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We present a design space for displays in public libraries; more specifically public displays related to events taking place in the library. The design space is developed from the perspective of the librarians and is intended to support libraries in rethinking, developing, and employing displays to communicate and support the events they host. It is based on a study of 18 concepts co-designed in eight participatory workshops scaling participation to a total of 88 professional librarians. By analyzing the concepts through inductive and iterative analysis, we have defined a design space consisting of 12 aspects, categorized in four themes: interaction-, content-, event-, and display-centric. We argue that the design space can both serve as (1) an analytical tool for understanding and categorizing information displays and identifying overarching design considerations and (2) a generative framework to inspire design across a wide variety of libraries.

Abstract Background Uterine clear cell carcinomas (CCC) represent less than 5% of uterine cancers. Their biological characteristics and clinical management remain uncertain. A multicenter study to explore both clinical and molecular features of these rare tumors was conducted. Methods This multicenter retrospective national study was performed within the French TMRG (Rare Gynecologic Malignant Tumors) network. Clinical data and, when available, FFPE blocks were collected. Clinical features, treatments, and outcome (progression-free survival (PFS) and overall survival (OS)) were analyzed and correlated to the protein (tissue micro-array), RNA (Nanostring nCounter® technology), and DNA (array-Comparative Genomic hybridization and target-next generation sequencing) levels using the tumor samples available. Results Sixty-eight patients with uterine CCC were enrolled, 61 from endometrial localization and 5 with cervix localization. Median age at diagnosis was 68.9 years old (range 19–89.7). Most tumors were diagnosed at an early stage (78% FIGO stage I–II). Hysterectomy (performed in 90%) and lymph node dissection (80%) were the most frequent surgical treatment. More than 70% of patients received external beam radiotherapy and 57% received brachytherapy. Nearly half (46%) of the patients received chemotherapy. After a median follow-up of 24.7 months, median PFS was 64.8 months (95 CI [5.3–124.4]) and median OS was 79.7 (IC95 [31.0–128.4]). Low hormone receptor expression (13% estrogen-receptor positive), frequent PI3K pathway alterations (58% PTEN loss, 50% PIK3CA mutations), and P53 abnormalities (41%) were observed. Mismatch repair deficiency was identified in 20%. P16 expression was associated with shorter PFS (HR = 5.88, 95 CI [1.56–25], p = 0.009). Transcriptomic analyzes revealed a specific transcriptomic profile notably with a high expression of immune response-associated genes in uterine CCC displaying a very good overall prognosis. Conclusions Uterine CCC reported to be potentially MSI high, hormone receptors negative, and sometimes TP53 mutated. However, some patients with immune response-associated features and better prognosis may be candidate to treatment de-escalation and immunotherapy.

Objective Two cohort studies in patients with multisystem inflammatory syndrome in children (MIS‐C) demonstrated contrasting results regarding the benefit of initial immunomodulatory treatment with intravenous immunoglobulin (IVIG) alone versus IVIG and glucocorticoids. We sought to determine whether application of different MIS‐C definitions and differing disease severity between cohorts underlay discrepant results. Methods The Overcoming COVID‐19 Public Health Surveillance Registry (OC‐19) included patients meeting the US Centers for Disease Control and Prevention (CDC) MIS‐C definition, whereas the Best Available Treatment Study (BATS) applied the World Health Organization (WHO) definition. We applied the WHO definition to the OC‐19 cohort and the CDC definition to the BATS cohort and determined the proportion that did not meet the alternate definition. We compared illness severity indicators between cohorts. Results Of 349 OC‐19 patients, 9.5% did not meet the WHO definition. Of 350 BATS patients, 10.3% did not meet the CDC definition. Most organ system involvement was similar between the cohorts, but more OC‐19 patients had WHO‐defined cardiac involvement (87.1% vs 79.4%, P = 0.008). OC‐19 patients were more often admitted to intensive care (61.0% vs 44.8%, P

