Miracle-dz/UniFAR-FTUs huggingface dataset:
Krait envenomation in Thailand

Purpose Three species in the genus Bungarus inhabit Thailand. Among these, Bungarus candidus (Malayan krait) is the most common and deadliest. Currently, the clinical manifestations of patients envenomed by kraits, especially Bungarus fasciatus (banded krait), have not been thoroughly investigated. This study was performed to elucidate the clinical manifestations and outcomes of patients bitten by kraits in Thailand. Materials and methods The data of krait envenomation cases that occurred during a 9-year period were obtained from the Ramathibodi Poison Center Toxic Exposure Surveillance System and retrospectively analyzed. Results In total, 78 cases of krait envenomation were included. Most patients were male (59.0%) and the median age was 28 years. All had minimal local effects. The median duration from the bite to the onset of neurological manifestations was 3 hours (range, 0.5–8 hours). Besides neurological effects, the patients also developed high blood pressure (67.4%), tachycardia (61.7%), hypokalemia (55.3%), and hyponatremia (17.6%). Severe hyponatremia (<120 mEq/L) was noted in four pediatric patients. Other clinical manifestations were bradycardia, abdominal pain, and rhabdomyolysis. The mortality rate was 6.4%, and all deaths occurred from B. candidus bites. Eighty-six percent of patients received antivenom. Most patients (75.6%) were intubated and underwent assisted ventilation for a median of 6 days (range, 1–37 days). The median length of hospital stay was 7 days. Some patients developed complications during hospitalization; the most common was pneumonia. These in-hospital complications were significantly associated with death. Conclusion Although krait bites caused only minimal local effects, the mortality rate was still high, particularly from Malayan krait bites. Besides neurological effects, other clinical manifestations were high blood pressure, tachycardia, hypokalemia, and hyponatremia. Thus, vital signs and electrolytes should be frequently and closely monitored in these patients. Apart from antivenom treatment, adequate supportive care including management of complications might help to decrease the mortality rate.
Earlier and more targeted treatment of neonatal sepsis

Neonatal sepsis occurs in 1-2/1000 live born neonates and accounts for 3-5% of deaths in term and more than 30% in extremely preterm infants(1). These mortality rates due to neonatal infections are unacceptably high. Immediate and targeted antibiotic treatment is crucial in order to improve survival in this vulnerable population. This article is protected by copyright. All rights reserved.
Low tumor purity is associated with poor prognosis, heavy mutation burden, and intense immune phenotype in colon cancer

Purpose Tumor purity is defined as the proportion of cancer cells in the tumor tissue. The impact of tumor purity on colon cancer (CC) prognosis, genetic profile, and microenvironment has not been thoroughly accessed. Materials and methods Clinical and transcriptomic data from three public datasets, GSE17536/17537, GSE39582, and TCGA, were retrospectively collected (n=1,248). Tumor purity of each sample was inferred by a computational method based on transcriptomic data. Survival-related analyses were performed on microarray dataset containing GSE17536/17537 and GSE39582 (n=794), whereas TCGA dataset was utilized for subsequent genomic analysis (n=454). Results Right-sided CC patients showed a significantly lower tumor purity. Low purity CC conferred worse survival, and tumor purity was identified as an independent prognostic factor. Moreover, high tumor purity CC patients benefited more from adjuvant chemotherapy. Subsequent genomic analysis found that the mutation burden was negatively associated with tumor purity, with only APC and KRAS significantly more mutated in high purity CC. However, no somatic copy number alteration event was correlated with tumor purity. Furthermore, immune-related pathways and immunotherapy-associated markers (programmed cell death protein 1 [PD-1], programmed death-ligand 1 [PD-L1], cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], Lymphocyte-activation gene 3 [LAG-3] and T-cell immunoglobulin and mucin-domain containing-3 [TIM-3]) were highly enriched in low purity samples. Notably, the relative proportion of M2 macrophages and neutrophils, which indicated worse survival in CC, was negatively associated with tumor purity. Conclusion Tumor purity exhibited potential value for CC prognostic stratification as well as adjuvant chemotherapy benefit prediction. The relative worse survival in low purity CC may attribute to higher mutation frequency in key pathways and purity-related microenvironmental changing.
Effects of experimental manipulation of hematocrit on avian flight performance in high- and low-altitude conditions

