Miracle-dz/UniFAR-FTUs huggingface dataset:
Metabolic Drug Response Phenotyping in Colorectal Cancer Organoids by LC-QTOF-MS

As metabolic rewiring is crucial for cancer cell proliferation, metabolic phenotyping of patient-derived organoids is desirable to identify drug-induced changes and trace metabolic vulnerabilities of tumor subtypes. We established a novel protocol for metabolomic and lipidomic profiling of colorectal cancer organoids by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) facing the challenge of capturing metabolic information from a minimal sample amount (<500 cells/injection) in the presence of an extracellular matrix (ECM). The best procedure of the tested protocols included ultrasonic metabolite extraction with acetonitrile/methanol/water (2:2:1, v/v/v) without ECM removal. To eliminate ECM-derived background signals, we implemented a data filtering procedure based on the p-value and fold change cut-offs, which retained features with signal intensities >120% compared to matrix-derived signals present in blank samples. As a proof-of-concept, the method was applied to examine the early metabolic response of colorectal cancer organoids to 5-fluorouracil treatment. Statistical analysis revealed dose-dependent changes in the metabolic profiles of treated organoids including elevated levels of 2′-deoxyuridine, 2′-O-methylcytidine, inosine and 1-methyladenosine and depletion of 2′-deoxyadenosine and specific phospholipids. In accordance with the mechanism of action of 5-fluorouracil, changed metabolites are mainly involved in purine and pyrimidine metabolism. The novel protocol provides a first basis for the assessment of metabolic drug response phenotypes in 3D organoid models.
Quaternion symmetry in relativistic molecular calculations: The Dirac–Hartree–Fock method

A symmetry scheme based on the irreducible corepresentations of the full symmetry group of a molecular system is presented for use in relativistic calculations. Consideration of time-reversal symmetry leads to a reformulation of the Dirac–Hartree–Fock equations in terms of quaternion algebra. Further symmetry reductions due to molecular point group symmetry are then manifested by a descent to complex or real algebra. Spatial symmetry will be restricted to D2h and subgroups, and it will be demonstrated that the Frobenius–Schur test can be used to characterize these groups as a whole. The resulting symmetry scheme automatically provides maximum point group and time-reversal symmetry reduction of the computational effort, also when the Fock matrix is constructed in a scalar basis, that is, from the same type of electron repulsion integrals over symmetry-adapted scalar basis functions as in nonrelativistic theory. An illustrative numerical example is given showing symmetry reductions comparable to the nonrela.
Insights into German Consumers’ Perceptions of Virtual Fencing in Grassland-Based Beef and Dairy Systems: Recommendations for Communication

Simple Summary Pasture-raised beef and dairy products are valued by consumers for their taste and higher animal welfare standards. Pasture grazing can be optimized using virtual fencing technology. The use of virtual fencing to guide cattle on pasture can contribute to biodiversity conservation by protecting environmentally sensitive areas. Concerns exist about consumers’ acceptance of virtual fencing in beef and dairy production. To explore consumers’ perception of virtual fencing, German consumers’ responses to information material about virtual fencing were analyzed. The results showed respondents’ uncertainty about the implementation of the technology with regard to its effects on animal welfare and possible social impact. Respondents showed readiness to support pasture grazing with their purchase decisions, yet struggled to see their personal advantages from the use of a specific grazing management practice. Thus, practitioners should consider keeping the focus in communication with consumers not on the technology but on tangible benefits, such as quality of pasture-raised products. Furthermore, state support is argued to be necessary to encourage livestock practitioners to adopt virtual fencing in cattle grazing for biodiversity conservation. Abstract The share of cattle grazing on grassland is decreasing in many European countries. While the production costs of intensive stall-based beef and dairy systems are usually lower per kg product, grazing-based systems provide more ecosystem services that are valued by consumers. Innovative grazing systems that apply virtual fencing technology can improve animal welfare, optimize grassland use as pasture, and contribute to biodiversity conservation. Although consumer demand for pasture-raised products could promote animal-friendly practices, consumer perception of virtual fencing remains unknown. To address this gap in research, this study developed information brochures with different lines of argumentation and tested the responses of German consumers using concurrent think aloud protocols. The results demonstrated ambivalence in consumers’ attitudes to virtual fencing. The participants supported the idea of cattle pasturing to promote animal welfare and foster biodiversity declaring a willingness to contribute not only by paying price premiums for pasture-raised products but also through seeking other possibilities of action and participation. However, participants raised concerns about the effects on animal welfare and the social ramifications of the technology. The study offers recommendations for addressing these issues in communication and further contributes to the understanding of consumers’ perceptions of innovation in animal production.
Vacuum Steam Treatment Effectiveness for Eradication of the Thousand Cankers Disease Vector and Pathogen in Logs From Diseased Walnut Trees

