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Abstract This is the first case report of a non‐small‐cell lung cancer (NSCLC) patient harboring HIP1‐ALK (H28:A20) and CTNNB1 p.S45del treated with first‐line alectinib. Approximately 5% of NSCLC patients are reported to have anaplastic lymphoma kinase (ALK) rearrangements, and among these EML4‐ALK is the most frequent fusion variant. However, in recent years the use of next‐generation sequencing (NGS) in clinical laboratories has become increasingly widespread, identifying a lot of new ALK fusion partners as well as a large quantity of co‐occurring genomic alterations. Unfortunately, the growing number of genomic alterations detected by NGS does not always correspond to adequate knowledge of their clinical significance, often resulting in an empiric treatment of patients harboring uncommon mutations.

Physical activity guidelines targeting different populations with and without chronic diseases or disabilities are required to meet the diverse functional and physiological needs experienced by different subgroups of people to achieve optimal health benefits. As the importance of physical activity guidelines in promoting optimal health and well-being becomes increasingly recognised, there is a critical need for their systematic evaluation to ensure they remain effective, applicable and aligned with evolving health needs and scientific insights. This study aims to systematically review, critically evaluate, and compare global physical activity and sedentary behaviour guidelines on frequency, intensity, time, and type of exercise for adults, pregnant and postpartum women, and people living with chronic conditions and/or disabilities. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols checklist. We will search the Allied and Complementary Medicine Database, APA PsycInfo, Cumulative Index of Nursing and Allied Health Literature, Cochrane Library, Education Resources Information Center, Google Scholar, MEDLINE, PubMed, Scopus, SPORTDiscus, Web of Science and grey literature databases from 2010 to October 2024. Two reviewers will independently select guidelines, extract data and assess methodological quality using the Appraisal of Guidelines for Research and Evaluation II Instrument . Key recommendations will be summarised and classified as ‘strong’ and ‘conditional’ based on established criteria. A comprehensive evaluation of current guidelines will identify their differences and similarities and reveal their relevance in practical settings. The findings will guide healthcare professionals, researchers and policymakers in implementing evidence-based recommendations for managing physical activity and sedentary behaviour in targeted populations. Additionally, we will highlight current knowledge gaps and potential shortcomings in existing guidelines. PROSPERO registration number: CRD42023491339.

Pediatric central nervous system (CNS) tumors represent the most common cause of cancer-related death in children aged 0-14 years. They differ from their adult counterparts, showing extensive clinical and molecular heterogeneity as well as a challenging histopathological spectrum that often impairs accurate diagnosis. Here, we use DNA methylation-based CNS tumor classification in combination with copy number, RNA-seq, and ChIP-seq analysis to characterize a newly identified CNS tumor type. In addition, we report histology, patient characteristics, and survival data in this tumor type. We describe a biologically distinct pediatric CNS tumor type (n = 31 cases) that is characterized by focal high-level amplification and resultant overexpression of either PLAGL1 or PLAGL2, and an absence of recurrent genetic alterations characteristic of other pediatric CNS tumor types. Both genes act as transcription factors for a regulatory subset of imprinted genes (IGs), components of the Wnt/β-Catenin pathway, and the potential drug targets RET and CYP2W1, which are also specifically overexpressed in this tumor type. A derived PLAGL-specific gene expression signature indicates dysregulation of imprinting control and differentiation/development. These tumors occurred throughout the neuroaxis including the cerebral hemispheres, cerebellum, and brainstem, and were predominantly composed of primitive embryonal-like cells lacking robust expression of markers of glial or neuronal differentiation (e.g., GFAP, OLIG2, and synaptophysin). Tumors with PLAGL1 amplification were typically diagnosed during adolescence (median age 10.5 years), whereas those with PLAGL2 amplification were diagnosed during early childhood (median age 2 years). The 10-year overall survival was 66% for PLAGL1-amplified tumors, 25% for PLAGL2-amplified tumors, 18% for male patients, and 82% for female patients. In summary, we describe a new type of biologically distinct CNS tumor characterized by PLAGL1/2 amplification that occurs predominantly in infants and toddlers (PLAGL2) or adolescents (PLAGL1) which we consider best classified as a CNS embryonal tumor and which is associated with intermediate survival. The cell of origin and optimal treatment strategies remain to be defined.

This study investigates the effectiveness of amplitude transformation in enhancing the performance and robustness of Multiscale Fuzzy Entropy for Alzheimer’s disease detection using electroencephalography signals. Multiscale Fuzzy Entropy is a complexity measure particularly sensitive to intra- and inter-subject variations in signal amplitude, as well as the selection of key parameters such as embedding dimension (m) and similarity criterion (r), which often result in inconsistent outcomes when applied to multivariate data, such as electroencephalography signals. To address these challenges and to generalize the possibility of adopting Multiscale Fuzzy Entropy as a diagnostic tool for Alzheimer’s disease, this research explores amplitude transformation preprocessing on electroencephalography signals in Multiscale Fuzzy Entropy calculation across varying parameters. The statistical analysis of the obtained results demonstrates that amplitude transformation preprocessing significantly enhances Multiscale Fuzzy Entropy’s ability to detect Alzheimer’s disease, achieving higher and more consistent significant comparison percentages, with an average of 73.2% across all parameter combinations, compared with only one raw data combination exceeding 65%. Clustering analysis corroborates these findings, showing that amplitude transformation improves the differentiation between Alzheimer’s disease patients and healthy subjects. These results highlight the potential of amplitude transformation to stabilize Multiscale Fuzzy Entropy performance, making it a more reliable tool for early Alzheimer’s disease detection.

IntroductionThe recent COVID-19 pandemic has compelled various governments to trace all contacts of a confirmed case, as well as to identify the locations visited by infected individuals. This task, that requires the activation of our autobiographical memories, can make a difference in the spread of the contagion and was based primarily on telephone interviews with infected people. In this study, we examined whether participants were able to provide contact tracing information and whether their memories were influenced by salient events occurring during the initial phases of the pandemic.MethodsParticipants were asked to fill in an online standardized form in which they recounted every day of the 2 weeks before, reporting as much information as possible. The time period selected included, among other things, the day on which the Italian government issued the decree initiating the COVID-19 lockdown. The task was completed twice, the first time relying solely on their memory, and the second time using external aids (diaries, mobile phones etc.). Reports were then coded using a scheme that segmented accounts into informational details, divided into two broad categories, internal and external.ResultsOur findings showed that (i) the use of external aids was effective only when participants had to recall the day furthest away or if to-be-recalled events have low distinctiveness, and (ii) memories of internal details were recalled better than memories of external details. Participants were overall accurate and reported a large amount of information about people and places. However, because of the connection with key pandemic-related events, the effect was somewhat stronger on specific days (e.g., the day in which the lockdown was announced).DiscussionThe results of this work could provide a useful tool for improving the design of contact tracing procedures in the event of an unwanted future public health crisis caused by a highly infectious agent.