ABSTRACT Heptose metabolites including ADP-d-glycero-β-d-manno-heptose (ADP-heptose) are involved in bacterial lipopolysaccharide and cell envelope biosynthesis. Recently, heptoses were also identified to have potent proinflammatory activity on human cells as novel microbe-associated molecular patterns. The gastric pathogenic bacterium Helicobacter pylori produces heptose metabolites, which it transports into human cells through its Cag type 4 secretion system. Using H. pylori as a model, we have addressed the question of how proinflammatory ADP-heptose biosynthesis can be regulated by bacteria. We have characterized the interstrain variability and regulation of heptose biosynthesis genes and the modulation of heptose metabolite production by H. pylori, which impact cell-autonomous proinflammatory human cell activation. HldE, a central enzyme of heptose metabolite biosynthesis, showed strong sequence variability between strains and was also variably expressed between strains. Amounts of gene transcripts in the hldE gene cluster displayed intrastrain and interstrain differences, were modulated by host cell contact and the presence of the cag pathogenicity island, and were affected by carbon starvation regulator A (CsrA). We reconstituted four steps of the H. pylori lipopolysaccharide (LPS) heptose biosynthetic pathway in vitro using recombinant purified GmhA, HldE, and GmhB proteins. On the basis of one- and two-dimensional nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry, the structures of major reaction products were identified as β-d-ADP-heptose and β-heptose-1-monophosphate. A proinflammatory heptose-monophosphate variant was also identified for the first time as a novel cell-active product in H. pylori bacteria. Separate purified HldE subdomains and variant HldE allowed us to uncover additional strain variation in generating heptose metabolites. IMPORTANCE Bacterial heptose metabolites, intermediates of lipopolysaccharide (LPS) biosynthesis, are novel microbe-associated molecular patterns (MAMPs) that activate proinflammatory signaling. In the gastric pathogen Helicobacter pylori, heptoses are transferred into host cells by the Cag type IV secretion system, which is also involved in carcinogenesis. Little is known about how H. pylori, which is highly strain variable, regulates heptose biosynthesis and downstream host cell activation. We report here that the regulation of proinflammatory heptose production by H. pylori is strain specific. Heptose gene cluster activity is modulated by the presence of an active cag pathogenicity island (cagPAI), contact with human cells, and the carbon starvation regulator A. Reconstitution with purified biosynthesis enzymes and purified bacterial lysates allowed us to biochemically characterize heptose pathway products, identifying a heptose-monophosphate variant as a novel proinflammatory metabolite. These findings emphasize that the bacteria use heptose biosynthesis to fine-tune inflammation and also highlight opportunities to mine the heptose biosynthesis pathway as a potential therapeutic target against infection, inflammation, and cancer.

Calcium-permeable AMPA-type glutamate receptors (CP-AMPARs) contribute to many forms of synaptic plasticity and pathology. They can be distinguished from GluA2-containing calcium-impermeable AMPARs by the inward rectification of their currents, which reflects voltage-dependent channel block by intracellular spermine. However, the efficacy of this weakly permeant blocker is differentially altered by the presence of AMPAR auxiliary subunits – including transmembrane AMPAR regulatory proteins, cornichons, and GSG1L – which are widely expressed in neurons and glia. This complicates the interpretation of rectification as a measure of CP-AMPAR expression. Here, we show that the inclusion of the spider toxin analog 1-naphthylacetyl spermine (NASPM) in the intracellular solution results in a complete block of GluA1-mediated outward currents irrespective of the type of associated auxiliary subunit. In neurons from GluA2-knockout mice expressing only CP-AMPARs, intracellular NASPM, unlike spermine, completely blocks outward synaptic currents. Thus, our results identify a functional measure of CP-AMPARs, that is unaffected by their auxiliary subunit content.

Introduction: Breast cancer (BC) is frequent with a poor prognosis in case of metastasis. The role of the environment has been poorly evaluated in its progression. We searched to assess whether a mixture of pollutants could be responsible of BC aggressiveness. Methods: Patients undergoing surgery for their BC were prospectively included in the METAPOP cohort. Forty-two POPs were extracted, among them 17 dioxins (PCDD/F), 16 polychlorobiphenyls (PCB), 8 polybromodiphenylethers (PBDE) and 2,2′,4,4′,5,5′-hexabromobiphenyl (PBB153) were measured in the adipose tissue surrounding the tumor. BC aggressiveness was defined using tumor size and metastasis (distant or lymph nodes). Two complementary models were used to evaluate the impact of the mixture of pollutants: the BKMR (Bayesian Kernel machine regression) and WQS (weighted quantile sum regression) models. The WQS estimates the weight (positive or negative) of a certain chemical based on its quantile and the BKMR model applies a kernel-based approach to estimate posterior inclusion probabilities. The sub-group of patients with a body mass index (BMI) > 22 kg/ m2 was also analyzed. Results: Ninety-one patients were included. Of these, 38 patients presented a metastasis, and the mean tumor size was 25.4 mm. The mean BMI was 24.5 kg/m2 (+/- 4.1). No statistical association was found in the general population. However, in patients with a BMI > 22 kg/ m2, our mixture was positively associated with tumor size (OR: 9.73 95 %CI: 1.30–18.15) and metastasis (OR = 3.98 95 %CI = 1.09–17.53) using the WQS model. Moreover, using the BKMR model on chemical families, dioxin like chemicals and PCDD were associated with a higher risk of metastasis. Discussion: These novel findings identified a mixture associated with breast cancer aggressiveness in patients with a BMI > 22 kg/ m2.

