Impact of ECG data format on the performance of machine learning models for the prediction of myocardial infarction

Background We aim to determine which electrocardiogram (ECG) data format is optimal for ML modelling, in the context of myocardial infarction prediction. We will also address the auxiliary objective of evaluating the viability of using digitised ECG signals for ML modelling. Methods Two ECG arrangements displaying 10s and 2.5 s of data for each lead were used. For each arrangement, conservative and speculative data cohorts were generated from the PTB-XL dataset. All ECGs were represented in three different data formats: Signal ECGs, Image ECGs, and Extracted Signal ECGs, with 8358 and 11,621 ECGs in the conservative and speculative cohorts, respectively. ML models were trained using the three data formats in both data cohorts. Results For ECGs that contained 10s of data, Signal and Extracted Signal ECGs were optimal and statistically similar, with AUCs [95% CI] of 0.971 [0.961, 0.981] and 0.974 [0.965, 0.984], respectively, for the conservative cohort; and 0.931 [0.918, 0.945] and 0.919 [0.903, 0.934], respectively, for the speculative cohort. For ECGs that contained 2.5 s of data, the Image ECG format was optimal, with AUCs of 0.960 [0.948, 0.973] and 0.903 [0.886, 0.920], for the conservative and speculative cohorts, respectively. Conclusion When available, the Signal ECG data should be preferred for ML modelling. If not, the optimal format depends on the data arrangement within the ECG: If the Image ECG contains 10s of data for each lead, the Extracted Signal ECG is optimal, however, if it only uses 2.5 s, then using the Image ECG data is optimal for ML performance.</p

Enzymatic- and temperature-sensitive controlled release of ultrasmall superparamagnetic iron oxides (USPIOs)

<p>Abstract</p> <p>Background</p> <p>Drug and contrast agent delivery systems that achieve controlled release in the presence of enzymatic activity are becoming increasingly important, as enzymatic activity is a hallmark of a wide array of diseases, including cancer and atherosclerosis. Here, we have synthesized clusters of ultrasmall superparamagnetic iron oxides (USPIOs) that sense enzymatic activity for applications in magnetic resonance imaging (MRI). To achieve this goal, we utilize amphiphilic poly(propylene sulfide)-<it>bl</it>-poly(ethylene glycol) (PPS-b-PEG) copolymers, which are known to have excellent properties for smart delivery of drug and siRNA.</p> <p>Results</p> <p>Monodisperse PPS polymers were synthesized by anionic ring opening polymerization of propylene sulfide, and were sequentially reacted with commercially available heterobifunctional PEG reagents and then ssDNA sequences to fashion biofunctional PPS-bl-PEG copolymers. They were then combined with hydrophobic 12 nm USPIO cores in the thin-film hydration method to produce ssDNA-displaying USPIO micelles. Micelle populations displaying complementary ssDNA sequences were mixed to induce crosslinking of the USPIO micelles. By design, these crosslinking sequences contained an EcoRV cleavage site. Treatment of the clusters with EcoRV results in a loss of R₂negative contrast in the system. Further, the USPIO clusters demonstrate temperature sensitivity as evidenced by their reversible dispersion at ~75°C and re-clustering following return to room temperature.</p> <p>Conclusions</p> <p>This work demonstrates proof of concept of an enzymatically-actuatable and thermoresponsive system for dynamic biosensing applications. The platform exhibits controlled release of nanoparticles leading to changes in magnetic relaxation, enabling detection of enzymatic activity. Further, the presented functionalization scheme extends the scope of potential applications for PPS-b-PEG. Combined with previous findings using this polymer platform that demonstrate controlled drug release in oxidative environments, smart theranostic applications combining drug delivery with imaging of platform localization are within reach. The modular design of these USPIO nanoclusters enables future development of platforms for imaging and drug delivery targeted towards proteolytic activity in tumors and in advanced atherosclerotic plaques.</p

Comparative Genome Analysis of Bifidobacterium longum subsp. infantis Strains Reveals Variation in Human Milk Oligosaccharide Utilization Genes among Commercial Probiotics

