Miracle-dz/UniFAR-FTUs huggingface dataset:
Implementation of Person-Centered Care: A Feasibility Study Using the WE-CARE Roadmap

Background: Person-Centered Care (PCC) is a promising approach towards improved quality of care and cost containment within health systems. It has been evaluated in Sweden and England. This feasibility study examines initial PCC implementation in a rehabilitation hospital for children in Poland. Methods: The WE-CARE Roadmap of enablers was used to guide implementation of PCC for patients with moderate scoliosis. A multi-disciplinary team of professionals were trained in the PCC approach and the hospital Information Technology (IT) system was modified to enhance PCC data capture. Semi-structured interviews were conducted with the nine health care professionals involved in the pilot study and three patients/parents receiving care. Transcribed data were analyzed via content analysis. Results: 51 patients and their families were treated via a PCC approach. High proportions of new PCC data fields were completed by the professionals. The professionals were able to implement the three core PCC routines and perceived benefits using the PCC approach. Patients and their families also perceived improved quality care. The WE-CARE framework enablers facilitated PCC implementation in this setting. Conclusions: This feasibility pilot study indicates that the Gothenburg PCC approach can be successfully transferred to a rehabilitation hospital in Poland with favorable perceptions of implementation by both professionals and patients/their families.
Extracellular Vesicle-Based Therapeutics for Heart Repair

Extracellular vesicles (EVs) are constituted by a group of heterogeneous membrane vesicles secreted by most cell types that play a crucial role in cell–cell communication. In recent years, EVs have been postulated as a relevant novel therapeutic option for cardiovascular diseases, including myocardial infarction (MI), partially outperforming cell therapy. EVs may present several desirable features, such as no tumorigenicity, low immunogenic potential, high stability, and fine cardiac reparative efficacy. Furthermore, the natural origin of EVs makes them exceptional vehicles for drug delivery. EVs may overcome many of the limitations associated with current drug delivery systems (DDS), as they can travel long distances in body fluids, cross biological barriers, and deliver their cargo to recipient cells, among others. Here, we provide an overview of the most recent discoveries regarding the therapeutic potential of EVs for addressing cardiac damage after MI. In addition, we review the use of bioengineered EVs for targeted cardiac delivery and present some recent advances for exploiting EVs as DDS. Finally, we also discuss some of the most crucial aspects that should be addressed before a widespread translation to the clinical arena.
Dietary Antioxidant Vitamins and Minerals and Breast Cancer Risk: Prospective Results from the SUN Cohort

There is growing interest in natural antioxidants and their potential effects on breast cancer (BC). Epidemiological evidence, however, is inconsistent. We prospectively evaluated the association between dietary intake of vitamins A, C, and E, selenium, and zinc and BC among 9983 female participants from the SUN Project, a Mediterranean cohort of university graduates. Participants completed a food frequency questionnaire at baseline, and biennial follow-up information about incident BC diagnosis was collected. Cases were ascertained through revision of medical charts and consultation of the National Death Index. Cox proportional hazards models were used to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CI). During an average follow-up of 11.3 years, 107 incident BC cases were confirmed. The multivariable HRs (95% CI) for BC comparing extreme tertiles of energy-adjusted dietary intakes were 1.07 (0.64–1.77; Ptrend = 0.673) for vitamin A, 1.00 (0.58–1.71; Ptrend = 0.846) for vitamin C, 0.92 (0.55–1.54; Ptrend = 0.728) for vitamin E, 1.37 (0.85–2.20; Ptrend = 0.135) for selenium, and 1.01 (0.61–1.69; Ptrend = 0.939) for zinc. Stratified analyses showed an inverse association between vitamin E intake and postmenopausal BC (HRT3 vs. T1 = 0.35; 95% CI, 0.14–0.86; Ptrend = 0.027). Our results did not suggest significant protective associations between dietary vitamins A, C, and E, selenium, or zinc and BC risk.
The Effect of Fusarium verticillioides Fumonisins on Fatty Acids, Sphingolipids, and Oxylipins in Maize Germlings

