Smartphone-Delivered Ecological Momentary Interventions Based on Ecological Momentary Assessments to Promote Health Behaviors: Systematic Review and Adapted Checklist for Reporting Ecological Momentary Assessment and Intervention Studies.

BACKGROUND: Healthy behaviors are crucial for maintaining a person's health and well-being. The effects of health behavior interventions are mediated by individual and contextual factors that vary over time. Recently emerging smartphone-based ecological momentary interventions (EMIs) can use real-time user reports (ecological momentary assessments [EMAs]) to trigger appropriate support when needed in daily life. OBJECTIVE: This systematic review aims to assess the characteristics of smartphone-delivered EMIs using self-reported EMAs in relation to their effects on health behaviors, user engagement, and user perspectives. METHODS: We searched MEDLINE, Embase, PsycINFO, and CINAHL in June 2019 and updated the search in March 2020. We included experimental studies that incorporated EMIs based on EMAs delivered through smartphone apps to promote health behaviors in any health domain. Studies were independently screened. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed. We performed a narrative synthesis of intervention effects, user perspectives and engagement, and intervention design and characteristics. Quality appraisal was conducted for all included studies. RESULTS: We included 19 papers describing 17 unique studies and comprising 652 participants. Most studies were quasi-experimental (13/17, 76%), had small sample sizes, and great heterogeneity in intervention designs and measurements. EMIs were most popular in the mental health domain (8/17, 47%), followed by substance abuse (3/17, 18%), diet, weight loss, physical activity (4/17, 24%), and smoking (2/17, 12%). Of the 17 studies, the 4 (24%) included randomized controlled trials reported nonstatistically significant effects on health behaviors, and 4 (24%) quasi-experimental studies reported statistically significant pre-post improvements in self-reported primary outcomes, namely depressive (P<.001) and psychotic symptoms (P=.03), drinking frequency (P<.001), and eating patterns (P=.01). EMA was commonly used to capture subjective experiences as well as behaviors, whereas sensors were rarely used. Generally, users perceived EMIs to be helpful. Common suggestions for improvement included enhancing personalization, multimedia and interactive capabilities (eg, voice recording), and lowering the EMA reporting burden. EMI and EMA components were rarely reported and were not described in a standardized manner across studies, hampering progress in this field. A reporting checklist was developed to facilitate the interpretation and comparison of findings and enhance the transparency and replicability of future studies using EMAs and EMIs. CONCLUSIONS: The use of smartphone-delivered EMIs using self-reported EMAs to promote behavior change is an emerging area of research, with few studies evaluating efficacy. Such interventions could present an opportunity to enhance health but need further assessment in larger participant cohorts and well-designed evaluations following reporting checklists. Future research should explore combining self-reported EMAs of subjective experiences with objective data passively collected via sensors to promote personalization while minimizing user burden, as well as explore different EMA data collection methods (eg, chatbots). TRIAL REGISTRATION: PROSPERO CRD42019138739; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=138739

Quantitative analysis of four rapid antigen assays for detection of pandemic H1N1 2009 compared with seasonal H1N1 and H3N2 influenza A viruses on nasopharyngeal aspirates from patients with influenza

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A network model of activities in primary care consultations.

OBJECTIVE:The objective of this study is to characterize the dynamic structure of primary care consultations by identifying typical activities and their inter-relationships to inform the design of automated approaches to clinical documentation using natural language processing and summarization methods. MATERIALS AND METHODS:This is an observational study in Australian general practice involving 31 consultations with 4 primary care physicians. Consultations were audio-recorded, and computer interactions were recorded using screen capture. Physical interactions in consultation rooms were noted by observers. Brief interviews were conducted after consultations. Conversational transcripts were analyzed to identify different activities and their speech content as well as verbal cues signaling activity transitions. An activity transition analysis was then undertaken to generate a network of activities and transitions. RESULTS:Observed activity classes followed those described in well-known primary care consultation models. Activities were often fragmented across consultations, did not flow necessarily in a defined order, and the flow between activities was nonlinear. Modeling activities as a network revealed that discussing a patient's present complaint was the most central activity and was highly connected to medical history taking, physical examination, and assessment, forming a highly interrelated bundle. Family history, allergy, and investigation discussions were less connected suggesting less dependency on other activities. Clear verbal signs were often identifiable at transitions between activities. DISCUSSION:Primary care consultations do not appear to follow a classic linear model of defined information seeking activities; rather, they are fragmented, highly interdependent, and can be reactively triggered. CONCLUSION:The nonlinearity of activities has significant implications for the design of automated information capture. Whereas dictation systems generate literal translation of speech into text, speech-based clinical summary systems will need to link disparate information fragments, merge their content, and abstract coherent information summaries

