A temporal classifier predicts histopathology state and parses acute-chronic phasing in inflammatory bowel disease patients.

Previous studies have conducted time course characterization of murine colitis models through transcriptional profiling of differential expression. We characterize the transcriptional landscape of acute and chronic models of dextran sodium sulfate (DSS) and adoptive transfer (AT) colitis to derive temporal gene expression and splicing signatures in blood and colonic tissue in order to capture dynamics of colitis remission and relapse. We identify sub networks of patient-derived causal networks that are enriched in these temporal signatures to distinguish acute and chronic disease components within the broader molecular landscape of IBD.

Towards routine employment of computational tools for antimicrobial resistance determination via high-throughput sequencing.

Antimicrobial resistance (AMR) is a growing threat to public health and farming at large. In clinical and veterinary practice, timely characterization of the antibiotic susceptibility profile of bacterial infections is a crucial step in optimizing treatment. High-throughput sequencing is a promising option for clinical point-of-care and ecological surveillance, opening the opportunity to develop genotyping-based AMR determination as a possibly faster alternative to phenotypic testing.

Anti-DFS70 Antibodies Among Patient and Healthy Population Cohorts in China: Results From a Multicenter Training Program Showing Spontaneous Abortion and Pediatric Systemic Autoimmune Rheumatic Diseases Are Common in Anti-DFS70 Positive Patients.

Objective: Anti-DFS70 antibodies correlating with the nuclear dense fine speckled (DFS) pattern in the HEp-2 indirect immunofluorescence assay (IFA) are less common in patients with systemic autoimmune rheumatic disease (SARD) than in healthy subjects and their clinical associations remain elusive. We hosted a multi-center HEp-2 IFA training program to improve the ability of clinical laboratories to recognize the DFS pattern and to investigate the prevalence and relevance of anti-DFS70 antibodies.

Methods: DFS pattern sera identified by HEp-2 IFA in 29 centers in China were redirected to a central laboratory for anti-DFS70 testing by line immunoblot assay (LIA), enzyme-linked immunosorbent assay (ELISA), and IFA with HEp-2 ELITE/DFS70-KO substrate.

Establishment of international autoantibody reference standards for the detection of autoantibodies directed against PML bodies, GW bodies, and NuMA protein.

Objectives: Reference materials are important in the standardization of autoantibody testing and only a few are freely available for many known autoantibodies. Our goal was to develop three reference materials for antibodies to PML bodies/multiple nuclear dots (MND), antibodies to GW bodies (GWB), and antibodies to the nuclear mitotic apparatus (NuMA).

Methods: Reference materials for identifying autoantibodies to MND (MND-REF), GWB (GWB-REF), and NuMA (NuMA-REF) were obtained from three donors and validated independently by seven laboratories.

Using adaptive genetic algorithms combined with high sensitivity single cell-based technology to detect bladder cancer in urine and provide a potential noninvasive marker for response to anti-PD1 immunotherapy.

Objective: To use adaptive genetic algorithms (AGA) in combination with single-cell flow cytometry technology to develop a noninvasive test to detect bladder cancer.

Materials And Methods: Fifty high grade, cystoscopy confirmed, superficial bladder cancer patients, and 15 healthy donor early morning urine samples were collected in an optimized urine collection media. These samples were then used to develop an assay to distinguish healthy from cancer patients' urine using AGA in combination with single-cell flow cytometry technology.

A negative role for the interleukin-2-inducible T-cell kinase (ITK) in human Foxp3+ TREG differentiation.

The Tec kinases ITK (interleukin-2-inducible T-cell kinase) and RLK (resting lymphocyte kinase) are critical components of the proximal TCR/CD3 signal transduction machinery, and data in mice suggest that ITK negatively modulates regulatory T cell (TREG) differentiation. However, whether Tec kinases modulate TREG development and/or function in human T cells remains unknown. Using a novel self-delivery siRNA platform (sdRNA), we found that ITK knockdown in human primary naïve peripheral blood CD4 T cells increased Foxp3+ expression under both TREG and T helper priming conditions.

Establishment of an international autoantibody reference standard for human anti-DFS70 antibodies: proof-of-concept study for a novel Megapool strategy by pooling individual specific sera.

