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.

Fluid Slip and Drag Reduction on Liquid-Infused Surfaces under High Static Pressure.

Liquid-infused surfaces (LIS) have been shown to reduce the huge frictional drag affecting microfluidic flow and are expected to be more robust than superhydrophobic surfaces when exposed to external pressure as the lubricant in LIS is incompressible. Here, we investigate the effect of applying static pressure on the effective slip length measured on Teflon wrinkled surfaces infused with silicone oil through pressure measurements in microfluidic devices. The effect of static pressure on LIS was found to depend on air content in the flowing water: for degassed water, the average effective slip length was beff = 2.16 ± 0.90 µm, irrespective of applied pressure. In gassed water, the average effective slip length was beff = 4.32 ± 1.06 µm at zero applied pressure, decreased by 55% to 2.37 ± 0.90 µm when the pressure was increased to 50 kPa, and then remained constant up to 200 kPa. The result is due to nanobubbles present on LIS, which are compressed or partially dissolved under pressure, and the effect is more evident when the size and portion of surface nanobubbles are higher. In contrast, on superhydrophobic wrinkles, the decline in beff was more sensitive to applied pressure, with beff = 6.8 ± 1.4 µm at 0 kPa and, on average, beff = -1 ± 3 µm for pressures higher than 50 kPa for both gassed and degassed water. Large fluctuations in the experimental measurements were observed on superhydrophobic wrinkles, suggesting the nucleation of large bubbles on the surface. The same pressure increase did not affect the flow on smooth substrates, on which gas nanobubbles were not observed. Contrary to expectations, we observed that drag reduction in LIS is affected by applied pressure, which we conclude is because, in a similar manner to superhydrophobic surfaces, they lose the interfacial gas, which lubricates the flow.

EcoPLOT: dynamic analysis of biogeochemical data.

MOTIVATION: We have created EcoPLOT (parameterized linkage of omics-driven technologies), a web-app for the dynamic, interactive analysis of biogeochemical datasets that combines state-of-the-art analysis tools to statistically and graphically explore environmental, geochemical and microbiome datasets. Using the iterative random forest, a machine learning algorithm, EcoPLOT allows for the de novo discovery of drivers which exhibit significant impact on plant, microbial or soil dynamics. AVAILABILITY AND IMPLEMENTATION: EcoPLOT is built entirely within the R language. It can be accessed through any system where R is installed, including Windows, Mac and most Linux systems. EcoPLOT is free to use and can be accessed at https://github.com/cdsanchez18/EcoPLOT.

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.

Slightly Depleted Lubricant-Infused Surfaces Are No Longer Slippery.

Textured surfaces infused with a lubricating fluid effectively reduce fouling and drag. These functions critically depend on the presence and distribution of the lubricant, which can be depleted by many mechanisms, including shear flow. We present a two-phase Couette flow computational dynamic simulation over lubricant-infused surfaces containing grooves oriented perpendicular to the flow direction, with the aim of revealing how interfacial slip, and therefore drag reduction, is impacted by lubricant depletion. We show that even a slight (20%) lubricant loss decreases slip to the point of making the lubricant superfluous, even for lubricants with lower viscosity than the flowing liquid and regardless of how well the lubricant wets the grooves. We explain that the drastic slip reduction is linked to a significant increase in the total viscous dissipation and to zero dissipation in the lubricant (similar to the one given by a no-slip boundary).

Detection of Nanobubbles on Lubricant-Infused Surfaces Using AFM Meniscus Force Measurements.

