Ethics of research engagement with Deaf people. A qualitative evidence synthesis.

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.

Truthfulness as the basis for ethical safeguards in deceptive research: An interview study with researchers.

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.

Astrocytic ß-catenin signaling via TCF7L2 regulates synapse development and social behavior.

The Wnt/ß-catenin pathway contains multiple high-confidence risk genes that are linked to neurodevelopmental disorders, including autism spectrum disorder. However, its ubiquitous roles across brain cell types and developmental stages have made it challenging to define its impact on neural circuit development and behavior. Here, we show that TCF7L2, which is a key transcriptional effector of the Wnt/ß-catenin pathway, plays a cell-autonomous role in postnatal astrocyte maturation and impacts adult social behavior. TCF7L2 was the dominant Wnt effector that was expressed in both mouse and human astrocytes, with a peak during astrocyte maturation. The conditional knockout of Tcf7l2 in postnatal astrocytes led to an enlargement of astrocytes with defective tiling and gap junction coupling. These mice also exhibited an increase in the number of cortical excitatory and inhibitory synapses and a marked increase in social interaction by adulthood. These data reveal an astrocytic role for developmental Wnt/ß-catenin signaling in restricting excitatory synapse numbers and regulating adult social behavior.

Hydrazone Molecular Switches with Paramagnetic Center as 19F Magnetic Resonance Imaging Relaxation Enhancement Agents for pH Imaging.

The design and synthesis of hydrazone-based switches with a CF3 reporting group for 19F 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 T1 and T2 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 19F signal, allowing for the tracking of a single narrow 19F 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.

Informed Consent and Debriefing When Deceiving Participants: A Systematic Review of Research Ethics Guidelines.

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.

Tuning the pH of Activation of Fluorinated Hydrazone-Based Switches─A Pathway to Versatile 19F Magnetic Resonance Imaging Contrast Agents.

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 pKa = 6 suitable for application in 19F MRI as contrast agents.

Design Principles of Responsive Relaxometric 19F Contrast Agents: Evaluation from the Point of View of Relaxation Theory and Experimental Data.

19F magnetic resonance imaging (MRI) is a promising tool in medical diagnostics. An important class of 19F 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 19F MRI. The results indicate potential advantages of other metal ions in addition to Gd3+ particularly Cu2+, Mn2+, Ni2+, Fe3+, and other lanthanoids as a part of 19F contrast agents.

Assessing the acceptability of individual studies that use deception: A systematic review of normative guidance documents.

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.

Vertex Deletion into Bipartite Permutation Graphs.

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.

Ratiometric pH-Responsive 19F Magnetic Resonance Imaging Contrast Agents Based on Hydrazone Switches.

Hydrazone-based molecular switches serve as efficient ratiometric pH-sensitive agents that can be tracked with 19F NMR/MRI and 1H NMR. Structural changes induced between pH 3 and 4 lead to signal appearance and disappearance at 1H and 19F NMR spectra allowing ratiometric pH measurements. The most pronounced are resonances of the CF3 group shifted by 1.8 ppm with 19F NMR and a hydrazone proton shifted by 2 ppm with 1H NMR.

19 F MRI Probes for Multimodal Imaging.

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.

The Participation of 3,3,3-Trichloro-1-nitroprop-1-ene in the [3 + 2] Cycloaddition Reaction with Selected Nitrile N-Oxides in the Light of the Experimental and MEDT Quantum Chemical Study.

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-CCCl3 interaction, these reactions follow a two-stage one-step mechanism in which formation of the O-C(CCl3) bond takes place once the C-C(NO2) 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.

Oilseed rape (Brassica napus): the importance of aminopeptidases in germination under normal and heavy metals stress conditions.

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.

A step towards gadolinium-free bioresponsive MRI contrast agent.

