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Mateusz Michał Tomczyk,1 Sławomir Boncel,1 Artur Herman,2 Tomasz Krawczyk,1 Agata Jakóbik-Kolon,1 Mirosława Pawlyta,3 Maciej Krzywiecki,4 Artur Chrobak,5 Masafumi Minoshima,6 Fuminori Sugihara,7 Kazuya Kikuchi,6 Nikodem Kuźnik1 1Faculty of Chemistry, Silesian University of Technology, Gliwice, Poland; 2Department of Semiconductor Materials Engineering, Faculty of Fundamental Problems of Technology, Wroclaw University of Science and Technology, Wrocław, Poland; 3Faculty of Mechanical Engineering, Silesian University of Technology, Gliwice, Poland; 4Institute of Physics – Center for Science and Education, Silesian University of Technology, Gliwice, Poland; 5August Chełkowski Institute of Physics, University of Silesia, Katowice, Poland; 6Graduate School of Engineering, Osaka University, Osaka, Japan; 7Immunology Frontier Research Center, Osaka University, Osaka, JapanCorrespondence: Nikodem Kuźnik; Sławomir Boncel Email nikodem.kuznik@polsl.pl; slawomir.boncel@polsl.plPurpose: Salicyl (Sal) – among other oxygen functionalities – multi-walled carbon nanotubes (MWCNTs) and their nanohybrids are investigated as promising contrast agents (CA) in magnetic resonance imaging (MRI) or drug delivery platforms, due to their unique properties. The preliminary results and the literature reports were the motivation to endow high r2 relaxivities, excellent dispersibility in water, and biocompatibility to superparamagnetic MWCNTs nanohybrids. It was hypothesized that these goals could be achieved by, not described in the literature yet, two-stage oxygen functionalization of MWCNTs.Results: Two structurally different MWCNT materials differing in diameters (44 and 12 nm) and the iron content (4.7% and 0.5%) are studied toward the functionalization effect on the T2 relaxometric properties. MWCNT oxidation is typically the first step of functionalization resulting in “first generation” oxygen functional groups (OFGs) on the surface. Until now, the impact of OFGs on the relaxivity of MWCNT was not truly recognized, but this study sheds light on this issue. By follow-up functionalization of oxidized MWCNT with 4-azidosalicylic acid through [2+1] cycloaddition of the corresponding nitrene, “second generation” of oxygen functional groups is grafted onto the nanohybrid, ie, Sal functionality.Conclusion: The introduced OFGs are responsible for an almost 30% increase in the relaxivity, which leads to remarkable r2 relaxivity of 951 mM− 1s− 1 (419 (mg/mL)− 1s− 1), the unprecedented value reported to date for this class of CAs. Also, the resulting nanohybrids express low cytotoxicity and superb diffusion after subcutaneous injection to a mouse.Keywords: multi-walled carbon nanotubes, magnetic resonance imaging, MRI contrast agents, carbon nanotube functionalization, T2 relaxivity

