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Clinical trials in metabolic dysfunction-associated steatohepatitis (MASH, formerly known as nonalcoholic steatohepatitis) require histologic scoring for assessment of inclusion criteria and endpoints. However, variability in interpretation has impacted clinical trial outcomes. We developed an artificial intelligence-based measurement (AIM) tool for scoring MASH histology (AIM-MASH). AIM-MASH predictions for MASH Clinical Research Network necroinflammation grades and fibrosis stages were reproducible (κ= 1) and aligned with expert pathologist consensus scores (κ= 0.62–0.74). The AIM-MASH versus consensus agreements were comparable to average pathologists for MASH Clinical Research Network scores (82% versus 81%) and fibrosis (97% versus 96%). Continuous scores produced by AIM-MASH for key histological features of MASH correlated with mean pathologist scores and noninvasive biomarkers and strongly predicted progression-free survival in patients with stage 3 (P< 0.0001) and stage 4 (P= 0.03) fibrosis. In a retrospective analysis of the ATLAS trial (NCT03449446), responders receiving study treatment showed a greater continuous change in fibrosis compared with placebo (P= 0.02). Overall, these results suggest that AIM-MASH may assist pathologists in histologic review of MASH clinical trials, reducing inter-rater variability on trial outcomes and offering a more sensitive and reproducible measure of patient responses.

Drawing from real-life scenarios and insights shared at the RAISE (Responsible AI for Social and Ethical Healthcare) conference, we highlight the critical need for AI in health care (AIH) to primarily benefit patients and address current shortcomings in health care systems such as medical errors and access disparities.

Metabolic dysfunction-associated steatohepatitis (MASH) is a major cause of liver-related morbidity and mortality, yet treatment options are limited. Manual scoring of liver biopsies, currently the gold standard for clinical trial enrollment and endpoint assessment, suffers from high reader variability. This study represents the most comprehensive multisite analytical and clinical validation of an artificial intelligence (AI)-based pathology system, AI-based measurement of metabolic dysfunction-associated steatohepatitis (AIM-MASH), to assist pathologists in MASH trial histology scoring. AIM-MASH demonstrated high repeatability and reproducibility compared to manual scoring. AIM-MASH-assisted reads by expert MASH pathologists were superior to unassisted reads in accurately assessing inflammation, ballooning, MAS ≥ 4 with ≥1 in each score category and MASH resolution, while maintaining non-inferiority in steatosis and fibrosis assessment. These findings suggest that AIM-MASH could mitigate reader variability, providing a more reliable assessment of therapeutics in MASH clinical trials.

Incorporating peer and professional social support features into remotely delivered, technology-supported physical activity interventions may increase their effectiveness. However, very little is known about survivors' preferences for potential social features. This study explored breast cancer survivors' preferences for both traditional (e.g., coaching calls and peer support) and innovative (i.e., message boards and competitions) social support features within remotely delivered, technology-supported physical activity interventions. Survivors [N = 96; Mage = 55.8 (SD = 10.2)] self-reported demographic and disease characteristics and physical activity. A subset (n = 28) completed semistructured phone interviews. Transcribed interviews were evaluated using a thematic content analysis approach and consensus review. Following interviews, the full sample self-reported preferences for social features for remotely delivered physical activity interventions via online questionnaires. Questionnaire data were analyzed using descriptive statistics. Four themes emerged from interview data: (a) technology increases social connectedness; (b) interest in professional involvement/support; (c) connecting with similar survivors; and (d) apprehension regarding competitive social features. Quantitative data indicated that most survivors were interested in social features including a coach (77.1 per cent), team (66.7 per cent), and exercise buddy (57.3 per cent). Survivors endorsed sharing their activity data with their team (80.0 per cent) and buddy (76.6 per cent), but opinions were mixed regarding a progress board ranking their activity in relation to other participants' progress. Survivors were interested in using a message board to share strategies to increase activity (74.5 per cent) and motivational comments (73.4 per cent). Social features are of overall interest to breast cancer survivors, yet preferences for specific social support features varied. Engaging survivors in developing and implementing remotely delivered, technology-supported social features may enhance their effectiveness.

In this synopsis, we summarize and comment on Baker and colleagues’ Cochrane review of studies on the population-level impact of community-wide physical activity (PA) interventions. Insufficient PA remains a major public health problem. Community-wide interventions offer an opportunity to extend reach by increasing the proportion of the population experiencing the intervention. A previous Cochrane review of community-wide PA interventions concluded that evidence for effectiveness was mixed. Hence, Baker and colleagues incorporated new data about community-based PA interventions. This Cochrane review concluded there is an overall lack of evidence that community-wide interventions improve PA outcomes at the population level. Recommendations are that future research should use high quality research design, more explicitly test ways to increase reach, and utilize objective measurements of PA to increase validity. We suggest that future research should first optimize the intervention by systematically evaluating treatment components and selecting a maximally efficient and effective treatment package.

