bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute exercise decreases insulin‐stimulated extracellular vesicles in conjunction with augmentation index in adults with obesity
Authors: Heiston Emily M. , Ballantyne Anna , La Salvia Sabrina , Musante Luca , Erdbrügger Uta , Malin Steven K. 
Published: January 2022

AbstractExtracellular vesicles (EVs) are often elevated in obesity and may modulate disease risk. Although acute exercise reduces fasting EVs in adults with obesity, no data exist on insulin‐mediated EV responses. This study evaluated the effects of exercise on EV responses to insulin in relation to vascular function. Ten (5M/5F) sedentary adults with obesity (34.3 ± 3.7 kg/m2) completed an evening control and acute exercise condition (70% to expend 400 kcal). Following an overnight fast, participants underwent a 2 h euglycaemic–hyperinsulinaemic clamp (90 mg/dl; 40 mU/m2/min) to determine metabolic insulin sensitivity (M‐value), phenotypes of medium‐ to large‐sized EVs, and aortic waveform measures. Endothelial (CD105+, CD41−/CD31+)‐, leukocyte (CD45+)‐, platelet (CD41+, CD41+/31+)‐ and tetraspanin (TX+)‐derived EVs, as well as platelet endothelial cell adhesion molecule (CD31+), were determined before and after the clamp using high resolution spectral flow cytometry. Although exercise did not alter fasting haemodynamics, it lowered the augmentation index (AIx75, P = 0.024) and increased the M‐value (P = 0.042). Further, exercise decreased all fasting EVs (P < 0.01) and decreased insulin‐stimulated TX+ (P = 0.060), CD31+ (P = 0.060) and CD41−/31+ (P = 0.045) compared to rest. Interestingly, greater insulin‐stimulated decreases in CD41−/31+ were associated with reduced AIx75 during the clamp (r = 0.62, P = 0.059), while insulin‐stimulated decreases in CD41+ (r = −0.68, P = 0.031), CD41+/31+ (r = −0.69, P = 0.262), TX+ (r = −0.66, P = 0.037) and CD31+ (r = −0.69, P = 0.028) correlated with M‐value following exercise. Thus, acute exercise may decrease fasting and insulin‐stimulated medium‐ to large‐size EVs in conjunction with improved M‐value and AIx75. More research is needed to understand effects of exercise on EVs in the regulation of glucose homeostasis and vascular function.Key points
Extracellular vesicles (EVs) are increased in states of obesity and may play a role in altered insulin sensitivity and blood pressure; aerobic exercise decreases fasting EV concentrations the following day in adults with obesity.
This study directly tested the effects of insulin on EVs and how a single bout of exercise impacts these responses.
Together, these data highlight the positive effects of a single bout of exercise on fasting and insulin‐stimulated EVs, with the latter relating to increased insulin sensitivity and decreased augmentation index.
These results support future research identifying EVs as mechanistic factors in glucose regulation and vascular function as well as clinical use of exercise to reduce cardiovascular disease risk.
Vitamin D and marine omega 3 fatty acid supplementation and incident autoimmune disease: VITAL randomized controlled trial
Authors: Hahn Jill , Cook Nancy R , Alexander Erik K , Friedman Sonia , Walter Joseph , Bubes Vadim , Kotler Gregory , Lee I-Min , Manson JoAnn E , Costenbader Karen H 
Published: January 2022

Abstract

Objective
To investigate whether vitamin D and marine derived long chain omega 3 fatty acids reduce autoimmune disease risk.

Design
Vitamin D and omega 3 trial (VITAL), a nationwide, randomized, double blind, placebo controlled trial with a two-by-two factorial design.

Setting
Nationwide in the United States.

Participants
25 871 participants, consisting of 12 786 men ≥50 years and 13 085 women ≥55 years at enrollment.

Interventions
Vitamin D (2000 IU/day) or matched placebo, and omega 3 fatty acids (1000 mg/day) or matched placebo. Participants self-reported all incident autoimmune diseases from baseline to a median of 5.3 years of follow-up; these diseases were confirmed by extensive medical record review. Cox proportional hazard models were used to test the effects of vitamin D and omega 3 fatty acids on autoimmune disease incidence.

Main outcome measures
The primary endpoint was all incident autoimmune diseases confirmed by medical record review: rheumatoid arthritis, polymyalgia rheumatica, autoimmune thyroid disease, psoriasis, and all others.