Background: Oncology research is increasingly adopting new clinical trial models that implement the concept of precision medicine. One of these is the basket clinical trial design. Basket clinical trials allow new treatments to be evaluated across multiple tumor types. Patients recruited to basket clinical trials share certain molecular characteristics of their cancer that are predictive of clinical benefit from the experimental treatment., Objective: Our aim was to describe the risks and benefits of basket clinical trials in oncology., Methods: Our study was prospectively registered in PROSPERO (CRD42023406401). We systematically searched PubMed, Embase, and ClinicalTrials.gov for reports of basket clinical trials in oncology published between 1 January, 2001, and 14 June, 2023. We measured the risk by treatment-related adverse events (grades 3, 4, and 5), and the benefit by objective response rate. We also extracted and analyzed data on progression-free survival and overall survival. When possible, data were meta-analyzed., Results: We included 126 arms of 75 basket clinical trials accounting for 7659 patients. The pooled objective response rate was 18.0% (95% confidence interval [CI] 14.8-21.1). The rate of treatment-related death was 0.7% (95% CI 0.4-1.0), while 30.4% (95% CI 24.2-36.7) of patients experienced grade 3/4 drug-related toxicity. The median progression-free survival was 3.1 months (95% CI 2.6-3.9), and the median overall survival was 8.9 months (95% CI 6.7-10.2)., Conclusions: Our results provide an empirical basis for communicating about the risks and benefits of basket clinical trials and for refining new models of clinical trials applied in precision medicine., Competing Interests: Declarations. Funding: The study was funded by the National Science Center, Poland, UMO-2019/35/N/HS1/00178 and UMO-2021/41/B/HS1/01123 ( www.ncn.gov.pl ); Karolina Strzebonska, Lucja Zaborowska, Katarzyna Klas, Maciej Polak, and Marcin Waligora received the funding. Additional support was obtained from a grant (U1C/W43/NO/28.04) under the Strategic Programme Excellence Initiative at Jagiellonian University. Conflict of interest: Simon Van Wambeke receives funding from IPSEN (travel and accommodation) and Janssen-Cilag (travel and accommodation; fees). Katarzyna Klas, Karolina Strzebonska, Lucja Zaborowska, Tomasz Krawczyk, Alicja Włodarczyk, Urszula Bąk-Kuchejda, Maciej Polak, and Marcin Waligora have no conflicts of interest that are directly relevant to the content of this article. Ethics approval: Not applicable. Consent to participate: Not applicable. Consent for publication: Not applicable. Availability of data and material: Data used for our analysis are publicly available on the Open Science Framework website ( https://osf.io/w4ke9/ ). Additional data are available upon request. Code availability: Not applicable. Author contributions: Conceptualization: KK, KS, MW. Investigation (data collection): KK, KS, LZ, AW, TK, UBK. Methodology: KK, KS, SVW, MW. Data curation: KK, KS, LZ, AW, TK, UBK. Formal analysis: KK, MP. Funding acquisition: KK, KS, MW. Project administration: KK, KS, MW. Resources: KK, KS. Supervision: SVW, MW. Visualization: KK. Software: KK, KS, MP, MW. Validation: KK, KS. Writing, original draft: KK, KS. Writing, review and editing: all authors., (© 2024. The Author(s).)

Introduction: Ovarian cancer is a significant cause of death among females. MiRNAs, particularly the miR-196 family, can influence tumor progression by targeting specific pathways. Detecting ovarian cancer early is challenging, highlighting the need for additional biomarkers such as miRNAs to improve diagnosis and treatment strategies., Material and Methods: Healthy controls and patients with high-grade serous carcinoma ( n = 50) were recruited for this study. Samples for testing were obtained from archival paraffin blocks obtained from intraoperative material., Results: The study found that miRNA 196a expression was significantly elevated in ovarian cancer patients compared to the control group ( p < 0.05). Higher miRNA 196a expression was also noted in patients with advanced FIGO stages (III, IV). Increased miRNA expression was significantly associated with higher mortality and chemoresistance (p < 0.05). Genotype analysis revealed differing distributions of SNPs (C/C, C/T, T/T) between the study and control groups, but no significant correlation with malignancy was observed., Conclusions: This study supports the critical role of microRNA-196a in the progression of ovarian cancer., Competing Interests: None, (Copyright © 2024 Termedia.)

Anticancer drugs show recalcitrance to conventional wastewater treatments; thus, they are present in aquatic systems and pose an environmental threat. Fungi represent a promising biological alternative for wastewater treatments. Therefore, the goals of this work were to assess the potential of white-rot fungi (Fomes fomentarius (CB13), Hypholoma fasciculare (CB15), Phyllotopsis nidulans (CB14), Pleurotus ostreatus (BWPH), and Trametes versicolor (CB8)) for removing bleomycin and vincristine, and to investigate the impacts of various conditions (shaking, aeration, or biomass immobilization) on the process. The removal capacities were measured using Ultra-Performance Liquid Chromatography (UPLC) coupled with Mass Spectrometry (MS) and preceded by Solid Phase Extraction (SPE). We further identified major drugs degradation products; determined the fungi's main enzyme activity profiles (laccase, manganese and lignin peroxidases); and examined the toxicities of post-processed samples against Lemna minor, Daphnia magna and Pseudomonas putida. In just 2 days, all strains (except for P. nidulans) removed >90 % of vincristine, nearly completely eliminating the drug over time. Bleomycin content reduction occurred with T. versicolor or H. fasciculare, respectively reaching 55 % and 83 % drug elimination after 9 days. Oxygen was found to be crucial for cytostatics degradation, with their highest removal rates occurring in samples with air supply (aeration or agitation). Laccase was the only tested enzyme associated with cytostatics elimination. Drug biodegradation was followed by detoxification, demonstrating the utility of fungi in cytostatics removal., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

