Plant YTHDF proteins are direct effectors of antiviral immunity against an N6-methyladenosine-containing RNA virus.

In virus-host interactions, nucleic acid-directed first lines of defense that allow viral clearance without compromising growth are of paramount importance. Plants use the RNA interference pathway as a basal antiviral immune system, but additional RNA-based mechanisms of defense also exist. The infectivity of a plant positive-strand RNA virus, alfalfa mosaic virus (AMV), relies on the demethylation of viral RNA by the recruitment of the cellular N6-methyladenosine (m6 A) demethylase ALKBH9B, but how demethylation of viral RNA promotes AMV infection remains unknown. Here, we show that inactivation of the Arabidopsis cytoplasmic YT521-B homology domain (YTH)-containing m6 A-binding proteins ECT2, ECT3, and ECT5 is sufficient to restore AMV infectivity in partially resistant alkbh9b mutants. We further show that the antiviral function of ECT2 is distinct from its previously demonstrated function in the promotion of primordial cell proliferation: an ect2 mutant carrying a small deletion in its intrinsically disordered region is partially compromised for antiviral defense but not for developmental functions. These results indicate that the m6 A-YTHDF axis constitutes a novel branch of basal antiviral immunity in plants.

Nonclinical evaluation of chronic cardiac contractility modulation on 3D human engineered cardiac tissues.

INTRODUCTION: Cardiac contractility modulation (CCM) is a medical device-based therapy delivering non-excitatory electrical stimulations to the heart to enhance cardiac function in heart failure (HF) patients. The lack of human in vitro tools to assess CCM hinders our understanding of CCM mechanisms of action. Here, we introduce a novel chronic (i.e., 2-day) in vitro CCM assay to evaluate the effects of CCM in a human 3D microphysiological system consisting of engineered cardiac tissues (ECTs). METHODS: Cryopreserved human induced pluripotent stem cell-derived cardiomyocytes were used to generate 3D ECTs. The ECTs were cultured, incorporating human primary ventricular cardiac fibroblasts and a fibrin-based gel. Electrical stimulation was applied using two separate pulse generators for the CCM group and control group. Contractile properties and intracellular calcium were measured, and a cardiac gene quantitative PCR screen was conducted. RESULTS: Chronic CCM increased contraction amplitude and duration, enhanced intracellular calcium transient amplitude, and altered gene expression related to HF (i.e., natriuretic peptide B, NPPB) and excitation-contraction coupling (i.e., sodium-calcium exchanger, SLC8). CONCLUSION: These data represent the first study of chronic CCM in a 3D ECT model, providing a nonclinical tool to assess the effects of cardiac electrophysiology medical device signals complementing in vivo animal studies. The methodology established a standardized 3D ECT-based in vitro testbed for chronic CCM, allowing evaluation of physiological and molecular effects on human cardiac tissues.

Systematic review of executive functions in children with self-limited epilepsy with centrotemporal spikes.

Self-limited Epilepsy with Centrotemporal Spikes (ECTS) is a self-limiting childhood epilepsy with an overall good prognosis. The neurocognitive profile of ECTS shows various degrees of neuropsychological impairment, with speech impairment and executive dysfunction being the most prominent. This review aimed to clarify the executive function (EF) profile of children with ECTS and the clinical variables' impact on these abilities. We conducted a systematic review of the relevant literature for articles published up to January 2021. Demographic and clinical characteristics were abstracted from the original records. EF tasks used in the studies were classified according to Diamond's model, which identified four components: working memory, inhibitory control, cognitive flexibility, and higher order EFs. Twenty-three studies were included. Among the included records, 14 studies examined working memory, 15 inhibitory control, 15 flexibility, 4 higher order EFs, and 2 general EFs. Results confirmed the presence of a specific impairment in two abilities: inhibitory control and cognitive flexibility. This review confirms the need to assess each EF both in verbal and visual-spatial tasks. The early detection of children with ECTS at risk of developing neuropsychological impairment could activate interventions and prevent worse school achievement, social functioning, and a poor quality of life. Systematic review registration: PROSPERO: CRD42021245959.

Distance learning ects and flipped classroom in the anatomy learning: comparative study of the use of augmented reality, video and notes.

