Comparing recalled versus experienced symptoms of breathlessness ratings: An ecological assessment study using mobile phone technology.

BACKGROUND AND OBJECTIVE: Recall of breathlessness is important for clinical care but might differ from the experienced (momentary) symptoms. This study aimed to characterize the relationship between momentary breathlessness ratings and the recall of the experience. It is hypothesized that recall is influenced by the peak (worst) and end (most recent) ratings of momentary breathlessness (peak-end rule). METHODS: This study used mobile ecological momentary assessment (mEMA) for assessing breathlessness in daily life through an application installed on participants' mobile phones. Breathlessness ratings (0-10 numerical rating scale) were recorded throughout the day and recalled each night and at the end of the week. Analyses were performed using regular and mixed linear regression. RESULTS: Eighty-four people participated. Their mean age was 64.4 years, 60% were female and 98% had modified Medical Research Council (mMRC) ≥ 1. The mean number of momentary ratings of breathlessness provided was 7.7 ratings/participant/day. Recalled breathlessness was associated with the mean, peak and end values of the day. The mean was most closely associated with the daily recall. Associations were strong for weekly values: peak breathlessness (beta = 0.95, r2  = 0.57); mean (beta = 0.91, r2  = 0.53); and end (beta = 0.67, r2  = 0.48); p < 0.001 for all. Multivariate analysis showed that peak breathlessness had the strongest influence on the breathlessness recalled at the end of the week. CONCLUSION: Over 1 week, recalled breathlessness is most strongly influenced by the peak breathlessness; over 1 day, it is mean breathlessness that participants most readily recalled.

Intimomedial mucoid arterial degeneration, a rare arterial disorder of forensic significance.

The body of a 43-year-old African woman with a history of aortic aneurysm and hypertension was forensically investigated after her sudden death. The cause of death was related to a cardiac tamponade due to a ruptured aneurysm of the ascending aorta. Post-mortem gross examination showed an abnormal whitish discoloration of the intima with fibrous thickening of the aortic wall. Several arteries (left main and circumflex coronaries, carotid, renal and iliac arteries) showed similar features. Upon histological examination, the aortic aneurysm as well as the other arteries sampled showed mucoid degeneration, excess mucopolysaccharides and pools of mucin inside the intima and the media associated with collagen and elastic fiber destruction and loss of smooth muscle cells. This pattern strongly suggested the diagnosis of intimomedial mucoid degeneration (IMMD), a rare arterial disorder consisting of a progressive deposition of mucin into the intima and media, with a strong prevalence in middle-aged black African females with high blood pressure. In addition to the typical features of IMMD, histological examination of the ascending aorta showed a thickening of the adventita with sparse mixed inflammatory infiltrates and fibrosis, suggesting an additional chronic infectious aortitis. No infectious agent was detected. The body of literature on IMMD is reviewed and the origin of death is discussed in this case report.

Surface-based mixed effects multilevel analysis of grouped human electrocorticography.

Electrocorticography (ECoG) in humans yields data with unmatched spatio-temporal resolution that provides novel insights into cognitive operations. However, the broader application of ECoG has been confounded by difficulties in accurately depicting individual data and performing statistically valid population-level analyses. To overcome these limitations, we developed methods for accurately registering ECoG data to individual cortical topology. We integrated this technique with surface-based co-registration and a mixed-effects multilevel analysis (MEMA) to control for variable cortical surface anatomy and sparse coverage across patients, as well as intra- and inter-subject variability. We applied this surface-based MEMA (SB-MEMA) technique to a face-recognition task dataset (n=22). Compared against existing techniques, SB-MEMA yielded results much more consistent with individual data and with meta-analyses of face-specific activation studies. We anticipate that SB-MEMA will greatly expand the role of ECoG in studies of human cognition, and will enable the generation of population-level brain activity maps and accurate multimodal comparisons.

Monitoring dietary intake and physical activity electronically: feasibility, usability, and ecological validity of a mobile-based Ecological Momentary Assessment tool.

