An evaluation of the quality of online perinatal depression information.

BACKGROUND: During the perinatal period (including pregnancy and up to 12 months after childbirth), expectant and new mothers are at an elevated risk of developing depression. Inadequate knowledge about perinatal depression and treatment options may contribute to the low help-seeking rates exhibited by perinatal people. The Internet can be an accessible source of information about perinatal depression; however, the quality of this information remains to be evaluated. The purpose of this study was to assess the quality of perinatal depression information websites. METHODS: After review, 37 websites were included in our sample. To assess overall website quality, we rated websites based on their reading level (Simple Measure of Gobbledegook; SMOG), information quality (DISCERN), usability (Patient Education Materials Assessment Tool; PEMAT), and visual design (Visual Aesthetics of Website Inventory; VisAWI). RESULTS: Websites often exceeded the National Institute of Health's recommended reading level of grades 6-8, with scores ranging from 6.8 to 13.5. Website information quality ratings ranged from 1.8 to 4.3 out of 5, with websites often containing insufficient information about treatment choices. Website usability ratings were negatively impacted by the lack of information summaries, visual aids, and tangible tools. Visual design ratings ranged from 3.2 to 6.6 out of 7, with a need for more creative design elements to enhance user engagement. CONCLUSIONS: This study outlines the characteristics of high-quality perinatal depression information websites. Our findings illustrate that perinatal depression websites are not meeting the needs of users in terms of reading level, information quality, usability, and visual design. Our results may be helpful in guiding healthcare providers to reliable, evidence-based online resources for their perinatal patients.

Ranking microbiome variance in inflammatory bowel disease: a large longitudinal intercontinental study.

OBJECTIVE: The microbiome contributes to the pathogenesis of inflammatory bowel disease (IBD) but the relative contribution of different lifestyle and environmental factors to the compositional variability of the gut microbiota is unclear. DESIGN: Here, we rank the size effect of disease activity, medications, diet and geographic location of the faecal microbiota composition (16S rRNA gene sequencing) in patients with Crohn's disease (CD; n=303), ulcerative colitis (UC; n = 228) and controls (n=161), followed longitudinally (at three time points with 16 weeks intervals). RESULTS: Reduced microbiota diversity but increased variability was confirmed in CD and UC compared with controls. Significant compositional differences between diseases, particularly CD, and controls were evident. Longitudinal analyses revealed reduced temporal microbiota stability in IBD, particularly in patients with changes in disease activity. Machine learning separated disease from controls, and active from inactive disease, when consecutive time points were modelled. Geographic location accounted for most of the microbiota variance, second to the presence or absence of CD, followed by history of surgical resection, alcohol consumption and UC diagnosis, medications and diet with most (90.3%) of the compositional variance stochastic or unexplained. CONCLUSION: The popular concept of precision medicine and rational design of any therapeutic manipulation of the microbiota will have to contend not only with the heterogeneity of the host response, but also with widely differing lifestyles and with much variance still unaccounted for.

CHARTS: a web application for characterizing and comparing tumor subpopulations in publicly available single-cell RNA-seq data sets.

BACKGROUND: Single-cell RNA-seq (scRNA-seq) enables the profiling of genome-wide gene expression at the single-cell level and in so doing facilitates insight into and information about cellular heterogeneity within a tissue. This is especially important in cancer, where tumor and tumor microenvironment heterogeneity directly impact development, maintenance, and progression of disease. While publicly available scRNA-seq cancer data sets offer unprecedented opportunity to better understand the mechanisms underlying tumor progression, metastasis, drug resistance, and immune evasion, much of the available information has been underutilized, in part, due to the lack of tools available for aggregating and analysing these data. RESULTS: We present CHARacterizing Tumor Subpopulations (CHARTS), a web application for exploring publicly available scRNA-seq cancer data sets in the NCBI's Gene Expression Omnibus. More specifically, CHARTS enables the exploration of individual gene expression, cell type, malignancy-status, differentially expressed genes, and gene set enrichment results in subpopulations of cells across tumors and data sets. Along with the web application, we also make available the backend computational pipeline that was used to produce the analyses that are available for exploration in the web application. CONCLUSION: CHARTS is an easy to use, comprehensive platform for exploring single-cell subpopulations within tumors across the ever-growing collection of public scRNA-seq cancer data sets. CHARTS is freely available at charts.morgridge.org.

