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European Radiology Oct 2023To comprehensively evaluate the glioma using quantitative susceptibility mapping (QSM).
OBJECTIVES
To comprehensively evaluate the glioma using quantitative susceptibility mapping (QSM).
MATERIALS AND METHODS
Forty-two patients (18 women; mean age, 45 years) with pathologically confirmed gliomas were retrospectively included. All the patients underwent conventional and advanced MRI examinations (QSM, DWI, MRS, etc.). Five patients underwent paired QSM (pre- and post-enhancement). Four Visually Accessible Rembrandt Image (VASARI) features and intratumoural susceptibility signal (ITSS) were observed. Three ROIs each were manually drawn separately in the tumour parenchyma with relatively high and low magnetic susceptibility. The association between the tumour's magnetic susceptibility and other MRI parameters was also analysed.
RESULTS
Morphologically, gliomas with heterogeneous ITSS were more similar to high-grade gliomas (p = 0.006, AUC: 0.72, sensitivity: 70%, and specificity: 73%). Heterogeneous ITSS was significantly associated with tumour haemorrhage, necrosis, diffusion restriction, and avid enhancement but did not change between pre- and post-enhanced QSM. Quantitatively, tumour parenchyma magnetic susceptibility had limited value in grading gliomas and identifying IDH mutation status, whereas the relatively low magnetic susceptibility of the tumour parenchyma helped identify oligodendrogliomas in IDH mutated gliomas (AUC = 0.78) with high specificity (100%). The relatively high tumour magnetic susceptibility significantly increased after enhancement (p = 0.039). Additionally, we found that the magnetic susceptibility of the tumour parenchyma was significantly correlated with ADC (r = 0.61) and Cho/NAA (r = 0.40).
CONCLUSIONS
QSM is a promising candidate for the comprehensive evaluation of gliomas, except for IDH mutation status. The magnetic susceptibility of tumour parenchyma may be affected by tumour cell proliferation.
KEY POINTS
• Morphologically, gliomas with a heterogeneous intratumoural susceptibility signal (ITSS) are more similar to high-grade gliomas (p = 0.006; AUC, 0.72; sensitivity, 70%; and specificity, 73%). Heterogeneous ITSS was significantly associated with tumour haemorrhage, necrosis, diffusion restriction, and avid enhancement but did not change between pre- and post-enhanced QSM. • Tumour parenchyma's relatively low magnetic susceptibility helped identify oligodendroglioma with high specificity. • Tumour parenchyma magnetic susceptibility was significantly correlated with ADC (r = 0.61) and Cho/NAA (r = 0.40).
Topics: Humans; Female; Middle Aged; Brain Neoplasms; Retrospective Studies; Sensitivity and Specificity; Glioma; Magnetic Resonance Imaging; Oligodendroglioma; Hemorrhage; Neoplasm Grading; Diffusion Magnetic Resonance Imaging
PubMed: 37095360
DOI: 10.1007/s00330-023-09647-4 -
Nature Communications Dec 2023Telomere length (TL) shortening is a pivotal indicator of biological aging and is associated with many human diseases. The genetic determinates of human TL have been...
Telomere length (TL) shortening is a pivotal indicator of biological aging and is associated with many human diseases. The genetic determinates of human TL have been widely investigated, however, most existing studies were conducted based on adult tissues which are heavily influenced by lifetime exposure. Based on the analyses of terminal restriction fragment (TRF) length of telomere, individual genotypes, and gene expressions on 166 healthy placental tissues, we systematically interrogate TL-modulated genes and their potential functions. We discover that the TL in the placenta is comparatively longer than in other adult tissues, but exhibiting an intra-tissue homogeneity. Trans-ancestral TL genome-wide association studies (GWASs) on 644,553 individuals identify 20 newly discovered genetic associations and provide increased polygenic determination of human TL. Next, we integrate the powerful TL GWAS with placental expression quantitative trait locus (eQTL) mapping to prioritize 23 likely causal genes, among which 4 are functionally validated, including MMUT, RRM1, KIAA1429, and YWHAZ. Finally, modeling transcriptomic signatures and TRF-based TL improve the prediction performance of human TL. This study deepens our understanding of causal genes and transcriptomic determinants of human TL, promoting the mechanistic research on fine-grained TL regulation.