In this article, we explore ethical issues of Deaf people's engagement in research. To focus on the perspectives of Deaf people, we investigated existing qualitative and mixed methods research within a qualitative evidence synthesis. Our synthesis is based on a systematic database search (Scopus, PubMed) and reference check of included papers which resulted in 27 eligible papers. We analyzed the data using thematic synthesis and developed 5 analytical themes. The results present research as a struggle for Deaf people and emphasize the need for changes regarding recognition of Deaf research in a cross-cultural context, maintaining equal and partner relations, and provision of accessible communication. Our research contributes to understanding what the ethical inclusion of Deaf people in research implies. It may also support the development of evidence-based normative recommendations and scientific cooperation between Deaf and hearing people., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Research participants are often deceived for methodological reasons. However, assessing the ethical acceptability of an individual study that uses deception is not straightforward. The academic literature is scattered on the subject and several aspects of the acceptability assessment are only scarcely addressed, which parallels reports of inconsistent ethics review. Therefore, we aimed to investigate where normative guidance documents agree and disagree about this assessment. A PRISMA-Ethics-guided systematic review of normative guidance documents that discuss deception of research participants was conducted. Our search strategy resulted in 55 documents that were subsequently analyzed through abductive thematic analysis. While guidance documents mention little about specific risks and opportunities of deception, our analysis describes a rich picture of the thresholds for acceptability of the risks and benefits of deception and their integration, the comparison with the risk-benefit analysis of alternative non-deceptive methods, and the bodies of people who are positioned to do the review. Our review reveals an agreement on the general process of assessing the acceptability of studies that use deception, although significant variability remains in the details and several topics are largely or completely unaddressed in guidance documents.

Ethical safeguards such as debriefing are often recommended or required for research studies in which participants are deceived. However, existing guidance on these safeguards seems insufficiently coherent and precise, which may be associated with their suboptimal implementation in practice. This study aimed to contribute to a more coherent and precise framework of ethical safeguards in deceptive studies through semi-structured interviews with a diverse sample of 24 researchers who had significant experience with deception. Interviewees discussed which ethical safeguards they implemented and how, as well as their relation to the notion of truthfulness (i.e., the intentional communication of true information). Moreover, interviewees provided a variety of reasons for and against implementing these safeguards, as well as how these reasons varied with the particular context of a study. Overall, the current study contributes to a more coherent and precise understanding of ethical safeguards in deceptive research that could be useful for guiding researchers and ethics reviewers in their ethical decision-making, although certain imprecisions and incoherent aspects remain in need of further investigation and normative reflection.

Informed consent and debriefing of research participants in studies that use deception are ethical safeguards for which existing scholarly work on their implementation remains variable and insufficiently clear. A systematic review of research ethics guidelines was conducted to sketch a picture of whether, why and how informed consent and debriefing are recommended when using deception. Documents roughly agreed on several general principles, but varied significantly in the specifics of why and whether these safeguards are necessary, in which conditions and how they should be implemented. Various aspects that appear in the literature could not be found in the guidelines. In our review, guidance was integrated and showed a variation of implementation strategies that could help in contextualizing these safeguards.

The design and synthesis of hydrazone-based switches with a CF 3 reporting group for 19 F pH imaging using relaxation rate changes were described. A paramagnetic center was introduced into the hydrazone molecular switch scaffold by substitution of an ethyl functional group with a paramagnetic complex. The mechanism of activation relies on a gradual increase in T 1 and T 2 magnetic resonance imaging (MRI) relaxation times as pH decreases due to E / Z isomerization, which results in a change in the distance between fluorine atoms and the paramagnetic center. Among the three possible variants of the ligand, the meta isomer was found to offer the highest potential changes in relaxation rates due to the significant paramagnetic relaxation enhancement (PRE) effect and a stable position of the 19 F signal, allowing for the tracking of a single narrow 19 F resonance for imaging purposes. The selection of the most suitable Gd(III) paramagnetic ion for complexation was conducted by theoretical calculations based on the Bloch-Redfield-Wangsness (BRW) theory, taking into account the electron-nucleus dipole-dipole and Curie interactions only. The results were verified experimentally, confirming the accuracy of theoretical predictions, good solubility, and stability of the agents in water and the reversible transition between E and Z-H + isomers. The results demonstrate the potential of this approach for pH imaging using relaxation rate changes instead of chemical shift.

