bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased nitric oxide metabolites in exhaled breath condensate after exposure to tobacco smoke
Authors: Balint B , Donnelly L E , Hanazawa T , Kharitonov S A , Barnes P J 
Published: July 2021

BACKGROUNDCigarette smoking reduces the level of exhaled nitric oxide (NO) in healthy subjects, although the mechanism is unclear. NO is a highly reactive molecule which can be oxidised or complexed with other biomolecules, depending on the microenvironment. The stable oxidation end products of NO metabolism are nitrite and nitrate. This study investigated the effect of smoking on NO metabolites in exhaled breath condensate.METHODSFifteen healthy current smokers were recruited together with 14 healthy non-smokers. Measurement of exhaled NO, lung function, and collection of exhaled breath condensate were performed. Nitrite, nitrite + nitrate, S-nitrosothiols, and nitrotyrosine levels were measured. The effect of inhaling two cigarettes in smokers was also evaluated. The mean level of exhaled NO in smokers was significantly lower than in non-smokers (4.3 (0.3) ppb v 5.5 (0.5) ppb, p<0.05).RESULTSThere was no difference in the levels of nitrite, nitrite + nitrate, S-nitrosothiols, and nitrotyrosine in the exhaled breath condensate at the baseline visit between smokers and non-smokers. After smoking, nitrite + nitrate levels were significantly but transiently increased (from 20.2 (2.8) μM to 29.8 (3.4) μM, p<0.05). There was no significant change in the levels of exhaled NO, nitrite, S-nitrosothiols, or nitrotyrosine 30 and 90 minutes after smoking.CONCLUSIONSThese findings suggest that acute smoking can increase the level of nitrate, but not nitrite, S-nitrosothiols, or nitrotyrosine in breath condensate. The deleterious effect of oxidant radicals induced by smoking may contribute to the epithelial damage of airways seen in smokers.
Prevalence of untreated asthma in a population sample of 6000 older adults in Bristol, UK
Authors: Dow L , Fowler L , Phelps L , Waters K , Coggon D , Kinmonth A L , Holgate S T 
Published: July 2021

BACKGROUNDA study was undertaken to estimate the prevalence of untreated asthma in older adults.METHODSA cross sectional population based survey of 6000 men and women aged 65 years and over was performed in 21 general practices in north Bristol, south west England. The main outcome measure was untreated asthma as defined by a two stage process comprising a respiratory questionnaire (symptoms suggestive of asthma or doctor diagnosed asthma not receiving respiratory treatment) followed by lung function tests (significant reversibility following bronchodilators or corticosteroids and/or significant within day variability in peak expiratory flow).RESULTS4792 of the 6000 participants (80%) completed the respiratory questionnaire and, of those not receiving respiratory treatment, 55 reported a previous doctor diagnosis of asthma and a further 696 had symptoms suggestive of asthma. Lung function testing in 280 of 501 randomly selected individuals from these groups resulted in 38 being defined as having asthma and an estimated population prevalence for untreated asthma of 2.4% (95% CI 1.6% to 3.6%) in men and 1.2% (95% CI 0.7% to 2.1%) in women. Most subjects (84%) with untreated asthma had moderate or severe disease. Untreated asthma was most common in individuals with doctor diagnosed asthma (21%) and those with breathlessness or wheeze (13–20%).CONCLUSIONUntreated asthma in the elderly is a common and important problem. Opportunistic use of appropriate lung function tests in older people with a history of doctor diagnosed asthma or wheeze or breathlessness at rest could identify untreated asthmatics who might benefit from treatment.
Fibrosing alveolitis in patients with rheumatoid arthritis as assessed by high resolution computed tomography, chest radiography, and pulmonary function tests
Authors: Dawson J K , Fewins H E , Desmond J , Lynch M P , Graham D R 
Published: July 2021

