Miracle-dz/UniFAR-FTUs huggingface dataset:
An action‐oriented framework for systems‐based solutions aimed at childhood obesity prevention in US Latinx and Latin American populations

Childhood obesity in US Latinx and Latin American populations is a persistent, complex public health issue and, as such, requires solutions grounded on systems science theory and methods. In this paper, we introduce an action‐oriented framework to design, implement, evaluate, and sustain whole‐of‐community systems changes for childhood obesity prevention in US Latinx and Latin American populations. Our framework covers six action steps: (1) foster multisectoral team; (2) map the system, its context, and drivers; (3) envision system‐wide changes; (4) effect system‐wide changes; (5) monitor, learn, and adapt; and (6) scale and sustain. We also propose 10 principles that put human and environmental rights and systems thinking at the center of these systems‐based solutions. For each action step, we provide a list of concrete activities, methods, approaches, and examples that can be used to guide and inform the work needed to achieve the expected outputs. Finally, we discuss how a wider adoption of systems science for childhood obesity prevention among US Latinx and Latin American populations can be encouraged and sustained.
Neuron-specific enolase concentrations for the prediction of poor prognosis of comatose patients after out-of-hospital cardiac arrest: an observational cohort study.

BACKGROUND Neuron-specific enolase (NSE) is a biomarker for neurological outcomes after cardiac arrest with the most evidence collected thus far; however, recommended prognostic cutoff values are lacking owing to the discrepancies in the published data. AIMS To establish NSE cutoff values for prognostication in the environment of a cardiac intensive care unit following out-of-hospital cardiac arrest (OHCA). METHODS A consecutive series of 82 patients admitted after OHCA were enrolled. Blood samples for the measurement of NSE levels were collected at admission and after 1, 3, 12, 24, 48, and 72 h. Neurological outcomes were quantified using the cerebral performance category (CPC) index. Each patient was classified into either the good (CPC ≤ 2) or poor prognosis (CPC ≥ 3) group. RESULTS Median NSE concentrations were higher in the poor prognosis group, and the difference reached significance at 48 and 74 h (84.4 ng/ml versus 22.9 ng/ml at 48 h and 152.1 ng/ml versus 18.7 ng/ml at 72 h, P < 0.001). Moreover, in the poor prognosis group, NSE increased significantly between 24 and 72 h (P < 0.001). NSE cutoffs for the prediction of poor prognosis after OHCA were 39.8 ng/ml, 78.7 ng/ml and 46.2 ng/ml for 24, 48, and 72 h, respectively. The areas under the curve were significant at each time point, with the highest values at 48 and 72 h after admission (0.849 and 0.964, respectively). CONCLUSION Elevated NSE concentrations with a rise in levels in serial measurements may be utilized in the prognostication algorithm after OHCA.
Differentiation in stem and leaf traits among sympatric lianas, scandent shrubs and trees in a subalpine cold temperate forest

Abstract The scandent shrub plant form is a variant of liana that has upright and self-supporting stems when young but later becomes a climber. We aimed to explore the associations of stem and leaf traits among sympatric lianas, scandent shrubs and trees, and the effects of growth form and leaf habit on variation in stem or leaf traits. We measured 16 functional traits related to stem xylem anatomy, leaf morphology and nutrient stoichiometry in eight liana, eight scandent shrub and 21 tree species co-occurring in a subalpine cold temperate forest at an elevation of 2600–3200 m in Southwest China. Overall, lianas, scandent shrubs and trees were ordered along a fast–slow continuum of stem and leaf functional traits, with some traits overlapping. We found a consistent pattern of lianas > scandent shrubs > trees for hydraulically weighted vessel diameter, maximum vessel diameter and theoretical hydraulic conductivity. Vessel density and sapwood density showed a pattern of lianas = scandent shrubs < trees, and lianas < scandent shrubs = trees, respectively. Lianas had significantly higher specific leaf area and lower carbon concentration than co-occurring trees, with scandent shrubs showing intermediate values that overlapped with lianas and trees. The differentiation among lianas, scandent shrubs and trees was mainly explained by variation in stem traits. Additionally, deciduous lianas were positioned at the fast end of the trait spectrum, and evergreen trees at the slow end of the spectrum. Our results showed for the first time clear differentiation in stem and leaf traits among sympatric liana, scandent shrub and tree species in a subalpine cold temperate forest. This work will contribute to understanding the mechanisms responsible for variation in ecological strategies of different growth forms of woody plants.
ngsComposer: an automated pipeline for empirically based NGS data quality filtering

