Discovering dominant tumor immune archetypes in a pan-cancer census.

Cancers display significant heterogeneity with respect to tissue of origin, driver mutations, and other features of the surrounding tissue. It is likely that individual tumors engage common patterns of the immune system-here "archetypes"-creating prototypical non-destructive tumor immune microenvironments (TMEs) and modulating tumor-targeting. To discover the dominant immune system archetypes, the University of California, San Francisco (UCSF) Immunoprofiler Initiative (IPI) processed 364 individual tumors across 12 cancer types using standardized protocols. Computational clustering of flow cytometry and transcriptomic data obtained from cell sub-compartments uncovered dominant patterns of immune composition across cancers. These archetypes were profound insofar as they also differentiated tumors based upon unique immune and tumor gene-expression patterns. They also partitioned well-established classifications of tumor biology. The IPI resource provides a template for understanding cancer immunity as a collection of dominant patterns of immune organization and provides a rational path forward to learn how to modulate these to improve therapy.

Health-Related Social Control and Perceived Stress Among High-Risk Latina Mothers with Type 2 Diabetes and Their At-Risk Adult Daughters.

BACKGROUND: Diabetes-related multi-morbidity and cultural factors place Latinas with diabetes at increased risk for stress, which can threaten illness management. Families provide an ideal focus for interventions that seek to strengthen interpersonal resources for illness management and, in the process, to reduce stress. The current study sought to examine whether participating in a dyadic intervention was associated with reduced perceived stress and, furthermore, whether this association was mediated by persuasion and pressure, two forms of health-related social control. METHOD: Latina mothers with diabetes and their at-risk adult daughters participated in either (1) a dyadic intervention that encouraged constructive collaboration to improve health behaviors and reduce stress, or (2) a usual-care minimal control condition. Actor-partner interdependence model analysis was used to estimate the effect of the intervention on dyads' perceived stress, and mother-daughter ratings of health-related social control as potential mediators. RESULTS: Results revealed that participating in the intervention was associated with significantly reduced perceived stress for daughters, but not for mothers (ß = - 3.00, p = 0.02; ß = - 0.57, p = 0.67, respectively). Analyses also indicated that the association between the intervention and perceived stress was mediated by persuasion, such that mothers' who experienced more health-related persuasion exhibited significantly less post-intervention perceived stress (indirect effect = - 1.52, 95% CI = [- 3.12, - 0.39]). Pressure exerted by others, however, did not evidence a mediating mechanism for either mothers or daughters. CONCLUSION: These findings buttress existing research suggesting that persuasion, or others' attempts to increase participants' healthy behaviors in an uncritical way, may be a driving force in reducing perceived stress levels.

Rise in Use of Digital Mental Health Tools and Technologies in the United States During the COVID-19 Pandemic: Survey Study.

BACKGROUND: Accompanying the rising rates of reported mental distress during the COVID-19 pandemic has been a reported increase in the use of digital technologies to manage health generally, and mental health more specifically. OBJECTIVE: The objective of this study was to systematically examine whether there was a COVID-19 pandemic-related increase in the self-reported use of digital mental health tools and other technologies to manage mental health. METHODS: We analyzed results from a survey of 5907 individuals in the United States using Amazon Mechanical Turk (MTurk); the survey was administered during 4 week-long periods in 2020 and survey respondents were from all 50 states and Washington DC. The first set of analyses employed two different logistic regression models to estimate the likelihood of having symptoms indicative of clinical depression and anxiety, respectively, as a function of the rate of COVID-19 cases per 10 people and survey time point. The second set employed seven different logistic regression models to estimate the likelihood of using seven different types of digital mental health tools and other technologies to manage one's mental health, as a function of symptoms indicative of clinical depression and anxiety, rate of COVID-19 cases per 10 people, and survey time point. These models also examined potential interactions between symptoms of clinical depression and anxiety, respectively, and rate of COVID-19 cases. All models controlled for respondent sociodemographic characteristics and state fixed effects. RESULTS: Higher COVID-19 case rates were associated with a significantly greater likelihood of reporting symptoms of depression (odds ratio [OR] 2.06, 95% CI 1.27-3.35), but not anxiety (OR 1.21, 95% CI 0.77-1.88). Survey time point, a proxy for time, was associated with a greater likelihood of reporting clinically meaningful symptoms of depression and anxiety (OR 1.19, 95% CI 1.12-1.27 and OR 1.12, 95% CI 1.05-1.19, respectively). Reported symptoms of depression and anxiety were associated with a greater likelihood of using each type of technology. Higher COVID-19 case rates were associated with a significantly greater likelihood of using mental health forums, websites, or apps (OR 2.70, 95% CI 1.49-4.88), and other health forums, websites, or apps (OR 2.60, 95% CI 1.55-4.34). Time was associated with increased odds of reported use of mental health forums, websites, or apps (OR 1.20, 95% CI 1.11-1.30), phone-based or text-based crisis lines (OR 1.20, 95% CI 1.10-1.31), and online, computer, or console gaming/video gaming (OR 1.12, 95% CI 1.05-1.19). Interactions between COVID-19 case rate and mental health symptoms were not significantly associated with any of the technology types. CONCLUSIONS: Findings suggested increased use of digital mental health tools and other technologies over time during the early stages of the COVID-19 pandemic. As such, additional effort is urgently needed to consider the quality of these products, either by ensuring users have access to evidence-based and evidence-informed technologies and/or by providing them with the skills to make informed decisions around their potential efficacy.