Human cytomegalovirus (HCMV) is an important pathogen for which new antiviral drugs are needed. HCMV, like other herpesviruses, encodes a nuclear egress complex (NEC) composed of two subunits, UL50 and UL53, whose interaction is crucial for viral replication. To explore whether small molecules can exert selective antiviral activity by inhibiting NEC subunit interactions, we established a homogeneous time-resolved fluorescence (HTRF) assay of these interactions and used it to screen >200,000 compound-containing wells. Two compounds, designated GK1 and GK2, which selectively inhibited this interaction in the HTRF assay with GK1 also active in a co-immunoprecipitation assay, exhibited more potent anti-HCMV activity than cytotoxicity or activity against another herpesvirus. At doses that substantially reduced HCMV plaque formation, GK1 and GK2 had little or no effect on the expression of viral proteins and reduced the co-localization of UL53 with UL50 at the nuclear rim in a subset of cells. GK1 and GK2 contain an acrylamide moiety predicted to covalently interact with cysteines, and an analog without this potential lacked activity. Mass spectrometric analysis showed binding of GK2 to multiple cysteines on UL50 and UL53. Nevertheless, substitution of cysteine 214 of UL53 with serine (C214S) ablated detectable inhibitory activity of GK1 and GK2 in vitro, and the C214S substitution engineered into HCMV conferred resistance to GK1, the more potent of the two inhibitors. Thus, GK1 exerts selective antiviral activity by targeting the NEC. Docking studies suggest that the acrylamide tethers one end of GK1 or GK2 to C214 within a pocket of UL53, permitting the other end of the molecule to sterically hinder UL50 to prevent NEC formation. Our results prove the concept that targeting the NEC with small molecules can selectively block HCMV replication. Such compounds could serve as a foundation for development of anti-HCMV drugs and as chemical tools for studying HCMV.

Type 1 Diabetes (T1D) is an autoimmune disease that affects millions of people worldwide. A critical issue in T1D patients is the managing of Postprandial Glucose Response (PGR), through the dosing of the insulin bolus to inject before meals. The Artificial Pancreas (AP), combining autonomous insulin delivery and blood glucose monitoring, is a promising solution. However, state-of-the-art APs require several information for bolus delivery, such as the estimated carbohydrate intake over the meals. This is mainly related to the limited knowledge of the determinants of PGR. Although meal carbohydrates are mostly considered as the major factor into, uencing PGR, other food components play a relevant role in PGRs, and thus, should be taken into account. Based on these considerations, a study to determine the effect of nutritional factors (i.e., carbohydrates, proteins, lipids, fibers, and energy intake) in the short and middle term on Blood Glucose Levels (BGLs) prediction was conducted by Machine Learning (ML) methods. A ML model able to predict the BGLs after 15, 30, 45, and 60 minutes from the meal leveraging on insulin doses, blood glucose, and nutritional factors in T1D patients on AP systems was implemented. More specifically, to investigate the impact of the nutritional factors on the model predictions, a Feed-Forward Neural Network, was fed with several dispositions of BGLs, insulin, and nutritional factors. Both public and self-produced data were used to validate the proposal. The results suggest that patient-specific information about nutritional factors can be significant for middle term postprandial BGLs predictions.

Abstract Background Potential relationships with the prognosis of patients with extensive‐stage non‐small cell lung cancer (ES‐SCLC) have been investigated without valid results. Methods A retrospective analysis of real‐world data of consecutive patients with ES‐SCLC admitted to our Medical Thoracic Oncology Unit was carried out from 2010 to 2020, focusing on identification of prognostic factors. Kaplan–Meier analysis was used to represent progression‐free survival (PFS) and overall survival (OS). Univariable and multivariable Cox models were used to investigate prognostic factors. Results The analysis included 244 patients. The median OS was 8 months (95% confidence interval [CI]: 8–10) and the median PFS was 5 months (95% CI: 5–6). The univariable analysis showed that factors associated with shorter OS were older age (p = 0.047), TNM stage 4 versus 3 (p 2 metastatic sites (p = 0.004). Mediastinal radiotherapy (RT) (p 1 irradiated site (p = 0.026), 3 and 4 chemotherapy (CT) lines versus 1 (p = 0.044 and 0.001, respectively), prophylactic cranial irradiation (PCI) (p

Abstract Prolonged sedentary behaviour is detrimental to health due to low contractile activity in large lower extremity muscle groups. This muscle inactivity can be measured with electromyography (EMG), but it is unknown how methodological factors affect responsiveness longitudinally. This study ranks 16 different EMG inactivity thresholds based on their responsiveness (absolute and standardized effect size, responsiveness) using data from a randomized controlled trial targeted at reducing and breaking up sedentary time (InPact, ISRCTN28668090). EMG inactivity duration and usual EMG inactivity bout duration (weighted median of bout lengths) were measured from large lower extremity muscle groups (quadriceps, hamstring) with EMG-sensing shorts. The results showed that the EMG inactivity threshold above signal baseline (3 μV) provided overall the best responsiveness indices. At baseline, EMG inactivity duration of 66.8 ± 9.6% was accumulated through 73.9 ± 36.0 s usual EMG inactivity bout duration, both of which were reduced following the intervention (−4.8 percentage points, −34.3 s). The proposed methodology can reduce variability in longitudinal designs and the detailed results can be used for sample size calculations. Reducing EMG inactivity duration and accumulating EMG inactivity in shorter bouts has a potential influence on muscle physiology and health.

