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Abstract Objective The present study investigated attentional biases in anxiety using facial expressions and eye-tracking measures. Method Seventy-six participants, between 18 and 36 years, took part in the study and were divided based on trait anxiety levels: Low, Moderate, and High. The stimuli were facial expressions, and the measures of interest were Probability of First Fixation and Proportion of Fixation Time. Results The results revealed vigilance biases towards expressions of disgust, regardless of anxiety level, and maintenance biases towards expressions of happiness, regardless of stimulus presentation time, in the Low Trait Anxiety group compared to the High Trait Anxiety group. Conclusion These findings raise questions related to the importance of using positive stimuli in anxiety treatment and the need to specify the types, levels, and characteristics of stimuli used in research.

Solid lipid nanoparticles (SLNs) represent promising nanostructures for drug delivery systems. This study successfully synthesized SLNs containing different proportions of babassu oil (BBS) and copaiba oleoresin (COPA) via the emulsification–ultrasonication method. Before SLN synthesis, the identification and quantification of methyl esters, such as lauric acid and β-caryophyllene, were performed via GC-MS analysis. These methyl esters were used as chemical markers and assisted in encapsulation efficiency experiments. A 22 factorial design with a center point was employed to assess the impact of stearic acid and Tween 80 on particle hydrodynamic diameter (HD) and polydispersity index (PDI). Additionally, the effects of temperature (8 ± 0.5 °C and 25 ± 1.0 °C) and time (0, 7, 15, 30, 40, and 60 days) on HD and PDI values were investigated. Zeta potential (ZP) measurements were utilized to evaluate nanoparticle stability, while transmission electron microscopy provided insights into the morphology and nanometric dimensions of the SLNs. The in vitro cytotoxic activity of the SLNs (10 µg/mL, 30 µg/mL, 40 µg/mL, and 80 µg/mL) was evaluated using the MTT assay with PC-3 and DU-145 prostate cancer cell lines. Results demonstrated that SLNs containing BBS and COPA in a 1:1 ratio exhibited a promising cytotoxic effect against prostate cancer cells, with a percentage of viable cells of 68.5% for PC-3 at a concentration of 30 µg/mL and 48% for DU-145 at a concentration of 80 µg/mL. These findings underscore the potential therapeutic applications of SLNs loaded with BBS and COPA for prostate cancer treatment.

Abstract Background This paper describes the protocol for the Nano X Image Guidance (Nano X IG) trial, a single-institution, clinical imaging study. The Nano X is a prototype fixed-beam radiotherapy system developed to investigate the feasibility of a low-cost, compact radiotherapy system to increase global access to radiation therapy. This study aims to assess the feasibility of volumetric image guidance with cone beam computed tomography (CBCT) acquired during horizontal patient rotation on the Nano X radiotherapy system. Methods In the Nano X IG study, we will determine whether radiotherapy image guidance can be performed with the Nano X radiotherapy system where the patient is horizontally rotated while scan projections are acquired. We will acquire both conventional CBCT scans and Nano X CBCT scans for 30 patients aged 18 and above and receiving radiotherapy for head/neck or upper abdomen cancers. For each patient, a panel of experts will assess the image quality of Nano X CBCT scans against conventional CBCT scans. Each patient will receive two Nano X CBCT scans to determine the image quality reproducibility, the extent and reproducibility of patient motion and assess patient tolerance. Discussion Fixed-beam radiotherapy systems have the potential to help ease the current shortfall and increase global access to radiotherapy treatment. Advances in image guidance could facilitate fixed-beam radiotherapy using horizontal patient rotation. The efficacy of this radiotherapy approach is dependent on our ability to image and adapt to motion due to rotation and for patients to tolerate rotation during treatment. Trial registration ClinicalTrials.gov, NCT04488224. Registered on 27 July 2020.

