The Value of Contrast-Enhanced Ultrasound (CEUS) in the Evaluation of Central Lung Cancer with Obstructive Atelectasis.

Purpose: To assess the diagnostic performance of contrast-enhanced ultrasound (CEUS) alongside contrast-enhanced computed tomography (CECT) in evaluating central lung cancer (CLC). Materials and Methods: From 2006 to 2022, 54 patients with CLC and obstructive atelectasis (OAT) underwent standardized examinations using CEUS in addition to CECT. The ability to differentiate CLC from atelectatic tissue in CECT and CEUS was categorized as distinguishable or indistinguishable. In CEUS, in distinguishable cases, the order of enhancement (time to enhancement) (OE; categorized as either an early pulmonary arterial [PA] pattern or a delayed bronchial arterial [BA] pattern of enhancement), the extent of enhancement (EE; marked or reduced), the homogeneity of enhancement (HE; homogeneous or inhomogeneous), and the decrease in enhancement (DE; rapid washout [<120 s] or late washout [≥120 s]) were evaluated. Results: The additional use of CEUS improved the diagnostic capability of CECT from 75.9% to 92.6% in differentiating a CLC from atelectatic tissue. The majority of CLC cases exhibited a BA pattern of enhancement (89.6%), an isoechoic reduced enhancement (91.7%), and a homogeneous enhancement (91.7%). Rapid DE was observed in 79.2% of cases. Conclusions: In cases of suspected CLC with obstructive atelectasis, the application of CEUS can be helpful in differentiating tumor from atelectatic tissue and in evaluating CLC.

Contrast-enhanced ultrasound of the liver: Vascular pathologies and interventions. / Kontrastmittelunterstützte Sonografie der Leber: vaskuläre Pathologien und Interventionen.

Over the past two decades, contrast-enhanced ultrasound (CEUS) has been established as a method complementary to B-mode ultrasound and color Doppler sonography for diagnosing vascular liver pathologies and interventions.The objective of this review is to elucidate the application of CEUS in diagnosing vascular pathologies and interventional procedures.Considering the limitations of ultrasound, CEUS presents a similar alternative to other imaging modalities, such as computed tomography and magnetic resonance imaging, for evaluating vascular pathologies, guiding interventions, identifying complications, and assessing outcomes post intervention. Due to its widespread availability and the absence of radiation exposure, CEUS should be employed as a primary modality. · CEUS plays an important role in the detection of vascular liver pathologies.. · CEUS is helpful in characterizing vascular pathologies.. · CEUS is helpful in guiding interventions and identifying complications..

The value of contrast-enhanced ultrasound in percutaneous biopsy of retroperitoneal masses.

PURPOSE: To evaluate the diagnostic yield of contrast-enhanced ultrasound (CEUS)-guided biopsy of retroperitoneal masses (RMs). MATERIALS AND METHODS: Between 2006 and 2023, 87 patients presented at our US center for biopsy of an RM. In all biopsies, CEUS was performed prior to the intervention. The technical success rate of biopsy, the presence of diagnostic tissue in solid tumor biopsy samples, the accuracy of the biopsy and the occurrence of post-interventional complications were evaluated. RESULTS: A US-guided biopsy could be conducted in 84/87 cases (96.6%). In 3/87 cases (3.4%), US-guided biopsy was impossible because the planned needle path was obstructed by vital structures. Of 84 lesions, 80 (95.2%) were solid lesions, and 4 (4.8%) were lesions containing fluid. In all solid tumors, 80/80 (100%), diagnostic vital tissue was successfully obtained. CEUS-guided biopsy showed a sensitivity of 93.2%, a specificity of 100%, a positive predictive value of 100%, a negative predictive value of 72.2%, and a diagnostic accuracy of 94.2% for the differentiation between malignant and benign RMs. In one of the 84 cases (1.2%), there was a complication of postinterventional abdominal pain. CONCLUSION: Percutaneous CEUS-guided biopsy is a safe procedure with a high diagnostic yield and a low complication rate.

E2F transcription factor-1 modulates expression of glutamine metabolic genes in mouse embryonic fibroblasts and uterine sarcoma cells.