A Systematic Review and Meta-Analysis of the Diagnostic Accuracy of the Advanced Clinical Solutions Word Choice Test as a Performance Validity Test.

Thorough assessment of performance validity has become an established standard of practice in neuropsychological assessment. While there has been a large focus on the development and cross-validation of embedded performance validity tests (PVTs) in recent years, new freestanding PVTs have also been developed, including the Word Choice Test (WCT) as part of the Advanced Clinical Solutions Effort System. And, while the WCT's general utility for identifying invalid performance has been demonstrated in the ensuing decade since its initial publication, optimal cut-scores and associated psychometric properties have varied widely across studies. This study sought to synthesize the existing diagnostic accuracy literature regarding the WCT via a systematic review and to conduct a meta-analysis to determine the performance validity cut-score that best maximizes sensitivity while maintaining acceptable specificity. A systematic search of the literature resulted in 14 studies for synthesis, with eight of those available for meta-analysis. Meta-analytic results revealed an optimal cut-score of ≤ 42 with 54% sensitivity and 93% specificity for identifying invalid neuropsychological test performance. Collectively, the WCT demonstrated adequate diagnostic accuracy as a PVT across a variety of populations. Recommendations for future studies are also provided.

Victoria Symptom Validity Test: A Systematic Review and Cross-Validation Study.

The Victoria Symptom Validity Test (VSVT) is a performance validity test (PVT) with over two decades of empirical backing, although methodological limitations within the extant literature restrict its clinical and research generalizability. Chief among these constraints includes limited consensus on the most accurate index within the VSVT and the most appropriate cut-scores within each VSVT validity index. The current systematic review synthesizes existing VSVT validation studies and provides additional cross-validation in an independent sample using a known-groups design. We completed a systematic search of the literature, identifying 17 peer-reviewed studies for synthesis (7 simulation designs, 7 differential prevalence designs, and 3 known-groups designs). The independent cross-validation sample consisted of 200 mixed clinical neuropsychiatric patients referred for outpatient neuropsychological evaluation. Across all indices, Total item accuracy produced the strongest psychometric properties at an optimal cut-score of ≤ 40 (62% sensitivity/88% specificity). However, ROC curve analyses for all VSVT indices yielded statistically significant areas under the curve (AUCs; .73-81), suggestive of moderate classification accuracy. Cut-scores derived using the independent cross-validation sample converged with some previous findings supporting cut-scores of ≤ 22 for Easy item accuracy and ≤ 40 for Total item accuracy, although divergent findings were noted for Difficult item accuracy. Overall, VSVT validity indicators have adequate diagnostic accuracy across populations, with the current study providing additional support for its use as a psychometrically sound PVT in clinical settings. However, caution is recommended among patients with certain verified clinical conditions (e.g., dementia) and those with pronounced working memory deficits due to concerns for increased risk of false positives.

Librarians collaborate successfully with nursing faculty and a writing centre to support nursing students doing professional doctorates.

This study explores how a three-way collaboration between a University library, writing centre and faculty created avenues of training and support for students within a Doctor of Nursing Practice (DNP) program in an American University. The role of each partner involved in the collaboration is discussed alongside the profile of the DNP students. Lesson planning and classroom techniques for DNP information literacy classes are described and feedback from the partners and the students are discussed. The study confirms that collaboration is effective in improving research and writing skills. D.I.

MetaSRA: normalized human sample-specific metadata for the Sequence Read Archive.

