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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.

Aims: The aim of this study was to investigate the effects of physical education (PE) class contents on 6-8 years school-age children's perceived exertion, psychological responses and cognitive functions. Materials and Methods: These dimensions were measured in 135 children (6.61 ± 0.58 years) before and after an 8-week different PE intervention programs [i.e. balance intervention program (BIP), game based program (GBP) or drama learning program (DLP)]. Results: With regard to the physical exertion, higher perceived exertion was found in BIP than in GBP and DLP (p < 0.01, ES = -0.5 to -1.0, small to moderate). Regarding cognitive functions, children of the GBP and the DLP significantly improved some of the cognitive functions test scores (p < 0.01 or 0.05, ES = 0.5 to 1.5, small to large). Conclusion: These results lead us to think that physical activity could be an effective tool for improving children's cognitive functions.

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.

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]

BACKGROUND: High levels of sedentary behavior in workplaces are currently recognized as an independent risk factor for cognitive dysfunction and poor mental health. However, sedentary patterns vary between workdays and non-workdays, which may influence cognitive functions. OBJECTIVE: The present study aimed to quantify and compare work and nonwork device-measured sedentary time (ST) and its association with cognitive function in Indian office workers. METHODS: In an ongoing randomized controlled trial (SMART-STEP), the baseline data of 136 full-time office workers, including accelerometer-measured sedentary patterns and cognitive functions, were analyzed. The ST was measured using a hip-worn accelerometer (Actigraph wGT3X-BT) for seven days, and executive functions were measured using computer-based tests. Linear regression models were employed to analyze the relationships between ST and executive function measures. RESULTS: The median daily ST of Indian office workers was 11.41 hours. The ST was greater on both workdays (11.43 hrs.) and non-workdays (11.14 hrs.) though different (F = 6.76, p = 0.001, ηp2 = 0.032). Office workers accumulate more prolonged sitting bouts (+21.36 min) during work days than non-workdays. No associations between device-measured ST and executive functions were observed. CONCLUSION: Indian office workers exhibited high ST patterns, especially on workdays. Although lower than workdays, Indian office workers exhibited more ST patterns during non-workdays than did their Western counterparts. Culturally adaptable workplace and leisure time physical activity interventions are needed to address the high ST of Indian office workers. [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]