Molecular switches have become an area of great interest in recent years. They are explored as high-density data storage and organic diodes in molecular electronics as well as chemosensors due to their ability to undergo a transition between well-defined structures under the action of external stimuli. One of the types of such switches is hydrazones. They work by changing the configuration from E to Z under the influence of pH or light. The change in configuration is accompanied by a change in the absorption band and changes in the nuclear magnetic resonance (NMR) spectrum. In this publication, the structure-property relationship of fluorinated hydrazone switches was established. A linear relationship between the Hammett substituent constants and the pH where the switching occurs was found. Introduction of strong electron-donating groups allowed obtaining a hydrazone switch of p K a = 6 suitable for application in 19 F MRI as contrast agents.

19 F magnetic resonance imaging (MRI) is a promising tool in medical diagnostics. An important class of 19 F MRI contrast agents is based on paramagnetic resonance enhancement. This effect allows an improvement in sensitivity by increasing the number of scans per unit of time or facilitates the development of responsive contrast agents that are based on changes in relaxation rates as a detection principle. In this work, Bloch-Redfield-Wangsness relaxation theory was used to predict the relaxation properties of existing lanthanoid and transition metal complexes of fluoroorganic ligands and to evaluate several design strategies for responsive contrast agents. Electron-nucleus dipole-dipole, Curie relaxation, and contact interactions were included in the model. Potential significance of chemical shift anisotropy-anisotropic dipolar shielding cross-correlation was discussed. The calculated and experimental results were well aligned. The presented model, along with the optimized field-dependent values of electronic relaxation times, could be used for the preliminary selection of the optimal metal ion for applications in 19 F MRI. The results indicate potential advantages of other metal ions in addition to Gd 3+ particularly Cu 2+ , Mn 2+ , Ni 2+ , Fe 3+ , and other lanthanoids as a part of 19 F contrast agents.

Apple growers in the Mid-Atlantic region of the U.S.A. have reported increased losses to bitter rot of apple. We tested the hypothesis that this increase is because the Colletotrichum population has developed resistance to commonly used single-mode-of-action (single-MoA) fungicides. We screened 220 Colletotrichum isolates obtained from 38 apple orchards in the Mid-Atlantic region for resistance to 11 fungicides in Fungicide Resistance Action Committee (FRAC) groups 1, 7, 9, 11, 12, and 29. Eleven (5%) of these isolates were resistant to FRAC group 1 with confirmed β-tubulin E198A mutations, and two (<1%) were also resistant to FRAC group 11 with confirmed cytochrome- b G143A mutations. Such low frequencies of resistant isolates indicate that fungicide resistance is unlikely to be the cause of any regional increase in bitter rot. A subsample of isolates was subsequently tested in vitro for sensitivity to every single-MoA fungicide registered for apple in the Mid-Atlantic U.S.A. (22 fungicides; FRAC groups 1, 3, 7, 9, 11, 12, and 29), and 13 fungicides were tested in field trials. These fungicides varied widely in efficacy both within and between FRAC groups. Comparisons of results from our in vitro tests with results from our field trials and other field trials conducted across the eastern U.S.A. suggested that EC 25 values (concentrations that reduce growth by 25%) are better predictors of fungicide efficacy in normal field conditions than EC 50 values. We present these results as a guideline for choosing single-MoA fungicides for bitter rot control in the Mid-Atlantic U.S.A.