Abstract Introduction Radiation therapy is a common cancer treatment, requiring timely information to help patients prepare for treatment. We pilot tested a low literacy, psycho‐educational talking book (written booklet, with accompanying audio recording) to examine (i) the effect of the tool on knowledge, anxiety and communication; (ii) acceptability, and (iii) how it was used in appointments. Methods A pre‐post design was employed. Patients scheduled to receive radiation therapy for any cancer were recruited from two hospitals in Sydney, Australia. Participants were sent the talking book before treatment planning and completed baseline and follow‐up surveys, before and after the intervention. Results Forty participants were recruited, and 39 completed all study assessments. Overall, knowledge increased after receiving the talking book by 3.8 points from 13.9 to 17.7/20 (95% confidence interval (CI) 2.7, 4.8, P

The translation initiation complex 4F (eIF4F) is a rate-limiting factor in protein synthesis. Alterations in eIF4F activity are linked to several diseases, including cancer and infectious diseases. To this end, coronaviruses require eIF4F complex activity to produce proteins essential for their life cycle. Efforts to target coronaviruses by abrogating translation have been largely limited to repurposing existing eIF4F complex inhibitors. Here, we report the results of a high throughput screen to identify small molecules that disrupt eIF4F complex formation and inhibit coronavirus RNA and protein levels. Of 338,000 small molecules screened for inhibition of the eIF4F-driven, CAP-dependent translation, we identified SBI-1232 and two structurally related analogs, SBI-5844 and SBI-0498, that inhibit human coronavirus OC43 (HCoV-OC43; OC43) with minimal cell toxicity. Notably, gene expression changes after OC43 infection of Vero E6 or A549 cells were effectively reverted upon treatment with SBI-5844 or SBI-0498. Moreover, SBI-5844 or SBI-0498 treatment effectively impeded the eIF4F complex assembly, with concomitant inhibition of newly synthesized OC43 nucleocapsid protein and OC43 RNA and protein levels. Overall, we identify SBI-5844 and SBI-0498 as small molecules targeting the eIF4F complex that may limit coronavirus transcripts and proteins, thereby representing a basis for developing novel therapeutic modalities against coronaviruses.

ABSTRACT BACKGROUND: This article systematically updates the literature on changes in visual functions during the phases of the normal menstrual cycle in women. OBJECTIVES: To update Guttridge's 1994 review of visual structures and functions associated with the menstrual cycle and broaden the search through psychophysical, neuroimaging and neurobehavioral measurements covering 1994-2020. DESIGN AND SETTING: Narrative review conducted in a neurosciences and behavior laboratory in Brazil. METHODS: The PubMed, Cochrane Clinical Answers and Google Scholar databases were searched. After screening and applying the eligibility criteria, 32 articles were examined. Through this analysis, the following information was extracted: (1) geographical distribution of the study; (2) sample size (according to age and phase of the menstrual cycle); (3) type of measurements according to psychophysical, neuroimaging and neurobehavioral instruments; (4) vision testing model; (5) visual subcategory evaluated; (6) categories of processed visual stimuli; and (7) main findings. RESULTS: The menstrual phases give rise to significant changes in visual functions, including in relation to orientation and spatial attention, visual campimetry and visual sensitivity. These relate specifically to the follicular and luteal phases. CONCLUSIONS: These findings theoretically expand the effects of menstrual cycles on visual functions found by Guttridge (1994). Despite some inconsistencies in the studies analyzed, it was found that visual processing during the follicular and luteal phases of the normal menstrual cycle of healthy women can explain physiological, cognitive, behavioral and social modulations.

Epigenetic changes are implicated in Acute myeloid leukemia (AML) tumorigenesis. Here, the authors show that the ubiquitin ligase RNF5 and its substrate RBBP4 contribute to AML development by regulating epigenetic-controlled transcription which determines AML sensitivity to HDAC inhibitors.

