The vast spectrum of aggressive B-cell non-Hodgkin neoplasms (B-NHL) encompasses several infrequent entities occurring in association with viral infections, posing diagnostic challenges for ...practitioners. In the emerging era of precision oncology, the molecular characterization of malignancies has acquired paramount significance. The pathophysiological comprehension of specific entities and the identification of targeted therapeutic options have seen rapid development. However, owing to their rarity, not all entities have undergone exhaustive molecular characterization.
Considerable heterogeneity exists in the extant body of work, both in terms of employed methodologies and the scale of cases studied. Presently, therapeutic strategies are predominantly derived from observations in diffuse large B-cell lymphoma (DLBCL), the most prevalent subset of aggressive B-NHL. Ongoing investigations into the molecular profiles of these uncommon virus-associated entities are progressively facilitating a clearer distinction from DLBCL, ultimately paving the way towards individualized therapeutic approaches.
This review consolidates the current molecular insights into aggressive and virus-associated B-NHL, taking into consideration the recently updated 5th edition of the WHO classification of hematolymphoid tumors (WHO-5HAEM) and the International Consensus Classification (ICC). Additionally, potential therapeutically targetable susceptibilities are highlighted, offering a comprehensive overview of the present scientific landscape in the field.
Summary
Background
The treatment of psoriasis has been revolutionized by the development of biologic therapies. However, the pathogenesis of psoriasis, in particular the role of the cutaneous ...microbiome, remains incompletely understood. Moreover, skin microbiome studies have relied heavily on 16S rRNA sequencing data in the absence of bacterial culture.
Objectives
To characterize and compare the cutaneous microbiome in 20 healthy controls and 23 patients with psoriasis using metagenomic analyses and to determine changes in the microbiome during treatment.
Methods
Swabs from lesional and nonlesional skin from patients with psoriasis, and from controls matched for site and skin microenvironment, were analysed using both 16S rRNA sequencing and traditional culture combined with mass spectrometry (MALDI‐TOF) in a prospective study.
Results
Psoriasis was associated with an increased abundance of Firmicutes and a corresponding reduction in Actinobacteria, most marked in lesional skin, and at least partially reversed during systemic treatment. Shifts in bacterial community composition in lesional sites were reflected in similar changes in culturable bacteria, although changes in the microbiota over repeated swabbing were detectable only with sequencing. The composition of the microbial communities varied by skin site and microenvironment. Prevotella and Staphylococcus were significantly associated with lesional skin, and Anaerococcus and Propionibacterium with nonlesional skin. There were no significant differences in the amount of bacteria cultured from the skin of healthy controls and patients with psoriasis.
Conclusions
Shifts in the cutaneous microbiome in psoriasis, particularly during treatment, may shed new light on the pathogenesis of the disease and may be clinically exploited to predict treatment response.
What's already known about this topic?
Alterations in the composition of the cutaneous microbiome have been described in psoriasis, although methodological differences in study design prevent direct comparison of results.
To date, most cutaneous microbiome studies have focused on 16S rRNA sequencing data, including both living and dead bacteria.
What does this study add?
This prospective observational study confirms that changes in the composition of the cutaneous microbiome, detected by 16S rRNA sequencing, are consistent with those identified by bacterial culture and mass spectrometry.
The changes in the microbiome during antipsoriasis therapy should be further investigated to determine whether these represent potential novel biomarkers of treatment response.
What is the translational message?
Characterization of cutaneous microbiota may ultimately move into the clinic to help facilitate treatment selection, not only by optimizing currently available treatments, but also by identifying new therapeutic targets.
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Linked Comment: Tobin. Br J Dermatol 2019; 181:1124–1125.
Background
Atopic dermatitis (AD) is a multifactorial inflammatory skin disease and an altered skin microbiota with an increase of Staphylococcus aureus has been reported. However, the role of fungi ...remains poorly investigated.
Objectives
We aimed to improve the understanding of the fungal skin microbiota, the mycobiota, in AD in relation to the bacterial colonization.
