REPOSITORY
THE NICOLAUS COPERNICUS UNIVERSITY
IN TORUŃ
is an institutional repository of Nicolaus Copernicus University in Toruń. The task of the Repository is to promote scientific achievements and research conducted at NCU and to support teaching.
Recent Submissions
Therapeutic oligonucleotide (nusinersen) metabolism in cerebrospinal fluid samples of patients with spinal muscular atrophy based on liquid chromatography coupled with mass spectrometry data
(Elsevier, 2026-03) Studzińska, Sylwia; Lemska, Anna; Szymarek, Jakub; Mazurkiewicz-Bełdzińska, Maria
Background: Spinal muscular atrophy (SMA) is a severe genetic neuromuscular disorder caused by a deficiency of the survival motor neuron protein. The introduction of antisense oligonucleotide therapy has markedly improved prognosis, particularly following approval of Nusinersen (Spinraza), the first SMA drug. Although modified with 2′-O-methoxyethyl and phosphorothioate groups, nusinersen is metabolized. Comprehensive characterization of these metabolites in cerebrospinal fluid is limited due to analytical challenges associated with antisense oligonucleotides. This study aimed to develop a first liquid-liquid/solid-phase extraction procedure combined with ion-pair ultra-high-performance liquid chromatography coupled with mass spectrometry for the extraction, separation, and identification of nusinersen and its metabolites in cerebrospinal fluid samples from SMA patients treated with Spinraza.
Results: A two-step sample preparation procedure provided high nusinersen recovery (89.2±1.8%), repeatability, eliminated matrix effects, and enabled 50-fold sample concentration. All of these proved essential for the detection and identification of low-abundance metabolites collected four months after dosing. Reliable metabolite identification requires sufficient chromatographic resolution, especially for metabolites differing by a single nucleotide with similar nominal m/z values. Consequently, careful ion-pair reagent selection and MS optimization are crucial for improving separation and sensitivity to detect low-abundance metabolites. Our results showed that propylamine and dimethylbutylamine may be used interchangeably, but the second one provides higher resolution. Accurate mass measurement and characteristic fragment ions derived from methylated nucleobases and phosphorothioate groups ensured reliable identification. Analysis of CSF samples from 17 pediatric SMA (at various dosing stages) patients revealed extensive in vivo metabolism, predominantly via 3′-exonucleolytic cleavage, yielding multiple N-shortmers. For the first time, interpatient variability was observed in nusinersen detectability and metabolite profiles of CSF samples.
Significance: To our knowledge, this is one of the first comprehensive studies demonstrating the applicability of the developed procedure to observe differences in the metabolism of nusinersen and, in the future, linking them to therapeutic effects, therapeutic monitoring, or the patient’s condition. The methodology addresses key bioanalytical challenges (reproducibility, purification, concentration, separation) and enables metabolite profiling in a complex biological matrix. Moreover, it provides a foundation for future investigations linking metabolism, drug exposure, and clinical response in SMA therapy.
Excess work incapacity during and after the COVID-19 pandemic in Poland: evidence from population-level social insurance data
(2026-03-23) Łyszczarz, Błażej; Wojtasik, Jakub
Background: COVID-19 disrupted occupational health and social protection systems; but, evidence on its medium- and long-term effects on work incapacity remains limited.
Objective: To quantify excess temporary and permanent work incapacity in Poland during and after the COVID-19 pandemic using population-level social insurance data.
Methods: This observational study used quarterly Social Insurance Institution administrative data (2015–2024) on rehabilitation benefits and disability pensions, by sex and ICD-10 chapter. Expected pre-pandemic trends (2015–2019) were modelled using log-linear regression. Excess incapacity for 2020–2024 was identified by comparing expected to observed incapacity rates.
