Miracle-dz/UniFAR-FTUs huggingface dataset:
The influence of scar on the spatio-temporal relationship between electrical and mechanical activation in heart failure patients.

AIMS The aim of this study was to determine the relationship between electrical and mechanical activation in heart failure (HF) patients and whether electromechanical coupling is affected by scar. METHODS AND RESULTS Seventy HF patients referred for cardiac resynchronization therapy or biological therapy underwent endocardial anatomo-electromechanical mapping (AEMM) and delayed-enhancement magnetic resonance (CMR) scans. Area strain and activation times were derived from AEMM data, allowing to correlate mechanical and electrical activation in time and space with unprecedented accuracy. Special attention was paid to the effect of presence of CMR-evidenced scar. Patients were divided into a scar (n = 43) and a non-scar group (n-27). Correlation between time of electrical and mechanical activation was stronger in the non-scar compared to the scar group [R = 0.84 (0.72-0.89) vs. 0.74 (0.52-0.88), respectively; P = 0.01]. The overlap between latest electrical and mechanical activation areas was larger in the absence than in presence of scar [72% (54-81) vs. 56% (36-73), respectively; P = 0.02], with smaller distance between the centroids of the two regions [10.7 (4.9-17.4) vs. 20.3 (6.9-29.4) % of left ventricular radius, P = 0.02]. CONCLUSION Scar decreases the association between electrical and mechanical activation, even when scar is remote from late activated regions.
Making sense out of missense mutations: Mechanistic dissection of Notch receptors through structure‐function studies in Drosophila

Notch signaling is involved in the development of almost all organ systems and is required post‐developmentally to modulate tissue homeostasis. Rare variants in Notch signaling pathway genes are found in patients with rare Mendelian disorders, while unique or recurrent somatic mutations in a similar set of genes are identified in cancer. The human genome contains four genes that encode Notch receptors, NOTCH1‐4, all of which are linked to genetic diseases and cancer. Although some mutations have been classified as clear loss‐ or gain‐of‐function alleles based on cellular or rodent based assay systems, the functional consequence of many variants/mutations in human Notch receptors remain unknown. In this review, I will first provide an overview of the domain structure of Notch receptors and discuss how each module is known to regulate Notch signaling activity in vivo using the Drosophila Notch receptor as an example. Next, I will introduce some interesting mutant alleles that have been isolated in the fly Notch gene over the past > 100 years of research and discuss how studies of these mutations have facilitated the understanding of Notch biology. By identifying unique alleles of the fly Notch gene through forward genetic screens, mapping their molecular lesions and characterizing their phenotypes in depth, one can begin to unravel new mechanistic insights into how different domains of Notch fine‐tune signaling output. Such information can be useful in deciphering the functional consequences of rare variants/mutations in human Notch receptors, which in turn can influence disease management and therapy.
Ion Mobility Separation Using a Dual-LIT Miniature Mass Spectrometer.

Ion mobility (IM) has been increasingly used in combination with mass spectrometry (MS) for chemical and biological analysis. While implementation of IM with MS usually requires complex instrumentation with delicate controls, in this study we explored the potential of performing IM separation using dual linear ion traps (LITs) in a miniature mass spectrometer, which was originally developed for performing comprehensive MS/MS scan functions with a simple instrumentation config-uration. The IM separation was achieved by ion transfer between the LITs with dynamic gas flow. Its performance was characterized for analysis of a broad range of chemical and biological compounds including small organic compounds such as trisaccharides, raffinose, cellotriose and melezitose, as well as protein conformers. The demonstrated technique serves as another example of developing powerful hybrid instrument functions with simple configurations and miniaturized sizes.
Hyperspectral Fluorescence LIDAR Based on a Liquid Crystal Tunable Filter for Marine Environment Monitoring

An innovative hyperspectral LIDAR instrument has been developed for applications in marine environment monitoring research activities, remotely detecting the fluorescence spectra produced in the spectral interval between 400 nm and 720 nm. The detection system is composed by a custom made photomultiplier charge integrating and measuring (CIM) unit, which makes automatic background signal subtraction, and a liquid crystal tunable filter (LCTF). The new instrument therefore has hyperspectral resolution and allows automatic background subtraction; it is compact and automated by custom software that permit to adapt the instrument properties depending on the environmental conditions. Laboratory tests to characterize the instrument performance have been carried out, concluding that this sensor can be employed in remote sites for Chl-a detection.
A simple phototheranostics strategy to continuously deliver singlet oxygen in dark and hypoxic tumor microenvironment.