Background International autoantibody standards, traditionally based on material obtained from plasmapheresis of single subjects, represent individual immune response and may not comprehend the heterogeneity of the general population. The anti-DFS70 autoantibody yields a characteristic dense fine speckled (DFS) nuclear pattern on indirect immunofluorescence assay on HEp-2 cells (HEp-2 IFA) and speaks against autoimmunity. We propose a novel strategy for developing autoantibody reference standards, based on stepwise pooling of serum samples from hundreds of individuals with anti-DFS70 antibodies.

T follicular helper cells restricted by IRF8 contribute to T cell-mediated inflammation.

The follicular helper T cell (T) are established regulators of germinal center (GC) B cells, whether T have pathogenic potential independent of B cells is unknown. Based on in vitro T cell differentiation, in vivo T cell transfer animal colitis model, and intestinal tissues of inflammatory bowel disease (IBD) patients, T and its functions in colitis development were analyzed by FACS, ChIP, ChIP-sequencing, WB, ELISA and PCR. Herein we demonstrate that intestinal tissues of patients and colon tissues obtained from Rag1 recipients of naïve CD4 T cells with colitis, each over-express T-associated gene products.

Emerging microRNAs in cancer diagnosis, progression, and immune surveillance.

MicroRNAs (miRNAs) are small noncoding RNAs that function in post-transcriptional regulation of gene expression. Dysregulation of miRNAs has been reported in different stages of cancer development and progression. This dysregulation results in different miRNA profiles between cancer and normal tissues.

β7 integrins contribute to intestinal tumor growth in mice.

The gut homing receptor integrin α4β7 is essential for the migration of pro-inflammatory T cells into the gut mucosa. Since intestinal neoplasia has been associated with chronic inflammation, we investigated whether interfering with gut-homing affects intestinal tumorigenesis. Using chemically induced and spontaneous intestinal tumor models we showed that lack of β7 integrin significantly impairs tumor growth without affecting tumor frequencies, with a mild translatable effect on overall survival.

Building a Personalized Cancer Treatment System.

This paper reports the process by which a personalized cancer treatment system was built, following a user-centered approach. We give some background on personalized cancer treatment, the particular tumor chemosensitivity assay supported by the system, as well as some quality and legal issues related to such health systems. We describe how Contextual Design was applied when building the system.

β8 Integrin Expression and Activation of TGF-β by Intestinal Dendritic Cells Are Determined by Both Tissue Microenvironment and Cell Lineage.

Activation of TGF-β by dendritic cells (DCs) expressing αvβ8 integrin is essential for the generation of intestinal regulatory T cells (Tregs) that in turn promote tolerance to intestinal Ags. We have recently shown that αvβ8 integrin is preferentially expressed by CD103(+) DCs and confers their ability to activate TGF-β and generate Tregs. However, how these DCs become specialized for this vital function is unknown.

Intestinal microbiota sustains inflammation and autoimmunity induced by hypomorphic RAG defects.

Omenn syndrome (OS) is caused by hypomorphic Rag mutations and characterized by a profound immunodeficiency associated with autoimmune-like manifestations. Both in humans and mice, OS is mediated by oligoclonal activated T and B cells. The role of microbial signals in disease pathogenesis is debated.

Biopiracy of natural products and good bioprospecting practice.

Background: Biopiracy mainly focuses on the use of biological resources and/or knowledge of indigenous tribes or communities without allowing them to share the revenues generated out of economic exploitation or other non-monetary incentives associated with the resource/knowledge.

Methods: Based on collaborations of scientists from five continents, we have created a communication platform to discuss not only scientific topics, but also more general issues with social relevance. This platform was termed 'PhytCancer -Phytotherapy to Fight Cancer' (www.

Vitamin A Impairs the Reprogramming of Tregs into IL-17-Producing Cells during Intestinal Inflammation.

Maintaining the identity of Foxp3(+) regulatory T cells (Tregs) is critical for controlling immune responses in the gut, where an imbalance between Tregs and T effector cells has been linked to inflammatory bowel disease. Accumulating evidence suggests that Tregs can convert into Th17 cells and acquire an inflammatory phenotype. In this study, we used an adoptive transfer model of Ag-specific T cells to study the contribution of different factors to the reprogramming of in vitro-generated Treg cells (iTreg) into IL-17-producing cells in a mouse model of gut inflammation in vivo.