Abstract Next-generation sequencing (NGS) enables massively parallel acquisition of large-scale omics data; however, objective data quality filtering parameters are lacking. Although a useful metric, evidence reveals that platform-generated Phred values overestimate per-base quality scores. We have developed novel and empirically based algorithms that streamline NGS data quality filtering. The pipeline leverages known sequence motifs to enable empirical estimation of error rates, detection of erroneous base calls and removal of contaminating adapter sequence. The performance of motif-based error detection and quality filtering were further validated with read compression rates as an unbiased metric. Elevated error rates at read ends, where known motifs lie, tracked with propagation of erroneous base calls. Barcode swapping, an inherent problem with pooled libraries, was also effectively mitigated. The ngsComposer pipeline is suitable for various NGS protocols and platforms due to the universal concepts on which the algorithms are based.
Embedding of polyaniline molecules on adhesive tape using successive ionic layer adsorption and reaction (SILAR) technique

Polyaniline molecules are embedded on adhesive tape using successive ionic layer adsorption and reaction (SILAR) technique. The infrared spectrum shows the existence of molecular vibrational modes associated with the presence of polyaniline molecules on the sample. With the addition of polyaniline molecules, the conductivity of adhesive tape increases. Surface conductivity increases with number of dipping cycle until it reaches a certain value. Beyond this value, surface conductivity begins to decrease. The surface conductivity of the sample is associated with the connectivity of the embedded polyaniline molecules. The connectivity increases as the number of dipping cycle progresses. Meanwhile, the decrease in surface conductivity is attributed to the eroding of existing embedded structure at higher number of dipping cycle.
Efficacy of a nanoparticle vaccine administered in-ovo against Salmonella in broilers

Salmonella is a zoonotic pathogen that persists in poultry. Salmonella vaccines that can be delivered in-ovo can be cost-effective and can decrease Salmonella load in poultry. This study evaluates the efficacy of a Salmonella chitosan-nanoparticle (CNP) vaccine, administered in-ovo, in broilers. CNP vaccine was synthesized with Salmonella Enteritidis (SE) outer-membrane-proteins (OMPs) and flagellin proteins. At embryonic-d18, one-hundred-thirty-six eggs were injected with 200μl PBS or 1000μg CNP into the amniotic cavity. At d1-of-age, 132 chicks were allocated in 6 pens/treatment with 11 chicks/pen. At d7, birds were orally challenged with 1×109 CFU/bird SE. At d1, 8h-post-challenge, d14, and d21, serum anti-SE-OMPs IgY were analyzed. At d14 and d21, cloacal swabs and bile anti-SE-OMPs IgA, CD4+/CD8+-T-cell ratios, and ceca SE loads were analyzed. At d21, cecal tonsil IL-1β, IL-10, and iNOS mRNA were analyzed. Body-weight-gain (BWG) and feed-conversion-ratio (FCR) were recorded weekly. Data were analyzed by Student’s t-test at P<0.05. There were no significant differences in BWG or FCR between vaccinated birds compared to control. At d1, CNP-vaccinated birds had 5.62% greater levels (P<0.05) of anti-SE-OMPs IgY, compared to control. At 8h-post-challenge, CNP-vaccinated birds had 6.39% greater levels (P<0.05) of anti-SE-OMPs IgY, compared to control. At 2wk-post-challenge, CNP-vaccinated birds had 7.34% lower levels (P<0.05) of anti-SE-OMPs IgY, compared to control. At 1wk-post-challenge, CNP-vaccinated birds had 15.30% greater levels (P<0.05) of bile anti-SE-OMPs IgA, compared to control. At d14 and d21, CNP-vaccinated birds had 0.62 and 0.85 Log10 CFU/g, decreased SE ceca load (P<0.05), respectively, compared to control. There were no significant differences in CD4+/CD8+-T-cell ratios between vaccinated birds compared to control. There were no significant differences in IL-1β, IL-10, iNOS mRNA between vaccinated birds compared to control. Findings demonstrate that the in-ovo administration of CNP vaccine can induce an antigen-specific immune response against SE and can decrease SE cecal load in broilers.
Production of isoquinoline alkaloids from the in vitro conserved Fumaria parviflora and their in vitro wound healing activity

