Mutant IDH inhibitors induce lineage differentiation in IDH-mutant oligodendroglioma.

A subset of patients with IDH-mutant glioma respond to inhibitors of mutant IDH (IDHi), yet the molecular underpinnings of such responses are not understood. Here, we profiled by single-cell or single-nucleus RNA-sequencing three IDH-mutant oligodendrogliomas from patients who derived clinical benefit from IDHi. Importantly, the tissues were sampled on-drug, four weeks from treatment initiation. We further integrate our findings with analysis of single-cell and bulk transcriptomes from independent cohorts and experimental models. We find that IDHi treatment induces a robust differentiation toward the astrocytic lineage, accompanied by a depletion of stem-like cells and a reduction of cell proliferation. Furthermore, mutations in NOTCH1 are associated with decreased astrocytic differentiation and may limit the response to IDHi. Our study highlights the differentiating potential of IDHi on the cellular hierarchies that drive oligodendrogliomas and suggests a genetic modifier that may improve patient stratification.

Aplicación de la clasificación de Robson como método útil para estandarizar el manejo del parto. Un ejercicio que reduce la tasa de cesáreas / Application of Robson's Ten Group Classification System to standardize patient management. A useful way to reduce cesarean rates

Introducción: La tasa de cesárea es un motivo de controversia y la clasificación de Robson es un método de estandarización que evalúa las causas de esta. En nuestro trabajo analizamos si las medidas de mejora de manejo prenatal e intraparto implementadas tras la revisión de Robson suponen un descenso de índice de cesáreas sin incrementar los de morbimortalidad neonatal y materna. Material y método: Estudio cuasi experimental antes-después, entre 2019 y 2020, con un total de 2.181 pacientes con parto en el Hospital Universitario de Valme (1.027 en el grupo 2019 y 1.154 en el de 2020). Resultados: Observamos que se produjo una disminución estadísticamente significativa de la tasa de cesárea entre 2019 y 2020 (21 vs. 15,8%; p = 0,001) sin ser relevante la reducción en ningún subgrupo de estudio. Hubo un menor índice de parto inducido (29,3 vs. 24,6%; p = 0.01), un aumento en la tasa de parto vaginal (79 vs. 84,2%; p = 0,001) tanto de eutócicos como instrumentales (57,9 vs. 60,3%; 21 vs. 23,9%; p = 0.005) y una baja estadísticamente significativa de la de cesáreas por fallo de inducción o no progresión del parto (NPP) (34,7 vs. 20,9%; p = 0,008). En las inducciones mediante balón de Cook observamos una disminución del índice de cesárea (45,3 vs. 22,2% p = 0,001). Hallamos que redujo el porcentaje de ingreso en la Unidad de Cuidados Intensivos Neonatales (UCIN) (10,5 vs. 7.6%; p = 0,016) y la morbilidad neonatal global (11,4 vs. 8,2%; p = 0,013) sin encontrar diferencia en los resultados maternos. Conclusiones: La aplicación de la clasificación de Robson puede ser un método útil para identificar grupos que requieran de medidas específicas destinadas a estandarizar el manejo de las pacientes, con lo que se permite reducir la tasa de cesáreas.(AU)

Background: Cesarean section rate is controversial and the Robson classification is a method for standardizing the evaluation of the causes of cesarean section. The aim of this study was to evaluate whether the measures to improve prenatal and intrapartum management implemented after the Robson classification evaluation lead to a decrease in the rate of cesarean sections without increasing the rates of neonatal and maternal morbidity and mortality. Material and method: Quasi-experimental study before-after,between-2019 and 2020, including a total of 2181 patients with delivery at Hospital-Universitario-Valme(1027 patients in Group-2019, and 1154 patients in group-2020).Results: We observed that there was a statistically significant decrease in the cesarean section rate between 2019 and 2020 (21.0% vs 15.8%; p = 0.001) without the decrease being significant in any study subgroup. There was a lower rate of induced labor(29.3% vs 24.6%; p = 0.01), an increased rate of vaginal delivery (79.0% vs 84.2%; p = 0.001), both eutocic and instrumental deliveries (57.9% vs 60.3%; 21% vs 23.9%; p = 0.005) and a statistically significant decrease in the rate of cesarean sections due to failure of induction or non-progression of labor(34.7% vs 20.9%;p = 0.008). In inductions using the balloon-Cook we observed a decrease in the rate of cesarean section (45.3% versus 22.2% p = 0.001). We found a decrease in the percentage of admission to the Neonatal ICU (10.5% vs 7.6%; p = 0.016) and global neonatal morbidity(11.4% vs 8.2%; p = 0.013) without observing a difference in maternal outcomes. Conclusions: The application of the Robson classification can be a useful method to identify groups that require the application of specific measures aimed at standardizing the management of these patients, thus allowing to reduce the rate of cesarean sections.(AU)