Data management plans (DMPs) have become nearly a worldwide requirement for research funding. To meet these new funding agency expectations, information professionals across domains and the world have worked to create resources and services to successfully implement and sometimes assess DMPs. This essay presents a series of case studies from different institutions across the globe to highlight current practices and share recommendations for future work. A summary of various projects related to DMP implementation, assessment, and evaluation in different contexts provides a useful overview of current practices. The essay concludes with recommendations for practical oversight and scoring to improve DMPs’ utility in enabling the sharing of data.

Abstract Background Homologous recombination deficiency is a marker of response to poly(ADP-ribose) polymerase inhibitors in different cancer types including ovary, prostate, and pancreatic cancer. To date, no report about poly(ADP-ribose) polymerase inhibitors has been published on cervical cancer. Case presentation Here we present the case of a patient with cervical cancer treated in this setting. A 49-year-old woman diagnosed with International Federation of Obstetricians and Gynecologists stage 2018 IIIC2 locally advanced undifferentiated cervical cancer received first-line chemoradiotherapy followed by carboplatin, paclitaxel, and bevacizumab with partial response. Because of a family history of cancers, the patient was tested and found positive for a pathogenic BRCA1 germline and somatic mutation, which motivated bevacizumab plus olaparib maintenance treatment. A simple hysterectomy was performed after 2 years stable disease; pathological report showed complete pathological response, and 12 months follow-up showed no recurrence. Conclusion Poly(ADP-ribose) polymerase inhibitors could be an alternative maintenance treatment for patients with persistent advanced cervical cancer previously treated with platinum, especially when familial history of cancers is reported. Clinical trials using poly(ADP-ribose) polymerase inhibitors for advanced cervical cancer are warranted.

Abstract Breast cancer (BC) is one of the most common causes of cancer in the world and the second leading cause of cancer deaths among women. Mortality is associated mainly with the development of metastases. Identification of the mechanisms involved in metastasis formation is, therefore, a major public health issue. Among the proposed risk factors, chemical environment and pollution are increasingly suggested to have an effect on the signaling pathways involved in metastatic tumor cells emergence and progression. The purpose of this article is to summarize current knowledge about the role of environmental chemicals in breast cancer progression, metastasis formation and resistance to chemotherapy. Through a scoping review, we highlight the effects of a wide variety of environmental toxicants, including persistent organic pollutants and endocrine disruptors, on invasion mechanisms and metastatic processes in BC. We identified the epithelial-to-mesenchymal transition and cancer-stemness (the stem cell-like phenotype in tumors), two mechanisms suspected of playing key roles in the development of metastases and linked to chemoresistance, as potential targets of contaminants. We discuss then the recently described pro-migratory and pro-invasive Ah receptor signaling pathway and conclude that his role in BC progression is still controversial. In conclusion, although several pertinent pathways for the effects of xenobiotics have been identified, the mechanisms of actions for multiple other molecules remain to be established. The integral role of xenobiotics in the exposome in BC needs to be further explored through additional relevant epidemiological studies that can be extended to molecular mechanisms.

Il notevole aumento delle pratiche partecipative nelle biblioteche francesi ci porta a mettere in discussione le intenzioni che presiedono e precedono la loro attuazione. Questo articolo mira a scoprire queste intenzioni attraverso lo studio di un programma culturale partecipativo organizzato dalla Bibliothèque municipale di Lione tra novembre 2016 e marzo 2017. I documenti programmatici consultati, le interviste condotte con i bibliotecari e l’osservazione delle attività partecipative consentono di mettere in evidenza tre motivi che definiscono i ruoli che la biblioteca pubblica desidera ricoprire oggi nella società francese: la biblioteca di ‘convivialité, la biblioteca di ‘encapacitation’ e la biblioteca di ‘engagement’.

