Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

L’architecture domestique des sites du 3e millénaire avant notre ère dans le Nord de la France

Die Zunahme der Entdeckungen in Nordwestfrankreich erlaubt es, eine erste Bilanz der endneolithischen Siedlungsarchitektur zu ziehen. Von mehreren im Laufe der ersten Hälfte des 3. Jahrtausends vor unserer Zeit, während der größten Ausbreitung der sog. Deûle-Escaut-Gruppe, errichteten Holzbauten konnten die gut erhaltenen Grundrisse komplett rekonstruiert, in ihren geographischen Kontext eingeordnet und in Hinsicht auf ihre Größe und Konstruktionstechniken miteinander verglichen werden. Die unterschiedlichen Architekturformen entsprechen vermutlich unterschiedlichen Funktionen. Einige imposante Gebäude weisen einen unleugbaren Prunkcharakter auf ; einige Fundplätze liegen in Einhegungen, die von Palisaden umgeben sind. Am anderen Ende des Areals liegt eine kleine Anzahl von Gebäuden bescheidenen Ausmaßes in Bereichen ohne Umfriedung, zudem wurde eine größere Anzahl von Gebäuden mittlerer Größe, mit einer Fläche von über 100 m ² entdeckt. Trotz offensichtlicher Unterschiede sind die Ähnlichkeiten zahlreich. Die Beibehaltung der Proportionen in der Organisation der Innenflächen und die Übertragung der Architekturmodelle über relativ weite Entfernungen veranschaulichen, dass das Wissen zwischen 2900 und 2400 vor unserer Zeit weitergegeben wurde. Die morphologischen Variationen dieser Wohnstrukturen über fünf Jahrhunderte, bieten die Gelegenheit ein typochronologisches Entwicklungsmodell für Nordfrankreich vorzuschlagen.The many discoveries of buildings in the North of France allow to present a first assessment on the domestic architecture of the end of the Neolithic. From several complete and well preserved plans, these wooden buildings constructed in the the first half of the IIIrd millennium BC during the main expansion of the group Deûle-Escaut, were placed back in their geographical contexts, dimensions and constructions systems compared. Different architectures probably reveal several functions. Some buildings have an undeniable ostentatious character and some settlements are surrounded with fences. A few small buildings, less frequent, are located in open spaces next to medium-sized buildings, with floor surfaces which exceeding 100 sq m. In spite of big differences, the resemblances are numerous. Preservation of the proportions in the internal organization and similar architectural patterns from one building to another, throughout a wide geographical area, illustrate a know-how sharing evolving between 2900 and 2400 BC. Morphological variations of these features overof five centuries offer the opportunity to propose a model of typo-chronological evolution for Northern France.La multiplication des découvertes de bâtiments dans le Nord-Ouest de la France permet de présenter un premier bilan sur l’architecture domestique de la fin du Néolithique. à partir de plusieurs plans complets et bien conservés, ces architectures de bois édifiées dans le courant de la première moitié du IIIe millénaire avant notre ère lors de l’expansion principale du groupe Deûle-Escaut, ont été replacées dans leur contexte géographique et confrontées dans leurs dimensions et leurs systèmes de construction. Les diverses architectures illustrent probablement des fonctions différentes. Certains édifices massifs affichent un caractère ostentatoire indéniable et quelques gisements se développent au sein d’enclos palissadés. A l’autre extrémité, de petits bâtiments, peu nombreux, sont implantés dans des espaces ouverts à côté de bâtiments de taille moyenne, les plus nombreux, dont les surfaces au sol sont toutefois supérieures à 100 m ² . Malgré des différences indéniables, les similitudes sont nombreuses. Le maintien des proportions dans l’organisation des espaces internes et les modèles architecturaux appliqués d’un édifice à l’autre, sur des distances géographiques relativement importantes, illustrent un partage des savoir-faire évoluant entre 2900 et 2400 avant notre ère. Les variations morphologiques de ces structures d’habitat, sur une séquence longue de cinq siècles, offrent l’opportunité de proposer un modèle d’évolution typo-chronologique pour le Nord de la France.Joseph Frédéric, Julien Maël, Leroy-Langelin Emmanuelle, Lorin Yann, Praud Ivan. L’architecture domestique des sites du 3e millénaire avant notre ère dans le Nord de la France. In: Revue archéologique de Picardie. Numéro spécial 28, 2011. pp. 249-273