Loop and surface operators in N=2 gauge theory and Liouville modular geometry

Recently, a duality between Liouville theory and four dimensional N=2 gauge theory has been uncovered by some of the authors. We consider the role of extended objects in gauge theory, surface operators and line operators, under this correspondence. We map such objects to specific operators in Liouville theory. We employ this connection to compute the expectation value of general supersymmetric 't Hooft-Wilson line operators in a variety of N=2 gauge theories.Comment: 60 pages, 11 figures; v3: further minor corrections, published versio

Conversational agents in healthcare: a systematic review.

Objective: Our objective was to review the characteristics, current applications, and evaluation measures of conversational agents with unconstrained natural language input capabilities used for health-related purposes. Methods: We searched PubMed, Embase, CINAHL, PsycInfo, and ACM Digital using a predefined search strategy. Studies were included if they focused on consumers or healthcare professionals; involved a conversational agent using any unconstrained natural language input; and reported evaluation measures resulting from user interaction with the system. Studies were screened by independent reviewers and Cohen's kappa measured inter-coder agreement. Results: The database search retrieved 1513 citations; 17 articles (14 different conversational agents) met the inclusion criteria. Dialogue management strategies were mostly finite-state and frame-based (6 and 7 conversational agents, respectively); agent-based strategies were present in one type of system. Two studies were randomized controlled trials (RCTs), 1 was cross-sectional, and the remaining were quasi-experimental. Half of the conversational agents supported consumers with health tasks such as self-care. The only RCT evaluating the efficacy of a conversational agent found a significant effect in reducing depression symptoms (effect size d = 0.44, p = .04). Patient safety was rarely evaluated in the included studies. Conclusions: The use of conversational agents with unconstrained natural language input capabilities for health-related purposes is an emerging field of research, where the few published studies were mainly quasi-experimental, and rarely evaluated efficacy or safety. Future studies would benefit from more robust experimental designs and standardized reporting. Protocol Registration: The protocol for this systematic review is registered at PROSPERO with the number CRD42017065917

EZH2 protein: A promising immunomarker for the detection of hepatocellular carcinomas in liver needle biopsies

Background and aims: A previous study of ours indicated that enhancer of zeste homologue 2 (EZH2) plays an important role in hepatocellular carcinoma (HCC) tumorigenesis. The aim of the present study was to investigate the potential diagnostic utility of EZH2 in HCC. Methods: Immunohistochemistry was performed to examine the expression dynamics of EZH2 in two independent surgical cohorts of HCC and non-malignant liver tissues to develop a diagnostic yield of EZH2, HSP70 and GPC3 for HCC detection. The diagnostic performances of EZH2 and a three-marker panel in HCC were re-evaluated by using an additional biopsy cohort. Results: Immunohistochemistry analysis demonstrated that the sensitivity and specificity of EZH2 for HCC detection was 95.8% and 97.8% in the testing cohort. Similar results were confirmed in the validation cohort. For diagnosis of well-differentiated HCCs, the sensitivity and specificity were 68.9% and 91.5% for EZH2, 62.5% and 98.5% for HSP70, 50.0% and 92.1% for GPC3, and 75.0% and 100% for a three-marker panel. In biopsies, positive cases for at least one marker increased from large regenerative nodule and hepatocellular adenoma (0/12) to focal nodular hyperplasia (2/20), dysplastic nodule (7/25), well-differentiated HCC (16/18) and moderately and poorly differentiated HCC (54/54). When at least two positive markers were considered, regardless of their identity, the positive cases were detected in 0/12 large regenerative nodules and hepatocellular adenomas, 0/20 focal nodular hyperplasias, 0/25 dysplastic nodules, 11/18 well-differentiated HCCs, 32/37 moderately differentiated HCCs and 15/17 poorly differentiated HCCs. Conclusion: Our findings suggest that EZH2 protein, as examined by immunohistochemistry, may serve as a promising diagnostic biomarker of HCCs, and the use of a three-marker panel (EZH2, HSP70 and GPC3) can improve the rate of detection of HCCs in liver biopsy tissues.published_or_final_versio