So far, the presence of nanobubbles on lubricant-infused surfaces (LIS) has been overlooked, because of the difficulty in detecting them in such a complex system. We recently showed that anomalously large interfacial slip measured on LIS is explained by the presence of nanobubbles [Vega-Sánchez, Peppou-Chapman, Zhu and Neto, Nat. Commun., 2022 13, 351]. Crucial to drawing this conclusion was the use of atomic force microscopy (AFM) force-distance spectroscopy (meniscus force measurements) to directly image nanobubbles on LIS. This technique provided vital direct evidence of the spontaneous nucleation of nanobubbles on lubricant-infused hydrophobic surfaces. In this paper, we describe in detail the data collection and analysis of AFM meniscus force measurements on LIS and show how these powerful measurements can quantify both the thickness and distribution of multiple coexisting fluid layers (i.e., gas and oil) over a nanostructured surface. Using this technique, thousands of force curves were automatically analyzed. The results show that the interfacial tension of the nanobubbles is reduced from 52 ± 9 mN m-1 to 39 ± 4 mN m-1 by the presence of the silicone oil layer.

Preoperative predictors of pathological lymph node metastasis in patients with renal cell carcinoma undergoing retroperitoneal lymph node dissection.

PURPOSE: Patients with locally advanced renal cell carcinoma represent a subset that may benefit from retroperitoneal lymph node dissection. We identified preoperative clinical predictors of positive lymph nodes in patients with renal cell carcinoma without distant metastasis who underwent retroperitoneal lymph node dissection. MATERIALS AND METHODS: We retrospectively analyzed data on a consecutive cohort of 1,270 patients with cTany Nany M0 renal cell carcinoma who were treated at a single institution from 1993 to 2012. Multivariate analysis was performed to determine preoperative predictors of pathologically positive lymph nodes in patients who underwent retroperitoneal lymph node dissection. A nomogram was developed to predict the probability of lymph node metastasis. Overall, cancer specific and recurrence-free survival was estimated using the Kaplan-Meier Method. RESULTS: We identified 1,270 patients with renal cell carcinoma without distant metastasis who had (564) or did not have (706) retroperitoneal lymph node dissection performed. Of the 564 patients 131 (23%) and 433 (77%) had pN1 and pN0 disease, and 60 (37%) and 29 (7.2%) had cN1pN0 and cN0pN1 disease, respectively. ECOG PS, cN stage, local symptoms and lactate dehydrogenase were associated with nodal metastasis on multivariable analysis. A nomogram was developed with a C-index of 0.89 that demonstrated excellent calibration. Differences in overall, cancer specific and recurrence-free survival among pNx, pN0 and pN1 cases were statistically significant (p <0.001). CONCLUSIONS: Local symptoms, ECOG PS, cN stage and lactate dehydrogenase were independent predictors of lymph node metastasis in patients who underwent retroperitoneal lymph node dissection. Our predictive nomogram using these factors showed excellent discrimination and calibration.

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 graft-versus-host disease.

Acute lower gastrointestinal GVHD (aLGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation. Although the intestinal microbiota is associated with the incidence of aLGI-GVHD, how the intestinal microbiota impacts treatment responses in aLGI-GVHD has not been thoroughly studied. In a cohort of patients with aLGI-GVHD (n = 37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and a disrupted fecal microbiome characterized by reduced abundances of Bacteroides ovatus. In a murine GVHD model aggravated by carbapenem antibiotics, introducing B. ovatus reduced GVHD severity and improved survival. These beneficial effects of Bacteroides ovatus were linked to its ability to metabolize dietary polysaccharides into monosaccharides, which suppressed the mucus-degrading capabilities of colonic mucus degraders such as Bacteroides thetaiotaomicron and Akkermansia muciniphila, thus reducing GVHD-related mortality. Collectively, these findings reveal the importance of microbiota in aLGI-GVHD and therapeutic potential of B. ovatus.

Microbiome alteration via fecal microbiota transplantation is effective for refractory immune checkpoint inhibitor-induced colitis.