Sex-specific airway hyperreactivity and sex-specific transcriptome remodeling in neonatal piglets challenged with intra-airway acid.

Acute airway acidification is a potent stimulus of sensory nerves and occurs commonly with gastroesophageal reflux disease, cystic fibrosis, and asthma. In infants and adults, airway acidification can acutely precipitate asthma-like symptoms, and treatment-resistant asthma can be associated with gastroesophageal reflux disease. Airway protective behaviors, such as mucus secretion and airway smooth muscle contraction, are often exaggerated in asthma. These behaviors are manifested through activation of neural circuits. In some populations, the neural response to acid might be particularly important. For example, the immune response in infants is relatively immature compared with adults. Infants also have a high frequency of gastroesophageal reflux. Thus, in the current study, we compared the transcriptomes of an airway-nervous system circuit (e.g., tracheal epithelia, nodose ganglia, and brain stem) in neonatal piglets challenged with intra-airway acid. We hypothesized that the identification of parallel changes in the transcriptomes of two neutrally connected tissues might reveal the circuit response, and, hence, molecules important for the manifestation of asthma-like features. Intra-airway acid induced airway hyperreactivity and airway obstruction in male piglets. In contrast, female piglets displayed airway obstruction without airway hyperreactivity. Pairwise comparisons revealed parallel changes in genes directly implicated in airway hyperreactivity ( scn10a) in male acid-challenged piglets, whereas acid-challenged females exhibited parallel changes in genes associated with mild asthma ( stat 1 and isg15). These findings reveal sex-specific responses to acute airway acidification and highlight distinct molecules within a neural circuit that might be critical for the manifestation of asthma-like symptoms in pediatric populations.

Reducing inappropriate arterial blood gas testing in a level III intensive care unit: a before-and-after observational study.

Background: Arterial blood gas (ABG) analysis is the most frequently performed test in intensive care units (ICUs), often without a specific clinical indication. This is costly and contributes to iatrogenic anaemia. Objectives: To reduce the number of ABG tests performed and the proportion that are inappropriate. Design, setting and participants: The indications for ABG analysis were surveyed at a 58-bed level III ICU during fortnightly periods before and after a multifaceted educational intervention which included the introduction of a clinical guideline. The number of ABG tests performed during the period July-December 2017 was compared with that for the period July-December 2018. Tests were predefined as inappropriate if performed at regular time intervals, at change of shift, concurrently with other blood tests or after a treatment was ceased on a stable patient or after ventilatory support or oxygen delivery was decreased in an otherwise stable patient. The study was enrolled on the Quality Improvement Projects Register and ethics approval was waived by the local ethics committee. Results: There was a 31.3% bed-day adjusted decrease in number of ABG tests performed (33 005 v 22 408; P < 0.001), representing an annual saving of A$770 000 and 100 litres of blood. The proportion of inappropriate ABG tests decreased by 47.3% (54.2% v 28.6%; P < 0.001) and the number of inappropriate ABG tests per bed-day decreased by 71% (2.8 v 0.8; P < 0.001). Patient outcomes before and after the intervention did not differ (standardised mortality ratio, 0.65 v 0.63; P = 0.22). Conclusion: Staff education and implementation of a clinical guideline resulted in substantial decreases in the number of ABG tests performed and the proportion of inappropriate ABG tests.