Metabolic reprogramming is considered as a hallmark of cancer and is clinically exploited as a novel target for therapy. The E2F transcription factor-1 (E2F1) regulates various cellular processes, including proliferative and metabolic pathways, and acts, depending on the cellular and molecular context, as an oncogene or tumor suppressor. The latter is evident by the observation that E2f1-knockout mice develop spontaneous tumors, including uterine sarcomas. This dual role warrants a detailed investigation of how E2F1 loss impacts metabolic pathways related to cancer progression. Our data indicate that E2F1 binds to the promoter of several glutamine metabolism-related genes. Interestingly, the expression of genes in the glutamine metabolic pathway were increased in mouse embryonic fibroblasts (MEFs) lacking E2F1. In addition, we confirm that E2f1-/- MEFs are more efficient in metabolizing glutamine and producing glutamine-derived precursors for proliferation. Mechanistically, we observe a co-occupancy of E2F1 and MYC on glutamine metabolic promoters, increased MYC binding after E2F1 depletion and that silencing of MYC decreased the expression of glutamine-related genes in E2f1-/- MEFs. Analyses of transcriptomic profiles in 29 different human cancers identified uterine sarcoma that showed a negative correlation between E2F1 and glutamine metabolic genes. CRISPR/Cas9 knockout of E2F1 in the uterine sarcoma cell line SK-UT-1 confirmed elevated glutamine metabolic gene expression, increased proliferation and increased MYC binding to glutamine-related promoters upon E2F1 loss. Together, our data suggest a crucial role of E2F1 in energy metabolism and metabolic adaptation in uterine sarcoma cells.

The Space of Equidistant Phylogenetic Cactuses.

An equidistant X-cactus is a type of rooted, arc-weighted, directed acyclic graph with leaf set X, that is used in biology to represent the evolutionary history of a set X of species. In this paper, we introduce and investigate the space of equidistant X-cactuses. This space contains, as a subset, the space of ultrametric trees on X that was introduced by Gavryushkin and Drummond. We show that equidistant-cactus space is a CAT(0)-metric space which implies, for example, that there are unique geodesic paths between points. As a key step to proving this, we present a combinatorial result concerning ranked rooted X-cactuses. In particular, we show that such graphs can be encoded in terms of a pairwise compatibility condition arising from a poset of collections of pairs of subsets of X that satisfy certain set-theoretic properties. As a corollary, we also obtain an encoding of ranked, rooted X-trees in terms of partitions of X, which provides an alternative proof that the space of ultrametric trees on X is CAT(0). We expect that our results will provide the basis for novel ways to perform statistical analyses on collections of equidistant X-cactuses, as well as new directions for defining and understanding spaces of more general, arc-weighted phylogenetic networks.

A distance-based model for convergent evolution.

Convergent evolution is an important process in which independent species evolve similar features usually over a long period of time. It occurs with many different species across the tree of life, and is often caused by the fact that species have to adapt to similar environmental niches. In this paper, we introduce and study properties of a distance-based model for convergent evolution in which we assume that two ancestral species converge for a certain period of time within a collection of species that have otherwise evolved according to an evolutionary clock. Under these assumptions it follows that we obtain a distance on the collection that is a modification of an ultrametric distance arising from an equidistant phylogenetic tree. As well as characterising when this modified distance is a tree metric, we give conditions in terms of the model's parameters for when it is still possible to recover the underlying tree and also its height, even in case the modified distance is not a tree metric.

Comments on and illustrations of the WFUMB CEUS liver guidelines: Rare malignant neuroendocrine and predominant epithelioid liver lesions.

The diagnosis or rare, non-hematologic malignant lesions of the liver may be a challenge owing to the rarity of the disease, and is usually made by histological confirmation. Ultrasound with color Doppler and contrast-enhanced, if required, taking into account the clinical background of the patient, may help to focus the differential diagnosis. In this review, we describe the pathological and ultrasound features of rare malignant neuroendocrine and predominantly epithelioid liver lesions including primary neuroendocrine tumor of the liver, Invasive mucinous cystic neoplasm of the liver, and also hepatoblastoma.

Comments on and illustrations of the WFUMB CEUS liver guidelines: Rare malignant mesenchymal liver lesions.

