Cytogenetic features in myelodysplastic syndromes

Myelodysplastic syndromes (MDS) comprise a group of bone marrow diseases characterized by profound heterogeneity in morphologic presentation, clinical course, and cytogenetic features. Roughly 50% of patients display clonal chromosome abnormalities. In several multicentric studies, the karyotype turned out to be one of the most important prognostic parameters and was incorporated into statistical models aiming for a better prediction of the individual prognosis like the International Prognostic Scoring System. However, due to the profound cytogenetic heterogeneity, the impact of many rare abnormalities as well as combinations of anomalies occurring in a substantial portion of patients with MDS is still unknown and can only be delineated on the basis of large international multicentric cooperations. Recently, the German–Austrian MDS Study Group presented cytogenetic findings in 2,072 patients with MDS, which serve as a basis for the characterization of the cytogenetic subgroups discussed in this article. The availability of new therapeutic options for low- and high-risk MDS targeted against distinct entities characterized by specific chromosome abnormalities, like 5q-deletions, monosomy 7, and complex abnormalities underlines the important role of cytogenetics for the clinical management of MDS. This article thus focuses on the clinical and prognostic relevance, the molecular background, and therapeutic perspectives in these three cytogenetic subgroups

Detection of Stock Manipulation Influencer Content using Supervised Learning

In recent years, social media influencers have emerged as key players in stock manipulation schemes. Despite their growing impact, methods to detect such activities remain scarcely explored. In this study, we examine the social media content of stock manipulation influencers (SMIs) implicated in a $100 million fraud case by the U.S. Securities and Exchange Commission (SEC) in 2022. Leveraging natural language processing (NLP) techniques, we first investigate the linguistic characteristics present in the social media content published by SMIs. Next, we develop and evaluate supervised learning models to detect manipulative content. Our results have significant implications for investors, regulators, and the broader financial community. They reveal the unique linguistic characteristics of SMI content and demonstrate the potential of machine-learning and deep-learning-based techniques in advancing fraud detection systems

FINFLUENCERS: OPINION MAKERS OR OPINION FOLLOWERS?

This paper explores the concept of Finfluencers: financial social network actors with high potential social influence. Our research aims to clarify whether Finfluencers drive or are influenced by the broader social network sentiment, thereby establishing their role as either opinion makers or opinion followers. Using a dataset of 71 million tweets focusing on stocks and cryptocurrencies, we grouped actors by their social networking potential (SNP). Next, we derived sentiment time series using state-ofthe- art sentiment models and applied the technique of Granger causality. Our findings suggest that the sentiment of Finfluencer actors on Twitter has short-term predictive power for the sentiment of the larger group of actors. We found stronger support for cryptocurrencies in comparison to stocks. From the perspective of financial market regulation, this study emphasizes the relevance of understanding sentiment on social networks and high social influence actors to anticipate scams and fraud

Ökonomische Bewertung der Integration temporärer Naturschutzmaßnahmen im Ökologischen Landbau - Beispiel Blühstreifen -

At the Hessian state domain Frankenhausen, an organic farm with comparatively high yield potential, the integration of nature conservation measures is tested. Economic investigations aim to identify costs and changes of performance due to the adaptation of production processes to nature conservation targets. The main focus is on temporary measures that, like field-flower strips, potentially promote biodiversity on arable land. Initial calculations show the costs that must be taken into account for wildflower strips with autochthonous species on arable land. The analysis particularly considers the complex intra-farm integration of the conservation measures as a special characteristic of organic agriculture systems

Comprehensive Laboratory Diagnostic Workup for Patients with Suspected Intraocular Lymphoma including Flow Cytometry, Molecular Genetics and Cytopathology.

