Machine Learning in Hypertension Detection: A Study on World Hypertension Day Data.

Many modifiable and non-modifiable risk factors have been associated with hypertension. However, current screening programs are still failing in identifying individuals at higher risk of hypertension. Given the major impact of high blood pressure on cardiovascular events and mortality, there is an urgent need to find new strategies to improve hypertension detection. We aimed to explore whether a machine learning (ML) algorithm can help identifying individuals predictors of hypertension. We analysed the data set generated by the questionnaires administered during the World Hypertension Day from 2015 to 2019. A total of 20206 individuals have been included for analysis. We tested five ML algorithms, exploiting different balancing techniques. Moreover, we computed the performance of the medical protocol currently adopted in the screening programs. Results show that a gain of sensitivity reflects in a loss of specificity, bringing to a scenario where there is not an algorithm and a configuration which properly outperforms against the others. However, Random Forest provides interesting performances (0.818 sensitivity - 0.629 specificity) compared with medical protocols (0.906 sensitivity - 0.230 specificity). Detection of hypertension at a population level still remains challenging and a machine learning approach could help in making screening programs more precise and cost effective, when based on accurate data collection. More studies are needed to identify new features to be acquired and to further improve the performances of ML models

Economic analysis of antenatal screening for human T-cell lymphotropic virus type 1 in Brazil: an open access cost-utility model

BACKGROUND: Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that causes severe diseases, such as aggressive cancer or progressive neurological disease. HTLV-1 affects mainly people in areas with low human development index and can be transmitted from mother to child, primarily through breastfeeding. Refraining from breastfeeding is an effective intervention to reduce the risk of infection in infants. However, HTLV-1 antenatal screening is not offered globally. According to WHO, the scarcity of cost-effectiveness studies is considered one of the major barriers to the implementation of policies to prevent HTLV-1 infection. Therefore, this study aimed to assess the cost-effectiveness of antenatal screening and postnatal interventions to prevent HTLV-1 mother-to-child transmission in Brazil and to develop an open-access, editable, mathematical model that can be used by other countries and regions to assess different scenarios. METHODS: In this cost-utility analysis, we constructed a decision tree and a Markov model to assess the cost-effectiveness of HTLV-1 antenatal screening and postnatal interventions (ie, avoidance of breastfeeding, by suppression of lactation with cabergoline, and provision of formula feed) to reduce transmission. For our model, we used data from Brazil and we took the perspective of the public health-care system to estimate costs. FINDINGS: The implementation of both screening and interventions would result in the prevention of 1039 infections in infants every year in Brazil with an incremental cost-effectiveness ratio (ICER) of US$11 415 per quality-adjusted life-year (QALY). 88$18 107·74 per QALY). HTLV-1 prevalence in pregnant women, the risk of HTLV-1 transmission when breastfeeding lasts for 6 months or more, and the cost of screening tests were the variables with the largest effect on ICER. INTERPRETATION: HTLV-1 antenatal screening is cost-effective in Brazil. An open-access model was developed, and this tool could be used to assess the cost-effectiveness of such policy globally, favouring the implementation of interventions to prevent HTLV-1 mother-to-child transmission worldwide. FUNDING: None. TRANSLATIONS: For the Portuguese and Spanish translations of the abstract see Supplementary Materials section

Fermionic Coset, Critical Level W^(2)_4-Algebra and Higher Spins

The fermionic coset is a limit of the pure spinor formulation of the AdS5xS5 sigma model as well as a limit of a nonlinear topological A-model, introduced by Berkovits. We study the latter, especially its symmetries, and map them to higher spin algebras. We show the following. The linear A-model possesses affine \AKMSA{pgl}{4}{4}_0 symmetry at critical level and its \AKMSA{psl}{4}{4}_0 current-current perturbation is the nonlinear model. We find that the perturbation preserves $\mathcal{W}^{(2)}_4$-algebra symmetry at critical level. There is a topological algebra associated to \AKMSA{pgl}{4}{4}_0 with the properties that the perturbation is BRST-exact. Further, the BRST-cohomology contains world-sheet supersymmetric symplectic fermions and the non-trivial generators of the $\mathcal{W}^{(2)}_4$-algebra. The Zhu functor maps the linear model to a higher spin theory. We analyze its \SLSA{psl}{4}{4} action and find finite dimensional short multiplets.Comment: 25 page