Welfare assessment of Thoroughbred horses naturally infected with gastrointestinal parasites in Southern Brazil: Quantifying the host-parasite relationship.

Horse welfare assessment (HWA) does not account for individual or herd parasite infection. This study investigated the connection between HWA and individual parasite fecal egg count (FEC) in 90 Thoroughbred horses. All horses were naturally infected with gastrointestinal parasites and were evaluated for individual welfare indicators and FEC monthly, for 12 months. Horses were divided into three groups of 30 mares, 30 foals aged between 13 and 16 months (G2013), and 30 foals aged between two months and one year (G2014). A horse welfare protocol was developed and 1024 assessments were carried out by five trained assessors. FEC ranged from 0 to 5,760 with 98.8 % showing small strongyle eggs. Body condition scores were ideal in 94.4 % of the evaluations (n = 967), and 95.8 % of all horses had good clinical and behavioral indicators. Despite the variation in FEC, the data found no significant association between FEC and the behavioral indicators. The study suggests that FEC alone should not be used as a determinant of welfare when animals are managed with good nutritional and health management practices.

Integrative spatial analysis reveals a multi-layered organization of glioblastoma.

Glioma contains malignant cells in diverse states. Here, we combine spatial transcriptomics, spatial proteomics, and computational approaches to define glioma cellular states and uncover their organization. We find three prominent modes of organization. First, gliomas are composed of small local environments, each typically enriched with one major cellular state. Second, specific pairs of states preferentially reside in proximity across multiple scales. This pairing of states is consistent across tumors. Third, these pairwise interactions collectively define a global architecture composed of five layers. Hypoxia appears to drive the layers, as it is associated with a long-range organization that includes all cancer cell states. Accordingly, tumor regions distant from any hypoxic/necrotic foci and tumors that lack hypoxia such as low-grade IDH-mutant glioma are less organized. In summary, we provide a conceptual framework for the organization of cellular states in glioma, highlighting hypoxia as a long-range tissue organizer.

Parir después de los 50 años. Estudio piloto observacional / Birth over 50: A pilot observational study

Objetivos: Evaluar si existe una mayor tasa de resultados obstétricos adversos, incontinencia urinaria posparto y problemas sexuales entre las mujeres que dan a luz después de los 50 años.Material y métodos: Estudio observacional ambispectivo de un solo centro. Se registraron la tasa de parto por cesárea, la diabetes gestacional, la preeclampsia, la restricción del crecimiento intrauterino (RCIU), la prematuridad, la incontinencia urinaria (Cuestionario de incontinencia en formato corto [ICIQ-SF]) y la disfunción sexual (índice de función sexual femenina [FSFI-6]). Resultados: Veinticinco (0,06%) de 38.510 nacimientos ocurrieron en mujeres mayores de 50 años durante el período de estudio en nuestro centro. Hubo 16 (64%) partos por cesárea. Siete (28%) mujeres padecieron diabetes gestacional. Se diagnosticó preeclampsia en 3 (12%) mujeres. Hubo 5 (20%) casos de RCIU. Hubo 5 (20%) partos prematuros. Las diferencias en la tasa de parto por cesárea, diabetes gestacional y RCIU entre el grupo de estudio y la población total fueron estadísticamente significativas. Los resultados de los cuestionarios ICIQ-SF y FSFI-6 se obtuvieron de 17 mujeres. Se encontró algún grado de incontinencia urinaria en 7 (41,1%) y disfunción sexual en 9 (52,9%) mujeres. Conclusiones: Los embarazos en mujeres mayores de 50 años parecen estar asociados con una mayor tasa de diabetes gestacional, RCIU y preeclampsia. Hay una alta prevalencia de incontinencia urinaria y problemas sexuales entre estas mujeres.(AU)