Results
25 871 participants were enrolled and followed for a median of 5.3 years. 18 046 self-identified as non-Hispanic white, 5106 as black, and 2152 as other racial and ethnic groups. The mean age was 67.1 years. For the vitamin D arm, 123 participants in the treatment group and 155 in the placebo group had a confirmed autoimmune disease (hazard ratio 0.78, 95% confidence interval 0.61 to 0.99, P=0.05). In the omega 3 fatty acids arm, 130 participants in the treatment group and 148 in the placebo group had a confirmed autoimmune disease (0.85, 0.67 to 1.08, P=0.19). Compared with the reference arm (vitamin D placebo and omega 3 fatty acid placebo; 88 with confirmed autoimmune disease), 63 participants who received vitamin D and omega 3 fatty acids (0.69, 0.49 to 0.96), 60 who received only vitamin D (0.68, 0.48 to 0.94), and 67 who received only omega 3 fatty acids (0.74, 0.54 to 1.03) had confirmed autoimmune disease.

Conclusions
Vitamin D supplementation for five years, with or without omega 3 fatty acids, reduced autoimmune disease by 22%, while omega 3 fatty acid supplementation with or without vitamin D reduced the autoimmune disease rate by 15% (not statistically significant). Both treatment arms showed larger effects than the reference arm (vitamin D placebo and omega 3 fatty acid placebo).

Study registration

ClinicalTrials.gov
NCT01351805
and
NCT01169259
Randomized trials on non-pharmaceutical interventions for COVID-19: a scoping review
Authors: Hirt Julian , Janiaud Perrine , Hemkens Lars G. 
Published: January 2022

ObjectiveWe aimed at providing a systematic overview of randomised trials assessing non-pharmaceutical interventions (NPIs) to prevent COVID-19.DesignScoping review.MethodsWe included all randomised trials assessing NPIs to prevent COVID-19 in any country and setting registered in ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform using the COVID-evidence platform (until 17 August 2021). We searched for corresponding publications in MEDLINE/PubMed, Google Scholar, the Living Overview of Evidence platform, and the Cochrane COVID-19 registry as well as for results posted in registries (until 14 November 2021). Descriptive statistics using numbers and percentages were used in the narrative synthesis of the results.ResultsWe identified 41 randomised trials. Of them, 12 were completed (29.3%) including 9 with published results. The 41 trials planned to recruit a median of 1700 participants (IQR 588–9500, range 30–35 256 399) with a median planned duration of 8 months (IQR 3–14, range 1–24). Most came from the USA (n=11, 26.8%). The trials mostly assessed protective equipment (n=11, 26.8%), COVID-19-related information and education programmes (n=9, 22.0%), access to mass events under specific safety measures (n=5, 12.2%), testing and screening strategies (n=5, 12.2%) and hygiene management (n=5, 12.2%).ConclusionsWorldwide, 41 randomised trials assessing NPIs have been initiated with published results available to inform policy decisions for only 9 of them. A long-term research agenda including behavioural, environmental, social and systems level interventions is urgently needed to guide policies and practices in the current and future public health emergencies.
IDEAL approach to the evaluation of machine learning technology in epilepsy surgery: protocol for the MAST trial
Authors: Chari Aswin , Adler Sophie , Wagstyl Konrad , Seunarine Kiran , Marcus Hani , Baldeweg Torsten , Tisdall Martin 
Published: January 2022

Epilepsy and epilepsy surgery lend themselves well to the application of machine learning (ML) and artificial intelligence (AI) technologies. This is evidenced by the plethora of tools developed for applications such as seizure detection and analysis of imaging and electrophysiological data. However, few of these tools have been directly used to guide patient management. In recent years, the Idea, Development, Exploration, Assessment, Long-Term Follow-Up (IDEAL) collaboration has formalised stages for the evaluation of surgical innovation and medical devices, and, in many ways, this pragmatic framework is also applicable to ML/AI technology, balancing innovation and safety.In this protocol paper, we outline the preclinical (IDEAL stage 0) evaluation and the protocol for a prospective (IDEAL stage 1/2a) study to evaluate the utility of an ML lesion detection algorithm designed to detect focal cortical dysplasia from structural MRI, as an adjunct in the planning of stereoelectroencephalography trajectories in children undergoing intracranial evaluation for drug-resistant epilepsy.
Direct and indirect effect of the COVID-19 pandemic on patients with cardiomyopathy
Authors: Hammersley Daniel J , Buchan Rachel J , Lota Amrit S , Mach Lukas , Jones Richard E , Halliday Brian P , Tayal Upasana , Meena Devendra , Dehghan Abbas , Tzoulaki Ioanna , Baksi A John , Pantazis Antonis , Roberts Angharad M , Prasad Sanjay K , Ware James S 
Published: January 2022

