A large collection of real-world pediatric sleep studies.

Despite being crucial to health and quality of life, sleep-especially pediatric sleep-is not yet well understood. This is exacerbated by lack of access to sufficient pediatric sleep data with clinical annotation. In order to accelerate research on pediatric sleep and its connection to health, we create the Nationwide Children's Hospital (NCH) Sleep DataBank and publish it at Physionet and the National Sleep Research Resource (NSRR), which is a large sleep data common with physiological data, clinical data, and tools for analyses. The NCH Sleep DataBank consists of 3,984 polysomnography studies and over 5.6 million clinical observations on 3,673 unique patients between 2017 and 2019 at NCH. The novelties of this dataset include: (1) large-scale sleep dataset suitable for discovering new insights via data mining, (2) explicit focus on pediatric patients, (3) gathered in a real-world clinical setting, and (4) the accompanying rich set of clinical data. The NCH Sleep DataBank is a valuable resource for advancing automatic sleep scoring and real-time sleep disorder prediction, among many other potential scientific discoveries.

The Association Between App-Administered Depression Assessments and Suicidal Ideation in User Comments: Retrospective Observational Study.

BACKGROUND: Many people use apps to help understand and manage their depression symptoms. App-administered questionnaires for the symptoms of depression, such as the Patient Health Questionnaire-9, are easy to score and implement in an app, but may not be accompanied by essential resources and access needed to provide proper support and avoid potential harm. OBJECTIVE: Our primary goal was to evaluate the differences in risks and helpfulness associated with using an app to self-diagnose depression, comparing assessment-only apps with multifeatured apps. We also investigated whether, what, and how additional app features may mitigate potential risks. METHODS: In this retrospective observational study, we identified apps in the Google Play store that provided a depression assessment as a feature and had at least five user comments. We separated apps into two categories based on those having only a depression assessment versus those that offered additional supportive features. We conducted theoretical thematic analyses over the user reviews, with thematic coding indicating the helpfulness of the app, the presence of suicidal ideation, and how and why the apps were used. We compared the results across the two categories of apps and analyzed the differences using chi-square statistical tests. RESULTS: We evaluated 6 apps; 3 provided only a depression assessment (assessment only), and 3 provided features in addition to self-assessment (multifeatured). User comments for assessment-only apps indicated significantly more suicidal ideation or self-harm (n=31, 9.4%) compared to comments for multifeatured apps (n=48, 2.3%; X21=43.88, P<.001). Users of multifeatured apps were over three times more likely than assessment-only app users to comment in favor of the app's helpfulness, likely due to features like mood tracking, journaling, and informational resources (n=56, 17% vs n=1223, 59% respectively; X21=200.36, P<.001). The number of users under the age of 18 years was significantly higher among assessment-only app users (n=40, 12%) than multifeatured app users (n=9, 0.04%; X21=189.09, P<.001). CONCLUSIONS: Apps that diagnose depression by self-assessment without context or other supportive features are more likely to be used by those under 18 years of age and more likely to be associated with increased user distress and potential harm. Depression self-assessments in apps should be implemented with caution and accompanied by evidence-based capabilities that establish proper context, increase self-empowerment, and encourage users to seek clinical diagnostics and outside help.

Usability of a Mobile App for Improving Literacy in Children With Hearing Impairment: Focus Group Study.

BACKGROUND: Children with hearing loss, even those identified early and who use hearing aids or cochlear implants, may face challenges in developing spoken language and literacy. This can lead to academic, behavioral, and social difficulties. There are apps for healthy children to improve their spoken language and literacy and apps that focus on sign language proficiency for children with hearing loss, but these apps are limited for children with hearing loss. Therefore, we have developed an app called Hear Me Read, which uses enhanced digital stories as therapy tools for speech, language, and literacy for children with hearing loss. The platform has therapist and parent/child modes that allow (1) the selection of high-quality, illustrated digital stories by a speech-language pathologist, parent, or child; (2) the modification of digital stories for a multitude of speech and language targets; and (3) the assignment of stories by a therapist to facilitate individualized speech and language goals. In addition, Hear Me Read makes the caregiver a core partner in engagement through functionality, whereby the caregiver can record video and audio of themselves to be played back by the child. OBJECTIVE: This study aimed to evaluate the user experience of the Hear Me Read app through a focus group study with caregivers and their children. METHODS: We recruited 16 participants (8 children with and without hearing loss and 8 caregivers) to participate in 1-hour focus groups. Caregivers and children interacted with the app and discussed their experiences through a semistructured group interview. We employed thematic analysis methods and analyzed the data. We used feedback from the focus group to improve the elements of the app for a larger clinical trial assessing the impact of the app on outcomes. RESULTS: We identified three themes: default needs, specific needs, and family needs. Participants found the app to be esthetically pleasing and easy to use. The findings of this study helped us to identify usability attributes and to amend app functionalities to best fit user needs. Caregivers and children appreciated the enhancements, such as highlighting of parts of speech and caregiver reading of video playback, which were made possible by the digital format. Participants expressed that the app could be used to enhance family reading sessions and family interaction. CONCLUSIONS: The findings from this focus group study are promising for the use of educational apps designed specifically for those with hearing loss who are pursuing listening and spoken language as a communication outcome. Further investigation is needed with larger sample sizes to understand the clinical impact on relevant language and literacy outcomes in this population.

