Evolving therapies in the treatment of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. The major etiologies and risk factors for HCC development are well defined and some of the steps involved in hepatocarcinogenesis have been elucidated in recent years. Therapeutic options that can be applied in curative or palliative intention are available and are dependent on the HCC stage. The therapeutic options fall into five main categories: (1) surgical interventions, including tumor resection and liver transplantation, (2) percutaneous interventions, including ethanol injection and radiofrequency thermal ablation, (3) transarterial interventions, including embolization and chemoembolization, (4) radiation therapy, and (5) drugs as well as gene and immune therapies. Until recently, no therapy existed for patients with advanced HCC. In 2007 a multikinase inhibitor (sorafenib) showed for the first time a significant increase in overall survival in patients with advanced HCC. Furthermore, several other agents that target different factors of hepatocarcinogenesis (eg, epidermal growth factor, insulin-like growth factors, hepatocyte growth factor, vascular endothelial growth factor, fibroblast growth factor, platelet-derived growth factor, and the transforming growth factors-α and -β), have emerged and been tested in clinical trials. This review gives an overview of the current therapeutic strategies and their clinical impact

Optical coherence tomography-guided versus angiography-guided implantation of everolimus-eluting bioresorbable vascular scaffolds: Comparison of coverage, apposition and clinical outcome. The ALSTER-OCT ABSORB registry

Background: Suboptimal implantation of everolimus-eluting bioresorbable vascular scaffolds (EE-BVS) leading to strut malapposition and lack of neointima coverage has been hypothesized to be linked to late BVS-thrombosis. Optical coherence tomography (OCT) allows assessing subtle differences in BVS-healing. We aimed to link 6-months OCT-data on EE-BVS coverage and malapposition to implantation technique and clinical outcome. Methods: Twenty-nine consecutive EE-BVS-patients were included. EE-BVS-implantation was guided by angiography in the first 17 patients (group 1). Vessel sizing prior to implantation and implantation result was assessed by OCT in the 12 following patients (group 2). EE-BVS-implantation was performed in both groups with adequate lesion preparation, sizing and systematic high-pressure post-dilatation. All patients received 6-months invasive control including OCT-analysis and clinical follow-up for 2 years. Results: The rate of uncovered struts was group 1: 10.8 ± 10.0%; group 2: 10.6 ± 8.2%, p = 0.934. Target lesion failure due to BVS-thrombosis occurred in 2/17 patients at 9 and 18 months (11.8%, group 1), and no patients in group 2 (p = 0.218). Conclusions: Optical coherence tomography analysis at 6-months following EE-BVS-implantation finds almost 90% of struts to be covered. No difference between OCT vs. angiography-guided EE-BVS-implantation was observed. OCT at 6-months was not able to predict late BVS-thrombosis of EE-BVS

Transdisciplinary research in support of land and water management in China and Southeast Asia : evaluation of four research projects

Unidad de excelencia María de Maeztu MdM-2015-0552Transdisciplinary research (TDR) aims at identifying implementable solutions to difficult sustainability problems and at fostering social learning. It requires a wellmanaged collaboration among multidisciplinary scientists and multisectoral stakeholders. Performing TDR is challenging, particularly for foreign researchers working in countries with different institutional and socio-cultural conditions. There is a need to synthesize and share experience among researchers as well as practitioners regarding how TDR can be conducted under specific contexts. In this paper, we aim to evaluate and synthesize our unique experience in conducting TDR projects in Asia. We applied guiding principles of TDR to conduct a formative evaluation of four consortium projects on sustainable land and water management in China, the Philippines, and Vietnam. In all projects, local political conditions restricted the set of stakeholders that could be involved in the research processes. The set of involved stakeholders was also affected by the fact that stakeholders in most cases only participate if they belong to the personal network of the project leaders. Language barriers hampered effective communication between foreign researchers and stakeholders in all projects and thus knowledge integration. The TDR approach and its specific methods were adapted to respond to the specific cultural, social, and political conditions in the research areas, also with the aim to promote trust and interest of the stakeholders throughout the project. Additionally, various measures were implemented to promote collaboration among disciplinary scientists. Based on lessons learned, we provide specific recommendations for the design and implementation of TDR projects in particular in Asia