Dysbiosis is associated with acute and long-term consequences for neonates. Probiotics can be effective in limiting the growth of bacteria associated with dysbiosis and promoting the healthy development of the infant microbiome. Given its adaptation to the infant gut, and promising data from animal and in vitro models, Bifidobacterium longum subsp. infantis is an attractive candidate for use in infant probiotics. However, strain-level differences in the ability of commercialized strains to utilize human milk oligosaccharides (HMOs) may have implications in the performance of strains in the infant gut. In this study, we characterized twelve B. infantis probiotic strains and identified two main variants in one of the HMO utilization gene clusters. Some strains possessed the full repertoire of HMO utilization genes (H5-positive strains), while H5-negative strains lack an ABC-type transporter known to bind core HMO structures. H5-positive strains achieved significantly superior growth on lacto-N-tetraose and lacto-N-neotetraose. In vitro, H5-positive strains had a significant fitness advantage over H5-negative strains, which was also observed in vivo in breastfed infants. This work provides evidence of the functional implications of genetic dierences among B. infantis strains and highlights that genotype and HMO utilization phenotype should be considered when selecting a strain for probiotic use in infants

Diabetes in Panama: Epidemiology, Risk Factors, and Clinical Management

ObjectivesTo draw evidence-based conclusions about the epidemiology, drivers, and management of diabetes in Panama based on a literature review and original analyses of large databases.MethodsA search about diabetes in Panama was conducted through PubMed. We used the final reports of 2 studies: the first Survey of Health and Life Quality, 2007, and the first Survey of Risk Factors Associated to Cardiovasular Diseases, 2010-2011, conducted in Panama and analyzed the databases. We reviewed the approach adopted by the Panamanian Social Security institution and the diabetes national guidelines published by the Panamanian Ministry of Health.FindingsThe prevalence of diabetes, as estimated in 1 database (ENSCAVI), was 5.4% (4.3% men; 6.0% women; OR = 1.41 [confidence interval 1.26-1.59]; 'P' ConclusionsDiabetes is a serious national public health threat in Panama. To address this problem in a public health modality, information from large databases was analyzed and presented to the Panamanian Ministry of Health to prompt constructive policy change to enhance diabetes prevention

Endochin-like quinolones (ELQs) and bumped kinase inhibitors (BKIs): Synergistic and additive effects of combined treatments against Neospora caninum infection in vitro and in vivo.

The apicomplexan parasite Neospora caninum is an important causative agent of congenital neosporosis, resulting in abortion, birth of weak offspring and neuromuscular disorders in cattle, sheep, and many other species. Among several compound classes that are currently being developed, two have been reported to limit the effects of congenital neosporosis: (i) bumped kinase inhibitors (BKIs) target calcium dependent protein kinase 1 (CDPK1), an enzyme that is encoded by an apicoplast-derived gene and found only in apicomplexans and plants. CDPK1 is essential for host cell invasion and egress; (ii) endochin-like quinolones (ELQs) are inhibitors of the cytochrome bc1 complex of the mitochondrial electron transport chain and thus inhibit oxidative phosphorylation. We here report on the in vitro and in vivo activities of BKI-1748, and of ELQ-316 and its respective prodrugs ELQ-334 and ELQ-422, applied either as single-compounds or ELQ-BKI-combinations. In vitro, BKI-1748 and ELQ-316, as well as BKI-1748 and ELQ-334, acted synergistically, while this was not observed for the BKI-1748/ELQ-422 combination treatment. In a N. caninum-infected pregnant BALB/c mouse model, the synergistic effects observed in vitro were not entirely reproduced, but 100% postnatal survival and 100% inhibition of vertical transmission was noted in the group treated with the BKI-1748/ELQ-334 combination. In addition, the combined drug applications resulted in lower neonatal mortality compared to treatments with single drugs

Lecanora sorediomarginata, a new epiphytic lichen species discovered along the Portuguese coast

Lecanora sorediomarginata Rodrigues, Terron & Elix sp. nov., described as new to science from Portugal, is characterized morphologically by a crustose whitish-grey to greenish thallus developing soralia from small, marginal warts and chemically by the presence of 3,5-dichloro-2'-O-methylnorstenosporic acid [major], 3,5-dichloro-2'-O-methylanziaic acid [minor], 3,5-dichloro-2'-O-methylnordivaricatic acid [minor], 5-chloro-2'-O-methylanziaic acid [trace], atranorin [minor], chloroatranorin [minor], and usnic acid [trace]. It is chemically similar to L. lividocinerea, to which it shows phylogenetic affinities based on ITS rDNA sequence analysis, and to L. sulphurella. Lecanora sorediomarginata is epiphytic on Pious pinaster and P. pinea, in pine forests on sand dunes along the Portuguese coast

A short-term treatment with BKI-1294 does not protect foetuses from sheep experimentally infected with Neospora caninum tachyzoites during pregnancy.