MOTIVATION: The NCBI's Sequence Read Archive (SRA) promises great biological insight if one could analyze the data in the aggregate; however, the data remain largely underutilized, in part, due to the poor structure of the metadata associated with each sample. The rules governing submissions to the SRA do not dictate a standardized set of terms that should be used to describe the biological samples from which the sequencing data are derived. As a result, the metadata include many synonyms, spelling variants and references to outside sources of information. Furthermore, manual annotation of the data remains intractable due to the large number of samples in the archive. For these reasons, it has been difficult to perform large-scale analyses that study the relationships between biomolecular processes and phenotype across diverse diseases, tissues and cell types present in the SRA. RESULTS: We present MetaSRA, a database of normalized SRA human sample-specific metadata following a schema inspired by the metadata organization of the ENCODE project. This schema involves mapping samples to terms in biomedical ontologies, labeling each sample with a sample-type category, and extracting real-valued properties. We automated these tasks via a novel computational pipeline. AVAILABILITY AND IMPLEMENTATION: The MetaSRA is available at metasra.biostat.wisc.edu via both a searchable web interface and bulk downloads. Software implementing our computational pipeline is available at http://github.com/deweylab/metasra-pipeline. CONTACT: cdewey@biostat.wisc.edu. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

The Relationship Among Perceived Stress, Symptoms, and Inflammation in Persons With Inflammatory Bowel Disease.

OBJECTIVES: Previous studies have demonstrated that stress is associated with increased disease activity in individuals with inflammatory bowel disease (IBD). The association between perceived stress and gastrointestinal inflammation is not well described. METHODS: Participants were recruited from a population-based registry of individuals with known IBD. Symptomatic disease activity was assessed using validated clinical indices: the Manitoba IBD Index (MIBDI) and Harvey Bradshaw Index (HBI) for Crohn's disease (CD), and Powell Tuck Index (PTI) for ulcerative colitis (UC). Perceived stress was measured using Cohen's Perceived Stress Scale (CPSS). Intestinal inflammation was determined through measurement of fecal calprotectin (FCAL), with a level exceeding 250 µg/g indicating significant inflammation. Logistic regressions were used to evaluate the association between intestinal inflammation, perceived stress, and disease activity. RESULTS: Of the 478 participants with completed surveys and stool samples, perceived stress was associated with symptomatic activity (MIBDI) for both CD and UC (1.07 per 1-point increase on the CPSS, 95% confidence interval (CI) 1.03-1.10 and 1.03-1.11, respectively). There was no significant association between perceived stress and intestinal inflammation for either CD or UC. Active symptoms (MIBDI ≤3) were associated with intestinal inflammation in UC (odds ratio (OR) 3.94, 95% CI 1.65-9.43), but not in CD (OR 0.98, 95% CI 0.51-1.88). CONCLUSIONS: Symptomatic disease activity was unrelated to intestinal inflammation in CD and only weakly associated in UC. Although there was a strong relationship between perceived stress and gastrointestinal symptoms, perceived stress was unrelated to concurrent intestinal inflammation. Longitudinal investigation is required to determine the directionality of the relationship between perceived stress, inflammation, and symptoms in IBD.

Association of common genetic variants in GPCPD1 with scaling of visual cortical surface area in humans.

Visual cortical surface area varies two- to threefold between human individuals, is highly heritable, and has been correlated with visual acuity and visual perception. However, it is still largely unknown what specific genetic and environmental factors contribute to normal variation in the area of visual cortex. To identify SNPs associated with the proportional surface area of visual cortex, we performed a genome-wide association study followed by replication in two independent cohorts. We identified one SNP (rs6116869) that replicated in both cohorts and had genome-wide significant association (P(combined) = 3.2 × 10(-8)). Furthermore, a metaanalysis of imputed SNPs in this genomic region identified a more significantly associated SNP (rs238295; P = 6.5 × 10(-9)) that was in strong linkage disequilibrium with rs6116869. These SNPs are located within 4 kb of the 5' UTR of GPCPD1, glycerophosphocholine phosphodiesterase GDE1 homolog (Saccharomyces cerevisiae), which in humans, is more highly expressed in occipital cortex compared with the remainder of cortex than 99.9% of genes genome-wide. Based on these findings, we conclude that this common genetic variation contributes to the proportional area of human visual cortex. We suggest that identifying genes that contribute to normal cortical architecture provides a first step to understanding genetic mechanisms that underlie visual perception.

