Miracle-dz/UniFAR-FTUs huggingface dataset:
Eligibility for early rhythm control in patients with atrial fibrillation in the UK Biobank

Objective The Early Treatment of Atrial Fibrillation for Stroke Prevention (EAST-AFNET4) trial showed a clinical benefit of early rhythm-control therapy in patients with recently diagnosed atrial fibrillation (AF). The generalisability of the results in the general population is not known. Methods Participants in the population-based UK Biobank were assessed for eligibility based on the EAST-AFNET4 inclusion/exclusion criteria. Treatment of all eligible participants was classified as early rhythm-control (antiarrhythmic drug therapy or AF ablation) or usual care. To assess treatment effects, primary care data and Hospital Episode Statistics were merged with UK Biobank data. Efficacy and safety outcomes were compared between groups in the entire cohort and in a propensity-matched data set. Results AF was present in 35 526/502 493 (7.1%) participants, including 8340 (988 with AF <1 year) with AF at enrolment and 27 186 with incident AF during follow-up. Most participants (22 003/27 186; 80.9%) with incident AF were eligible for early rhythm-control. Eligible participants were older (70 years vs 63 years) and more likely to be female (42% vs 21%) compared with ineligible patients. Of 9004 participants with full primary care data, 874 (9.02%) received early rhythm-control. Safety outcomes were not different between patients receiving early rhythm-control and controls. The primary outcome of EAST-AFNET 4, a composite of cardiovascular death, stroke/transient ischaemic attack and hospitalisation for heart failure or acute coronary syndrome occurred less often in participants receiving early rhythm-control compared with controls in the entire cohort (HR 0.82, 95% CI 0.71 to 0.94, p=0.005). In the propensity-score matched analysis, early rhythm-control did not significantly decrease of the primary outcome compared with usual care (HR 0.87, 95% CI 0.72 to 1.04, p=0.124). Conclusion Around 80% of participants diagnosed with AF in the UK population are eligible for early rhythm-control. Early rhythm-control therapy was safe in routine care.
Unified Systolic Architecture for High – Throughput VLSI Implementation of Prime – Factor Discrete Fourier, Discrete Hartley, and Discrete Cosine Transforms

— In this paper, we have suggested unified systolic mesh architecture for the implementation of prime – factor discrete Fourier transform (DFT), discrete Hartley transform (DHT), and discrete cosine transform (DCT). Also, we have suggested a new decomposition scheme and a highly compact bilayer systolic architecture for high throughput computation of prime – factor DHT. It is shown further, that the proposed DHT structure can be used for efficient computation of prime – factor DFT, and DCT, as well. The transposition of the intermediate matrix is avoided in the unified systolic architecture by orthogonal processing of data during the pair of matrix multiplications. In the proposed bilayer DHT structure, the transposition of intermediate output is avoided by orthogonal alignment of the arrays of output layer with respect to the arrays of input layer. Both the structures, therefore, provide saving in hardware, as well as, time, which are required for transposition in the existing architectures. The area and time complexities of the proposed bilayer DHT structure is nearly (1/4) and (1/2) times that of the unified architecture, respectively, while both the structures require nearly the same amount of hardware.
Estimands in cluster-randomized trials: choosing analyses that answer the right question

Abstract Background Cluster-randomized trials (CRTs) involve randomizing groups of individuals (e.g. hospitals, schools or villages) to different interventions. Various approaches exist for analysing CRTs but there has been little discussion around the treatment effects (estimands) targeted by each. Methods We describe the different estimands that can be addressed through CRTs and demonstrate how choices between different analytic approaches can impact the interpretation of results by fundamentally changing the question being asked, or, equivalently, the target estimand. Results CRTs can address either the participant-average treatment effect (the average treatment effect across participants) or the cluster-average treatment effect (the average treatment effect across clusters). These two estimands can differ when participant outcomes or the treatment effect depends on the cluster size (referred to as ‘informative cluster size’), which can occur for reasons such as differences in staffing levels or types of participants between small and large clusters. Furthermore, common estimators, such as mixed-effects models or generalized estimating equations with an exchangeable working correlation structure, can produce biased estimates for both the participant-average and cluster-average treatment effects when cluster size is informative. We describe alternative estimators (independence estimating equations and cluster-level analyses) that are unbiased for CRTs even when informative cluster size is present. Conclusion We conclude that careful specification of the estimand at the outset can ensure that the study question being addressed is clear and relevant, and, in turn, that the selected estimator provides an unbiased estimate of the desired quantity.
Independent APOE4 knock‐in mouse models display reduced brain APOE protein, altered neuroinflammation, and simplification of dendritic spines