The diagnosis or rare mesenchymal malignant lesions of the liver may be a challenge owing to the rarity of the disease and is usually made by histological confirmation. An ultrasound examination with, if required, color Doppler sonography and contrast-enhanced ultrasound, taking into account the clinical background of the patient, may help to focus the differential diagnosis. In this review, we describe the pathological and ultrasound features of several rare mesenchymal malignant liver lesions which include undifferentiated sarcoma of the liver, leiomyosarcoma, angiosarcoma, fibrosarcoma, liposarcoma, and epithelioid hemangioendothelioma.

Comments and illustrations of the WFUMB CEUS liver guidelines: Rare malignant hematological liver lesions.

Diagnosing rare hematological malignancies in the liver is often challenging owing to their infrequency, and confirmation generally necessitates histological examination. Due to the rarity of these lesions, there are limited data concerning their appearance on ultrasound and, specifically, contrast-enhanced ultrasound. In this review, we describe the pathological and ultrasound features of several hematological malignant liver lesions, including lymphoma of the liver and chloroma. Furthermore, two specific forms of liver lymphoma are described: mucosa-associated lymphoid tissue (MALT) lymphoma andplasmacytoma of the liver.

Diversities and the Generalized Circumradius.

The generalized circumradius of a set of points A⊆Rd with respect to a convex body K equals the minimum value of λ≥0 such that a translate of λK contains A. Each choice of K gives a different function on the set of bounded subsets of Rd; we characterize which functions can arise in this way. Our characterization draws on the theory of diversities, a recently introduced generalization of metrics from functions on pairs to functions on finite subsets. We additionally investigate functions which arise by restricting the generalized circumradius to a finite subset of Rd. We obtain elegant characterizations in the case that K is a simplex or parallelotope.

Towards unravelling biological mechanisms behind radiation-induced oral mucositis via mass spectrometry-based proteomics.

Objective: Head and neck cancer (HNC) accounts for almost 890,000 new cases per year. Radiotherapy (RT) is used to treat the majority of these patients. A common side-effect of RT is the onset of oral mucositis, which decreases the quality of life and represents the major dose-limiting factor in RT. To understand the origin of oral mucositis, the biological mechanisms post-ionizing radiation (IR) need to be clarified. Such knowledge is valuable to develop new treatment targets for oral mucositis and markers for the early identification of "at-risk" patients. Methods: Primary keratinocytes from healthy volunteers were biopsied, irradiated in vitro (0 and 6 Gy), and subjected to mass spectrometry-based analyses 96 h after irradiation. Web-based tools were used to predict triggered biological pathways. The results were validated in the OKF6 cell culture model. Immunoblotting and mRNA validation was performed and cytokines present in cell culture media post-IR were quantified. Results: Mass spectrometry-based proteomics identified 5879 proteins in primary keratinocytes and 4597 proteins in OKF6 cells. Amongst them, 212 proteins in primary keratinocytes and 169 proteins in OKF6 cells were differentially abundant 96 h after 6 Gy irradiation compared to sham-irradiated controls. In silico pathway enrichment analysis predicted interferon (IFN) response and DNA strand elongation pathways as mostly affected pathways in both cell systems. Immunoblot validations showed a decrease in minichromosome maintenance (MCM) complex proteins 2-7 and an increase in IFN-associated proteins STAT1 and ISG15. In line with affected IFN signalling, mRNA levels of IFNß and interleukin 6 (IL-6) increased significantly following irradiation and also levels of secreted IL-1ß, IL-6, IP-10, and ISG15 were elevated. Conclusion: This study has investigated biological mechanisms in keratinocytes post-in vitro ionizing radiation. A common radiation signature in keratinocytes was identified. The role of IFN response in keratinocytes along with increased levels of pro-inflammatory cytokines and proteins could hint towards a possible mechanism for oral mucositis.

Baekduia alba sp. nov., a novel representative of the order Solirubrobacterales isolated from temperate grassland soil.

