Identifying and characterising asthma subgroups at high risk of severe exacerbations using machine learning and longitudinal real-world data.

Objectives: To identify and characterise distinct subgroups of patients with asthma with severe acute exacerbations (AEs) by using a multistep clustering methodology that combines supervised and unsupervised machine learning.

Methods: This cohort study used anonymised, all-payer medical and prescription US claim data from October 2015 to May 2022. First, gradient-boosted decision trees were trained to predict AE in 4 132 973 patients with asthma, of whom 86 735 experienced AE.

Health care-seeking behaviors for acute asthma: A US cross-sectional survey.

Background: Understanding patient motivations for acute care-seeking behavior for asthma attacks could guide interventions to improve outcomes and mitigate health care resource use.

Objective: To characterize health care-seeking behaviors and motivations of patients in the United States who obtain care for an asthma attack in urgent care (UC), emergency department (ED), or hospital settings.

Methods: A cross-sectional survey was conducted online between July and August 2023 among adults in a market research panel treated for asthma in the past 12 months and who had experienced an asthma attack that required care in an UC, ED, or hospital or an oral corticosteroid prescription.

Ray tracing optimization: a new method for intraocular lens power calculation in regular and irregular corneas.

To develop a novel algorithm based on ray tracing, simulated visual performance and through-focus optimization for an accurate intraocular lens (IOL) power calculation. Custom-developed algorithms for ray tracing optimization (RTO) were used to combine the natural corneal higher-order aberrations (HOAs) with multiple sphero-cylindrical corrections in 210 higher order statistical eye models for developing keratoconus. The magnitude of defocus and astigmatism producing the maximum Visual Strehl was considered as the optimal sphero-cylindrical target for IOL power calculation.

Comparing preservation substrates under field conditions for efficient DNA recovery in bone.

Often bones are the only biological material left for the identification of human remains. As situations may occur where samples need to be stored for an extended period without access to cooling, appropriate storage of the bone samples is necessary for maintaining the integrity of DNA for profiling. To simulate DNA preservation under field conditions, pig rib bones were used to evaluate the effects of bone cleaning, buffer composition, storage temperature, and time on DNA recovery from bone samples.

Apixaban Use in Obese Patients: A Review of the Pharmacokinetic, Interventional, and Observational Study Data.

Relatively little is known about the influence of extreme body weight on the pharmacokinetics (PK), pharmacodynamics (PD), efficacy, and safety of drugs used in many disease states. While direct oral anticoagulants (DOACs) have an advantage over warfarin in that they do not require routine drug monitoring, some may regard this convenience as less compelling in obese patients. Some consensus guidelines discourage using DOACs in patients weighing > 120 kg or with a body mass index > 35-40 kg/m, given a sparsity of available data in this population and the concern that fixed dosing in obese patients might lead to decreased drug exposure and lower efficacy.

Super enhancers define regulatory subtypes and cell identity in neuroblastoma.

Half of the children diagnosed with neuroblastoma (NB) have high-risk disease, disproportionately contributing to overall childhood cancer-related deaths. In addition to recurrent gene mutations, there is increasing evidence supporting the role of epigenetic deregulation in disease pathogenesis. Yet, comprehensive cis-regulatory network descriptions from NB are lacking.

Single-cell transcriptomic analyses provide insights into the developmental origins of neuroblastoma.

Neuroblastoma is a pediatric tumor of the developing sympathetic nervous system. However, the cellular origin of neuroblastoma has yet to be defined. Here we studied the single-cell transcriptomes of neuroblastomas and normal human developing adrenal glands at various stages of embryonic and fetal development.

ShinyButchR: Interactive NMF-based decomposition workflow of genome-scale datasets.