APOE is an immunomodulator in the brain and the major genetic risk factor for late‐onset Alzheimer's disease (AD). Targeted replacement APOE mice (APOE‐TR) have been a useful tool to study the effects of APOE isoforms on brain neurochemistry and activity prior to and during AD. We use newly available APOE knock‐in mice (JAX‐APOE) to compare phenotypes associated with APOE4 across models. Similar to APOE4‐TR mice, JAX‐E4 mouse brains showed 27% lower levels of APOE protein compared with JAX‐E3 (p < 0.001). We analyzed several neuroinflammatory molecules that have been associated with APOE genotype. SerpinA3 was much higher in APOE4‐TR mice to APOE3‐TR mice, but this effect was not seen in JAX‐APOE mice. There were higher levels of IL‐3 in JAX‐E4 brains compared with JAX‐E3, but other neuroinflammatory markers (IL6, TNFα) were not affected by APOE genotype. In terms of neuronal structure, basal dendritic spine density in the entorhinal cortex was 39% lower in JAX‐E4 mice compared with JAX‐E3 mice (p < 0.001), again similar to APOE‐TR mice. One‐week treatment with ibuprofen significantly increased dendritic spine density in the JAX‐E4 mice, consistent with our previous finding in APOE‐TR mice. Behaviorally, there was no effect of APOE genotype on Barnes Maze learning and memory in 6‐month‐old JAX‐APOE mice. Overall, the experiments performed in JAX‐APOE mice validated findings from APOE‐TR mice, identifying particularly strong effects of APOE4 genotype on lower APOE protein levels and simplified neuron structure. These data demonstrate pathways that could promote susceptibility of APOE4 brains to AD pathological changes.
Opioid Dependence and Overdose After Surgery

Objective: To determine: (1) incidence of “opioid never events” (ONEs), defined as the development of opioid dependence or overdose in an opioid-naive surgical patient who is prescribed opioids postoperatively and (2) risk factors predicting ONEs. Background: Patients receiving opioids after surgery are at risk of experiencing life-threatening opioid-related adverse events. Methods: An electronic medical record review identified surgical patients at an academic medical center between January 1, 2015, and December 31, 2018, followed through March 31, 2020. ONEs were determined by International Classification of Diseases, Ninth/10th Revision (ICD-9/10) codes, and electronic medical record review. Results: A total of 35,335 opioid-naive surgical patients received a perioperative opioid prescription. The median follow-up was 3.47 years (range: 1.25–5.25 years). ONEs occurred in 0.19% (67/35,335) of patients. The ONE rate was 5.6 per 10,000 person-years of follow-up. Ten of 67 ONE patients overdosed on opioids. The median time to ONE was 1.6 years; the highest ONE rate was observed 1 to 2 years after surgery. In multivariate analysis, patients receiving opioid prescriptions 90 to 180 or 90 to 360 days after surgery had the highest risk of developing ONEs [hazard ratio (HR)=6.39, confidence interval (CI): 3.72–10.973; HR=6.87, CI: 4.24–11.12, respectively]. Surgical specialty (HR=5.21, 2.65–0.23) and patient age (HR=4.17, CI: 2.50–6.96) were also risk factors for ONEs. Persistent opioid use 90 to 360 days after surgery was present in 45% of patients developing ONEs. Conclusions: Postoperative opioid dependence or overdose is a significant health problem, affecting roughly 2 per 1000 opioid-naive surgical patients prescribed an opioid and followed for 5 years. Risk factors for the development of ONEs include opioid use 3 to 12 months after surgery, patient age, and surgical procedure.
Low-frequency HIV-1 drug resistance mutations in antiretroviral naïve individuals in Botswana