Fusarium verticillioides causes multiple diseases of Zea mays (maize) including ear and seedling rots, contaminates seeds and seed products worldwide with toxic chemicals called fumonisins. The role of fumonisins in disease is unclear because, although they are not required for ear rot, they are required for seedling diseases. Disease symptoms may be due to the ability of fumonisins to inhibit ceramide synthase activity, the expected cause of lipids (fatty acids, oxylipins, and sphingolipids) alteration in infected plants. In this study, we explored the impact of fumonisins on fatty acid, oxylipin, and sphingolipid levels in planta and how these changes affect F. verticillioides growth in maize. The identity and levels of principal fatty acids, oxylipins, and over 50 sphingolipids were evaluated by chromatography followed by mass spectrometry in maize infected with an F. verticillioides fumonisin-producing wild-type strain and a fumonisin-deficient mutant, after different periods of growth. Plant hormones associated with defense responses, i.e., salicylic and jasmonic acid, were also evaluated. We suggest that fumonisins produced by F. verticillioides alter maize lipid metabolism, which help switch fungal growth from a relatively harmless endophyte to a destructive necrotroph.
Volitional learning promotes theta phase coding in the human hippocampus

Significance While behavioral evidence shows that volitionally controlled learning benefits human memory, little is known about the neural mechanisms underlying this effect. Insights from spatial navigation research in rodents point to the relevance of hippocampal theta oscillations. However, the mechanisms through which theta might support the beneficial effects of active learning in humans are currently unknown. Here, we demonstrate hippocampal theta oscillations increase during volitional learning, promoting a segregation of task-relevant representational signals according to their semantic content. Our results constitute a direct link to the animal literature on hippocampal theta oscillations and its relation to volition and memory processes. Electrophysiological studies in rodents show that active navigation enhances hippocampal theta oscillations (4–12 Hz), providing a temporal framework for stimulus-related neural codes. Here we show that active learning promotes a similar phase coding regime in humans, although in a lower frequency range (3–8 Hz). We analyzed intracranial electroencephalography (iEEG) from epilepsy patients who studied images under either volitional or passive learning conditions. Active learning increased memory performance and hippocampal theta oscillations and promoted a more accurate reactivation of stimulus-specific information during memory retrieval. Representational signals were clustered to opposite phases of the theta cycle during encoding and retrieval. Critically, during active but not passive learning, the temporal structure of intracycle reactivations in theta reflected the semantic similarity of stimuli, segregating conceptually similar items into more distant theta phases. Taken together, these results demonstrate a multilayered mechanism by which active learning improves memory via a phylogenetically old phase coding scheme.
Low expression of tRF‐Pro‐CGG predicts poor prognosis in pancreatic ductal adenocarcinoma

tRFs (tRNA‐derived RNA fragments) have been reported to facilitate cancer progression in multiple cancers. However, their role in pancreatic ductal adenocarcinoma (PDAC) remains to be determined. In this study, we mainly investigated the expression of tRF‐Pro‐CGG in pancreatic ductal adenocarcinoma and evaluated its relationship with the clinicopathology and survival time of patients.
Airway Hyperresponsiveness: From Molecules to Bedside Selected Contribution: Airway contractility and smooth muscle Ca 2 (cid:1) signaling in lung slices from different mouse strains

