Absence of BCL-2 expression identifies a subgroup of AML with distinct phenotypic, molecular, and clinical characteristics

Acute myeloid leukemia (AML) is a hematologic malignancy characterized by the rapid and uncontrolled clonal growth of myeloid lineage cells in the bone marrow. The advent of oral, selective inhibitors of the B-cell leukemia/lymphoma-2 (BCL-2) apoptosis pathway, such as venetoclax, will likely induce a paradigm shift in the treatment of AML. However, the high cost of this treatment and the risk of additive toxicity when used in combination with standard chemotherapy represent limitations to its use and underscore the need to identify which patients are most-and least-likely to benefit from incorporation of venetoclax into the treatment regimen. Bone marrow specimens from 93 newly diagnosed AML patients were collected in this study and evaluated for BCL-2 protein expression by immunohistochemistry. Using this low-cost, easily, and readily applicable analysis method, we found that 1 in 5 AML patients can be considered as BCL-2(-). In addition to a lower bone marrow blast percentage, this group exhibited a favorable molecular profile characterized by lower WT1 expression and underrepresentation of FLT3 mutations. As compared to their BCL-2(+) counterparts, the absence of BCL-2 expression was associated with a favorable response to standard chemotherapy and overall survival, thus potentially precluding the necessity for venetoclax add-on

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Engaging Content Experience- Utilizing the Strossle recommendation capabilities, across publishers’ websites

The project aims at exploring the process of designing recommender systems from a users’ perspective. Recommendations are the systems that can help users navigate in the overload of information, that is currently available online. This project focuses on the recommender network of Strossle, which provides article recommendations across various publishers’ websites. User-centered research has been performed to understand the current system and how that influences the users’ perceived experience. The goal was to develop a more engaging content experience for the Strossle recommendation system. This is done by means of participatory design methods. As people tend to use recommendations very sporadic and they often do not really know what they are looking for. The emphasis was on finding the balance between exploratory browsing and navigating towards the users’ preferences. In order to achieve this, a more dynamic widget has been developed that offers navigation in various related topics

Engaging Content Experience- Utilizing the Strossle recommendation capabilities, across publishers’ websites

The project aims at exploring the process of designing recommender systems from a users’ perspective. Recommendations are the systems that can help users navigate in the overload of information, that is currently available online. This project focuses on the recommender network of Strossle, which provides article recommendations across various publishers’ websites. User-centered research has been performed to understand the current system and how that influences the users’ perceived experience. The goal was to develop a more engaging content experience for the Strossle recommendation system. This is done by means of participatory design methods. As people tend to use recommendations very sporadic and they often do not really know what they are looking for. The emphasis was on finding the balance between exploratory browsing and navigating towards the users’ preferences. In order to achieve this, a more dynamic widget has been developed that offers navigation in various related topics

Social attention and profiles of expressive language in young autistic children

Socio-communicative interaction is known to be central to language acquisition in typically developing (TD) children. As such, TD infants’ natural inclination for the socially relevant events in their environment is said to facilitate the acquisition process. Atypicalities in interactions with others as well as a reduced tendency to orient towards naturally occurring social stimuli lie at the core of the characterization of autism spectrum disorder. Interestingly though, despite initial and persistent socio-communicative disabilities, around 70% of autistic children eventually manage to acquire functional speech.In this dissertation, I provide an in-depth description of the social attention and linguistic abilities of 61 three- to five-year-old autistic children, including many with no or limited language, and 61 age-matched TD children. More specifically, this dissertation is divided into three parts, each of which reports studies based on specific population samples pooled from this larger sample of 122 children.Part 1 reports findings from three passive free-viewing eye-tracking tasks which target different features of visual social attention in the two groups of children. The three tasks assess whether the children are sensitive to the socially relevant information in the presented stimuli: pointing fingers, the eyes and the mouth regions, and gaze direction. Results from eye-tracking task 1 showed that autistic children failed to discriminate intentional and incidental pointing gestures. Results from eye-tracking task 2 showed that both autistic and TD children’s visual attention were attracted by the mouth as an adult started speaking, but that TD, and not autistic, children rapidly shifted their attention back to the eyes as the actor continued speaking. Results from eye-tracking task 3 showed that autistic children were sensitive to gaze direction by showing a typical preference for direct over obvious averted gaze and an atypical preference for subtle averted over direct gaze. In addition, results indicated that autistic children’s social attention abilities were not linked to either concurrent or later levels of expressive vocabulary. Overall, the results in Part 1 suggest that autistic children, regardless of their level of language, present both preserved and diminished patterns of social attention.Part 2 seeks to qualitatively describe oral productions retrieved from detailed transcriptions of naturalistic speech samples (a parent-child interaction and an experimenter-child interaction) in a subsample of 59 autistic children. A cluster analysis revealed the existence of five different patterns of linguistic behavior in this sample. The five clusters were then described and compared in terms of language, psychometric and demographic measures. Clusters 1 and 4, identified as verbal, produced mainly phrases and isolated words, respectively. Clusters 2, 3 and 5 were identified as non- or minimally verbal. Cluster 2 produced barely anything. Cluster 3 produced a fair amount of preverbal and syllabic productions. Cluster 5 produced a lot of syllabic productions, especially. Age and socioeconomic status, typical language development predictors, were not related to cluster membership. Cognitive abilities and autistic symptomatology severity, however, were related to cluster membership, with children in clusters 1 and 4 having higher cognitive abilities and milder autistic symptomatology than those in clusters 2, 3 and 5. It is very likely that the causes for the success or failure to acquire language by that point differ between clusters.Part 3 reports a detailed investigation of the structural language and acoustical specificities of the speech of a subsample of the ten most verbal autistic children, matched pairwise on age, nonverbal IQ, and socioeconomic status with a subsample of ten TD children. Results showed that, in a very strictly matched sample of autistic and TD children, few between-group differences remained in the structural language and acoustical features of their speech. The autistic children significantly differed from their peers only by a restricted use of vocabulary items during spontaneous speech (diminished lexical diversity), which is likely to be constrained by the production of echolalic utterances. This detailed analysis confirms that some autistic children are able to achieve very high levels of language in terms of structure and phonological system by preschool age.Taken together, the results of the three parts combined illustrate the great heterogeneity of language acquisition trajectories in ASD. The lack of a consistent association between typical predictors and patterns of language acquisition and language profiles in the ASD group suggest that looking at autistic language acquisition and development through an exclusively typical lens may not suffice to understand its complexity.Doctorat en Langues, lettres et traductologieinfo:eu-repo/semantics/nonPublishe

Circulations de fluides et interactions eau/roche passées et actuelles dans la pile sédimentaire du site de Meuse/Haute-Marne (apport des isotopes du Sr et conséquences)

MONTPELLIER-BU Sciences (341722106) / SudocSudocFranceF

Coding procedure for analysis of early linguistic productions

This project describes a complete coding procedure that leads to phonological and acoustics analysis of early linguistic productions. This procedure: - Consists of manual segmentation and phonetic transcription - Includes semi-automatic phone segmentation - Uses audio recordings collected in natural settings - Is applicable to a developmental window spreading from first vocal productions to first full-blown sentences - Concerns steps of both early typical language development and atypical language development located in this developmental windo