ABSTRACT Despite widely held assumptions that hematocrit (Hct) is a key determinant of aerobic capacity and exercise performance, this relationship has not often been tested rigorously in birds and results to date are mixed. Migration in birds involves high-intensity exercise for long durations at various altitudes. Therefore, it provides a good model system to examine the effect of Hct on flight performance and physiological responses of exercise at high altitude. We treated yellow-rumped warblers (Setophaga coronata) with avian erythropoietin (EPO) and anti-EPO to experimentally manipulate Hct and assessed flight performance at low and high altitudes using a hypobaric wind tunnel. We showed that anti-EPO-treated birds had lower Hct than vehicle- and EPO-treated birds post-treatment. Anti-EPO-treated birds also had marginally lower exercise performance at low altitude, committing a higher number of strikes (mistakes) in the first 30 min of flight. However, anti-EPO-treated birds performed significantly better at high altitude, attaining a higher altitude in a ramped altitude challenge to 3000 m equivalent altitude, and with a longer duration of flight at high altitude. Birds exercising at high altitude showed decreased Hct, increased glucose mobilization and decreased antioxidant capacity, regardless of treatment. In summary, we provide experimental evidence that the relationship between Hct and exercise performance is dependent on altitude. Future studies should investigate whether free-living birds adaptively modulate their Hct, potentially through a combination of erythropoiesis and plasma volume regulation (i.e. hemodilution), based on the altitude they fly at during migratory flight. Summary: Manipulation of hematocrit in yellow-rumped warblers provides experimental evidence that the relationship between hematocrit and exercise performance is dependent on altitude.
Chagas disease mortality in Brazil: A Bayesian analysis of age-period-cohort effects and forecasts for two decades

Background Chagas disease (CD) is a neglected chronic parasitic infection and a public health problem that is preventable, and has serious complications. In this study, the effects of age, period and birth cohort (APC Effects) on the evolution of the mortality of that disease in Brazil, from 1980–2014, according to sex and geographic region of the country, were analyzed. Mortality forecasts from the years 2015 to 2034 were estimated. Methods This is an ecological cross-sectional study in which death records and population data were extracted from the DATASUS (Department of Information Technology of the National Health System) website, in age groups from 20–24 years of age to 80 years and over, from 1980 to 2014. The rates were standardized according to age and sex distributions using the direct method. The APC models were estimated using the Bayesian approach, and the INLA (Integrated Nested Laplace Approximations) method was used for parameter inference. Super dispersion of the data was considered, and we included unstructured random terms in the models. Results During the analyzed period, there were 178,823 deaths in Brazil (3.85 annual deaths per 100,000 inhabitants). It was found that temporal effects on CD mortality varied by sex and region. In general, there was an increase in mortality rates up to 30 years of age, and the mortality rates were higher between 50 and 64 years of age. On average, men died five years younger than women. Mortality rates were highest in the Central West and Southeast regions. The Central West, Southeast and Southern regions had a reduction over time in the rate of CD deaths between 2000 and 2014. The mortality rate in the Northeast was not statistically different in any period analyzed, while the North had tendency to increase; however, a significant risk increase was only observed between 1995 and 1999. The rate of mortality was high in older birth cohorts. The overall prediction for the next two decades showed a progressive decline in CD mortality, which will be highest among the young. The expected average reduction was 76.1% compared to the last observed period (2010–2014) and the last predicted (2030–2034) period. The average reduction ranged from 86% in the 20–24 age group to 50% in the 80 and over age group. Conclusions In the present study, a higher death rate was observed for ages above 30 years, especially 50 to 64 years, and in the older birth cohorts. We believe these results can be related to period effects of vector control actions and preventive and care measures by the health system of Brazil, in addition to demographic changes in the period. The differences among the regions reflect socioeconomic inequities and access to the healthcare systems in the Brazilian population.
Is Group-Based or Individual-Based Intervention more Effective for Quality of Life Outcomes in Children with Developmental Coordination Disorder? A Systematic Review