Objectives In this first large-scale analysis of neurological emergency admissions in England, we determine the number and types of emergency admissions with neurological emergency diagnostic codes, how many are under the care of a neurologist or neurosurgeon and how such admissions vary by levels of deprivation.Design Retrospective empirical research employing a derived list of neurological emergency diagnostic codesSetting This study used the Hospital Episode Statistics data set for the financial year 2019/2020 based on 17 million in-year inpatient admissions in England including 6.5 million (100%) emergency admissions with any diagnosis codes.Results There were 1.4 million (21.2%) emergency inpatient admissions with a mention of any neurological code, approx. 248 455 (3.8%) with mention of a specific neurological emergency code from the derived list, and 72 485 (1.1%) included such a code as the primary reason for admission. The highest number of in-year admissions for adults was for epilepsy (145 995), with epilepsy as the primary diagnostic code in 15 945 (10.9%). Acute nerve root/spinal cord syndrome (41 215), head injury (29 235) and subarachnoid haemorrhage (18 505) accounted for the next three highest number of admissions. 3230 (1.4%) in-year emergency hospital admissions with mention of a neurological emergency code were under the care of a neurologist or neurosurgeon, with only 1315 (0.9%) admissions with mention of an epilepsy code under a neurologist. There was significant variation for epilepsy and functional neurological disorders (FNDs) in particular by Index of Multiple Deprivation decile. The association between deprivation and epilepsy and FND was significant with p-values of 2.5e-6 and 1.5e-8, respectively.Conclusions This study has identified important findings in relation to the burden of neurological emergency admissions but further work is needed, with greater clinical engagement in diagnostic coding, to better understand the implications for workforce and changes to service delivery needing to be implemented.

Resumo O objetivo desta pesquisa foi adaptar a Structured Interview for Assessing Perceptual Anomalies (SIAPA) para o Brasil para ser utilizada como instrumento de autorrelato. Utilizou-se uma amostra não probabilística de 854 universitários, a maioria do sexo masculino (51,4 %) e com idades entre 16 e 65 anos (M = 23,7; DP = 6,8). Após a tradução e validação semântica da SIAPA, testaram-se os parâmetros de validade e precisão por meio de análises fatoriais, coeficientes alfa de Cronbach e análises via Teoria de Resposta ao Item (TRI). Os resultados confirmaram a adequação psicométrica da medida, apontando uma solução unidimensional com altas cargas no fator geral e alta consistência interna (α = 0,88; Ω = 0,88). Acredita-se que o objetivo proposto tenha sido satisfeito, de modo que, ao final da pesquisa, contou-se com uma medida válida e fidedigna que pode ser utilizada, tanto para rastreio quanto para pesquisa, para compreender e diagnosticar anomalias perceptuais.

Health care has had to adapt rapidly to COVID-19, and this in turn has highlighted a pressing need for tools to facilitate remote visits and monitoring. Digital health technology, including body-worn devices, offers a solution using digital outcomes to measure and monitor disease status and provide outcomes meaningful to both patients and health care professionals. Remote monitoring of physical mobility is a prime example, because mobility is among the most advanced modalities that can be assessed digitally and remotely. Loss of mobility is also an important feature of many health conditions, providing a read-out of health as well as a target for intervention. Real-world, continuous digital measures of mobility (digital mobility outcomes or DMOs) provide an opportunity for novel insights into health care conditions complementing existing mobility measures. Accepted and approved DMOs are not yet widely available. The need for large collaborative efforts to tackle the critical steps to adoption is widely recognised. Mobilise-D is an example. It is a multidisciplinary consortium of 34 institutions from academia and industry funded through the European Innovative Medicines Initiative 2 Joint Undertaking. Members of Mobilise-D are collaborating to address the critical steps for DMOs to be adopted in clinical trials and ultimately health care. To achieve this, the consortium has developed a roadmap to inform the development, validation and approval of DMOs in Parkinson’s disease, multiple sclerosis, chronic obstructive pulmonary disease and recovery from proximal femoral fracture. Here we aim to describe the proposed approach and provide a high-level view of the ongoing and planned work of the Mobilise-D consortium. Ultimately, Mobilise-D aims to stimulate widespread adoption of DMOs through the provision of device agnostic software, standards and robust validation in order to bring digital outcomes from concept to use in clinical trials and health care.