Objectives: To assess whether there is a higher rate of adverse obstetric outcomes, postpartum urinary incontinence, and sexual problems among women who give birth over 50. Material and methods: A single-center ambispective observational study. Rate of cesarean birth, gestational diabetes, preeclampsia, intrauterine growth restriction (IUGR), prematurity, urinary incontinence (Incontinence Questionnaire Short Form [ICIQ-SF]), and sexual dysfunction (Female Sexual Function Index [FSFI-6]) were recorded. Results: Twenty-five (0.06%) of 38,510 births occurred in women over 50 during the study period. There were 16 (64%) cesarean births. Seven (28%) women had gestational diabetes. Preeclampsia was diagnosed in 3 (12%) women. There were 5 (20%) cases of IUGR. There were 5 (20%) preterm births. The differences in the rate of cesarean birth, gestational diabetes, and IUGR between the study group and the total population were statistically significant. The results of the ICIQ-SF and FSFI-6 questionnaires were obtained from 17 women. Some degree of urinary incontinence was found in 7 (41.1%) and sexual dysfunction in 9 (52.9%) women. Conclusions: Pregnancies in women over 50 may be associated with a higher rate of gestational diabetes, IUGR, and preeclampsia. There is a high prevalence of urinary incontinence and sexual problems among these women.(AU)

An historical "wreck": A transcriptome assembly of the naval shipworm, Teredo navalis Linnaeus, 1978.

Historically famous for their negative impact on human-built marine wood structures, mollusc shipworms play a central ecological role in marine ecosystems. Their association with bacterial symbionts, providing cellulolytic and nitrogen-fixing activities, underscores their exceptional wood-eating and wood-boring behaviours, improving energy transfer and the recycling of essential nutrients locked in the wood cellulose. Importantly, from a molecular standpoint, a minute of omic resources are available from this lineage of Bivalvia. Here, we produced and assembled a transcriptome from the globally distributed naval shipworm, Teredo navalis (family Teredinidae). The transcriptome was obtained by sequencing the total RNA from five equidistant segments of the whole body of a T. navalis specimen. The quality of the produced assembly was accessed with several statistics, revealing a highly contiguous (1194 N50) and complete (over 90% BUSCO scores for Eukaryote and Metazoan databases) transcriptome, with nearly 38,000 predicted ORF, more than half being functionally annotated. Our findings pave the way to investigate the unique evolutionary biology of these highly modified bivalves and lay the foundation for an adequate gene annotation of a full genome sequence of the species.

A whole-body transcriptome assembly of the annelid worm Hediste diversicolor.

The Annelida phylum is composed of a myriad of species exhibiting key phenotypic adaptations. They occupy key ecological niches in a variety of marine, freshwater and terrestrial ecosystems. Importantly, the increment of omic resources is rapidly modifying the taxonomic landscape and knowledge of species belonging to this phylum. Here, we comprehensively characterised and annotated a transcriptome of the common ragworm, Hediste diversicolor (OF Müller). This species belongs to the family Nereididae and inhabits estuarine and lagoon areas on the Atlantic coasts of Europe and North America. Ecologically, H. diversicolor plays an important role in benthic food webs. Given its commercial value, H. diversicolor is a promising candidate for aquaculture development and production in farming facilities, under a circular economy framework. We used Illumina next-generation sequencing technology, to produce a total of 105 million (M) paired-end (PE) raw reads and generate the first whole-body transcriptome assembly of H. diversicolor species. This high-quality transcriptome contains 69,335 transcripts with an N50 transcript length of 2313 bp and achieved a BUSCO gene completeness of 97.7% and 96% in Eukaryota and Metazoa lineage-specific profile libraries. Our findings offer a valuable resource for multiple biological applications using this species.

Population Genomics Reveals the Underlying Structure of the Small Pelagic European Sardine and Suggests Low Connectivity within Macaronesia.