BACKGROUND: The establishment of the ECTS (European Credit Transfer System) is one of the pillars of the European Space of Higher Education. This way of accounting for the time spent in training has two essential parts, classroom teaching (work with the professor) and distance learning (work without the professor, whether in an individual or collective way). Much has been published on the distance learning part, but less on the classroom teaching section. In this work, the authors investigate didactic strategies and associated aids for distance learning work in a concept based on flipped classroom where transmitting information is carried out with aids that the professor prepares, so that the student works in an independent way before the classes, thus being able to dedicate the classroom teaching time to more complex learning and being able to count on the professor's help. METHODS: Three teaching aids applied to the study of anatomy have been compared: Notes with images, videos, and augmented reality. Four dimensions have been compared: the time spent, the acquired learnings, the metacognitive perception, and the prospects of the use of augmented reality for study. RESULTS: The results show the effectiveness, in all aspects, of augmented reality when compared with the rest of aids. The questionnaire assessed the acquired knowledge through a course exam, where 5.60 points were obtained for the notes group, 6.54 for the video group, and 7.19 for the augmented reality group. That is 0.94 more points for the video group compared with the notes and 1.59 more points for the augmented reality group compared with the notes group. CONCLUSIONS: This research demonstrates that, although technology has not been sufficiently developed for education, it is expected that it can be improved in both the autonomous work of the student and the academic training of health science students and that we can teach how to learn. Moreover, one can see how the grades of the students who studied with augmented reality are more grouped and that there is less dispersion in the marks compared with other materials.

The Actual (Un)usefulness of the Bologna System in Medical Education.

INTRODUCTION: Faculty of Medicine, University of Sarajevo has officially started working on 22.11.1944, and is the oldest faculty in the medical field in Bosnia and Herzegovina. At the same time there are two systems of organization of the teaching process, the old system and the Bologna system. AIM: To analyze the implementation of the Bologna system, and making an overview of its justification. MATERIAL AND METHODS: Answers from questionnaires from total of 459 students were analyzed (197 who had studied under the old system and 262 who studied under the Bologna system), so total of four generations of the Bologna system. They filled out a questionnaire in which they evaluated the teaching process. Student's opinion about quality of medical education was measured by modified Lickert scale. RESULTS: Students of old system are older than students of the Bologna process, whose average age is increasing from generation to generation, given the growing number of students who repeat a year. All students of old system repeated an academic year once or several times (p <0.05). Analysis of average grades showed statistically significant difference (p <0.05), where students in the Bologna system had higher averages than students who were studying under the old system. The presence of large number of female students, in both systems is significant (p <0.05). Out of 33 questions about satisfaction of class, 15 were answered with better average grade from students of the Bologna system. A slight improvement in the Bologna system is in terms of the evaluation of the quality of the educational process (teachers, methods, effects). The only significant progress has been proven in terms of rating the degree of computerization of the educational process-general records on enrolled students (old system vs Bologna system-3,44 vs 3,63), record of attendance (3,47 vs 3,73), obtaining certificates (3,08 vs 3,84), method of registration of exam (2,98 vs 3,71), method of practical exam (3,06 vs 3,36) and theoretical methods of taking exam (3,01 vs 3,14). Average grades where no average grade, on any issue, does not reach grade 4 of Likert Scale, talks about real problems of education in medical field. CONCLUSION: In a relatively large sample (four generations of students) true benefit and progress of the Bologna system has not been proven, in comparison to the old system. Bologna system has eased the students in the administrative sense by introduction of computerization of faculties, but the old problems and old questions about the organization's process and delivery have not been eliminated.

Electronic voltage and current transformers testing device.

A method for testing electronic instrument transformers is described, including electronic voltage and current transformers (EVTs, ECTs) with both analog and digital outputs. A testing device prototype is developed. It is based on digital signal processing of the signals that are measured at the secondary outputs of the tested transformer and the reference transformer when the same excitation signal is fed to their primaries. The test that estimates the performance of the prototype has been carried out at the National Centre for High Voltage Measurement and the prototype is approved for testing transformers with precision class up to 0.2 at the industrial frequency (50 Hz or 60 Hz). The device is suitable for on-site testing due to its high accuracy, simple structure and low-cost hardware.

Temperature effects on the conductance, spin-valley polarization and tunneling magnetoresistance of single magnetic silicene junctions.