BACKGROUND: Despite the growing body of research on complex lifestyle behaviors (eg, Dietary Intake [DI] and Physical Activity [PA]), monitoring of these behaviors has been hampered by a lack of suitable methods. A possible solution to this deficiency is mobile-based Ecological Momentary Assessment (mEMA), which enables researchers to collect data on participants' states in real-time by means of a smartphone application. However, feasibility, usability, and ecological validity need to be anticipated and managed in order to enhance the validity of mEMA. OBJECTIVE: To examine the feasibility, usability, and ecological validity of a mEMA application (app) with regard to DI and PA among Dutch vocational education students. METHODS: The students (n=30) participated in the mEMA study for seven consecutive days. They downloaded the mEMA app on their smartphone. Feasibility and usability of the mEMA app were evaluated by completing an online evaluation after seven days of participation. Ecological validity was measured by assessing the degree to which the content of the mEMA app approximated the real-world setting that was being examined, through several multiple-choice questions. RESULTS: Compliance rates, as registered by the mEMA app, declined 46% over a seven-day period, while self-reported compliance, as measured with an online evaluation questionnaire afterwards, indicated a smaller decrease in compliance (29%). The students evaluated the mEMA app as feasible and usable. Ecological validity analyses showed that all DI and almost all PA multiple-choice options were covered with the compound response categories. CONCLUSIONS: The mEMA app offers the opportunity to assess complex health behaviors (eg, DI and PA) in real-time settings, in which specifically routinized behaviors are involved. However, the mEMA app faced several challenges that needed to be overcome in order to improve its validity. Overall, the present study showed that the mEMA app is a usable and ecologically valid tool to measure DI and PA behaviors among vocational education students, but compliance is still limited.

Feasibility study of using mobile phone-based experience sampling to assess drug checking by opioid street drug users.

BACKGROUND: To date, evaluations of take-home fentanyl (and/or benzodiazepine) test strip use - the most common form of drug checking services - and potential effects on overdose risk have relied on retrospective accounts for some preceding time period, usually a week to several months. Such accounts, however, are subject to recall and memory biases. This pilot study assessed the feasibility of using experiential sampling to collect daily information in situ on drug checking and associated overdose risk reduction - the primary outcomes - among a sample of street opioid users and compared the results to retrospective reports. METHODS: We recruited 12 participants from a Chicago-based syringe services program. Participants were 18 years of age or older, reported using opioids purchased on the street 3 + times per week in the past month, and had an available Android mobile phone. A phone-based app was programmed to collect daily drug checking information and provided to each participant along with a supply of fentanyl and benzodiazepine test strips and instructions for use over 21 days. Comparable retrospective data were collected via follow-up in-person surveys at the conclusion of daily report collection. RESULTS: We found a reasonably high rate of daily reporting (63.5%) with participants submitting reports on 160 "person-days" out of 252 possible days. Participants submitted daily reports an average of 13 of 21 days. Reports of test strip use frequency varied between the retrospective and daily reports with a relatively higher percentage of days/time using test strips obtained from the daily reports. We also found higher proportions reporting overdose risk reduction behaviors on the daily reports compared with the retrospective reviews. CONCLUSIONS: We believe the results support using daily experience sampling to collect information on drug checking behaviors among street drug users. Although resource intensive in comparison to retrospective reports, daily reporting potentially provides more detailed information on test strip use and its association with overdose risk reduction and, ultimately, fewer overdoses. Needed are larger trials and validation studies of daily experience sampling to identify the optimum protocol for collecting accurate information on drug checking and overdose risk reduction behavior.

High-Throughput Microenvironment Microarray (MEMA) High-Resolution Imaging.

The interaction between cells and their surrounding microenvironment has a crucial role in determining cell fate. In many pathological conditions, the microenvironment drives disease progression as well as therapeutic resistance. A number of challenges arise for researchers examining these cell-microenvironment interactions: (1) Tissue microenvironments are combinatorial and dynamic systems, and in pathological situations like cancer, microenvironments become infamously chaotic and highly heterogeneous. (2) Cells exhibit heterogeneous phenotypes, and even rare cell subpopulations can have a substantial role in tissue homeostasis and disease progression. This chapter discusses technical aspects relevant to dissecting cell-microenvironment interaction using the Microenvironment Microarray (MEMA) platform, which is a cell-based functional high-throughput screening of interactions between cells and combinatorial microenvironments at the single-cell level. MEMA provides insights into how cell phenotype and function is elicited by microenvironmental components. In this chapter, we describe automating a high-throughput and high-resolution imaging pipeline for single-cell-resolution analysis.