Objectives(1) To evaluate the prevalence and hospitalisation rate of COVID-19 infections among patients with dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) in the Royal Brompton and Harefield Hospital Cardiovascular Research Centre (RBHH CRC) Biobank. (2) To evaluate the indirect impact of the pandemic on patients with cardiomyopathy through the Heart Hive COVID-19 study. (3) To assess the impact of the pandemic on national cardiomyopathy-related hospital admissions.Methods(1) 1236 patients (703 DCM, 533 HCM) in the RBHH CRC Biobank were assessed for COVID-19 infections and hospitalisations; (2) 207 subjects (131 cardiomyopathy, 76 without heart disease) in the Heart Hive COVID-19 study completed online surveys evaluating physical health, psychological well-being, and behavioural adaptations during the pandemic and (3) 11 447 cardiomyopathy-related hospital admissions across National Health Service (NHS) England were studied from NHS Digital Hospital Episode Statistics over 2019–2020.ResultsA comparable proportion of patients with cardiomyopathy in the RBHH CRC Biobank had tested positive for COVID-19 compared with the UK population (1.1% vs 1.6%, p=0.14), but a higher proportion of those infected were hospitalised (53.8% vs 16.5%, p=0.002). In the Heart Hive COVID-19 study, more patients with cardiomyopathy felt their physical health had deteriorated due to the pandemic than subjects without heart disease (32.3% vs 13.2%, p=0.004) despite only 4.6% of the cardiomyopathy cohort reporting COVID-19 symptoms. A 17.9% year-on-year reduction in national cardiomyopathy-related hospital admissions was observed in 2020.ConclusionPatients with cardiomyopathy had similar reported rates of testing positive for COVID-19 to the background population, but those with test-proven infection were hospitalised more frequently. Deterioration in physical health amongst patients could not be explained by COVID-19 symptoms, inferring a significant contribution of the indirect consequences of the pandemic.Trial registration numberNCT04468256
Acquired Resistance to EZH2 Inhibitor GSK343 Promotes the Differentiation of Human DLBCL Cell Lines toward an ABC-Like Phenotype
Authors: Preston Samuel E.J. , Emond Audrey , Pettersson Filippa , Dupéré-Richer Daphné , Abraham Madelyn Jean , Riva Alberto , Kinal Mena , Rys Ryan N. , Johnson Nathalie A. , Mann Koren K. , del Rincón Sonia V. , Licht Jonathan D. , Miller Wilson H. 
Published: January 2022

Abstract
Diffuse large B-cell lymphoma (DLBCL) accounts for 40% of non-Hodgkin lymphoma, and 30% to 40% of patients will succumb to relapsed/refractory disease (rrDLBCL). Patients with rrDLBCL generally have low long-term survival rates due to a lack of efficient salvage therapies. Small-molecule inhibitors targeting the histone methyltransferase EZH2 represent an emerging group of novel therapeutics that show promising clinical efficacy in patients with rrDLBCL. The mechanisms that control acquired resistance to this class of targeted therapies, however, remain poorly understood. Here, we develop a model of resistance to the EZH2 inhibitor (EZH2i) GSK343 and use RNA-seq data and in vitro investigation to show that GCB (germinal center B-cell)-DLBCL cell lines with acquired drug resistance differentiate toward an ABC (activated B-cell)-DLBCL phenotype. We further observe that the development of resistance to GSK343 is sufficient to induce cross-resistance to other EZH2i. Notably, we identify the immune receptor SLAMF7 as upregulated in EZH2i-resistant cells, using chromatin immunoprecipitation profiling to uncover the changes in chromatin landscape remodeling that permit this altered gene expression. Collectively, our data reveal a previously unreported response to the development of EZH2i resistance in DLBCL, while providing strong rationale for pursuing investigation of dual-targeting of EZH2 and SLAMF7 in rrDLBCL.
HER2 Mediates PSMA/mGluR1-Driven Resistance to the DS-7423 Dual PI3K/mTOR Inhibitor in PTEN Wild-type Prostate Cancer Models
Authors: Gómez Valentí , Galazi Myria , Weitsman Gregory , Monypenny James , Al-Salemee Fahad , Barber Paul R. , Ng Kenrick , Beatson Richard , Szokol Bálint , Orfi László , Mullen Greg , Vanhaesebroeck Bart , Chowdhury Simon , Leung Hing Y. , Ng Tony 
Published: January 2022

