Visualizing machine learning-based predictions of postpartum depression risk for lay audiences.

OBJECTIVES: To determine if different formats for conveying machine learning (ML)-derived postpartum depression risks impact patient classification of recommended actions (primary outcome) and intention to seek care, perceived risk, trust, and preferences (secondary outcomes). MATERIALS AND METHODS: We recruited English-speaking females of childbearing age (18-45 years) using an online survey platform. We created 2 exposure variables (presentation format and risk severity), each with 4 levels, manipulated within-subject. Presentation formats consisted of text only, numeric only, gradient number line, and segmented number line. For each format viewed, participants answered questions regarding each outcome. RESULTS: Five hundred four participants (mean age 31 years) completed the survey. For the risk classification question, performance was high (93%) with no significant differences between presentation formats. There were main effects of risk level (all P < .001) such that participants perceived higher risk, were more likely to agree to treatment, and more trusting in their obstetrics team as the risk level increased, but we found inconsistencies in which presentation format corresponded to the highest perceived risk, trust, or behavioral intention. The gradient number line was the most preferred format (43%). DISCUSSION AND CONCLUSION: All formats resulted high accuracy related to the classification outcome (primary), but there were nuanced differences in risk perceptions, behavioral intentions, and trust. Investigators should choose health data visualizations based on the primary goal they want lay audiences to accomplish with the ML risk score.

Who needs what (features) when? Personalizing engagement with data-driven self-management to improve health equity.

OBJECTIVES: To examine the feasibility of promoting engagement with data-driven self-management of health among individuals from minoritized medically underserved communities by tailoring the design of self-management interventions to individuals' type of motivation and regulation in accordance with the Self-Determination Theory. METHODS: Fifty-three individuals with type 2 diabetes from an impoverished minority community were randomly assigned to four different versions of an mHealth app for data-driven self-management with the focus on nutrition, Platano; each version was tailored to a specific type of motivation and regulation within the SDT self-determination continuum. These versions included financial rewards (external regulation), feedback from expert registered dietitians (RDF, introjected regulation), self-assessment of attainment of one's nutritional goals (SA, identified regulation), and personalized meal-time nutrition decision support with post-meal blood glucose forecasts (FORC, integrated regulation). We used qualitative interviews to examine interaction between participants' experiences with the app and their motivation type (internal-external). RESULTS: As hypothesized, we found a clear interaction between the type of motivation and Platano features that users responded to and benefited from. For example, those with more internal motivation reported more positive experience with SA and FORC than those with more external motivation. However, we also found that Platano features that aimed to specifically address the needs of individuals with external regulation did not create the desired experience. We attribute this to a mismatch in emphasis on informational versus emotional support, particularly evident in RDF. In addition, we found that for participants recruited from an economically disadvantaged community, internal factors, such as motivation and regulation, interacted with external factors, most notably with limited health literacy and limited access to resources. CONCLUSIONS: The study suggests feasibility of using SDT to tailor design of mHealth interventions for promoting data-driven self-management to individuals' motivation and regulation. However, further research is needed to better align design solutions with different levels of self-determination continuum, to incorporate stronger emphasis on emotional support for individuals with external regulation, and to address unique needs and challenges of underserved communities, with particular attention to limited health literacy and access to resources.

Socioeconomic factors, stress, hair cortisol, and white matter microstructure in children.

Socioeconomic disadvantage has been linked to increased stress exposure in children and adults. Exposure to stress in childhood has been associated with deleterious effects on cognitive development and well-being throughout the lifespan. Further, exposure to stress has been associated with differences in brain development in children, both in cortical and subcortical gray matter. However, less is known about the associations among socioeconomic disadvantage, stress, and children's white matter development. In this study, we investigated whether socioeconomic disparities would be associated with differences in white matter microstructure in the cingulum bundle, as has been previously reported. We additionally investigated whether any such differences could be explained by differences in stress exposure and/or physiological stress levels. White matter tracts were measured via diffusion tensor imaging in 58 children aged 5-9 years. Results indicated that greater exposure to stressful life events was associated with higher child hair cortisol concentrations. Further, physiological stress, as indexed by hair cortisol concentrations, were associated with higher fractional anisotropy in the cingulum bundle. These results have implications for better understanding how perceived and physiological stress may alter neural development during childhood.

From Reflection to Action: Combining Machine Learning with Expert Knowledge for Nutrition Goal Recommendations.