Towards a national ecosystem assessment in Germany

We present options for a National Ecosystem Assessment in Germany (NEA-DE) that could inform decision-makers on the state and trends of ecosystems and ecosystem services. Characterizing a NEA-DE, we argue that its cross-sectoral, integrative approach would have the advantages of increased scientific understanding, addressing specific policy questions and creating science-policy dialogues. Challenges include objections against a utilitarian perspective, reservations concerning power relations, and responsibilities concerning the funding

The International Virus Bioinformatics Meeting 2023

The 2023 International Virus Bioinformatics Meeting was held in Valencia, Spain, from 24–26 May 2023, attracting approximately 180 participants worldwide. The primary objective of the conference was to establish a dynamic scientific environment conducive to discussion, collaboration, and the generation of novel research ideas. As the first in-person event following the SARS-CoV-2 pandemic, the meeting facilitated highly interactive exchanges among attendees. It served as a pivotal gathering for gaining insights into the current status of virus bioinformatics research and engaging with leading researchers and emerging scientists. The event comprised eight invited talks, 19 contributed talks, and 74 poster presentations across eleven sessions spanning three days. Topics covered included machine learning, bacteriophages, virus discovery, virus classification, virus visualization, viral infection, viromics, molecular epidemiology, phylodynamic analysis, RNA viruses, viral sequence analysis, viral surveillance, and metagenomics. This report provides rewritten abstracts of the presentations, a summary of the key research findings, and highlights shared during the meeting

Y-box protein-1/p18 fragment identifies malignancies in patients with chronic liver disease

<p>Abstract</p> <p>Background</p> <p>Immunohistochemical detection of cold shock proteins is predictive for deleterious outcome in various malignant diseases. We recently described active secretion of a family member, denoted Y-box (YB) protein-1. We tested the clinical and diagnostic value of YB-1 protein fragment p18 (YB-1/p18) detection in blood for malignant diseases.</p> <p>Methods</p> <p>We used a novel monoclonal anti-YB-1 antibody to detect YB-1/p18 by immunoblotting in plasma samples of healthy volunteers (n = 33), patients with non-cancerous, mostly inflammatory diseases (n = 60), hepatocellular carcinoma (HCC; n = 25) and advanced solid tumors (n = 20). YB-1/p18 was then tested in 111 patients with chronic liver diseases, alongside established tumor markers and various diagnostic measures, during evaluation for potential liver transplantation.</p> <p>Results</p> <p>We developed a novel immunoblot to detect the 18 kD fragment of secreted YB-1 in human plasma (YB-1/p18) that contains the cold-shock domains (CSD) 1-3 of the full-length protein. YB-1/p18 was detected in 11/25 HCC and 16/20 advanced carcinomas compared to 0/33 healthy volunteers and 10/60 patients with non-cancerous diseases. In 111 patients with chronic liver disease, YB-1/p18 was detected in 20 samples. Its occurrence was not associated with advanced Child stages of liver cirrhosis or liver function. In this cohort, YB-1/p18 was not a good marker for HCC, but proved most powerful in detecting malignancies other than HCC (60% positive) with a lower rate of false-positive results compared to established tumor markers. Alpha-fetoprotein (AFP) was most sensitive in detecting HCC, but simultaneous assessment of AFP, CA19-9 and YB-1/p18 improved overall identification of HCC patients.</p> <p>Conclusions</p> <p>Plasma YB-1/p18 can identify patients with malignancies, independent of acute inflammation, renal impairment or liver dysfunction. The detection of YB-1/p18 in human plasma may have potential as a tumor marker for screening of high-risk populations, e.g. before organ transplantation, and should therefore be evaluated in larger prospective studies.</p

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements