University of Szeged

The 2-carboxamide derivatives of estrone (E1) and estradiol (E2) offer untapped anticancer potential, mimicking active 2-methoxyestradiol (2ME2). We synthesized a 12-member library via a mesyl chloride (MsCl)-mediated protocol that overcame steric hindrances plaguing conventional couplings. Amidation of 3-OAc-protected 2-carboxyestrone (2-1CE) using standard activating agents (DCC, CDI and ethyl chloroformate) failed or gave low conversions/complex mixtures, which we attribute to steric congestion around the reaction centre, including the C-2 substituent and the incoming amine partner. In contrast, MsCl activation under basic conditions delivered morpholine, pyrrolidine, pyrimidine, diethyl-, cyclopropyl-, and bis(methoxyethyl)amides in 61–92% yields after purification. Stereoselective reduction afforded E2 analogues, fully characterized by NMR/HRMS. Bioscreening against A549, DU-145, HeLa, MCF-7 (cancerous) and MRC-5 (non-cancerous) cells demonstrated cancer selective cytotoxicity of cyclopropylamides (IC₅₀ 11.4–16.7 μM), with p53/p21/Bax/caspase-3-mediated apoptosis confirmed by gene profiling. This work underscores the superior activation potential of MsCl for 2-carboxyestrogen amidation and positions cyclopropyl-2-carboxamides as high-potential leads for next-generation steroid chemotherapeutics and mechanistic studies. • 2-carboxyestrone via regioselective Friedel-Crafts acylation/haloform reaction. • MsCl-mediated C-2 amidation with different amines enabled. • Route to structurally diverse C-2-carboxamides for bioevaluation. • Cyclopropyl carboxamides show cancer-selective potency. • SAR favors primary amine-derived C-2 carboxamides.

The Iron Gates gorge, where the Danube River cuts through the Carpathian Mountains, represents a key corridor for understanding fluvial dynamics in Central and Southeast Europe. This study presents new insights into the formation and Quaternary evolution of the Lower Danube Gorge through high-resolution morphometric analyses and relative and absolute dating of terrace sequences within the gorge and the downstream alluvial plain.The earliest fluvial terraces, located at elevations between 270 and 320 m, mark the initial phase of river incision. Terraces T8 to T5 formed during this period and are correlated with mid–late Pliocene fine alluvial deposits and late Pliocene–early Quaternary coarser alluvial fan sediments downstream. The transition from upper (T8–T5) to lower terraces (T4–T1) in the gorge mirrors a comparable sequence in the Danube lowlands, where 7–8 alluvial terraces are identified, representing the shift from upper deltaic and alluvial fan deposits to the lower Danube plain.This longitudinal correlation highlights a regional change from lateral fluvial erosion and downstream vertical aggradation to dominant fluvial incision and terrace formation during the Middle–Late Quaternary, influenced by ongoing tectonic uplift and glacial–interglacial climate cycles. Fossil assemblages support a Late Pliocene–Early Quaternary age for the upper terraces, while newly obtained OSL dates for the younger terraces at the gorge exit (T3–T1) correspond to Marine Isotope Stages 3–1.The results reinforce the antecedent drainage model for the Danube at the Iron Gates, suggesting episodic incision superimposed on an actively uplifting landscape.Acknowledgments: This research was funded by the ChronoCarp project (Contract no. 760055/23.05.2023, project code CF 253/29.11.2022, PNRR-III-C9 2022-I8).

Students’ performance in mathematics is a major focus of education research. One of the cornerstones of mathematical performance is arithmetic skills. The system of arithmetic skills is a complex one, the components of which can play different roles in the developmental processes. This study investigated number facts, general arithmetic skills, and students’ views on the importance of knowing multiplication number facts to better understand the possibly changing role of these components. Participants were 3<sup>rd</sup>, 5<sup>th</sup>, and 7<sup>th</sup> grade students (N = 254). The results suggest that even in their early years of schooling, students possess strong beliefs about the value of knowing multiplication number facts by heart. However, many continue to struggle with recalling answers, such as 7 times 8, within three seconds. This cross-sectional development study also reveals the evolving role of number facts in students’ arithmetic performance.