Ca signaling in from different mouse strains. To investigate the hypothesis that altered Ca 2 (cid:1) signaling in airway smooth muscle cells (SMCs) is responsible for airway hyperreactivity, we compared, with the use of confocal and phase-contrast microscopy, the airway contractility and Ca 2 (cid:1) changes in SMCs induced by acetylcholine (ACh) in lung slices from different mouse strains (A/J, Balb/C, and C3H/ HeJ). The airways from each mouse strain displayed a con-centration-dependent contraction to ACh. The contractile response of the airways of the C3H/HeJ mice was found, in contrast to earlier studies, to be much greater and faster than that of A/J and Balb/C mice. This difference in airway reactivity can be, in part, attributable to halothane, a volatile anesthetic that was previously used during in vivo measurements of airway reactivity but found here to signiﬁcantly alter the ACh contractile response of airways in lung slices. The ACh-induced Ca 2 (cid:1) response of the airway SMCs in all of the various mouse strains was also concentration dependent. The magnitude of the initial Ca 2 (cid:1) increase and the frequency of the subsequent Ca 2 (cid:1) oscillations induced by ACh increased with ACh concentration. However, no differences in the Ca 2 (cid:1) responses to ACh could be distinguished between the mouse strains. These results suggest that the mechanism responsible for airway hyperreactivity in different mouse strains resides with the Ca 2 (cid:1) sensitivity of the contractile apparatus of the SMCs rather than with the Ca 2 signaling itself. ﬂuorescence ratio (F/F 0 ) normalized to the initial ﬂuores- cence (F 0 ). Drug application. ACh and halothane were dissolved in sHBSS, and a 10 (cid:5) concentrated solution was added (15 (cid:3) l) to the bath solution (135 (cid:3) l) in which the ﬁnal working concentration was obtained by dilution. All experiments were con- ducted at room temperature. Statistics. Statistical analysis was performed with the one- way ANOVA and the Kruskal-Wallis ANOVA on ranks (all pairwise multiple comparison procedures (cid:7) Student-New-man-Keuls method). Values are given as means (cid:8) SE. A P value of (cid:9) 0.05 was considered to be statistically signiﬁcant.
Progress in the Development of Eukaryotic Elongation Factor 2 Kinase (eEF2K) Natural Product and Synthetic Small Molecule Inhibitors for Cancer Chemotherapy

Eukaryotic elongation factor 2 kinase (eEF2K or Ca2+/calmodulin-dependent protein kinase, CAMKIII) is a new member of an atypical α-kinase family different from conventional protein kinases that is now considered as a potential target for the treatment of cancer. This protein regulates the phosphorylation of eukaryotic elongation factor 2 (eEF2) to restrain activity and inhibit the elongation stage of protein synthesis. Mounting evidence shows that eEF2K regulates the cell cycle, autophagy, apoptosis, angiogenesis, invasion, and metastasis in several types of cancers. The expression of eEF2K promotes survival of cancer cells, and the level of this protein is increased in many cancer cells to adapt them to the microenvironment conditions including hypoxia, nutrient depletion, and acidosis. The physiological function of eEF2K and its role in the development and progression of cancer are here reviewed in detail. In addition, a summary of progress for in vitro eEF2K inhibitors from anti-cancer drug discovery research in recent years, along with their structure–activity relationships (SARs) and synthetic routes or natural sources, is also described. Special attention is given to those inhibitors that have been already validated in vivo, with the overall aim to provide reference context for the further development of new first-in-class anti-cancer drugs that target eEF2K.
Fibrinogen Interaction with Astrocyte ICAM-1 and PrPC Results in the Generation of ROS and Neuronal Death

Many neuroinflammatory diseases, like traumatic brain injury (TBI), are associated with an elevated level of fibrinogen and short-term memory (STM) impairment. We found that during TBI, extravasated fibrinogen deposited in vasculo-astrocyte interfaces, which was associated with neurodegeneration and STM reduction. The mechanisms of this fibrinogen-astrocyte interaction and its functional role in neurodegeneration are still unclear. Cultured mouse brain astrocytes were treated with fibrinogen in the presence or absence of function-blocking antibody or peptide against its astrocyte receptors intercellular adhesion molecule-1 (ICAM-1) or cellular prion protein (PrPC), respectively. Fibrinogen interactions with astrocytic ICAM-1 and PrPC were characterized. The expression of pro-inflammatory markers, generations of reactive oxygen species (ROS) and nitric oxide (NO) in astrocytes, and neuronal death caused by astrocyte-conditioned medium were assessed. Data showed a strong association between fibrinogen and astrocytic ICAM-1 or PrPC, overexpression of pro-inflammatory cytokines and overproduction of ROS and NO, resulting in neuronal apoptosis and death. These effects were reduced by blocking the function of astrocytic ICAM-1 and PrPC, suggesting that fibrinogen association with its astrocytic receptors induce the release of pro-inflammatory cytokines, resulting in oxidative stress, and ultimately neuronal death. This can be a mechanism of neurodegeneration and the resultant STM reduction seen during TBI.
Glutacetine® Biostimulant Applied on Wheat under Contrasting Field Conditions Improves Grain Number Leading to Better Yield, Upgrades N-Related Traits and Changes Grain Ionome