Background: Individuals living with human immunodeficiency virus (HIV) who experience virological failure (VF) after combination antiretroviral therapy (cART) initiation may have had low-frequency drug resistance mutations (DRMs) at cART initiation. There are no data on low-frequency DRMs among cART-naïve HIV-positive individuals in Botswana. Methods: We evaluated the prevalence of low-frequency DRMs among cART-naïve individuals previously sequenced using Sanger sequencing. The generated pol amplicons were sequenced by next-generation sequencing. Results: We observed low-frequency DRMs (detected at <20% in 33/103 (32%) of the successfully sequenced individuals, of whom four also had mutations detected at >20%. K65R was the most common low-frequency DRM detected in 8 individuals. Eighty-two of the 103 individuals had follow-up viral load data while on cART. Twenty-seven of the 82 individuals harbored low-frequency DRMs. Only 12 of 82 individuals experienced VF. The following low-frequency DRMs were observed in four individuals experiencing VF: K65R, K103N, V108I, and Y188C. No statistically significant difference was observed in the prevalence of low-frequency DRMs between individuals experiencing VF (4/12) and those not experiencing VF (23/70) (P = .97). However, individuals with non-nucleoside reverse transcriptase inhibitors-associated low-frequency DRMs were 2.68 times more likely to experience VF (odds ratio, 2.68; 95% confidential interval, 0.4–13.9) compared with those without (P = .22). Conclusion: Next-generation sequencing was able to detect low-frequency DRMs in this cohort in Botswana, but these DRMs did not contribute significantly to VF.
Modeling Week Activity Schedules for Travel Demand Models

Activity schedules are an important input for travel demand models. This paper presents a model to generate activity schedules for one week. The approach, called actiTopp, is based on the concept of utility-based regression models and stepwise modeling. In contrast to most of the existing models, actiTopp covers the time period of one week. Few models have covered one week; thus, the activity generation approach of this simulation period is rare. Analysis of weekly activity behavior shows stability between different days (e.g., working durations). Hence, the model explicitly takes these aspects into account, for example, by defining time budgets to spread durations within the week. For model estimation, the study used data from the German Mobility Panel (MOP). This annual survey collects representative data on the travel behavior of the German population. The data from 2004–2013 provide more than 17,500 activity schedules for one week, with more than 450,000 activities. Selected results are shown for the model application to 2014 MOP data, which the study used for validation purposes. The mean value of activities per person and week show a difference of 0.3 activity. To evaluate the model, the study used Kolmogorov-Smirnov tests with a significance level of α = 0.001. For the activity type distribution of the 2014 sample, the analysis could not reject the null hypothesis of equality of the distribution of the model and the survey data at this significance level.
The Influence of Dementia Beliefs and Knowledge on Perceived Dementia Worry: An Empirical Study Among Adults in Rural China

Alzheimer’s disease and related dementias are more prevalent in rural areas than in urban areas in China. This study aims to examine the role of dementia beliefs and knowledge in influencing dementia worry among rural adults in China. Data were generated in a cross-sectional survey of 577 participants. Hierarchical regression analyses found that both the beliefs and knowledge of dementia contributed to higher levels of dementia worry. The propensity score matching method affirmed the robustness of regression results. In addition, those aged 45-64 reported higher worry about dementia than those aged 65 or older, while being married was related to lower dementia worry. As one of the first kind studies that examined dementia worry in rural Chinese population, our findings suggest that policy and practice efforts should address cultural beliefs of dementia as they contributed to higher worry about dementia in rural areas.
Investigation of the conformation of human prion protein in ethanol solution using molecular dynamics simulations

Abstract When the conformation of protein is changed from its natural state to a misfolded state, some diseases will happen like prion disease. Prion diseases are a set of deadly neurodegenerative diseases caused by prion protein misfolding and aggregation. Monohydric alcohols have a strong influence on the structure of protein. However, whether monohydric alcohols inhibit amyloid fibrosis remains uncertain. Here, to elucidate the effect of ethanol on the structural stability of human prion protein, molecular dynamics simulations were employed to analyze the conformational changes and dynamics characteristics of human prion proteins at different temperatures. The results show that the extension of β-sheet occurs more easily and the α-helix is more easily disrupted at high temperatures. We found that ethanol can destroy the hydrophobic interactions and make the hydrogen bonds stable, which protects the secondary structure of the protein, especially at 500 K. Communicated by Ramaswamy H. Sarma
Ferroptosis Inhibitors as New Therapeutic Insights into Radiation-Induced Heart Disease.