Topics: Adult; Humans; Female; Pregnancy; Genome-Wide Association Study; Placenta; Telomere Shortening; Telomere; Gene Expression Profiling
PubMed: 38129441
DOI: 10.1038/s41467-023-44355-z -
World Journal of Emergency Surgery :... Oct 2023The creation of an ileostomy or colostomy is a common surgical event, both in elective and in emergency context. The main aim of stoma creation is to prevent... (Review)
Review
BACKGROUND
The creation of an ileostomy or colostomy is a common surgical event, both in elective and in emergency context. The main aim of stoma creation is to prevent postoperative complications, such as the anastomotic leak. However, stoma-related complications can also occur and their morbidity is not negligible, with a rate from 20 to 70%. Most stomal complications are managed conservatively, but, when this approach is not resolutive, surgical treatment becomes necessary. The aim of this mapping review is to get a comprehensive overview on the incidence, the risk factors, and the management of the main early and late ostomy complications: stoma necrosis, mucocutaneous separation, stoma retraction, stoma prolapse, parastomal hernia, stoma stenosis, and stoma bleeding.
MATERIAL AND METHODS
A complete literature research in principal databases (PUBMED, EMBASE, SCOPUS and COCHRANE) was performed by Multidisciplinary Italian Study group for STOmas (MISSTO) for each topic, with no language restriction and limited to the years 2011-2021. An international expert panel, from MISSTO and World Society of Emergency Surgery (WSES), subsequently reviewed the different issues, endorsed the project, and approved the final manuscript.
CONCLUSION
Stoma-related complications are common and require a step-up management, from conservative stoma care to surgical stoma revision. A study of literature evidence in clinical practice for stoma creation and an improved management of stoma-related complications could significantly increase the quality of life of patients with ostomy. Solid evidence from the literature about the correct management is lacking, and an international consensus is needed to draw up new guidelines on this subject.
Topics: Humans; Quality of Life; Ostomy; Surgical Stomas; Colostomy; Ileostomy
PubMed: 37817218
DOI: 10.1186/s13017-023-00516-5 -
Nature Communications Jan 2024Although chromatin organizations in plants have been dissected at the scales of compartments and topologically associating domain (TAD)-like domains, there remains a gap...
Although chromatin organizations in plants have been dissected at the scales of compartments and topologically associating domain (TAD)-like domains, there remains a gap in resolving fine-scale structures. Here, we use Micro-C-XL, a high-throughput chromosome conformation capture (Hi-C)-based technology that involves micrococcal nuclease (instead of restriction enzymes) and long cross-linkers, to dissect single nucleosome-resolution chromatin organization in Arabidopsis. Insulation analysis reveals more than 14,000 boundaries, which mostly include chromatin accessibility, epigenetic modifications, and transcription factors. Micro-C-XL reveals associations between RNA Pols and local chromatin organizations, suggesting that gene transcription substantially contributes to the establishment of local chromatin domains. By perturbing Pol II both genetically and chemically at the gene level, we confirm its function in regulating chromatin organization. Visible loops and stripes are assigned to super-enhancers and their targeted genes, thus providing direct insights for the identification and mechanistic analysis of distal CREs and their working modes in plants. We further investigate possible factors regulating these chromatin loops. Subsequently, we expand Micro-C-XL to soybean and rice. In summary, we use Micro-C-XL for analyses of plants, which reveal fine-scale chromatin organization and enhancer-promoter loops and provide insights regarding three-dimensional genomes in plants.
Topics: Chromatin; Nucleosomes; Promoter Regions, Genetic; Transcription Factors; Genome
PubMed: 38167349
DOI: 10.1038/s41467-023-44347-z -
BioRxiv : the Preprint Server For... Dec 2023Initial classification of acute leukemia involves the assignment of blasts to cell states within the hematopoietic hierarchy based on morphological and immunophenotypic...
Initial classification of acute leukemia involves the assignment of blasts to cell states within the hematopoietic hierarchy based on morphological and immunophenotypic features. Yet, these traditional classification approaches lack precision, especially at the level of immature blasts. Single-cell RNA-sequencing (scRNA-seq) enables precise determination of cell state using thousands of markers, thus providing an opportunity to re-examine present-day classification schemes of acute leukemia. Here, we developed a detailed reference map of human bone marrow hematopoiesis from 263,519 single-cell transcriptomes spanning 55 cellular states. Cell state annotations were benchmarked against purified cell populations, and in-depth characterization of gene expression programs underlying hematopoietic differentiation was undertaken. Projection of single-cell transcriptomes from 175 samples spanning acute myeloid leukemia (AML), mixed phenotype acute leukemia (MPAL), and acute erythroid leukemia (AEL) revealed 11 subtypes involving distinct stages of hematopoietic differentiation. These included AML subtypes with notable lymphoid or erythroid lineage priming, challenging traditional diagnostic boundaries between AML, MPAL, and AEL. Quantification of lineage priming in bulk patient cohorts revealed specific genetic alterations associated with this unconventional lineage priming. Integration of transcriptional and genetic information at the single-cell level revealed how genetic subclones can induce lineage restriction, differentiation blocks, or expansion of mature myeloid cells. Furthermore, we demonstrate that distinct cellular hierarchies can co-exist within individual patients, providing insight into AML evolution in response to varying selection pressures. Together, precise mapping of hematopoietic cell states can serve as a foundation for refining disease classification in acute leukemia and understanding response or resistance to emerging therapies.
