Transforming Digital Phenotyping Raw Data Into Actionable Biomarkers, Quality Metrics, and Data Visualizations Using Cortex Software Package: Tutorial.

As digital phenotyping, the capture of active and passive data from consumer devices such as smartphones, becomes more common, the need to properly process the data and derive replicable features from it has become paramount. Cortex is an open-source data processing pipeline for digital phenotyping data, optimized for use with the mindLAMP apps, which is used by nearly 100 research teams across the world. Cortex is designed to help teams (1) assess digital phenotyping data quality in real time, (2) derive replicable clinical features from the data, and (3) enable easy-to-share data visualizations. Cortex offers many options to work with digital phenotyping data, although some common approaches are likely of value to all teams using it. This paper highlights the reasoning, code, and example steps necessary to fully work with digital phenotyping data in a streamlined manner. Covering how to work with the data, assess its quality, derive features, and visualize findings, this paper is designed to offer the reader the knowledge and skills to apply toward analyzing any digital phenotyping data set. More specifically, the paper will teach the reader the ins and outs of the Cortex Python package. This includes background information on its interaction with the mindLAMP platform, some basic commands to learn what data can be pulled and how, and more advanced use of the package mixed with basic Python with the goal of creating a correlation matrix. After the tutorial, different use cases of Cortex are discussed, along with limitations. Toward highlighting clinical applications, this paper also provides 3 easy ways to implement examples of Cortex use in real-world settings. By understanding how to work with digital phenotyping data and providing ready-to-deploy code with Cortex, the paper aims to show how the new field of digital phenotyping can be both accessible to all and rigorous in methodology.

Hepatitis B Birth Dose Vaccination Improvement Initiative: The 24-Hour Baby Bundle.

BACKGROUND: An estimated 25,000 infants are born to mothers diagnosed with hepatitis B virus (HBV) each year in the United States. Administration of the birth dose HBV vaccine prevents transmission during delivery. Despite national guidelines promoting vaccination within 24 hours of birth, fewer than 70% of infants receive the dose in their first 3 days of life. To improve compliance with national recommendations, Northwestern Medicine implemented a bundled care initiative in the well newborn nursery, entitled the 24-hour baby bundle (24-HBB). PURPOSE: Evaluate the 24-HBB's effect on improving time to HBV vaccine administration. METHODS: The 24-HBB was created by an interdisciplinary team and implemented on February 17, 2020. Bundled care begins at 23 hours of life, starting with the HBV vaccine, followed by bath, weight, and congenital heart disease screening, and ending with metabolic screening. We conducted a retrospective cohort study of 22,057 infants born at Northwestern Medicine Prentice Women's Hospital in Chicago, Illinois. Our sample included preintervention birthdates between February 16, 2019, and January 16, 2020, and postintervention birthdates between March 17, 2020, and February 16, 2021, with a 2-month washout education period between January 17, 2020, and March 16, 2020. RESULTS: Hepatitis B virus immunization within 24 hours increased significantly from 43.83% to 66.90% (P < .0001). In addition, overall hepatitis B immunization prior to discharge significantly increased after implementation of the 24-HBB (98.18% vs 98.82%, P < .0001). IMPLICATIONS FOR PRACTICE AND RESEARCH: The 24-HBB is effective at increasing rates of HBV immunization within 24 hours of birth. Newborn nurseries may benefit from similar initiatives to prevent hepatitis B infection, satisfy national recommendations, and promote childhood vaccination compliance.

The Digital Navigator: Standardizing Human Technology Support in App-Integrated Clinical Care.