Nuclear Localization of DNAJB6 is Associated with Survival of Patients with Esophageal Cancer and Reduces AKT Signaling and Proliferation of Cancer Cells

Abstract BACKGROUND & AIMS: The DnaJ (Hsp40) homolog, subfamily B, member 6 (DNAJB6) is part of a family of proteins that regulate chaperone activities. One of its isoforms, DNAJB6a, contains a nuclear localization signal and regulates β-catenin signaling during breast cancer development. We investigated the role of DNAJB6 in pathogenesis of esophageal squamous cell carcinoma (ESCC). METHODS: We performed immunohistochemical analyses of primary ESCC samples and lymph node metastases from a cohort of 160 patients, who underwent esophagectomy with no pre-operative chemo-radiotherapy at Hong Kong Queen Mary Hospital. Data were collected on patient outcomes over a median time of 12.1±2.9 months. Retrospective survival association analyses were performed. Wild-type and mutant forms of DNAJB6a were overexpressed in cancer cell lines (KYSE510, KYSE 30TSI, KYSE140, and KYSE70TS), which were analyzed in proliferation and immunoblot assays, or injected subcutaneously into nude mice. Levels of DNAJB6 were knocked down in ESCC cell lines (KYSE450 and T.Tn), immortalized normal esophageal epithelial cell lines (NE3 and NE083), and other cells with short hairpin RNAs or by genome engineering. Bimolecular fluorescence complementation was used to study interactions between proteins in living cells. RESULTS: In primary ESCC samples, patients whose tumors had high nuclear levels of DNAJB6 had longer overall survival times (19.2±1.8 months; 95% confidence interval [CI], 15.6-22.8 months) than patients whose tumors had low nuclear levels of DNAJB6 (12.6±1.4 months; 95% CI, 9.8-15.4 months; P=.004, by log rank test). Based on Cox regression analysis, patients whose tumors had high nuclear levels of DNAJB6 had a lower risk of death than those with low levels (hazard ratio=0.562; 95% CI, 0.379-0.834; P=.004). Based on log rank analysis and Cox regression analysis, the combination of nuclear level of DNAJB6 and the presence of lymph node metastases at diagnosis could be used to stratify patients into groups with good or bad outcomes (P<.0005 for both analyses). There was a negative association between the nuclear level of DNAJB6 and the presence of lymph node metastases (P=.022; Pearson χ2 test). Cancer cell lines that overexpressed DNAJB6a formed tumors more slowly in nude mice than control cells or cells that expressed a mutant form of DNAJB6a that did not localize to the nucleus. DNAJB6 knockdown in cancer cell lines promoted their growth as xenograft tumors in mice. A motif of histidine, proline, and aspartic acid (HPD) in the J domain of DNAJB6a was required for its tumor suppressive effects and signaling via AKT1. Loss of DNAJB6a resulted in upregulation of AKT signaling in cancer cell lines and immortalized esophageal epithelial cells. Expression of a constitutively active form of AKT1 restored proliferation to tumor cells that overexpressed DNAJB6a, and DNAJB6a formed a complex with AKT1 in living cells. Expression of DNAJB6a reduced the sensitivity of ESCC to AKT inhibitors; the expression level of DNAJB6a affected AKT signaling in multiple cancer cell lines. CONCLUSIONS: Nuclear localization of DNAJB6 is associated with longer survival times of patients with ESCC. DNAJB6a reduces AKT signaling, and DNAJB6 expression in cancer cells reduces their proliferation and growth of xenograft tumors in mice. DNAJB6a might be developed as biomarker for progression of ESCC.postprin