Abstract Logs of high-value eastern black walnut (Juglans nigra L.) are commonly exported from the United States for production of veneer and lumber. Veneer logs are not debarked to minimize degradation of wood quality and reduce moisture loss. Thousand cankers disease (TCD) is caused by the walnut twig beetle (Pityophthorus juglandis Blackman) and the fungal pathogen, Geosmithia morbida M. Kolarik, E. Freeland, C. Utley and N. Tisserat sp. nov., which colonize the inner bark of Juglans species. Effective eradication of these organisms by heat or chemical fumigation treatment is required for walnut logs prior to export. Because vacuum steam is an effective and efficient means of heating round wood, its use in eliminating the TCD causal agents was evaluated using Juglans logs (12- to 44-cm small end diameter and 1.7- to 1.9-m length) fromTCD-symptomatic trees in Oregon and Washington State. Five replicate trials with three logs per load were conducted in a portable vacuum chamber to test two treatment schedules: 60°C for 60 min and 56°C for 30 min. Complete elimination of P. juglandis and G. morbida was achieved when using a minimum of 56°C at 5-cm targeted depth from bottom of bark furrow into the sapwood and held for 30 min. Treatment cycle time ranged from 298 to 576 min depending on log diameter and initial log temperature. Artificial inoculation of J. nigra trees with G. morbida within the TCD range in Pennsylvania was minimally successful in producing adequately colonized logs for experimental trials.
Improving Provision of Preanesthetic Information Through Use of the Digital Conversational Agent “MyAnesth”: Prospective Observational Trial

Background Due to time limitations, the preanesthetic consultation (PAC) is not the best time for patients to integrate information specific to their perioperative care pathway. Objective The main objectives of this study were to evaluate the effectiveness of a digital companion on patients' knowledge of anesthesia and their satisfaction after real-life implementation. Methods We conducted a prospective, monocentric, comparative study using a before-and-after design. In phase 1, a 9-item self-reported anesthesia knowledge test (Delphi method) was administered to patients before and after their PAC (control group: PAC group). In phase 2, the study was repeated immediately after the implementation of a digital conversational agent, MyAnesth (@+PAC group). Patients’ satisfaction and their representations for anesthesia were also assessed using a Likert scale and the Abric method of hierarchized evocation. Results A total of 600 tests were distributed; 205 patients and 98 patients were included in the PAC group and @+PAC group, respectively. Demographic characteristics and mean scores on the 9-point preinformation test (PAC group: 4.2 points, 95% CI 3.9-4.4; @+PAC: 4.3 points, 95% CI 4-4.7; P=.37) were similar in the two groups. The mean score after receiving information was better in the @+PAC group than in the PAC group (6.1 points, 95% CI 5.8-6.4 points versus 5.2 points, 95% CI 5.0-5.4 points, respectively; P<.001), with an added value of 0.7 points (95% CI 0.3-1.1; P<.001). Among the respondents in the @+PAC group, 82% found the information to be clear and appropriate, and 74% found it easily accessible. Before receiving information, the central core of patients’ representations for anesthesia was focused on the fear of being put to sleep and thereafter on caregiver skills and comfort. Conclusions The implementation of our digital conversational agent in addition to the PAC improved patients' knowledge about their perioperative care pathway. This innovative audiovisual support seemed clear, adapted, easily accessible, and reassuring. Future studies should focus on adapting both the content and delivery of a digital conversational agent for the PAC in order to maximize its benefit to patients.
Diadema setosum: isolation of bioactive secondary metabolites with cytotoxic activity toward human cervical cancer