Continuous irradiation during photodynamic therapy (PDT) process inevitably induces tumor hypoxia, thereby weakening the PDT effect. In the PDT induced temporary hypoxia, sustainably providing singlet oxygen from stored chemical energy may enhance the cell killing effect and boost the phototheranostics. Herein, we present a phototheranostics (DPPTPE@PEG-Py NPs) by using 2-pyridone based diblock polymer (PEG-Py) to encapsulate a semiconducting heavy atom free pyrrolopyrrolidone-tetraphenylethylene (DPPTPE) with high singlet oxygen generation ability both in dichloromethane and water. In the phototheranostics, the designed PEG-Py can trap the 1O2 generated from DPPTPE under laser irradiation and form a stable intermediate of endoperoxide, which can then chemically release 1O2 in both dark and hypoxic tumor microenvironment. In comparison with DSPE-PEG encapsulated DPPTPE (DPPTPE@DSPE-PEG), much lower half maximum inhibitory concentration (IC50) was observed in four types of cancer cell lines, including HeLa, HCT-116, A549 and MCF-7 under laser irradiation after being uptaken by DPPTPE@PEG-Py NPs. Furthermore, the fluorescence imaging guided phototherapy study demonstrates that our designed phototheranostics could completely inhibit the tumor growth with the help of laser. This study provides a paradigm to develop highly efficient photosensitizers with photodynamic and photothermal capability for personalized cancer therapy.
Epac1 null mice have nephrogenic diabetes insipidus with deficient corticopapillary osmotic gradient and weaker collecting duct tight junctions

The cAMP‐mediator Epac1 (RapGef3) has high renal expression. Preliminary observations revealed increased diuresis in Epac1−/− mice. We hypothesized that Epac1 could restrict diuresis by promoting transcellular collecting duct (CD) water and urea transport or by stabilizing CD paracellular junctions to reduce osmolyte loss from the renal papillary interstitium.
Processing of Real‐World, Dynamic Natural Stimuli in Autism is Linked to Corticobasal Function

Many individuals with autism spectrum disorder (ASD) have been shown to perceive everyday sensory information differently compared to peers without autism. Research examining these sensory differences has primarily utilized nonnatural stimuli or natural stimuli using static photos with few having utilized dynamic, real‐world nonverbal stimuli. Therefore, in this study, we used functional magnetic resonance imaging to characterize brain activation of individuals with high‐functioning autism when viewing and listening to a video of a real‐world scene (a person bouncing a ball) and anticipating the bounce. We investigated both multisensory and unisensory processing and hypothesized that individuals with ASD would show differential activation in (a) primary auditory and visual sensory cortical and association areas, and in (b) cortical and subcortical regions where auditory and visual information is integrated (e.g. temporal‐parietal junction, pulvinar, superior colliculus). Contrary to our hypotheses, the whole‐brain analysis revealed similar activation between the groups in these brain regions. However, compared to controls the ASD group showed significant hypoactivation in the left intraparietal sulcus and left putamen/globus pallidus. We theorize that this hypoactivation reflected underconnectivity for mediating spatiotemporal processing of the visual biological motion stimuli with the task demands of anticipating the timing of the bounce event. The paradigm thus may have tapped into a specific left‐lateralized aberrant corticobasal circuit or loop involved in initiating or inhibiting motor responses. This was consistent with a dual “when versus where” psychophysical model of corticobasal function, which may reflect core differences in sensory processing of real‐world, nonverbal natural stimuli in ASD. Autism Res 2020, 13: 539–549. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.
Characterisation of the PS-PMMA Interfaces in Microphase Separated Block Copolymer Thin Films by Analytical (S)TEM

