https://hdl.handle.net/20.500.14178/901 2026-06-06T05:49:28Z https://hdl.handle.net/20.500.14178/3815 Feasibility and Preliminary Outcomes of Group–Based Cognitive Remediation and Emotion Skills Training (CREST) for Adult Women With Anorexia Nervosa and Bulimia Nervosa: A Pilot Pre–Post Study Minařík, Petr; Wohlinová, Kristýna; Dostálová, Veronika; Bočková, Natálie; Suchý, Jiří; Papežová, Hana Introduction: Cognitive and emotional deficits are common in eating disorders (EDs), especially anorexia nervosa (AN) and bulimia nervosa (BN), and can hinder engagement and recovery. This pilot single-group pre-post study examined the feasibility and preliminary outcomes of group-based Cognitive Remediation and Emotion Skills Training (CREST) for adult women with AN/BN in a day care programme setting. Methods: Fifty seven women enroled; 32 completed the 5-week, 10-session programme. Completers and non-completers were compared to identify predictors of adherence. Emotional functioning was assessed using symptom and trait self-report measures, including the TAS-20, Zung Self-Rating Anxiety Scale, BDI-II, EDE-Q, TEQ, and the Self-Compassion Scale. Feasibility was evaluated based on enrolment, completion rates, and treatment adherence. Results: Preliminary analyses indicated decreases in anxiety (SAS, p < 0.001) and depression (BDI-II, p < 0.001), alongside higher self-compassion (SCS, p < 0.001). Results should be interpreted cautiously given the absence of a control group and notable attrition; improvements may reflect combined effects of CREST and standard multidisciplinary care. Higher BMI and shorter illness duration were associated with completion; in regression, only more previous hospitalisations remained significant. Conclusions: Pilot findings suggest that group-based CREST may represent a feasible adjunctive intervention for patients with AN and BN. Further controlled studies are required to disentangle its specific effects from standard care to confirm its effectiveness. 2026-01-01T00:00:00Z https://hdl.handle.net/20.500.14178/3798 CD64-Targeted Polymer-Drug Conjugates Exploit Cathepsin K-Dependent Payload Release for Selective Elimination of Immunosuppressive Macrophages Musil, Dominik; Krhutová, Markéta; Blažková, Kristýna; Kramná, Anežka; Brázdová, Andrea; Výmolová, Barbora; Houdová Megová, Magdalena; Hadzima, Martin; Kryštůfek, Robin; Šubr, Vladimír; Kostka, Libor; Etrych, Tomáš; Ormsby, Tereza; Sácha, Pavel; Ambramson, Jakub; Konvalinka, Jan Selective depletion of immunosuppressive macrophages in the tumor microenvironment is a promising strategy in cancer therapy. CD64 is broadly expressed on myeloid cells, including both pro-inflammatory M1-like and immunosuppressive M2-like macrophages that resemble tumor-associated macrophages (TAMs), and thus represents an attractive entry receptor for targeted payload delivery. We developed HPMA-based CD64-targeted polymer-drug conjugates (CD64-TPDCs) that combine multivalent receptor engagement with enzyme-responsive payload release. These copolymers are decorated with the CD64-binding cyclic peptide cp33 and carry the cytotoxic payload mertansine (DM1) bound via cathepsin-cleavable peptide linkers. Multivalent cp33 presentation on the polymer markedly increased the apparent affinity for human CD64, resulting in subnanomolar binding and selective recognition of CD64-expressing cells, significantly improving the binding potency of monovalent cp33 peptide. In polarized M2-like human monocyte-derived macrophages (MDMs), we showed that cytotoxic Gly-Phe-Leu-Gly-DM1 CD64-TPDCs selectively induced apoptosis. In contrast, M1-like MDMs were largely spared despite expressing higher levels of CD64. In M2-like MDMs, CD64-TPDCs rapidly accumulated in lysosomes, whereas in M1-like cells, they remained largely confined to endosomes. To elucidate the basis of this selectivity, we profiled expression of cathepsins in polarized MDMs. We found that M2-like MDMs display substantially higher levels of cathepsin K, establishing a model in which cathepsin K is the major protease responsible for Gly-Phe-Leu-Gly linker cleavage and DM1 release in M2-like macrophages. These findings demonstrate that CD64-TPDCs can be engineered to exploit subset-specific trafficking and cathepsin K-dependent linker cleavage for the selective elimination of M2-like macrophages. This work provides a generalizable design principle for stimuli-responsive PDCs that may actively target immunosuppressive myeloid cells in tumors. 