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The large diversity of marine microorganisms harboured by oceans plays an important role in planet sustainability by driving globally important biogeochemical cycles; all primary and most secondary production in the oceans is performed by microorganisms. The largest part of the planet is covered by cold environments; consequently, cold-adapted microorganisms have crucial functional roles in globally important environmental processes and biogeochemical cycles cold-adapted extremophiles are a remarkable model to shed light on the molecular basis of survival at low temperature. The indigenous populations of Antarctic and Arctic microorganisms are endowed with genetic and physiological traits that allow them to live and effectively compete at the temperatures prevailing in polar regions. Some genes, e.g. glycosyltransferases and glycosylsynthetases involved in the architecture of the cell wall, may have been acquired/retained during evolution of polar strains or lost in tropical strains. This present work focusses on temperature and its role in shaping microbial adaptations; however, in assessing the impacts of climate changes on microbial diversity and biogeochemical cycles in polar oceans, it should not be forgotten that physiological studies need to include the interaction of temperature with other abiotic and biotic factors. [ABSTRACT FROM AUTHOR]

Salt marshes occupying the tidal fringe of estuaries and protected coasts provide valuable ecosystem services, and remote sensing is a powerful tool for their large-scale monitoring. However, in order to apply remote sensing techniques to evaluate the ecological state of salt marshes, a deeper understanding is needed about the interactions between field biophysical parameters and the sensor's reflectance. The main objective of this work is to analyze and quantify the influence of different biophysical parameters characterizing stands oì Spartirla alterniflora marshes in the Bahia Bianca Estuary, Argentina, on their spectral response. Spectral reflectance at high resolution was measured in S. alterniflora canopies under natural conditions, manipulating standing biomass by means of successive harvestings. Reflectance data were acquired using a FieldSpec® spectroradiometer, which measures in the visible, near-infrared, and shortwave-infrared spectral bands. Based on these reflectance data, spectral indices such as the normalized difference vegetation index (NDVI) were calculated for each biomass condition. Biomass, leaf area index (LAI), percent canopy cover (PCC), water content, and soil properties were also evaluated. LAI, PCC, and biomass were positively correlated between each other. As a general trend, as biomass decreased, absorption in red wavelengths decreased and reflectance in near-infrared increased. Several indices explained the variability in LAI, biomass, and PCC. For example, NDVIRouse had a positive regression with PCC CR² = 0.80, N= 75) and LAI (R² = 0.67, N= 75). Results indicate that LAI, biomass, and PCC of Spartina alterniflora could be accurately determined from spectral data. [ABSTRACT FROM AUTHOR]

Nitrogen inputs and microbial nitrogen cycling were investigated along a 79 km transect into the Greenland Ice Sheet (GrIS) during the main ablation season in summer 2010. The depletion of dissolved nitrate and production of ammonium (relative to icemelt) in cryoconite holes on Leverett Glacier, within 7.5 km of the ice sheet margin, suggested microbial uptake and ammonification respectively. Positive in situ acetylene assays indicated nitrogen fixation both in a debris-rich 100 m marginal zone and up to 5.7 km upslope on Leverett Glacier (with rates up to 16.3 µmoles C2H4 m-2 day-1). No positive acetylene assays were detected > 5.7 km into the ablation zone of the ice sheet. Potential nitrogen fixation only occurred when concentrations of dissolved and sediment-bound inorganic nitrogen were undetectable. Estimates of nitrogen fluxes onto the transect suggest that nitrogen fixation is likely of minor importance to the overall nitrogen budget of Leverett Glacier and of negligible importance to the nitrogen budget on the main ice sheet itself. Nitrogen fixation is however potentially important as a source of nitrogen to microbial communities in the debrisrich marginal zone close to the terminus of the glacier, where nitrogen fixation may aid the colonization of subglacial and moraine-derived debris. [ABSTRACT FROM AUTHOR]

No overall increased risk of lymphoma associated with antibodies to human herpesvirus-8 was found in 526 lymphomas and 599 controls (odds ratio (OR)=1.04, 95% confidence interval (CI)=0.62-1.75); significant increases were noted for 19 lymphoplasmacytic lymphomas (OR=4.47, 95% CI=1.34-14.85) and nine low-grade lymphoma/lymphoma B-cell NOS (OR=5.82, 95% CI=1.07-31.73). [ABSTRACT FROM AUTHOR]

