Pathobiont-induced suppressive immune imprints thwart T cell vaccine responses.

Pathobionts have evolved many strategies to coexist with the host, but how immune evasion mechanisms contribute to the difficulty of developing vaccines against pathobionts is unclear. Meanwhile, Staphylococcus aureus (SA) has resisted human vaccine development to date. Here we show that prior SA exposure induces non-protective CD4 T cell imprints, leading to the blunting of protective IsdB vaccine responses.

Machine learning based DNA melt curve profiling enables automated novel genotype detection.

Surveillance for genetic variation of microbial pathogens, both within and among species, plays an important role in informing research, diagnostic, prevention, and treatment activities for disease control. However, large-scale systematic screening for novel genotypes remains challenging in part due to technological limitations. Towards addressing this challenge, we present an advancement in universal microbial high resolution melting (HRM) analysis that is capable of accomplishing both known genotype identification and novel genotype detection.

Universal digital high-resolution melting for the detection of pulmonary mold infections.

Unlabelled: Invasive mold infections (IMIs) are associated with high morbidity, particularly in immunocompromised patients, with mortality rates between 40% and 80%. Early initiation of appropriate antifungal therapy can substantially improve outcomes, yet early diagnosis remains difficult to establish and often requires multidisciplinary teams evaluating clinical and radiological findings plus supportive mycological findings. Universal digital high-resolution melting (U-dHRM) analysis may enable rapid and robust diagnoses of IMI.

Universal Digital High-Resolution Melt Analysis for the Diagnosis of Bacteremia.

Fast and accurate diagnosis of bloodstream infection is necessary to inform treatment decisions for septic patients, who face hourly increases in mortality risk. Blood culture remains the gold standard test but typically requires approximately 15 hours to detect the presence of a pathogen. We, therefore, assessed the potential for universal digital high-resolution melt (U-dHRM) analysis to accomplish faster broad-based bacterial detection, load quantification, and species-level identification directly from whole blood.

Universal Digital High Resolution Melt for the detection of pulmonary mold infections.

Background: Invasive mold infections (IMIs) such as aspergillosis, mucormycosis, fusariosis, and lomentosporiosis are associated with high morbidity and mortality, particularly in immunocompromised patients, with mortality rates as high as 40% to 80%. Outcomes could be substantially improved with early initiation of appropriate antifungal therapy, yet early diagnosis remains difficult to establish and often requires multidisciplinary teams evaluating clinical and radiological findings plus supportive mycological findings. Universal digital high resolution melting analysis (U-dHRM) may enable rapid and robust diagnosis of IMI.

Universal digital high resolution melt analysis for the diagnosis of bacteremia.

Unlabelled: Fast and accurate diagnosis of bloodstream infection is necessary to inform treatment decisions for septic patients, who face hourly increases in mortality risk. Blood culture remains the gold standard test but typically requires ∼15 hours to detect the presence of a pathogen. Here, we assess the potential for universal digital high-resolution melt (U-dHRM) analysis to accomplish faster broad-based bacterial detection, load quantification, and species-level identification directly from whole blood.

Data-driven noise modeling of digital DNA melting analysis enables prediction of sequence discriminating power.

Motivation: The need to rapidly screen complex samples for a wide range of nucleic acid targets, like infectious diseases, remains unmet. Digital High-Resolution Melt (dHRM) is an emerging technology with potential to meet this need by accomplishing broad-based, rapid nucleic acid sequence identification. Here, we set out to develop a computational framework for estimating the resolving power of dHRM technology for defined sequence profiling tasks.

Improving Quantitative Power in Digital PCR through Digital High-Resolution Melting.

Applying digital PCR (dPCR) technology to challenging clinical and industrial detection tasks has become more prevalent because of its capability for absolute quantification and rare target detection. However, practices learned from quantitative PCR (qPCR) that promote assay robustness and wide-ranging utility are not readily applied in dPCR. These include internal amplification controls to account for false-negative reactions and amplicon high-resolution melt (HRM) analysis to distinguish true positives from false positives.

Assessment of Ventriculoperitoneal Shunt Function Using Ultrasound Characterization of Valve Interface Oscillation as a Proxy.

Objective Ventricular shunts are a mainstay of hydrocephalus treatment, but the detection of its clinical failure often relies on circumstantial evidence. A direct, non-interventional method for reliably evaluating cerebrospinal fluid (CSF) function does not exist due to the difficulty of measuring in vivo flow characteristics. The objective of this study is to apply a novel method of ultrasound monitoring to characterize the oscillation observed during pulsatile CSF flow and failure states in an in vitro and cadaveric model.

Quantification of Muscle Tissue Properties by Modeling the Statistics of Ultrasound Image Intensities Using a Mixture of Gamma Distributions in Children With and Without Cerebral Palsy.

Objectives: To investigate whether quantitative ultrasound (US) imaging, based on the envelope statistics of the backscattered US signal, can describe muscle properties in typically developing children and those with cerebral palsy (CP).

Methods: Radiofrequency US data were acquired from the rectus femoris muscle of children with CP (n = 22) and an age-matched cohort without CP (n = 14) at rest and during maximal voluntary isometric contraction. A mixture of gamma distributions was used to model the histogram of the echo intensities within a region of interest in the muscle.

Ultrasound characterization of interface oscillation as a proxy for ventriculoperitoneal shunt function.

Hydrocephalus, where cerebrospinal fluid (CSF) production rate is greater than reabsorption rate, leads to impaired neurological function if left untreated. Ventriculoperitoneal shunts (VPS) are implanted in the brain ventricles to route CSF. VPS systems have a high failure rate, and failure symptoms resemble symptoms of common maladies.