Abstract Aims: To examine whether group-based or individual-based treatment programs are more effective for quality of life (QOL) outcomes in children with developmental coordination disorder (DCD). Methods: A systematic search of the literature was conducted, in accordance with the PRISMA guidelines. Quality of the papers was assessed using the Modified Downs and Black Checklist. Peer-reviewed clinical experimental studies of children diagnosed with DCD with any QOL related outcome measure were included, of all years, languages, and approaches of intervention. Results: Sixteen studies were identified for inclusion, of mixed methodological qualities (predominantly low). Improvement of QOL with both group-based and individual-based interventions were shown, though large degrees of heterogeneity were observed in study designs, participants, modes of interventions, durations, and outcome measures utilized. Conclusions: The effectiveness of group-based versus individual-based interventions on QOL of children with DCD is unclear. There is a pressing need for a high quality, powered trials, utilizing the randomized control trial paradigm, comparing both intervention approaches with standardized treatment approaches and outcome measures to determine and compare the effect on QOL of children with DCD.
Implementing delayed cord clamping in premature infants

The practice of delayed cord clamping (DCC) in premature infants has proven benefit to the neonate. In a community-based perinatal centre, the practice of DCC for more than 60 s for premature infants with gestational age of <35 weeks was identified to occur infrequently at 20% in 2013. The perinatology group in conjunction with nursery, labour and delivery, and obstetric staff sought to improve adherence to the best practice of DCC for premature infants. In an effort to achieve this goal, we developed an evidence-based clinical practice guideline, included key stakeholders in its development and provided timely feedback to delivery providers about DCC performance. The frequency of DCC for this population improved from 19.5% in 2013 to 85% in 2017. The success in improving this best practice is attributed to the involvement of the multidisciplinary team who developed the guideline, and the sustained improvement was encouraged with the continued reaffirmation of DCC goals to delivery providers.
A broadband CPW-fed dual circularly polarized slot antenna with modified L-shaped monopoles

In this letter, a novel broadband dual circularly polarized (CP) square slot antenna based on coplanar waveguide (CPW) feed is presented. Two orthogonal modified L-shaped monopoles fed by the CPW structure are designed to achieve dual circularly polarization. Through digging several rectangular notches while adding extra needle shaped tuning strip between two monopoles, wide impedance bandwidth (IMBW), wide axial ratio bandwidth (ARBW) and high port isolation are realized. Finally, in order to verify the analysis, a prototype is fabricated and measured. The measured available −10 dB IMBW of each port is 76% (from 1.8GHz to 4.0GHz), which covers the whole 3 dB ARBW of 67% (from 1.87GHz to 3.75GHz). Besides, the port isolation is below −25 dB and the cross polarization level is over −15 dB across the entire operating band, which proves the proposed antenna a good candidate for communication systems.
Mass spectrometry imaging of lipids: untargeted consensus spectra reveal spatial distributions in Niemann-Pick disease type C1[S]

Mass spectrometry imaging (MSI) is a tool to rapidly map the spatial location of analytes without the need for tagging or a reporter system. Niemann-Pick disease type C1 (NPC1) is a neurodegenerative, lysosomal storage disorder characterized by accumulation of unesterified cholesterol and sphingolipids in the endo-lysosomal system. Here, we use MSI to visualize lipids including cholesterol in cerebellar brain tissue from the NPC1 symptomatic mouse model and unaffected controls. To complement the imaging studies, a data-processing pipeline was developed to generate consensus mass spectra, thereby using both technical and biological image replicates to assess differences. The consensus spectra are used to determine true differences in lipid relative abundance; lipid distributions can be determined in an unbiased fashion without prior knowledge of location. We show the cerebellar distribution of gangliosides GM1, GM2, and GM3, including variants of lipid chain length. We also performed MALDI-MSI of cholesterol. Further analysis of lobules IV/V and X of the cerebellum gangliosides indicates regional differences. The specificity achieved highlights the power of MSI, and this new workflow demonstrates a universal approach for addressing reproducibility in imaging experiments applied to NPC1.
Mitochondrial and glycolytic remodeling during nascent neural differentiation of human pluripotent stem cells