BACKGROUNDFibrosing alveolitis (FA) is a common and serious complication of rheumatoid arthritis (RA). Before the availability of high resolution computed tomographic (HRCT) scanning, it was difficult to diagnose accurately without recourse to biopsy. Prospective studies have reported a prevalence of interstitial lung disease (ILD) of 19–44%. The term ILD used by these authors encompasses a variety of appearances on HRCT scans. This prospective study used HRCT scanning to determine the true prevalence of FA in hospital outpatients with RA, and to study associated clinical characteristics.METHODSOne hundred and fifty consecutive patients with RA were selected from a hospital outpatient department, irrespective of the presence or absence of chest disease. All underwent a detailed clinical assessment, chest HRCT scanning, and conventional chest radiography within 4 weeks of full pulmonary function tests.RESULTSSeventy percent of patients were current or reformed cigarette smokers. Twenty eight (19%) had FA, most frequently of reticular pattern, and 12 of this group (43%) also had emphysematous bullae. None of the previously suggested risk factors for developing FA were confirmed. Fifty four percent of patients with HRCT evidence of FA had bilateral basal chest crackles, 82% had a reduced carbon monoxide transfer factor (Tlco), 14% had restrictive pulmonary function tests, and 14% had bilateral chest radiographic signs of FA.CONCLUSIONSHRCT evidence of FA was present in 19% of hospital outpatients with RA. Abnormalities on chest examination or on full pulmonary function tests, even without restrictive changes or chest radiographic abnormalities, should prompt physicians to request a chest HRCT scan when investigating dyspnoea in patients with RA.
Prognostic value of CD4+ lymphocytes in pleural cavity of patients with non-small cell lung cancer
Authors: Takahashi K , Saito S , Kamamura Y , Katakawa M , Monden Y 
Published: July 2021

BACKGROUNDFor patients with non-small cell lung cancer the TNM staging system and other conventional prognostic factors fail to predict accurately the outcome of treatment and survival. This study attempts to determine the prognostic value for survival of the proportions of CD4+ lymphocytes in the pleural cavity (PLY) of patients with resectable non-small cell lung cancer.METHODSLymphocytes in the pleural cavity separated from 51 patients with non-small cell lung cancer were examined by flow cytometry to measure the proportions of CD4+ PLY. Univariate and multivariate analyses were performed to assess the association between the proportion of CD4+ PLY and survival.RESULTSThe 5 year survival rate of patients with percentage CD4+ PLY of ⩽30% was 84% whereas that of patients with %CD4+ PLY >30% was 26.9%. The difference in survival between the %CD4+ PLY ⩽30% and %CD4+ PLY >30% groups was significant (p<0.0001). The %CD4+ PLY in those who survived for 5 years was significantly lower than that in the patients who died within 5 years (p<0.0001). The difference in survival between patients with stage IA and IB lung cancer with %CD4+ PLY ⩽30% and those with %CD4+ PLY >30% was also significant (p =0.015). Multivariate analysis showed that the proportion of CD4+ PLY (hazard ratio=6.9, 95% CI 0.045 to 0.47) and nodal status (hazard ratio=22.7, 95% CI 0.006 to 1.806) are significant and independent prognostic factors for the survival of patients with lung cancer.CONCLUSIONSThe proportion of CD4+ PLY may help to select patients who are likely to have a poorer prognosis after surgery and therefore may be suitable for consideration of adjuvant treatments. These results need confirmation in a larger prospective study.
Alternative methods for assessing bronchodilator reversibility in chronic obstructive pulmonary disease
Authors: Hadcroft J , Calverley P M A 
Published: July 2021

