
Factors associated with stroke among adult patients with hypertension in Ayder Comprehensive Specialized Hospital, Tigray, Ethiopia, 2018: A case-control study

Background Globally, the burden of stroke is increasing at an alarming rate. Factors associated with stroke among hypertensive patients are not consistent across different studies and there are limited studies particularly to hypertensive stroke in the particular setting. This study aimed to assess factors associated with stroke among patients with hypertension in Ayder Comprehensive Specialized Hospital, Mekelle, Tigray, Ethiopia, in 2018. Methods Hospital-based case-control study was conducted from February to April 2018. Cases were adult hypertensive patients with stroke and controls were adult hypertensive patients without a stroke. Cases and controls were identified from the patient’s card review. Using a systematic random sampling technique 89 cases and 356 controls were included in this study. Record review, physical measurement, and interview techniques were used to collect data. Data was entered and analyzed by using SPSS version 23. Variables with a p-value of less than 0.25 in the bivariate logistic regression were selected for multivariable logistic regression. The adjusted odds ratio and 95% confidence interval were used to determine the association. P-value <0.05 was used to declare statistical significance. Results The mean age of cases and controls were 56.3 years (SD±13.53) and 51.9 years (SD±12.67) respectively. Lost to follow-up (AOR = 2.474, 95%CI: 1.368–4.929), alcohol drinking (AOR = 2.440, 95%CI: 1.291–4.613), use of excessive salt in diet (AOR = 3.249, 95%CI: (1.544–6.837), medication non-adherence (AOR = 3.967, 95%CI: 2.256–6.973), uncontrolled systolic blood pressure, (AOR = 3.196, 95%CI: 1.60–6.382), uncontrolled diastolic blood pressure (AOR = 2.204, 95%CI: 1.130–4.297) and high cholesterol level (AOR = 2.413, 95%CI: 1.319–4.414) were found to be significant factors. Conclusion Lost to follow-up, alcohol drinking, uses of excessive salt in diet, medication non-adherence, and uncontrolled systolic and diastolic blood pressure were associated with stroke. Health education on lifestyle practices and hypertension-related complications in each follow-up visit is very essential for improving the primary stroke prevention.
Assisted migration across fixed seed zones detects adaptation lags in two major North American tree species

Abstract Boreal forests are experiencing dramatic climate change, having warmed 1.0°–1.9°C over the last century. Yet forest regeneration practices are often still dictated by a fixed seed zone framework, in which seeds are both harvested from and planted into predefined areas. Our goal was to determine whether seedlings sourced from southern seed zones in Minnesota USA are already better adapted to northerly seed zones because of climate change. Bur oak (Quercus macrocarpa) and northern red oak (Quercus rubra) seedlings from two seed zones (i.e., tree ecotypes) were planted into 16 sites in two northern seed zones and measured for 3 yr. Our hypotheses were threefold: (1) tree species with more southern geographic distributions would thrive in northern forests where climate has already warmed substantially, (2) southern ecotypes of these species would have higher survival and growth than the northern ecotype in northern environments, and (3) natural selection would favor seedlings that expressed phenotypic and phenological traits characteristic of trees sourced from the more southern seed zone. For both species, survival was high (>93%), and southern ecotypes expressed traits consistent with our climate adaptation hypotheses. Ecotypic differences were especially evident for red oak; the southern ecotype had had higher survival, lower specific leaf area (SLA), faster height and diameter growth, and extended leaf phenology relative to the northern ecotype. Bur oak results were weaker, but the southern ecotype also had earlier budburst and lower SLA than the northern ecotype. Models based on the fixed seed zones failed to explain seedling performance as well as those with continuous predictors (e.g., climate and geographical position), suggesting that plant adaptations within current seed zone delineations do align with changing climate conditions. Adding support for this conclusion, natural selection favored traits expressed by the more southern tree ecotypes. Collectively, these results suggest that state seed sourcing guidelines should be reexamined to permit plantings across seed zones, a form of assisted migration. More extensive experiments (i.e., provenance trails) are necessary to make species‐specific seed transfer guidelines that account for climate trends while also considering the precise geographic origin of seed sources.
Identification of Normal Pressure Hydrocephalus by Disease-Specific Patterns of Brain Stiffness and Damping Ratio.