We have used the enzymatic in situ hybridization method to investigate the presence of Epstein-Barr virus (EBV) genome in lymph node tissues from patients with Hodgkin's disease. Also, 11 patients with persistent human immuno-deficiency virus-associated generalized lymphadenopathy as well as seven autopsy cases with no Hodgkin's disease, formed part of these studies. EBV DNA-positive reaction was demonstrated in Reed-Sternberg cells and variants in seven of 16 cases and in the small accompanying lymphocyte cell population in 14 of the 16 cases. It was also found in eight of the 11 cases with persistent generalized lymphadenopathy but in none of the lymph nodes from negative selective autopsy cases. Our results indicate that the colorimetric in situ hybridization technique is useful in EBV nucleic acid detection and cell-type localization in Hodgkin's disease. Additionally, the detection of EBV genome, not only in the diagnostic cells but in the small lymphocyte cell components, could provide new insights into the potential role of this agent in the pathogenesis of Hodgkin's disease. [ABSTRACT FROM PUBLISHER]

Lymphoid follicles are the main B-cell areas in peripheral lymphoid tissues. These structures commonly consist of germinal centre (GC) and mantle zone (MZ) regions. In the present work, human tonsillar B cells belonging to these two compartments were purified by a combination of density centrifugation and separation techniques involving the recognition by monoclonal antibodies of specific surface molecules followed by panning and magnetic bead selection. These purified populations were identified as GC and MZ cells by three different criteria; (I) GC cells showed the phenotype IgO CD20-1bright CD38-1 CD44 and peanut agglutinin (PNA)-1, and MZ cells were IgD CD20-1, dim CD38 CD44-1 and PNA ; (2) morphologically, MZ cells appeared as small resting lymphocytes whereas GC cells consisted of large blastic cells of the germinal centre: (3) functionally, most GC, but not MZ. cells underwent apoptosis early in culture. The isolation of GC and MZ cells allowed the study of their proliferative response. As a result of these studies, GC cells were demonstrated to inhibit the proliferation of MZ cells in response to B-cell mitogens (Staphylococcus aureus Cowan I and anti-μ plus BCGF) in a concentration-dependent way; 50% inhibition was reached at a GC/MZ cell ratio of l.2. This effect did not require GC-cell DNA synthesis since similar results were obtained with irradiated GC cells. Neither was it due to a non-specific toxic effect since GC cells did not alter the proliferative response of autologous T cells to mitogens [phytohaemagglutin and anti-CD3), The inhibition required cellular contact between GC and MZ cells, and was not restricted by histocompatibility barriers. These data suggest the possible existence ofa new regulatory pathway wilhin peripheral B-cell areas. [ABSTRACT FROM AUTHOR]

We have studied by the in situ hybridization method the presence of Epstein-Barr virus (EBV) DNA genome in lymph node tissues from 11 patients with persistent generalized lymphadenopathy. Using a biotinylated EBV DNA probe, we demonstrated EBV nucleic acid in scattered germinal centre cells in eight of the 11 cases. Our results suggest that EBV is not a determinant factor in the pathogenesis of this lymphadenopathy, but support its possible implication in B cell malignant transformation in cases of AIDS-associated lymphoma. [ABSTRACT FROM PUBLISHER]

We report the case of a man with generalized osteosclerosis secondary to well-differentiated lymphocytic lymphoma. This finding is considered to be exceptional in this type of lymphoma, especially when other organs were not found to be involved. A year after the diagnosis was established the patient appeared to be in relatively good health. The radiological pattern showed no change from the original studies, nor was there any evidence of neoplastic involvement in any other location. [ABSTRACT FROM AUTHOR]