The last 30 years of gadolinium-based "static" MRI contrast agents motivated to investigate bioresponsive agents with endogenous paramagnets. Iron(III) chelated by N,O-aminophenol skeleton of high versatility, and tuning potential was studied. The two-step convenient route of the ligand is characterized by high selectivity and allows for building a tunable chelate system. Functionalization with galactose endows a bioresponsive character sensitive to the enzyme activity. Direct relaxometric measurements of the resulting complexes revealed extremely high relaxivity of 5.62 mmol/dm3·s-1 comparable to classic gadolinium complexes. Enzymatic hydrolysis leads to relaxivity change by over 80%. Phantom MRI studies prove the bioresponsive character by contras percentage change within the range 40-275%. Cytotoxicity studies showed 70-90% viability of HeLa cells of the iron complexes. Proposed iron-based chelates with galactosidase-sensitive fragment express unequivocal relaxivity and MRI contras change and good biocompatibility. Therefore, these complexes are a promising step towards modern, bioresponsive MRI contrast agents with a "human-friendly" metal.

White-rot fungi-mediated biodegradation of cytostatic drugs - bleomycin and vincristine.

The contamination of the environment with anticancer drugs, which show recalcitrance to conventional wastewater treatment, has become a significant ecological threat. Fungi represent a promising non-conventional biological alternative for water conditioning. The aim of this work was to evaluate the efficacy of five white-rot fungi (Fomes fomentarius (CB13), Hypholoma fasciculare (CB15), Phyllotopsis nidulans (CB14), Pleurotus ostreatus (BWPH) and Trametes versicolor (CB8)) in the removal of bleomycin and vincristine. The removal capacity was measured at 0, 4, 9, and 14 days of incubation using SPE-UPLC-MS. The enzymatic profiles of laccase, manganese, and lignin peroxidases and wide range of eco- and cytotoxicity, assays of the post-process samples were also conducted. We observed >94% vincristine elimination by F. fomentarius, H. fasciculare and T. versicolor after only 4 days. Bleomycin removal occurred after a minimum of 9 days and only when the drug was incubated with T. versicolor (36%) and H. fasciculare (25%). The removal of both cytostatics was associated with laccase production, and the loss of eco- and cytotoxicity, especially in regard to viability of Lemna minor and Daphnia magna, as well as fibroblasts morphology.

Oxygen Functional Groups on MWCNT Surface as Critical Factor Boosting T2 Relaxation Rate of Water Protons: Towards Improved CNT-Based Contrast Agents.

PURPOSE: 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.

Click chemistry as a tool in biosensing systems for sensitive copper detection.

Copper detection for diagnostic purposes is an appealing field due to the important biological role copper plays as a trace metal. A convenient strategy for sensing copper is to utilize its catalytic ability. Therefore, this review summarizes approaches for copper determination by CuI-catalyzed azide/alkyne cycloaddition (CuAAC). The concept was introduced in 2006 and all contributions made up to the middle of 2020 are covered in this review. The issue is divided into three categories: electrochemical, visual, and fluorescence-based methods. The advantages, as well as the disadvantages, of every group, are discussed in detail. The methodology which allows for the determination of copper content in water and human biological samples from 5 s up to 48 h without complex instrumentation are discussed. The reported range of limit of detection (LOD) was 0.38 aM-20 µM, with 1-10 nM being the typical range. The most successful strategies involved using DNA chains or enzymes in the sensing systems.

MiRNA-103/107 in Primary High-Grade Serous Ovarian Cancer and Its Clinical Significance.

High levels of miRNA-103/107 are associated with poor outcomes in the case of breast cancer patients. MiRNA-103/107-DICER axis may be one of the key regulators of cancer aggressiveness. MiRNA-103/107 expression levels have never been related to patients' clinicopathological data in epithelial ovarian cancer. We aimed to assess miRNA-103/107 expression levels in high grade serous ovarian cancer tissues. Expression levels of both miRNAs were related to the clinicopathological features and survival. We also evaluated expression levels of miRNA-103/107 and DICER in selected ovarian cancer cell lines (A2780, A2780cis, SK-OV-3, OVCAR3). We assessed the relative expression of miRNA-103/107 (quantitative reverse transcription-polymerase chain reaction) in fifty archival formalin-fixed paraffin-embedded tissue samples of primary high grade serous ovarian cancer. Then, miRNA-103/107 and DICER expression levels were evaluated in selected ovarian cancer cell lines. Additionally, DICER, N-/E-cadherin protein levels were assessed with the use of western blot. We identified miRNA-107 up-regulation in ovarian cancer in comparison to healthy tissues (p = 0.0005). In the case of miRNA-103, we did not observe statistically significant differences between cancerous and healthy tissues (p = 0.07). We did not find any correlations between miRNA-103/107 expression levels and clinicopathological features. Kaplan-Meier survival (disease-free and overall survival) analysis revealed that both miRNAs could not be considered as prognostic factors. SK-OV-3 cancer cell lines were characterized by high expression of miRNA-103/107, relatively low expression of DICER (western-blot), and relatively high N-cadherin levels in comparison to other ovarian cancer cell lines. Clinical and prognostic significance of miRNA-103/107 was not confirmed in our study.