ABSTRACT As human pluripotent stem cells (hPSCs) exit pluripotency, they reportedly switch from glycolytic energy production to primarily mitochondrial metabolism. Here, we show that upon ectoderm differentiation to neural precursor cells (NPCs), hPSCs increase glycolytic rate, ultimately producing more carbon as lactate than is consumed as glucose. However, glucose, lactate and pyruvate utilization decrease to half their PSC levels by the NPC stage, establishing a more quiescent metabolic state. Furthermore, we characterize a metabolic exit event within the first 24 h of differentiation, plausibly necessary to transition hPSCs out of the pluripotent state. Contrary to current thinking, mitochondrial mass does not increase during NPC induction. Instead, mitochondrial DNA copies and mitochondrial activity decrease, suggesting that mitochondrial metabolism either requires suppression, or is not required, for nascent ectoderm differentiation. Our work, therefore, contrasts with the dogma that the hPSC state is primarily glycolytic, transitioning to an oxidative metabolism upon the loss of the pluripotent state. Instead, we show that heightened glycolytic metabolism is acquired, indicating that metabolic modulation of both glycolysis and mitochondrial metabolism occurs during exit from pluripotency in hPSCs. Highlighted Article: In contrast to the established models of metabolic development, during early neural differentiation of human pluripotent stem cells mitochondrial metabolism decreases while the glycolytic contribution to metabolism increases.
Digital Imaging Combined with Genome-Wide Association Mapping Links Loci to Plant-Pathogen Interaction Traits1[OPEN]

Computer vision allows the identification of genes controlling uncharacterized lesion traits in Arabidopsis. Plant resistance to generalist pathogens with broad host ranges, such as Botrytis cinerea (Botrytis), is typically quantitative and highly polygenic. Recent studies have begun to elucidate the molecular genetic basis of plant-pathogen interactions using commonly measured traits, including lesion size and/or pathogen biomass. However, with the advent of digital imaging and high-throughput phenomics, there are a large number of additional traits available to study quantitative resistance. In this study, we used high-throughput digital imaging analysis to investigate previously poorly characterized visual traits of plant-pathogen interactions related to disease resistance using the Arabidopsis (Arabidopsis thaliana)/Botrytis pathosystem. From a large collection of visual lesion trait measurements, we focused on color, shape, and size to test how these aspects of the Arabidopsis/Botrytis interaction are genetically related. Through genome-wide association mapping in Arabidopsis, we show that lesion color and shape are genetically separable traits associated with plant disease resistance. Moreover, by employing defined mutants in 23 candidate genes identified from the genome-wide association mapping, we demonstrate links between loci and each of the different plant-pathogen interaction traits. These results expand our understanding of the functional mechanisms driving plant disease resistance.
Concordance between laboratories in metal ion testing in patients with metal-on-metal hip implants.