Background It is not currently clear what impact alternative nicotine-delivery products (electronic cigarettes, heated tobacco products and snus) have on smoking rates and cigarette sales. Objective To assess whether access to these products promotes smoking in the population. Design and data sources We examined associations of alternative nicotine product use and sales with smoking rates and cigarette sales overall, and in different age and socioeconomic groups, and compared smoking prevalence over time in countries with contrasting regulations of these products. For electronic cigarettes, we examined data from countries with historically similar smoking trajectories but differing current electronic cigarette regulations (United Kingdom and United States of America vs. Australia, where sales of nicotine-containing electronic cigarettes are banned); for heated tobacco, we used data from countries with state tobacco monopolies, where cigarette and heated tobacco sales data are available (Japan, South Korea), and for snus we used data from Sweden. Analysis methods We pre-specified dynamic time series analyses to explore associations between use and sales of alternative nicotine-delivery products and smoking prevalence and cigarette sales, and time series analyses to compare trends of smoking prevalence in countries with different nicotine product policies. Results Because of data and analysis limitations (see below), results are only tentative and need to be interpreted with caution. Only a few findings reached statistical significance and for most results the Bayes factor indicated inconclusive evidence. We did not find an association between rates of smoking and rates of the use of alternative nicotine products. The increase in heated tobacco product sales in Japan was accompanied by a decrease in cigarette sales. The decline in smoking prevalence seems to have been slower in Australia than in the United Kingdom overall, and slower than in both the United Kingdom and the United States of America among young people and also in lower socioeconomic groups. The decline in cigarette sales has also accelerated faster in the United Kingdom than in Australia. Limitations Most of the available data had insufficient data points for robust time series analyses. The assumption of our statistical approach that causal interactions are more likely to be detected when longer-term changes are screened out may not apply for short time series and in product interaction scenarios, where short-term fluctuations can be caused by, for example, fluctuations in prosperity or product supplies. In addition, due to dual use, prevalence figures for smoking and alternative product use overlap. The ecological study design limits the causal inferences that can be made. Longer time periods are needed for any effects of exclusive use of the new products on smoking prevalence to emerge. Conclusions We detected some indications that alternative nicotine products are competing with cigarettes rather than promoting smoking and that regulations that allow their sales are associated with a reduction rather than an increase of smoking, but the findings are inconclusive because of insufficient data points and issues with the assumptions of the pre-specified statistical analyses. Future work As further prevalence and sales data emerge the analyses will become more informative. Accessing sales figures in particular is the current research priority. Study registration The project is registered on Open Science Framework https://osf.io/bd3ah. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (NIHR129968) and will be published in full in Public Health Research; Vol. 11, No. 7. See the NIHR Journals Library website for further project information. Plain language summary Alternative nicotine-delivery products are now available which are much less hazardous than cigarettes. These include electronic cigarettes (which contain no tobacco), Swedish snus (oral tobacco with low levels of cancer-causing chemicals) and heated tobacco products. There is concern that these products attract young people to smoking and discourage smokers from quitting (i.e. increase smoking), but it is also possible that they help smokers quit and steer young people who find nicotine attractive away from smoking, or that they have no effect on smoking. To clarify which of these end results is likely, we looked at data on smoking and on the use of these alternative products over time, and also compared data on smoking from countries that have similar tobacco control history, but that either allow (i.e. United Kingdom and United States of America) or ban the sale of electronic cigarettes (i.e. Australia). As the sale of heated tobacco products increased in Japan, sales of cigarettes seem to have gone down, suggesting that this product is competing with cigarettes rather than encouraging their use. We also found that the drop in smoking may have been slower in Australia than in the United Kingdom. For young people and those on low income specifically, the reduction in smoking was slower in Australia than in both the United Kingdom and United States of America. Allowing alternative nicotine products to be sold seems to have been linked with lowered rather than increased rates of smoking. Our findings, however, are uncertain because only limited data were available. Clearer conclusions will become possible as more data on the use and especially on the sales of alternative nicotine products are collected. Scientific summary Background The key controversy surrounding reduced-risk alternative nicotine-delivery products (ANDs), comprising electronic cigarettes (ECs), snus and heated tobacco products (HTPs), concerns their effects on smoking prevalence. They may promote smoking by enticing adolescents to cigarette use and by reducing quitting in smokers (e.g. by allowing them to circumvent smoke-free regulation), but it is also possible that ANDs redirect young nicotine seekers away from smoking and help smokers quit, or they may have no clear impact on smoking. Alternative nicotine-delivery systems have been used for a number of years, and some information may already exist in data on smoking prevalence and on AND and cigarette sales that can contribute to answering this question. If, in countries with substantial AND use, the trends in the historical decline in smoking rates and cigarette sales have slowed down or reversed, and this is not happening in countries that restrict or ban ANDs, this would be consistent with the ‘gateway into smoking’ hypothesis, while the opposite finding would suggest that these products are replacing rather than promoting smoking. A finding that ANDs have no net effect on smoking prevalence and cigarette sales, or that currently available data do not provide a clear answer, would also have implications both for policies (which will need to take account of the uncertainty) and for future research (which can aim to fill the gaps). Objectives We aimed to answer the following research questions (RQs): Is there an association between the prevalence of smoking and prevalence of AND use (in the population in general, in young adults and in different socioeconomic groups), in different countries and for different AND products? Is there an association between sales of different AND products and cigarette sales? Are there any differences in time trends of smoking prevalence (overall, in young adults and in different socioeconomic groups) and cigarette sales following the