Molecular dynamics analysis of the structural and dynamic properties of the functionally enhanced hepta-variant of mouse 5-aminolevulinate synthase.

Heme biosynthesis, a complex, multistage, and tightly controlled process, starts with 5-aminolevulinate (ALA) production, which, in metazoa and certain bacteria, is a reaction catalyzed by 5-aminolevulinate synthase (ALAS), a pyridoxal 5'-phosphate (PLP)-dependent enzyme. Functional aberrations in ALAS are associated with several human diseases. ALAS can adopt open and closed conformations, with segmental rearrangements of a C-terminal, 16-amino acid loop and an α-helix regulating accessibility to the ALAS active site. Of the murine erythroid ALAS (mALAS2) forms previously engineered to assess the role of the flexible C-terminal loop versus mALAS2 function one stood out due to its impressive gain in catalytic power. To elucidate how the simultaneously introduced seven mutations of this activity-enhanced variant affected structural and dynamic properties of mALAS2, we conducted extensive molecular dynamics simulation analysis of the dimeric forms of wild-type mALAS2, hepta-variant and Rhodobacter capsulatus ALAS (aka R. capsulatus HemA). This analysis revealed that the seven simultaneous mutations in the C-terminal loop, which extends over the active site of the enzyme, caused the bacterial and murine proteins to adopt different conformations. Specifically, a new ß-strand in the mutated 'loop' led to interaction with two preexisting ß-strands and formation of an anti-parallel three-stranded ß-sheet, which likely endowed the murine hepta-variant a more 'stable' open conformation than that of wild-type mALAS2, consistent with a kinetic mechanism involving a faster closed-to-open conformation transition and product release for the mutated than wild-type enzyme. Further, the dynamic behavior of the mALAS2 protomers was strikingly different in the two dimeric forms.

Quarterly intrinsic disorder digest (April-May-June, 2014).

This is the 6th issue of the Digested Disorder series that continues to use only 2 criteria for inclusion of a paper to this digest: The publication date (a paper should be published within the covered time frame) and the topic (a paper should be dedicated to any aspect of protein intrinsic disorder). The current digest issue covers papers published during the second quarter of 2014; i.e., during the period of April, May, and June of 2014. Similar to previous issues, the papers are grouped hierarchically by topics they cover, and for each of the included papers a short description is given on its major findings.

Not an exception to the rule: the functional significance of intrinsically disordered protein regions in enzymes.

Intrinsically disordered protein regions (IDPRs) are remarkably common and have unique and important biological functions. Enzymes have long been considered an exception to the rule of protein intrinsic disorder due to the structural requirements for catalysis. Although functionally significant IDPRs have been described in several enzymes, there has been no study quantifying the extent of this phenomenon. We have conducted a multilevel computational analysis of missing regions in X-ray crystal structures in the PDB and predicted disorder in 66 representative proteomes. We found that the fraction of predicted disorder was higher in non-enzymes than enzymes, because non-enzymes were more likely to be fully disordered. However, we also found that transferases, hydrolases and enzymes with multiple assigned functional classifications were similar to non-enzymes in terms of the length of the longest continuous stretch of predicted disorder. Both eukaryotic enzymes and non-enzymes had a greater disorder content than was seen in bacteria. Disorder at the proteome level appears to emerge in response to organismic and functional complexity, and enzymes are not an exception to this rule.

Physicochemical sequence characteristics that influence S-palmitoylation propensity.

Over the past 30 years, several hundred eukaryotic proteins spanning from yeast to man have been shown to be S-palmitoylated. This post-translational modification involves the reversible addition of a 16-carbon saturated fatty acyl chain onto the cysteine residue of a protein where it regulates protein membrane association and distribution, conformation, and stability. However, the large-scale proteome-wide discovery of new palmitoylated proteins has been hindered by the difficulty of identifying a palmitoylation consensus sequence. Using a bioinformatics approach, we show that the enrichment of hydrophobic and basic residues, the cellular context of the protein, and the structural features of the residues surrounding the palmitoylated cysteine all influence the likelihood of palmitoylation. We developed a new palmitoylation predictor that incorporates these identified features, and this predictor achieves a Matthews Correlation Coefficient of .74 using 10-fold cross validation, and significantly outperforms existing predictors on unbiased testing sets. This demonstrates that palmitoylation sites can be predicted with accuracy by taking into account not only physiochemical properties of the modified cysteine and its surrounding residues, but also structural parameters and the subcellular localization of the modified cysteine. This will allow for improved predictions of palmitoylated residues in uncharacterized proteins. A web-based version of this predictor is currently under development.