Mathematical models for estimating effective diffusion parameters of spherical drug delivery devices

Mathematical modeling of drug delivery is of increasing academic and industrial importance in manyaspects. In this paper, we propose an optimization approach for the estimation of the parameters characterizing the diffusion process of a drug from a spherical porous polymer device to an external finite volume. The approach is based on a nonlinear least-squares method and a novel mathematical model which takes into consideration both boundary layer effect and initial burst phenomenon. Ananalytical solution to the model is derived and a formula for the ratio of the mass released in a given time interval and the total mass released in infinite time is also obtained. The approach has been tested using experimental data of the diffusion of prednisolone 21-hemisuccinate sodium saltfrom spherical devices made of porous poly(2-hydroxyethyl methacrylate) hydrogels. The effectiveness and accuracy of the method are well demonstrated by the numerical results. The model was used to determine the diffusion parameters including the effective diffusion coefficient of the drug from a series of devices that vary in both the porous structure and the drug loading levels. The computed diffusion parameters are discussed in relation to the physical properties of the devices

Detecting copy number status and uncovering subclonal markers in heterogeneous tumor biopsies

<p>Abstract</p> <p>Background</p> <p>Genomic aberrations can be used to determine cancer diagnosis and prognosis. Clinically relevant novel aberrations can be discovered using high-throughput assays such as Single Nucleotide Polymorphism (SNP) arrays and next-generation sequencing, which typically provide aggregate signals of many cells at once. However, heterogeneity of tumor subclones dramatically complicates the task of detecting aberrations.</p> <p>Results</p> <p>The aggregate signal of a population of subclones can be described as a linear system of equations. We employed a measure of allelic imbalance and total amount of DNA to characterize each locus by the copy number status (gain, loss or neither) of the strongest subclonal component. We designed simulated data to compare our measure to existing approaches and we analyzed SNP-arrays from 30 melanoma samples and transcriptome sequencing (RNA-Seq) from one melanoma sample.</p> <p>We showed that any system describing aggregate subclonal signals is underdetermined, leading to non-unique solutions for the exact copy number profile of subclones. For this reason, our illustrative measure was more robust than existing Hidden Markov Model (HMM) based tools in inferring the aberration status, as indicated by tests on simulated data. This higher robustness contributed in identifying numerous aberrations in several loci of melanoma samples. We validated the heterogeneity and aberration status within single biopsies by fluorescent <it>in situ </it>hybridization of four affected and transcriptionally up-regulated genes E2F8, ETV4, EZH2 and FAM84B in 11 melanoma cell lines. Heterogeneity was further demonstrated in the analysis of allelic imbalance changes along single exons from melanoma RNA-Seq.</p> <p>Conclusions</p> <p>These studies demonstrate how subclonal heterogeneity, prevalent in tumor samples, is reflected in aggregate signals measured by high-throughput techniques. Our proposed approach yields high robustness in detecting copy number alterations using high-throughput technologies and has the potential to identify specific subclonal markers from next-generation sequencing data.</p

Tamoxifen for the treatment of myeloproliferative neoplasms: A Phase II clinical trial and exploratory analysis