introduction of ANDs between countries that had similar tobacco control measures prior to ANDs emerging locally, but that have allowed EC sales [United Kingdom (UK) and United States of America (USA)] or banned them (Australia)? Methods We examined data from the countries and data sets described below that allow examinations of links between AND use and smoking rates, and between cigarette and AND sales. We also compared trajectories of smoking prevalence over time in countries with contrasting legislative and policy frameworks concerning ANDs. Countries selected Regarding prevalence data (RQ1), we explored links between the prevalence of EC use and cigarette smoking in the UK and USA (where data on EC use and cigarette use are available), Sweden (the only EU country where snus use is allowed and where data on snus and cigarette use are available) and Japan (where in addition to smoking prevalence data, at least some data on HTP use are available). We also looked at links between prevalence of smoking and sales of ANDs in Japan and South Korea, where data on HTP sales were available. Regarding sales data (RQ2), we explored links between sales of cigarettes and snus in Sweden, and between sales of cigarettes and sales of HTPs in Japan and South Korea. No comprehensive data on EC sales are available for the UK and USA, because ECs are produced by a large number of manufacturers, but we looked at ‘hybrid’ links between the prevalence of EC use and sales of cigarettes in the UK and USA. We also explored whether time trends in cigarette use and sales in the UK and USA, where ECs are allowed, differ from those in Australia, where sales of nicotine-containing ECs are banned (RQ3). The three countries have a broadly similar history and formats of tobacco control otherwise. Data sources Where more than one survey was available per country, we selected the survey to use based on: quality of smoking and AND use measures years covered representativeness of samples and weighting number of time points (monthly/quarterly breakdown) sample size quality of socioeconomic status (SES) information. For the UK, we used the Health Survey for England (HSE) for prevalence and HM Revenue and Customs National Statistics Tobacco Bulletin for cigarette sales data. For the USA, we used the National Health Interview Survey (NHIS) and the National Youth Tobacco Survey (NYTS) for prevalence of smoking. NielsenIQ data on cigarette sales were purchased from Chicago Booth. For Australia, we used the National Drug Strategy Household Survey (NDSHS) for prevalence of smoking and Euromonitor International reports for cigarette sales data. For Japan, we used the National Health and Nutrition Survey for prevalence, Tobacco Institute of Japan data for cigarettes sales and Philip Morris International reports for HTP sales data. For South Korea, we used the Korea National Health and Nutrition Examination Survey (KHANES) for prevalence, and Korea Tobacco and Ginseng Corporation (KT&G) reports for sales data. For Sweden, we used the Swedish Council for Information on Alcohol and Other Drugs (CAN): Monitor Studies for prevalence and Swedish Match AB provided data for cigarette and snus sales directly by e-mail. See Chapter 2 – Methods, Survey data chosen for details of where these surveys were available. For analyses looking at the interplay between cigarettes and EC/HTP use (RQ1), we included data on smoking from 2005 until the most recent available year up to 2019, before the COVID-19 epidemic started. The same timeframe was used, where available, for analyses exploring the interplay of cigarettes and EC/HTP sales (RQ2). This allowed for modelling of smoking and cigarette sales for at least 5 years prior to the emergence of these newer products. For snus, we analysed the data from 2007 to 2019. For analyses looking at trends in cigarette smoking in the UK, USA and Australia we used data from 2004 onwards as the NDSHS is triennial and we wanted to include 2004 as a proxy for 2005. Similarly, for the NYTS, which used to be biannual, we included 2004 as a proxy for 2005. For analyses looking at trends in cigarette sales for the UK, USA and Australia we looked at data from 2010 as sales data for Australia were only available from that year. Statistical methods We pre-specified in our statistical analysis plan that we would use dynamic time series applying generalised least squares (GLS) models to explore the association between prevalence of smoking and product use, as well as cigarette and product sales. Regression models were used to compare trends in smoking prevalence between countries where EC use is allowed or banned. The analyses were adjusted for two policy variables which are believed to have the strongest effect on smoking prevalence and cigarette sales and that have been implemented at different time points in most countries: the introduction of bans on smoking in public spaces where they occurred during the study period; and increases in cigarette prices exceeding normal trends (25% increase in 2010 in Australia, 37% in October 2010 in Japan, 80% increase in 2015 in South Korea, 14% increase in 2009 in the USA and 11% increase in 2015 in the UK). Each policy was modelled as a step level change, coded as one after the introduction of the policy and zero before. Unfortunately, the available data had insufficient data points for robust time series analyses. We carried out the planned analyses to adhere to the original plan, but the results need to be considered as only tentative and interpreted cautiously. Due to the short time series, it is possible that underlying trends were not correctly identified and removed, resulting in confounding. For example, in the majority of analyses, trends were identified as linear and first-order differencing was used. However, studies suggest that the decline in smoking prevalence follows a more monotonic curvilinear decline over time, which was not identified in the short series and would have required higher differencing. Conversely, with short-term non-granular time series, there is a risk of removing trends which in fact reflect short-term changes and perhaps a casual association between series. In addition, because of the short series, more sophisticated time series models, such as autoregressive integrated moving average with explanatory variable (ARIMAX), could not be used for the majority of analyses because these require more time-points. ARIMAX models have several benefits over GLS, including the use of transfer functions to model lags between multiple time series and inclusion of seasonal autocorrelation. Finally, short time series are highly influenced by outliers, and these can dominate the output from models. Longer time series are not influenced in the same way. These factors can all result in spurious associations. We used Bayes factors (BF) to help us to determine whether non-significant results provided evidence of no effect or were due to data being insensitive, with BF between 1/3 and 1 suggesting no or weak evidence for the null hypothesis, BF between 1/3 and 1/10 suggesting moderate evidence, and 1/10 or lower as strong evidence for the null hypothesis. Results Only a few associations were detected. Regarding RQ1, we did not find an association between rates of smoking and rates of alternative nicotine product use, potentially due to the analyses being under-powered. Regarding RQ2, the increase in sales of HTPs in Japan was accompanied by a decrease in sales of cigarettes (b = −1.09, p