Abstract Fumaria parviflora Lam. is a rare herbaceous annual plant, with a well-known richness of isoquinoline alkaloids. It is threaten due to expansion on construction in the Mediterranean coastal region. We established callus culture protocol aiming at in vitro conservation of this plant. Murashige and Skoog medium fortified with a combination of 0.5 mg/l 1-naphthaleneacetic acid (NAA) and 1 mg/l 6-benzylaminopurine (BAP) showed optimal callus initiation. UPLC-MS/MS profiling revealed that calli induced on the tested media were able to produce isoquinoline alkaloids. Eight alkaloids were isolated from aerial parts of the cultivated plant and their cytotoxicity against Human skin fibroblast (HF) and wound healing activity using in vitro scratch assay were determined. Structural similarity between the isolated alkaloids enabled structure activity relationship (SAR) study. Sanguinarine displayed the potent activity compared to the other alkaloids. Iminium ion and methylenedioxy potentiated the activity. Graphical Abstract
HIV-associated nephropathy: Protocol and rationale for an exploratory genotype-phenotype study in a sub-Saharan African population

Background HIV-positive persons of African descent are disproportionately affected by chronic kidney disease (CKD). Deterioration to end-stage kidney disease (ESKD) also occurs in this population at a higher frequency. There remains a lot to learn about the genetic susceptibility to CKD in HIV positive patients, and the pathophysiology of progression to ESKD. Objectives We will conduct an exploratory genotype-phenotype study in HIV-positive persons with CKD in Aminu Kano Teaching Hospital, Nigeria, to determine blood-based differential gene expression biomarkers in different kidney risk groups according to the KDIGO 2012 criteria. Methods We will consecutively screen 150 HIV-positive adults (≥18 years of age) attending the HIV clinic of Aminu Kano Teaching Hospital, Kano, Nigeria, for CKD based on proteinuria and elevation of estimated glomerular filtration rate. Among these, two separate groups of 16 eligible participants each (n = 32) will be selected in the four (4) KDIGO 2012 kidney risk categories. The groups will be matched for age, sex, viral suppression level and antiretroviral (ARV) regimen. In the first group (n = 16), we will determine differential gene expression markers in peripheral blood mononuclear cells using mRNA-sequencing (RNA-Seq). We will validate the differential expression markers in the second group (n = 16) using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Using a systems-based approach, we will construct, visualize and analyze gene-gene interaction networks to determine the potential biological roles of identified differential expression markers based on published literature and publicly available databases. Results Our exploratory study will provide valuable information on the potential roles of differential expression biomarkers in the pathophysiology of HIV-associated kidney disease by identifying novel biomarkers in different risk categories of CKD in a sub-Saharan African population. The results of this study will provide the basis for population-based genome-wide association studies to guide future personalized medicine approaches. Conclusion Validated biomarkers can be potential targets for the development of stage-specific therapeutic interventions, an essential paradigm in precision medicine.
Causal associations of short and long sleep durations with 12 cardiovascular diseases: linear and nonlinear Mendelian randomization analyses in UK Biobank.