SLAMF4 Is a Negative Regulator of Expansion of Cytotoxic Intraepithelial CD8+ T Cells That Maintains Homeostasis in the Small Intestine.

Background & Aims: Intraepithelial T lymphocyte cells (IEL) are the first immune cells to respond to pathogens; they help maintain the integrity of the epithelial barrier. We studied the function of the mouse glycoprotein Signaling Lymphocyte Activation Molecule Family receptor (SLAMF) 4 (encoded by Slamf4) on the surface of CD8αβ αβ T-cell receptor (TCR)(+) IELs, and the roles of these cells in homeostasis of the small intestine in mice.

Methods: SLAMF4(-) CD8(+) αβTCR(+) cells isolated from spleens of OT-I Rag1(-/-) mice were induced to express gut-homing receptors and transferred to C57BL/6J mice; levels of SLAMF4(+) cells were measured in small intestine tissues.

[A survey about client orientation and wayfinding in Chilean hospitals].

Background: Sense of orientation in hospitals can be tricky considering the large extension of buildings and the inadequate signage.

Aim: To report some of the findings of a larger research project on wayfinding and patient navigation in Chilean hospitals.

Material And Methods: Five hundred nine hospital users waiting for attention in three hospitals were contacted and asked to answer a survey that lasted 10 minutes, about wayfinding and sense of orientation within the hospital.

Interplay of nutrients and microbial metabolites in intestinal immune homeostasis: distinct and common mechanisms of immune regulation in the small bowel and colon.

The intestinal mucosa is the largest body surface exposed to the environment. While there are common features when comparing immune responses along the intestinal mucosa, the small bowel and colon exhibit striking differences in their mechanisms driving immune regulation. The vitamin A (VA) metabolite all-trans retinoic acid (RA) signaling via RA nuclear receptors plays a key role in immune homeostasis in the small bowel, and recent work indicates that RA is required for establishing immune tolerance to dietary antigens in the upper intestinal tract by inducing α4β7(+)CCR9(+) gut-tropic TREG.

Interleukin-10 receptor signaling in innate immune cells regulates mucosal immune tolerance and anti-inflammatory macrophage function.

Intact interleukin-10 receptor (IL-10R) signaling on effector and T regulatory (Treg) cells are each independently required to maintain immune tolerance. Here we show that IL-10 sensing by innate immune cells, independent of its effects on T cells, was critical for regulating mucosal homeostasis. Following wild-type (WT) CD4(+) T cell transfer, Rag2(-/-)Il10rb(-/-) mice developed severe colitis in association with profound defects in generation and function of Treg cells.

Internalization of Clostridium perfringens α-toxin leads to ERK activation and is involved on its cytotoxic effect.

Clostridium perfringens phospholipase C (CpPLC), also called α-toxin, plays a key role in the pathogenesis of gas gangrene. CpPLC may lead to cell lysis at concentrations that cause extensive degradation of plasma membrane phospholipids. However, at sublytic concentrations it induces cytotoxicity without inducing evident membrane damage.

β7 integrins are required to give rise to intestinal mononuclear phagocytes with tolerogenic potential.

Background And Objective: While pro-inflammatory monocyte trafficking to the intestine has been partially characterised, the molecules required for migration of tolerogenic mononuclear phagocytes (dendritic cells (DC) and macrophages) are unknown. We hypothesised that the gut-homing receptor integrin α4β7 is required for this process.

Methods: We used a T cell-mediated colitis model to study the role of α4β7 in the innate immune compartment.

The oxysterol-CXCR2 axis plays a key role in the recruitment of tumor-promoting neutrophils.

Tumor-infiltrating immune cells can be conditioned by molecules released within the microenvironment to thwart antitumor immune responses, thereby facilitating tumor growth. Among immune cells, neutrophils play an important protumorigenic role by favoring neoangiogenesis and/or by suppressing antitumor immune responses. Tumor-derived oxysterols have recently been shown to favor tumor growth by inhibiting dendritic cell migration toward lymphoid organs.

Study on the mechanical and environmental properties of concrete containing cathode ray tube glass aggregate.

Cathode ray tube (CRT) glass is considered a hazardous material due to its lead toxicity. In addition, current disposal practices are being phased out due to their adverse environmental impacts. In this project, CRT glass was used as a fine aggregate replacement in concrete.