Abstract Background Cervical cancer is the second most common cancer in women worldwide. Infection with certain human papillomavirus (HPV) genotypes is the most important risk factor associated with cervical cancer. This study analysed the distribution of type-specific HPV infection among women with normal and abnormal cytology, to assess the potential benefit of prophylaxis with anti-HPV vaccines. Methods Cervical samples of 2,461 women (median age 34 years; range 15-75) from the centre of Spain were tested for HPV DNA. These included 1,656 samples with normal cytology (NC), 336 with atypical squamous cells of undetermined significance (ASCUS), 387 low-grade squamous intraepithelial lesions (LSILs), and 82 high-grade squamous intraepithelial lesions (HSILs). HPV detection and genotyping were performed by PCR using 5'-biotinylated MY09/11 consensus primers, and reverse dot blot hybridisation. Results HPV infection was detected in 1,062 women (43.2%). Out of these, 334 (31%) samples had normal cytology and 728 (69%) showed some cytological abnormality: 284 (27%) ASCUS, 365 (34%) LSILs, and 79 (8%) HSILs. The most common genotype found was HPV 16 (28%) with the following distribution: 21% in NC samples, 31% in ASCUS, 26% in LSILs, and 51% in HSILs. HPV 53 was the second most frequent (16%): 16% in NC, 16% in ASCUS, 19% in LSILs, and 5% in HSILs. The third genotype was HPV 31 (12%): 10% in NC, 11% in ASCUS, 14% in LSILs, and 11% in HSILs. Co-infections were found in 366 samples (34%). In 25%, 36%, 45% and 20% of samples with NC, ASCUS, LSIL and HSIL, respectively, more than one genotype was found. Conclusions HPV 16 was the most frequent genotype in our area, followed by HPV 53 and 31, with a low prevalence of HPV 18 even in HSILs. The frequency of genotypes 16, 52 and 58 increased significantly from ASCUS to HSILs. Although a vaccine against HPV 16 and 18 could theoretically prevent approximately 50% of HSILs, genotypes not covered by the vaccine are frequent in our population. Knowledge of the epidemiological distribution is necessary to predict the effect of vaccines on incidence of infection and evaluate cross-protection from current vaccines against infection with other types.

Highlights • Semi-automatic method to standardize the study of Neutrophil Extracellular Traps. • Quantification of Neutrophil Extracellular Traps in paraffin-embedded tissues. • Extracellular Traps identified as colocalization of Myeloperoxidase and Histone. • Area of Neutrophil Extracellular Traps is calculated per μm2. • Confocal Microscopy provides information about the structure of Extracellular Traps. Abstract Detection and quantification of Neutrophil Extracellular Traps (NETs) in tissue samples has become a topic of great interest to understand their pathological role in various diseases. We describe a semi-automatic method of visualization and quantification of NETs in paraffin-embedded intracoronary thrombus aspirate samples. This study is based on colocalization of myeloperoxidase (MPO) and citrullinated histone 3 (H3Cit) as hallmark of the presence of NETs. For the analysis we used the confocal immunofluorescence microscopy technology to quantify the number of fields and the total area (in μm2) containing NETs in each thrombus sample. This observer-independent quantification method could be a useful tool to standardize the study of NETs in paraffin-embedded tissues, enabling comparison of results among different laboratories. [ABSTRACT FROM AUTHOR]

Introduction and Objectives: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1ra) reduce cardiovascular events through different mechanisms, but their association with cancer remains unclear. The aim of this study was to compare the effect of combined treatment (SGLT2i and GLP1ra) and monotherapy (SGLT2i or GLP1ra) on hospitalization and/or death from cancer in a general population and a subgroup of patients with cardiovascular disease (CVD)., Methods: We conducted a nonconcurrent observational prospective study of patients prescribed SGLT2i, GLP1ra, or both. Multinomial propensity scores were performed in the entire population and in a subgroup of patients with CVD. A multivariate Cox regression analysis was used to determine the hazard ratio (HR) for age, sex, risk factors, and treatment for each outcome., Results: We included 14 709 patients (11366 with SGLT2i, 1016 with GLP1ra, and 2327 with both treatments) from treatment initiation. Diabetes was present in 97% of the patients. The subgroup with CVD included 4957 (33.7%) patients. After a median of 33 months of follow-up, the risk of adverse cancer events was similar between patients with and without CVD (3.4% or 3.7%, respectively). The main risk factors for cancer mortality were male sex and age. Combined treatment and its duration reduced the risk of cancer mortality compared with monotherapy with SGLT2i or GLP1ra in the overall population (HR, 0.2216; 95%CI, 0.1106-0.4659; P<.001; and HR, 0.1928; 95%CI, 0.071-0.5219; P=.001, respectively) and in the subgroup of patients with CVD (HR, 0.2879; 95%CI, 0.0878-0.994; P<.049; and HR, 0.1329; 95%CI, 0.024-0.6768; P=.014, respectively)., Conclusions: Initiation of combined therapy (SGLT2i and GLP1ra) vs monotherapy with SGLT2i or GLP1ra was associated with a lower risk of cancer mortality, mostly in diabetic patients with or without CVD. Although clinical trials are needed, these results might be explained by the complementary mechanisms of these drugs, including their antiproliferative, anti-inflammatory, and metabolic effects. Future clinical trials and mechanistic studies will clarify the possible role of these drugs in carcinogenesis., (Copyright © 2024 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