Gastrointestinal symptoms before and during menses in healthy women.

BACKGROUND: Little is known as to the extent gastrointestinal (GI) complaints are reported by women around menses. We aimed to describe GI symptoms that occurred premenstrually and during menses in healthy women, and to specifically assess the relationship of emotional symptoms to GI symptoms around menses. METHODS: We recruited healthy, premenopausal adult women with no indication of GI, gynecologic, or psychiatric disease who were attending an outpatient gynecology clinic for well-woman care. They completed a survey that queried menstrual histories and the presence of GI and emotional symptoms. We compared the prevalence of primary GI symptoms (abdominal pain, diarrhea, constipation, nausea, vomiting), as well as pelvic pain and bloating, in the 5 days preceding menses and during menses, and assessed whether emotional symptoms or other factors were associated with the occurrence of GI symptoms. RESULTS: Of 156 respondents, 73% experienced at least one of the primary GI symptoms either pre- or during menses, with abdominal pain (58% pre; 55% during) and diarrhea (24% pre; 28% during) being the most common. Those experiencing any emotional symptoms versus those without were more likely to report multiple (2 or more) primary GI symptoms, both premenstrually (depressed p = 0.006; anxiety p = 0.014) and during menses (depressed p < 0.001; anxiety p = 0.008). Fatigue was also very common (53% pre; 49% during), and was significantly associated with multiple GI symptoms in both menstrual cycle phases (pre p < 0.001; during p = 0.01). CONCLUSIONS: Emotional symptoms occurring in conjunction with GI symptoms are common perimenstrually, and as such may reflect shared underlying processes that intersect brain, gut, and hormonal pathways.

Angular versus spatial resolution trade-offs for diffusion imaging under time constraints.

Diffusion weighted magnetic resonance imaging (DW-MRI) are now widely used to assess brain integrity in clinical populations. The growing interest in mapping brain connectivity has made it vital to consider what scanning parameters affect the accuracy, stability, and signal-to-noise of diffusion measures. Trade-offs between scan parameters can only be optimized if their effects on various commonly-derived measures are better understood. To explore angular versus spatial resolution trade-offs in standard tensor-derived measures, and in measures that use the full angular information in diffusion signal, we scanned eight subjects twice, 2 weeks apart, using three protocols that took the same amount of time (7 min). Scans with 3.0, 2.7, 2.5 mm isotropic voxels were collected using 48, 41, and 37 diffusion-sensitized gradients to equalize scan times. A specially designed DTI phantom was also scanned with the same protocols, and different b-values. We assessed how several diffusion measures including fractional anisotropy (FA), mean diffusivity (MD), and the full 3D orientation distribution function (ODF) depended on the spatial/angular resolution and the SNR. We also created maps of stability over time in the FA, MD, ODF, skeleton FA of 14 TBSS-derived ROIs, and an information uncertainty index derived from the tensor distribution function, which models the signal using a continuous mixture of tensors. In scans of the same duration, higher angular resolution and larger voxels boosted SNR and improved stability over time. The increased partial voluming in large voxels also led to bias in estimating FA, but this was partially addressed by using "beyond-tensor" models of diffusion.

Molecular encoding of stimulus features in a single sensory neuron type enables neuronal and behavioral plasticity.

Neurons modify their transcriptomes in response to an animal’s experience. How specific experiences are transduced to modulate gene expression and precisely tune neuronal functions are not fully defined. Here, we describe the molecular profile of a thermosensory neuron pair in C. elegans experiencing different temperature stimuli. We find that distinct salient features of the temperature stimulus including its duration, magnitude of change, and absolute value are encoded in the gene expression program in this single neuron, and identify a novel transmembrane protein and a transcription factor whose specific transcriptional dynamics are essential to drive neuronal, behavioral, and developmental plasticity. Expression changes are driven by broadly expressed activity-dependent transcription factors and corresponding cis -regulatory elements that nevertheless direct neuron- and stimulus-specific gene expression programs. Our results indicate that coupling of defined stimulus characteristics to the gene regulatory logic in individual specialized neuron types can customize neuronal properties to drive precise behavioral adaptation.

