Mucus-degrading Bacteroides link carbapenems to aggravated graft-versus-host disease.

The intestinal microbiota is an important modulator of graft-versus-host disease (GVHD), which often complicates allogeneic hematopoietic stem cell transplantation (allo-HSCT). Broad-spectrum antibiotics such as carbapenems increase the risk for intestinal GVHD, but mechanisms are not well understood. In this study, we found that treatment with meropenem, a commonly used carbapenem, aggravates colonic GVHD in mice via the expansion of Bacteroides thetaiotaomicron (BT). BT has a broad ability to degrade dietary polysaccharides and host mucin glycans. BT in meropenem-treated allogeneic mice demonstrated upregulated expression of enzymes involved in the degradation of mucin glycans. These mice also had thinning of the colonic mucus layer and decreased levels of xylose in colonic luminal contents. Interestingly, oral xylose supplementation significantly prevented thinning of the colonic mucus layer in meropenem-treated mice. Specific nutritional supplementation strategies, including xylose supplementation, may combat antibiotic-mediated microbiome injury to reduce the risk for intestinal GVHD in allo-HSCT patients.

Developing and Validating a Computer-Based Training Tool for Inferring 2D Cross-Sections of Complex 3D Structures.

OBJECTIVE: Developing and validating a novel domain-agnostic, computer-based training tool for enhancing 2D cross-section understanding of complex 3D structures. BACKGROUND: Understanding 2D cross-sections of 3D structures is a crucial skill in many disciplines, from geology to medical imaging . It requires a complex set of spatial/visualization skills including mental rotation, spatial structure understanding, and viewpoint projection. Prior studies show that experts differ from novices in these skills. METHOD: We have developed a novel training tool for inferring 2D cross-sections of 3D structures using a participatory design methodology. We used a between-subject study design, with 60 participants, to evaluate the training tool. Our primary effectiveness evaluation was based on pre- and postspatial tests that measured both cross-section abilities and specific spatial skills: viewpoint, mental rotation, and card rotation. RESULTS: Results showed significant performance gains on inferring 2D cross-sections for participants of the training group. Our tool improves two other spatial skills as well: mental rotation and viewpoint visualization. CONCLUSION: Our training tool was effective not only in enhancing 2D cross-section understanding of complex 3D structures, but also in improving mental rotation and viewpoint visualization skills. APPLICATION: Our tool can be beneficial in different fields such as medical imaging, biology, geology, and engineering. For example, an application of our tool is in medical/research labs to train novice segmenters in ongoing manual 3D segmentation tasks. It can also be adapted in other contexts, such as training children, older adults, and individuals with very low spatial skills.

Investigating synapse formation and function using human pluripotent stem cell-derived neurons.

A major goal of stem-cell research is to identify conditions that reliably regulate their differentiation into specific cell types. This goal is particularly important for human stem cells if they are to be used for in vivo transplantation or as a platform for drug development. Here we describe the establishment of procedures to direct the differentiation of human embryonic stem cells and human induced pluripotent stem cells into forebrain neurons that are capable of forming synaptic connections. In addition, HEK293T cells expressing Neuroligin (NLGN) 3 and NLGN4, but not those containing autism-associated mutations, are able to induce presynaptic differentiation in human induced pluripotent stem cell-derived neurons. We show that a mutant NLGN4 containing an in-frame deletion is unable to localize correctly to the cell surface when overexpressed and fails to enhance synapse formation in human induced pluripotent stem cell-derived neurons. These findings establish human pluripotent stem cell-derived neurons as a viable model for the study of synaptic differentiation and function under normal and disorder-associated conditions.

Bacteroides ovatus alleviates dysbiotic microbiota-induced intestinal graft-versus-host disease.

Acute gastrointestinal intestinal GVHD (aGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation, and the intestinal microbiota is known to impact on its severity. However, an association between treatment response of aGI-GVHD and the intestinal microbiota has not been well-studied. In a cohort of patients with aGI-GVHD (n=37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and loss of Bacteroides ovatus from the microbiome. In a mouse model of carbapenem-aggravated GVHD, introducing Bacteroides ovatus reduced severity of GVHD and improved survival. Bacteroides ovatus reduced degradation of colonic mucus by another intestinal commensal, Bacteroides thetaiotaomicron, via its ability to metabolize dietary polysaccharides into monosaccharides, which then inhibit mucus degradation by Bacteroides thetaiotaomicron and reduce GVHD-related mortality.

Metacognitive accuracy across cognitive and physical task domains.