One major conundrum of modern microbiology is the large pangenome (gene pool) present in microbes, which is much larger than those found in complex organisms such as humans. Here, we argue that this diversity of gene pools carried by different strains is maintained largely due to the control exercised by viral predation. Viruses maintain a high strain diversity through time that we describe as constant-diversity equilibrium, preventing the hoarding of resources by specific clones. Thus, viruses facilitate the release and degradation of dissolved organic matter in the ocean, which may lead to better ecosystem functioning by linking top-down to bottom-up control. By maintaining this equilibrium, viruses act as a key element of the adaptation of marine microbes to their environment and likely evolve as a single evolutionary unit.

Background: Although atrial fibrosis has a relevant impact on ablation success rate, experimental studies have reported that extensive fibrosis may be accompanied by a reduced burden secondary to a prominent depression of atrial excitability., Objectives: We aimed to identify clinical and echocardiographic factors associated with extensive left atrial myopathy (ELAM), to analyze the predictive ability of established scores (AF score, APPLE, and DR-FLASH) and assess outcomes in terms of AF recurrence, left atrial flutter, and post-procedural heart failure admissions., Methods: A total of 950 consecutive patients undergoing the first AF ablation were included. A 3D electroanatomical mapping system (CARTO3, Biosense Webster) was created using a multipolar mapping catheter (PentaRay, Biosense Webster). ELAM was defined as ≥ 50% low voltage area. A subanalysis with four groups was also created (< 10%; 10-20%; 10-20%; and > 30%). Logistic regressions, Cox proportional hazards models, and log-rank test were used to test the predictors independently associated with the presence of ELAM and AF recurrence. The model was prospectively validated in a cohort of 150 patients obtaining an excellent ability for prediction AUC 0.90 (CI 95% 0.84-0.96)., Results: Overall, 78 (8.42%) presented ELAM. Age, female sex, persistent AF, first-degree AV block, and E/e' were significant predictors. The model incorporating these factors outperformed the existing scores (AUC = 0.87). During a mean follow-up of 20 months (IQR 9 to 36), patients with ELAM presented a higher rate of AF recurrence (42.02% vs 26.01%, p = 0.030), left atrial flutter (26.03% vs 8.02%, p < 0.001), and post-procedural heart failure admissions (12.01% vs 0.61%, p < 0.001) than non-ELAM patients., Conclusions: This study reveals the incidence and clinical factors associated with ELAM in AF, highlighting age, female, persistent AF, first-degree AV block, and E/e'. Importantly, the presence of ELAM is associated with poorer outcomes in terms of recurrence and HF admission., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Dark pigmented snow and glacier ice algae on glaciers and ice sheets contribute to accelerating melt. The biological controls on these algae, particularly the role of viruses, remain poorly understood. Giant viruses, classified under the nucleocytoplasmic large DNA viruses (NCLDV) supergroup (phylum Nucleocytoviricota), are diverse and globally distributed. NCLDVs are known to infect eukaryotic cells in marine and freshwater environments, providing a biological control on the algal population in these ecosystems. However, there is very limited information on the diversity and ecosystem function of NCLDVs in terrestrial icy habitats., Results: In this study, we investigate for the first time giant viruses and their host connections on ice and snow habitats, such as cryoconite, dark ice, ice core, red and green snow, and genomic assemblies of five cultivated Chlorophyta snow algae. Giant virus marker genes were present in almost all samples; the highest abundances were recovered from red snow and the snow algae genomic assemblies, followed by green snow and dark ice. The variety of active algae and protists in these GrIS habitats containing NCLDV marker genes suggests that infection can occur on a range of eukaryotic hosts. Metagenomic data from red and green snow contained evidence of giant virus metagenome-assembled genomes from the orders Imitervirales, Asfuvirales, and Algavirales., Conclusion: Our study highlights NCLDV family signatures in snow and ice samples from the Greenland ice sheet. Giant virus metagenome-assembled genomes (GVMAGs) were found in red snow samples, and related NCLDV marker genes were identified for the first time in snow algal culture genomic assemblies; implying a relationship between the NCLDVs and snow algae. Metatranscriptomic viral genes also aligned with metagenomic sequences, suggesting that NCLDVs are an active component of the microbial community and are potential "top-down" controls of the eukaryotic algal and protistan members. This study reveals the unprecedented presence of a diverse community of NCLDVs in a variety of glacial habitats dominated by algae., (© 2024. The Author(s).)