PubMed: 38234771
DOI: 10.1101/2023.12.26.573390 -
Functional & Integrative Genomics Sep 2023Analysis of natural diversity in wild/cultivated plants can be used to understand the genetic basis for plant breeding programs. Recent advancements in DNA sequencing... (Review)
Review
Analysis of natural diversity in wild/cultivated plants can be used to understand the genetic basis for plant breeding programs. Recent advancements in DNA sequencing have expanded the possibilities for genetically altering essential features. There have been several recently disclosed statistical genetic methods for discovering the genes impacting target qualities. One of these useful methods is the genome-wide association study (GWAS), which effectively identifies candidate genes for a variety of plant properties by examining the relationship between a molecular marker (such as SNP) and a target trait. Conventional QTL mapping with highly structured populations has major limitations. The limited number of recombination events results in poor resolution for quantitative traits. Only two alleles at any given locus can be studied simultaneously. Conventional mapping approach fails to work in perennial plants and vegetatively propagated crops. These limitations are sidestepped by association mapping or GWAS. The flexibility of GWAS comes from the fact that the individuals being examined need not be linked to one another, allowing for the use of all meiotic and recombination events to increase resolution. Phenotyping, genotyping, population structure analysis, kinship analysis, and marker-trait association analysis are the fundamental phases of GWAS. With the rapid development of sequencing technologies and computational methods, GWAS is becoming a potent tool for identifying the natural variations that underlie complex characteristics in crops. The use of high-throughput sequencing technologies along with genotyping approaches like genotyping-by-sequencing (GBS) and restriction site associated DNA (RAD) sequencing may be highly useful in fast-forward mapping approach like GWAS. Breeders may use GWAS to quickly unravel the genomes through QTL and association mapping by taking advantage of natural variances. The drawbacks of conventional linkage mapping can be successfully overcome with the use of high-resolution mapping and the inclusion of multiple alleles in GWAS.
Topics: Humans; Trees; Genome-Wide Association Study; Plant Breeding; Chromosome Mapping; Alleles; Crops, Agricultural
PubMed: 37700096
DOI: 10.1007/s10142-023-01224-8 -
Cell Discovery Mar 2024Single-cell whole-genome sequencing methods have undergone great improvements over the past decade. However, allele dropout, which means the inability to detect both...
Single-cell whole-genome sequencing methods have undergone great improvements over the past decade. However, allele dropout, which means the inability to detect both alleles simultaneously in an individual diploid cell, largely restricts the application of these methods particularly for medical applications. Here, we develop a new single-cell whole-genome sequencing method based on third-generation sequencing (TGS) platform named Refresh-seq (restriction fragment ligation-based genome amplification and TGS). It is based on restriction endonuclease cutting and ligation strategy in which two alleles in an individual cell can be cut into equal fragments and tend to be amplified simultaneously. As a new single-cell long-read genome sequencing method, Refresh-seq features much lower allele dropout rate compared with SMOOTH-seq. Furthermore, we apply Refresh-seq to 688 sperm cells and 272 female haploid cells (secondary polar bodies and parthenogenetic oocytes) from F1 hybrid mice. We acquire high-resolution genetic map of mouse meiosis recombination at low sequencing depth and reveal the sexual dimorphism in meiotic crossovers. We also phase the structure variations (deletions and insertions) in sperm cells and female haploid cells with high precision. Refresh-seq shows great performance in screening aneuploid sperm cells and oocytes due to the low allele dropout rate and has great potential for medical applications such as preimplantation genetic diagnosis.