OBJECTIVES The aim of this study was to perform a whole-brain analysis of alterations in brain mechanical properties due to normal pressure hydrocephalus (NPH). MATERIALS AND METHODS Magnetic resonance elastography (MRE) examinations were performed on 85 participants, including 44 cognitively unimpaired controls, 33 with NPH, and 8 who were amyloid-positive with Alzheimer clinical syndrome. A custom neural network inversion was used to estimate stiffness and damping ratio from patches of displacement data, accounting for edges by training the network to estimate the mechanical properties in the presence of missing data. This learned inversion was first compared with a standard analytical approach in simulation experiments and then applied to the in vivo MRE measurements. The effect of NPH on the mechanical properties was then assessed by voxel-wise modeling of the stiffness and damping ratio maps. Finally, a pattern analysis was performed on each individual's mechanical property maps by computing the correlation between each person's maps with the expected NPH effect. These features were used to fit a classifier and assess diagnostic accuracy. RESULTS The voxel-wise analysis of the in vivo mechanical property maps revealed a unique pattern in participants with NPH, including a concentric pattern of stiffening near the dural surface and softening near the ventricles, as well as decreased damping ratio predominantly in superior regions of the white matter (family-wise error corrected P < 0.05 at cluster level). The pattern of viscoelastic changes in each participant predicted NPH status in this cohort, separating participants with NPH from the control and the amyloid-positive with Alzheimer clinical syndrome groups, with areas under the receiver operating characteristic curve of 0.999 and 1, respectively. CONCLUSIONS This study provides motivation for further development of the neural network inversion framework and demonstrates the potential of MRE as a novel tool to diagnose NPH and provide a window into its pathogenesis.
Titania/Electro-Reduced Graphene Oxide Nanohybrid as an Efficient Electrochemical Sensor for the Determination of Allura Red

Titania/electro-reduced graphene oxide nanohybrids (TiO2/ErGO) were synthesized by the hydrolysis of titanium sulfate in graphene oxide suspension and in situ electrochemical reduction. It provides a facile and efficient method to obtain nanohybrids with TiO2 nanoparticles (TiO2 NPs) uniformly coated by graphene nanoflakes. TiO2/ErGO nanohybrids were characterized by transmission electron microscopy, X-ray diffraction, cyclic voltammogram, and electrochemical impedance spectroscopy in detail. Compared with pure ErGO and TiO2 NPs, TiO2/ErGO nanohybrids greatly enhanced the electrocatalytic activity and voltammetric response of Allura Red. In the concentration range of 0.5–5.0 μM, the anodic peak currents of Allura Red were linearly correlated to their concentrations. However, the linear relationship was changed to the semi-logarithmic relationship at a higher concentration region (5.0–800 μM). The detection limit (LOD) was 0.05 μM at a signal-to-noise ratio of 3. The superior sensing performances of the proposed sensor can be ascribed to the synergistic effect between TiO2 NPs and ErGO, which provides a favorable microenvironment for the electrochemical oxidation of Allura Red. The proposed TiO2/ErGO/GCE showed good reproducibility and stability both in determination and in storage, and it can accurately detect the concentration of Allura Red in milk drinks, providing an efficient platform for the sensitive determination of Allura Red with high reliability, simplicity, and rapidness.
Methods of Granulocyte Isolation from Human Blood and Labeling with Multimodal Superparamagnetic Iron Oxide Nanoparticles

This in vitro study aimed to find the best method of granulocyte isolation for subsequent labeling with multimodal nanoparticles (magnetic and fluorescent properties) to enable detection by optical and magnetic resonance imaging (MRI) techniques. The granulocytes were obtained from venous blood samples from 12 healthy volunteers. To achieve high purity and yield, four different methods of granulocyte isolation were evaluated. The isolated granulocytes were labeled with multimodal superparamagnetic iron oxide nanoparticles (M-SPIONs) coated with dextran, and the iron load was evaluated qualitatively and quantitatively by MRI, near-infrared fluorescence (NIRF) and inductively coupled plasma mass spectrometry (ICP-MS). The best method of granulocyte isolation was Percoll with Ficoll, which showed 95.92% purity and 94% viability. After labeling with M-SPIONs, the granulocytes showed 98.0% purity with a yield of 3.5 × 106 cells/mL and more than 98.6% viability. The iron-loading value in the labeled granulocytes, as obtained by MRI, was 6.40 ± 0.18 pg/cell. Similar values were found with the ICP-MS and NIRF imaging techniques. Therefore, our study shows that it is possible to isolate granulocytes with high purity and yield and labeling with M-SPIONs provides a high internalized iron load and low toxicity to cells. Therefore, these M-SPION-labeled granulocytes could be a promising candidate for future use in inflammation/infection detection by optical and MRI techniques.
Systematic review of in vitro studies evaluating tooth bleaching efficacy.

PURPOSE To review and assess the literature on in vitro studies evaluating tooth bleaching efficacy considering the use of a negative control, type of tooth substrate, storage medium, color evaluation methods, and evaluation time points. METHODS The following databases were searched: PubMed (MEDLINE), Web of Science. Search used Medical Subject Headings (MeSH) in PubMed in addition to free text. The following limits were applied: English, articles published between January 1989 and October 2017. Additional free text key terms included: in vitro, tooth bleaching, placebo, negative control, overall CIELAB color change (ΔE*ab), change in shade guide units (ΔSGU), tooth color stabilization, evaluation time points, bovine teeth, and staining. Search was repeated in Web of Science but no additional articles were identified. A total of 11 studies were included for qualitative and quantitative analysis. RESULTS The meta-analysis of nine included studies that reported ΔE*ab values, revealed that the NC statistically exceeded the perceptibility threshold (PT) of 1.2 (P< 0.05). The estimate was 2.872 with lower and upper bounds of 1.955 and 3.790, respectively. CLINICAL SIGNIFICANCE Randomized controlled trials are gold standards to evaluate bleaching efficacy of different materials. However, in vitro studies offer a way to screen for potential bleaching efficacy. It is vital to determine an appropriate cut-off value for determining bleaching efficacy in vitro and further apply for clinical relevance.
GC-MS Metabolite Profile and Identification of Unusual Homologous Cannabinoids in High Potency Cannabis sativa