AIMS Observational studies have suggested strong associations between sleep duration and many cardiovascular diseases (CVDs), but causal inferences have not been confirmed. We aimed to determine the causal associations between genetically predicted sleep duration and 12 CVDs using both linear and nonlinear Mendelian randomization (MR) designs. METHODS AND RESULTS Genetic variants associated with continuous, short (≤6 h) and long (≥9 h) sleep durations were used to examine the causal associations with 12 CVDs among 404 044 UK Biobank participants of White British ancestry. Linear MR analyses showed that genetically predicted sleep duration was negatively associated with arterial hypertension, atrial fibrillation, pulmonary embolism, and chronic ischaemic heart disease after correcting for multiple tests (P < 0.001). Nonlinear MR analyses demonstrated nonlinearity (L-shaped associations) between genetically predicted sleep duration and four CVDs, including arterial hypertension, chronic ischaemic heart disease, coronary artery disease, and myocardial infarction. Complementary analyses provided confirmative evidence of the adverse effects of genetically predicted short sleep duration on the risks of 5 out of the 12 CVDs, including arterial hypertension, pulmonary embolism, coronary artery disease, myocardial infarction, and chronic ischaemic heart disease (P < 0.001), and suggestive evidence for atrial fibrillation (P < 0.05). However, genetically predicted long sleep duration was not associated with any CVD. CONCLUSION This study suggests that genetically predicted short sleep duration is a potential causal risk factor of several CVDs, while genetically predicted long sleep duration is unlikely to be a causal risk factor for most CVDs.
Microalgal extract from thermotolerant Coelastrella sp. F50 retards the liver tumor progression by targeting hepatic cancer stem cells

Microalgae extracts have shown antitumor activities. However, the antitumor mechanism of them is not yet completely clear, especially the effect on cancer stem cells (CSCs). This study aimed to elucidate the antitumor activity and mechanism of microalgal extract from thermotolerant Coelastrella sp. F50 (F50) in hepatocellular carcinoma (HCC). Oncogenic behaviors were analyzed using cell proliferation, colony formation, invasion, sphere formation, and side population cells (SPCs) assays in HCC cells after F50 treatment. The molecular mechanism was further studied by quantitative real‐time PCR, immunoblot, and immunofluorescence analyses. The chemopreventive efficacy of F50 was evaluated in rat orthotopic hepatoma, and the hepatic pathologies were investigated by immunohistochemical, immunoblot, and immunofluorescence analyses. F50 specifically suppressed hepatic CSCs (tumor spheres, drug efflux, CD133/ABCG2 CSCs markers) with no cytotoxicity in vitro. In the animal experiments, prophylactic F50 administration significantly attenuated tumor progression and improved liver function in HCC‐bearing rats. In the mechanistic analysis, F50 potentially inhibited cyclooxygenase‐2 (COX‐2)/prostaglandin E2 (PGE2) axis in HCC cells and rat hepatoma, and exogenous PGE2 restored CSCs properties in F50‐treated HCC cells. In summary, F50 extract inhibits hepatic CSCs by COX‐2/PGE2 downregulation and may facilitate a novel phytotherapy for HCC prevention.
Digital Polymerase Chain Reaction for Assessment of Mutant Mitochondrial Carry-over after Nuclear Transfer for In Vitro Fertilization.

BACKGROUND The quantification of mitochondrial DNA heteroplasmy for the diagnosis of mitochondrial disease or after mitochondrial donation, is performed mainly using next-generation sequencing strategies (NGS). Digital PCR (dPCR) has the potential to offer an accurate alternative for mutation load quantification. METHODS We assessed the mutation load of 23 low-input human samples at the m.11778 locus, which is associated with Leber's hereditary optic neuropathy (LHON) using 2 droplet digital PCR platforms (Stilla Naica and Bio-Rad QX200) and the standard NGS strategy. Assay validation was performed by analyzing a titration series with mutation loads ranging from 50% to 0.01%. RESULTS A good concordance in mutation rates was observed between both dPCR techniques and NGS. dPCR established a distinctly lower level of background noise compared to NGS. Minor alleles with mutation loads lower than 1% could still be detected, with standard deviations of the technical replicates varying between 0.07% and 0.44% mutation load. Although no significant systematic bias was observed when comparing dPCR and NGS, a minor proportional bias was detected. A slight overestimation of the minor allele was observed for the NGS data, most probably due to amplification and sequencing errors in the NGS workflow. CONCLUSION dPCR has proven to be an accurate tool for the quantification of mitochondrial heteroplasmy, even for samples harboring a low mutation load (<1%). In addition, this alternative technique holds multiple benefits compared to NGS (e.g., less hands-on time, more straightforward data-analysis, and a lower up-front capital investment).
Genetic Characterization of Clostridium botulinum Isolated from the First Case of Infant Botulism in Korea