Wheat is one of the most important cereals for human nutrition, but nitrogen (N) losses during its cultivation cause economic problems and environmental risks. In order to improve N use efficiency (NUE), biostimulants are increasingly used. The present study aimed to evaluate the effects of Glutacetine®, a biostimulant sprayed at 5 L ha−1 in combination with fertilizers (urea or urea ammonium nitrate (UAN)), on N-related traits, grain yield components, and the grain quality of winter bread wheat grown at three field sites in Normandy (France). Glutacetine® improved grain yield via a significant increase in the grain number per spike and per m2, which also enhanced the thousand grain weight, especially with urea. The total N in grains and the NUE tended to increase in response to Glutacetine®, irrespective of the site or the form of N fertilizer. Depending on the site, spraying Glutacetine® can also induce changes in the grain ionome (analyzed by X-ray fluorescence), with a reduction in P content observed (site 2 under urea nutrition) or an increase in Mn content (site 3 under UAN nutrition). These results provide a roadmap for utilizing Glutacetine® biostimulant to enhance wheat production and flour quality in a temperate climate.
Sonographic Assessment of Complex Ultrasound Morphology Adnexal Tumors in Pregnant Women with the Use of IOTA Simple Rules Risk and ADNEX Scoring Systems

Background: To evaluate the accuracy of subjective assessment (SA), the International Ovarian Tumor Analysis (IOTA) group Simple Rules Risk (SRR) and the Assessment of Different NEoplasias in the adneXa (ADNEX) model for the preoperative differentiation of adnexal masses in pregnant women. Methods: The study population comprised 36 pregnant women (median age: 28.5 years old, range: 20–42 years old) with a mean gestation age of 13.5 (range: 8–31) weeks at diagnosis. Tumors were prospectively classified by local sonographers as probably benign or probably malignant using SA. Final tumor histological diagnosis was used as the reference standard in all cases. Logistic regression SRR and ADNEX models were used to obtain a risk score for every case. Serum CA125 and human epidydimis protein 4 (HE4) concentrations were also retrieved and the Risk of Ovarian Malignancy Algorithm (ROMA) value was calculated. The calculated predictive values included positive and negative likelihood ratios of ultrasound and biochemical tests. Results: Final histology confirmed 27 benign and 9 malignant (including 2 borderline) masses. The highest sensitivity (89%) and specificity (70%) were found for the subjective tumor assessment. Although no malignancy was classified as benign using the SRR criteria (sensitivity = 100%), the specificity of this scoring system was only 37%. At the cut-off risk level of >20%, the ADNEX model had a sensitivity of 78% and a specificity of 70%. Serum levels of CA125, HE4 and the ROMA risk model correctly identified adnexal malignant tumors with a sensitivity of 67%, 25% and 25%, respectively. Corresponding specificities were 72%, 100% and 100%, respectively. The highest positive and negative likelihood ratios were found for SA (LR+ = 3.0 and LR− = 0.16, respectively). Overall diagnostic accuracy of all predictive methods used in this study were similar (range: 70–75%) except for SRR (53%). Conclusion: Subjective assessment remains the best predictive method in complex adnexal masses found at prenatal ultrasound in pregnant women. For less experienced sonographers, both the SRR and ADNEX scoring systems may be also used for the characterization of such tumors, while serum tumor markers CA125 and HE4, along with the ROMA algorithm appear to be less accurate.
Higher Impulse Electromyostimulation Contributes to Psychological Satisfaction and Physical Development in Healthy Men