Non-negative matrix factorization (NMF) has been widely used for the analysis of genomic data to perform feature extraction and signature identification due to the interpretability of the decomposed signatures. However, running a basic NMF analysis requires the installation of multiple tools and dependencies, along with a steep learning curve and computing time. To mitigate such obstacles, we developed ShinyButchR, a novel R/Shiny application that provides a complete NMF-based analysis workflow, allowing the user to perform matrix decomposition using NMF, feature extraction, interactive visualization, relevant signature identification, and association to biological and clinical variables.

National Physician Survey for Nonvalvular Atrial Fibrillation (NVAF) Anticoagulation Comparing Knowledge, Attitudes and Practice of Cardiologist to PCPs.

Introduction: NVAF is estimated to affect between 6.4 and 7.4 million Americans in 2018, and increases the risk of stroke 5-fold.

A VCO-Based CMOS Readout Circuit for Capacitive MEMS Microphones.

Microelectromechanical systems (MEMS) microphone sensors have significantly improved in the past years, while the readout electronic is mainly implemented using switched-capacitor technology. The development of new battery powered "always-on" applications increasingly requires a low power consumption. In this paper, we show a new readout circuit approach which is based on a mostly digital Sigma Delta ( Σ Δ ) analog-to-digital converter (ADC).

Deconvolution of single-cell multi-omics layers reveals regulatory heterogeneity.

Integrative analysis of multi-omics layers at single cell level is critical for accurate dissection of cell-to-cell variation within certain cell populations. Here we report scCAT-seq, a technique for simultaneously assaying chromatin accessibility and the transcriptome within the same single cell. We show that the combined single cell signatures enable accurate construction of regulatory relationships between cis-regulatory elements and the target genes at single-cell resolution, providing a new dimension of features that helps direct discovery of regulatory patterns specific to distinct cell identities.

Implementation of a Piezo-diagnostics Approach for Damage Detection Based on PCA in a Linux-Based Embedded Platform.

The implementation of damage-detection methods for continuously assessing structural integrity entails systems with attractive features such as storage capabilities, memory capacity, computational complexity and time-consuming processing. In this sense, embedded hardware platforms are a promising technology for developing integrated solutions in Structural Health Monitoring. In this paper, design, test, and specifications for a standalone inspection prototype are presented, which take advantage of piezo-diagnostics principle, statistical processing via Principal Component Analysis (PCA) and embedded systems.

SNDR Limits of Oscillator-Based Sensor Readout Circuits.

This paper analyzes the influence of phase noise and distortion on the performance of oscillator-based sensor data acquisition systems. Circuit noise inherent to the oscillator circuit manifests as phase noise and limits the SNR. Moreover, oscillator nonlinearity generates distortion for large input signals.

Thioxylated cyclosporin A for studying protein-drug interactions.

Single atom substitution of cyclosporin A (CsA) through thioxylation has been used to study the structure-activity relationship of the immunosuppressive complex, involving the CsA receptor protein cyclophilin 18 (Cyp18) and the immunological target protein phosphatase calcineurin (CaN), illustrating the contributions of peptide backbone in protein-drug interaction. Moreover, the subtle difference between thioxylation positions in CsA has led to a remarkable change in the quenching effect on Cyp18 intrinsic fluorescence. Using the thioxylated compound Cs7 as an isosteric derivative of CsA in competition assay, the experiment has led to the determination of k value in solution.

Conformational Heterogeneity of Cyclosporin A in Cyclophilin 18 Binding.

The immunosuppressive drug cyclosporin A (CsA) binds to its receptor protein cyclophilin 18 (Cyp18) in two distinct kinetic phases, while the mechanism remains elusive. Stopped-flow measurements coupled with titration and competition experiments were used to investigate the puzzling two-phase process of CsA and Cyp18 interaction. This study leads to the dissection of different conformational fractions of either direct fast binding or slow binding with rate-limiting conformational inter-conversion and the real-time measurement of kon value (8.

Algorithm for the Construction of a Global Enzymatic Network to be Used for Gene Network Reconstruction.