Botulism is a neuroparalytic disease caused by a neurotoxin produced by Clostridium botulinum. This study aimed to genetically characterize C. botulinum strain isolated from the first case of infant botulism in Korea reported on June 17, 2019. We isolated C. botulinum strain CB-27 from a stool sample of the patient and analyzed the toxin types and toxin gene cluster compositions of the strain using a mouse bioassay, real-time PCR, and genome sequencing. Toxin gene cluster analysis showed that strain CB-27 possesses a C. botulinum neurotoxin type A harboring an unexpressed B gene. Although the nucleotide and amino acid sequences of toxin genes as well as the toxin gene cluster arrangements in strain CB-27 were identical to those of the known strain CDC_69094, the total nucleotide sequences of the toxin gene clusters of CB-27 differed from those of CDC_69094 by 0.47%, indicating genetic diversity of toxin gene clusters of CB-27 among other previously reported C. botulinum strains. To our knowledge, this is the first description of a C. botulinum strain with two separate toxin gene clusters in Korea.
The relationship between liver histology and thyroid function tests in patients with non-alcoholic fatty liver disease (NAFLD)

Background Data on the role of hypothyroidism in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis are conflicting, although selective Thyroid Hormone Receptor (THR)-β agonists have been identified as potential therapy in patients with non-alcoholic steatohepatitis (NASH). Therefore, we investigated the association between hypothyroidism and NAFLD histological features potentially associated with progressive liver disease. Methods Between 2014 and 2016, consecutive patients with histologically proven NAFLD and frozen serum available for thyroid function tests assessment were included. NAFLD was staged according to the NAFLD Activity Score (NAS), and fibrosis according to Kleiner. NASH was defined as NAS ≥4, significant fibrosis as F2-F4 and significant steatosis as S2-S3. Thyroid function tests (TFT; TSH, FT3, FT4, rT3), TPO-Ab and Tg-Ab were also assessed. Results Fifty-two patients were analyzed: median age 54 years, 58% females, LSM 7.8 kPa, 27% diabetics, 14% hypothyroid. At histology, NASH was present in 21 (40%), F2-F4 in 28 (54%) and S2-S3 in 30 (58%) patients. Rates of hypothyroidism were similar independently of the presence of NASH (p = 0.11), significant fibrosis (p = 0.21) or steatosis (p = 0.75). However, hypothyroid patients displayed a higher NAS (p = 0.02) and NASH (p = 0.06) prevalence. At multivariate analysis, TFT were not independently associated with histology. Conclusion Hypothyroidism was highly prevalent in NAFLD patients, and was associated with increased NAFLD activity, but not with fibrosis and steatosis severity. Thus, thyroid dysfunction might play a direct and/or indirect in the pathogenesis of NAFLD and NASH.
Systemic CLIP-seq analysis and game theory approach to model microRNA mode of binding

Abstract microRNAs (miRNAs) associate with Ago proteins to post-transcriptionally silence gene expression by targeting mRNAs. To characterize the modes of miRNA-binding, we developed a novel computational framework, called optiCLIP, which considers the reproducibility of the identified peaks among replicates based on the peak overlap. We identified 98 999 binding sites for mouse and human miRNAs, from eleven Ago2 CLIP-seq datasets. Clustering the binding preferences, we found heterogeneity of the mode of binding for different miRNAs. Finally, we set up a quantitative model, named miRgame, based on an adaptation of the game theory. We have developed a new algorithm to translate the miRgame into a score that corresponds to a miRNA degree of occupancy for each Ago2 peak. The degree of occupancy summarizes the number of miRNA-binding sites and miRNAs targeting each binding site, and binding energy of each miRNA::RNA heteroduplex in each peak. Ago peaks were stratified accordingly to the degree of occupancy. Target repression correlates with higher score of degree of occupancy and number of miRNA-binding sites within each Ago peak. We validated the biological performance of our new method on miR-155-5p. In conclusion, our data demonstrate that miRNA-binding sites within each Ago2 CLIP-seq peak synergistically interplay to enhance target repression.