Eukaryotic genomes contain a variety of endogenous viral elements (EVEs), which are mostly derived from RNA and ssDNA viruses that are no longer functional and are considered to be "genomic fossils." Genomic surveys of EVEs, however, are strongly biased toward animals and plants, whereas protists, which represent the majority of eukaryotic diversity, remain poorly represented. Here, we show that protist genomes harbor tens to thousands of diverse, ~14 to 40 kbp long dsDNA viruses. These EVEs, composed of virophages, Polinton-like viruses, and related entities, have remained hitherto hidden owing to poor sequence conservation between virus groups and their repetitive nature that precluded accurate short-read assembly. We show that long-read sequencing technology is ideal for resolving virus insertions. Many protist EVEs appear intact, and most encode integrases, which suggests that they have actively colonized hosts across the tree of eukaryotes. We also found evidence for gene expression in host transcriptomes and that closely related virophage and Polinton-like virus genomes are abundant in viral metagenomes, indicating that many EVEs are probably functional viruses.

Photoheterotrophic bacteria harvest light energy using either proton-pumping rhodopsins or bacteriochlorophyll (BChl)-based photosystems. The bacterium Sphingomonas glacialis AAP5 isolated from the alpine lake Gossenköllesee contains genes for both systems. Here, we show that BChl is expressed between 4°C and 22°C in the dark, whereas xanthorhodopsin is expressed only at temperatures below 16°C and in the presence of light. Thus, cells grown at low temperatures under a natural light-dark cycle contain both BChl-based photosystems and xanthorhodopsins with a nostoxanthin antenna. Flash photolysis measurements proved that both systems are photochemically active. The captured light energy is used for ATP synthesis and stimulates growth. Thus, S. glacialis AAP5 represents a chlorophototrophic and a retinalophototrophic organism. Our analyses suggest that simple xanthorhodopsin may be preferred by the cells under higher light and low temperatures, whereas larger BChl-based photosystems may perform better at lower light intensities. This indicates that the use of two systems for light harvesting may represent an evolutionary adaptation to the specific environmental conditions found in alpine lakes and other analogous ecosystems, allowing bacteria to alternate their light-harvesting machinery in response to large seasonal changes of irradiance and temperature.

Aims:  The mechanisms of coronary thrombosis can influence prognosis after ST-elevation myocardial infarction (STEMI) and allow for different treatment groups to be identified; an association between neutrophil extracellular traps (NETs) and unfavorable clinical outcomes has been suggested. Our aim was to determine the role played by NETs in coronary thrombosis and their influence on prognosis. The role of other histological features in prognosis and the association between NETs and bacteria in the coronary thrombi were also explored., Methods and Results:  We studied 406 patients with STEMI in which coronary thrombi were consecutively obtained by aspiration during angioplasty between 2012 and 2018. Analysis of NETs in paraffin-embedded thrombi was based on the colocalization of specific NET components by means of confocal microscopy. Immunohistochemistry stains were used to identify plaque fragments. Fluorescence in situ hybridization was used to detect bacteria.NETs were detected in 51% of the thrombi (NET density, median [interquartile range]: 25% [17-38%]). The median follow-up was 47 months (95% confidence interval [CI] 43-51); 105 (26%) patients experienced major adverse cardiac events (MACE). A significant association was found between the presence of NETs in coronary aspirates and the occurrence of MACE in the first 30 days after infarction (hazard ratio 2.82; 95% CI 1.26-6.35, p  = 0.012), mainly due to cardiac deaths and stent thrombosis., Conclusion:  The presence of NETs in coronary thrombi was associated with a worse prognosis soon after STEMI. In some patients, NETs could be a treatment target and a feasible way to prevent reinfarction., Competing Interests: None declared., (Thieme. All rights reserved.)