Envisioning an artificial intelligence documentation assistant for future primary care consultations: A co-design study with general practitioners

Abstract Objective The study sought to understand the potential roles of a future artificial intelligence (AI) documentation assistant in primary care consultations and to identify implications for doctors, patients, healthcare system, and technology design from the perspective of general practitioners. Materials and Methods Co-design workshops with general practitioners were conducted. The workshops focused on (1) understanding the current consultation context and identifying existing problems, (2) ideating future solutions to these problems, and (3) discussing future roles for AI in primary care. The workshop activities included affinity diagramming, brainwriting, and video prototyping methods. The workshops were audio-recorded and transcribed verbatim. Inductive thematic analysis of the transcripts of conversations was performed. Results Two researchers facilitated 3 co-design workshops with 16 general practitioners. Three main themes emerged: professional autonomy, human-AI collaboration, and new models of care. Major implications identified within these themes included (1) concerns with medico-legal aspects arising from constant recording and accessibility of full consultation records, (2) future consultations taking place out of the exam rooms in a distributed system involving empowered patients, (3) human conversation and empathy remaining the core tasks of doctors in any future AI-enabled consultations, and (4) questioning the current focus of AI initiatives on improved efficiency as opposed to patient care. Conclusions AI documentation assistants will likely to be integral to the future primary care consultations. However, these technologies will still need to be supervised by a human until strong evidence for reliable autonomous performance is available. Therefore, different human-AI collaboration models will need to be designed and evaluated to ensure patient safety, quality of care, doctor safety, and doctor autonomy. </jats:sec

Chronic hepatitis B: whom to treat and for how long? Propositions, challenges, and future directions

Recent guidelines of the American Association for the Study of Liver Diseases, the European Association for the Study of the Liver, and the Asian Pacific Association for the Study of the Liver 2008 update of the “Asian-Pacific consensus statement on the management of chronic hepatitis B” offer comprehensive recommendations for the general management of chronic hepatitis B (CHB). These recommendations highlight preferred approaches to the prevention, diagnosis, and treatment of CHB. Nonetheless, the results of recent studies have led to an improved understanding of the disease and a belief that current recommendations on specific therapeutic considerations, including CHB treatment initiation and cessation criteria, particularly in patient populations with special circumstances, can be improved. Twelve experts from the Asia-Pacific region formed the Asia-Pacific Panel Recommendations for the Optimal Management of Chronic Hepatitis B (APPROACH) Working Group to review, challenge, and assess relevant new data and inform future updates of CHB treatment guidelines. The significance of and controversy about reported findings were discussed and debated in an expert meeting of the Working Group in Beijing, China, in November 2008. This review paper attempts to identify areas requiring improved CHB management and provide suggestions for future guideline updates, with special emphasis on treatment initiation and duration

Brainstem and Spinal Cord Circuitry Regulating REM Sleep and Muscle Atonia

Previous work has suggested, but not demonstrated directly, a critical role for both glutamatergic and GABAergic neurons of the pontine tegmentum in the regulation of rapid eye movement (REM) sleep.To determine the in vivo roles of these fast-acting neurotransmitters in putative REM pontine circuits, we injected an adeno-associated viral vector expressing Cre recombinase (AAV-Cre) into mice harboring lox-P modified alleles of either the vesicular glutamate transporter 2 (VGLUT2) or vesicular GABA-glycine transporter (VGAT) genes. Our results show that glutamatergic neurons of the sublaterodorsal nucleus (SLD) and glycinergic/GABAergic interneurons of the spinal ventral horn contribute to REM atonia, whereas a separate population of glutamatergic neurons in the caudal laterodorsal tegmental nucleus (cLDT) and SLD are important for REM sleep generation. Our results further suggest that presynaptic GABA release in the cLDT-SLD, ventrolateral periaqueductal gray matter (vlPAG) and lateral pontine tegmentum (LPT) are not critically involved in REM sleep control.These findings reveal the critical and divergent in vivo role of pontine glutamate and spinal cord GABA/glycine in the regulation of REM sleep and atonia and suggest a possible etiological basis for REM sleep behavior disorder (RBD)