TULIP 5

International audienceTulip is an information visualization framework dedicated to the analysis and visualization of relational data. Based on more than 16 years of research and development, Tulip is built on a suite of tools and techniques, that can be used to address a large variety of domain-specific problems. With \tulip, we aim to provide Python and/or C++ developers a complete library, supporting the design of interactive information visualization applications for relational data, that can be customized to address a wide range of visualization problems. In its current iteration, \tulip enables the development of algorithms, visual encodings, interaction techniques, data models, and domain-specific visualizations. This development pipeline makes the framework efficient for creating research prototypes as well as developing end-user applications. The recent addition of a complete Python programming layer wraps up Tulip as an ideal tool for fast prototyping and treatment automation, allowing to focus on problem solving, and as a great system for teaching purposes at all education levels

Establishment of a consensus protocol to explore the brain pathobiome in patients with mild cognitive impairment and Alzheimer\u27s disease: Research outline and call for collaboration.

Microbial infections of the brain can lead to dementia, and for many decades microbial infections have been implicated in Alzheimer\u27s disease (AD) pathology. However, a causal role for infection in AD remains contentious, and the lack of standardized detection methodologies has led to inconsistent detection/identification of microbes in AD brains. There is a need for a consensus methodology; the Alzheimer\u27s Pathobiome Initiative aims to perform comparative molecular analyses of microbes in post mortem brains versus cerebrospinal fluid, blood, olfactory neuroepithelium, oral/nasopharyngeal tissue, bronchoalveolar, urinary, and gut/stool samples. Diverse extraction methodologies, polymerase chain reaction and sequencing techniques, and bioinformatic tools will be evaluated, in addition to direct microbial culture and metabolomic techniques. The goal is to provide a roadmap for detecting infectious agents in patients with mild cognitive impairment or AD. Positive findings would then prompt tailoring of antimicrobial treatments that might attenuate or remit mounting clinical deficits in a subset of patients

Synchronous adenocarcinoma and carcinoid tumor of the terminal ileum in a Crohn's disease patient

BACKGROUND: Several malignancies have been described in association with inflammatory bowel diseases, the most common being adenocarcinoma. Carcinoid tumor and Crohn disease has also been previously reported, however the coexistence of both neoplasms is quite rare and the clinical diagnosis is very difficult. Here we report what we believe to be the fourth case of a mixed adenocarcinoid tumor coexisting with Crohn's disease. CASE REPORT: The patient presented with clinical and radiological features of intestinal obstruction. Laparotomy showed a stricturing lesion in the last 6 cm of the terminal ileum with proximal dilation. Only the histology of the resected surgical specimen proved the presence of a mixed adenocarcinoid tumor involving the terminal ileum. CONCLUSION: Carcinoid tumor should be suspected in elderly patients with Crohn's disease presenting with intestinal obstruction and laparotomy should be considered to exclude malignancy

Congenital deficiency reveals critical role of ISG15 in skin homeostasis

Ulcerating skin lesions are manifestations of human ISG15 deficiency, a type I interferonopathy. However, chronic inflammation may not be their exclusive cause. We describe two siblings with recurrent skin ulcers that healed with scar formation upon corticosteroid treatment. Both had a homozygous nonsense mutation in the ISG15 gene, leading to unstable ISG15 protein lacking the functional domain. We characterized ISG15(-/-) dermal fibroblasts, HaCaT keratinocytes, and human induced pluripotent stem cell-derived vascular endothelial cells. ISG15-deficient cells exhibited the expected hyperinflammatory phenotype, but also dysregulated expression of molecules critical for connective tissue and epidermis integrity, including reduced collagens and adhesion molecules, but increased matrix metalloproteinases. ISG15(-/-) fibroblasts exhibited elevated ROS levels and reduced ROS scavenger expression. As opposed to hyperinflammation, defective collagen and integrin synthesis was not rescued by conjugation-deficient ISG15. Cell migration was retarded in ISG15(-/-) fibroblasts and HaCaT keratinocytes, but normalized under ruxolitinib treatment. Desmosome density was reduced in an ISG15(-/-) 3D epidermis model. Additionally, there were loose architecture and reduced collagen and desmoglein expression, which could be reversed by treatment with ruxolitinib/doxycycline/TGF-beta 1. These results reveal critical roles of ISG15 in maintaining cell migration and epidermis and connective tissue homeostasis, whereby the latter likely requires its conjugation to yet unidentified targets

Revisited experimental comparison of node-link and matrix representations

Visualizing network data is applicable in domains such as biology, engineering, and social sciences. We report the results of a study comparing the effectiveness of the two primary techniques for showing network data: node-link diagrams and adjacency matrices. Specifically, an evaluation with a large number of online participants revealed statistically significant differences between the two visualizations. Our work adds to existing research in several ways. First, we explore a broad spectrum of network tasks, many of which had not been previously evaluated. Second, our study uses a large dataset, typical of many real-life networks not explored by previous studies. Third, we leverage crowdsourcing to evaluate many tasks with many participants

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer.

Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM -/- patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

Clinical Effectiveness of Transversus Abdominis Plane (TAP) Block versus Local Anesthesia Wound Infiltration for Postoperative Pain Relief After Laparoscopic Appendicectomy in Children: A Study Protocol for a Multicenter Double-Blind Randomized Controlled Phase III Trial

Geoffrey Bloy,1 Amelie Jurine,1 Yann Chaussy,2 Frederic Auber,2 Pierre-Gregoire Guinot,3 Belaid Bouhemad,3 Michel Francois,4 Lucie Vettoretti,1 Sebastien Pili-Floury,5 Maxime Nguyen,3 Guillaume Besch5 1CHU Besançon, Département d’Anesthésie Réanimation Chirurgicale, Besançon, F-25000, France; 2Université de Franche-Comté, CHU Besançon, SINERGIES, Service de Chirurgie Pédiatrique, Besançon, F-25000, France; 3University of Burgundy and Franche-Comté, Dijon University Hospital, INSERM LNC UMR1231, FCS Bourgogne Franche-Comté LipSTIC LabEx, Dijon, F-21000, France; 4Université de Bourgogne, CHU Dijon, Service de Chirurgie Pédiatrique, Dijon, F-21000, France; 5Université de Franche-Comté, CHU Besançon, SINERGIES, Département d’Anesthésie Réanimation Chirurgicale, Besançon, F-25000, FranceCorrespondence: Guillaume Besch, Département d’Anesthésie Réanimation Chirurgicale, CHU Besançon, 3 bvd Alexandre Fleming, Besançon, 25030, France, Tel +3381218958, Fax +3381669331, Email [email protected]: Postoperative pain relief after laparoscopic appendicectomy is a key determinant of early rehabilitation in children. Recent guidelines recommend performing either a transversus abdominis plane (TAP) block or local anesthesia (LA) wound infiltration as part of multimodal postoperative analgesia after appendectomy. To date, the clinical effectiveness of TAP block versus LA wound infiltration has never been compared. The hypothesis of this study is that the TAP block may provide a greater opioid-sparing effect after laparoscopic appendicectomy in children than LA wound infiltration.Study Design and Methods: We designed a multicenter double-blind randomized controlled phase III trial and aim to include 110 children who undergo laparoscopic appendicectomy. Children are randomized to receive either TAP block (TAP group) or LA wound infiltration (infiltration group). Multimodal analgesia is standardized in the two groups using the same protocol, which includes the stepwise prescription of paracetamol, phloroglucinol, ketoprofene, and nalbuphine according to the hetero-evaluation of pain performed by the nurses who were blinded to the treatment allocated using the validated FLACC scale. The primary outcome is the total dose of nalbuphine administered within 24 hours after surgery.Discussion: No study has specifically compared the clinical effectiveness of TAP block versus LA wound infiltration for postoperative pain relief after laparoscopic appendectomy in children. This paper describes the protocol for a randomized trial that addresses this issue. The results of this trial will be useful for editing guidelines with a higher level of evidence on this topic.Keywords: laparoscopic appendectomy, TAP block, wound infiltration, analgesia, childre

The ecological causes of functional distinctiveness in communities

Recent work has shown that evaluating functional trait distinctiveness, the average trait distance of a species to other species in a community offers promising insights into biodiversity dynamics and ecosystem functioning. However, the ecological mechanisms underlying the emergence and persistence of functionally distinct species are poorly understood. Here, we address the issue by considering a heterogeneous fitness landscape whereby functional dimensions encompass peaks representing trait combinations yielding positive population growth rates in a community. We identify four ecological cases contributing to the emergence and persistence of functionally distinct species. First, environmental heterogeneity or alternative phenotypic designs can drive positive population growth of functionally distinct species. Second, sink populations with negative population growth can deviate from local fitness peaks and be functionally distinct. Third, species found at the margin of the fitness landscape can persist but be functionally distinct. Fourth, biotic interactions (positive or negative) can dynamically alter the fitness landscape. We offer examples of these four cases and guidelines to distinguish between them. In addition to these deterministic processes, we explore how stochastic dispersal limitation can yield functional distinctiveness. Our framework offers a novel perspective on the relationship between fitness landscape heterogeneity and the functional composition of ecological assemblages