The European sardine (Sardina pilchardus, Walbaum 1792) is indisputably a commercially important species. Previous studies using uneven sampling or a limited number of makers have presented sometimes conflicting evidence of the genetic structure of S. pilchardus populations. Here, we show that whole genome data from 108 individuals from 16 sampling areas across 5000 km of the species' distribution range (from the Eastern Mediterranean to the archipelago of Azores) support at least three genetic clusters. One includes individuals from Azores and Madeira, with evidence of substructure separating these two archipelagos in the Atlantic. Another cluster broadly corresponds to the center of the distribution, including the sampling sites around Iberia, separated by the Almeria-Oran front from the third cluster that includes all of the Mediterranean samples, except those from the Alboran Sea. Individuals from the Canary Islands appear to belong to the Mediterranean cluster. This suggests at least two important geographical barriers to gene flow, even though these do not seem complete, with many individuals from around Iberia and the Mediterranean showing some patterns compatible with admixture with other genetic clusters. Genomic regions corresponding to the top outliers of genetic differentiation are located in areas of low recombination indicative that genetic architecture also has a role in shaping population structure. These regions include genes related to otolith formation, a calcium carbonate structure in the inner ear previously used to distinguish S. pilchardus populations. Our results provide a baseline for further characterization of physical and genetic barriers that divide European sardine populations, and information for transnational stock management of this highly exploited species towards sustainable fisheries.

Unravelling the main immune repertoire of Paracentrotus lividus following Vibrio anguillarum bath challenge.

Paracentrotus lividus is the most abundant echinoid species in the North East Atlantic Ocean and Mediterranean Sea. Although there is abundant genomic information of the species, there is no deep characterisation of the genes involved in the immune response. Here, a reference transcriptome of male and female coelomocytes was produced. The generated P. lividus transcriptome assembly has 203,511 transcripts, N50 transcript length of 1079 bp, and more than 90% estimated gene completeness in Eukaryota and Metazoa BUSCO databases, respectively. Differential gene expression analyses showed 54 and 55 up-regulated genes in P. lividus female and male coelomocyte tissues, respectively. These results suggest a similar immune gene repertoire between sexes. To examine the immune response, P. lividus was challenged with Vibrio anguillarum, one of the candidate pathogens for bald disease. Immune parameters were evaluated at cell and humoral levels, as well as the expression analysis of immune related genes at an early response stage. No differences were found at cellular and humoral levels with the exception of the increase of nitric oxide in perivisceral fluid of challenged animals. At the gene expression level, a total of 2721 genes were upregulated in challenged animals, 13.6 times higher expression than control group. Our analysis revealed that four major KEGG pathways were enriched in challenged animals: Autophagy (KEGG:04140), Endocytosis (KEGG:04144), Phagosome (KEGG:04145) and Protein processing in endoplasmic reticulum (KEGG:04141). Several toll-like receptors (TLR), scavenger receptors cysteine-rich (SRCR) or nucleotide-binding oligomerisation domain like receptors (NLR) were identified as major family genes for pathogen recognition and immune defence. This study provides a valuable transcriptomic resource and unfolds the molecular basis of immune response to V. anguillarum exposure. Overall, our findings contribute to the conservation effort of the P. lividus populations, as well as its sustainable exploitation in an aquaculture context.

Dataset of the complete mitogenome of the deep-sea sailfin roughshark, Oxynotus paradoxus Frade, 1929.

Chondrichthyans comprise a diverse group of vertebrate species with extraordinary ecological relevance. Yet, multiple members of this evolutionary lineage are associated with significant extinction risk. The sailfin roughshark Oxynotus paradoxus is a deep-water benthic shark currently listed as vulnerable due to population declines in parts of its range. Here we provide the first complete mitochondrial genome of O. paradoxus, comprising also the first record for the genus and family Oxynotidae. These data can facilitate future monitoring of the genetic diversity in this and related species. Genomic DNA was extracted from O. paradoxus collected in the eastern North Atlantic off western Portugal (37.59°N, 9.51°W) and sent for Illumina Paired-End (2 × 150 bp) library construction and whole genome sequencing on a Novaseq6000 platform. Trimmomatic (version 0.38) was used to remove adapters and MitoZ (version 3.4) to assemble and annotate the mitogenome. This mitogenome with 17 100 bp has a total of 38 genes, 13 of which are protein-coding genes, 23 transfer RNA genes, and 2 ribosomal RNA genes. Eight transfer RNAs and 1 protein-coding gene (NADH dehydrogenase subunit 6, NAD6) are in the complementary strand. In the provided phylogenetic inference, with all available and verified Squalomorphii mitogenomes, the four orders are well separated, and as expected, O. paradoxus is placed in the Squaliformes order. This data reinforces the need for more genomic resources for the Oxynotidae family.