Alzheimer’s disease (AD) is a neurodegenerative brain disorder that affects cognitive functioning and memory. Current diagnostic tools, including neuroimaging techniques and cognitive questionnaires, present limitations such as invasiveness, high costs, and subjectivity. In recent years, interest has grown in using electroencephalography (EEG) for AD detection due to its non-invasiveness, low cost, and high temporal resolution. In this regard, this work introduces a novel metric for AD detection by using multiscale fuzzy entropy (MFE) to assess brain complexity, offering clinicians an objective, cost-effective diagnostic tool to aid early intervention and patient care. To this purpose, brain entropy patterns in different frequency bands for 35 healthy subjects (HS) and 35 AD patients were investigated. Then, based on the resulting MFE values, a specific detection algorithm, able to assess brain complexity abnormalities that are typical of AD, was developed and further validated on 24 EEG test recordings. This MFE-based method achieved an accuracy of 83% in differentiating between HS and AD, with a diagnostic odds ratio of 25, and a Matthews correlation coefficient of 0.67, indicating its viability for AD diagnosis. Furthermore, the algorithm showed potential for identifying anomalies in brain complexity when tested on a subject with mild cognitive impairment (MCI), warranting further investigation in future research.

Background Some pregnant smokers try e-cigarettes, but effectiveness and safety of such use are unknown. Objectives To compare effectiveness and safety of nicotine patches and e-cigarettes in pregnancy. Design A pragmatic multi-centre randomised controlled trial. Setting Twenty-three hospitals across England, and a Stop Smoking Service in Scotland. Participants One thousand one hundred and forty pregnant daily smokers (12–24 weeks’ gestation) motivated to stop smoking, with no strong preference for using nicotine patches or e-cigarettes. Interventions Participants in the e-cigarette arm were posted a refillable e-cigarette device with two 10 ml bottles of tobacco-flavoured e-liquid (18 mg nicotine). Participants in the nicotine patches arm were posted a 2-week supply of 15 mg/16-hour nicotine patches. Supplies were provided for up to 8 weeks. Participants sourced further supplies themselves as needed. Participants in both arms received support calls prior to their target quit date, on the quit date, and weekly for the next 4 weeks. Outcome measures The primary outcome was validated prolonged abstinence at the end of pregnancy. Participants lost to follow-up or not providing biochemical validation were included as non-abstainers. Secondary outcomes included self-reported abstinence at different time points, treatment adherence and safety outcomes. Results Only 55% of self-reported abstainers mailed back useable saliva samples. Due to this, validated sustained abstinence rates were low (6.8% vs. 4.4% in the e-cigarettes and nicotine patches arms, respectively, risk ratio = 1.55, 95% confidence interval 0.95 to 2.53; Bayes factor = 2.7). In a pre-specified sensitivity analysis that excluded abstainers using non-allocated products, the difference became significant (6.8% vs. 3.6%, risk ratio = 1.93, 95% confidence interval 1.14 to 3.26; Bayes factor = 10). Almost a third of the sample did not set a target quit date and the uptake of support calls was low, as was the initial product use. At end of pregnancy, 33.8% versus 5.6% of participants were using their allocated product in the e-cigarettes versus nicotine patches arm (risk ratio = 6.01, 95% confidence interval 4.21 to 8.58). Regular use of e-cigarettes in the nicotine patches arm was more common than use of nicotine replacement products in the e-cigarette arm (17.8% vs. 2.8%). Rates of adverse events and adverse birth outcomes were similar in the two study arms, apart from participants in the e-cigarette arm having fewer infants with low birthweight (

ObjectiveCycling is an important part of children's active travel, but its measurement using accelerometry is a challenge. The aim of the present study was to evaluate physical activity duration and intensity, and sensitivity and specificity of free-living cycling measured with a thigh-worn accelerometer.MethodsParticipants were 160 children (44 boys) aged 11.5 ± 0.9 years who wore a triaxial Fibion® accelerometer on right thigh for 8 days, 24 h per day, and reported start time and duration of all cycling, walking and car trips to a travel log. Linear mixed effects models were used to predict and compare Fibion-measured activity and moderate-to-vigorous activity duration, cycling duration and metabolic equivalents (METs) between the travel types. Sensitivity and specificity of cycling bouts during cycling trips as compared to walking and car trips was also evaluated.ResultsChildren reported a total of 1,049 cycling trips (mean 7.08 ± 4.58 trips per child), 379 walking trips (3.08 ± 2.81) and 716 car trips (4.79 ± 3.96). There was no difference in activity and moderate-to-vigorous activity duration (p > .105), a lower cycling duration (−1.83 min, p

Abstract Background To prevent nosocomial transmission of SARS-CoV-2, infection prevention control (IPC) measures are implemented for patients with symptoms compatible with COVID-19 until reliable test results are available. This delays admission to the most appropriate ward based on the medical condition. SARS-CoV-2 rapid antigen detection (RAD) tests and point-of-care (POC) rapid RT-PCR (VitaPCR) were introduced at emergency department (ED) at Skåne University Hospital, Sweden in late 2020, but the consequence on patient flow and targeted admission is unknown. Methods Patients presenting at the emergency department of a referral hospital (N = 2940) between 13-Nov-2020 and 12-Jan-2021 were included. The study period was delimited into three periods by the introduction of RAD tests and the VitaPCR. Participant data was collected from hospital records, and outcome variables were Length-of-Stay (LoS), intrahospital transfers and targeted admission to COVID-19 ward. Results Compared to baseline (RT-PCR only), RAD tests reduced ED Length-of-Stay (LoS) for participants with positive tests. Negative VitaPCR results reduced mean hospital LoS by 1.5 (95% CI 0.3–2.7) days and admissions to COVID-19 wards from 34.5 (95% CI 28.9–40.5) to 14.7 (95% CI 11.1–19.1) per 100 admissions and reduced transfers between hospital wards in the first 5 days from 50.0 (95% CI 45.0–55.0) to 34.0 (95% CI 30.3–37.9) per 100 admissions. Conclusion RAD tests enabled prompt detection of SARS-CoV-2 infection which had pronounced effects on LoS at the ED. Negative VitaPCR enabled cessation of IPC measures and a negative test was associated with increased targeted admissions, reduced intrahospital transfers and shorter LoS at the hospital.

Simple Summary: Patients with RAS-mutant metastatic colorectal cancer are typically treated with chemotherapy, with or without bevacizumab, as the first-line therapy. Over time, tumors in some patients may undergo plasma clearance of RAS, transitioning from being RAS-mutant to RAS-wild type, a phenomenon known as "RAS conversion" or "neo-RAS wild type". The current review focuses on this phenomenon's incidence, evaluation methodologies, and therapeutic implications, with a focus on the role that bevacizumab plays in it and its prospects. The management of metastatic colorectal cancer in patients harboring RAS mutations primarily involves chemotherapy, often combined with bevacizumab, as a standard first-line treatment. However, emerging evidence suggests that tumors in a subset of these patients may experience a conversion from RAS-mutant status to RAS wild type (wt) during or after chemotherapy, a process referred to as "RAS conversion" or "neo-RAS wt". Understanding the mechanisms driving the neo-RAS wt phenomenon is crucial for its application in personalized medicine. Hypotheses suggest that selective pressure from chemotherapy may lead to a decrease in the number of mutant RAS clones or an outgrowth of pre-existing RAS wt clones. Further research is needed to validate these mechanisms and understand the impact of the neo-RAS wt phenomenon on long-term outcomes, such as overall survival and progression-free survival. This review provides a comprehensive overview of the current understanding of the neo-RAS wt phenomenon, including its incidence, potential mechanisms, and clinical implications. [ABSTRACT FROM AUTHOR]

This study investigates the effectiveness of amplitude transformation in enhancing the performance and robustness of Multiscale Fuzzy Entropy for Alzheimer's disease detection using electroencephalography signals. Multiscale Fuzzy Entropy is a complexity measure particularly sensitive to intra- and inter-subject variations in signal amplitude, as well as the selection of key parameters such as embedding dimension (m) and similarity criterion (r), which often result in inconsistent outcomes when applied to multivariate data, such as electroencephalography signals. To address these challenges and to generalize the possibility of adopting Multiscale Fuzzy Entropy as a diagnostic tool for Alzheimer's disease, this research explores amplitude transformation preprocessing on electroencephalography signals in Multiscale Fuzzy Entropy calculation across varying parameters. The statistical analysis of the obtained results demonstrates that amplitude transformation preprocessing significantly enhances Multiscale Fuzzy Entropy's ability to detect Alzheimer's disease, achieving higher and more consistent significant comparison percentages, with an average of 73.2% across all parameter combinations, compared with only one raw data combination exceeding 65%. Clustering analysis corroborates these findings, showing that amplitude transformation improves the differentiation between Alzheimer's disease patients and healthy subjects. These results highlight the potential of amplitude transformation to stabilize Multiscale Fuzzy Entropy performance, making it a more reliable tool for early Alzheimer's disease detection. [ABSTRACT FROM AUTHOR]