Abstract In our promising project toward discovery of secondary metabolites with potential anticancer activity against human cervical cancer, seven marine organisms were screened for their cytotoxic activity against HeLa cancer cell line using MTT colorimetric assay. The crude extract of the outer shell of Diadema setosum showed promising activity with 88.02% inhibition at a concentration 250 µg/ml. Chromatographic investigation of the Ethyl acetate fraction, which is the main contributor to the activity (IC50= 43.1 ± 5.94 µg/ml), led to isolation of five compounds. Structures of the isolates (1-5) were elucidated by 1 D and 2 D NMR spectroscopy and HR-ESI-MS analysis. 5α,8α-epidioxycholest-6-en-3β ol (2) and 5α,8α-epidioxycholest-6,9(11)-en-3β ol (3) showed the highest cytotoxic activity with IC50 values 12.1 ± 2.74 µg/ml and 21.8 ± 6.32 µg/ml, respectively. Epidioxy steroids with cholestane nucleus could be a prospective candidate for the development of drugs for treatment of human cervical cancer. Graphical Abstract
The Dual-Angle Method for Fast, Sensitive T1 Measurement in Vivo with Low-Angle Adiabatic Pulses

A new method for measuring T1 based on a measurement of the ratio, R, of the steady-state partially saturated NMR signals acquired at two fixed low flip angles (<90°) and a single sequence-repetition period, TR, is presented, The flip angles are chosen to optimize both the signal-to-noise ratio per unit time relative to the best possible Ernst-angle performance and the sensitivity with which a measurement of R can resolve differences in T1. A flip-angle pair at of around (60°, 15°) yields 70-79% of the maximum achievable Ernst-angle signal-to-noise ratio and a near-linear dependence of R on TR/T1 with gradient of about 2:1 over the range 0.1 ≤ TR/T1 ≤ 1. Errors in hip-angle and excitation-field (B1) inhomogeneity result in roughly proportionate errors in the apparent T1. The method is best implemented with adiabatic low-angle pulses such as B1-independent rotation (BIR-4) or BIR-4 phase-cycled (BIRP) pulses, which permit measurements with surface coils. Experimental validation was obtained at 2 T by comparison of unlocalized inversion-recovery and dual-angle proton (1H) and phosphorus (31P) measurements from vials containing doped water with 0.04 ≤ T1 ≤ 2.8 s and from the metabolites in the calf muscles of eight human volunteers. Calf muscle values of 6 ± 0.5 s for phosphocreatine and around 3.7 ± 0.8 s for the adenosine triphosphates (ATP) were in good agreement with inversion-recovery T1 values and values from the literature. Use of the dual-angle method accelerated T1 measurement time by about fivefold over inversion recovery. The dual-angle method was implemented in a one-dimensional localized surface-coil 31P spectroscopy sequence, producing consistent T1 measurements from phantoms, the calf muscle, and the human liver. 31P T1 values of ATP in the livers of six volunteers were about 0.5 ± 0.1 to 0.6 ± 0.2 s: the total exam times were about 35 minutes per subject. The method is ideally suited to low-sensitivity and/or low-concentration moieties, such as in 31P NMR in vivo, where study-time limitations are critical, and for rapid 1H T1 imaging.
Bringing New Methods to the Seed Proteomics Platform: Challenges and Perspectives