Background: Mental health apps offer scalable care, yet clinical adoption is hindered by low user engagement and integration challenges into clinic workflows. Human support staff called digital navigators, trained in mental health technology, could enhance care access and patient adherence and remove workflow burdens from clinicians. While the potential of this role is clear, training staff to become digital navigators and assessing their impact are primary challenges. Methods: We present a detailed manual/framework for implementation of the Digital Navigator within a short-term, cognitive-behavioral therapy-focused hybrid clinic. We analyze patient engagement, satisfaction, and digital phenotyping data quality outcomes. Data from 83 patients, for the period spanning September 2022 to September 2023, included Digital Navigator satisfaction, correlated with demographics, mindLAMP app satisfaction, engagement, and passive data quality. Additionally, average passive data across 33 clinic patients from November 2023 to January 2024 were assessed for missingness. Results: Digital Navigator satisfaction averaged 18.8/20. Satisfaction was not influenced by sex, race, gender, or education. Average passive data quality across 33 clinic patients was 0.82 at the time this article was written. Digital Navigator satisfaction scores had significant positive correlation with both clinic app engagement and perception of that app. Conclusions: Results demonstrate preliminary support and patient endorsement for the Digital Navigator role and positive outcomes around digital engagement and digital phenotyping data quality. Through sharing training resources and standardizing the role, we aim to enable clinicians and researchers to adapt and utilize the Digital Navigator for their own needs.

Discrepancy Between Reported and Calculated Pain Reduction in Patients With Spinal Cord Stimulation Therapy and Lack of Agreement Between Patient Satisfaction and Degree of Pain Relief.

OBJECTIVES: This study aimed to determine agreement between reported percentage pain reduction (RPPR) and calculated percentage pain reduction (CPPR) in patients with percutaneous spinal cord stimulation (SCS) implants, and to correlate RPPR and CPPR with patient satisfaction. We also sought to determine which patient-reported outcome measures are most improved in patients with SCS. MATERIALS AND METHODS: Fifty patients with percutaneous spinal cord stimulator implants with a mean follow-up of 51.1 months were interviewed and surveyed to assess their pain level, impression of degree of pain relief, satisfaction with the therapy, and desire to have the device again. Baseline pain level was obtained from their preimplant records. RESULTS: Overall, RPPR was found to be 53.3%, whereas CPPR was 44.4%. Of all patients, 21 reported <50% pain reduction; however, most of these (12/21, 57%) were satisfied with the outcome of therapy. In terms of individual improvement in outcomes, activities of daily life was the most improved measure at 82%, followed by mood, sleep, medication use, and health care utilization at 74%, 62%, 50%, and 48%, respectively. CONCLUSIONS: RPPR appears to be a complex outcome measure that may not agree with CPPR. Overall RPPR is greater than the CPPR. On the basis of our data, these independently valid measures should not be used interchangeably. A 50% pain reduction threshold is not a requisite for patient satisfaction and desire to have the device again. Activities of daily living was the most improved measure in this cohort, followed by mood, sleep, medication usage, and decrease in health care utilization.

Integrative Review of Music and Music Therapy Interventions on Functional Outcomes in Children with Acquired Brain Injury.

Acquired brain injury (ABI) can result in a multitude of impairments to physical, cognitive, communicative, psychological, and psychosocial functioning. Music interventions are emerging as a valuable form of intervention in the rehabilitation of children with ABI, stimulating brain functions involved in movement, cognition, speech, emotions, and sensory perceptions. To date, the literature detailing the impact of music and music therapy interventions on functional outcomes in children with ABI has not been reviewed systematically. To address this, Whittemore and Knafl's five-stage integrative review framework was employed, which includes (a) problem identification, (b) literature search, (c) data evaluation, (d) data analysis and synthesis, and (e) presentation of the findings. A total of 388 articles were retrieved, and 8 studies met the inclusion criteria. Analysis and synthesis resulted in 3 overarching themes: outcomes of using music therapy in pediatric ABI, music therapy as a motivator in pediatric ABI rehabilitation, and collaboration. The review highlights the pivotal role of music as a motivational catalyst that promotes adherence to rehabilitative intervention. Nevertheless, it underscores a significant gap in empirical research within the field, emphasizing the necessity for larger, more rigorous studies.

Transoral Excision of a Hypopharyngeal Liposarcoma.

