Cell type signatures in cell-free DNA fragmentation profiles reveal disease biology

Cell-free DNA fragmentation; CancerFragmentación de ADN libre de células; CáncerFragmentació d'ADN lliure de cèl·lules; CàncerCirculating cell-free DNA (cfDNA) fragments have characteristics that are specific to the cell types that release them. Current methods for cfDNA deconvolution typically use disease tailored marker selection in a limited number of bulk tissues or cell lines. Here, we utilize single cell transcriptome data as a comprehensive cellular reference set for disease-agnostic cfDNA cell-of-origin analysis. We correlate cfDNA-inferred nucleosome spacing with gene expression to rank the relative contribution of over 490 cell types to plasma cfDNA. In 744 healthy individuals and patients, we uncover cell type signatures in support of emerging disease paradigms in oncology and prenatal care. We train predictive models that can differentiate patients with colorectal cancer (84.7%), early-stage breast cancer (90.1%), multiple myeloma (AUC 95.0%), and preeclampsia (88.3%) from matched controls. Importantly, our approach performs well in ultra-low coverage cfDNA datasets and can be readily transferred to diverse clinical settings for the expansion of liquid biopsy.We would like to thank the patients and their families for agreeing to participate in this study. We would like to thank the Genomics Core at KU Leuven for the use of the sequencing facilities. Funding was received from the European Union’s Horizon 2020 research and innovation program under grant agreement No 824110 – EASI-Genomics (J.R.V.) and the Marie Skłodowska-Curie grant agreement No 813707 (MATER), from Kom Op Tegen Kanker (Stand up to Cancer) KOTK/2018/11468, from the Flemish cancer society (2016/10728/2603 to A.C.), and FWO-SBO grant S003422N, and from Agentschap Innoveren en Ondernemen (VLAIO; Flanders Innovation & Entrepreneurship grant HBC.2018.2108). S.T. was supported by FWO SB/1S74420N. Institutional support was received from the KU Leuven, C1- C14/18/092, C14/22/125, and C3/20/100 to J.R.

Primary mesenteric liposarcoma. Report of a case

Primary mesenteric liposarcomas are very rare neoplasms. The authors report a case of mesenteric liposarcoma recently observed. The patient presented with a history of dyspeptic syndrome, meteorism and abdominal pain associated with a change in bowel habit and constipation. On physical examination there was a large, well-circumscribed, abdominal mass. Computed tomography revealed an abdominal, dishomogeneous, low-density mass. Surgical excision with a tumour-free margin was achieved. The histologic appearances were those of a well-differentiated liposarcoma (atypical lipomatous tumour). The patient is alive and disease-free 33 months after the surgery. Primary mesenteric liposarcoma is often resectable and requires aggressivesurgical management; in consideration of the high risk of tumour recurrence, the treatment of choice is a wide surgical excisio

Detection of incipient tumours by screening of circulating plasma DNA: hype or hope?

Background: The last half-decade has been marked by a rapid expansion of research efforts in the field of so-called liquid biopsies, thereby investigating the potential of blood-derived cell-free tumour DNA (ctDNA) markers for application in clinical oncological management. The analysis of cfDNA appears to be particularly attractive for therapy monitoring purposes, while in terms of early cancer diagnosis and screening the potentials are just starting to be explored. Challenges, both of biological and technical nature, need to be addressed. One such challenge is to overcome the low levels of ctDNA in the circulation, intrinsic to many early-stage cancers. Methods: Here, we give an overview of the features of ctDNA and the approaches that are currently being applied with the ultimate aim to detect tumours in a presymptomatic stage. Conclusion: Although many studies report encouraging results, further technical development and larger studies are warranted before application of ctDNA analysis may find its place in clinic

Detection of incipient tumours by screening of circulating plasma DNA: hype or hope?

Background: The last half-decade has been marked by a rapid expansion of research efforts in the field of so-called liquid biopsies, thereby investigating the potential of blood-derived cell-free tumour DNA (ctDNA) markers for application in clinical oncological management. The analysis of cfDNA appears to be particularly attractive for therapy monitoring purposes, while in terms of early cancer diagnosis and screening the potentials are just starting to be explored. Challenges, both of biological and technical nature, need to be addressed. One such challenge is to overcome the low levels of ctDNA in the circulation, intrinsic to many early-stage cancers. Methods: Here, we give an overview of the features of ctDNA and the approaches that are currently being applied with the ultimate aim to detect tumours in a presymptomatic stage. Conclusion: Although many studies report encouraging results, further technical development and larger studies are warranted before application of ctDNA analysis may find its place in clinic.status: publishe

Antimicrobial activity of <i>Inula helenium</i> L. essential oil against Gram-positive and Gram-negative bacteria and <i>Candida</i> spp.

In this work we report results regarding the in vitro antimicrobial activity of Inula helenium L. dried root extracts obtained by stepwise supercritical fluid extraction (SFE) and by hydrodistillation (HD). Inula helenium L. (Compositae family) is a perennial plant widely occurring in Europe and East Asia. Its oil is one of the richest sources of sesquiterpenoid lactones, which have strong anthelminthic activity and have the potential to induce detoxifying enzymes. Inula helenium L. roots (C-040705130905) were purchased from Minardi (Bagnacavallo-Ravenna, Italy). Supercritical CO2 extraction was performed in a laboratory apparatus equipped with a 400 cm3 extraction vessel operated in the single-pass mode of passing CO2 through the fixed bed of charged vegetable particles. Extraction was carried out in a semibatch mode: batch charging of vegetable matter and continuous flow solvent. HD was performed for 4 h in a circulatory Clevenger-type apparatus up to exhaustion of the oil contained in the matrix, which was the same material as used in the SFE