Self-tracking can help personalize self-management interventions for chronic conditions like type 2 diabetes (T2D), but reflecting on personal data requires motivation and literacy. Machine learning (ML) methods can identify patterns, but a key challenge is making actionable suggestions based on personal health data. We introduce GlucoGoalie, which combines ML with an expert system to translate ML output into personalized nutrition goal suggestions for individuals with T2D. In a controlled experiment, participants with T2D found that goal suggestions were understandable and actionable. A 4-week in-the-wild deployment study showed that receiving goal suggestions augmented participants' self-discovery, choosing goals highlighted the multifaceted nature of personal preferences, and the experience of following goals demonstrated the importance of feedback and context. However, we identified tensions between abstract goals and concrete eating experiences and found static text too ambiguous for complex concepts. We discuss implications for ML-based interventions and the need for systems that offer more interactivity, feedback, and negotiation.

Material hardship, prefrontal cortex-amygdala structure, and internalizing symptoms in children.

Material hardship, or difficulty affording basic resources such as food, housing, utilities, and health care, increases children's risk for internalizing problems. The uncinate fasciculus (UNC) and two of the gray matter regions it connects-the orbitofrontal cortex (OFC) and amygdala-may play important roles in the neural mechanisms underlying these associations. We investigated associations among material hardship, UNC microstructure, OFC and amygdala structure, and internalizing symptoms in children. Participants were 5-9-year-old children (N = 94, 61% female) from socioeconomically diverse families. Parents completed questionnaires assessing material hardship and children's internalizing symptoms. High-resolution, T1-weighted magnetic resonance imaging (n = 51), and diffusion tensor imaging (n = 58) data were acquired. UNC fractional anisotropy (FA), medial OFC surface area, and amygdala gray matter volume were extracted. Greater material hardship was significantly associated with lower UNC FA, smaller amygdala volume, and higher internalizing symptoms in children, after controlling for age, sex, and family income-to-needs ratio. Lower UNC FA significantly mediated the association between material hardship and internalizing symptoms in girls but not boys. These findings are consistent with the notion that material hardship may lead to altered white matter microstructure and gray matter structure in neural networks critical to emotion processing and regulation.

Adapting the stage-based model of personal informatics for low-resource communities in the context of type 2 diabetes.

Growing availability of self-monitoring technologies creates new opportunities for collection of personal health data and their use in personalized health informatics interventions. However, much of the previous empirical research and existing theories of individuals' engagement with personal data focused on early adopters and data enthusiasts. Less is understood regarding ways individuals from medically underserved low-income communities who live with chronic diseases engage with self-monitoring in health. In this research, we adapted a widely used theoretical framework, the stage-based model of personal informatics, to the unique attitudes, needs, and constraints of low-income communities. We conducted a qualitative study of attitudes and perceptions regarding tracking and planning in health and other contexts (e.g., finances) among low-income adults living with type 2 diabetes. This study showed distinct differences in participants' attitudes and behaviors around tracking and planning, as well as wide variability in their sense of being in charge of different areas of one's life. Ultimately, we found a strong connection between these two: perceptions of being in charge seems to be strongly connected to an individual's proactive or reactive tracking and planning in that area. Whereas individuals with a greater sense of being in charge of their health were more proactive, meaning they were likely to engage with all the stages of personal informatics model on their own, those with less of a sense of being in charge were more likely to be reactive-relying on their healthcare providers for several critical stages of self-monitoring (deciding what data to collect, integrating data from multiple sources, reflecting over patterns in collected data, and arriving at conclusions and implications for action). Perhaps as a result, these individuals were less likely to experience increases in self-awareness and self-knowledge, common motivating factors to engaging in self-monitoring in the future. We argue that adapting this framework in a way that highlights gaps in individuals' engagement has a number of important implications for future research in biomedical informatics and for the design of new interventions that promote engagement with self-monitoring, and that are robust in light of fragmented engagement.

Infants of mothers with higher physiological stress show alterations in brain function.

Chronic stress has been increasingly linked with aberrations in children's behavioral, cognitive, and social development, yet the effect of chronic physiological stress on neural development during the first year of life is largely unknown. The present study aims to link a physiological index of chronic stress (maternal hair cortisol concentration) to maturational differences in infant functional brain development during the first year of life. Participants were 94 mother-infant dyads. To index chronic physiological stress, maternal hair samples were assayed for the previous three months' cortisol output. To examine the development of brain function during the first year of life, six-to-twelve-month-old infants (N = 94) completed a resting electroencephalography (EEG) recording. Infants of mothers with evidence of higher physiological stress showed increased relative low-frequency (theta) power and reduced relative high-frequency (alpha, high-gamma) power, compared to infants of mothers with evidence of low physiological stress. This pattern of findings is consistent with other studies suggesting that early life stress may lead to alterations in patterns of infant brain development. These findings are important given that maturational lags in brain development can be long-lasting and are associated with deficits in cognitive and emotional development. The present research also suggests that reducing maternal physiological stress may be a useful target for future interventions aiming to foster neurodevelopment during the first year of life.