Radiation-induced heart disease (RIHD) is a significant cause of morbidity in breast and other mediastinal cancers. The many molecular and cellular patho-mechanisms that have a role in RIHD are not completely understood. Endothelial injury, oxidative stress, and inflammation, as well as endoplasmic reticulum and mitochondrial damage, are considered the primary causes of RIHD. Ferroptosis is a newly discovered type of cell death that results from iron-dependent lipid peroxide accumulation. As ferroptosis plays an important role in the pathogenesis of cardiovascular diseases, it seems that it has a significant effect on RIHD. It was recently shown that ionizing radiation (IR) generates severe ferroptosis, which is a critical component of Radiotherapy-mediated normal cell toxicity. These findings support the use of a ferroptosis inhibitor to reduce RIHD. In this perspective review, we summarize the role of ferroptosis in pathogens of cardiovascular disease and radiation toxicity, and we will introduce ferroptosis inhibitors as a new strategy to prevent or reduce RIHD.
Echocardiographic predictors of symptomatic cardiotoxicity among patients undergoing chemotherapy: A systematic review and meta-analysis

Background: Chemotherapeutic agents have been associated with cardiotoxicity; thus, they require close monitoring. Several echocardiographic variables have been investigated as early predictors of symptomatic cardiotoxicity in patients undergoing chemotherapy. Objective: To identify if global longitudinal strain (GLS) is a better predictor of symptomatic cardiotoxicity compared to left ventricular ejection fraction (LVEF) in patients receiving chemotherapy. Methods: MEDLINE, Scopus, and Cochrane Central Register of Controlled Trials were searched from inception through December 2020. Adults who developed symptomatic cardiotoxicity (New York Heart Association [NYHA] Class III–IV heart failure, cardiac arrest, or cardiac death) after undergoing chemotherapy with pre- and postchemotherapy echocardiographic measures of cardiac function were included. The primary focus was on the prediction of symptomatic cardiotoxicity. Estimates were reported as random effects hazard ratios (HR) with 95% confidence intervals (CI). Results: Four studies met inclusion criteria. The most common malignancy identified in the included studies was breast cancer, and the most common chemotherapeutic agent utilized was anthracyclines. Most studies utilized the Simpson biplane method to measure echocardiographic parameters. Pooled results demonstrated no significant association between LVEF and the prediction of symptomatic cardiotoxicity (HR 1.48; 95% CI, 0.96–2.27; P = 0.07). However, 2 studies that analyzed GLS found it to be a strong predictor of symptomatic cardiotoxicity (HR 1.46; 95% CI, 1.34–1.58; P < .001). There was no significant association between symptomatic cardiotoxicity and baseline left ventricular end diastolic volume, end systolic volume, or end diastolic volume index. Conclusions: GLS may predict symptomatic cardiotoxicity and be used to monitor patients on chemotherapy for symptomatic cardiac dysfunction. While the pooled results for baseline LVEF identified that it is not a predictor of symptomatic cardiotoxicity, this differs from the findings of the only randomized trial included in this meta-analysis. The data for baseline GLS as a predictor of symptomatic cardiotoxicity is encouraging, but definite evidence that GLS may be superior to LVEF is lacking. Prospective randomized, blinded trials are required to identify if 1 echocardiographic parameter may be superior to the other.
Effect of irrigation with treated wastewater on bermudagrass (Cynodon dactylon (L.) Pers.) production and soil characteristics and estimation of plant nutritional input