Block copolymer (BCP) self-assembly is a promising tool for next generation lithography as microphase separated polymer domains in thin films can act as templates for surface nanopatterning with sub-20 nm features. The replicated patterns can, however, only be as precise as their templates. Thus, the investigation of the morphology of polymer domains is of great importance. Commonly used analytical techniques (neutron scattering, scanning force microscopy) either lack spatial information or nanoscale resolution. Using advanced analytical (scanning) transmission electron microscopy ((S)TEM), we provide real space information on polymer domain morphology and interfaces between polystyrene (PS) and polymethylmethacrylate (PMMA) in cylinder- and lamellae-forming BCPs at highest resolution. This allows us to correlate the internal structure of polymer domains with line edge roughnesses, interface widths and domain sizes. STEM is employed for high-resolution imaging, electron energy loss spectroscopy and energy filtered TEM (EFTEM) spectroscopic imaging for material identification and EFTEM thickness mapping for visualisation of material densities at defects. The volume fraction of non-phase separated polymer species can be analysed by EFTEM. These methods give new insights into the morphology of polymer domains the exact knowledge of which will allow to improve pattern quality for nanolithography.
Finite-Time Tracking Control for a Class of Uncertain Strict-Feedback Nonlinear Systems With State Constraints: A Smooth Control Approach

This article is concerned with the finite-time tracking control problem for a class of strict-feedback nonlinear systems involving state constraints, unknown nonlinearities, and nonvanishing disturbances. Unlike the literature that mainly focuses on a $C^{0}$ finite-time controller, in this article, a novel $C^{1}$ smooth finite-time adaptive neural network (NN) controller is proposed by employing a smooth switch between the fractional and cubic form state feedback. The proposed controller not only avoids the singularity but also makes it possible to implement the dynamic surface control (DSC) technique. By applying the adaptive NN control technique, together with barrier Lyapunov functions (BLFs) and a generalized first-order filter including both linear and fractional terms, the desired fast finite-time control performance of the closed-loop nonlinear systems can be guaranteed, and meanwhile, the state constraints are never violated. Under the proposed control scheme, the tracking control problems of nonlinear systems with output constraint and full-state constraints are, respectively, discussed. It is explicitly shown that all the internal error signals are driven to converge into small regions in a finite time. Finally, the effectiveness of the control scheme is also confirmed by the applications to the control of a second-order nonlinear system and an uncertain ship autopilot.
The Administration of Tenofovir Disoproxil Fumarate for Pregnant Japanese Women with Chronic Hepatitis B

The appropriate management of hepatitis B virus (HBV) infection during pregnancy has not been established in Japan. We herein report five HBV-infected pregnant Japanese women who received tenofovir disoproxil fumarate (TDF). Two of them had been born after the introduction of nationwide immunoprophylaxis and were vertically infected with HBV, highlighting the need to address mother-to-child transmission further. In both entecavir-experienced and nucleoside/nucleotide analog-naïve mothers, TDF suppressed HBV replication without serious adverse events. All five children were free from congenital disorders, growth impairment, and HBV infection. TDF showed safety and efficacy for pregnant woman with chronic hepatitis B and might have helped prevent mother-to-child transmission.
Angiomotin links ROCK and YAP signaling in mechanosensitive differentiation of neural stem cells

Mechanical cues regulate the function of a broad range of stem cells in culture and in tissue. For example, soft substrates promote the neuronal differentiation of neural stem cells (NSCs) by suppressing cytoskeletal contractility. However, the mechanisms that link cytoskeletal signaling to the transcriptional regulatory processes that ultimately govern stiffness-dependent NSC fate commitment are not fully understood. Here, we show that Angiomotin (AMOT), which can bind both F-actin and the neurosuppressive transcriptional coactivator Yes-associated protein (YAP), is critical for mechanotransduction in NSCs. On soft substrates, loss of AMOT substantially reduces neurogenesis, whereas on stiff substrates, loss of AMOT negates the rescue of neurogenesis normally induced by pharmacologic inhibition of myosin activity. Furthermore, overexpression of a phospho-mimetic S175E AMOT mutant, which has been established to enhance AMOT–YAP binding, increases β-catenin activity and rescues neurogenesis on stiff substrates. Together, our data identify AMOT as an important intermediate signal transducer that allows NSCs to sense and respond to extracellular stiffness cues.
Bullying at work and work-related stress in healthcare workers: a cross sectional study.