Clinical and laboratory predictors of COVID-19 severity are now well described and combined to propose mortality or severity scores. However, they all necessitate saturable equipment such as scanners, or procedures difficult to implement such as blood gas measures. To provide an easy and fast COVID-19 severity risk score upon hospital admission, and keeping in mind the above limits, we sought for a scoring system needing limited invasive data such as a simple blood test and co-morbidity assessment by anamnesis. A retrospective study of 303 patients (203 from Bordeaux University hospital and an external independent cohort of 100 patients from Paris Pitié-Salpêtrière hospital) collected clinical and biochemical parameters at admission. Using stepwise model selection by Akaike Information Criterion (AIC), we built the severity score Covichem. Among 26 tested variables, 7: obesity, cardiovascular conditions, plasma sodium, albumin, ferritin, LDH and CK were the independent predictors of severity used in Covichem (accuracy 0.87, AUROC 0.91). Accuracy was 0.92 in the external validation cohort (89% sensitivity and 95% specificity). Covichem score could be useful as a rapid, costless and easy to implement severity assessment tool during acute COVID-19 pandemic waves.

PurposeObjective structured clinical examinations (OSCE) evaluate clinical reasoning, communication skills, and interpersonal behavior during medical education. In France, clinical training has long relied on bedside clinical practice in academic hospitals. The need for a simulated teaching environment has recently emerged, due to the increasing number of students admitted to medical schools, and the necessity of objectively evaluating practical skills. This study aimed at investigating the relationships between OSCE grades and current evaluation modalities.MethodsThree-hundred seventy-nine 4th-year students of University-of-Paris Medical School participated to the first large-scale OSCE at this institution, consisting in three OSCE stations (OSCE#1-3). OSCE#1 and #2 focused on cardiovascular clinical skills and competence, whereas OSCE#3 focused on relational skills while providing explanations before planned cholecystectomy. We investigated correlations of OSCE grades with multiple choice (MCQ)-based written examinations and evaluations of clinical skills and behavior (during hospital traineeships); OSCE grade distribution; and the impact of integrating OSCE grades into the current evaluation in terms of student ranking.ResultsThe competence-oriented OSCE#1 and OSCE#2 grades correlated only with MCQ grades (r = 0.19, P0.75). Conversely, the behavior-oriented OSCE#3 grades correlated with traineeship skill and behavior grades (r = 0.19, PConclusionThis large-scale French experience showed that OSCE designed to assess a combination of clinical competence and behavioral skills, increases the discriminatory capacity of current evaluations modalities in French medical schools.

Refractive errors are common eye disorders of public health importance worldwide. Ocular axial length (AL) is the major determinant of refraction and thus of myopia and hyperopia. We conducted a meta-analysis of genome-wide association studies for AL, combining 12,531 Europeans and 8,216 Asians. We identified eight genome-wide significant loci for AL (RSPO1, C3orf26, LAMA2, GJD2, ZNRF3, CD55, MIP, and ALPPL2) and confirmed one previously reported AL locus (ZC3H11B). Of the nine loci, five (LAMA2, GJD2, CD55, ALPPL2, and ZC3H11B) were associated with refraction in 18 independent cohorts (n = 23,591). Differential gene expression was observed for these loci in minus-lens-induced myopia mouse experiments and human ocular tissues. Two of the AL genes, RSPO1 and ZNRF3, are involved in Wnt signaling, a pathway playing a major role in the regulation of eyeball size. This study provides evidence of shared genes between AL and refraction, but importantly also suggests that these traits may have unique pathways.