Methods
Skin swabs of 16 AD patients and 16 healthy controls (HC) from four different skin sites, that is antecubital crease, dorsal neck, glabella and vertex from multiple time points were analysed by DNA sequencing of the internal transcribed spacer region 1 (ITS1) and 16S rRNA gene for fungi and bacteria, respectively.
Results
Malassezia spp. were the predominant fungi in all subjects but with a decreased dominance in severe AD patients in favour of non‐Malassezia fungi, for example Candida spp. For bacteria, a decrease of Cutibacterium spp. in AD patients in favour of Staphylococcus spp., particularly S. aureus, was observed. Further, both bacterial and fungal community compositions of severe AD patients significantly differed from mild‐to‐moderate AD patients and HC with the latter two having overall similar microbiota showing some distinctions in bacterial communities.
Conclusions
We conclude that severe AD is associated with a pronounced dysbiosis of the microbiota with increased fungal diversity. Potentially infectious agents, for example Staphylococcus and Candida, were increased in severe AD.
Resolving the phylogenetic relationships among birds is a classical problem in systematics, and this is particularly so when it comes to understanding the relationships among Neoaves. Previous ...phylogenetic inference of birds has been limited to mitochondrial genomes or a few nuclear genes. Here, we apply deep brain transcriptome sequencing of nine bird species (several passerines, hummingbirds, dove, parrot, and emu), using next-generation sequencing technology to understand features of transcriptome evolution in birds and how this affects phylogenetic inference, and combine with data from two bird species using first generation technology. The phylogenomic data matrix comprises 1,995 genes and a total of 0.77 Mb of exonic sequence. First, we find an unexpected heterogeneity in the evolution of base composition among avian lineages. There is a pronounced increase in guanine + cytosine (GC) content in the third codon position in several independent lineages, with the strongest effect seen in passerines. Second, we evaluate the effect of GC content variation on phylogenetic reconstruction. We find important inconsistencies between the topologies obtained with or without taking GC variation into account, each supporting different conclusions of past studies and also influencing hypotheses on the evolution of the trait of vocal learning. Third, we demonstrate a link between GC content evolution and recombination rate and, focusing on the zebra finch lineage, find that recombination seems to drive GC content. Although we cannot reveal the causal relationships, this observation is consistent with the model of GC-biased gene conversion. Finally, we use this unparalleled amount of avian sequence data to study the rate of molecular evolution, calibrated by fossil evidence and augmented with data from alligator transcriptome sequencing. There is a 2- to 3-fold variation in substitution rate among lineages with passerines being the most rapidly evolving and ratites the slowest. This study illustrates the potential of next-generation sequencing for phylogenomic studies but also the pitfalls when using genome-wide data with heterogeneous base composition.
In pemphigoid diseases, direct immunofluorescence can be used to differentiate 2 patterns of antibody deposition at the dermal-epidermal junction; u- and n-serrated pattern. The u-serrated pattern is ...found in epidermolysis bullosa acquisita, and n-serrated pattern in all other pemphigoid diseases. To determine the detection frequency of these serrated patterns and the optimal thickness of biopsy cryosections, 2 patient cohorts obtained form our routine autoimmune laboratory were analysed; a retrospective cohort (n = 226) and a prospective cohort (n = 156). AQ1 In 76% (291/382) of biopsies, a pattern was recog-nized, of which 96% (278/291) and 4% (13/291) had an n- or u-serrated pattern, respectively. A u-serrated pattern was seen in all epidermolysis bullosa acquisita biopsies confirmed by serology. No antibodies against type VII collagen were detected in any of the sera from biopsies with n-serrated pattern. No differences between the detection frequencies of serrated pattern were seen with respect to age, sex, biopsy site, or section thickness, while the detection frequency was higher in patients with serum anti-BP180 reactivity compared with those without. In conclusion, serrated pattern analysis using direct immunofluorescence has a high detection frequency and specificity for epidermolysis bullosa acquisita and will further facilitate the diagnosis of latter disorder.