Reward and punishment learning deficits among bipolar disorder subtypes

Objectives: Bipolar disorder (BD) is defined by alternation of depressive and (hypo)manic states. An essential dimension related to mood fluctuations is reward sensitivity. The expression of mood disorders can be modulated by environmental factors and life events, as well as by their subsequent learning related to reward or punishment sensitivity. According to the dimensional focus of the Research Domain Criteria, BD subtypes may be conceptualized as a spectrum in which reward sensitivity is a key dimension of pathology. Here, we examine reward maximizations vs. punishment avoidance learning in patients with BD during intercritical phase to test this hypothesis. Methods: Patients with BD-I (n=45), BD-II (n=34) and age and gender matched (n=30) healthy controls (HC) participated to the study. They performed an instrumental learning task designed to dissociate reward-based from punishment-based reinforcement learning. Computational modeling was used to identify the mechanisms underlying reinforcement learning performance. Results: Behavioral results showed a significant reward learning deficit across BD subtypes compared to HC. Conversely, BD-I patients performed better during punishment avoidance learning than BD-II patients. Computational analysis indicated that the observed reward-based learning deficit was captured by a lower reinforcement magnitude in both BD subtypes, when compared to HC. The punishment-based learning deficit was captured by a higher choice randomness in the BD-II compared to BD-I patients’ group. Conclusions: Our results are consistent with the reward hyposensitivity theory in BD. Furthermore, our results also suggest that studying punishment avoidance learning across BD subtypes could be useful for classification and consequent treatment tailoring in BD

Neural interactions in the human frontal cortex dissociate reward and punishment learning

How human prefrontal and insular regions interact while maximizing rewards and minimizing punishments is unknown. Capitalizing on human intracranial recordings, we demonstrate that the functional specificity toward reward or punishment learning is better disentangled by interactions compared to local representations. Prefrontal and insular cortices display non-selective neural populations to reward and punishment. The non-selective responses, however, give rise to context-specific interareal interactions. We identify a reward subsystem with redundant interactions between the orbitofrontal and ventromedial prefrontal cortices, with a driving role of the latter. In addition, we find a punishment subsystem with redundant interactions between the insular and dorsolateral cortices, with a driving role of the insula. Finally, switching between reward and punishment learning is mediated by synergistic interactions between the two subsystems. These results provide a unifying explanation of distributed cortical representations and interactions supporting reward and punishment learning

Bacterial survival in radiopharmaceutical solutions: a critical impact on current practices

Abstract Background The aim of this brief communication is to highlight the potential bacteriological risk linked to the processes control of radiopharmaceutical preparations made in a radiopharmacy laboratory. Survival rate of Pseudomonas aeruginosa (ATCC: 27853) or Staphylococcus aureus (ATCC: 25923) or Staphylococcus epidermidis (ATCC: 1228) in multidose technetium-99 m solution was studied. Results Depending on the nature and level of contamination by pathogenic bacteria, the lethal effect of radioactivity is not systematically observed. We found that P. aeruginosa was indeed affected by radioactivity. However, this was not the case for S. epidermidis, as the quantity of bacteria found in both solutions (radioactive and non-radioactive) was rapidly reduced, probably due to a lack of nutrients. Finally, the example of S. aureus is an intermediate case where we observed that high radioactivity affected the bacteria, as did the absence of nutrients in the reaction medium. The results were discussed in the light of current practices on the sterility test method, which recommends waiting for radioactivity to decay before carrying out the sterility test. Conclusion In terms of patient safety, the results run counter to current practice and the latest EANM recommendation of 2021 that radiopharmaceutical preparations should be decayed before sterility testing

Predict Score: A New Biological and Clinical Tool to Help Predict Risk of Intensive Care Transfer for COVID-19 Patients