An Ancestral Major Histocompatibility Complex Organization in Cartilaginous Fish: Reconstructing MHC Origin and Evolution.

Cartilaginous fish (sharks, rays, and chimeras) comprise the oldest living jawed vertebrates with a mammalian-like adaptive immune system based on immunoglobulins (Ig), T-cell receptors (TCRs), and the major histocompatibility complex (MHC). Here, we show that the cartilaginous fish "adaptive MHC" is highly regimented and compact, containing (i) a classical MHC class Ia (MHC-Ia) region containing antigen processing (antigen peptide transporters and immunoproteasome) and presenting (MHC-Ia) genes, (ii) an MHC class II (MHC-II) region (with alpha and beta genes) with linkage to beta-2-microglobulin (ß2m) and bromodomain-containing 2, (iii) nonclassical MHC class Ib (MHC-Ib) regions with 450 million-year-old lineages, and (iv) a complement C4 associated with the MHC-Ia region. No MHC-Ib genes were found outside of the elasmobranch MHC. Our data suggest that both MHC-I and MHC-II genes arose after the second round of whole-genome duplication (2R) on a human chromosome (huchr) 6 precursor. Further analysis of MHC paralogous regions across early branching taxa from all jawed vertebrate lineages revealed that Ig/TCR genes likely arose on a precursor of the huchr9/12/14 MHC paralog. The ß2m gene is linked to the Ig/TCR genes in some vertebrates suggesting that it was present at 1R, perhaps as the donor of C1 domain to the primordial MHC gene. In sum, extant cartilaginous fish exhibit a conserved and prototypical MHC genomic organization with features found in various vertebrates, reflecting the ancestral arrangement for the jawed vertebrates.

Mitochondrial replication's role in vertebrate mtDNA strand asymmetry.

Mitogenomes are defined as compact and structurally stable over aeons. This perception results from a vertebrate-centric vision, where few types of mtDNA rearrangements are described. Here, we bring a new light to the involvement of mitochondrial replication in the strand asymmetry of the vertebrate mtDNA. Using several species of deep-sea hatchetfish (Sternoptychidae) displaying distinct mtDNA structural arrangements, we unravel the inversion of the coding direction of protein-coding genes (PCGs). This unexpected change is coupled with a strand asymmetry nucleotide composition reversal and is shown to be directly related to the strand location of the Control Region (CR). An analysis of the fourfold redundant sites of the PCGs (greater than 6000 vertebrates), revealed the rarity of this phenomenon, found in nine fish species (five deep-sea hatchetfish). Curiously, in Antarctic notothenioid fishes (Trematominae), where a single PCG inversion (the only other record in fish) is coupled with the inversion of the CR, the standard asymmetry is disrupted for the remaining PCGs but not yet reversed, suggesting a transitory state. Our results hint that a relaxation of the classic vertebrate mitochondrial structural stasis promotes disruption of the natural balance of asymmetry of the mtDNA. These findings support the long-lasting hypothesis that replication is the main molecular mechanism promoting the strand-specific compositional bias of this unique and indispensable molecule.

Programs, Origins, and Niches of Immunomodulatory Myeloid Cells in Gliomas.

Gliomas are incurable malignancies notable for an immunosuppressive microenvironment with abundant myeloid cells whose immunomodulatory properties remain poorly defined. Here, utilizing scRNA-seq data for 183,062 myeloid cells from 85 human tumors, we discover that nearly all glioma-associated myeloid cells express at least one of four immunomodulatory activity programs: Scavenger Immunosuppressive, C1Q Immunosuppressive, CXCR4 Inflammatory, and IL1B Inflammatory. All four programs are present in IDH1 mutant and wild-type gliomas and are expressed in macrophages, monocytes, and microglia whether of blood or resident myeloid cell origins. Integrating our scRNA-seq data with mitochondrial DNA-based lineage tracing, spatial transcriptomics, and organoid explant systems that model peripheral monocyte infiltration, we show that these programs are driven by microenvironmental cues and therapies rather than myeloid cell type, origin, or mutation status. The C1Q Immunosuppressive program is driven by routinely administered dexamethasone. The Scavenger Immunosuppressive program includes ligands with established roles in T-cell suppression, is induced in hypoxic regions, and is associated with immunotherapy resistance. Both immunosuppressive programs are less prevalent in lower-grade gliomas, which are instead enriched for the CXCR4 Inflammatory program. Our study provides a framework to understand immunomodulatory myeloid cells in glioma, and a foundation to develop more effective immunotherapies.