Molecular encoding of stimulus features in a single sensory neuron type enables neuronal and behavioral plasticity.

Neurons modify their transcriptomes in response to an animal's experience. How specific experiences are transduced to modulate gene expression and precisely tune neuronal functions are not fully defined. Here, we describe the molecular profile of a thermosensory neuron pair in C. elegans experiencing different temperature stimuli. We find that distinct salient features of the temperature stimulus, including its duration, magnitude of change, and absolute value, are encoded in the gene expression program in this single neuron type, and we identify a novel transmembrane protein and a transcription factor whose specific transcriptional dynamics are essential to drive neuronal, behavioral, and developmental plasticity. Expression changes are driven by broadly expressed activity-dependent transcription factors and corresponding cis-regulatory elements that nevertheless direct neuron- and stimulus-specific gene expression programs. Our results indicate that coupling of defined stimulus characteristics to the gene regulatory logic in individual specialized neuron types can customize neuronal properties to drive precise behavioral adaptation.

Generation of anti-GD2 CAR macrophages from human pluripotent stem cells for cancer immunotherapies.

Macrophages armed with chimeric antigen receptors (CARs) provide a potent new option for treating solid tumors. However, genetic engineering and scalable production of somatic macrophages remains significant challenges. Here, we used CRISPR-Cas9 gene editing methods to integrate an anti-GD2 CAR into the AAVS1 locus of human pluripotent stem cells (hPSCs). We then established a serum- and feeder-free differentiation protocol for generating CAR macrophages (CAR-Ms) through arterial endothelial-to-hematopoietic transition (EHT). CAR-M produced by this method displayed a potent cytotoxic activity against GD2-expressing neuroblastoma and melanoma in vitro and neuroblastoma in vivo. This study provides a new platform for the efficient generation of off-the-shelf CAR-Ms for antitumor immunotherapy.

Quality of Late-Life Depression Information on the Internet: Website Evaluation Study.

BACKGROUND: The internet can increase the accessibility of mental health information and improve the mental health literacy of older adults. The quality of mental health information on the internet can be inaccurate or biased, leading to misinformation. OBJECTIVE: This study aims to evaluate the quality, usability, and readability of websites providing information concerning depression in later life. METHODS: Websites were identified through a Google search and evaluated by assessing quality (DISCERN), usability (Patient Education Materials Assessment Tool), and readability (Simple Measure of Gobbledygook). RESULTS: The overall quality of late-life depression websites (N=19) was adequate, and the usability and readability were poor. No significant relationship was found between the quality and readability of the websites. CONCLUSIONS: The websites can be improved by enhancing information quality, usability, and readability related to late-life depression. The use of high-quality websites may improve mental health literacy and shared treatment decision-making for older adults.

Examining Anxiety Treatment Information Needs: Web-Based Survey Study.

BACKGROUND: Several treatments for anxiety are available, which can make treatment decisions difficult. Resources are often produced with limited knowledge of what information is of interest to consumers. This is a problem because there is limited understanding of what people want to know when considering help for anxiety. OBJECTIVE: This study aimed to examine the information needs and preferences concerning treatment options for anxiety by assessing the following: what information people consider to be important when they are considering treatment options for anxiety, what information people have received on psychological and medication treatment in the past, how they received this information in the past, and whether there are any differences in information needs between specific samples and demographic groups. METHODS: Using a web-based survey, we recruited participants from a peer-support association website (n=288) and clinic samples (psychology, n=113; psychiatry, n=64). RESULTS: Participants in all samples wanted information on a broad range of topics pertaining to anxiety treatment. However, they reported that they did not receive the desired amount of information. Participants in the clinic samples rated the importance of information topics higher than did those in the self-help sample. When considering the anxiety treatment information received in the past, most respondents indicated receiving information from informational websites, family doctors, and mental health practitioners. In terms of what respondents want to learn about, high ratings of importance were given to topics concerning treatment effectiveness, how it works, advantages and disadvantages, what happens when it stops, and common side effects. CONCLUSIONS: It is challenging for individuals to obtain anxiety-related information on the range of topics they desire through currently available information sources. It is also difficult to provide comprehensive information during typical clinical visits. Providing evidence-based information on the web and in a brochure format may help consumers make informed choices and support the advice provided by health professionals.