Immune checkpoint inhibitors (ICIs) target advanced malignancies with high efficacy but also predispose patients to immune-related adverse events like immune-mediated colitis (IMC). Given the association between gut bacteria with response to ICI therapy and subsequent IMC, fecal microbiota transplantation (FMT) represents a feasible way to manipulate microbial composition in patients, with a potential benefit for IMC. Here, we present a large case series of 12 patients with refractory IMC who underwent FMT from healthy donors as salvage therapy. All 12 patients had grade 3 or 4 ICI-related diarrhea or colitis that failed to respond to standard first-line (corticosteroids) and second-line immunosuppression (infliximab or vedolizumab). Ten patients (83%) achieved symptom improvement after FMT, and three patients (25%) required repeat FMT, two of whom had no subsequent response. At the end of the study, 92% achieved IMC clinical remission. 16S rRNA sequencing of patient stool samples revealed that compositional differences between FMT donors and patients with IMC before FMT were associated with a complete response after FMT. Comparison of pre- and post-FMT stool samples in patients with complete responses showed significant increases in alpha diversity and increases in the abundances of Collinsella and Bifidobacterium, which were depleted in FMT responders before FMT. Histologically evaluable complete response patients also had decreases in select immune cells , including CD8+ T cells, in the colon after FMT when compared with non-complete response patients (n = 4). This study validates FMT as an effective treatment strategy for IMC and gives insights into the microbial signatures that may play a critical role in FMT response.

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.

Nanobubbles explain the large slip observed on lubricant-infused surfaces.

Lubricant-infused surfaces hold promise to reduce the huge frictional drag that slows down the flow of fluids at microscales. We show that infused Teflon wrinkled surfaces induce an effective slip length 50 times larger than expected based on the presence of the lubricant alone. This effect is particularly striking as it occurs even when the infused lubricant's viscosity is several times higher than that of the flowing liquid. Crucially, the slip length increases with increasing air content in the water but is much higher than expected even in degassed and plain Milli-Q water. Imaging directly the immersed interface using a mapping technique based on atomic force microscopy meniscus force measurements reveals that the mechanism responsible for this huge slip is the nucleation of surface nanobubbles. Using a numerical model and the height and distribution of these surface nanobubbles, we can quantitatively explain the large fluid slip observed in these surfaces.

Transpelvic Magnetic Stimulation Enhances Penile Microvascular Perfusion in a Rat Model: A Novel Interventional Strategy to Prevent Penile Fibrosis after Cavernosal Nerve Injury.

PURPOSE: Penile microvascular dysfunction is a known contributor to erectile dysfunction (ED) and penile fibrosis has been shown to impair microvascular perfusion (MVP). Our objectives were to: (i) determine beneficial effects of TPMS to modulate penile MVP, (ii) determine its mechanism, (iii) evaluate impact of cavernosal nerve injury (CNI) on penile MVP, and (iv) determine time-course of cavernosal tissue elastin changes after CNI in rats. MATERIALS AND METHODS: Adult male rats (n=5) were anesthetized and subjected to TPMS (13%, 15%, and 17%) and MVP changes were recorded using laser speckle contrast imaging (LSCI). Another group of male rats were subjected to either bilateral cavernosal nerve injury (CNI; n=7) or sham surgery (n=7). After recovery, animals were monitored for MVP using LSCI before and after TPMS. Rat penile tissues were harvested and analyzed for fibrosis using a marker for elastin. RESULTS: Rat TPMS resulted in a stimulus dependent increase in MVP; maximal perfusion was observed at 17%. L-N(G)-Nitroarginine methyl ester (L-NAME) resulted in a marked decrease in TPMS induced MVP increase (393.33 AU vs. 210.67 AU). CNI resulted in 40% to 50% decrease in MVP. CNI produced a remarkable increase in elastin deposits that are noticeable throughout the cavernosal tissues post injury. CONCLUSIONS: TPMS is a novel and non-invasive intervention to improve penile MVP after CNI. Potential application includes treatment of ED and sexual function preservation following cancer treatment, possibly through improved penile hemodynamics that might help prevent penile hypoxia and fibrosis.

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.