This is the first case report of a non‐small‐cell lung cancer (NSCLC) patient harboring HIP1‐ALK (H28:A20) and CTNNB1 p.S45del treated with first‐line alectinib. Approximately 5% of NSCLC patients are reported to have anaplastic lymphoma kinase (ALK) rearrangements, and among these EML4‐ALK is the most frequent fusion variant. However, in recent years the use of next‐generation sequencing (NGS) in clinical laboratories has become increasingly widespread, identifying a lot of new ALK fusion partners as well as a large quantity of co‐occurring genomic alterations. Unfortunately, the growing number of genomic alterations detected by NGS does not always correspond to adequate knowledge of their clinical significance, often resulting in an empiric treatment of patients harboring uncommon mutations. [ABSTRACT FROM AUTHOR]

André Nyberg,1,* Sara Lundell,1,* Ulla-Maija Pesola,1 Åsa Audulv,2 Karin Wadell1,3 1Department of Community Medicine and Rehabilitation, Physiotherapy, Umeå University, Umeå, Sweden; 2Department of Nursing, Umeå University, Umeå, Sweden; 3Department of Public Health and Clinical Medicine, Division of Medicine, Umeå University, Umeå, Sweden*These authors contributed equally to this workCorrespondence: André Nyberg, Department of Community Medicine and Rehabilitation, Physiotherapy, Umeå University, Umeå, 901 87, Sweden, Tel +46 90 786 66 39, Email andre.nyberg@umu.seBackground: Lack of routines and competence among healthcare professionals have been reported as barriers to COPD management in long-term care. Online education could be used as a strategy to make COPD education more accessible.Purpose: The aim of this study was to evaluate a digital COPD education program for healthcare professionals in long-term care regarding feasibility, knowledge and working procedures.Methods: A randomized controlled feasibility trial with a convergent mixed methods design was conducted. Two municipalities in Sweden were randomized to intervention (n=20) or control (n=17). The intervention was a digital COPD education program accessible for three months. Data was collected through questionnaires on COPD-specific knowledge, conceptual knowledge, feasibility and usage of the COPD Web platform. Repeated individual interviews using a semi-structured interview guide was also performed. Quantitative and qualitative findings were merged using a mixed methods design.Results: The digital COPD education program appears feasible based on the expressed satisfaction of the healthcare workers and their reports that it supported them in their work. Across questionnaires, objective COPD-specific knowledge increased by 14 to 16 percentage points in the intervention group compared to 0 to 6 percentage points in the control group (p=0.001). The objective increase in COPD-specific knowledge was also captured in the interviews, where a perceived increase in knowledge led to increased security and focus on COPD management. Few changes in working procedures were expressed, but participants felt that attention was raised regarding COPD and the importance of preventive healthcare services. In addition, increased knowledge of healthcare services provided by other involved professions was emphasized, leading to discussions with other professions in relation to COPD management.Conclusion: A digital COPD education program is feasible and can increase the COPD-specific knowledge of healthcare professionals in long-term care, leading to increased focus on COPD-related issues. More comprehensive measures, including organizational changes, might be needed to change working procedures.Keywords: e-health, feasibility, work task, qualitative longitudinal research, questionnaire

Abstract Background Current guidelines recommend endoscopic surveillance for Barrett oesophagus (BE), but the value of surveillance is still debated. Using a combination of primary care, secondary care and cancer registry datasets, we examined the impact of a prior BE diagnosis, clinical and risk factors on survival from oesophageal cancer and adenocarcinoma. Methods Retrospective cohort study of patients aged 50 and above diagnosed with malignant oesophageal cancer between 1993 and 2014 using Clinical Practice Research Datalink (CPRD). All prior BE diagnoses and endoscopies were identified from CPRD and Hospital Episode Statistics. Histology information was obtained from linked cancer registry data. We used flexible parametric models to estimate excess hazard ratios (EHRs) for relative survival. We simulated the potential impact of lead‐time by adding random lead‐times from a variety of distributions to all those with prior BE. Results Among our oesophageal cancer (n = 7503) and adenocarcinoma (n = 1476) cohorts only small percentages, 3.4% and 5.3%, respectively, had a prior BE diagnosis. Two‐year relative survival was better among patients with BE: 48.0% (95% CI 41.9–54.9) compared to 25.2% (24.3–26.2) without. Patients with BE had a better prognosis (EHR = 0.53, 0.41–0.68). Survival was higher even if patients with BE had fewer than two endoscopies (50.0%; 43.6–57.3). A survival benefit was still observed after lead‐time adjustment, with a 20% absolute difference in 2‐year survival using a 5 year mean sojourn time. Conclusions Patients with a prior BE diagnosis had a survival advantage. This was not fully explained by surveillance endoscopies.

ObjectiveTo clarify the extent to which smokers in the general population experience tobacco withdrawal symptoms and whether such experience differs in those who continue to smoke and those who stopped smoking.MethodsWe included relevant questions in the nationally-representative China Health Literacy Survey (CHLS) conducted in 2018–2019. Among 87,028 participants, there were 22,115 ever-smokers aged 20–69 years who provided information on their smoking history and their experience of tobacco withdrawal symptoms. Multivariate logistic regressions were conducted to explore the association between withdrawal symptoms and other variables.ResultsAmong ever-smokers, there were 19,643 (88.8%) current smokers and 2,472 (11.2%) ex-smokers. Among current smokers, 61.3% reported having tried to quit smoking in the past. Overall, 61.1% of current smokers reported experiencing withdrawal symptoms: 69.9% of those who tried to quit smoking in the past and 47.5% of those who did not. A lower proportion of ex-smokers experienced withdrawal symptoms (46.3%) and the difference remained significant after controlling for demographic characteristics (OR = 1.76, 95% CI 1.62–1.93, P < 0.001). The most commonly reported withdrawal symptoms in both current smokers and ex-smokers were craving, restlessness and anxiety. In the multivariable-adjusted analyses, those who experienced withdrawal symptoms when they tried to quit smoking (OR: 2.05, 95% CI: 1.86–2.27) were less likely to successfully quit.ConclusionsThe clinical picture of the tobacco withdrawal syndrome is the same in current smokers and in ex-smokers, but ex-smokers are less likely to have experienced it. The experience of discomfort when unable to smoke is common and seems likely to be a major factor contributing to maintaining smoking behavior not just among individuals seeking help with quitting smoking, but among smokers generally.

