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Many patients wish to receive end-of-life care at home. Liberal professionals are necessarily called upon to help in these situations. The issues most frequently raised are the management of specific symptoms, lack of knowledge of palliative care support structures, and a feeling of isolation among caregivers., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Aplastic anaemia (AA) of the chronic type with severe cytopenia is very frequently a difficult therapeutic problem. Patients with granulocyte values below 0.5 G/l are threatened by infections, incl. sepsis possibly with a fatal outcome. If the pool of stem cells for granulocytes is not completely exhausted and can respond to growth factors, these patients can be treated either chronically and/or in risk situations (e.g. injury, surgery) with preparations of the type of a recombinant, granulocyte colony stimulating factor (rhG-CSF), or granulocyte and monocyte colony stimulating factor (rhGM-CSF). The authors present a review of diagnostic and therapeutic algorithms in patients with the AA syndrome and summarize their own experience with the preparation Neupogen Roche (rhG-CSF).

NiFe-based oxo-hydroxides are highly active for the oxygen evolution reaction but require complex synthesis and are poorly durable when deposited on foreign supports. Herein we demonstrate that easily processable, Earth-abundant and cheap Fe-Ni alloys spontaneously develop a highly active NiFe oxo-hydroxide surface, exsolved upon electrochemical activation. While the manufacturing process and the initial surface state of the alloys do not impact the oxygen evolution reaction performance, the growth/composition of the NiFe oxo-hydroxide surface layer depends on the alloying elements and initial atomic Fe/Ni ratio, hence driving oxygen evolution reaction activity. Whatever the initial Fe/Ni ratio of the Fe-Ni alloy (varying between 0.004 and 7.4), the best oxygen evolution reaction performance (beyond that of commercial IrO 2 ) and durability was obtained for a surface Fe/Ni ratio between 0.2 and 0.4 and includes numerous active sites (high Ni III /Ni II capacitive response) and high efficiency (high Fe/Ni ratio). This knowledge paves the way to active and durable Fe-Ni alloy oxygen-evolving electrodes for alkaline water electrolysers., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

In this paper, we propose a holistic AI-based pharmacovigilance optimization approach using patient's social media data. Instead of focusing on the detection and identification of Adverse Drug Events (ADE) in social media posts in single time points, we propose a holistic approach that looks at the evolution of different user behavior indicators in time. We examine various NLP-based indicators such as word frequency, semantic similarity, Adverse Drug Reactions mentions, and sentiment analysis. We introduce a classification approach to identify normal vs. abnormal time periods based on patient comments. This approach, along with user behavior indicators, can optimize the pharmacovigilance process by flagging the need for immediate attention and further investigation. We specifically focus on the Levothyrox® case in France, which sparked media attention due to changes in the medication formula and affected patient behavior on medical forums. For classification, we propose a deep learning architecture called Word Cloud Convolutional Neural Network (WC-CNN), trained on word clouds from patient comments. We evaluate different temporal resolutions and NLP pre-processing techniques, finding that monthly resolution and the proposed indicators can effectively detect new safety signals, with an accuracy of 75%. We have made the code open source, available via github., Competing Interests: Declaration of competing interest All authors have participated in (a) conception and design, or analysis and interpretation of the data; (b) drafting the article or revising it critically for important intellectual content; and (c) approval of the final version. This manuscript has not been submitted to, nor is under review at, another journal or other publishing venue. The authors have no affiliation with any organization with a direct or indirect financial interest in the subject matter discussed in the manuscript., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Efforts to modulate the function of tumor-associated myeloid cell are underway to overcome the challenges in immunotherapy and find a cure. One potential therapeutic target is integrin CD11b, which can be used to modulate the myeloid-derived cells and induce tumor-reactive T-cell responses. However, CD11b can bind to multiple different ligands, leading to various myeloid cell functions such as adhesion, migration, phagocytosis, and proliferation. This has created a major challenge in understanding how CD11b converts the differences in the receptor-ligand binding into subsequent signaling responses and using this information for therapeutic development., Methods: This study aimed to investigate the antitumor effect of a carbohydrate ligand, named BG34-200, which modulates the CD11b + cells. We have applied peptide microarrays, multiparameter FACS (fluorescence-activated cell analysis) analysis, cellular/molecular immunological technology, advanced microscopic imaging, and transgenic mouse models of solid cancers, to study the interaction between BG34-200 carbohydrate ligand and CD11b protein and the resulting immunological changes in the context of solid cancers, including osteosarcoma, advanced melanoma, and pancreatic ductal adenocarcinoma (PDAC)., Results: Our results show that BG34-200 can bind directly to the activated CD11b on its I (or A) domain, at previously unreported peptide residues, in a multisite and multivalent manner. This engagement significantly impacts the biological function of tumor-associated inflammatory monocytes (TAIMs) in osteosarcoma, advanced melanoma, and PDAC backgrounds. Importantly, we observed that the BG34-200-CD11b engagement triggered endocytosis of the binding complexes in TAIMs, which induced intracellular F-actin cytoskeletal rearrangement, effective phagocytosis, and intrinsic ICAM-1 (intercellular adhesion molecule I) clustering. These structural biological changes resulted in the differentiation in TAIMs into monocyte-derived dendritic cells, which play a crucial role in T-cell activation in the tumor microenvironment., Conclusions: Our research has advanced the current understanding of the molecular basis of CD11b activation in solid cancers, revealing how it converts the differences in BG34 carbohydrate ligands into immune signaling responses. These findings could pave the way for the development of safe and novel BG34-200-based therapies that modulate myeloid-derived cell functions, thereby enhancing immunotherapy for solid cancers., Competing Interests: Competing interests: None declared, (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Antisense ncRNAs in yeast control Tyl mobility (12,13) and PHO84 transcription through histone modifications (11,12) in an RNA-interference-independent manner14 (Supplementary Fig. 1). The regulatory ncRNAs are distinct from the canonical [...], Non-coding (nc)RNAs are key players in numerous biological processes such as gene regulation, chromatin domain formation and genome stability (1,2). Large ncRNAs interact with histone modifiers (3-5) and are involved in cancer development (6), X-chromosome inactivation (7) and autosomal gene imprinting (8). However, despite recent evidence showing that pervasive transcription is more widespread than previously thought (9), only a few examples mediating gene regulation in eukaryotes have been described (10).In Saccharomyces cerevisiae, the bona-fide regulatory ncRNAs are destabilized by the Xrn1 5'-3' RNA exonuclease (11,12) (also known as Kem1), but the genomewide characterization of the entire regulatory ncRNA family remains elusive. Here, using strand-specific RNA sequencing (RNA-seq), we identify a novel class of 1,658 Xrn1 -sensitive unstable transcripts (XUTs) in which 66% are antisense to open reading frames. These transcripts are polyadenylated and RNA polymerase II (RNAPII)-dependent. The majority of XUTs strongly accumulate in lithium-containing media, indicating that they might have a role in adaptive responses to changes in growth conditions. Notably, RNAPII chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq) analysis of Xrn1-deficient strains revealed a significant decrease of RNAPII occupancy over 273 genes with antisense XUTs. These genes show an unusual bias for H3K4me3 marks and require the Set1 histone H3 lysine 4 methyl-transferase for silencing. Furthermore, abolishing H3K4me3 triggers the silencing of other genes with antisense XUTs, supporting a model in which H3K4me3 antagonizes antisense ncRNA repressive activity. Our results demonstrate that antisense ncRNA-mediated regulation is a general regulatory pathway for gene expression in S.cerevisiae.