BACKGROUNDBronchodilator reversibility testing is recommended in all patients with chronic obstructive pulmonary disease (COPD) but does not predict improvements in breathlessness or exercise performance. Two alternative ways of assessing lung mechanics—measurement of end expiratory lung volume (EELV) using the inspiratory capacity manoeuvre and application of negative expiratory pressure (NEP) during tidal breathing to detect tidal airflow limitation—do relate to the degree of breathlessness in COPD. Their usefulness as end points in bronchodilator reversibility testing has not been examined.METHODSWe studied 20 patients with clinically stable COPD (mean age 69.9 (1.5) years, 15 men, forced expiratory volume in one second (FEV1) 29.5 (1.6)% predicted) with tidal flow limitation as assessed by their maximum flow-volume loop. Spirometric parameters, slow vital capacity (SVC), inspiratory capacity (IC), and NEP were measured seated, before and after nebulised saline, and at intervals after 5 mg nebulised salbutamol and 500 μg nebulised ipratropium bromide. The patients attended twice and the treatment order was randomised.RESULTSMean FEV1, FVC, SVC, and IC were unchanged after saline but the degree of tidal flow limitation varied. FEV1improved significantly after salbutamol and ipratropium (0.11 (0.02) l and 0.09 (0.02) l, respectively) as did the other lung volumes with further significant increases after the combination. Tidal volume and mean expiratory flow increased significantly after all bronchodilators but breathlessness fell significantly only after the combination treatment. The initial NEP score was unrelated to subsequent changes in lung volume.CONCLUSIONSNEP is not an appropriate measurement of acute bronchodilator responsiveness. Changes in IC were significantly larger than those in FEV1and may be more easily detected. However, our data showed no evidence for separation of “reversible” and “irreversible” groups whatever outcome measure was adopted.
Machine learning potentials for extended systems: a perspective
Authors: Behler Jörg , Csányi Gábor 
Published: July 2021

Abstract
In the past two and a half decades machine learning potentials have evolved from a special purpose solution to a broadly applicable tool for large-scale atomistic simulations. By combining the efficiency of empirical potentials and force fields with an accuracy close to first-principles calculations they now enable computer simulations of a wide range of molecules and materials. In this perspective, we summarize the present status of these new types of models for extended systems, which are increasingly used for materials modelling. There are several approaches, but they all have in common that they exploit the locality of atomic properties in some form. Long-range interactions, most prominently electrostatic interactions, can also be included even for systems in which non-local charge transfer leads to an electronic structure that depends globally on all atomic positions. Remaining challenges and limitations of current approaches are discussed.

Graphic Abstract
Prolonged Length of Stay in the Emergency Department and Mortality in Critically Ill Elderly Patients with Infections: A Retrospective Multicenter Study
Authors: Choi Wonjin , Woo Seon Hee , Kim Dae Hee , Lee June Young , Lee Woon Jeong , Jeong Sikyoung , Cha Kyungman , Youn Chun Song , Park Sanghyun 
Published: July 2021

Background. This study aimed at investigating whether the length of stay (LOS) in the emergency department (ED) is associated with mortality in elderly patients with infections admitted to the intensive care unit (ICU). Delayed admission to the ICU may be associated with adverse clinical outcomes in elderly patients with infections. Methods. This was a retrospective study conducted with subjects over 65 years of age admitted to the ICU from 5 EDs. We recorded demographic data, clinical findings, initial laboratory results, and ED LOS. Outcomes were all-cause in-hospital mortality and hospital LOS. A multivariable regression model was applied to identify factors predictive of mortality. Results. A total of 439 patients admitted to the ICU via the ED were included in this study, 132 (30.1%) of whom died in the hospital. The median (IQR) age was 78 (73, 83) years. In multivariable analysis, a history of malignancy (OR: 3.76; 95% CI: 1.88–7.52;

p
<
0.001

), high lactate level (OR: 1.13; 95% CI: 1.01–1.27;

p
=
0.039

), and ED LOS (OR: 1.01; 95% CI: 1.00–1.02;

p
=
0.039

) were independent risk factors for all-cause in-hospital admission. Elderly patients with an ED LOS >12 hours had a longer hospital LOS (

p
=
0.018

), and those with an ED LOS > 24 hours had a longer hospital LOS and higher mortality rate (

p
=
0.044
,

p
=
0.008

). Conclusions. This study shows that prolonged ED LOS is independently associated with all-cause in-hospital mortality in elderly patients with infections requiring ICU admission. ED LOS should be considered in strategies to prevent adverse outcomes in elderly patients with infections who visit the ED.
Vein of Marshall Ethanol Infusion: Feasibility, Pitfalls, and Complications in Over 700 Patients
Authors: Kamakura Tsukasa , Derval Nicolas , Duchateau Josselin , Denis Arnaud , Nakashima Takashi , Takagi Takamitsu , Ramirez F. Daniel , André Clémentine , Krisai Philipp , Nakatani Yosuke , Tixier Romain , Chauvel Rémi , Cheniti Ghassen , Kusano Kengo , Cochet Hubert , Sacher Frédéric , Hocini Mélèze , Jaïs Pierre , Haïssaguerre Michel , Pambrun Thomas 
Published: July 2021

Background:
Vein of Marshall (VOM) ethanol infusion is a relatively new therapeutic option for atrial tachyarrhythmias. We aimed to evaluate the feasibility, pitfalls, and complications associated with this procedure in a large cohort of patients.