BACKGROUND Testing of whole blood or serum metal ion levels has become an important part of assessing and monitoring the performance of metal-on-metal bearings, both in hip resurfacing arthroplasty and in total hip replacement. The aim of this study was to determine the concordance between 2 laboratories testing cobalt and chromium ion levels in patients with metal-on-metal bearings. METHODS Serum and whole blood samples from patients who had undergone metal-on-metal resurfacing or large-diameter total hip arthroplasty were tested for cobalt and chromium ions in laboratory A (a recognized laboratory) and laboratory B (tasked with testing clinical specimens). Laboratory A performed cobalt and chromium testing on whole blood, and laboratory B performed cobalt testing on whole blood and chromium testing on serum. RESULTS Samples from 104 patients were tested. Laboratory B reported lower whole blood cobalt levels than laboratory A. Furthermore, laboratory A reported that all patients had elevated whole blood cobalt ion levels compared to the normal reference values for the laboratory, whereas laboratory B reported that 46 patients (44.2%) had whole blood cobalt ion levels within the normal reference range for the laboratory. CONCLUSION This comparative study highlights the importance of using a single laboratory for metal ion testing, as values generated from different laboratories may not be directly comparable. With recent literature suggesting that whole blood cobalt levels as low as 1 ppb may be a predictor of adverse reactions to metal debris, accurate clinical measurement needs to be increasingly exact.
Using a semi‐mechanistic model to identify the main sources of variability of metformin pharmacokinetics

Metformin pharmacokinetics (PK) is highly variable, and researchers have for years tried to shed light on determinants of inter‐individual (IIV) and inter‐occasion variability (IOV) of metformin PK. We set out to identify the main sources of PK variability using a semi‐mechanistic model. We assessed the influence of subject characteristics, including seven genetic variants. Data from three studies of healthy individuals with PK measurements of plasma and urine after single dose or at steady‐state were used in this study. In total, 87 subjects were included (16 crossover subjects). Single nucleotide polymorphisms in ATM, OCT1, OCT2, MATE1 and MATE2‐K were investigated as dominant, recessive or additive. A three‐compartment model with transit absorption and renal elimination with a proportional error was fitted to the data using NONMEM 7.3. Oral parameters were separated from disposition parameters as dose‐dependent absolute bioavailability was determined with support from urine data. Clearance was expressed as net renal secretion and filtration, assuming full fraction unbound and fraction excreted. Mean transit time and peripheral volume of distribution were identified as the main sources of variability according to estimates, with 94% IOV and 95% IIV, respectively. Clearance contributed only with 16% IIV. Glomerular filtration rate and body‐weight were the only covariates found to affect metformin net secretion, reducing IIV to 14%. None of the genetic variants were found to affect metformin PK. Based on our analysis, finding covariates explaining absorption of metformin is much more valuable in understanding variability and avoiding toxicity than elimination.
DNA demethylase ROS1 negatively regulates the imprinting of DOGL4 and seed dormancy in Arabidopsis thaliana

Significance Genomic imprinting is a form of epigenetic regulation causing parent-of-origin differential expression of maternally or paternally inherited alleles. The DNA demethylase DME regulates the imprinting of many genes in the Arabidopsis endosperm. It is not known whether and how other DNA demethylases may also regulate imprinting. Here, we discovered that the DNA demethylase ROS1 negatively regulates DOGL4 imprinting via demethylation of the DOGL4 promoter on the paternal allele. Additionally, we found that DOGL4 negatively regulates seed dormancy and abscisic acid (ABA) response and that ROS1 regulates seed dormancy and ABA response by controlling DOGL4 expression. Our results thus suggest a different mechanism of regulation of gene imprinting and reveal important roles of ROS1 in the regulation of seed dormancy and ABA response. Genomic imprinting is a form of epigenetic regulation resulting in differential gene expression that reflects the parent of origin. In plants, imprinted gene expression predominantly occurs in the seed endosperm. Maternal-specific DNA demethylation by the DNA demethylase DME frequently underlies genomic imprinting in endosperm. Whether other more ubiquitously expressed DNA demethylases regulate imprinting is unknown. Here, we found that the DNA demethylase ROS1 regulates the imprinting of DOGL4. DOGL4 is expressed from the maternal allele in endosperm and displays preferential methylation and suppression of the paternal allele. We found that ROS1 negatively regulates imprinting by demethylating the paternal allele, preventing its hypermethylation and complete silencing. Furthermore, we found that DOGL4 negatively affects seed dormancy and response to the phytohormone abscisic acid and that ROS1 controls these processes by regulating DOGL4. Our results reveal roles for ROS1 in mitigating imprinted gene expression and regulating seed dormancy.