Magnetic silicene junctions are versatile structures with spin-valley polarization and magnetoresistive capabilities. Here, we investigate the temperature effects on the transport properties of single magnetic silicene junctions. We use the transfer matrix method and the Landauer-Büttiker formalism to calculate the transmittance, conductance, spin-valley polarization and tunneling magnetoresistance. We studied the case for T = 0 K, finding the specific parameters where the spin-valley polarization and the tunneling magnetoresistance reach optimized values. Regarding the temperature effects, we find that its impact is not the same on the different transport properties. In the case of the conductance, depending on the spin-valley configuration the resonant peaks disappear at different temperatures. The spin polarization persists at a considerable value up to T=80 K, contrary to the valley polarization which is more susceptible to the temperature effects. In addition, a stepwise spin-valley polarization can be achieved at low temperature. The tunneling magnetoresistance is attenuated considerably as the temperature rises, decreasing more than two orders of magnitude after T=20 K. These findings indicate that in order to preserve the spin-valley polarization and magnetoresistive capabilities of magnetic silicene junctions is fundamental to modulate the temperature adequately.

Acute effects of cardiac contractility modulation stimulation in conventional 2D and 3D human induced pluripotent stem cell-derived cardiomyocyte models.

Cardiac contractility modulation (CCM) is a medical device therapy whereby non-excitatory electrical stimulations are delivered to the myocardium during the absolute refractory period to enhance cardiac function. We previously evaluated the effects of the standard CCM pulse parameters in isolated rabbit ventricular cardiomyocytes and 2D human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) monolayers, on flexible substrate. In the present study, we sought to extend these results to human 3D microphysiological systems to develop a robust model to evaluate various clinical CCM pulse parameters in vitro. HiPSC-CMs were studied in conventional 2D monolayer format, on stiff substrate (i.e., glass), and as 3D human engineered cardiac tissues (ECTs). Cardiac contractile properties were evaluated by video (i.e., pixel) and force-based analysis. CCM pulses were assessed at varying electrical 'doses' using a commercial pulse generator. A robust CCM contractile response was observed for 3D ECTs. Under comparable conditions, conventional 2D monolayer hiPSC-CMs, on stiff substrate, displayed no contractile response. 3D ECTs displayed enhanced contractile properties including increased contraction amplitude (i.e., force), and accelerated contraction and relaxation slopes under standard acute CCM stimulation. Moreover, 3D ECTs displayed enhanced contractility in a CCM pulse parameter-dependent manner by adjustment of CCM pulse delay, duration, amplitude, and number relative to baseline. The observed acute effects subsided when the CCM stimulation was stopped and gradually returned to baseline. These data represent the first study of CCM in 3D hiPSC-CM models and provide a nonclinical tool to assess various CCM device signals in 3D human cardiac tissues prior to in vivo animal studies. Moreover, this work provides a foundation to evaluate the effects of additional cardiac medical devices in 3D ECTs.

A qualitative awake EEG score for the diagnosis of continuous spike and waves during sleep (CSWS) syndrome in self-limited focal epilepsy (SFE): A case-control study.

PURPOSE: To determine whether awake EEG criteria can differentiate epileptic encephalopathy with continuous spike and waves during sleep (EE-CSWS) at the time of cognitive regression from typical, self-limited focal epilepsy (SFE). METHODS: This retrospective case-control study was based on the analysis of awake EEGs and included 15 patients with EE-CSWS and 15 age-matched and sex-matched patients with typical SFE. The EEGs were anonymised and scored by four independent readers. The following qualitative and quantitative EEG indices were analysed: slow-wave index (SLWI), spike-wave index (SWI), spike-wave frequency (SWF), long spike-wave clusters (CLSW) and EEG score (between grades 0 and 4). Sensitivity and specificity were assessed using receiver operating characteristic (ROC) curves and their reproducibility with a kappa test. RESULTS: Based on a highly sensitive cut-off, EE-CSWS patients were 8.4 times more likely than those with SFE to have an SLWI > 6%, 15 times more likely to have an SWI > 10 % and six times more likely to have a CLSW of ≥ 1 s. There was substantial agreement between readers (with kappa values of 0.64, 0.69 and 0.67). EE-CSWS patients were 13 times more likely to have an SWF of > 11 % and 149 times more likely to have an EEG score of ≥ 3 than typical SFE patients. Agreement about these ratings was almost perfect (kappa 0.91 and 0.86). CONCLUSION: An EEG score of ≥ 3 on a 20-min awake EEG differentiates typical SFE from EE-CSWS at the time of cognitive regression, with good reliability across readers with different levels of expertise.