PubMed: 38443370
DOI: 10.1038/s41421-023-00638-9 -
Current Hematologic Malignancy Reports Dec 2023The length of telomeres, protective structures at the chromosome ends, is a well-established biomarker for pathological conditions including multisystemic syndromes... (Review)
Review
PURPOSE OF REVIEW
The length of telomeres, protective structures at the chromosome ends, is a well-established biomarker for pathological conditions including multisystemic syndromes called telomere biology disorders. Approaches to measure telomere length (TL) differ on whether they estimate average, distribution, or chromosome-specific TL, and each presents their own advantages and limitations.
RECENT FINDINGS
The development of long-read sequencing and publication of the telomere-to-telomere human genome reference has allowed for scalable and high-resolution TL estimation in pre-existing sequencing datasets but is still impractical as a dedicated TL test. As sequencing costs continue to fall and strategies for selectively enriching telomere regions prior to sequencing improve, these approaches may become a promising alternative to classic methods. Measurement methods rely on probe hybridization, qPCR or more recently, computational methods using sequencing data. Refinements of existing techniques and new approaches have been recently developed but a test that is accurate, simple, and scalable is still lacking.
Topics: Humans; Forecasting; Telomere
PubMed: 37947937
DOI: 10.1007/s11899-023-00717-4 -
International Journal of Clinical... Oct 2023Despite significant warnings of adverse effects, antipsychotics continue to be prescribed for managing the behavioural and psychological symptoms of dementia (BPSD) in... (Review)
Review
BACKGROUND
Despite significant warnings of adverse effects, antipsychotics continue to be prescribed for managing the behavioural and psychological symptoms of dementia (BPSD) in care homes. Information provided by staff working within care homes is a factor that can influence prescribing decisions in residents with BPSD.
AIM
The review aimed to capture care home staff views towards antipsychotics for residents with BPSD and separately analyse tools utilized in the studies, mapping them onto the theory of planned behaviour (TPB).
METHOD
A comprehensive literature search published in ten databases was conducted between May and July 2020 and updated in July 2021. Studies published in full with no date restriction were included and quality assessed using CROSS checklist. A thematic framework approach was applied to extract data and study tools which were then mapped onto the TPB.
RESULTS
Fourteen studies (2059 participants) were included. Findings identified four overarching themes: attitudes toward antipsychotics (e.g. antipsychotics as an appropriate strategy and effectiveness); barriers to deprescribing (e.g. lower staff education, lack of resources and time, poor medication reviews); measures implemented (e.g. nonpharmacological interventions, medication reviews); and perceived needs of staff (e.g. need for training, financial or clinical support). Identified tools addressed seven but not all components of TPB namely, behavioural, normative and control beliefs, attitude, perceived behavioural control, intention and behaviour.
CONCLUSION
The positive attitudes toward antipsychotics, the identified barriers to deprescribing and the existing tools not addressing all components of the TPB provide the impetus for further research.
Topics: Humans; Nursing Homes; Antipsychotic Agents; Dementia; Attitude of Health Personnel
PubMed: 37773304
DOI: 10.1007/s11096-023-01645-2 -
Nucleic Acids Research Jul 2023Much of the human genetics variant repertoire is composed of single nucleotide variants (SNV) and small insertion/deletions (indel) but structural variants (SV) remain a...
Much of the human genetics variant repertoire is composed of single nucleotide variants (SNV) and small insertion/deletions (indel) but structural variants (SV) remain a major part of our modified DNA. SV detection has often been a complex question to answer either because of the necessity to use different technologies (array CGH, SNP array, Karyotype, Optical Genome Mapping…) to detect each category of SV or to get an appropriate resolution (Whole Genome Sequencing). Thanks to the deluge of pangenomic analysis, Human geneticists are accumulating SV and their interpretation remains time consuming and challenging. The AnnotSV webserver (https://www.lbgi.fr/AnnotSV/) aims at being an efficient tool to (i) annotate and interpret SV potential pathogenicity in the context of human diseases, (ii) recognize potential false positive variants from all the SV identified and (iii) visualize the patient variants repertoire. The most recent developments in the AnnotSV webserver are: (i) updated annotations sources and ranking, (ii) three novel output formats to allow diverse utilization (analysis, pipelines), as well as (iii) two novel user interfaces including an interactive circos view.
Topics: Humans; Genome, Human; High-Throughput Nucleotide Sequencing; INDEL Mutation; Polymorphism, Single Nucleotide; Restriction Mapping; Sequence Analysis, DNA; Whole Genome Sequencing; Disease; Software
PubMed: 37216590
DOI: 10.1093/nar/gkad426