Abstract The aim of this study was to analyze the contrast sensitivity of spatial luminance and the color discrimination thresholds of the protan, deutan, and tritan axes of people with leprosy. This study included 8 subjects with leprosy (M = 4, W = 4, M = 33.38 ± 8.7) and 8 healthy subjects (M = 4, W = 4, M = 30.89 ± 5.8). The contrast sensitivity was evaluated by the Metropsis software version 11.0 with vertical sinusoidal grids of frequencies of 0.2, 0.5, 1, 5, 10, and 16 cycles per degree of visual angle (cpd) and color vision by the desaturated Lanthony D15 tests and the trivector and ellipse protocols of the Cambridge Color Test. The results showed significant differences between the groups in the processing of spatial frequencies of 0.2 (U = 14; p = .018); 5.0 (U = 45.0; p = .001); 10.0 (U = 45.0; p = .001), and 16.0 (U = 45.0; p = .001) cpd. The difference in color recognition through D15d (U = 4.0; p = .002). Ellipse 2 (U = 10.0; p = .012) and ellipse 3 (U = 9.0; p = .009) were discriminated against. Overall, the results indicate that leprosy changes the visual processing of low, medium, and high spatial frequencies, as well as the sensitivity of the short wavelength (tritan line of confusion) and long (protan line of confusion) cones.

Workflow management systems represent, manage, and execute multistep computational analyses and offer many benefits to bioinformaticians. They provide a common language for describing analysis workflows, contributing to reproducibility and to building libraries of reusable components. They can support both incremental build and re-entrancy-the ability to selectively re-execute parts of a workflow in the presence of additional inputs or changes in configuration and to resume execution from where a workflow previously stopped. Many workflow management systems enhance portability by supporting the use of containers, high-performance computing (HPC) systems, and clouds. Most importantly, workflow management systems allow bioinformaticians to delegate how their workflows are run to the workflow management system and its developers. This frees the bioinformaticians to focus on what these workflows should do, on their data analyses, and on their science. RiboViz is a package to extract biological insight from ribosome profiling data to help advance understanding of protein synthesis. At the heart of RiboViz is an analysis workflow, implemented in a Python script. To conform to best practices for scientific computing which recommend the use of build tools to automate workflows and to reuse code instead of rewriting it, the authors reimplemented this workflow within a workflow management system. To select a workflow management system, a rapid survey of available systems was undertaken, and candidates were shortlisted: Snakemake, cwltool, Toil, and Nextflow. Each candidate was evaluated by quickly prototyping a subset of the RiboViz workflow, and Nextflow was chosen. The selection process took 10 person-days, a small cost for the assurance that Nextflow satisfied the authors' requirements. The use of prototyping can offer a low-cost way of making a more informed selection of software to use within projects, rather than relying solely upon reviews and recommendations by others.

The present work introduces an automated and smart system (named CageView) used to monitor a mouse, detect motion, and control access to food in accordance with experimental schedules. We describe the components of the CageView platform and give a summarized description on how we employed a convolutional neural network to detect and recognize a mouse in real time before presenting the results of a case study. In particular, CageView is a programmable and remotely operable system such that (1) an experimenter at a remote workstation may set up a feeding and fasting schedule that allows feeding and fasting without requiring the physical presence of a staff member, (2) the experimenter can control access to food in real time regardless of the preset schedule, (3) the experimenter has real-time access to a live video feed to assess the mouse, (4) an artificial intelligence system tracks the mouse’s location and physical activity, and (5) a record is kept of activity, which can be displayed as a 2D representation of mouse movement or a histogram showing mouse movement in 15-min blocks for the duration of the experiment.

Introduction Influenza epidemics and pandemics cause significant morbidity and mortality. An effective response to a potential pandemic requires the infrastructure to rapidly detect, characterise, and potentially contain new and emerging influenza strains at both an individual and population level. The objective of this study is to use data gathered simultaneously from community and hospital sites to develop a model of how influenza enters and spreads in a population.Methods and analysis Starting in the 2018–2019 season, we have been enrolling individuals with acute respiratory illness from community sites throughout the Seattle metropolitan area, including clinics, childcare facilities, Seattle-Tacoma International Airport, workplaces, college campuses and homeless shelters. At these sites, we collect clinical data and mid-nasal swabs from individuals with at least two acute respiratory symptoms. Additionally, we collect residual nasal swabs and data from individuals who seek care for respiratory symptoms at four regional hospitals. Samples are tested using a multiplex molecular assay, and influenza whole genome sequencing is performed for samples with influenza detected. Geospatial mapping and computational modelling platforms are in development to characterise the regional spread of influenza and other respiratory pathogens.Ethics and dissemination The study was approved by the University of Washington’s Institutional Review Board (STUDY00006181). Results will be disseminated through talks at conferences, peer-reviewed publications and on the study website (www.seattleflu.org).