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Summary: Background: We studied the poorly-known dynamics of circulating DNA (cir-nDNA), as monitored prospectively over an extended post-surgery period, in patients with cancer. Methods: On patients with stage III colon cancer (N = 120), using personalised molecular tags we carried out the prospective, multicenter, blinded cohort study of the post-surgery serial analysis of cir-nDNA concentration. 74 patients were included and 357 plasma samples tested. Findings: During post-operative follow-up, the patients’ median cir-nDNA concentration was greater (P 18 months post-surgery, the data suggest that the persistence of NETs formation is not due to the adjuvant CT. Interpretation: (1), Given the inter-patient heterogeneity, the post-surgery cir-nDNA level cannot be considered a reliable value, and caution must be exercised when determining mutation allele frequency or the mutation status; and (2), specific studies must be undertaken to investigate the possible clinical impact of the persistent, low-grade inflammation resulting from elevated NETs levels, such as observed in these post-surgery patients, given that such levels are known to potentially induce adverse cardiovascular or thrombotic events. Funding: This work was supported by the H2020 European ERA-NET grant on Translational Cancer Research (TRANSCAN-2).

Summary: Pancreatic ductal adenocarcinoma (PDAC) poses significant clinical challenges, often presenting as unresectable with limited biopsy options. Here, we show that circulating tumor cells (CTCs) offer a promising alternative, serving as a “liquid biopsy” that enables the generation of in vitro 3D models and highly aggressive in vivo models for functional and molecular studies in advanced PDAC. Within the retrieved CTC pool (median 65 CTCs/5 mL), we identify a subset (median content 8.9%) of CXCR4+ CTCs displaying heightened stemness and metabolic traits, reminiscent of circulating cancer stem cells. Through comprehensive analysis, we elucidate the importance of CTC-derived models for identifying potential targets and guiding treatment strategies. Screening of stemness-targeting compounds identified stearoyl-coenzyme A desaturase (SCD1) as a promising target for advanced PDAC. These results underscore the pivotal role of CTC-derived models in uncovering therapeutic avenues and ultimately advancing personalized care in PDAC.

Abstract Somatic copy number alterations (SCNAs) are pervasive in advanced human cancers, but their prevalence and spatial distribution in early-stage, localized tumors and their surrounding normal tissues are poorly characterized. Here, we perform multi-region, single-cell DNA sequencing to characterize the SCNA landscape across tumor-rich and normal tissue in two male patients with localized prostate cancer. We identify two distinct karyotypes: ‘pseudo-diploid’ cells harboring few SCNAs and highly aneuploid cells. Pseudo-diploid cells form numerous small-sized subclones ranging from highly spatially localized to broadly spread subclones. In contrast, aneuploid cells do not form subclones and are detected throughout the prostate, including normal tissue regions. Highly localized pseudo-diploid subclones are confined within tumor-rich regions and carry deletions in multiple tumor-suppressor genes. Our study reveals that SCNAs are widespread in normal and tumor regions across the prostate in localized prostate cancer patients and suggests that a subset of pseudo-diploid cells drive tumorigenesis in the aging prostate.

Abstract Background the problem in early diagnosis of sporadic cancer is understanding the individual’s risk to develop disease. In response to this need, global scientific research is focusing on developing predictive models based on non-invasive screening tests. A tentative solution to the problem may be a cancer screening blood-based test able to discover those cell requirements triggering subclinical and clinical onset latency, at the stage when the cell disorder, i.e. atypical epithelial hyperplasia, is still in a subclinical stage of proliferative dysregulation. Methods a well-established procedure to identify proliferating circulating tumor cells was deployed to measure the cell proliferation of circulating non-haematological cells which may suggest tumor pathology. Moreover, the data collected were processed by a supervised machine learning model to make the prediction. Results the developed test combining circulating non-haematological cell proliferation data and artificial intelligence shows 98.8% of accuracy, 100% sensitivity, and 95% specificity. Conclusion this proof of concept study demonstrates that integration of innovative non invasive methods and predictive-models can be decisive in assessing the health status of an individual, and achieve cutting-edge results in cancer prevention and management.

Background:. Microsurgery has a steep learning curve. Synthetic simulators have proven to be useful training tools for the initial learning stages, as well as being ethically sound, viable, safe, and cost-effective. The objective of this review was to determine the quality, effectiveness, and validity of these simulators as well as to assess their ability to evaluate microsurgical skills. Methods:. A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed. We searched databases (Web of Science, Scopus, and PubMed) to identify original articles describing synthetic training models for microsurgery. Three reviewers evaluated articles for inclusion following predefined selection criteria. Data were extracted from full-texts of included articles. Results:. Thirty-nine studies met the inclusion criteria. A total of 38 different devices have been recorded. Microsurgical training devices offer a low-cost, fast, and consistent method to concretely quantify and assess the initial microsurgical skills of trainees using standardized exercises that can be scored by the examiner. According to the authors, the outcomes were satisfactory, with a tangible improvement in microsurgical abilities, despite the lack of a common comparison scale. Conclusions:. Thanks to their availability, cost, and effectiveness, synthetic models are the recommended option to train basic, intermediate and advanced procedures before executing them on in vivo models.