BACKGROUND Bullying is a serious and growing problem affecting a significant proportion of healthcare professionals, a professional category exposed to work-related stress. Workplace bullying has been defined as a set of negative behaviours consisting in harassment, offense or negative influence on work that are directed to the members of the organization and that occur regularly and repeatedly over a period, becoming part of the context of work. STUDY DESIGN We performed a cross-sectional study using the HSE questionnaire and defining the sample size considering the number of healthcare workers of a big hospital and then calculating it with EpiInfo™ software. 191 people have been enrolled. METHODS The study was divided into three steps. The first one to identify, among the workers, those who were exposed to bullying at work and those who were not. The second one has been aimed at assessing the presence of work-related stress through the administration of the HSE questionnaire. The third step has been aimed at performing the statistical analysis of the data. For each single domain explored by the questionnaire the score obtained was treated as a linear variable and the median and interquartile range (IQR) was calculated. After, a non-parametric analysis (Wilcoxon rank-sum test) was performed in order to define the statistical significance of the observed differences. RESULTS All the 191 questionnaires were self-administered by the Health Care Workers under study and correctly filled in without any multiple or missing responses. Considering the scores obtained to question n. 21, that investigates "bullying at work", we obtained two groups: High-Exposure Group (total, males and females), and Low-Exposure Group (total, males and females). In the High-Exposure Group, two critical domains were found: Demands and Control (total, male and female samples). The differences with the Low-Exposure Group were statistically significant. In the Low-Exposure Group the critical domain was Manager Support (total and female samples). The differences with the High Exposure Group were not statistically significant. CONCLUSION This study aimed to show how the exposure to bullying can influence the perception of psychosocial risks. It seems that the workers most exposed to bullying also have worse scores on the HSE questionnaire, particularly for two domains: Demands and Control. That is consistent with the most recent scientific literature.
Key Considerations for Accurate Exposures in Ecotoxicological Assessments of Perfluorinated Carboxylates and Sulfonates

Toxicity reference values for per‐ and polyfluoroalkyl substances (PFAS) vary even when the same test organism is studied. Although the need to confirm dosing solution concentrations is widely accepted, there are no experimental data to inform best practices when PFAS solutions are prepared. Laboratory data indicate that dissolution time of PFAS solids causes statistically significant deviations between nominal and measured concentrations. Mixing times for select PFAS varied between 2 and 5 h, depending on carbon fluorine chain‐length. Environ Toxicol Chem 2021;40:677–688. © 2020 SETAC
Surgically accelerated orthodontic techniques and periodontal response: a systematic review.