Abstract Patients with non‐small cell lung cancer (NSCLC) and uncommon epidermal growth factor receptor (EGFR) mutation are characterized by high heterogeneity, and globally considered to have a worse prognosis than patients with the two common mutations; exon 19 deletion, and exon 21 L858R. Nevertheless, some uncommon mutations do confer sensitivity to tyrosine kinase inhibitors (TKIs) which is comparable with common mutations. In particular, some compound EGFR mutations seem to be characterized by a favorable prognosis. Unfortunately, the rarity of complex EGFR mutations results in difficult clinical decision‐making. Herein, to the best of our knowledge, we report the first case of an NSCLC patient with an EGFR triple mutation containing T785A/L861Q/H297_E298 who was successfully treated with afatinib.

The present study introduces a brain–computer interface designed and prototyped to be wearable and usable in daily life. Eight dry electroencephalographic sensors were adopted to acquire the brain activity associated with motor imagery. Multimodal feedback in extended reality was exploited to improve the online detection of neurological phenomena. Twenty-seven healthy subjects used the proposed system in five sessions to investigate the effects of feedback on motor imagery. The sample was divided into two equal-sized groups: a “neurofeedback” group, which performed motor imagery while receiving feedback, and a “control” group, which performed motor imagery with no feedback. Questionnaires were administered to participants aiming to investigate the usability of the proposed system and an individual’s ability to imagine movements. The highest mean classification accuracy across the subjects of the control group was about 62% with 3% associated type A uncertainty, and it was 69% with 3% uncertainty for the neurofeedback group. Moreover, the results in some cases were significantly higher for the neurofeedback group. The perceived usability by all participants was high. Overall, the study aimed at highlighting the advantages and the pitfalls of using a wearable brain–computer interface with dry sensors. Notably, this technology can be adopted for safe and economically viable tele-rehabilitation.

Abstract Background There is currently a lack of information on full anogenital evaluation of women with a previous history of anogenital neoplasia. Methods Retrospective analysis of the Homerton Anogenital Neoplasia Service records from January 2012 to March 2017, to identify all new referrals of women with previous anogenital neoplasia, who had had at least one complete examination of all anogenital sites. Multizonal anogenital disease (MZD) was defined as the presence of high-grade squamous intraepithelial lesions (HSIL)/carcinoma concurrently at two or more of the following sites/zones: perianus, anal canal, vulva, vagina or cervix. Results 253 women were included, mean age was 47 (SD=15) years and median duration of follow-up was 12 (IQR=21) months. Fifty-six women (22%) were diagnosed with MZD at first assessment and/or during follow-up. Current smokers (RR=1.84, 95% CI 1.21–2.79, p=0.004) and women on immunodulators/immunosuppressive drugs (RR=2.57, 95% CI 1.72-3.86, p

Abstract Background Prolonged (excessive) sitting is detrimentally associated with cardiovascular, metabolic and mental health. Moreover, prolonged sitting has been associated with poor executive function, memory, attention and visuospatial skills, which are important cognitive aspects of work performance. Breaking up prolonged sitting with standing or light-intensity exercises at the workplace is recognized as a potential measure in improving cognition. However, preliminary evidence, primarily from acute laboratory experiments, has enabled formulating hypothesis on the possible mechanistic pathways. Hence, the aim of this mapping review is to gather preliminary evidence and substantiate possible physiological mechanisms underpinning the putative effects of breaking prolonged sitting on improving cognitive function among sedentary office workers. Mapping method We searched four databases to identify relevant studies that explored the effects of uninterrupted sitting on cognitive function. First, we introduce how prolonged sitting increases the risks of hyperglycemia, autonomic stability, inflammation, adverse hormonal changes and restrictions in cerebral blood flow (CBF) and alters cognitive function. Second, we elucidate the direct and indirect effects of breaking up prolonged sitting time that may prevent a decline in cognitive performance by influencing glycaemic variability, autonomic stability, hormones (brain derived neurotrophic factor, dopamine, serotonin), vascular functions, and CBF. We highlight the importance of breaking up prolonged sitting on metabolic, vascular and endocrine functions, which in turn may improve cognitive functions and eventually foster work productivity. Improved synaptic transmission or neuroplasticity due to increased brain glucose and mitochondrial metabolism, increased endothelial shear and CBF, increased brain neurotrophic factors (dopamine) and accelerated anti-inflammatory functions are some of the hypothetical mechanisms underpinning improved cognitive functions. Conclusion We postulate that improving cognitive function by breaking up prolonged sitting periods is biologically plausible with the myriad of (suggested) physiological mechanisms. Future experimental studies to ascertain the aforementioned hypothetical mechanisms and clinical trials to break sedentary behavior and improve cognitive functions in sedentary office workers are warranted.

BackgroundBoth reducing sitting and increasing physical exercise promote health but exercising more does not necessarily reduce sitting time. One reason for this non-dependency may be that different aspects of exercise motivation are differently related to sitting time. Identifying the type of exercise motivation that would also be associated with sitting time can help to reduce sitting indirectly through increased exercise, thus bringing greater benefits.MethodsThe present study explored the association between quality of motivations toward physical activity with physical activity and sitting time in a total of 373 adults (age range = 23–81; women n = 256). The short version of international physical activity questionnaire (IPAQ) was used for measuring physical activity and sitting time. Reasons for exercising regularly were measured with the Self-Regulated Questionnaire–Exercise (SRQ-E), including four regulation subscales to assess regulation styles (i.e., intrinsic motivation, identified regulation, introjected regulation and external regulation). Confirmatory factor analysis (CFA) was used to test the four subscales of SRQ-E (latent variables) with the data obtained using AMOS v.23 (Analysis of Moment Structures). Then, structural equation model (SEM) with maximum likelihood estimates was used to test the hypothesized model.ResultsThe results indicated that only intrinsic motivation, but not identified, introjected or external motivation, toward physical activity predicted both physical activity and sitting time. Higher intrinsic motivation toward physical activity was associated with both higher physical activity and lower sitting time. In addition, physical activity was a mediator for lower sitting time when the source was intrinsic motivation.ConclusionPrevious studies have shown low between and within participant correlation between sitting time and physical activity, and interventions have generally failed to both increase physical activity while decreasing sitting time. The present cross-sectional results suggest that targeting increased physical activity by increased intrinsic motivation has the potential to both increase physical activity and decrease sitting time.