Sea ice continues to decline across many regions of the Arctic, with remaining ice becoming increasingly younger and more dynamic. These changes alter the habitats of microbial life that live within the sea ice, which support healthy functioning of the marine ecosystem and provision of resources for human-consumption, in addition to influencing biogeochemical cycles (e.g. air-sea CO 2 exchange). With the susceptibility of sea ice ecosystems to climate change, there is a pressing need to fill knowledge gaps surrounding sea ice habitats and their microbial communities. Of fundamental importance to this goal is the development of new methodologies that permit effective study of them. Based on outcomes from the DiatomARCTIC project, this paper integrates existing knowledge with case studies to provide insight on how to best document sea ice microbial communities, which contributes to the sustainable use and protection of Arctic marine and coastal ecosystems in a time of environmental change., (© 2021. The Author(s).)

Importance: Severe coronavirus disease 2019 (COVID-19) is characterized by the intense formation of neutrophil extracellular traps (NETs), leading to the occlusion of microvessels, as shown in pulmonary samples. The occurrence of ST-elevated myocardial infarction (STEMI) is a serious cardiac manifestation of COVID-19; the intrinsic mechanism of coronary thrombosis appears to still be unknown., Objective: To determine the role of NETs in coronary thrombosis in patients with COVID-19., Design, Setting, and Participants: This was a consecutive series of patients with COVID-19 at an academic tertiary hospital in Madrid, Spain, who underwent primary coronary interventions for STEMI in which coronary aspirates were obtained in the catheterization laboratory using a thrombus aspiration device. Patients with COVID-19 who experienced a STEMI between March 23 and April 11, 2020, from whom coronary thrombus samples were aspirated during primary coronary intervention, were included in the analysis. These patients were compared with a series conducted from July 2015 to December 2015 of patients with STEMI., Main Outcomes and Measures: The presence and quantity of NETs in coronary aspirates from patients with STEMI and COVID-19. The method for the analysis of NETs in paraffin-embedded coronary thrombi was based on the use of confocal microscopy technology and image analysis for the colocalization of myeloperoxidase-DNA complexes and citrullinated histone H3. Immunohistochemical analysis of thrombi was also performed. Clinical and angiographic variables were prospectively collected., Results: Five patients with COVID-19 were included (4 men [80%]; mean [SD] age, 62 [14] years); the comparison group included 50 patients (44 males [88%]; mean [SD] age, 58 [12] years). NETs were detected in the samples of all 5 patients with COVID-19, and the median density of NETs was 61% (95% CI, 43%-91%). In the historical series of patients with STEMI, NETs were found in 34 of 50 thrombi (68%), and the median NET density was 19% (95% CI, 13%-22%; P < .001). All thrombi from patients with COVID-19 were composed of fibrin and polymorphonuclear cells. None of them showed fragments of atherosclerotic plaque or iron deposits indicative of previous episodes of plaque rupture., Conclusions and Relevance: In this small case series of patients with COVID-19 and myocardial infarction, NETs seem to play a major role in the pathogenesis of STEMI in COVID-19 disease. Our findings support the idea that targeting intravascular NETs might be a relevant goal of treatment and a feasible way to prevent coronary thrombosis in patients with severe COVID-19 disease.