Magnetic resonance imaging (MRI) is one of the most powerful imaging tools today, capable of displaying superior soft-tissue contrast. This review discusses developments in the field of 19 F MRI multimodal probes in combination with optical fluorescence imaging (OFI), 1 H MRI, chemical exchange saturation transfer (CEST) MRI, ultrasonography (USG), X-ray computed tomography (CT), single photon emission tomography (SPECT), positron emission tomography (PET), and photoacoustic imaging (PAI). In each case, multimodal 19 F MRI probes compensate for the deficiency of individual techniques and offer improved sensitivity or accuracy of detection over unimodal counterparts. Strategies for designing 19 F MRI multimodal probes are described with respect to their structure, physicochemical properties, biocompatibility, and the quality of images., (© 2021 Wiley-VCH GmbH.)

A permutation graph can be defined as an intersection graph of segments whose endpoints lie on two parallel lines ℓ 1 and ℓ 2 , one on each. A bipartite permutation graph is a permutation graph which is bipartite. In this paper we study the parameterized complexity of the bipartite permutation vertex deletion problem, which asks, for a given n -vertex graph, whether we can remove at most k vertices to obtain a bipartite permutation graph. This problem is NP -complete by the classical result of Lewis and Yannakakis [20]. We analyze the structure of the so-called almost bipartite permutation graphs which may contain holes (large induced cycles) in contrast to bipartite permutation graphs. We exploit the structural properties of the shortest hole in a such graph. We use it to obtain an algorithm for the bipartite permutation vertex deletion problem with running time O ( 9 k · n 9 ) , and also give a polynomial-time 9-approximation algorithm., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s) 2022.)

Background: Oilseed rape is one of the most important oilseed crops worldwide, crucial in the food and feed industries. Different environment and climatic conditions can influence its sustainable cultivation and crop yield. Aminopeptidases are crucial enzymes in many physiological processes in all organisms, including humans, so it is important to learn their behavior in food and feed sources. This study presents, for the first time, a detailed discussion on the importance of aminopeptidases, during the oilseed rape germination process, under standard and stress conditions., Results: During the germination of oilseed rape under standard conditions, a significant increase in aminopeptidases activity toward N-terminal amino acids - phenylalanine (Phe), alanine (Ala), glycine (Gly), leucine (Leu), proline (Pro), methionine (Met) - was observed. The change was substrate specific, with the highest increase being observed for Gly (3.2-fold), followed by Ala (2.9-fold), Pro (2.5-fold), Met (1.5-fold), and Phe (1.3-fold). Generally, N-terminal Phe was preferentially cleaved. Germination under stress conditions, caused by several heavy metal ions (e.g. divalent copper, zinc, cadmium, and lead ions), negatively influenced the plants' growth and quality, but significantly enhanced the expression of genes encoding aminopeptidases (or potentially activated aminopeptidases precursors), which was related to the dramatic increase of their activity., Conclusions: The activity/concentration of aminopeptidases in plants is adjusted to the needs at each stage of development and stress factors occurrence. The most significant increase of activity toward N-terminal Gly and Pro proved the key role of aminopeptidases in the defense mechanisms, by supplying the plants with osmoprotectants and organic nitrogen. The results provide new concepts of oilseed rape growth and cultivation under different conditions. © 2021 Society of Chemical Industry., (© 2021 Society of Chemical Industry.)

The regioselective zw-type [3 + 2] cycloaddition (32CA) reactions of a series of aryl-substituted nitrile N -oxides (NOs) with trichloronitropropene (TNP) have been both experimentally and theoretically studied within the Molecular Electron Density Theory (MEDT). Zwitterionic NOs behave as moderate nucleophiles while TNP acts as a very strong electrophile in these polar 32CA reactions of forward electron density flux, which present moderate activation Gibbs free energies of 22.8-25.6 kcal·mol -1 and an exergonic character of 28.4 kcal·mol -1 that makes them irreversible and kinetically controlled. The most favorable reaction is that involving the most nucleophilic MeO-substituted NO. Despite Parr functions correctly predicting the experimental regioselectivity with the most favorable O-CCCl 3 interaction, these reactions follow a two-stage one-step mechanism in which formation of the O-C(CCl 3 ) bond takes place once the C-C(NO 2 ) bond is already formed. The present MEDT concludes that the reactivity differences in the series of NOs come from their different nucleophilic activation and polar character of the reactions, rather than any mechanistic feature.