Metacognition is often considered a critical component of learning and higher-order cognition; however, does metacognitive accuracy remain constant across all tasks, specifically in tasks that involve physical or procedural components? To investigate the consistency of metacognitive judgments across various task types, participants completed word and number recall tasks, and also completed three simple physical skill tasks (e.g., catching a ball in a cup). Participants made metacognitive judgments about their performance in all tasks. Results indicated that while participants demonstrated traditional levels of relative metacognitive accuracy in more cognitive tasks, participants were significantly more accurate in their judgments for physical skill tasks. In other words, relative accuracy for metacognitive judgments in physical tasks appears to be significantly higher than for cognitive tasks. This represents the first such demonstration of this effect and suggests that characteristics of physical tasks somehow improve participants' judgments of how well they have learned.

Diet-derived metabolites and mucus link the gut microbiome to fever after cytotoxic cancer treatment.

Not all patients with cancer and severe neutropenia develop fever, and the fecal microbiome may play a role. In a single-center study of patients undergoing hematopoietic cell transplant (n = 119), the fecal microbiome was characterized at onset of severe neutropenia. A total of 63 patients (53%) developed a subsequent fever, and their fecal microbiome displayed increased relative abundances of Akkermansia muciniphila, a species of mucin-degrading bacteria (P = 0.006, corrected for multiple comparisons). Two therapies that induce neutropenia, irradiation and melphalan, similarly expanded A. muciniphila and additionally thinned the colonic mucus layer in mice. Caloric restriction of unirradiated mice also expanded A. muciniphila and thinned the colonic mucus layer. Antibiotic treatment to eradicate A. muciniphila before caloric restriction preserved colonic mucus, whereas A. muciniphila reintroduction restored mucus thinning. Caloric restriction of unirradiated mice raised colonic luminal pH and reduced acetate, propionate, and butyrate. Culturing A. muciniphila in vitro with propionate reduced utilization of mucin as well as of fucose. Treating irradiated mice with an antibiotic targeting A. muciniphila or propionate preserved the mucus layer, suppressed translocation of flagellin, reduced inflammatory cytokines in the colon, and improved thermoregulation. These results suggest that diet, metabolites, and colonic mucus link the microbiome to neutropenic fever and may guide future microbiome-based preventive strategies.

Working through the pain: working memory capacity and differences in processing and storage under pain.

It has been suggested that pain perception and attention are closely linked at both a neural and a behavioural level. If pain and attention are so linked, it is reasonable to speculate that those who vary in working memory capacity (WMC) should be affected by pain differently. This study compares the performance of individuals who differ in WMC as they perform processing and memory span tasks while under mild pain and not. While processing performance under mild pain does not interact with WMC, the ability to store information for later recall does. This suggests that pain operates much like an additional processing burden, and that the ability to overcome this physical sensation is related to differences in WMC.

Smartphone display size can cause distortions in perceptual estimates of size.

Everyday we consume massive amounts of visual information on mobile devices like smartphones. However, are there consequences for viewing information on these devices? In 2 experiments, participants viewed several target objects on two differently sized virtual smartphone displays, and then made a judgment of the size of each target item. Results from both experiments confirm that smartphone display size does impact user perceptions of size, such that larger displays cause users to significantly underestimate the size of objects. This effect held when target items were presented alone, or concurrently with a non-target referent. This is the first study to confirm such an effect and suggests that the size of a smartphone display can negatively influence the accuracy of users' visual perception. Thus, beyond aesthetics or cost, it must be realized that the choice of device might have additional perceptual consequences for consumers.

Author Correction: Fecal microbiota transplantation for refractory immune checkpoint inhibitor-associated colitis.

In the version of this article originally published, an author was missing from the author list. Alexander J. Lazar should have been included between Jorge M. Blando and James P. Allison. The author has been added to the list, and the author contributions section has been updated to include Alexander J. Lazar's contribution to the study. The error has been corrected in the print, PDF and HTML versions of the manuscript.

Disfluent presentations lead to the creation of more false memories.

The creation of false memories within the Deese-Roediger-McDermott (DRM) paradigm has been shown to be sensitive to many factors such as task instructions, participant mood, or even presentation modality. However, do other simple perceptual differences also impact performance on the DRM and the creation of false memories? This study explores the potential impact of changes in perceptual disfluency on DRM performance. To test for a potential influence of disfluency on false memory creation, participants viewed lists under either perceptually disfluent conditions or not. Results indicated that disfluency did significantly impact performance in the DRM paradigm; more disfluent presentations significantly increased the recall and recognition of unpresented information, although they did not impact recall or recognition of presented information. Thus, although disfluency did impact performance, disfluency did not produce a positive benefit related to overall task performance. This finding instead suggests that more disfluent presentations can increase the likelihood that false memories are created, and provide little positive performance benefit.

Graphically Hearing: Enhancing Understanding of Geospatial Data through an Integrated Auditory and Visual Experience.

Effective presentation of data is critical to a users understanding of it. In this manuscript, we explore research challenges associated with presenting large geospatial datasets through a multimodal experience. We also suggest an interaction schema that enhances users cognition of geographic information through a user-driven display that visualizes and sonifies geospatial data.

Fecal microbiota transplantation for refractory immune checkpoint inhibitor-associated colitis.