BackgroundDespite functional and cognitive benefits, few adults and older adults do strength training twice per week with sufficient intensity. Exercise-based active video games (exergaming) may amplify the cognitive benefits of exercise and increase adherence and motivation toward training. However, the benefits of a well-defined and monitored dose of strength training, executed simultaneously or sequentially with a cognitive element, has received little attention. In this study we have two aims: First, to systematically gather the available evidence; second, to suggest possible ways to promote strength exergaming innovations.MethodsWe systematically reviewed randomized controlled trials using simultaneous or sequent combined strength and cognitive training or strength exergaming to improve cognitive or functional outcomes in adults and older adults.ResultsAfter screening 1,785 studies (Google Scholar, ACM Digital Library, IEEE Xplore Library, PsycARTICLES, Scopus, Cochrane Library and PubMed) we found three eligible studies. Of the two studies using sequent strength and cognitive training, one showed improved functionality, but the other showed negative effects on cognition. The third study using simultaneous intervention, reported a positive influence on both cognition and function, when compared with either strength training alone or a control group. Moderate level of evidence was showed on GRADE analysis.ConclusionThe existing little evidence suggests that strength and cognitive training improves cognition and function in adults and older adults. The following suggestions may help to promote further innovation: (1) ensure minimal dosage of strength training (30–60 min, 2 × /week), (2) use machine-based strength training devices to control volume and intensity (to prevent cognitive components from interfering with strength training), (3) include power training by using cognitive tasks requiring rapid reactions, and (4) add cognitive memory tasks (to extend the cognitive benefits of strength training per se), and (5) include motivational exergame elements to increase adherence.

Abstract Background Chronic obstructive pulmonary disease (COPD) is one of the most common and deadliest chronic diseases worldwide. Since COPD is a chronic and progressive disease, treatment is necessary throughout life. For people with COPD who cannot live independently, long-term care facilities are often required. However, knowledge is very limited about aspects of importance for effective COPD management in these settings in accordance with current treatment guidelines. The aim of this study was to explore aspects of importance in long-term care facilities for providing interventions according to treatment guidelines for people with COPD, from the perspective of healthcare professionals, in an effort to prove novel knowledge that could be used to facilitate implementation of treatment guidelines in these settings. Methods A qualitative study was performed in northern Sweden. In Sweden, municipalities are responsible for providing long-term care. Interviews with 36 healthcare professionals (nurses, physiotherapists, occupational therapists and dieticians) in municipal healthcare were conducted and analysed using qualitative content analysis with triangulation by the authors. Results The overarching theme that emerged from the analysis was Groping around in the dark for adequate COPD management. This represents healthcare professionals’ experiences of working with a complex diagnosis somewhat overlooked in the municipal healthcare, an underdog in the healthcare system. The groping around in the dark theme further represents the healthcare professionals’ lack of COPD-related competence, lack of interprofessional collaboration, and insufficient communication with the county council. The fragile group of people with COPD and their relatives were considered in need of support adapted to their context, but routines and resources for COPD management were limited. This lack of routines and resources also resulted in professionals being pragmatic and adopting short-term solutions without focusing on specific needs related to the diagnosis. Conclusions The COPD management in long-term care settings showed several insufficiencies, indicating a large gap between clinical practice and treatment guidelines for COPD. It is crucial to improve COPD management in long-term care settings. Consequently, several actions are needed, such as increasing professional competence, establishing new routines, acknowledging and making COPD a higher priority, as well as adapting treatment guidelines to the context.

Abstract Background Children’s habitual physical activity, including active travel and catching public transit (walking and cycling to and from destinations), and independent mobility (mobility without an adult) have decreased. Public transit trips are physically active and can provide access to hobbies independent of parents, but there is no device-measured data about children’s total physical activity time following the introduction of free public transit. Our aim is to compare physical activity and independent mobility between children living in two Finnish towns, one with a recently introduced free public transit system, and the other without free public transit. Methods The city of Mikkeli has provided free public transit for all comprehensive school children since 2017. Various districts from Mikkeli, and the reference town of Kouvola (towns from South-Eastern Finland with a comparative population size and geographical structure), are selected based on their accessibility and the availability of public transit services. Samples of 10–12-year-old children will be recruited through primary schools. We will compare moderate-to-vigorous physical activity time, sitting time (a thigh-worn Fibion® device) and independent mobility (a participatory mapping method, PPGIS) of children: 1) who live in towns with and without free public transit, 2) who live and go to school in districts with high vs. low perceived and objective access to free public transit, and 3) who report using vs. not using free public transit. In addition, ethnography will be used to get insights on the social and cultural effects of the free public transit on children’s and parent’s everyday life. Discussion There is a need for scalable solutions that can increase children’s physical activity independent of their socioeconomic background or place of residence. This project will give information on how a political action to provide free public transit for children is associated with their total physical activity time and independent mobility patterns, therefore providing highly relevant information for political decision-making and for promoting independent physical activity in children.

COVID-19 is an ongoing global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Although it primarily attacks the respiratory tract, inflammation can also affect the central nervous system (CNS), leading to chemo-sensory deficits such as anosmia and serious cognitive problems. Recent studies have shown a connection between COVID-19 and neurodegenerative diseases, particularly Alzheimer’s disease (AD). In fact, AD appears to exhibit neurological mechanisms of protein interactions similar to those that occur during COVID-19. Starting from these considerations, this perspective paper outlines a new approach based on the analysis of the complexity of brain signals to identify and quantify common features between COVID-19 and neurodegenerative disorders. Considering the relation between olfactory deficits, AD, and COVID-19, we present an experimental design involving olfactory tasks using multiscale fuzzy entropy (MFE) for electroencephalographic (EEG) signal analysis. Additionally, we present the open challenges and future perspectives. More specifically, the challenges are related to the lack of clinical standards regarding EEG signal entropy and public data that can be exploited in the experimental phase. Furthermore, the integration of EEG analysis with machine learning still requires further investigation.

Why use poetry to enhance the individual's ability to read and understand the text? How do we assist people with intellectual disabilities, specifically Down syndrome, with an opportunity to bring richer and deeper meaning to what they read? The special education community is waking up to the possibilities for expression which exist for individuals with Down syndrome. For several decades we have assumed that an IQ or intelligence number can assist professionals in determining just how far someone can go or how much we can teach. In reviewing the literature for individuals with other learning disabilities, and those very distinct and effective strategies, we can now ask, why not use these same strategies for the intellectually disabled, specifically those with Down syndrome? (Contains 2 figures.)