BACKGROUND Reduction in orthodontic treatment time is gaining popularity due to patient demands. Several new techniques of acceleratory orthodontic treatment have been introduced to effectively treat the malocclusion in a shorter time period with minimal adverse effects. OBJECTIVE The objective of this systematic review is to critically evaluate the potential effect of accelerated surgically assisted orthodontic techniques on periodontal tissues. MATERIALS AND METHODS Electronic databases used to perform the search were Medline (Ovid), EMBASE, PubMed, Scopus, Cochrane, Google Scholar, and hand searching of the literature was also performed. SELECTION CRITERIA Only randomized control trials (RCTs) that assessed the relationship between accelerated surgically assisted orthodontic techniques and its effects on periodontium were included. DATA COLLECTION AND ANALYSIS The Joanna Briggs Institute (JBI) critical appraisal checklist tool (2016) was used to assess the finally selected studies. Among these studies, five evaluated corticotomy-facilitated orthodontics, two tested accelerated tooth movement with piezocision, one compared corticotomy-facilitated orthodontics with piezocision, and one studied the effects of periodontally accelerated osteogenic orthodontics. The duration of these studies was relatively short and had moderate to high risk of bias. RESULTS Literature search identified 225 records from 5 databases and 50 articles from the partial grey literature (Google scholar) search. Finally, nine eligible RCTs were included in the review. LIMITATIONS Most of the included studies were of a high risk of bias due to high experimental heterogeneity and small sample size. Long-term follow-up of the periodontal response to these interventions was also lacking. CONCLUSIONS There is an absence of evidence considering the lack of long-term follow-up and small sample size therefore, the results of this review should be carefully interpreted. IMPLICATIONS Due to the need for more studies with less risk of bias, these techniques should be implemented in dental practice with caution. With stronger evidence, the study may be confirmed to provide quicker desired results for orthodontic patients. REGISTRATION This study protocol was not registered. FUNDING No funding was obtained for this systematic review.
A transparent and defensible process for applicant selection within a Canadian emergency medicine residency program.

OBJECTIVES The Canadian Resident Matching Service (CaRMS) selection process has come under scrutiny due to the increasing number of unmatched medical graduates. In response, we outline our residency program's selection process including how we have incorporated best practices and novel techniques. METHODS We selected file reviewers and interviewers to mitigate gender bias and increase diversity. Four residents and two attending physicians rated each file using a standardized, cloud-based file review template to allow simultaneous rating. We interviewed applicants using four standardized stations with two or three interviewers per station. We used heat maps to review rating discrepancies and eliminated rating variance using Z-scores. The number of person-hours that we required to conduct our selection process was quantified and the process outcomes were described statistically and graphically. RESULTS We received between 75 and 90 CaRMS applications during each application cycle between 2017 and 2019. Our overall process required 320 person-hours annually, excluding attendance at the social events and administrative assistant duties. Our preliminary interview and rank lists were developed using weighted Z-scores and modified through an organized discussion informed by heat mapped data. The difference between the Z-scores of applicants surrounding the interview invitation threshold was 0.18-0.3 standard deviations. Interview performance significantly impacted the final rank list. CONCLUSIONS We describe a rigorous resident selection process for our emergency medicine training program which incorporated simultaneous cloud-based rating, Z-scores, and heat maps. This standardized approach could inform other programs looking to adopt a rigorous selection process while providing applicants guidance and reassurance of a fair assessment.
Experimental DNA Demethylation Associates with Changes in Growth and Gene Expression of Oak Tree Seedlings

Epigenetic modifications such as DNA methylation, where methyl groups are added to cytosine base pairs, have the potential to impact phenotypic variation and gene expression, and could influence plant response to changing environments. One way to test this impact is through the application of chemical demethylation agents, such as 5-Azacytidine, which inhibit DNA methylation and lead to a partial reduction in DNA methylation across the genome. In this study, we treated 5-month-old seedlings of the tree, Quercus lobata, with foliar application of 5-Azacytidine to test whether a reduction in genome-wide methylation would cause differential gene expression and change phenotypic development. First, we demonstrate that demethylation treatment led to 3–6% absolute reductions and 6.7–43.2% relative reductions in genome-wide methylation across CG, CHG, and CHH sequence contexts, with CHH showing the strongest relative reduction. Seedlings treated with 5-Azacytidine showed a substantial reduction in new growth, which was less than half that of control seedlings. We tested whether this result could be due to impact of the treatment on the soil microbiome and found minimal differences in the soil microbiome between two groups, although with limited sample size. We found no significant differences in leaf fluctuating asymmetry (i.e., deviations from bilateral symmetry), which has been found in other studies. Nonetheless, treated seedlings showed differential expression of a total of 23 genes. Overall, this study provides initial evidence that DNA methylation is involved in gene expression and phenotypic variation in seedlings and suggests that removal of DNA methylation affects plant development.