Abstract Phytochemical investigation of the lipids extracted from seeds of Cannabis sativa by GC-MS showed 43 cannabinoids, 16 of which are new. The extract is dominated by Δ9-tetrahydrocannabinolic acid (A) and its neutral derivative trans-Δ9-tetrahydrocannabinol-C5 (THC) Cis and trans-Δ9-tetrahydrocannabinol-C7 isomers with an ethyl-pentyl branched chain together with minor amounts of trans-Δ9-tetrahydrocannabinol with a methyl-pentyl C6 branched side chain were identified as new natural compounds. Four cannabichromene isomers with a C5 side chain are postulated to be derived from the double bond migration at the terminal isoprenyl unit. C7 cannabichromene together with the neutral and acidic forms of cannabinol-C7 were also detected. The mass spectrum of these homologues as trimethylsilyl (TMS) derivatives are presented, and the fragmentation patterns are discussed.
IoT-Stream: A Lightweight Ontology for Internet of Things Data Streams and Its Use with Data Analytics and Event Detection Services †

With the proliferation of sensors and IoT technologies, stream data are increasingly stored and analysed, but rarely combined, due to the heterogeneity of sources and technologies. Semantics are increasingly used to share sensory data, but not so much for annotating stream data. Semantic models for stream annotation are scarce, as generally, semantics are heavy to process and not ideal for Internet of Things (IoT) environments, where the data are frequently updated. We present a light model to semantically annotate streams, IoT-Stream. It takes advantage of common knowledge sharing of the semantics, but keeping the inferences and queries simple. Furthermore, we present a system architecture to demonstrate the adoption the semantic model, and provide examples of instantiation of the system for different use cases. The system architecture is based on commonly used architectures in the field of IoT, such as web services, microservices and middleware. Our system approach includes the semantic annotations that take place in the pipeline of IoT services and sensory data analytics. It includes modules needed to annotate, consume, and query data annotated with IoT-Stream. In addition to this, we present tools that could be used in conjunction to the IoT-Stream model and facilitate the use of semantics in IoT.
Making it happen: Challenges and transformations in health care processes, people management, and decision-making

First of all, the reduction of resources allocated to finance health services provision. During the past financial crisis, many European countries were severely affected by the economic downturn and, consequently, they have been having to reduce health spending to rein in public budgets. Healthcare systems are, in those countries, founded for three-fourths from public sources. Policies and actions to reduce spending growth encompassed controls in the recruitment of public health workforce, cuts to the budget to providers, and the containment of spending in current expenses (e.g. pharmaceutical and medical devices). Health systems are now challenged to identify innovative managerial tools to cope with a limited public spending capacity. Among these approaches, this special issue provides evidence on the effectiveness of Supply Chain Management (Buttigieg et al.) and budget impact analysis (Foglia et al.).
Use and utility of serologic tests for rheumatoid arthritis in primary care.

INTRODUCTION In this retrospective, register-based population study, we evaluated if anti-citrullinated protein antibodies (ACPA) is a better choice than immunoglobulin M rheumatoid factor (IgM RF) in primary care when rheumatoid arthritis (RA) is suspected, as it determines predictive values in real-life settings. Furthermore, the study described ordering patterns to investigate the benefit of repeated testing. METHODS Test result, requisitioning unit, test date and the patient's social security number were collected from the Department of Clinical Immunology at Odense University Hospital in 2007-2016 and merged with patient diagnoses from the Danish National Patient Registry. RESULTS Overall, 5% were diagnosed with RA. IgM RF remained the preferred test during the entire period. Test sensitivity was 61% for IgM RF and 54% for ACPA. The test specificity was 88% for IgM RF and 96% for ACPA. Positive predictive value (PPV) was higher for ACPA than for IgM RF (30% versus 12%) and negative predictive value (NPV) was equal (99%) in primary care. Few individuals seroconverted from negative to positive (ACPA 2% and IgM RF 5%) and positive to negative (ACPA 3% and IgM RF 6%). CONCLUSIONS ACPA has a higher PPV for RA than IgM RF, whereas their NPV is identical. ACPA is the better choice when testing for RA in primary care. Seroconversion is rare, and it is only rarely relevant to retest. FUNDING The Department of Clinical immunology at Odense University Hospital funded the study. TRIAL REGISTRATION not relevant.