The Use of Mobile-Based Ecological Momentary Assessment (mEMA) Methodology to Assess Dietary Intake, Food Consumption Behaviours and Context in Young People: A Systematic Review.

Mobile-based ecological momentary assessment (mEMA) offers a novel method for dietary assessment and may reduce recall bias and participant burden. This review evaluated mEMA methodology and the feasibility, acceptability and validity as a dietary assessment method in young people. Five databases were searched from January 2008 to September 2021 for studies including healthy young people aged 16-30 years and used mEMA for obtaining dietary intake data, food consumption behaviours and/or contextual factors. Data on the method used to administer mEMA, compliance with recording and validation were extracted. A total of 46 articles from 39 independent studies were included, demonstrating a wide variation in mEMA methods. Signal-contingent prompting (timed notification to record throughout the day) was used in 26 studies, 9 used event-contingent (food consumption triggered recordings), while 4 used both. Monitoring periods varied and most studies reported a compliance rate of 80% or more. Two studies found mEMA to be burdensome and six reported mEMA as easy to use. Most studies (31/39) reported using previously validated questions. mEMA appears to be a feasible and acceptable methodology to assess dietary intake and food consumption in near real time.

Small interfering RNA for cancer treatment: overcoming hurdles in delivery.

In many ways, cancer cells are different from healthy cells. A lot of tactical nano-based drug delivery systems are based on the difference between cancer and healthy cells. Currently, nanotechnology-based delivery systems are the most promising tool to deliver DNA-based products to cancer cells. This review aims to highlight the latest development in the lipids and polymeric nanocarrier for siRNA delivery to the cancer cells. It also provides the necessary information about siRNA development and its mechanism of action. Overall, this review gives us a clear picture of lipid and polymer-based drug delivery systems, which in the future could form the base to translate the basic siRNA biology into siRNA-based cancer therapies.

The Use of Social Media and mEMA Technology in Comparing Compliance Rate Among Users.

Compliance can be defined as the extent to which a person's behavior corresponds with agreed recommendations. Within the context of lifestyle intervention, this may refer to physical activity, diet modifications, or lifestyle intervention program attendance or attrition. For lifestyle intervention programs to be successful (as measured against a variety of health and lifestyle markers), it is crucial for individuals to comply as best they can to the recommendations or instructions provided by the researchers. Those who disengage prematurely are likely to have poorer treatment outcomes. Hence, a better understanding and an added component, such as engagement, is vital to the development of successful compliance rates. Technology, such as the mobile-based Ecological Momentary Assessment (mEMA), has been used by researchers to collect data on participants through their smartphones. Studies have also used social media and mEMA in the past for topics such as chronic conditions, physical activity, weight management, and dietary behaviors. This article reports the results of two approaches to dietary monitoring using social media and mEMA technology and the lessons learned from the two studies for improving participant compliance.

Microenvironment-Induced Non-sporadic Expression of the AXL and cKIT Receptors Are Related to Epithelial Plasticity and Drug Resistance.

The existence of rare cancer cells that sporadically acquire drug-tolerance through epigenetic mechanisms is proposed as one mechanism that drives cancer therapy failure. Here we provide evidence that specific microenvironments impose non-sporadic expression of proteins related to epithelial plasticity and drug resistance. Microarrays of robotically printed combinatorial microenvironments of known composition were used to make cell-based functional associations between microenvironments, which were design-inspired by normal and tumor-burdened breast tissues, and cell phenotypes. We hypothesized that specific combinations of microenvironment constituents non-sporadically impose the induction of the AXL and cKIT receptor tyrosine kinase proteins, which are known to be involved in epithelial plasticity and drug-tolerance, in an isogenic human mammary epithelial cell (HMEC) malignant progression series. Dimension reduction analysis reveals type I collagen as a dominant feature, inducing expression of both markers in pre-stasis finite lifespan HMECs, and transformed non-malignant and malignant immortal cell lines. Basement membrane-associated matrix proteins, laminin-111 and type IV collagen, suppress AXL and cKIT expression in pre-stasis and non-malignant cells. However, AXL and cKIT are not suppressed by laminin-111 in malignant cells. General linear models identified key factors, osteopontin, IL-8, and type VIα3 collagen, which significantly upregulated AXL and cKIT, as well as a plasticity-related gene expression program that is often observed in stem cells and in epithelial-to-mesenchymal-transition. These factors are co-located with AXL-expressing cells in situ in normal and breast cancer tissues, and associated with resistance to paclitaxel. A greater diversity of microenvironments induced AXL and cKIT expression consistent with plasticity and drug-tolerant phenotypes in tumorigenic cells compared to normal or immortal cells, suggesting a reduced perception of microenvironment specificity in malignant cells. Microenvironment-imposed reprogramming could explain why resistant cells are seemingly persistent and rapidly adaptable to multiple classes of drugs. These results support the notion that specific microenvironments drive drug-tolerant cellular phenotypes and suggest a novel interventional avenue for preventing acquired therapy resistance.