In this synopsis, we summarize and comment on Baker and colleagues' Cochrane review of studies on the population-level impact of community-wide physical activity (PA) interventions. Insufficient PA remains a major public health problem. Community-wide interventions offer an opportunity to extend reach by increasing the proportion of the population experiencing the intervention. A previous Cochrane review of community-wide PA interventions concluded that evidence for effectiveness was mixed. Hence, Baker and colleagues incorporated new data about community-based PA interventions. This Cochrane review concluded there is an overall lack of evidence that community-wide interventions improve PA outcomes at the population level. Recommendations are that future research should use high quality research design, more explicitly test ways to increase reach, and utilize objective measurements of PA to increase validity. We suggest that future research should first optimize the intervention by systematically evaluating treatment components and selecting a maximally efficient and effective treatment package.

Breaking up sitting time with light- or moderate-intensity physical activity may help to alleviate some negative health effects of sedentary behavior, but few studies have examined ways to effectively intervene. This feasibility study examined the acceptability of a new technology (NEAT!) developed to interrupt prolonged bouts (≥20 min) of sedentary time among adults with type 2 diabetes. Eight of nine participants completed a 1-month intervention and agreed that NEAT!made them more conscious of sitting time. Most participants (87.5 %) expressed a desire to use NEAT!in the future. Sedentary time decreased by 8.1 ± 4.5 %, and light physical activity increased by 7.9 ± 5.5 % over the 1-month period. The results suggest that NEAT!is an acceptable technology to intervene on sedentary time among adults with type 2 diabetes. Future studies are needed to examine the use of the technology among larger samples and determine its effects on glucose and insulin levels.

Breaking up sitting time with light- or moderate-intensity physical activity may help to alleviate some negative health effects of sedentary behavior, but few studies have examined ways to effectively intervene. This feasibility study examined the acceptability of a new technology (NEAT!) developed to interrupt prolonged bouts (≥20 min) of sedentary time among adults with type 2 diabetes. Eight of nine participants completed a 1-month intervention and agreed that NEAT! made them more conscious of sitting time. Most participants (87.5 %) expressed a desire to use NEAT! in the future. Sedentary time decreased by 8.1 ± 4.5 %, and light physical activity increased by 7.9 ± 5.5 % over the 1-month period. The results suggest that NEAT! is an acceptable technology to intervene on sedentary time among adults with type 2 diabetes. Future studies are needed to examine the use of the technology among larger samples and determine its effects on glucose and insulin levels.

In this synopsis and commentary on the Morrison and colleagues article published in Telemedicine and e-Health (18:2, 137-144, 2012), we provide a brief review of effective design features of e-Health interventions as well as a discussion on future directions. The Internet is being used more frequently to deliver health behavior interventions; however, it is unclear which design features contribute to intervention outcomes. Morrison and colleagues conducted a review using critical interpretive synthesis techniques to identify design features that mediate the effects of e-Health intervention outcomes. A total of four design features were identified (social context and support, contacts with intervention, tailoring, and self-management) that may mediate the effect of the intervention on outcomes. This review provides a preliminary conceptual framework to guide future evaluations of the effects of e-Health design features on intervention outcomes. Future research should target optimizing e-Health interventions to determine which design features should be included as well as how they contribute to outcomes.

In this synopsis and commentary on the Morrison and colleagues article published in Telemedicine and e-Health (18:2, 137–144, 2012), we provide a brief review of effective design features of e-Health interventions as well as a discussion on future directions. The Internet is being used more frequently to deliver health behavior interventions; however, it is unclear which design features contribute to intervention outcomes. Morrison and colleagues conducted a review using critical interpretive synthesis techniques to identify design features that mediate the effects of e-Health intervention outcomes. A total of four design features were identified (social context and support, contacts with intervention, tailoring, and self-management) that may mediate the effect of the intervention on outcomes. This review provides a preliminary conceptual framework to guide future evaluations of the effects of e-Health design features on intervention outcomes. Future research should target optimizing e-Health interventions to determine which design features should be included as well as how they contribute to outcomes.

Hemorrhage and hemorrhagic shock instigate intestinal damage and inflammation. Multiple components of the innate immune response, including complement and neutrophil infiltration, are implicated in this pathology. To investigate the interaction of complement activation and other components of the innate immune response during hemorrhage, we treated mice after hemorrhage with CR2-fH, a targeted inhibitor of the alternative complement pathway and assessed intestinal damage and inflammation 2 h after hemorrhage. In wild-type mice, CR2-fH attenuated hemorrhage-induced, midjejunal damage and inflammation as determined by decreased mucosal damage, macrophage infiltration, leukotriene B4, IL-12p40, and TNF- production. The critical nature of intestinal macrophage infiltration and activation in the response to hemorrhage was further determined using mice pretreated with clodronate-containing liposomes. The absence of either macrophages or IL-12p70 attenuated intestinal damage. These data suggest that complement activation and macrophage infiltration with IL-12p70 production are critical to hemorrhage-induced midjejunal damage and inflammation.