Objective: In this subanalysis of the prospective randomized multicenter SENTICOL 2 study, we compared the quality of life (QoL), in two arms, in association with lower-limb consequences in women with early stage cervical cancer undergoing randomized sentinel lymph node (SLN) sampling alone or SLN sampling and full pelvic lymphadenectomy.Methods: 206 patients with an early stage cervical cancer and a negative SLN, were randomized. Every patient had a SLN detection based on a combination of radio-isotope (Nanocis®) and blue dye (Bleu Patenté®) injections. One hundred and One patients, the “standard” group, had complete pelvic lymphadenectomy, 105 patients, the “SLN alone” group, had SLN biopsy without lymphadenectomy. At each visit (V0: preoperative, V1: 1 month, V2: 3 months and V3: 6 months following surgery) the patients completed a Short Form Health Survey (SF36) questionnaire and another questionnaire related to leg lymphedema. SF36 scores variations (compared to the baseline values) were assessed with a standard analysis and by an evaluation of the area under the curve (AUC). Several lower-limb circumferences and signs were also determined.Results: General characteristics of the patients were well–balanced between groups. Physical function and general health dimensions of the SF36 scale were significantly improved at V1 and V2 in the “SLN alone” group. Mental health was also statistically better in the “SLN alone” group at V2. Other dimensions were similar. The two groups had similar evaluation at V3. AUC of SF36 sub-scores was also in favor of the “SLN alone” arm, but the difference was not statistically significant. The analysis about the lymphedema of the legs showed a reduced (but not significant) risk in the “SLN alone” group for the top-of-thigh and the mid-thigh perimeters. Lymphedema symptoms reported by the patients were significantly less severe in the “SLN alone” group.Conclusion: Our study demonstrates a trend for a better quality of life and less severe leg heaviness and leg fatigue when a full pelvic lymphadenectomy is avoided.

After concomitant chemo-radiation therapy, 20 to 30% of advanced cervical cancers recur in irradiated territory. Pelvic exenteration remains a therapeutic option for selected patients. However, this procedure remains complex because of tissue fragility after radiotherapy and their associated co-morbidities. Minimally invasive surgery such as robotically assisted laparoscopy may overcome these surgical challenges. The objective of this study was to evaluate the feasibility of pelvic exenteration with robotically assisted laparoscopy.Patients who underwent this procedure between 2015 and 2016 were included. Patients characteristics, treatment indication, intraoperative events, immediate and late complications, and histological outcomes were recorded.The data of 6 patients were analyzed. The primary cancer staging ranged from IB1 to IIB. All cases were loco-regional recurrence and 2 cases presented with with vesico-vaginal fistula. All patients had a history of pelvic irradiation. The mean operative time was 6.7 h. No complications occurred during surgery. The average hospital stay was 11.5 days. Immediate complications were mostly represented by urinary tract infections (4/5). Histological margins were clear in 67% (4/6), and a focal involvement was found in 33% (2/6) of cases. Late complications occurred within 82 days on average and included stenosis of ileal anastomosis, wound infection, acute renal failure, and pulmonary embolism. Revision surgery was necessary in 2 cases. There were 3 local recurrences occurring within an average of 215 days.In the light of these results, pelvic exenteration by robotically assisted laparoscopy may represent a valuable treatment modality of recurrent cervical cancer with low immediate postoperative morbidity.

Background: Breast cancer (BC) is a major public health concern with over 2 million new cases diagnosed and over 600,000 deaths in 2018 in women worldwide. When distant metastases are present at diagnosis, the 5-year survival rate is only 26%. Recent studies have suggested that persistent organic pollutants (POPs) that accumulate in adipose tissue (AT) can influence tumor phenotype and stimulate cellular processes important for metastasis such as invasion. We, therefore, tested the hypothesis that POP exposure is associated with BC metastasis. Methods: We conducted an exploratory case-control study in which the concentrations of 49 POPs were measured in both AT and serum samples from BC patients, with or without lymph node metastasis, who underwent partial or total mastectomies, lymph node biopsies and sampling of the adipocytic tumor microenvironment. Adjusted, unconditional logistic models were used to study the associations between the POP concentrations and the risk of metastasis and other hallmarks of cancer aggressiveness. Results: 2.3.7.8-TCDD concentrations in AT are positively associated with the risk of metastasis in 43 patients who have BMIs equal or higher than 25 kg/m2 (odds ratio: 4.48 (1.32–20.71)). Furthermore, the concentrations of 2.3.7.8-TCDD and two coplanar PCBs (77&169) in AT also were positively associated with the risk of lymph node metastasis and the tumor size. Conclusion: Our study suggests that 2.3.7.8-TCDD and some PCBs contribute to the development of tumor metastasis and other hallmarks of cancer aggressiveness. While these results should be considered with caution, this is the first study to identify such potential risk factors. Larger longitudinal studies are necessary to confirm our results.Clinical Trial Protocol Record: 2013-A00663-42. Keywords: Breast cancer, Environmental exposure, Adipose tissue, Serum, Organochlorine pesticides, Endocrine disrupting chemicals, Polychlorinated biphenyls, Perfluoroalkyl acid, Dioxins