Strain 0141_2T was isolated from a temperate grassland soil in Germany and was found to be affiliated with the order Solirubrobacterales. It is most closely related to Baekduia soli BR7-21T, with 98.1 % 16S rRNA gene sequence similarity. Cells are rod-shaped, non-motile, stain Gram-positive and can have multiple vesicles in the cell surface. Polyhydroxybutyrate is accumulated within the cells. Catalase- and oxidase-positive. It is a mesophilic aerobe and grows best around neutral to slightly acidic pH in R2A medium. The major fatty acids are C18 : 1 ω9c, iso-C16 : 0, C18 : 0, C16 : 0, C16 : 1 ω7c and C17 : 1 ω8c. Diphosphatidylglycerol is present. The predominant respiratory quinone is MK-7(H4). Meso-diaminopimelic acid is the diagnostic diamino acid in the cell-wall peptidoglycan. The G+C content of genomic DNA is 72.9 mol%. Based on the results of phenotypic, chemotaxonomic, genomic and phylogenetic analysis, we propose the novel species Baekduia alba sp. nov. with the type strain 0141_2T (=DSM 104299T=LMG 30000T=CECT 9239T).

Invasion of a Horticultural Plant into Forests: Lamium galeobdolon argentatum Affects Native Above-Ground Vegetation and Soil Properties.

Horticultural trade is considered the most important pathway for the introduction of non-native plant species. Numerous horticultural plants are spreading from private gardens and public green space into natural habitats and have the potential to alter native biodiversity and ecosystem functioning. We assessed the invasiveness of the horticultural plant Lamium galeobdolon subsp. argentatum. We documented its spread in semi-natural habitats in the surroundings of Basel, Switzerland, over the past decades. We compared the performance of L. g. argentatum with that of the native subspecies Lamium galeobdolon galeobdolon based on surveys in forests and a pot experiment under standardized conditions. We also assessed whether the two subspecies differentially affect native forest vegetation and various physical, chemical and biological soil properties. The horticultural L. g. argentatum has tripled its occurrence in forests in the region of Basel in the last four decades. Lamium g. argentatum had both a higher growth rate and regeneration capacity than the native subspecies. Furthermore, L. g. argentatum reduced native plant species richness and changed the species composition of the ground vegetation, in addition to altering several soil properties in deciduous forests. Lamium g. argentatum should therefore be considered an invasive taxon.

Preoperative fibrinogen/CRP score predicts survival in upper urothelial tract carcinoma patients undergoing radical curative surgery.

PURPOSE: Upper tract urothelial carcinoma (UTUC) represents an often aggressive malignancy associated with poor prognosis. Therefore, finding reliable prognostic biomarkers in patients undergoing curative surgery for improved risk stratification is crucial. We evaluated the prognostic value of the Fibrinogen/C-reactive protein (FC)-score in a cohort of surgically treated UTUC patients. METHODS: 170 patients with radiologically and histologically verified UTUC who underwent radical curative surgery between 1990 and 2020, were included. The FC-score was calculated for each patient, with patients receiving 1 point each if Fibrinogen and/or CRP levels were elevated above the 25th or 75th percentile, respectively. Patients were divided into three subgroups according to their FC-score of 0, 1 or 2 point(s). Kaplan-Meier analysis, uni- and multivariable Cox proportional hazard models were implemented. We determined cancer-specific survival (CSS) as primary endpoint, whereas overall survival (OS) and recurrence-free survival (RFS) were considered secondary endpoints. RESULTS: High FC-score (2 points) was significantly associated with adverse histological features such as vascular invasion (OR = 4.08, 95%CI 1.18-14.15, p = .0027) and tumour necrosis (OR = 6.67, 95%CI 1.35-32.96, p = 0.020). Both, uni- and multivariable Cox proportional hazard models showed the FC-score as a significant predictor for CSS (univariable analysis: FC-score = 1: HR = 1.90, 95%CI 0.92-3.93, p = 0.085 | FC-score = 2: HR = 2.86, 95%CI 1.22-6.72, p = 0.016). Furthermore, in univariable analysis, patients with higher FC-score had significantly shorter OS (FC-score = 1: HR = 1.32, 95%CI 0.70-2.49, p = 0.387 | FC-score = 2: HR = 2.19, 95%CI 1.02-4.67, p = 0.043). However, this did not prevail in multivariable analysis. CONCLUSION: The FC-score represents a novel potential biomarker in patients with UTUC undergoing radical curative surgery.

Hepatic lipid overload triggers biliary epithelial cell activation via E2Fs.