Unveiling Hidden Prints: Optically stimulated luminescence for latent fingerprint detection

Fluorescent lighting and optical techniques have been widely utilized to enhance the detection of latent fingerprints. However, the development of new techniques is imperative to expand the range of surfaces from which latent fingerprints can be detected. When relying on traditional methods, fingerprint evidence can remain undetected or even disregarded due to insufficient detection and limited detail, especially when dealing with a luminescent background.In this study, we propose the utilization of optically stimulated luminescence (OSL) applied to a Ba2SiO4 matrix, co-doped with Eu2+ and Dy3+, as a powerful method for visualizing latent fingerprints on various surfaces, including thin plastic bags, rigid duct tape, thin aluminum foil, and glass slices. This technique effectively eliminates any luminescent background and significantly enhances optical imaging.This represents the first successful application of OSL in the development of latent fingerprints, thus paving the way for more efficient and effective forensic techniques in the future

Primary mediastinal large B-cell lymphoma is characterized by large-scale copy-neutral loss of heterozygosity.

Development of primary mediastinal B-cell lymphoma (PMBL) is driven by cumulative genomic aberrations. We discovered a unique copy-neutral loss of heterozygosity (CN-LOH) landscape of PMBL which distinguishes this tumor from other B-cell malignancies, including the biologically related diffuse large B-cell lymphoma. Using single nucleotide polymorphism array analysis we identified large-scale CN-LOH lesions in 91% (30/33) of diagnostic PMBLs and both investigated PMBL-derived cell lines. Altogether, the cohort showed 157 extra-large (25.3-248.4 Mb) CN-LOH lesions affecting up to 14 chromosomes per case (mean of 4.4) and resulting in a reduction of heterozygosity an average of 9.9% (range 1.3-51%) of the genome. Predominant involvement of terminal chromosomal segments suggests the implication of B-cell specific crossover events in the pathogenesis of PMBL. Notably, CN-LOH stretches non-randomly clustered on 6p (60%), 15 (37.2%), and 17q (40%), and frequently co-occurred with homozygous mutations in the MHC I (6p21), B2M (15q15), and GNA13 (17q23) genes, respectively, as shown by preliminary whole-exome/genome sequencing data. Altogether, our findings implicate CN-LOH as a novel and distinct mutational process contributing to the molecular pathogenesis of PMBL. The aberration acting as "second hit" in the Knudson hypothesis, ranks as the major mechanism converting to homozygosity the PMBL-related driver genes. Screening of the cohort of 199 B cell leukemia/lymphoma whole-genomes revealed significant differences in the CN-LOH landscape of PMBL and other B-cell malignancies, including the biologically related diffuse large B-cell lymphoma

A phase II trial proposal of total neoadjuvant treatment with primary chemotherapy, stereotactic body radiation therapy, and intraoperative radiation therapy in borderline resectable pancreatic adenocarcinoma

The current management guidelines recommend that patients with borderline resectable pancreatic adenocarcinoma (BRPC) should initially receive neoadjuvant chemotherapy. The addition of advanced radiation therapy modalities, including stereotactic body radiation therapy (SBRT) and intraoperative radiation therapy (IORT), could result in a more effective neoadjuvant strategy, with higher rates of margin-free resections and improved survival outcomes

Metabolic disorders and gastroenteropancreatic-neuroendocrine tumors (GEP-NETs): How do they influence each other? An Italian Association of Medical Oncology (AIOM)/ Italian Association of Medical Diabetologists (AMD)/ Italian Society of Endocrinology (SIE)/ Italian Society of Pharmacology (SIF) multidisciplinary consensus position paper

: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a heterogeneous group of malignancies derived from neuroendocrine cells that can occur anywhere along the gastrointestinal tract. GEP-NETs incidence has been steadily increasing over the past decades, in parallel with the increasing incidence of the metabolic syndrome (MetS). It is not yet fully known whether the MetS components (such as obesity, dyslipidemia and type 2 diabetes) could be involved in the etiology of GEP-NETs or could influence their outcomes. In this review, a panel of experts of the Italian Association of Medical Oncology (AIOM), Italian Association of Medical Diabetologists (AMD), Italian Society of Endocrinology (SIE), and Italian Society of Pharmacology (SIF) provides a critical view of the experimental and clinical evidence about the association of GEP-NETs risk, outcomes, and therapies with the metabolic disorders typical of MetS. The potential therapeutic strategies for an optimal management of patients with both GEP-NETs and MetS are also discussed

Corticosteroids in oncology: Use, overuse, indications, contraindications. An Italian Association of Medical Oncology (AIOM)/ Italian Association of Medical Diabetologists (AMD)/ Italian Society of Endocrinology (SIE)/ Italian Society of Pharmacology (SIF) multidisciplinary consensus position paper

Corticosteroids (CSs) are widely used in oncology, presenting several different indications. They are useful for induction of apoptosis in hematological neoplasms, for management of anaphylaxis and cytokine release/hypersensitivity reaction and for the symptomatic treatment of many tumour- and treatment-related complications. If the employment of CSs in the oncological setting results in several benefits for patients and satisfaction for clinicians, on the other hand, many potential adverse events (AEs), both during treatment and after withdrawal of CSs, as well as the duality of the effects of these compounds in oncology, recommend being cautious in clinical practice. To date, several gray zones remain about indications, contraindications, dose, and duration of treatment. In this article, a panel of experts provides a critical review on CSs therapy in oncology, focusing on mechanisms of action and pharmacological characteristics, current and emerging therapeutic indications/contraindications, AEs related to CSs treatment, and the impact on patient outcome