Liposarcomas are the most common soft tissue sarcoma in adults, whereas liposarcomas of the head and neck, particularly the hypopharynx, are incredibly rare - with approximately 50 cases reported in the literature. We present a case of an otherwise healthy and asymptomatic 42-year-old male who presented dramatically after vomiting up a large soft tissue mass. The lesion was surgically removed via transoral approach with blue laser, and diagnosis of well-differentiated liposarcoma was made via MDM2 gene amplification by FISH. Oral extrusion is a rare feature of this disease. This is the first documented case of an orally extruded liposarcoma to present in an otherwise asymptomatic and healthy patient, demonstrating how this entity may be indolent until initial presentation. Laryngoscope, 2024.

Design and Evaluation of Chimeric Plasmodium falciparum Circumsporozoite Protein-Based Malaria Vaccines.

Efficacy data on two malaria vaccines, RTS,S and R21, targeting Plasmodium falciparum circumsporozoite protein (PfCSP), are encouraging. Efficacy may be improved by induction of additional antibodies to neutralizing epitopes outside of the central immunodominant repeat domain of PfCSP. We designed four rPfCSP-based vaccines in an effort to improve the diversity of the antibody response. We also evaluated P. falciparum merozoite surface protein 8 (PfMSP8) as a malaria-specific carrier protein as an alternative to hepatitis B surface antigen. We measured the magnitude, specificity, subclass, avidity, durability, and efficacy of vaccine-induced antibodies in outbred CD1 mice. In comparison to N-terminal- or C-terminal-focused constructs, immunization with near full-length vaccines, rPfCSP (#1) or the chimeric rPfCSP/8 (#2), markedly increased the breadth of B cell epitopes recognized covering the N-terminal domain, junctional region, and central repeat. Both rPfCSP (#1) and rPfCSP/8 (#2) also elicited a high proportion of antibodies to conformation-dependent epitopes in the C-terminus of PfCSP. Fusion of PfCSP to PfMSP8 shifted the specificity of the T cell response away from PfCSP toward PfMSP8 epitopes. Challenge studies with transgenic Plasmodium yoelii sporozoites expressing PfCSP demonstrated high and consistent sterile protection following rPfCSP/8 (#2) immunization. Of note, antibodies to conformational C-terminal epitopes were not required for protection. These results indicate that inclusion of the N-terminal domain of PfCSP can drive responses to protective, repeat, and non-repeat B cell epitopes and that PfMSP8 is an effective carrier for induction of high-titer, durable anti-PfCSP antibodies.

Case series: Congenital enterovirus infection-associated haemophagocytic lymphohistiocytosis and subsequent neutropaenia.

Congenital enterovirus infection can be associated with a pro-inflammatory state triggering haemophagocytic lymphohistiocytosis (HLH). Enteroviruses are also known to cause transient neutropenia in healthy children. Two infants presented with temperature instability, lethargy, thrombocytopaenia, hepatosplenomegaly and evidence of hyperinflammation in the setting of perinatal maternal rash and household contacts with gastrointestinal symptoms. Whilst HLH was successfully treated in both, protracted neutropenia persisted. Immune dysregulation with enterovirus in the neonatal period can provoke the generation of autoantibodies to hematologic cells giving rise to conditions such as autoimmune neutropenia. Sustained neutropaenia, after resolution of secondary infectious forms of HLH, requires investigation for underlying aetiologies.

Morphogenic Modeling of Corrosion Reveals Complex Effects of Intermetallic Particles.

Corrosion processes are often discussed as stochastic events. Here, it is shown that some of these seemingly random processes are not driven by nanoscopic fluctuations but rather by the spatial distribution of micrometer-scale heterogeneities that trigger fast reactions associated with corrosion. Using a novel excitable reaction-diffusion model, corrosion waves traveling over the metal surface and the associated material loss are described. This resulting nonuniform corrosion penetration, seen as a height loss in modeling, exposes buried intermetallic particles, which depending on the local electrochemical state of the surface trigger or block new waves. Informed by quantitative experimental data for the Mg-Al-Zn alloy AZ31B, wave speeds, wave widths, and average material loss are accurately captured. Morphogenic mitigation based on wave-breaking microparticles is also simulated. While AZ31B corrosion is identified as a process driven by rare-wave events, this study predicts several other corrosion regimes that proceed via spots or patchy patterns, opening the door for new protection, design, and prediction strategies.