Impaired or invalid? Limitations of assessing performance validity using the Boston Naming Test.

The Boston Naming Test (BNT) has been proposed as an embedded performance validity test (PVT), though replication is needed to provide further empirical support of its simultaneous use as a cognitive ability measure and embedded PVT. This cross-sectional study examined BNT performance in a mixed neuropsychiatric sample of 137 patients with/without cognitive impairment. Four independent criterion PVTs classified 109 (80%) as valid and 28 (20%) as invalid. BNT raw and demographically-corrected T-scores were significantly higher among the valid group with small effect sizes (ηp2 = 0.04-0.05). Raw/T-scores differentiated valid/invalid groups, but with low classification accuracy (areas under the curve [AUCs] = 0.68/0.63), and unacceptably weak sensitivities (i.e. 7%/18%). When separated by impairment status, raw score accuracy appreciably increased (AUC = 0.87; 61% sensitivity/89% specificity) among unimpaired patients, whereas T-score accuracy, while significant, remained low (AUC = 0.68; 21% sensitivity/89% specificity). Conversely, among impaired patients, neither the raw (AUC = 0.59) nor T-score (AUC = 0.60) accurately identified invalid performance. In sum, BNT scores were not able to differentiate valid from invalid performance when cognitive impairment was present, and therefore showed limited overall utility as embedded PVTs. These findings further caution against inferring performance validity from measures in which a single score is used to assess both cognitive ability and validity.

SpatialCorr identifies gene sets with spatially varying correlation structure.

Recent advances in spatially resolved transcriptomics technologies enable both the measurement of genome-wide gene expression profiles and their mapping to spatial locations within a tissue. A first step in spatial transcriptomics data analysis is identifying genes with expression that varies spatially, and robust statistical methods exist to address this challenge. While useful, these methods do not detect spatial changes in the coordinated expression within a group of genes. To this end, we present SpatialCorr, a method for identifying sets of genes with spatially varying correlation structure. Given a collection of gene sets pre-defined by a user, SpatialCorr tests for spatially induced differences in the correlation of each gene set within tissue regions, as well as between and among regions. An application to cutaneous squamous cell carcinoma demonstrates the power of the approach for revealing biological insights not identified using existing methods.

Do anxiety websites have the answers people are looking for?

OBJECTIVES AND METHODS: A wealth of online anxiety information exists but much of it is not evidence-based or well-balanced. This study evaluated anxiety websites (N = 20) on readability, quality, usability, visual design, and content. RESULTS: Overall, websites were of reasonable quality but only half were considered understandable according to the PEMAT usability scale (70% cutoff value). The average reading level across websites was 11.2 (SMOG), which is higher than NIH recommended grade 6-7 level. Websites had variable design features and a trending association suggested websites with better design come up earlier in search results. The number of topics covered varied across websites and most did not adequately cover all topics of interest. Most websites included information about psychological and self-help treatments, how treatment works, and what treatment entails. The Top 5 websites were: (1) Anxiety BC, (2) ADAA, (3) Mind, (4) Beyond Blue, and (5) Web MD. CONCLUSIONS: This is the first study to evaluate existing anxiety information websites based on the dimensions described above and their relationship to Google search results. PRACTICE IMPLICATIONS: This study highlights the importance of considering several dimensions in developing mental health resources and provides direction for strategies to improve existing websites and/or develop new resources.