We investigated the clinicopathological features and prognostic factors of patients with peripheral T-cell lymphoma (PTCL) in 13 sites across Spain. Relevant clinical antecedents, CD30 expression and staining pattern, prognostic indices using the International Prognostic Index and the Intergruppo Italiano Linfomi system, treatments, and clinical outcomes were examined. A sizeable proportion of 175 patients had a history of immune-related disorders (autoimmune 16%, viral infections 17%, chemo/radiotherapy-treated carcinomas 19%). The median progression-free survival (PFS) and overall survival (OS) were 7·9 and 15·8 months, respectively. Prognostic indices influenced PFS and OS, with a higher number of adverse factors resulting in shorter survival (P < 0·001). Complete response (CR) to treatment was associated with better PFS (62·6 vs. 4 months; P < 0·001) and longer OS (67·0 vs. 7·3 months; P < 0·001) compared to no CR. CD30 was expressed across all subtypes; >15% of cells were positive in anaplastic lymphoma kinase-positive and -negative anaplastic large-cell lymphoma and extranodal natural killer PTCL groups. We observed PTCL distribution across subtypes based on haematopathological re-evaluation. Poor prognosis, effect of specific prognostic indices, relevance of histopathological sub-classification, and response level to first-line treatment on outcomes were confirmed. Immune disorders amongst patients require further examination involving genetic studies and identification of associated immunosuppressive factors., (© 2020 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Follicular lymphoma (FL) is an indolent but largely incurable disease. Some patients suffer histological transformation to a more aggressive subtype with poorer prognosis. This study aimed to improve our understanding of the genetics underlying FL histological transformation, and to identify genetic drivers or promoters of the transformation by elucidating the differences between FL samples from patients who did and did not transform. We conducted targeted massive parallel sequencing of 22 pre-transformed FL/transformed diffuse large B-cell lymphoma pairs and 20 diagnostic samples from non-transformed FL patients. Additionally, 22 matched samples from 11 transformed FL patients (pre-transformed FL and diffuse large B-cell lymphoma) and 9 non-transformed FLs were studied for copy number variation using SNP arrays. We identified recurrently mutated genes that were enriched at transformation, most notably LRP1B, GNA13 and POU2AF1, which have roles in B-cell differentiation, GC architecture and migration. Mutations in POU2AF1 might be associated with lower levels of expression, were more frequent in transformed FLs, and seemed to be specific to transformed- compared with de novo-diffuse large B-cell lymphomas. Pre-transformed FLs carried more mutations per sample and had greater subclonal heterogeneity than non-transformed FLs. Finally, we identified four mutated genes in FL samples that differed between patients who did and did not transform: NOTCH2, DTX1, UBE2A and HIST1H1E. The presence of mutations in these genes was associated with shorter time to transformation when mutated in the FL biopsies. This information might be useful for identifying patients at higher risk of transformation., Competing Interests: The authors have declared that no competing interests exist.

The oncogenic capacity of cyclin D1 has long been established in breast cancer. CCND1 amplification has been identified in a subset of patients with poor prognosis, but there are conflicting data regarding the predictive value of cyclin D1 protein overexpression. This study was designed to analyze the expression of cyclin D1 and its correlation with CCND1 amplification and their prognostic implications in invasive breast cancer. By using the tissue microarray technique, we performed an immunohistochemical study of ER, PR, HER2, p53, cyclin D1, Ki67 and p16 in 179 invasive breast carcinoma cases. The FISH method was performed to detect HER2/Neu and CCND1 amplification. High cyclin D1 expression was identified in 94/179 (52%) of invasive breast cancers. Cyclin D1 overexpression and CCND1 amplification were significantly associated (p = 0.010). Overexpression of cyclin D1 correlated with ER expression, PR expression and Luminal subtypes (p<0.001), with a favorable impact on overall survival in the whole series. However, in the Luminal A group, high expression of cyclin D1 correlated with shorter disease-free survival, suggesting that the prognostic role of cyclin D1 depends on the molecular subtype. CCND1 gene amplification was detected in 17 cases (9%) and correlated significantly with high tumor grade (p = 0.038), high Ki-67 protein expression (p = 0.002), and the Luminal B subtype (p = 0.002). Patients with tumors with high amplification of CCND1 had an increased risk of recurrence (HR = 2.5; 95% CI, 1.2-4.9, p = 0.01). These findings suggest that CCND1 amplification could be useful for predicting recurrence in invasive breast cancer.

Primary breast lymphoma is a rare form of extra-nodal lymphoid neoplasm. The most common histological type is the diffuse large B-cell lymphoma, which represents 60-80% of all the cases. Our study analyzes the mutational profile of the primary lymphoma of the breast through targeted massive sequencing with a panel of 38 genes in a group of 17 patients with primary breast diffuse large B-cell lymphoma. Seventy-point-five percent of the patients presented with stage IE and 29.5% with stage IIE. 44% of the cases correspond to lymphomas with germinal center phenotype and 33.3% to activated B-cell. The genes with a higher mutational frequency include PIM1 (in 50% of the analyzed samples), MYD88 (39%), CD79B, PRDM1 and CARD11 (17%), KMT2D , TNFIAP3 and CREBBP (11%). The profile of mutant genes involves mostly the NFκB signaling pathway. The high frequency of mutations in PIM1 compared with other lymphomas may have implications in the clinical presentation and evolution of this type of lymphoma., Competing Interests: CONFLICTS OF INTEREST The authors declare no competing financial interests.