Current therapies for myeloproliferative neoplasms (MPNs) improve symptoms but have limited effect on tumor size. In preclinical studies, tamoxifen restored normal apoptosis in mutated hematopoietic stem/progenitor cells (HSPCs). TAMARIN Phase-II, multicenter, single-arm clinical trial assessed tamoxifen’s safety and activity in patients with stable MPNs, no prior thrombotic events and mutated JAK2 V617F, CALR ins5 or CALR del52 peripheral blood allele burden ≥20% (EudraCT 2015-005497-38). 38 patients were recruited over 112w and 32 completed 24w-treatment. The study’s A’herns success criteria were met as the primary outcome (≥ 50% reduction in mutant allele burden at 24w) was observed in 3/38 patients. Secondary outcomes included ≥25% reduction at 24w (5/38), ≥50% reduction at 12w (0/38), thrombotic events (2/38), toxicities, hematological response, proportion of patients in each IWG-MRT response category and ELN response criteria. As exploratory outcomes, baseline analysis of HSPC transcriptome segregates responders and non-responders, suggesting a predictive signature. In responder HSPCs, longitudinal analysis shows high baseline expression of JAK-STAT signaling and oxidative phosphorylation genes, which are downregulated by tamoxifen. We further demonstrate in preclinical studies that in JAK2V617F+ cells, 4-hydroxytamoxifen inhibits mitochondrial complex-I, activates integrated stress response and decreases pathogenic JAK2-signaling. These results warrant further investigation of tamoxifen in MPN, with careful consideration of thrombotic risk

Rabies-Specific Antibodies: Measuring Surrogates of Protection against a Fatal Disease

Antibodies play a central role in prophylaxis against many infectious agents. While neutralization is a primary function of antibodies, the Fc- and complement-dependent activities of these multifunctional proteins may also be critical in their ability to provide protection against most viruses. Protection against viral pathogens in vivo is complex, and while virus neutralization—the ability of antibody to inactivate virus infectivity, often measured in vitro—is important, it is often only a partial contributor in protection. The rapid fluorescent focus inhibition test (RFFIT) remains the “gold standard” assay to measure rabies virus–neutralizing antibodies. In addition to neutralization, the rabies-specific antigen-binding activity of antibodies may be measured through enzyme-linked immunosorbent assays (ELISAs), as well as other available methods. For any disease, in selecting the appropriate assay(s) to use to assess antibody titers, assay validation and how they are interpreted are important considerations—but for a fatal disease like rabies, they are of paramount importance. The innate limitations of a one-dimensional laboratory test for rabies antibody measurement, as well as the validation of the method of choice, must be carefully considered in the selection of an assay method and for the interpretation of results that might be construed as a surrogate of protection

Clustering of metabolic syndrome components in a Middle Eastern diabetic and non-diabetic population

<p>Abstract</p> <p>Background</p> <p>Metabolic syndrome (MetS) encompasses a cluster of coronary heart disease and diabetes mellitus risk factors. In this study, we aimed to elucidate the factors underlying the clustering of MetS components in diabetic and non-diabetic individuals.</p> <p>Methods</p> <p>Factor analysis was performed on 2978 (1652 non-diabetic and 1326 diabetic) participants. Entering waist circumference, homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides, high-density lipoprotein-cholesterol (HDL-C) and systolic blood pressure (SBP), we performed exploratory factor analysis in diabetic and non-diabetic individuals separately. The analysis was repeated after replacing triglycerides and HDL-C with triglycerides to HDL-C ratio (triglycerides/HDL-C). MetS was defined by either adult treatment panel III (ATPIII), international diabetes federation (IDF) criteria, or by the modified form of IDF using waist circumference cut-off points for Iranian population.</p> <p>Results</p> <p>The selection of triglycerides and HDL-C as two distinct variables led to identifying two factors explaining 61.3% and 55.4% of the total variance in non-diabetic and diabetic participants, respectively. In both diabetic and non-diabetic subjects, waist circumference, HOMA-IR and SBP loaded on factor 1. Factor 2 was mainly determined by triglycerides and HDL-C. Factor 1 and 2 were directly and inversely associated with MetS, respectively. When triglycerides and HDL-C were replaced by triglycerides/HDL-C, one factor was extracted, which explained 47.6% and 38.8% of the total variance in non-diabetic and diabetic participants, respectively.</p> <p>Conclusion</p> <p>This study confirms that in both diabetic and non-diabetic participants the concept of a single underlying factor representing MetS is plausible.</p