2026-01-01T00:00:00Z https://hdl.handle.net/20.500.14178/3743 One-year multicenter surveillance of Fosfomycin resistance Enterobacterales: the rise of FosA3-producing P. mirabilis Chudějová, Kateřina; Mattioni Marchetti, Vittoria; Zaccaria, Vita; Kanova, Stepanka; Šrámková, Anna; Krůtová, Marcela; Ryšková, Lenka; Kroneislová, Gabriela; Horvathova, Beata; Tejkalova, Renata; Krejci, Eva; Vagnerova, Iva; Zemanova, Zuzana; Bitar, Ibrahim The global rise of antimicrobial resistance has renewed interest in fosfomycin (FOS), an old antibiotic with activity against multidrug-resistant Enterobacterales . However, resistance to FOS is increasing, driven by impaired drug uptake, target modification, and by fosA -encoded enzymatic inactivation. This study assessed the prevalence and molecular basis of FOS resistance among Enterobacterales collected in Czech tertiary care hospitals in 2024. A total of 211 preliminary FOS-resistant isolates were obtained from nine hospitals across the Czech Republic, predominantly Proteus mirabilis (n=149) and Escherichia coli (n=57). All isolates showed elevated FOS MICs, and the PPF test identified FosA activity in 34/211 isolates. Carbon-source growth testing demonstrated widespread impairment of GlpT and UhpT transporters (93.8 % affecting both). PCR confirmed fosA genes in 14 isolates (9 P. mirabilis , 5 E. coli ). WGS revealed fosA3 as the dominant variant (85.7 %), followed by fosA4 (14.3 %). P. mirabilis isolates primarily belonged to ST185 and ST135, forming two Czech-specific fosA3 clusters with limited relatedness to international genomes. FosA-producing E. coli displayed broader diversity (ST69, ST58, ST550, ST1308). FosA4 was detected exclusively in E. coli . Most fosA -positive strains co-harbored ESBL genes, predominantly bla <inf>CTX-M-65</inf>. SNP-based phylogenies indicated local clonal circulation of fosA3 -positive P. mirabilis ST185, whereas E. coli isolates showed heterogeneous international linkages. Analysis of GlpT/UhpT/MurA identified numerous amino acid substitutions, though only a minority were predicted to affect protein function. This study documents the first broader emergence of plasmid-mediated FOS resistance in Czech Enterobacterales and underscores the importance of continuous genomic surveillance of fosA -mediated resistance. 2026-01-01T00:00:00Z https://hdl.handle.net/20.500.14178/3741 Analyses of ATP7B mRNA in Nasopharyngeal Swab Samples Increase Yields of Wilson Disease Molecular Genetic Diagnostics Steiner Mrázová, Lenka; Vrbacká, Alena; Majer, Filip; Stránecký, Viktor; Nosková, Lenka; Záhoráková, Daniela; Májovská, Jitka; Bitar, Ibrahim; Klempíř, Jiří; Šaligová, Jana; Majlingová, Stella; Giertlová, Mária; Drenčáková, Petra; Harvanová, Denisa; Solařová, Pavla; Brůha, Radan; Dušek, Petr; Kmoch, Stanislav; Sikora, Jakub; Jedličková, Ivana Wilson disease (WD) is an autosomal recessive disorder of copper transport caused by bi-allelic pathogenic variants in the ATPase copper transporting beta gene (ATP7B). Results of standard genetic diagnostics remain inconclusive in 3%-20% of WD patients in part due to problematic assessment of variants of unknown or conflicting pathogenicity (synonymous variants included). Correct interpretation of potential effects of such variants can be substantially enhanced by RNA analyses. This strategy is, however, of limited utility in WD patients because of predominant liver expression of ATP7B. To avoid invasive bioptic liver collection and increase WD diagnostic yields, we searched for a surrogate tissue sample and identified profiles of ATP7B transcripts in nasopharyngeal swabs that were comparable to liver. Amplicons spanning ATP7B Exons 3-21 were prepared from the swab material and analysed by long-read nanopore sequencing to enable the detection of splicing changes and variant phasing. Diagnostic utility of this novel in vivo methodology was demonstrated by characterization of mRNA splicing abnormalities caused by synonymous ATP7B variants c.1488C>T (p.(Gly496=)), c.2241C>T (p.(Ile747=)), c.2292C>T (p.(Phe764=)), and a nonsense variant c.2336G>A (p.(Trp779Ter)) in four WD patients, who were not genetically resolved by standard techniques. Nasopharyngeal swab sampling is minimally invasive and allows effective analyses of mRNA to detect and/or validate effects of ATP7B variants in WD patients. Conclusive genetic diagnosis attained by this novel technique may facilitate family counselling and substantiate initiation of copper-chelation therapy in presymptomatic individuals. 2026-01-01T00:00:00Z