Background: Students’ mathematical reasoning is often limited by their difficulty in linking abstract mathematical concepts with meaningful real-life contexts. In many classrooms, mathematics is perceived as disconnected from students’ sociocultural experiences, which can hinder the development of deeper reasoning processes. Aims: This study aims to profile students’ mathematical reasoning abilities within the Alkhairaat sociocultural context and to examine how contextual integration influences reasoning across different ability levels. Method: A sequential explanatory mixed-methods design was employed involving 33 eighth-grade students in a madrasah. Quantitative data were collected through a mathematical reasoning test embedded in the Alkhairaat context and analyzed using the Rasch measurement model (Ministep 5.10.4.0) to evaluate the instrument’s psychometric quality and map students’ reasoning abilities. Qualitative data were then obtained through clinical interviews to explore students’ cognitive processes when solving contextual problems. Results: Rasch analysis indicated acceptable psychometric properties, with item reliability of 0.67 and person reliability of 0.58. Wright Map analysis categorized students into three ability levels: high (12.12%), medium (66.67%), and low (21.21%). The findings show that the Alkhairaat context functions differently across ability levels: as a cognitive tool for abstraction among high-ability students, as procedural scaffolding for medium-ability students, and primarily as an affective anchor for low-ability students. Conclusion: Integrating sociocultural contexts such as Alkhairaat values can support mathematical reasoning by providing meaningful entry points for abstraction. However, its effectiveness depends on students’ initial proficiency, indicating the need for additional instructional support for lower-ability learners.

A tanulmány a kereskedelmi egészségmeghatározók (Commercial Determinants of Health – CDOH) fogalmát értelmezi újra, az intézményi elmélet szempontjait beemelve. A szerzők szerint a vállalatok nemcsak gazdasági szereplők, hanem intézményesített társadalmi aktorok, akik befolyásolják a jogi, politikai és kulturális normákat is. A cikk három hatalmi dimenziót különít el – strukturális, diskurzív és intézményi –, és rámutat arra, hogy a vállalati hatalom beágyazódik a társadalmi intézményekbe. A tanulmány szerint a közegészségügynek rendszerszintű szemléletet kell alkalmaznia, hogy hatékonyan reagáljon a kereskedelmi érdekek egészségkárosító hatásaira.

A tanulmány a jólléti gazdaság (wellbeing economy) koncepciójának mérési lehetőségeit elemzi, különbséget téve a valódi előrehaladás és a pusztán retorikai („window dressing”) intézkedések között. A szerzők hat alapelvet határoznak meg annak megítélésére, hogy egy gazdaságpolitikai irány valóban a társadalmi jólétet szolgálja-e: társadalmi igazságosság, környezeti fenntarthatóság, közegészségügyi indikátorok integrálása, átlátható döntéshozatal, gazdasági struktúrák vizsgálata és demokratikus részvétel. A tanulmány szerint a jólléti gazdaság nem új mutatók bevezetését, hanem a gazdasági gondolkodás alapjainak átalakítását igényli.

Circular RNAs (circRNAs) emerged as promising non-invasive cancer biomarkers due to their stability, abundance in body fluids, and regulatory potential. However, circRNA differential expression analysis (DEA) remains challenging, largely owing to lack of consensus on important preprocessing strategies such as filtering and normalization. While well-established bulk RNA-sequencing frameworks are commonly applied to circRNA data, newer approaches such as CIRI-DE (part of CIRI3 suite) integrate both linear and circular transcript information to improve detection. Despite developments, an assessment of these integrative strategies is lacking, and the critical impact of filtering on DEA model performance has not been comprehensively evaluated. Results: In this study, we evaluated the impact of multiple normalization and filtering strategies on circRNA DEA using five experimental datasets, including two in-house blood platelet sets and semi-parametric simulated in silico datasets. Our results emphasize the importance of selecting an appropriate filtering threshold, as overly lenient filtering substantially reduced model performance across datasets. We found edgeR's filterByExpr() strategy particularly effective in handling zero counts in circRNA data, while also generating the most reliable results across most datasets. Furthermore, by incorporating linear and circular information as described in CIRI-DE, most methods identified a higher number of differentially expressed (DE) circRNAs compared to circular counts alone. Notably, circRNAs identified by both CIRI-DE and the modified bulk RNA-sequencing pipelines showed substantial overlap. Conclusion: Our findings demonstrate that automated filtering combined with linear-aware normalization significantly enhances the sensitivity and reproducibility of circRNA DEA, providing a standardized framework for more reliable biomarker discovery in transcriptomic research.

In constitutional complaint proceedings, the Constitutional Court held that the mandatory imposition of life imprisonment on violent multiple recidivists - subject to the statutory conditions - does not constitute a disproportionate restriction of either the right to personal liberty or the right to a fair trial.

Abstract One of the 17th-century manuscripts of the Franciscan order in Hungary contains a hitherto unrecorded census, as evidenced by both Hungarian and European book sources: this is the list of the books of the Marian Province (Provincia Sanctae Mariae). In 1647, when the catalogue was compiled, there were already 19 convents in the diocese. These were the convents that were able to submit their books at the request of the provincial. The catalogue, which comprises almost 500 items, is of particular significance as it is the only inventory of the library of any Marian convent from this period that has survived. The 1647 book catalogue is of significant interest as it provides a comprehensive overview of the book supply of the members of the Order, the potential reading material, and the spirit of the collection. It is therefore considered to be one of the fundamental documents of the period in terms of literacy.