We report the first case series of immune checkpoint inhibitors (ICI)-associated colitis successfully treated with fecal microbiota transplantation, with reconstitution of the gut microbiome and a relative increase in the proportion of regulatory T-cells within the colonic mucosa. These preliminary data provide evidence that modulation of the gut microbiome may abrogate ICI-associated colitis.

If it's hard to read, it changes how long you do it: reading time as an explanation for perceptual fluency effects on judgment.

Perceptual manipulations, such as changes in font type or figure-ground contrast, have been shown to increase judgments of difficulty or effort related to the presented material. Previous theory has suggested that this is the result of changes in online processing or perhaps the post-hoc influence of perceived difficulty recalled at the time of judgment. These two experiments seek to examine by which mechanism (or both) the fluency effect is produced. Results indicate that disfluency does in fact change in situ reading behavior, and this change significantly mediates judgments. Eye movement analyses corroborate this suggestion and observe a difference in how people read a disfluent presentation. These findings support the notion that readers are using perceptual cues in their reading experiences to change how they interact with the material, which in turn produces the observed biases.

Enhancing visuospatial performance through video game training to increase learning in visuospatial science domains.

Although previous research has demonstrated that performance on visuospatial assessments can be enhanced through relevant experience, an unaddressed question is whether such experience also produces a similar increase in target domains (such as science learning) where visuospatial abilities are directly relevant for performance. In the present study, participants completed either spatial or nonspatial training via interaction with video games and were then asked to read and learn about the geologic topic of plate tectonics. Results replicate the benefit of playing appropriate video games in enhancing visuospatial performance and demonstrate that this facilitation also manifests itself in learning science topics that are visuospatial in nature. This novel result suggests that visuospatial training not only can impact performance on measures of spatial functioning, but also can affect performance in content areas in which these abilities are utilized.

Feedback preferences and impressions of waiting.

OBJECTIVE: Three experiments examined the effects of various feedback displays on user preference, apparent waiting durations, waiting time reasonableness, and other user experience measures. BACKGROUND: User interface guidelines advocate keeping users informed about system status; however, the duration estimation literature shows that focusing on temporal information makes the wait seem longer. How can designers reconcile these issues? METHODS: In three experiments, students chose movies from a simulated movie database and then were shown feedback displays (static, sequential dots, constant-rate progress bars, or variable-rate progress bars) for different durations. Users judged how reasonable the wait was and how long it lasted and then ranked their preference for the dialogs. RESULTS: The pattern of preference results was different from duration-related judgments. Users preferred feedback that provided more information. On the other hand, when judging duration, users perceived simpler interfaces as being most reasonable. CONCLUSION: Different types of feedback are required for reducing perceived wait and increasing preference. Ratings of wait time reasonableness were consistent with the attentional gate theory of prospective timing; attention-demanding activity caused the wait to seem less reasonable. Preference, on the other hand, requires keeping users informed about the progress of operations. APPLICATION: Users prefer more feedback rather than less, even if it makes the wait seem less reasonable. However, the constant progress bar performed at the top of both reasonableness and preference, keeping users informed without increasing arousal or focusing attention on temporal stimuli. Other options are also discussed to make duration perceptions more reasonable.

To scroll or not to scroll: scrolling, working memory capacity, and comprehending complex texts.

OBJECTIVE: The purpose of these experiments was to examine the effects of user characteristics on learning from scrolling interfaces. BACKGROUND: Although scrolling Web pages are now common, few studies have explored the effects of scrolling on understanding the content that is being conveyed. METHOD: This set of studies investigated whether presenting text in two particular formats has an effect on comprehension for readers who differ in working memory capacity. RESULTS: Results from both studies indicated that a scrolling format reduced understanding of complex topics from Web pages, especially for readers who were lower in working memory capacity. CONCLUSION: These findings show that the way text is presented can interact with learner abilities to affect learning outcomes. APPLICATION: These results have implications for both educational technology and human interfaces that present information using displays that can vary in size and construction.

An examination of the seductive details effect in terms of working memory capacity.

Previous work on learning from text has demonstrated that although illustrated text can enhance comprehension, illustrations can also sometimes lead to poor learning outcomes when they are not relevant to understanding the text This phenomenon is known as the seductive details effect. The first experiment was designed to test whether the ability to control one's attention, as measured by working memory span tasks, would influence the processing of a scientific text that contained seductive (irrelevant) images, conceptually relevant images, or no illustrations. Understanding was evaluated using both an essay response and an inference verification task. Results indicated that low working memory capacity readers are especially vulnerable to the seductive details effect. In the second experiment, this issue was explored further, using eye-tracking methodology to evaluate the reading patterns of individuals who differed in working memory capacity as they read the same seductively illustrated scientific text Results indicated that low working memory individuals attend to seductive illustrations more often than not and, also, for a longer duration than do those individuals high in working memory capacity.