In recent years, climate change has greatly affected rainfall and air temperature levels leading to a reduction in water resources in Southern Europe. This fact has emphasized the need to focus on the use of non-conventional water resources for agricultural irrigation. The reuse of treated wastewater (TWW) can represent a sustainable solution, reducing the consumption of freshwater (FW) and the need for mineral fertilisers. The main aim of this study was to assess, in a three-year period, the effects of TWW irrigation compared to FW on the biomass production of bermudagrass [Cynodon dactylon (L.) Pers. ] plants and soil characteristics and to estimate the nutritional input provided by TWW irrigation. TWW was obtained by a constructed wetland system (CWs) which was used to treat urban wastewater. The system had a total surface area of 100 m2. An experimental field of bermudagrass was set up close to the system in a Sicilian location (Italy), using a split-plot design for a two-factor experiment with three replications. Results highlighted a high organic pollutant removal [five days biochemical oxygen demand (BOD5): 61%, chemical oxygen demand (COD): 65%] and a good efficiency in nutrients [total nitrogen (TN): 50%, total phosphorus (TP): 42%] of the CWs. Plants irrigated with TWW showed higher dry aboveground dry-weight (1259.3 kg ha-1) than those irrigated with FW (942.2 kg ha-1), on average. TWW irrigation approximately allowed a saving of 50.0 kg TN ha-1 year-1, 24.0 kg TP ha-1 year-1 and 29.0 kg K ha-1 year-1 on average with respect to commonly used N-P-K fertilisation programme for bermudagrass in the Mediterranean region. Soil salinity increased significantly (p ≤ 0.01) over the years and was detected to be higher in TWW-irrigated plots (+6.34%) in comparison with FW-irrigated plots. Our findings demonstrate that medium-term TWW irrigation increases the biomass production of bermudagrass turf and contributes to save significant amounts of nutrients, providing a series of agronomic and environmental benefits.
Experiences of nurses and coordinators in a childhood obesity prevention trial based on motivational interviewing within Swedish child health services

ABSTRACT Purpose To explore the experiences of nurses and coordinators in the PRIMROSE childhood obesity prevention trial, and to understand the factors that might help to improve the outcome of future primary prevention of obesity. Methods Using a qualitative approach, data were obtained by interviewing nine intervention nurses and three regional study coordinators. All participants were female. The interviews were transcribed and analysed using content analysis. Results Two themes emerged: The nurses experienced that it was rewarding to participate in the trial, but challenging to combine the intervention with regular work; and The study coordinators experienced that they were in a difficult position handling the conflicting needs of the research group and the nurses’ commitment to usual child health care services. The importance of support, encouragement, briefer and simpler intervention, and adaptation of the training in motivational interviewing to the setting was emphasized. Stress and lack of time were major barriers to deliver the intervention as intended. Conclusions Although the PRIMROSE intervention was developed in collaboration with representatives from the child health services, and additional research funding was provided to compensate for time spent working with the trial, nurses experienced stress and time constraints.
Controlling Spin-Orbit Coupling to Tailor Type-II Dirac Bands.

NiTe2, a type-II Dirac semimetal with a strongly tilted Dirac band, has been explored extensively to understand its intriguing topological properties. Here, using density functional theory calculations, we report that the strength of the spin-orbit coupling (SOC) in NiTe2 can be tuned by Se substitution. This results in negative shifts of the bulk Dirac point (BDP) while preserving the type-II Dirac band. Indeed, combined studies using scanning tunneling spectroscopy and angle-resolved photoemission spectroscopy confirm that the BDP in the NiTe2-xSex alloy moves from +0.1 eV (NiTe2) to -0.3 eV (NiTeSe) depending on the Se concentrations, indicating the effective tunability of type-II Dirac Fermions. Our results demonstrate an approach to tailor the type-II Dirac band in NiTe2 by controlling the SOC strength via chalcogen substitution. This approach can be applicable to different types of topological materials.
Optimization of culture medium and scale-up production of astaxanthin using corn steep liquor as substrate by response surface methodology

Abstract Astaxanthin is a natural carotenoid with strong antioxidant activity. In this paper, the effects of carbon source, corn steep liquor, distiller grains, and initial pH on the growth and astaxanthin production of Phaffia rhodozyma D3 were evaluated. The optimal medium composition was 32 g/L glucose, 12 g/L corn steep liquor as nitrogen source, and the initial pH was 6.7. Phaffia rhodozyma D3 was cultured in a shake flask under these optimized conditions, the biomass was 6.47 g/L, the astaxanthin/OD475 was 15.16, and the astaxanthin content was 1.41 mg/g. The astaxanthin content was further increased to 4.70 mg/g by the combination of TiO2 stimulation and the expanding cultivation of P. rhodozyma D3 in a 5 L fermenter, which was 2.81 times that of the control group. Expanding fermentation implies the possibility of large-scale production in the astaxanthin industry. Corn steep liquor was used as an alternative nitrogen source to culture P. rhodozyma D3, which could both reduce the production cost of astaxanthin and increased the by-products utilization rate.