For centuries, crop plants have represented the basis of the daily human diet. Among them, cereals and legumes, accumulating oils, proteins, and carbohydrates in their seeds, distinctly dominate modern agriculture, thus play an essential role in food industry and fuel production. Therefore, seeds of crop plants are intensively studied by food chemists, biologists, biochemists, and nutritional physiologists. Accordingly, seed development and germination as well as age- and stress-related alterations in seed vigor, longevity, nutritional value, and safety can be addressed by a broad panel of analytical, biochemical, and physiological methods. Currently, functional genomics is one of the most powerful tools, giving direct access to characteristic metabolic changes accompanying plant development, senescence, and response to biotic or abiotic stress. Among individual post-genomic methodological platforms, proteomics represents one of the most effective ones, giving access to cellular metabolism at the level of proteins. During the recent decades, multiple methodological advances were introduced in different branches of life science, although only some of them were established in seed proteomics so far. Therefore, here we discuss main methodological approaches already employed in seed proteomics, as well as those still waiting for implementation in this field of plant research, with a special emphasis on sample preparation, data acquisition, processing, and post-processing. Thereby, the overall goal of this review is to bring new methodologies emerging in different areas of proteomics research (clinical, food, ecological, microbial, and plant proteomics) to the broad society of seed biologists.
Electrospun Conductive Nanofiber Yarns Accelerating Mesenchymal Stem Cells Differentiation and Maturation into Schwann Cell-Like Cells Under a Combination of Electrical Stimulation and Chemical Induction

Development of multifunctional tube-filling materials is required to improve the performances of the existing nerve guidance conduits (NGCs) in the repair of long-gap peripheral nerve (PN) injuries. In this study, composite nanofiber yarns (NYs) based on poly(p-dioxanone) (PPDO) biopolymer and different concentrations of carbon nanotubes (CNTs) were manufactured by utilizing a modified electrospinning apparatus. We confirmed the successful incorporation of CNTs into the PPDO nanofibers of as-fabricated composite NYs. The PPDO/CNT NYs exhibited similar morphology and structure in comparison with pure PPDO NYs. However, the PPDO/CNT NYs showed obviously enhanced mechanical properties and electrical conductivity compared to PPDO NYs. The biological tests revealed that the addition of CNTs had no negative effects on the cell growth, and proliferation of rabbit Schwann cells (rSCs), but it better maintained the phenotype of rSCs. We also demonstrated that the electrical stimulation (ES) significantly enhanced the differentiation capability of human adipose-derived mesenchymal stem cells (hADMSCs) into SC-like cells (SCLCs) on the PPDO/CNT NYs. More importantly, a unique combination of ES and chemical induction was found to further enhance the maturation of hADMSC-SCLCs on the PPDO/CNT NYs by notably upregulating the expression levels of SC myelination-associated gene markers and increasing the growth factor secretion. Overall, this study showed that our electrically conductive PPDO/CNT composite NYs could provide a beneficial microenvironment for various cell activities, making them an attractive candidate as NGC-infilling substrates for PN regeneration applications.
The Relationship between Under-Nutrition and Hypertension among Ellisras Children and Adolescents Aged 9 to 17 Years

Background: Globally, under-nutrition and hypertension in children has been associated with the risk of developing cardiovascular disease (CVD) in adulthood. The main objective of this study was to investigate the relationship between under-nutrition and hypertension, furthermore, to determine the risk of developing hypertension due to under-nutrition. Methods: The study comprised of 1701 participants (874 boys and 827 girls) between the ages of 9 and 17 years old. All anthropometric and blood pressure measurements were taken according to standard procedures. Mid-upper arm circumference (MUAC), body mass index (BMI), upper arm fat area (UFA), total upper arm area (TUAA) and upper arm muscle area (UMA) of Ellisras children were compared with the National Health and Nutrition Examination Survey III reference population. The linear regression models were used to determine the relationship between under-nutrition with hypertension for unadjusted and then adjusted for age and gender. The logistic regression model was used to determine the risk of under-nutrition on developing hypertension for unadjusted and adjusted for age and gender. Results: There was a positive significant (p < 0.0001) association between all under-nutrition variables (MUAC, BMI, UFA, TUAA and UMA) and systolic blood pressure (SBP; beta ranges between 0.84 and 2.78), and diastolic blood pressure (DBP; beta ranges between 0.3 and 1.08 before adjusting and after adjusting for age and gender (SBP, beta ranges between 0.59 and 2.00 and DBP (beta ranges between 0.24 and 0.80. Conclusion: The prevalence of under-nutrition was high while the prevalence of hypertension was low in this study. The mean under-nutrition variables (BMI, UFA, UMA and MUAC) of Ellisras children were far lower compared to the NHANES III reference population. Hypertension was significantly associated with under-nutrition in this study.
Delayed Judgments of Learning Are Associated With Activation of Information From Past Experiences: A Neurobiological Examination