MiRNAs in endometrioid endometrial cancer metastatic loci derived from positive lymph nodes.

INTRODUCTION: MicroRNAs (miRNAs) take part in tumorigenesis and show aberrant expression levels in cancerous tissues. We aimed to perform miRNA profiling of endometrioid endometrial cancer (EEC) metastatic loci derived from lymph nodes. Identification of aberrant miRNAs in positive lymph nodes could contribute to establishing new diagnostic markers and therapeutic targets. MATERIAL AND METHODS: During the screening phase of the study, we performed profiling of 754 human miRNAs in endometrioid endometrial cancer tissues, microdissected metastatic loci from lymph nodes and healthy lymph nodes (Taqman Array). Selection of candidate miRNAs and subsequent validation using quantitative reverse transcription polymerase chain reaction (qRT-PCR) in 50 tissue samples were performed. RESULTS: After the screening phase of the study, five miRNAs were selected (hsa-miR-18b, hsa-miR-148a-5p, hsa-miR-204, hsa-miR-424, hsa-miR-129-1-3p). Validation revealed that miRNA-204 and miRNA-424 were highly downregulated in metastatic tissues compared with endometrial cancer samples (hsa-miR-204-P = .0008; hsa-miR-424-P = .0001). Receiver operating characteristic curves, which were constructed to compare endometrioid endometrial cancer and positive endometrioid endometrial cancer lymph nodes yielded the following area under the curves (AUCs): hsa-miR-204-.802 (96% confidence interval CI 0.676-0.927), hsa-miR-424-.84 (95% CI 0.711-0.969). CONCLUSIONS: Compared with primary endometrioid endometrial cancer tissue, metastatic loci derived from positive lymph nodes are characterized by profound downregulation of miRNA-204 and miRNA-424.

Sonographic and Elastographic Features of Extra- and Intrathyroidal Ectopic Thymus Mimicking Malignancy: Differential Diagnosis in Children.

Thyroid nodules with ultrasound (US) cancer risk features and extra-thyroid lesions suggesting malignant lymph nodes, require prompt diagnosis, especially in children. The US pattern of intrathyroidal ectopic thymus (IET) can strongly suggest papillary thyroid carcinoma (PTC). The extra-thyroid ectopic thymic tissue (EET) can mimic pathological lymph nodes in US. The aim of the study has been to demonstrate US features and diagnostic methods, allowing finally to confirm the presence of IET and EET in children. The US and elastographic features of 16 ectopic thymic tissue (ET) lesions were analyzed so as to describe the typical characteristics of ET and to define the best method to differentiate ET and malignant lesions. Among 16 analyzed lesions, 11 lesions were IET, and 5 were EET adjacent to the thyroid connective tissue capsule. Most of IET were located in the middle part of the right lobe and were fusiform or oval in shape. All the lesions were solid, hypoechoic, and heterogeneous with bright internal echoes. Among IET, 73% of lesions had well- or very well-defined margins. In strain elastography of IET lesions, the strain ratio was similar in all lesions, and its value ranged from 0.95 to 1.09. Despite the low prevalence of IET and cervical EET, clinicians and radiologists should be aware of US characteristics of such lesions. The confirmation of their benign character is absolutely required. Elastography is a useful tool to initially differentiate PTC and IET. However, due to high risk of malignancy in thyroid lesions in children, similarity of US features of PTC and IET, and due to the possibility of malignancy in ET, only cytological evaluation provides definitive diagnosis.