Participatory decision-making for cancer care in a high-risk sample of low income Mexican-American breast cancer survivors: The role of acculturation.

BACKGROUND: Despite declining cancer incidence and mortality rates, Latina patients continue to have lower 5-year survival rates compared to their non-Hispanic white counterparts. Much of this difference has been attributed to lack of healthcare access and poorer quality of care. Research, however, has not considered the unique healthcare experiences of Latina patients. METHODS: Latina women with prior diagnoses of stage 0-III breast cancer were asked to complete a cross-sectional survey assessing several socio-demographic factors along with their experiences as cancer patients. Using a series of linear regression models in a sample of 68 Mexican-American breast cancer survivors, we examined the extent to which patients' ratings of provider interpersonal quality of care were associated with patients' overall healthcare quality, and how these associations varied by acculturation status. RESULTS: Findings for Latina women indicated that both participatory decision-making (PDM) (ß = 0.62, p < .0001) and trust (ß = 0.53, p = .02) were significantly associated with patients' ratings of healthcare quality. The interaction between acculturation and PDM further suggested that participating in the decision-making process mattered more for less acculturated than for more acculturated patients (ß = -0.51, p ≤ .01). CONCLUSIONS: The variation across low and high acculturated Latinas in their decision-making process introduces a unique challenge to health care providers. Further understanding the relationship between provider-patient experiences and ratings of overall healthcare quality is critical for ultimately improving health outcomes.

Attenuated Amiloride-Sensitive Current and Augmented Calcium-Activated Chloride Current in Marsh Rice Rat (Oryzomys palustris) Airways.

Prolonged heat and sea salt aerosols pose a challenge for the mammalian airway, placing the protective airway surface liquid (ASL) at risk for desiccation. Thus, mammals inhabiting salt marshes might have acquired adaptations for ASL regulation. We studied the airways of the rice rat, a rodent that inhabits salt marshes. We discovered negligible Na+ transport through the epithelial sodium channel (ENaC). In contrast, carbachol induced a large Cl- secretory current that was blocked by the calcium-activated chloride channel (CaCC) inhibitor CaCCinhi-A01. Decreased mRNA expression of α, ß, and γ ENaC, and increased mRNA expression of the CaCC transmembrane member 16A, distinguished the rice rat airway. Rice rat airway cultures also secreted fluid in response to carbachol and displayed an exaggerated expansion of the ASL volume when challenged with 3.5% NaCl. These data suggest that the rice rat airway might possess unique ion transport adaptations to facilitate survival in the salt marsh environment.

Mapping the space of genomic signatures.

We propose a computational method to measure and visualize interrelationships among any number of DNA sequences allowing, for example, the examination of hundreds or thousands of complete mitochondrial genomes. An "image distance" is computed for each pair of graphical representations of DNA sequences, and the distances are visualized as a Molecular Distance Map: Each point on the map represents a DNA sequence, and the spatial proximity between any two points reflects the degree of structural similarity between the corresponding sequences. The graphical representation of DNA sequences utilized, Chaos Game Representation (CGR), is genome- and species-specific and can thus act as a genomic signature. Consequently, Molecular Distance Maps could inform species identification, taxonomic classifications and, to a certain extent, evolutionary history. The image distance employed, Structural Dissimilarity Index (DSSIM), implicitly compares the occurrences of oligomers of length up to k (herein k = 9) in DNA sequences. We computed DSSIM distances for more than 5 million pairs of complete mitochondrial genomes, and used Multi-Dimensional Scaling (MDS) to obtain Molecular Distance Maps that visually display the sequence relatedness in various subsets, at different taxonomic levels. This general-purpose method does not require DNA sequence alignment and can thus be used to compare similar or vastly different DNA sequences, genomic or computer-generated, of the same or different lengths. We illustrate potential uses of this approach by applying it to several taxonomic subsets: phylum Vertebrata, (super)kingdom Protista, classes Amphibia-Insecta-Mammalia, class Amphibia, and order Primates. This analysis of an extensive dataset confirms that the oligomer composition of full mtDNA sequences can be a source of taxonomic information. This method also correctly finds the mtDNA sequences most closely related to that of the anatomically modern human (the Neanderthal, the Denisovan, and the chimp), and that the sequence most different from it in this dataset belongs to a cucumber.