Results: Temporary work incapacity increased substantially and remained elevated, resulting in 104,392 more rehabilitation benefits than expected, mostly after the acute pandemic phase. The largest increases occurred for mental disorders (over-80% above expected levels by late 2024) and musculoskeletal diseases, particularly among men (over-30% in some periods). In contrast, permanent work incapacity declined below expected levels, with 49,281 fewer disability pensions awarded, predominantly among men. The largest reductions were observed for circulatory diseases (up to 27% below expected levels) and neoplasms (19%), while musculoskeletal conditions were the only group with excess permanent incapacity, primarily affecting women.
Conclusions: Our findings reveal a divergence between excess temporary work incapacity and reduced permanent disability, likely reflecting the combined effects of health system disruption, delays in benefit adjudication, and pandemic-related mortality displacement. These results have implications for social insurance and rehabilitation policies, underscoring the need to strengthen mental health care, return-to-work pathways and monitoring of disability adjudication.
Once Again, Evictionism Is Not a Solution: Response to Professor Walter Block
(2025) Dominiak, Łukasz
The present paper argues that Professor Walter Block’s evictionism is not a solution to the abortion dilemma. Being a response to Professor Block’s recent article published in this journal, my piece submits (in some respects once again) that evictionism should be rejected because contrary to what it claims: (1) the unwanted fetus is not a trespasser; (2) there are insufficient reasons to support the premise that our life and thus our concomitant self-ownership status begins at the moment of conception; (3) evictionism entails positive duties; (4) evictionism conflicts with the homestead principle; (5) instead of being an original solution to the abortion dilemma, evictionism collapses into a well-known doctrine of doing and allowing; and (6) eviction is not the gentlest way possible of securing the woman’s rights.
Evictionism and Duties of the Fetus: Seeking Common Ground with Walter Block on Abortion
(Mises Institute, 2025) Dominiak, Łukasz; Wysocki, Igor
In the present article we argue that Walter E. Block’s (2025) recent rejoinder to our critique (DW 2023a) of evictionism—Block’s well-known libertarian solution to the abortion dilemma—does not succeed. However, instead of limiting ourselves merely to addressing Block’s latest objections, we seek to identify possible common ground between evictionism and our charge that it entails an untenable position according to which the fetus is a duty-bearer. We do so by pinpointing the theses that a friend of evictionism would have to modify in order to defend this doctrine against our criticism and by trying to gauge the cost of doing so. The argument we put forth suggests that possible common ground could be found in relaxing the evictionist thesis that the unwanted fetus forfeits its rights and instead accepting the view that the woman’s right to her body vests her with a particularly strong prerogative to defend it against the unwanted fetus—a prerogative that justifies infringing upon the fetus’s unforfeited rights.
Experts' Opinions on the Impact of Community Archives on Archival Science, Archival Institutions and the Archival Profession
(State Archival Service of Ukraine, 2025-04-14) Wiśniewska-Drewniak, Magdalena; Kapała, Adriana
The article analyzes interviews with 12 experts from Poland and abroad on their perceptions of the impact of community (independent) archives on archival science as an academic discipline, on heritage institutions (especially public archives) and on the archival profession. The purpose of the work is to present the partial results of the project entitled «The impact of independent community archives». Methodology. Data were collected through semi-structured qualitative interviews, which were then analyzed using a priori codes (based on literature and previous interviews with community archivists), supplemented with new codes – new meanings observed during the iterative analysis performed by two team members. Scientific novelty: The article is the first study analyzing expert opinions on the impact of community archives, comparing views of different types of experts (e. g. academics, advocates for community archives, active or former community archivists). Prospects for further studies: Future research should also analyze the contributions of people from other cultures, continents and archival traditions, and should be based on sources that directly describe the influence of community archives on archival science and archival practice. Conclusions. Experts pointed to the significance of community archives in reshaping the foundations of archival science (e. g. terminology, archival value). Experts from Anglophone countries and Chile emphasized the relationship of community archives to decolonization of archives and critical archival studies. Experts from continental Europe focused on the acceptance of the existence of grassroots archives and their distinct archival practices. Some experts noted the impact on archival education. Experts variously assessed the effect on the practice of public archives.