Research in metacognition suggests that the information people use to predict their memory performance can vary depending on the contexts in which they make their predictions. For example, if people judge their memories after a delay from initial encoding, they may be more likely to use retrieved information about the past encoding experience than if they judged memories immediately after encoding. Although this seems intuitive, past behavioral and neuroimaging work has not tested whether delayed memory judgments are more strongly coupled with information about past experiences than immediate memory judgments. We scanned participants using functional MRI while they encoded paired associates and made predictions about their future memory performance either immediately after encoding or after a delay. Consistent with the hypothesis that people use retrieved information about past experiences to inform delayed memory judgments, our results showed that activation patterns associated with past experience were more strongly coupled with delayed memory judgments than with immediate ones.
Risk Factors Associated With Young-Onset Colorectal Adenomas and Cancer: A Systematic Review and Meta-Analysis of Observational Research

The risk of young-onset colorectal adenomas and cancer (yCRAC) in adults less than 50 years of age is increasing. We conducted a systematic review and meta-analysis of epidemiologic studies to identify lifestyle and clinical risk factors associated with yCRAC risk. We searched Medline, EMBASE, and Cochrane Database of Systematic Reviews for studies which: used an epidemiologic study design, involved individuals with yCRAC, evaluated at least 1 lifestyle or clinical factor, and applied multivariable regression approaches. We critically appraised the quality of included studies and calculated pooled measures of association (e.g. odds ratio [OR]) and 95% confidence intervals (CI) using random-effects models. We identified 499 articles in our search with 9 included in a narrative synthesis and 6 included in a meta-analysis. We found in the pooled analysis that smoking and alcohol consumption were lifestyle factors associated with yCRAC, as were clinical factors including obesity elevated blood glucose, elevated blood pressure, and elevated triglycerides. We identified lifestyle and clinical risk factors associated with risk of yCRAC, which have potential implications for informing preventive efforts and modifying screening to target at-risk populations.
Approaches to Test the Neurotoxicity of Environmental Contaminants in the Zebrafish Model: From Behavior to Molecular Mechanisms

The occurrence of neuroactive chemicals in the aquatic environment is on the rise and poses a potential threat to aquatic biota of currently unpredictable outcome. In particular, subtle changes caused by these chemicals to an organism's sensation or behavior are difficult to tackle with current test systems that focus on rodents or with in vitro test systems that omit whole‐animal responses. In recent years, the zebrafish (Danio rerio) has become a popular model organism for toxicological studies and testing strategies, such as the standardized use of zebrafish early life stages in the Organisation for Economic Co‐operation and Development's guideline 236. In terms of neurotoxicity, the zebrafish provides a powerful model to investigate changes to the nervous system from several different angles, offering the ability to tackle the mechanisms of action of chemicals in detail. The mechanistic understanding gained through the analysis of this model species provides a good basic knowledge of how neuroactive chemicals might interact with a teleost nervous system. Such information can help infer potential effects occurring to other species exposed to neuroactive chemicals in their aquatic environment and predicting potential risks of a chemical for the aquatic ecosystem. In the present article, we highlight approaches ranging from behavioral to structural, functional, and molecular analysis of the larval zebrafish nervous system, providing a holistic view of potential neurotoxic outcomes. Environ Toxicol Chem 2021;40:989–1006. © 2020 SETAC