The integration of remote sensing and socio-economic data is crucial for policy making in regions suffering from water scarcity and climate change. We present a framework that combines remotely sensed estimates of biomass and water use from FAO’s Water Productivity Open-access portal (WaPOR) (V2) with an ensemble of calibrated mathematical programming models to assess the impact of water reallocations on rain-fed and irrigated land use and production in water-stressed basins. We evaluated our model in the Upper Litani Basin of Lebanon using two water reallocation policies: (i) quotas that progressively reduces water allocation for irrigation up to 100%, at 1% intervals and (ii) a pricing policy that increases the agricultural water price up to 0.25 USD/m3, at 0.0025 USD/m3 intervals. Our results reveal that 1) the impacts of water availability reductions due to quotas on profit and employment are less-than-proportional when water allocation is reduced by 50%; 2) irrigators responses to prices are inelastic until a price increase of 0.03 USD/m3, become significantly more elastic afterwards, and again become inelastic above a price increase of 0.06 USD/m3; 3) higher water prices progressively reduce profit and labor, significantly reduce water use over the elastic interval (where irrigators cultivating low value-added crops shift to rainfed agriculture), and increase tariff revenue during the inelastic interval (where irrigators largely stick to their crop portfolios and pay the higher water prices). Our results reveal nontrivial uncertainties and tipping points, thus highlighting the value of combining reliable water use data with multi-model and multi-scenario ensembles in informing robust policies.

This review aims to provide a comprehensive overview of various aspects related to cosmetic product packaging, highlighting both advancements and challenges in the field. Initially, it offers a general description of the main materials used in cosmetic containers, including plastic, glass, paper, and aluminum. This is followed by an analysis of the existing EU legislative frameworks that govern cosmetic packaging, encompassing chemical, food, and waste regulations. The paper also discusses recent EU regulatory proposals and guidelines from trade associations aimed at enhancing the sustainability of cosmetic packaging materials. Additionally, the role of recycled and bio-based packaging materials in promoting environmental sustainability is analyzed. Overall, this review aims to provide insights for experts in the field on how to balance safety, functionality, and environmental responsibility in cosmetic packaging.

Archive tissues are the most available source of human tissues useful for molecular analysis in translational research. The main issues for those specimens are the modification and degradation of biomolecules, namely proteins, DNA, and RNA. In the last decade, several high-throughput analytical methods have been applied to archive tissues. Although histological tissues are fixed in neutral-buffered formalin nowadays, in the recent past, Bouin’s solution was also used in tissue processing. The present study aims to investigate the feasibility of nCounter Nanostring hybridization in quantifying mRNA in highly degraded samples, such as Bouin’s fixed and paraffin-embedded (BFPE) tissues, in comparison to the standard formalin-fixed and paraffin-embedded (FFPE) tissues as a source of RNA. A total of 16 paraffin-embedded tissue blocks from eight patients were analyzed (8 were FFPE and 8 were BEPE). Nanostring technology was applied to 300 ng of each RNA sample, whereas 360 ng of the same templates were retrotranscribed and submitted to qPCR and ddPCR. Our results show that the Nanostring technology outperforms the reference methods (ddPCR and qPCR) in detecting target mRNA in FFPE and BFPE samples. However, even Nanostring technology does not escape the limitation imposed by the degradation of the RNA templates, which could lead to misleading conclusions on the gene expression level.

Open partial horizontal laryngectomies (OPHLs) represent a valuable therapeutic option for tumors of the intermediate T-category and, in selected cases, for locally advanced tumors with low-volume extra-laryngeal extension. The eligibility of patients treated with this type of surgery has increased with the introduction of the modular approach to OPHL planning. This strategy follows the introduction of the classification proposed by the European Laryngological Society, based on the extent of horizontal resection. Optimization of the selection is the result of a meticulous work-up process involving close cooperation between experienced surgeons and radiologists, followed by final quality control by pathologists. Computed tomography and magnetic resonance imaging are study methods whose pearls and pitfalls are well known, especially when performed at a high level of expertise. In this paper, based on the experience of two high-volume centers, a checklist of 20 questions addressed by the surgeon to the radiologist before planning an OPHL was proposed. Considerations regarding case selection are reported for each of the questioned parameters. A very simple question-and-answer process is easy to understand and mainly addressed by less experienced colleagues who wish to increase their knowledge and skills in performing this type of surgery.