A retrospective study on IVF outcome in euthyroid patients with anti-thyroid antibodies: effects of levothyroxine, acetyl-salicylic acid and prednisolone adjuvant treatments

<p>Abstract</p> <p>Background</p> <p>Anti-thyroid antibodies (ATA), even if not associated with thyroid dysfunction, are suspected to cause poorer outcome of in vitro fertilization (IVF).</p> <p>Methods</p> <p>We retrospectively analyzed: (a) the prevalence of ATA in euthyroid infertile women, (b) IVF outcome in euthyroid, ATA+ patients, and (c) the effect of adjuvant treatments (levothyroxine alone or associated with acetylsalicylic acid and prednisolone) on IVF results in ATA+ patients. One hundred twenty-nine euthyroid, ATA+ women undergoing IVF were compared with 200 matched, ATA-controls. During IVF cycle, 38 ATA+ patients did not take any adjuvant treatment, 55 received levothyroxin (LT), and 38 received LT +acetylsalicylic acid (ASA)+prednisolone (P).</p> <p>Results</p> <p>The prevalence of ATA among euthyroid, infertile patients was 10.5%, similar to the one reported in euthyroid women between 18 and 45 years. ATA+ patients who did not receive any adjuvant treatment showed significantly poorer ovarian responsiveness to stimulation and IVF results than controls. ATA+ patients receiving LT responded better to ovarian stimulation, but had IVF results as poor as untreated ATA+ women. Patients receiving LT+ASA+P had significantly higher pregnancy and implantation rates than untreated ATA+ patients (PR/ET 25.6% and IR 17.7% vs. PR/ET 7.5% and IR 4.7%, respectively), and overall IVF results comparable to patients without ATA (PR/ET 32.8% and IR 19%).</p> <p>Conclusion</p> <p>These observations suggest that euthyroid ATA+ patients undergoing IVF could have better outcome if given LT+ASA+P as adjuvant treatment. This hypothesis must be verified in further randomized, prospective studies.</p

Latent profile analysis in frontotemporal lobar degeneration and related disorders: clinical presentation and SPECT functional correlates

<p>Abstract</p> <p>Background</p> <p>Frontotemporal Lobar Degeneration (FTLD) thus recently renamed, refers to a spectrum of heterogeneous conditions. This same heterogeneity of presentation represents the major methodological limit for the correct evaluation of clinical designation and brain functional correlates. At present, no study has investigated clinical clusters due to specific cognitive and behavioural disturbances beyond current clinical criteria.</p> <p>The aim of this study was to identify clinical FTLD presentation, based on cognitive and behavioural profile, and to define their SPECT functional correlations.</p> <p>Methods</p> <p>Ninety-seven FTLD patients entered the study. A clinical evaluation and standardised assessment were preformed, as well as a brain SPECT perfusion imaging study. Latent Profile Analysis on clinical, neuropsychological, and behavioural data was performed. Voxel-basis analysis of SPECT data was computed.</p> <p>Results</p> <p>Three specific clusters were identified and named "pseudomanic behaviour" (LC1), "cognitive" (LC2), and "pseudodepressed behaviour" (LC3) endophenotypes. These endophenotypes showed a comparable hypoperfusion in left temporal lobe, but a specific pattern involving: medial and orbitobasal frontal cortex in LC1, subcortical brain region in LC2, and right dorsolateral frontal cortex and insula in LC3.</p> <p>Conclusion</p> <p>These findings provide evidence that specific functional-cluster symptom relationship can be delineated in FTLD patients by a standardised assessment. The understanding of the different functional correlates of clinical presentations will hopefully lead to the possibility of individuating diagnostic and treatment algorithms.</p