The Neospora caninum Calcium-dependent protein kinase 1 (NcCDPK1) inhibitor BKI-1294 had demonstrated excellent efficacy in a pregnant mouse model of neosporosis, and was also highly efficacious in a pregnant sheep model of toxoplasmosis. In this work, we present the efficacy of BKI-1294 treatment (dosed 5 times orally every 48 h) starting 48 h after intravenous infection of sheep with 105 Nc-Spain7 tachyzoites at mid-pregnancy. In the dams, BKI-1294 plasma concentrations were above the IC50 for N. caninum for 12-15 days. In treated sheep, when they were compared to untreated ones, we observed a minor increase in rectal temperature, higher IFNγ levels after blood stimulation in vitro, and a minor increase of IgG levels against N. caninum soluble antigens through day 28 post-infection. Additionally, the anti-NcSAG1 and anti-NcSAG4 IgGs were lower in treated dams on days 21 and 42 post-infection. However, BKI-1294 did not protect against abortion (87% foetal mortality in both infected groups, treated and untreated) and did not reduce transplacental transmission, parasite load or lesions in placentomes and foetal brain. The lack of foetal protection was likely caused by short systemic exposure in the dams and suboptimal foetal exposure to this parasitostatic drug, which was unable to reduce replication of the likely established N. caninum tachyzoites in the foetus at the moment of treatment. New BKIs with a very low plasma clearance and good ability to cross the blood-brain and placental barriers need to be developed

Global selective sweep of a highly inbred genome of the cattle parasite Neospora caninum

Neospora caninum, a cyst-forming apicomplexan parasite, is a leading cause of neuromuscular diseases in dogs as well as fetal abortion in cattle worldwide. The importance of the domestic and sylvatic life cycles of Neospora, and the role of vertical transmission in the expansion and transmission of infection in cattle, is not sufficiently understood. To elucidate the population genomics of Neospora, we genotyped 50 isolates collected worldwide from a wide range of hosts using 19 linked and unlinked genetic markers. Phylogenetic analysis and genetic distance indices resolved a single genotype of N. caninum. Whole-genome sequencing of 7 isolates from 2 different continents identified high linkage disequilibrium, significant structural variation, but only limited polymorphism genome-wide, with only 5,766 biallelic single nucleotide polymorphisms (SNPs) total. Greater than half of these SNPs (∼3,000) clustered into 6 distinct haploblocks and each block possessed limited allelic diversity (with only 4 to 6 haplotypes resolved at each cluster). Importantly, the alleles at each haploblock had independently segregated across the strains sequenced, supporting a unisexual expansion model that is mosaic at 6 genomic blocks. Integrating seroprevalence data from African cattle, our data support a global selective sweep of a highly inbred livestock pathogen that originated within European dairy stock and expanded transcontinentally via unisexual mating and vertical transmission very recently, likely the result of human activities, including recurrent migration, domestication, and breed development of bovid and canid hosts within similar proximities

Scientific drilling of Lake Chalco, Basin of Mexico (MexiDrill)

The primary scientific objective of MexiDrill, the Basin of Mexico Drilling Program, is development of a continuous, high-resolution ∼400 kyr lacustrine record of tropical North American environmental change. The field location, in the densely populated, water-stressed Mexico City region gives this record particular societal relevance. A detailed paleoclimate reconstruction from central Mexico will enhance our understanding of long-term natural climate variability in the North American tropics and its relationship with changes at higher latitudes. The site lies at the northern margin of the Intertropical Convergence Zone (ITCZ), where modern precipitation amounts are influenced by sea surface temperatures in the Pacific and Atlantic basins. During the Last Glacial Maximum (LGM), more winter precipitation at the site is hypothesized to have been a consequence of a southward displacement of the mid-latitude westerlies. It thus represents a key spatial node for understanding large-scale hydrological variability of tropical and subtropical North America and is at an altitude (2240 m a.s.l.), typical of much of western North America. In addition, its sediments contain a rich record of pre-Holocene volcanic history; knowledge of the magnitude and frequency relationships of the area's explosive volcanic eruptions will improve capacity for risk assessment of future activity. Explosive eruption deposits will also be used to provide the backbone of a robust chronology necessary for full exploitation of the paleoclimate record. Here we report initial results from, and outreach activities of, the 2016 coring campaign