Relationships between genes are best represented using networks constructed from information of different types, with metabolic information being the most valuable and widely used for genetic network reconstruction. Other types of information are usually also available, and it would be desirable to systematically include them in algorithms for network reconstruction. Here, we present an algorithm to construct a global metabolic network that uses all available enzymatic and metabolic information about the organism.

Identification of immunity-related genes in Arabidopsis and cassava using genomic data.

Recent advances in genomic and post-genomic technologies have provided the opportunity to generate a previously unimaginable amount of information. However, biological knowledge is still needed to improve the understanding of complex mechanisms such as plant immune responses. Better knowledge of this process could improve crop production and management.

Identification of ta-siRNAs and cis-nat-siRNAs in cassava and their roles in response to cassava bacterial blight.

Trans-acting small interfering RNAs (ta-siRNAs) and natural cis-antisense siRNAs (cis-nat-siRNAs) are recently discovered small RNAs (sRNAs) involved in post-transcriptional gene silencing. ta-siRNAs are transcribed from genomic loci and require processing by microRNAs (miRNAs). cis-nat-siRNAs are derived from antisense RNAs produced by the simultaneous transcription of overlapping antisense genes.

Bioinformatic identification of cassava miRNAs differentially expressed in response to infection by Xanthomonas axonopodis pv. manihotis.

Background: microRNAs (miRNAs) are short RNA molecules that control gene expression by silencing complementary mRNA. They play a crucial role in stress response in plants, including biotic stress. Some miRNAs are known to respond to bacterial infection in Arabidopsis thaliana but it is currently unknown whether these responses are conserved in other plants and whether novel species-specific miRNAs could have a role in defense.

Altered functional connectivity between the insula and the cingulate cortex in patients with temporomandibular disorder: a pilot study.

Background: Among the most common chronic pain conditions, yet poorly understood, are temporomandibular disorders (TMDs), with a prevalence estimate of 3-15% for Western populations. Although it is increasingly acknowledged that central nervous system mechanisms contribute to pain amplification and chronicity in TMDs, further research is needed to unravel neural correlates that might abet the development of chronic pain.

Objective: The insular cortex (IC) and cingulate cortex (CC) are both critically involved in the experience of pain.

Follistatin improves skeletal muscle healing after injury and disease through an interaction with muscle regeneration, angiogenesis, and fibrosis.

Recovery from skeletal muscle injury is often incomplete because of the formation of fibrosis and inadequate myofiber regeneration; therefore, injured muscle could benefit significantly from therapies that both stimulate muscle regeneration and inhibit fibrosis. To this end, we focused on blocking myostatin, a member of the transforming growth factor-β superfamily and a negative regulator of muscle regeneration, with the myostatin antagonist follistatin. In vivo, follistatin-overexpressing transgenic mice underwent significantly greater myofiber regeneration and had less fibrosis formation compared with wild-type mice after skeletal muscle injury.

Changes in regional gray and white matter volume in patients with myofascial-type temporomandibular disorders: a voxel-based morphometry study.

Aims: To use magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) to search for evidence of altered brain morphology in patients with temporomandibular disorders (TMD).

Methods: Using VBM, regional gray and white matter volume was investigated in nine TMD patients and nine carefully matched healthy controls.

Results: A decrease in gray matter volume occurred in the left anterior cingulate gyrus, in the right posterior cingulate gyrus, the right anterior insular cortex, left inferior frontal gyrus, as well as the superior temporal gyrus bilaterally in the TMD patients.

Technical tricks when using the reamer irrigator aspirator technique for autologous bone graft harvesting.

This report describes technical tricks for using the reamer irrigator aspirator to harvest autologous bone graft from the femur. This device is a focus of interest in orthopaedics because it can be used to harvest bone graft from the femoral canal and medial condyle in voluminous quantities. Moreover, according to some authors, the osteogenic potential of this graft is at least as effective as that of autogenous bone obtained from the iliac crest.