MAVMET trial: maraviroc and/or metformin for metabolic dysfunction associated fatty liver disease in adults with suppressed HIV.

OBJECTIVE: Metabolic dysfunction associated fatty liver disease (MAFLD) is over-represented in people with HIV (PWH). Maraviroc (MVC) and/or metformin (MET) may reduce MAFLD by influencing inflammatory pathways and fatty acid metabolism. DESIGN: Open-label, 48-week randomized trial with a 2 x 2 factorial design. SETTING: Multicenter HIV clinics. PARTICIPANTS: Nondiabetic, virologically suppressed PLWH, aged at least 35 years, with confirmed/suspected MAFLD (≥1 biochemical/anthropometric/radiological/histological features). INTERVENTION: Adjunctive MVC; MET; MVC+MET vs. antiretroviral therapy (ART) alone. PRIMARY OUTCOME: Change in liver fat fraction (LFF) between baseline and week-48 using magnetic resonance proton density fat fraction (MR PDFF). RESULTS: Six sites enrolled 90 participants (93% male; 81% white; median age 52 [interquartile range, IQR 47-57] years) between March 19, 2018, and November 11, 2019. Seventy percent had imaging/biopsy and at least one 1 MAFLD criteria. The analysis included 82/90 with week-0 and week-48 scans. Median baseline MR PDFF was 8.9 (4.6-17.1); 40, 38, 8, and 14% had grade zero, one, two, and three steatosis, respectively. Mean LFF increased slightly between baseline and follow-up scans: 2.22% MVC, 1.26% MET, 0.81% MVC+MET, and 1.39% ART alone. Prolonged intervention exposure (delayed week-48 scans) exhibited greater increases in MR PDFF (estimated difference 4.23% [95% confidence interval, 95% CI 2.97-5.48], P  < 0.001). There were no differences in predicted change for any intervention compared to ART alone: MVC (-0.42% [95% CI -1.53 to 0.68, P  = 0.45]), MET (-0.62 [-1.81 to 0.56, P  = 0.30]), and MVC+MET (-1.04 [-2.74 to 0.65, P  = 0.23]). Steatosis grade remained unchanged in 55% and increased in 24%. CONCLUSION: Baseline levels of liver fat were lower than predicted. Contrary to our hypothesis, neither MVC, MET, or the combination significantly reduced liver fat as measured by MRPDFF compared to ART alone.

Adverse childhood experiences and biomarkers of inflammation in a diverse cohort of early school-aged children.

Objective: The objective of this study was to evaluate the relationship between ACEs and inflammatory profiles (i.e., pro- and anti-) in early childhood and to examine whether patterns differ for racial/ethnic subgroups. Study design: Using longitudinal data from the Multidimensional Assessment of Preschoolers Study (MAPS) (N = 122), we examined the relationship between adverse childhood experiences (ACEs) beginning at birth, C -reactive protein (CRP), and both pro-inflammatory (i.e., IL-1 ß, IL-6, TNF, and CRP) and anti-inflammatory (i.e. IL-4 and IL-10) biomarkers during early school age (ages 6-8 years). Results: No children in the sample were reported to have experienced 0 ACES, 7% had 1 ACE, 51% had 2-3 ACEs, and 42% had 4 or more ACEs accumulated by the early school-age wave (ESA). There were no significant associations between cumulative ACEs and inflammatory markers. However, parental substance abuse, a specific ACE, was positively correlated with a pro-inflammatory profile at early school age (r = 0.18, p<.05). Specifically, substance abuse as an ACE was associated with higher levels of pro-inflammatory markers such as IL-1 ß and IL-6. Additionally, Hispanics with ACEs had higher levels of CRP than Black and white individuals. Conclusions: Children with histories of ACEs, especially those with parental substance abuse, may have higher levels of inflammation. Better understanding the role of inflammation in the development of chronic diseases for individuals with ACEs may allow earlier identification and prevention of disease during childhood for those at the highest risk.