The Library of Integrated Network-Based Cellular Signatures NIH Program: System-Level Cataloging of Human Cells Response to Perturbations.

The Library of Integrated Network-Based Cellular Signatures (LINCS) is an NIH Common Fund program that catalogs how human cells globally respond to chemical, genetic, and disease perturbations. Resources generated by LINCS include experimental and computational methods, visualization tools, molecular and imaging data, and signatures. By assembling an integrated picture of the range of responses of human cells exposed to many perturbations, the LINCS program aims to better understand human disease and to advance the development of new therapies. Perturbations under study include drugs, genetic perturbations, tissue micro-environments, antibodies, and disease-causing mutations. Responses to perturbations are measured by transcript profiling, mass spectrometry, cell imaging, and biochemical methods, among other assays. The LINCS program focuses on cellular physiology shared among tissues and cell types relevant to an array of diseases, including cancer, heart disease, and neurodegenerative disorders. This Perspective describes LINCS technologies, datasets, tools, and approaches to data accessibility and reusability.

Histopathologic differences partially distinguish syndromic aortic diseases.

A variety of syndromic diseases such as Marfan syndrome, Loeys-Dietz syndrome, and bicuspid aortic valve with aneurysm along with risk factors of smoking and hypertension result in ascending aortic aneurysms and dissections. Historically, a complicated variety of terms have been used to describe a range of histopathologies that are present in resected specimens. As a result, no consistent patterns of histopathology have been reported. We used the recent Society for Cardiovascular Pathology/Association for European Cardiovascular Pathology consensus statement on nomenclature and diagnostic criteria for noninflammatory aortic disease to blindly evaluate 148 surgically resected specimens. We found that overall patterns of histopathologic changes could separately cluster bicuspid aortic valve and nonsyndromic subjects from Marfan and Loeys-Dietz subjects. Marfan syndrome cases significantly had more overall medial degeneration and mucoid extracellular matrix accumulation than other syndromes. Smooth muscle cell nuclei loss was a feature of aging and not a feature of Marfan or Loeys-Dietz syndrome subjects. We conclude that a consistent use of histologic and histopathologic descriptors can help discriminate different etiologies of ascending aortic aneurysms.

Combinatorial Microenvironments Impose a Continuum of Cellular Responses to a Single Pathway-Targeted Anti-cancer Compound.

Tumor microenvironments are a driver of resistance to anti-cancer drugs. Dissecting cell-microenvironment interactions into tractable units of study presents a challenge. Here, we assess the impact of hundreds of tumor-inspired microenvironments, in parallel, on lapatinib responses in four cancer cell lines. Combinations of ECM and soluble factors were printed on stiffness-tunable substrata to generate a collection of controlled microenvironments in which to explore cell-based functional responses. Proliferation, HER2 protein expression and phosphorylation, and morphology were measured in single cells. Using dimension reduction and linear modeling, the effects of microenvironment constituents were identified and then validated empirically. Each of the cell lines exhibits unique microenvironment-response patterns. Fibronectin, type IV collagen, and matrix rigidity are significant regulators of lapatinib resistance in HER2-amplified breast cancer cells. Small-molecule inhibitors were identified that could attenuate microenvironment-imposed resistance. Thus, we demonstrate a strategy to identify resistance- and sensitivity-driving microenvironments to improve the efficacy of anti-cancer therapeutics.