Abstract
Prostate cancer remains a major cause of male mortality. Genetic alteration of the PI3K/AKT/mTOR pathway is one of the key events in tumor development and progression in prostate cancer, with inactivation of the PTEN tumor suppressor being very common in this cancer type. Extensive evaluation has been performed on the therapeutic potential of PI3K/AKT/mTOR inhibitors and the resistance mechanisms arising in patients with PTEN-mutant background. However, in patients with a PTEN wild-type phenotype, PI3K/AKT/mTOR inhibitors have not demonstrated efficacy, and this remains an area of clinical unmet need. In this study, we have investigated the response of PTEN wild-type prostate cancer cell lines to the dual PI3K/mTOR inhibitor DS-7423 alone or in combination with HER2 inhibitors or mGluR1 inhibitors. Upon treatment with the dual PI3K/mTOR inhibitor DS-7423, PTEN wild-type prostate cancer CWR22/22RV1 cells upregulate expression of the proteins PSMA, mGluR1, and the tyrosine kinase receptor HER2, while PTEN-mutant LNCaP cells upregulate androgen receptor and HER3. PSMA, mGluR1, and HER2 exert control over one another in a positive feedback loop that allows cells to overcome treatment with DS-7423. Concomitant targeting of PI3K/mTOR with either HER2 or mGluR1 inhibitors results in decreased cell survival and tumor growth in xenograft studies. Our results suggest a novel therapeutic possibility for patients with PTEN wild-type PI3K/AKT-mutant prostate cancer based in the combination of PI3K/mTOR blockade with HER2 or mGluR1 inhibitors.
Sex‐Specific Temporal Trends in Hypertensive Crisis Hospitalizations in the United States
Authors: Ebinger Joseph E. , Liu Yunxian , Driver Matthew , Ji Hongwei , Bairey Merz C. Noel , Rader Florian , Albert Christine M. , Cheng Susan 
Published: January 2022

Background
Despite recent improvements in hypertension control overall, the extent to which these trends apply to the most extreme forms of elevated blood pressure—hypertensive crises requiring hospitalization—in both women and men at risk remains unknown.

Methods and Results

Using data from the National Inpatient Sample, we estimated sex‐pooled and sex‐specific temporal trends in hypertensive crisis hospitalization and case fatality rates over serial time periods: years 2002 to 2006, 2007 to 2011, and 2012 to 2014. Over the entire study period (years 2002–2014), there were an estimated 918 392±9331 hypertensive crisis hospitalizations and 4377±157 in‐hospital deaths. Hypertensive crisis represented 0.23%±0.002% of all hospitalizations during the entire study period: 0.24%±0.002% for men and 0.22%±0.002% for women. In multivariable analyses adjusting for age, race or ethnicity, and cardiovascular conditions, the odds of experiencing a hospitalization primarily for hypertensive crisis increased annually for both men (odds ratio [OR], 1.083 per year; 95% CI, 1.08–1.09) and women (OR, 1.07 per year, 95% CI, 1.07–1.08) with a higher rate of increase observed in men compared with women (
P
<0.001). The multivariable‐adjusted odds of death during hypertensive crisis hospitalization decreased annually and similarly for men (OR, 0.89 per year; 95% CI, 0.86–0.92) and for women (0.92 per year; 95% CI, 0.90–0.94).

Conclusions
Hypertensive crisis hospitalizations have steadily increased, slightly more among men than women, along with an observed increase in the burden of cardiovascular conditions. These trends, observed despite contemporaneous improvements in hypertension prevention and control nationwide, warrant further investigations to identify contributing factors that could be amenable to targeted interventions.
Latent functional connectivity underlying multiple brain states
Authors: McCormick Ethan M. , Arnemann Katelyn L. , Ito Takuya , Hanson Stephen José , Cole Michael W. 
Published: January 2022

Abstract
Functional connectivity (FC) studies have predominantly focused on resting state, where ongoing dynamics are thought to reflect the brain’s intrinsic network architecture, which is thought to be broadly relevant because it persists across brain states (i.e., is state-general). However, it is unknown whether resting state is the optimal state for measuring intrinsic FC. We propose that latent FC, reflecting shared connectivity patterns across many brain states, better captures state-general intrinsic FC relative to measures derived from resting state alone. We estimated latent FC independently for each connection using leave-one-task-out factor analysis in seven highly distinct task states (24 conditions) and resting state using fMRI data from the Human Connectome Project. Compared with resting-state connectivity, latent FC improves generalization to held-out brain states, better explaining patterns of connectivity and task-evoked activation. We also found that latent connectivity improved prediction of behavior outside the scanner, indexed by the general intelligence factor (g). Our results suggest that FC patterns shared across many brain states, rather than just resting state, better reflect state-general connectivity. This affirms the notion of “intrinsic” brain network architecture as a set of connectivity properties persistent across brain states, providing an updated conceptual and mathematical framework of intrinsic connectivity as a latent factor.
Taxonomizing Non-at-Issue Contents
Authors: Sander Thorsten 
Published: January 2022