Socioeconomic Disparities in Chronic Physiologic Stress Are Associated With Brain Structure in Children.

BACKGROUND: Socioeconomic factors have been consistently linked with the structure of children's hippocampus and anterior cingulate cortex (ACC). Chronic stress-as indexed by hair cortisol concentration-may represent an important mechanism underlying these associations. Here, we examined associations between hair cortisol and children's hippocampal and ACC structure, including across hippocampal subfields, and whether hair cortisol mediated associations between socioeconomic background (family income-to-needs ratio, parental education) and the structure of these brain regions. METHODS: Participants were 5- to 9-year-old children (N = 94; 61% female) from socioeconomically diverse families. Parents and children provided hair samples that were assayed for cortisol. High-resolution, T1-weighted magnetic resonance imaging scans were acquired, and FreeSurfer 6.0 was used to compute hippocampal volume and rostral and caudal ACC thickness and surface area (n = 37 with both child hair cortisol and magnetic resonance imaging data; n = 41 with both parent hair cortisol and magnetic resonance imaging data). RESULTS: Higher hair cortisol concentration was significantly associated with smaller CA3 and dentate gyrus hippocampal subfield volumes but not with CA1 or subiculum volume. Higher hair cortisol was also associated with greater caudal ACC thickness. Hair cortisol significantly mediated associations between parental education level and CA3 and dentate gyrus volumes; lower parental education level was associated with higher hair cortisol, which in turn was associated with smaller volume in these subfields. CONCLUSIONS: These findings point to chronic physiologic stress as a potential mechanism through which lower parental education level leads to reduced hippocampal volume. Hair cortisol concentration may be an informative biomarker leading to more effective prevention and intervention strategies aimed at childhood socioeconomic disadvantage.

A Simple Technique for Accurate Transfer of Secondary Copings in a Tooth-Supported Telescopic Prosthesis.

Residual ridge resorption is a rapid, progressive, irreversible, and inevitable process of bone resorption. Long-standing teeth and implants have been shown to have maintained the bone around them without resorption. Thus, overdenture therapy has been proven to be beneficial in situations where few remaining teeth are present. In addition to the various advantages seen with tooth-supported telescopic overdentures, a few shortcomings can also be expected, including unseating of the overdenture, increased bulk of the prosthesis, secondary caries, etc. The precise transfer of the secondary telescopic copings to maintain the spatial relationship, without any micromovement, remains the most critical step in ensuring the success of the tooth-supported telescopic prosthesis. Thus, a simple and innovative technique of splinting the secondary copings was devised to prevent distortion and micromovement and maintain its spatial relationship.

30S Subunit-dependent activation of the Sorangium cellulosum So ce56 aminoglycoside resistance-conferring 16S rRNA methyltransferase Kmr.

Methylation of bacterial 16S rRNA within the ribosomal decoding center confers exceptionally high resistance to aminoglycoside antibiotics. This resistance mechanism is exploited by aminoglycoside producers for self-protection while functionally equivalent methyltransferases have been acquired by human and animal pathogenic bacteria. Here, we report structural and functional analyses of the Sorangium cellulosum So ce56 aminoglycoside resistance-conferring methyltransferase Kmr. Our results demonstrate that Kmr is a 16S rRNA methyltransferase acting at residue A1408 to confer a canonical aminoglycoside resistance spectrum in Escherichia coli. Kmr possesses a class I methyltransferase core fold but with dramatic differences in the regions which augment this structure to confer substrate specificity in functionally related enzymes. Most strikingly, the region linking core ß-strands 6 and 7, which forms part of the S-adenosyl-l-methionine (SAM) binding pocket and contributes to base flipping by the m(1)A1408 methyltransferase NpmA, is disordered in Kmr, correlating with an exceptionally weak affinity for SAM. Kmr is unexpectedly insensitive to substitutions of residues critical for activity of other 16S rRNA (A1408) methyltransferases and also to the effects of by-product inhibition by S-adenosylhomocysteine (SAH). Collectively, our results indicate that adoption of a catalytically competent Kmr conformation and binding of the obligatory cosubstrate SAM must be induced by interaction with the 30S subunit substrate.

Molecular recognition and modification of the 30S ribosome by the aminoglycoside-resistance methyltransferase NpmA.