Order, Disorder, and Everything in Between.

In addition to the "traditional" proteins characterized by the unique crystal-like structures needed for unique functions, it is increasingly recognized that many proteins or protein regions (collectively known as intrinsically disordered proteins (IDPs) and intrinsically disordered protein regions (IDPRs)), being biologically active, do not have a specific 3D-structure in their unbound states under physiological conditions. There are also subtler categories of disorder, such as conditional (or dormant) disorder and partial disorder. Both the ability of a protein/region to fold into a well-ordered functional unit or to stay intrinsically disordered but functional are encoded in the amino acid sequence. Structurally, IDPs/IDPRs are characterized by high spatiotemporal heterogeneity and exist as dynamic structural ensembles. It is important to remember, however, that although structure and disorder are often treated as binary states, they actually sit on a structural continuum.

Resolving the ambiguity: Making sense of intrinsic disorder when PDB structures disagree.

Missing regions in X-ray crystal structures in the Protein Data Bank (PDB) have played a foundational role in the study of intrinsically disordered protein regions (IDPRs), especially in the development of in silico predictors of intrinsic disorder. However, a missing region is only a weak indication of intrinsic disorder, and this uncertainty is compounded by the presence of ambiguous regions, where more than one structure of the same protein sequence "disagrees" in terms of the presence or absence of missing residues. The question is this: are these ambiguous regions intrinsically disordered, or are they the result of static disorder that arises from experimental conditions, ensembles of structures, or domain wobbling? A novel way of looking at ambiguous regions in terms of the pattern between multiple PDB structures has been demonstrated. It was found that the propensity for intrinsic disorder increases as the level of ambiguity decreases. However, it is also shown that ambiguity is more likely to occur as the protein region is placed within different environmental conditions, and even the most ambiguous regions as a set display compositional bias that suggests flexibility. The results suggested that ambiguity is a natural result for many IDPRs crystallized under different conditions and that static disorder and wobbling domains are relatively rare. Instead, it is more likely that ambiguity arises because many of these regions were conditionally or partially disordered.

Quarterly intrinsic disorder digest (January-February-March, 2014).

This is the 5th issue of the Digested Disorder series that represents a reader's digest of the scientific literature on intrinsically disordered proteins. We continue to use only 2 criteria for inclusion of a paper to this digest: The publication date (a paper should be published within the covered time frame) and the topic (a paper should be dedicated to any aspect of protein intrinsic disorder). The current digest issue covers papers published during the first quarter of 2014; i.e., during the period of January, February, and March of 2014. Similar to previous issues, the papers are grouped hierarchically by topics they cover, and for each of the included papers a short description is given on its major findings.

Digested disorder, Quarterly intrinsic disorder digest (October-November-December, 2013).

This is the 4th issue of the Digested Disorder series that represents reader's digest of the scientific literature on intrinsically disordered proteins. The only 2 criteria for inclusion in this digest are the publication date (a paper should be published within the covered time frame) and topic (a paper should be dedicated to any aspect of protein intrinsic disorder). The current digest issue covers papers published during the fourth quarter of 2013; i.e. during the period of October, November, and December of 2013. Similar to previous issues, the papers are grouped hierarchically by topics they cover, and for each of the included paper a short description is given on its major findings.

Digested disorder: Quarterly intrinsic disorder digest (July-August-September, 2013).

The current literature on intrinsically disordered proteins grows fast. To keep interested readers up to speed with this literature, we continue a "Digested Disorder" project and represent a new issue of reader's digest of the research papers and reviews on intrinsically disordered proteins. The only 2 criteria for inclusion in this digest are the publication date (a paper should be published within the covered time frame) and topic (a paper should be dedicated to any aspect of protein intrinsic disorder). The current digest issue covers papers published during the third quarter of 2013; i.e., during the period of June, July, and September of 2013. Similar to previous issues, the papers are grouped hierarchically by topics they cover, and for each of the included paper a short description is given on its major findings.

Digested disorder: Quarterly intrinsic disorder digest (April-May-June, 2013).

The current literature on intrinsically disordered proteins is overwhelming. To keep interested readers up to speed with this literature, we continue a "Digested Disorder" project and represent a series of reader's digest type articles objectively representing the research papers and reviews on intrinsically disordered proteins. The only 2 criteria for inclusion in this digest are the publication date (a paper should be published within the covered time frame) and topic (a paper should be dedicated to any aspect of protein intrinsic disorder). The current digest issue covers papers published during the period of April, May, and June of 2013. The papers are grouped hierarchically by topics they cover, and for each of the included paper a short description is given on its major findings.