Introduction and Objectives: Thrombus aspiration allows analysis of intracoronary material in patients with ST-segment elevation myocardial infarction. Our objective was to characterize this material by immunohistology and to study its possible association with patient progress., Methods: This study analyzed a prospective cohort of 142 patients undergoing primary angioplasty with positive coronary aspiration. Histological examination of aspirated samples included immunohistochemistry stains for the detection of plaque fragments. The statistical analysis comprised histological variables (thrombus age, degree of inflammation, presence of plaque), the patients' clinical and angiographic features, estimation of survival curves, and logistic regression analysis., Results: Among the histological markers, only the presence of plaque (63% of samples) was associated with postinfarction clinical events. Factors associated with 5-year event-free survival were the presence of plaque in the aspirate (82.2% vs 66.0%; P = .033), smoking (82.5% smokers vs 66.7% nonsmokers; P = .036), culprit coronary artery (83.3% circumflex or right coronary artery vs 68.5% anterior descending artery; P = .042), final angiographic flow (80.8% II-III vs 30.0% 0-I; P < .001) and left ventricular ejection fraction ≥ 35% at discharge (83.7% vs 26.7%; P < .001). On multivariable Cox regression analysis with these variables, independent predictors of event-free survival were the presence of plaque (hazard ratio, 0.37; 95%CI, 0.18-0.77; P = .008), and left ventricular ejection fraction (hazard ratio, 0.92; 95%CI, 0.88-0.95; P < .001)., Conclusions: The presence of plaque in the coronary aspirate of patients with ST elevation myocardial infarction may be an independent prognostic marker. CD68 immunohistochemical stain is a good method for plaque detection., (Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Classical Hodgkin lymphoma (cHL) is frequently related to Epstein-Barr virus (EBV) infection. Its malignant capacity is attributed to disruption of an EBV-host balance influenced by environmental and genetic drivers. EBV structures activate Type I interferon (IFN) pathway of the innate immunity, therefore, genetic polymorphisms could influence this response. We explored the impact of four single nucleotide polymorphisms (SNPs) on EBV-associated cHL susceptibility. Toll-like receptors 9 (TLR9&#95;rs5743836), and 3 (TLR3&#95;rs3775291), Interleukin-28B (IL28B&#95;rs12979860), and DEAD-box polypeptide 58 (DDX58&#95;rs10813831) were genotyped in 73 EBV-positive and 106 EBV-negative cHL patients and 396 controls. Only DDX58&#95;rs10813831 T-allele was decreased among EBV-positive cHL compared to controls. A stratified analysis in EBV-positive cHL showed that the reduced rate was associated with younger age and nodular sclerosis. In conclusion, DDX58&#95;rs10813831 T-allele may be associated with a reduced risk of nodular sclerosis EBV-related cHL, which suggests a role for RIG-I (retinoic acid-inducible gene I), encoded by DDX58, in these cases.

The large diversity of marine microorganisms harboured by oceans plays an important role in planet sustainability by driving globally important biogeochemical cycles; all primary and most secondary production in the oceans is performed by microorganisms. The largest part of the planet is covered by cold environments; consequently, cold-adapted microorganisms have crucial functional roles in globally important environmental processes and biogeochemical cycles cold-adapted extremophiles are a remarkable model to shed light on the molecular basis of survival at low temperature. The indigenous populations of Antarctic and Arctic microorganisms are endowed with genetic and physiological traits that allow them to live and effectively compete at the temperatures prevailing in polar regions. Some genes, e.g. glycosyltransferases and glycosylsynthetases involved in the architecture of the cell wall, may have been acquired/retained during evolution of polar strains or lost in tropical strains. This present work focusses on temperature and its role in shaping microbial adaptations; however, in assessing the impacts of climate changes on microbial diversity and biogeochemical cycles in polar oceans, it should not be forgotten that physiological studies need to include the interaction of temperature with other abiotic and biotic factors., (© 2016 Elsevier Ltd All rights reserved.)