International audienceBackground: The COVID-19 crisis has strained world health care systems. This study aimed to develop an innovative prediction score using clinical and biological parameters (PREDICT score) to anticipate the need of intensive care of COVID-19 patients already hospitalized in standard medical units. Methods: PREDICT score was based on a training cohort and a validation cohort retrospectively recruited in 2020 in the Marseille University Hospital. Multivariate analyses were performed, including clinical, and biological parameters, comparing a baseline group composed of COVID-19 patients exclusively treated in standard medical units to COVID-19 patients that needed intensive care during their hospitalization. Results: Independent variables included in the PREDICT score were: age, Body Mass Index, Respiratory Rate, oxygen saturation, C-reactive protein, neutrophil–lymphocyte ratio and lactate dehydrogenase. The PREDICT score was able to correctly identify more than 83% of patients that needed intensive care after at least 1 day of standard medical hospitalization. Conclusions: The PREDICT score is a powerful tool for anticipating the intensive care need for COVID-19 patients already hospitalized in a standard medical unit. It shows limitations for patients who immediately need intensive care, but it draws attention to patients who have an important risk of needing intensive care after at least one day of hospitalization

KDM6B drives epigenetic reprogramming associated with lymphoid stromal cell early commitment and immune properties

International audienceMature lymphoid stromal cells (LSCs) are key organizers of immune responses within secondary lymphoid organs. Similarly, inflammation-driven tertiary lymphoid structures depend on immunofibroblasts producing lymphoid cytokines and chemokines. Recent studies have explored the origin and heterogeneity of LSC/immunofibroblasts, yet the molecular and epigenetic mechanisms involved in their commitment are still unknown. This study explored the transcriptomic and epigenetic reprogramming underlying LSC/immunofibroblast commitment. We identified the induction of lysine demethylase 6B (KDM6B) as the primary epigenetic driver of early immunofibroblast differentiation. In addition, we observed an enrichment for KDM6B gene signature in murine inflammatory fibroblasts and pathogenic stroma of patients with autoimmune diseases. Last, KDM6B was required for the acquisition of LSC/immunofibroblast functional properties, including the up-regulation of CCL2 and the resulting recruitment of monocytes. Overall, our results reveal epigenetic mechanisms that participate in the early commitment and immune properties of immunofibroblasts and support the use of epigenetic modifiers as fibroblast-targeting strategies in chronic inflammation

Cartographie du phosphore dans des bâtiments allongés du Néolithique dans le Nord de la France, en Belgique et au Luxembourg

Ziel dieser Arbeit ist ein besseres Verständnis der Funktionszuweisung der neolithischen Langbauten mittels Verteilungskarten des Phosphors und deren Evolution. Ein besonderer Akzent liegt auf den jüngeren Studien mehrerer endneolithischer Häuser. Die Karten wurden mithilfe von systematischen Phosphortests und einigen gezielteren Gesamt-Phosphatanalysen erstellt. Im Bereich der Funktionszuweisung und der Organisation der Gebäude zeichnen sich bereits einige Tendenzen ab, selbst wenn nicht alle Studien dieser Gebäude abgeschlossen sind. Die ersten Ergebnisse lassen grundlegende Aspekte der Methodologie und Taphonomie erkennen und ermöglichen es die zukünftigen Studien in den betroffenen Regionen zu orientieren.The goal of this paper is a better understanding of the use of neolithic longhouses by phosphorus cartographies, as well as the evolution of this use. A special accent is put on most recent results that include a number of Late Neolithic houses. The cartographies have been based on systematic phosphorus tests and some more focalized analyses of total phosphate. Certain tendencies are appearing in terms of house organisation and use, even if all the studies and analyses are not yet finalized. Some fundamental aspects of methodology and taphonomy are also the result of these first attempts and permit to orient future studies in the concerned regions.L’objectif de ce travail est la meilleure compréhension de l’affectation des bâtiments allongés du Néolithique par le biais de cartographies du phosphore et de leur évolution. Un accent particulier est mis sur les dernières études récentes qui comprennent plusieurs maisons du Néolithique final. Les cartographies ont été menées à l’aide de tests de phosphore systématiques et de quelques analyses de phosphate total plus ciblées. Certaines tendances se dessinent en matière d’affectation et d’organisation des bâtiments, même si les études de ces bâtiments ne sont pas toutes achevées. Des aspects fondamentaux de méthodologie et de taphonomie ressortent de ces premiers résultats et permettent d’orienter les études futures dans les régions concernées.Fechner Kai, De Lil Agnès, Clavel Viviane, Hus Jozef, Teheux Eric, Broes Frédéric, Dugois Fred, Elleboode Emmanuelle, Fournand Sandrine, Gaillard Denis, Heller Frédéric, Julien Maël, Leroy-Langelin Emmanuelle, Lorin Yann, Marchal Jean-Philippe, Naton Henri-Georges, Poirier Christian, Praud Ivan, Slachmuylder Jean-Louis. Cartographie du phosphore dans des bâtiments allongés du Néolithique dans le Nord de la France, en Belgique et au Luxembourg. In: Revue archéologique de Picardie. Numéro spécial 28, 2011. pp. 275-298