Abstract
The author argues that there is no such thing as a unique and general taxonomy of non-at-issue contents. Accordingly, we ought to shun large categories such as “conventional implicature” (Grice), “F-implicature” (Horn), “CI” (Potts), “Class B” (Tonhauser, Beaver, Roberts & Simons) or the like. As an alternative, we may, first, describe the “semantic profile” of linguistic devices as accurately as possible. Second, we may explicitly tailor our categories to particular theoretical purposes.
Optofluidic Platform for Rapid On-Chip Analysis of Total Phosphorus in Surface Water Using Absorption Spectrometry
Authors: Zhao Kun , Li Chang , Wan Liang , Luo Fangzhou , Cheng Zhiliang , Duan Jinge , Wang Ning 
Published: January 2022

Optofluidic devices are of high interest for online monitoring and analyzing biochemical targets in water by integrating the complex on-chip pretreatment of target analytes and spectral analysis. Compared with the traditional bulk equipment, versatile optical detection and biochemical analysis are more easily integrated on an optofluidic chip, which promotes the development of on-chip real-time rapid detection and monitoring. Here, we report an optofluidic platform for online monitoring total phosphorous in water by absorption spectrometry, which naturally combines the merits of both the photo-Fenton effect and microfluidics to realize the rapid on-chip digestion of phosphate at room temperature and normal pressure. The functional cells for chromogenic reaction and optical absorption detection are, respectively, fabricated on the platform to analyze the content of total phosphorus in surface water. In the experiment, the on-chip digestion time of phosphate is dramatically declined to 8.6 sec, and thus, the detection time is greatly shortened to a few minutes. The detection range of total phosphorus is demonstrated as 0.005–1.00 mg L−1, which satisfies the detection requirements of most environmental water samples. Its availability for measuring the total phosphorous in real water samples is also verified. Predictably, this platform is adapted to on-chip analysis of many other biochemical targets in water.
The Economic Case Against Time Travel: Using Science Fiction Ideas to Emphasize Economic Processes in the Classroom
Authors: Swinton John R. 
Published: January 2022

I describe a though experiment in which students can consider the importance of the profit motive, the passage of time, and the dissemination of information in various markets by imagining that time travel is possible. The thought experiment allows students to conclude that because the economic conditions that would result from time travel do not exist outside of the theoretical market models, certain types of time travel cannot exist. But, more importantly, it provides a tool to help students think more deeply about the assumptions of the economic models presented. JEL Classifications: A1, A2, D8, I20
Indices and Indicators Developed to Evaluate the “Strengthening Community Actions” Mechanism of the Ottawa Charter for Health Promotion: A Scoping Review
Authors: Saadati Fatemeh , Nadrian Haidar , Golkar Mostafa Hosseini , Taghdisi Mohammad-Hossein , Gilani Neda , Ghassab-Abdollahi Nafiseh , Fathifar Zahra 
Published: January 2022

Objective To determine 1) the indexes/indicators used for evaluating the “strengthening community actions” mechanism of the Ottawa Charter for Health Promotion and 2) to extract the characteristics and key components of the indexes/indicators using a scoping review. Data Source:In May 2020, the search was conducted across three databases: Medline (via PubMed), Embase, and Scopus. Inclusion and Exclusion Criteria: All primary studies relating to development, identification, and measurement of health promotion indices/indicators associated to the “strengthening community actions” were included. The review articles were excluded. Data Extraction The data were extracted to a data-charting form that was developed by the research team. Two authors reviewed the extracted data. Data Synthesis To summarize and report the data, a descriptive numerical analysis and a narrative descriptive synthesizing approach were used. Results In total, 93 study articles were included. A majority of studies (82%) were conducted in developed countries. Different types of recognized indices were categorized into seven groups: social cohesion (n = 3), community capacity (n = 1), community participation (n = 7), social capital (n = 6), social network (n = 3), social support (n = 1), and others (n = 5). Conclusions Having a collection of “strengthening community actions” indices/indicators in hand, health policymakers and health promotion specialists might be able to do their best in considering, selecting, and applying the most appropriate indices/indicators while evaluating community health promotion interventions in different settings.