Background and Objectives: This study investigated the various impulse effects of whole-body electromyostimulation (WB-EMS) on psychophysiological responses and adaptations. Materials and Methods: The participants included fifty-four men between 20 and 27 years of age who practiced isometric exercises for 20 min, three days a week, for 12 weeks while wearing WB-EMS suits, which enabled the simultaneous activation of eight muscle groups with three types of impulse intensities. Participants were allocated to one of four groups: control group (CON), low-impulse-intensity group (LIG), mid-impulse-intensity group (MIG), and high-impulse-intensity group (HIG). Psychophysiological conditions were measured at week 0, week 4, week 8, and week 12. Results: Compared with the CON, (1) three psychological conditions in LIG, MIG, and HIG showed positive tendencies every four weeks, and the analysis of covariance (ANCOVA) test revealed that body image (p = 0.004), body shape (p = 0.007), and self-esteem (p = 0.001) were significantly different among the groups. (2) Body weight, fat mass, body mass index, and percent fat in the CON showed decreasing tendencies, whereas those in LIG, MIG, and HIG showed a noticeable decrease, which revealed that there were significant differences among the groups. Specifically, a higher impulse intensity resulted in a greater increase in muscle mass. (3) Although there was no interaction effect in the abdominal visceral fat area, there were significant interactions in the abdominal subcutaneous fat (ASF) and total fat (ATF) areas. Both the ASF and ATF in the CON showed decreasing tendencies, whereas those in other groups showed a noticeable decrease. The ANCOVA revealed that the ASF (p = 0.002) and ATF (p = 0.001) were significantly different among the groups. In particular, the higher the impulse intensity, the greater the decrease in abdominal fat. Conclusions: This study confirmed that high-impulse-intensity EMS can improve psychophysiological conditions. In other words, healthy young adults felt that the extent to which their body image, body shape, and self-esteem improved depended on how intense their EMS impulse intensities were. The results also showed that higher levels of impulse intensity led to improved physical conditions.
Superoxide is promoted by sucrose and affects amplitude of circadian rhythms in the evening

Significance Distinguishing the effects of light and sugars in photoautotrophic cells is challenging. The circadian system is a regulatory network that integrates light and metabolic signals and controls rhythmic physiology and growth. Our experimental approach has defined a light-independent, sugar-regulated transcriptome in Arabidopsis and revealed reactive oxygen species (ROS) as a prominent feature. ROS are byproducts of photosynthetic metabolism and oscillate with circadian rhythms but have not previously been demonstrated as inputs to the plant circadian oscillator. Our data suggest a role for superoxide as a rhythmic sugar signal which acts in the evening and affects circadian gene expression and growth. Plants must coordinate photosynthetic metabolism with the daily environment and adapt rhythmic physiology and development to match carbon availability. Circadian clocks drive biological rhythms which adjust to environmental cues. Products of photosynthetic metabolism, including sugars and reactive oxygen species (ROS), are closely associated with the plant circadian clock, and sugars have been shown to provide metabolic feedback to the circadian oscillator. Here, we report a comprehensive sugar-regulated transcriptome of Arabidopsis and identify genes associated with redox and ROS processes as a prominent feature of the transcriptional response. We show that sucrose increases levels of superoxide (O2–), which is required for transcriptional and growth responses to sugar. We identify circadian rhythms of O2–-regulated transcripts which are phased around dusk and find that O2– is required for sucrose to promote expression of TIMING OF CAB1 (TOC1) in the evening. Our data reveal a role for O2– as a metabolic signal affecting transcriptional control of the circadian oscillator in Arabidopsis.