This review aims to provide a comprehensive overview of various aspects related to cosmetic product packaging, highlighting both advancements and challenges in the field. Initially, it offers a general description of the main materials used in cosmetic containers, including plastic, glass, paper, and aluminum. This is followed by an analysis of the existing EU legislative frameworks that govern cosmetic packaging, encompassing chemical, food, and waste regulations. The paper also discusses recent EU regulatory proposals and guidelines from trade associations aimed at enhancing the sustainability of cosmetic packaging materials. Additionally, the role of recycled and bio-based packaging materials in promoting environmental sustainability is analyzed. Overall, this review aims to provide insights for experts in the field on how to balance safety, functionality, and environmental responsibility in cosmetic packaging. [ABSTRACT FROM AUTHOR]

Archive tissues are the most available source of human tissues useful for molecular analysis in translational research. The main issues for those specimens are the modification and degradation of biomolecules, namely proteins, DNA, and RNA. In the last decade, several high-throughput analytical methods have been applied to archive tissues. Although histological tissues are fixed in neutral-buffered formalin nowadays, in the recent past, Bouin's solution was also used in tissue processing. The present study aims to investigate the feasibility of nCounter Nanostring hybridization in quantifying mRNA in highly degraded samples, such as Bouin's fixed and paraffin-embedded (BFPE) tissues, in comparison to the standard formalin-fixed and paraffin-embedded (FFPE) tissues as a source of RNA. A total of 16 paraffin-embedded tissue blocks from eight patients were analyzed (8 were FFPE and 8 were BEPE). Nanostring technology was applied to 300 ng of each RNA sample, whereas 360 ng of the same templates were retrotranscribed and submitted to qPCR and ddPCR. Our results show that the Nanostring technology outperforms the reference methods (ddPCR and qPCR) in detecting target mRNA in FFPE and BFPE samples. However, even Nanostring technology does not escape the limitation imposed by the degradation of the RNA templates, which could lead to misleading conclusions on the gene expression level. [ABSTRACT FROM AUTHOR]

Over the past two years, the scientific community has witnessed an exponential growth in research focused on identifying prognostic biomarkers for melanoma, both in pre-clinical and clinical settings. This surge in studies reflects the need of developing effective prognostic indicators in the field of melanoma. The aim of this work is to review the scientific literature on the most recent findings on the development or validation of prognostic biomarkers in melanoma, in the attempt of providing both clinicians and researchers with an updated broad synopsis of prognostic biomarkers in cutaneous melanoma. While the field of prognostic biomarkers in melanoma appears promising, there are several complexities and limitations to address. The interdependence of clinical, histological, and molecular features requires accurate classification of different biomarker families. Correlation does not imply causation, and adjustments for confounding factors are often overlooked. In this scenario, large-scale studies based on high-quality clinical trial data can provide more reliable evidence. It is essential to avoid oversimplification by focusing on a single biomarker, as the interactions among multiple factors contribute to define the disease course and patient's outcome. Furthermore, implementing well-supported evidence in real-life settings can help advance prognostic biomarker research in melanoma. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic and lethal disease. Gasdermins are primarily associated with necrosis via membrane permeabilization and pyroptosis, a lytic pro-inflammatory type of cell death. In this study, GSDMC upregulation during PDAC progression is reported. GSDMC directly induces genes related to stemness, EMT, and immune evasion. Targeting Gsdmc in murine PDAC models reprograms the immunosuppressive tumor microenvironment, rescuing the recruitment of anti-tumor immune cells through CXCL9. This not only results in diminished tumor initiation, growth and metastasis, but also enhances the response to KRAS G12D inhibition and PD-1 checkpoint blockade, respectively. Mechanistically, it is discovered that ADAM17 cleaves GSDMC, releasing nuclear fragments binding to promoter regions of stemness, metastasis, and immune evasion-related genes. Pharmacological inhibition of GSDMC cleavage or prevention of its nuclear translocation is equally effective in suppressing GSDMC's downstream targets and inhibiting PDAC progression. The findings establish GSDMC as a potential therapeutic target for enhancing treatment response in this deadly disease., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Somatic copy number alterations (SCNAs) are pervasive in advanced human cancers, but their prevalence and spatial distribution in early-stage, localized tumors and their surrounding normal tissues are poorly characterized. Here, we perform multi-region, single-cell DNA sequencing to characterize the SCNA landscape across tumor-rich and normal tissue in two male patients with localized prostate cancer. We identify two distinct karyotypes: 'pseudo-diploid' cells harboring few SCNAs and highly aneuploid cells. Pseudo-diploid cells form numerous small-sized subclones ranging from highly spatially localized to broadly spread subclones. In contrast, aneuploid cells do not form subclones and are detected throughout the prostate, including normal tissue regions. Highly localized pseudo-diploid subclones are confined within tumor-rich regions and carry deletions in multiple tumor-suppressor genes. Our study reveals that SCNAs are widespread in normal and tumor regions across the prostate in localized prostate cancer patients and suggests that a subset of pseudo-diploid cells drive tumorigenesis in the aging prostate., (© 2024. The Author(s).)