Argininosuccinic aciduria fosters neuronal nitrosative stress reversed by Asl gene transfer

Argininosuccinate lyase (ASL) belongs to the hepatic urea cycle detoxifying ammonia, and the citrulline-nitric oxide (NO) cycle producing NO. ASL-deficient patients present argini-nosuccinic aciduria characterised by hyperammonaemia, multiorgan disease and neurocognitive impairment despite treatment aiming to normalise ammonaemia without considering NO imbalance. Here we show that cerebral disease in argininosuccinic aciduria involves neuronal oxidative/nitrosative stress independent of hyperammonaemia. Intravenous injection of AAV8 vector into adult or neonatal ASL-deficient mice demonstrates long-term correction of the hepatic urea cycle and the cerebral citrulline-NO cycle, respectively. Cerebral disease persists if ammonaemia only is normalised but is dramatically reduced after correction of both ammonaemia and neuronal ASL activity. This correlates with behavioural improvement and reduced cortical cell death. Thus, neuronal oxidative/nitrosative stress is a distinct pathophysiological mechanism from hyperammonaemia. Disease amelioration by simultaneous brain and liver gene transfer with one vector, to treat both metabolic pathways, provides new hope for hepatocerebral metabolic diseases

Unravelling the intra-familial correlations and heritability of tumor types in MEN1, a GTE study.

BACKGROUND: Multiple Endocrine Neoplasia syndrome type 1 (MEN1), which is secondary to mutation of the MEN1 gene, is a rare autosomal-dominant disease that predisposes mutation carriers to endocrine tumors. Most studies demonstrated the absence of direct genotype-phenotype correlations. The existence of a higher risk of death in the GTE-cohort associated with a mutations in the JunD interacting domain, suggests heterogeneity across families in disease expressivity. This study aims to assess the existence of modifying genetic factors by estimating the intra-familial correlations and heritability of the six main tumor types in MEN1. METHODS: The study included 797 patients from 265 kindred and studied seven phenotypic criteria: parathyroid and pancreatic neuroendocrine tumors (NETs), pituitary, adrenal, bronchial and thymic tumors (ThNETs) and the presence of metastasis. Intra-familial correlations and heritability estimates were calculated from family tree data using specific validated statistical analysis software. RESULTS: Intra-familial correlations were significant and decreased along parental degrees distance for pituitary, adrenal and th-NETs. The heritability of these three tumor types was consistently strong and significant with 64% (Standard Error [SE]=0.13; p < 0.001) for pituitary tumor, 65% (SE=0,21; p < 0.001) for adrenal tumors, and 97% (SE=0.41; p=0.006) for thNETs. CONCLUSION: The present study shows the existence of modifying genetic factors for thymus, adrenal and pituitary MEN1 tumor types. The identification of at-risk subgroups of individuals within cohorts is the first step towards personalization of care. Next generation sequencing on this subset of tumors will help identify the molecular basis of MEN1 variable genetic expressivity