Clinical trial links oncolytic immunoactivation to survival in glioblastoma.

Immunotherapy failures can result from the highly suppressive tumour microenvironment that characterizes aggressive forms of cancer such as recurrent glioblastoma (rGBM)1,2. Here we report the results of a first-in-human phase I trial in 41 patients with rGBM who were injected with CAN-3110-an oncolytic herpes virus (oHSV)3. In contrast to other clinical oHSVs, CAN-3110 retains the viral neurovirulence ICP34.5 gene transcribed by a nestin promoter; nestin is overexpressed in GBM and other invasive tumours, but not in the adult brain or healthy differentiated tissue4. These modifications confer CAN-3110 with preferential tumour replication. No dose-limiting toxicities were encountered. Positive HSV1 serology was significantly associated with both improved survival and clearance of CAN-3110 from injected tumours. Survival after treatment, particularly in individuals seropositive for HSV1, was significantly associated with (1) changes in tumour/PBMC T cell counts and clonal diversity, (2) peripheral expansion/contraction of specific T cell clonotypes; and (3) tumour transcriptomic signatures of immune activation. These results provide human validation that intralesional oHSV treatment enhances anticancer immune responses even in immunosuppressive tumour microenvironments, particularly in individuals with cognate serology to the injected virus. This provides a biological rationale for use of this oncolytic modality in cancers that are otherwise unresponsive to immunotherapy (ClinicalTrials.gov: NCT03152318 ).

Extensive gene loss parallels kidney aglomerulism in Syngnathidae.

The eccentric seahorses, seadragons, pipehorses and pipefishes (Syngnathidae) have an aglomerular kidney1. Here, we show that nephron genes2 conserved in Bilateria are secondarily eroded/deleted in Syngnathidae genomes. A transcriptome enrichment analysis suggests the predominance of excretion processes in the Syngnathidae kidney. In a lineage where crypsis and idleness are tightly associated, we propose that aglomerulism evolved as an energy-saving strategy.

Examination of gammarid transcriptomes reveals a widespread occurrence of key metabolic genes from epibiont bdelloid rotifers in freshwater species.

Previous data revealed the unexpected presence of genes encoding for long-chain polyunsaturated fatty acid (LC-PUFA) biosynthetic enzymes in transcriptomes from freshwater gammarids but not in marine species, even though closely related species were compared. This study aimed to clarify the origin and occurrence of selected LC-PUFA biosynthesis gene markers across all published gammarid transcriptomes. Through systematic searches, we confirmed the widespread occurrence of sequences from seven elongases and desaturases involved in LC-PUFA biosynthesis, in transcriptomes from freshwater gammarids but not marine species, and clarified that such occurrence is independent from the gammarid species and geographical origin. The phylogenetic analysis established that the retrieved elongase and desaturase sequences were closely related to bdelloid rotifers, confirming that multiple transcriptomes from freshwater gammarids contain contaminating rotifers' genetic material. Using the Adineta steineri genome, we investigated the genomic location and exon-intron organization of the elongase and desaturase genes, establishing they are all genome-anchored and, importantly, identifying instances of horizontal gene transfer. Finally, we provide compelling evidence demonstrating Bdelloidea desaturases and elongases enable these organisms to perform all the reactions for de novo biosynthesis of PUFA and, from them, LC-PUFA, an advantageous trait when considering the low abundance of these essential nutrients in freshwater environments.

Diagnosis and Treatment of Paraneoplastic Neurologic Syndromes.