BACKGROUND Intraocular lymphoma (IOL) presents a real challenge in daily diagnostics. Cyto- and/or histopathology of vitreous body represent the diagnostic cornerstones. Yet, false negative results remain common. Therefore, we analyzed the diagnostic significance of flow cytometry (FC) within the workup algorithm of IOL and compared its sensitivity with the results obtained from routine cytopathology and molecular genetics; Methods: Seven patients undergoing vitrectomy due to suspected IOL were investigated by FC and parallel cytopathology and, if available, digital droplet PCR (ddPCR) for MYD88 L265P; Results: Four out of seven patients were finally diagnosed with IOL. Among the IOL patients, cytopathology confirmed the presence of lymphoma cells in only two cases. In contrast, FC was positive for IOL in all four cases, and FC additionally confirmed the lack of IOL in the remaining patients. In IOL patients diagnosed by FC and with available ddPCR, the diagnosis of IOL was confirmed by the presence of the MYD88 L265P mutation in all three patients; Conclusions: The combination with FC was superior to cytopathology alone in the diagnostic work-up of IOL, and it showed an excellent correlation with ddPCR results. A comprehensive diagnostic panel consisting of cytopathology, FC and molecular genetics should be considered for the work-up of suspected IOL

Treatment of poor-risk myelodysplastic syndromes and acute myeloid leukemia with a combination of 5-azacytidine and valproic acid

5-azacytidine (AZA) has become standard treatment for patients with higher-risk myelodysplastic syndrome (MDS). Response rate is about 50% and response duration is limited. Histone deactylase (HDAC) inhibitors are attractive partners for epigenetic combination therapy. We treated 24 patients with AZA (100 mg/m2, 5 days) plus valproate (VPA; continuous dosing, trough serum level 80–110 μg/ml). According to WHO classification, 5 patients had MDS, 2 had MDS/MPD, and 17 had acute myeloid leukemia (AML). Seven patients (29%) had previously received intensive chemotherapy, and five had previous HDAC inhibitor treatment. The overall response rate was 37% in the entire cohort but significantly higher (57%) in previously untreated patients, especially those with MDS (64%). Seven (29%) patients achieved CR (29%) and two PR (8%), respectively. Hematological CR was accompanied by complete cytogenetic remission according to conventional cytogenetics in all evaluable cases. Some patients also showed complete remission according to FISH on bone marrow mononuclear cells and CD34+ peripheral blood cells, as well as by follow-up of somatic mitochondrial DNA mutations. Four additional patients achieved at least marrow remissions. Factors influencing response were AML (vs. MDS), marrow blast count, pretreatment, transfusion dependency, concomitant medication with hydroxyurea, and valproic acid (VPA) serum level. This trial is the first to assess the combination of AZA plus VPA without additional ATRA. A comparatively good CR rate, relatively short time to response, and the influence of VPA serum levels on response suggest that VPA provided substantial additional benefit. However, the importance of HDAC inhibitors in epigenetic combination therapy can only be proven by randomized trials

Targeted deep sequencing of CD34+ cells from peripheral blood can reproduce bone marrow molecular profile in myelodysplastic syndromes

Altres ajuts: José Carreras Leukämie-Stiftung, Award/Grant number: project AR 14/34

Prognostic impact of a suboptimal number of analyzed metaphases in normal karyotype lower-risk MDS

Conventional karyotype is one of the most relevant prognostic factors in MDS. However, about 50% of patients with MDS have a normal karyotype. Usually, 20-25 normal metaphases (nMP) are considered to be optimal to exclude small abnormal clones which might be associated with poor prognosis. This study evaluated the impact of examining a suboptimal number of metaphases in patients recruited to the EUMDS Registry with low and intermediate-1 risk according to IPSS. Only 179/1049 (17%) of patients with a normal karyotype had a suboptimal number of nMP, defined as less than 20 metaphases analyzed. The outcome (overall survival and progression-free survival) of patients with suboptimal nMP was not inferior to those with higher numbers of analyzed MP both in univariate and multivariate analyses. For patients with an abnormal karyotype, 224/649 (35%) had a suboptimal number of MP assessed, but this did not impact on outcome. For patients with a normal karyotype and suboptimal numbers of analyzable metaphases standard evaluation might be acceptable for general practice, but we recommend additional FISH-analyses or molecular techniques, especially in candidates for intensive interventions