During severe or chronic hepatic injury, biliary epithelial cells (BECs) undergo rapid activation into proliferating progenitors, a crucial step required to establish a regenerative process known as ductular reaction (DR). While DR is a hallmark of chronic liver diseases, including advanced stages of non-alcoholic fatty liver disease (NAFLD), the early events underlying BEC activation are largely unknown. Here, we demonstrate that BECs readily accumulate lipids during high-fat diet feeding in mice and upon fatty acid treatment in BEC-derived organoids. Lipid overload induces metabolic rewiring to support the conversion of adult cholangiocytes into reactive BECs. Mechanistically, we found that lipid overload activates the E2F transcription factors in BECs, which drive cell cycle progression while promoting glycolytic metabolism. These findings demonstrate that fat overload is sufficient to reprogram BECs into progenitor cells in the early stages of NAFLD and provide new insights into the mechanistic basis of this process, revealing unexpected connections between lipid metabolism, stemness, and regeneration.

Dominance of mixed ether/ester, intact polar membrane lipids in five species of the order Rubrobacterales: Another group of bacteria not obeying the "lipid divide".

The composition of the core lipids and intact polar lipids (IPLs) of five Rubrobacter species was examined. Methylated (ω-4) fatty acids (FAs) characterized the core lipids of Rubrobacter radiotolerans, R. xylanophilus and R. bracarensis. In contrast, R. calidifluminis and R. naiadicus lacked ω-4 methyl FAs but instead contained abundant (i.e., 34-41 % of the core lipids) ω-cyclohexyl FAs not reported before in the order Rubrobacterales. Their genomes contained an almost complete operon encoding proteins enabling production of cyclohexane carboxylic acid CoA thioester, which acts as a building block for ω-cyclohexyl FAs in other bacteria. Hence, the most plausible explanation for the biosynthesis of these cyclic FAs in R. calidifluminis and R. naiadicus is a recent acquisition of this operon. All strains contained 1-O-alkyl glycerol ether lipids in abundance (up to 46 % of the core lipids), in line with the dominance (>90 %) of mixed ether/ester IPLs with a variety of polar headgroups. The IPL head group distribution of R. calidifluminis and R. naiadicus differed, e.g. they lacked a novel IPL tentatively assigned as phosphothreoninol. The genomes of all five Rubrobacter species contained a putative operon encoding the synthesis of the 1-O-alkyl glycerol phosphate, the presumed building block of mixed ether/ester IPLs, which shows some resemblance with an operon enabling ether lipid production in various other aerobic bacteria but requires more study. The uncommon dominance of mixed ether/ester IPLs in Rubrobacter species exemplifies our recent growing awareness that the lipid divide between archaea and bacteria/eukaryotes is not as clear cut as previously thought.

Capillimicrobium parvum gen. nov., sp. nov., a novel representative of Capillimicrobiaceae fam. nov. within the order Solirubrobacterales, isolated from a grassland soil.

The order Solirubrobacterales is a deep-branching lineage within the phylum Actinomycetota. Most representatives have been isolated from terrestrial environments. A strain isolated from a grassland soil was found to be affiliated with this order and therefore characterized by a polyphasic approach. Cells of strain 0166_1T are Gram-positive, short rods, non-motile, non-spore-forming and divide by binary fission. A surface layer with protrusions covers the majority of the cells. Strain 0166_1T grows optimally around neutral to slightly alkaline pH (pH 7.1-7.9) and at temperatures between 24-36 °C in SSE/HD 1 : 10 medium. It grows optimally with 0-0.5% NaCl (w/v) but can withstand concentrations up to 5 %. The major fatty acids are C18 : 1 ω9c, C16 : 1 ω7c, C17 : 0 cyclo ω7c, C18 : 1 ω7c methyl and C19 : 0 cyclo ω9c. The major polar lipids are diphosphatidylglycerol, two unidentified phospholipids and one unidentified glycolipid. MK-7(H4) and MK-7(H2) are the predominant respiratory quinones. meso-2,6-Diaminopimelic acid is the diagnostic diamino acid in the cell-wall peptidoglycan. The G+C content for strain 0166_1T is 72.8 mol%. 16S rRNA gene sequence analysis indicated that this bacterium was related to Conexibacter arvalis KV-962T and Conexibacter stalactiti YC2-25T with 95.5 and 95.2 % sequence similarity, respectively. Based on the phenotypic, genomic and phylogenetic data, we propose the novel species Capillimicrobium parvum sp. nov. (type strain 0166_1T=DSM 104329T=LMG 29999T=CECT 9240T) of the novel genus Capillimicrobium gen. nov. within the novel family Capillimicrobiaceae fam. nov.

The Evolution of Ecological Diversity in Acidobacteria.

Acidobacteria occur in a large variety of ecosystems worldwide and are particularly abundant and highly diverse in soils. In spite of their diversity, only few species have been characterized to date which makes Acidobacteria one of the most poorly understood phyla among the domain Bacteria. We used a culture-independent niche modeling approach to elucidate ecological adaptations and their evolution for 4,154 operational taxonomic units (OTUs) of Acidobacteria across 150 different, comprehensively characterized grassland soils in Germany. Using the relative abundances of their 16S rRNA gene transcripts, the responses of active OTUs along gradients of 41 environmental variables were modeled using hierarchical logistic regression (HOF), which allowed to determine values for optimum activity for each variable (niche optima). By linking 16S rRNA transcripts to the phylogeny of full 16S rRNA gene sequences, we could trace the evolution of the different ecological adaptations during the diversification of Acidobacteria. This approach revealed a pronounced ecological diversification even among acidobacterial sister clades. Although the evolution of habitat adaptation was mainly cladogenic, it was disrupted by recurrent events of convergent evolution that resulted in frequent habitat switching within individual clades. Our findings indicate that the high diversity of soil acidobacterial communities is largely sustained by differential habitat adaptation even at the level of closely related species. A comparison of niche optima of individual OTUs with the phenotypic properties of their cultivated representatives showed that our niche modeling approach (1) correctly predicts those physiological properties that have been determined for cultivated species of Acidobacteria but (2) also provides ample information on ecological adaptations that cannot be inferred from standard taxonomic descriptions of bacterial isolates. These novel information on specific adaptations of not-yet-cultivated Acidobacteria can therefore guide future cultivation trials and likely will increase their cultivation success.

Differential Response of Acidobacteria to Water Content, Soil Type, and Land Use During an Extended Drought in African Savannah Soils.

Although climate change is expected to increase the extent of drylands worldwide, the effect of drought on the soil microbiome is still insufficiently understood as for dominant but little characterized phyla like the Acidobacteria. In the present study the active acidobacterial communities of Namibian soils differing in type, physicochemical parameters, and land use were characterized by high-throughput sequencing. Water content, pH, major ions and nutrients were distinct for sandy soils, woodlands or dry agriculture on loamy sands. Soils were repeatedly sampled over a 2-year time period and covered consecutively a strong rainy, a dry, a normal rainy and a weak rainy season. The increasing drought had differential effects on different soils. Linear modeling of the soil water content across all sampling locations and sampling dates revealed that the accumulated precipitation of the preceding season had only a weak, but statistically significant effect, whereas woodland and irrigation exerted a strong positive effect on water content. The decrease in soil water content was accompanied by a pronounced decrease in the fraction of active Acidobacteria (7.9-0.7%) while overall bacterial community size/cell counts remained constant. Notably, the strongest decline in the relative fraction of Acidobacteria was observed after the first cycle of rainy and dry season, rather than after the weakest rainy season at the end of the observation period. Over the 2-year period, also the ß-diversity of soil Acidobacteria changed. During the first year this change in composition was related to soil type (loamy sand) and land use (woodland) as explanatory variables. A total of 188 different acidobacterial sequence variants affiliated with the "Acidobacteriia," Blastocatellia, and Vicinamibacteria changed significantly in abundance, suggesting either drought sensitivity or formation of dormant cell forms. Comparative physiological testing of 15 Namibian isolates revealed species-specific and differential responses in viability during long-term continuous desiccation or drying-rewetting cycles. These different responses were not determined by phylogenetic affiliation and provide a first explanation for the effect of drought on soil Acidobacteria. In conclusion, the response of acidobacterial communities to water availability is non-linear, most likely caused by the different physiological adaptations of the different taxa present.