Paraneoplastic antibody syndromes result from the anti-tumor antibody response against normal antigens ectopically expressed by tumor cells. Although this antibody response plays an important role in helping clear a nascent or established tumor, the engagement of antigens expressed in healthy tissues can lead to complex clinical syndromes with challenging diagnosis and management. The majority of known paraneoplastic antibody syndromes have been found to affect the central and peripheral nervous system. The present review provides an update on the pathophysiology of paraneoplastic neurologic syndromes, as well as recommendations for their diagnosis and treatment.

Towards optimal use of antithrombotic therapy of people with cancer at the end of life: A research protocol for the development and implementation of the SERENITY shared decision support tool.

BACKGROUND: Even though antithrombotic therapy has probably little or even negative effects on the well-being of people with cancer during their last year of life, deprescribing antithrombotic therapy at the end of life is rare in practice. It is often continued until death, possibly resulting in excess bleeding, an increased disease burden and higher healthcare costs. METHODS: The SERENITY consortium comprises researchers and clinicians from eight European countries with specialties in different clinical fields, epidemiology and psychology. SERENITY will use a comprehensive approach combining a realist review, flash mob research, epidemiological studies, and qualitative interviews. The results of these studies will be used in a Delphi process to reach a consensus on the optimal design of the shared decision support tool. Next, the shared decision support tool will be tested in a randomised controlled trial. A targeted implementation and dissemination plan will be developed to enable the use of the SERENITY tool across Europe, as well as its incorporation in clinical guidelines and policies. The entire project is funded by Horizon Europe. RESULTS: SERENITY will develop an information-driven shared decision support tool that will facilitate treatment decisions regarding the appropriate use of antithrombotic therapy in people with cancer at the end of life. CONCLUSIONS: We aim to develop an intervention that guides the appropriate use of antithrombotic therapy, prevents bleeding complications, and saves healthcare costs. Hopefully, usage of the tool leads to enhanced empowerment and improved quality of life and treatment satisfaction of people with advanced cancer and their care givers.

PacBio Hi-Fi genome assembly of the Iberian dolphin freshwater mussel Unio delphinus Spengler, 1793.

Mussels of order Unionida are a group of strictly freshwater bivalves with nearly 1,000 described species widely dispersed across world freshwater ecosystems. They are highly threatened showing the highest record of extinction events within faunal taxa. Conservation is particularly concerning in species occurring in the Mediterranean biodiversity hotspot that are exposed to multiple anthropogenic threats, possibly acting in synergy. That is the case of the dolphin freshwater mussel Unio delphinus Spengler, 1793, endemic to the western Iberian Peninsula with recently strong population declines. To date, only four genome assemblies are available for the order Unionida and only one European species. We present the first genome assembly of Unio delphinus. We used the PacBio HiFi to generate a highly contiguous genome assembly. The assembly is 2.5 Gb long, possessing 1254 contigs with a contig N50 length of 10 Mbp. This is the most contiguous freshwater mussel genome assembly to date and is an essential resource for investigating the species' biology and evolutionary history that ultimately will help to support conservation strategies.

A PacBio Hi-Fi Genome Assembly of the Painter's Mussel Unio pictorum (Linnaeus, 1758).

The highly diverse group of freshwater mussels from order Unionida is found in the world's freshwater systems due to several fascinating evolutionary adaptations, including "parental care," and most notably, an obligatory parasitic phase in their early life cycle, called glochidia, which infests and uses fish for nutrition and dispersal. Freshwater mussels play essential ecological roles in freshwater habitats, including water filtration, sediment bioturbation, and nutrient cycling. However, these species are also highly threatened, being one of the faunal groups with the highest recorded extinction rate in the wild. Genomics methods have an incredible potential to promote biodiversity conservation, allowing the characterization of population health, identification of adaptive genetic elements, delineation of conservation units, and providing a framework for predictive assessments of the impact of anthropogenic threats and climate change. Unfortunately, only six freshwater mussel species have had their whole genomes sequenced to date, and only two of these are European species. Here, we present the first genome assembly of the Painter's Mussel, Unio pictorum (Linnaeus, 1758), the type species representative of the order and the most widespread species of the genus in Europe. We used long-read PacBio Hi-Fi sequencing reads to produce a highly contiguous assembly that will pave the way for the study of European freshwater mussels in the Genome Era.