Colorectal cancer (CRC) is one of the most prevalent cancers, with over one million new cases per year. Overall, prognosis of CRC largely depends on the disease stage and metastatic status. As ...precision oncology for patients with CRC continues to improve, this study aimed to integrate genomic, transcriptomic, and proteomic analyses to identify significant differences in expression during CRC progression using a unique set of paired patient samples while considering tumour heterogeneity.
We analysed fresh-frozen tissue samples prepared under strict cryogenic conditions of matched healthy colon mucosa, colorectal carcinoma, and liver metastasis from the same patients. Somatic mutations of known cancer-related genes were analysed using Illumina's TruSeq Amplicon Cancer Panel; the transcriptome was assessed comprehensively using Clariom D microarrays. The global proteome was evaluated by liquid chromatography-coupled mass spectrometry (LC‒MS/MS) and validated by two-dimensional difference in-gel electrophoresis. Subsequent unsupervised principal component clustering, statistical comparisons, and gene set enrichment analyses were calculated based on differential expression results.
Although panomics revealed low RNA and protein expression of CA1, CLCA1, MATN2, AHCYL2, and FCGBP in malignant tissues compared to healthy colon mucosa, no differentially expressed RNA or protein targets were detected between tumour and metastatic tissues. Subsequent intra-patient comparisons revealed highly specific expression differences (e.g., SRSF3, OLFM4, and CEACAM5) associated with patient-specific transcriptomes and proteomes.
Our research results highlight the importance of inter- and intra-tumour heterogeneity as well as individual, patient-paired evaluations for clinical studies. In addition to changes among groups reflecting CRC progression, we identified significant expression differences between normal colon mucosa, primary tumour, and liver metastasis samples from individuals, which might accelerate implementation of precision oncology in the future.
Nasal polyposis often is characterized by a persistent inflammation of the sinonasal mucosa, disease recurrence after medical or surgical intervention, and asthma comorbidity. Dysregulated complement ...activation may contribute to immunologic alterations and disease. To date, there is only scattered knowledge on the source and regulation of the central complement factors in the pathogenesis of nasal polyps. Here, we aim to study complement signatures, especially the C3-C3aR axis, and focus on cellular sources and targets in nasal polyps. Expression of complement factors, including C3, C5, and the anaphylatoxin receptors, was analyzed in nasal polyp tissue samples, the corresponding inferior turbinates, and healthy controls using transcriptomic methods and protein measurements. Distinct patterns of complement expression were found in nasal polyps compared to controls, characterized by an increased C3 activation and an increase in C3aR-bearing cells. In contrast, no difference was shown for epithelial-dependent C3 production. Besides low intracellular C3-expression levels for lymphocytes in general, we could identify an enlarged B lymphocyte population in nasal polyps displaying high amounts of intracellular C3. Our data suggest a prominent role for the C3-C3aR-axis in nasal polyps and, for the first time, describe a B cell population containing high levels of intracellular C3, suggesting a new role of B cells in the maintenance of the inflammation by complement.
During the last few years, DNA and RNA sequencing have started to play an increasingly important role in biological and medical applications, especially due to the greater amount of sequencing data ...yielded from the new sequencing machines and the enormous decrease in sequencing costs. Particularly, Illumina/Solexa sequencing has had an increasing impact on gathering data from model and non-model organisms. However, accurate and easy to use tools for quality filtering have not yet been established. We present ConDeTri, a method for content dependent read trimming for next generation sequencing data using quality scores of each individual base. The main focus of the method is to remove sequencing errors from reads so that sequencing reads can be standardized. Another aspect of the method is to incorporate read trimming in next-generation sequencing data processing and analysis pipelines. It can process single-end and paired-end sequence data of arbitrary length and it is independent from sequencing coverage and user interaction. ConDeTri is able to trim and remove reads with low quality scores to save computational time and memory usage during de novo assemblies. Low coverage or large genome sequencing projects will especially gain from trimming reads. The method can easily be incorporated into preprocessing and analysis pipelines for Illumina data.
Freely available on the web at http://code.google.com/p/condetri.
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