With more than half of the world population infected, Helicobacterinfection is an important public health issue associated with gastrointestinal cancers and inflammatory bowel disease. Animal studies indicate that complement and oxidative stress play a role in Helicobacterinfections. Hemorrhage (HS) induces tissue damage that is attenuated by blockade of either complement activation or oxidative stress products. Therefore, we hypothesized that chronic Helicobacter hepaticusinfection would modulate HS-induced intestinal damage and inflammation. To test this hypothesis, we examined HS-induced jejunal damage and inflammation in uninfected and H. hepaticus-infected mice. Helicobacter hepaticusinfection increased HS-induced midjejunal mucosal damage despite attenuating complement activation. In addition, infection alone increased chemokine secretion, changing the HS-induced neutrophil infiltration to a macrophage-mediated inflammatory response. The HS-induced macrophage infiltration correlated with increased secretion of tumor necrosis factor- and nitric oxide in the infected mice. Together, these data indicate that Helicobacterinfection modulates the mechanism of HS-induced intestinal damage and inflammation from a complement-mediated response to a macrophage response with elevated tumor necrosis factor- and nitric oxide. These data indicate that chronic low-level infections change the response to trauma and should be considered when designing and administering therapeutics.

Our previous study indicated that normal serum contains complement-fixing natural IgM antibodies reacting with a large variety of randomly generated protein carboxy-termini. Here we show that the “carboxy-terminal” IgM (C-IgM) antibodies specifically react with short peptide sequences located immediately at the protein carboxy-terminus. The specificity of C-IgM–peptide interactions is tentatively defined by three to four amino acid residues. All carboxy-terminal peptides in a large peptide library apparently react with C-IgM antibodies. Immobilized synthetic peptides also react with C-IgM antibodies. No interaction of C-IgM antibodies with internal peptide sequences has been observed. C-IgM antibodies are present in germ-free and in athymic adult rats and are absent in newborn rats. The natural ubiquity of protein carboxy-termini in biological structures suggests that C-IgM could play an important role in antigen clearance and presentation to the immune system. From a practical viewpoint, the recognition of carboxy-terminal peptides by complement-fixing C-IgM antibodies has profound implications for the use of peptide- and protein-derivatized delivery vehicles and artificial materials.Molecular Therapy (2001) 3, 821–830; doi: 10.1006/mthe.2001.0340

We offer a synopsis and commentary on J. Fanning and colleagues' article "Increasing Physical Activity with Mobile Devices: A Meta-Analysis" published in the Journal of Medical Internet Research. Although regular physical activity has a range of benefits, very few adults in the USA meet recommended guidelines for daily physical activity. The meta-analysis of Fanning et al. (2012) aimed to synthesize the results of research using mobile devices to increase physical activity. Their review identified 11 studies that used mobile technologies, including short message service (SMS), apps, or personal digital assistant (PDA) to improve physical activity behaviors among participants. Fanning et al. conclude that while literature in this area is limited to date, there is initial support for the efficacy of mobile-based interventions for improving physical activity. Included studies varied greatly, and the majority used only SMS to influence physical behaviors, meaning generalization of results to other forms of mobile technologies may be premature. This review does, however, provide a foundation for understanding how mobile-based interventions may be used efficaciously for the development of future interventions to improve health behaviors.

We offer a synopsis and commentary on J. Fanning and colleagues’ article “Increasing Physical Activity with Mobile Devices: A Meta-Analysis” published in the Journal of Medical Internet Research. Although regular physical activity has a range of benefits, very few adults in the USA meet recommended guidelines for daily physical activity. The meta-analysis of Fanning et al. (2012) aimed to synthesize the results of research using mobile devices to increase physical activity. Their review identified 11 studies that used mobile technologies, including short message service (SMS), apps, or personal digital assistant (PDA) to improve physical activity behaviors among participants. Fanning et al. conclude that while literature in this area is limited to date, there is initial support for the efficacy of mobile-based interventions for improving physical activity. Included studies varied greatly, and the majority used only SMS to influence physical behaviors, meaning generalization of results to other forms of mobile technologies may be premature. This review does, however, provide a foundation for understanding how mobile-based interventions may be used efficaciously for the development of future interventions to improve health behaviors.

Features the Ten Year Gala, a comedy show performed by the Acme Comedy Company in the United States. Venue of the show; Members of the comedy group; Profile of the comedians.

Profiles Craig Wright, Twin Cities playwright. Personal background; Career development; Interests and hobbies.