Aminoglycosides are potent, broad spectrum, ribosome-targeting antibacterials whose clinical efficacy is seriously threatened by multiple resistance mechanisms. Here, we report the structural basis for 30S recognition by the novel plasmid-mediated aminoglycoside-resistance rRNA methyltransferase A (NpmA). These studies are supported by biochemical and functional assays that define the molecular features necessary for NpmA to catalyze m(1)A1408 modification and confer resistance. The requirement for the mature 30S as a substrate for NpmA is clearly explained by its recognition of four disparate 16S rRNA helices brought into proximity by 30S assembly. Our structure captures a "precatalytic state" in which multiple structural reorganizations orient functionally critical residues to flip A1408 from helix 44 and position it precisely in a remodeled active site for methylation. Our findings provide a new molecular framework for the activity of aminoglycoside-resistance rRNA methyltransferases that may serve as a functional paradigm for other modification enzymes acting late in 30S biogenesis.

Site-directed mutants of 16S rRNA reveal important RNA domains for KsgA function and 30S subunit assembly.

KsgA is an rRNA methyltransferase important to the process of small subunit biogenesis in bacteria. It is ubiquitously found in all life including archaea and eukarya, where the enzyme is referred to as Dim1. Despite the emergence of considerable data addressing KsgA function over the last several years, details pertaining to RNA recognition are limited, in part because the most accessible substrate for in vitro studies of KsgA is the 900000 Da 30S ribosomal subunit. To overcome challenges imposed by size and complexity, we adapted recently reported techniques to construct in vivo assembled mutant 30S subunits suitable for use in in vitro methyltransferase assays. Using this approach, numerous 16S rRNA mutants were constructed and tested. Our observations indicate that the 790 loop of helix 24 plays an important role in overall catalysis by KsgA. Moreover, the length of helix 45 also is important to catalysis. In both cases loss of catalytic function occurred without an increase in the production of N(6)-methyladenosine, a likely indication that there was no critical reduction in binding strength. Both sets of observations support a "proximity" mechanism of KsgA function. We also report that several of the mutants constructed failed to assemble properly into 30S subunits, while some others did so with reduced efficiency. Therefore, the same technique of generating mutant 30S subunits can be used to study ribosome biogenesis on the whole.

The adenosine dimethyltransferase KsgA recognizes a specific conformational state of the 30S ribosomal subunit.

The methyltransferase KsgA modifies two adjacent adenosines in 16S rRNA by adding two methyl groups to the N(6) position of each nucleotide. Unlike nearly all other rRNA modifications, these modifications and the responsible enzyme are highly conserved phylogenetically, suggesting that the modification system has an important role in ribosome biogenesis. It has been known for some time that KsgA recognizes a complex pre-30S substrate in vitro, but there is disagreement in the literature as to what that substrate can be. That disagreement is resolved in this report; KsgA is unable to methylate 30S subunits in the translationally active conformation, but rather can modify 30S when in an experimentally well established translationally inactive conformation. Recent 30S crystal structures provide some basis for explaining why it is impossible for KsgA to methylate 30S in the translationally active conformation. Previous work identified one set of ribosomal proteins important for efficient methylation by KsgA and another set refractory methylation. With the exception of S21 the recent crystal structures of 30S also instructs that the proteins important for KsgA activity all exert their influence indirectly. Unfortunately, S21, which is inhibitory to KsgA activity, has not had its position determined by X-ray crystallography. A reevaluation of published biophysical data on the location also suggests that the refractory nature of S21 is also indirect. Therefore, it appears that KsgA solely senses the conformation 16S rRNA when carrying out its enzymatic activity.

Recognition of a complex substrate by the KsgA/Dim1 family of enzymes has been conserved throughout evolution.

Ribosome biogenesis is a complicated process, involving numerous cleavage, base modification and assembly steps. All ribosomes share the same general architecture, with small and large subunits made up of roughly similar rRNA species and a variety of ribosomal proteins. However, the fundamental assembly process differs significantly between eukaryotes and eubacteria, not only in distribution and mechanism of modifications but also in organization of assembly steps. Despite these differences, members of the KsgA/Dim1 methyltransferase family and their resultant modification of small-subunit rRNA are found throughout evolution and therefore were present in the last common ancestor. In this paper we report that KsgA orthologs from archaeabacteria and eukaryotes are able to complement for KsgA function in bacteria, both in vivo and in vitro. This indicates that all of these enzymes can recognize a common ribosomal substrate, and that the recognition elements must be largely unchanged since the evolutionary split between the three domains of life.