Updated guidance on the management of cancer treatment-induced bone loss (CTIBL) in pre- and postmenopausal women with early-stage breast cancer.

INTRODUCTION: Adjuvant endocrine therapy induces bone loss and increases fracture risk in women with hormone-receptor positive, early-stage breast cancer (EBC). We aimed to update a previous position statement on the management of aromatase inhibitors (AIs) induced bone loss and now included premenopausal women. METHODS: We conducted a systematic literature search of the medical databases from January 2017 to May 2020 and assessed 144 new studies. RESULTS: Extended use of AIs beyond 5 years leads to persistent bone loss in breast cancer extended adjuvant trials and meta-analyses. In addition to bone mineral density (BMD), vertebral fracture assessment (VFA) and trabecular bone score (TBS) were shown to independently predict fracture risk in real life prospective studies. FRAX® tool does not seem to be reliable for assessing fracture risk in CTIBL. In premenopausal women, there is strong evidence that intravenous zoledronate prevents bone loss but weak conflicting evidence on reducing disease recurrence from independent randomised controlled trials (RCTs). In postmenopausal women, the strongest evidence for fracture prevention is for denosumab based on a well-powered RCT while there is strong evidence for bisphosphonates (BPs) to prevent and reduce CTIBL but no convincing data on fractures. Adjuvant denosumab has failed to show anticancer benefits in a large, well-designed RCT. DISCUSSION AND CONCLUSIONS: Extended use of AIs and persistent bone loss from recent data reinforce the need to evaluate fracture risk in EBC women initiated on AIs. Fracture risk should be assessed with clinical risk factors and BMD along with VFA, but FRAX is not adapted to CTIBL. Anti-resorptive therapy should be considered in those with a BMD T-score < -2.0 SD or with ≥ 2 clinical risk factors including a BMD T-score < -1.0 SD. In premenopausal women, intravenous zoledronate is the only drug reported to prevent bone loss and may have additional anticancer benefits. In postmenopausal women, either denosumab or BPs can be prescribed for fracture prevention with pertinent attention to the rebound phenomenon after stopping denosumab. Adjuvant BPs, in contrast to denosumab, have shown high level evidence for reducing breast cancer recurrence in high-risk post-MP women which should be taken into account when choosing between these two.

The impact of the Bologna process on nursing higher education in Europe: a review.

BACKGROUND: Changes are occurring in global higher education. Nursing is not exempt from these changes, and must adapt in order to be competitive in a global market. The Bologna process has been integral in the last decade in modernizing European higher education. However, modernization does not occur without challenges. This paper addresses the Bologna process and the challenges it presents to nursing higher education in Europe. OBJECTIVE: To describe the Bologna Process as it relates to European nursing education. DESIGN AND METHODOLOGY: Literature review via searches of the following electronic databases: Academic Search Premier, MEDLINE, PubMed, ERIC, and CINAHL. Search criteria included Bologna process, European higher education, nursing education, quality assurance, and ECTS. RESULTS: Twenty-four peer-reviewed articles were included as well as one peer-reviewed presentation, one commission report, and one book. CONCLUSION: Further investigation is required to address the complexities of the Bologna process and its evolutionary changes as it relates to nursing education in Europe. Change is not always easy, and is often complex, especially as it relates to cross-border education that involves governmental regulation. Bologna-member countries need to adapt to the ever-changing higher education environment or fall behind.

Pertinencia de los créditos académicos / Appropriateness of academic credits

Se realizó una revisión sobre el sistema de créditos académicos y su aplicación en la educación superior, partiendo del concepto de créditos académicos, que surgen como una necesidad para establecer comparaciones y equivalencias a escala internacional, además de permitir la movilidad estudiantil y profesoral. Se revisa su aplicación en las universidades de Europa, Norteamérica y América Latina, y se expresan las consideraciones en Cuba donde existe la experiencia solamente en la formación posgraduada. Se toman en consideraciones los conclaves celebrados en Europa y Latinoamérica sobre el tema.

The system of academic credits and its implementation in the higher education was made based on the concept of academic credits emerging from the need of making comparisons and finding equivalences at international scale, in addition to facilitating the mobility of professors and students to other institutions. Its implementation in European, American and Latin American universities was reviewed and the final considerations about this issue in Cuba, where the experience accumulated just in the graduate education, were also stated. This paper took into account the events about this topic held in Europe and Latin America.