Methods:
Successful ethanol infusion, VOM-related lesion extent, and serious complications were evaluated in 713 consecutive patients treated with VOM ethanol infusion.

Results:

While feasible in 88.9% of cases, VOM ethanol infusion failure mainly resulted from nonidentification (6.2%), noncannulation (1.5%), or ethanol infusion in the wrong vein (1.7%). The Vieussens valve was a helpful landmark and was visible in 63.2% of cases. Multivariable analysis identified previous coronary sinus ablation as the only predictor for nonidentification. The mean area of VOM-related endocardial scarring was 10.2±5.3 cm
2
. VOM dissection (10.7%), iodine leakage (3.0%), and VOM morphology without visible branches (3.0%) were associated with smaller VOM-related scarring (5.0±3.9, 6.6±3.5, and 4.7±2.3 cm
2
, with a
P
<0.0001,
P
<0.044, and
P
<0.0001, respectively). Ethanol infusion in a wrong vein was associated with less mitral line block (72.7% versus 95.8%,
P
=0.012). A total of 14 serious complications (2.0%) occurred: 7 tamponades, of which were 6 delayed and treated with pericardiocentesis (2 of these patients had per-procedural VOM perforation), 4 strokes, 1 anaphylactic shock, 1 atrioventricular block, and 1 left appendage isolation. Only 4 of these complications occurred during the procedure.

Conclusions:
Although limited by previous coronary sinus ablation, VOM ethanol infusion is a highly feasible treatment for atrial tachyarrhythmia, with a low rate of serious complications.
Sex-Specific Associations of Genetically Predicted Circulating Lp(a) (Lipoprotein(a)) and Hepatic
LPA
Gene Expression Levels With Cardiovascular Outcomes: Mendelian Randomization and Observational Analyses
Authors: Guertin Jakie , Kaiser Yannick , Manikpurage Hasanga , Perrot Nicolas , Bourgeois Raphaëlle , Couture Christian , Wareham Nicholas J. , Bossé Yohan , Pibarot Philippe , Stroes Erik S.G. , Mathieu Patrick , Clavel Marie-Annick , Thériault Sébastien , Boekholdt S. Matthijs , Arsenault Benoit J. 
Published: July 2021

Background:
Elevated Lp(a) (Lipoprotein(a)) levels are associated with coronary artery disease (CAD), ischemic stroke (IS), and calcific aortic valve stenosis (CAVS). Studies investigating the association between Lp(a) levels and these diseases in women have yielded inconsistent results.

Methods:

To investigate the association of Lp(a) with sex-specific cardiovascular outcomes, we determined the association between genetically predicted Lp(a) levels (using 27 single nucleotide polymorphisms at the
LPA
locus) and hepatic
LPA
expression (using 80 single nucleotide polymorphisms at the
LPA
locus associated with
LPA
mRNA expression in liver samples from the Genotype-Tissue Expression dataset) on CAD, IS, and CAVS using individual participant data from the UK Biobank: 408 403 participants of European ancestry (37 102, 4283, and 2574 with prevalent CAD, IS, and CAVS, respectively). The long-term association between Lp(a) levels and incident CAD, IS, and CAVS was also investigated in European Prospective Investigation into Cancer and Nutrition-Norfolk: 18 721 participants (3964, 846, and 424 with incident CAD, IS, and CAVS, respectively).

Results:

Genetically predicted plasma Lp(a) levels were positively and similarly associated with prevalent and incident CAD and CAVS in men and women. Genetically predicted plasma Lp(a) levels were associated with prevalent and incident IS when we studied men and women pooled together, and in men only. Genetically predicted
LPA
expression levels were associated with prevalent CAD and CAVS in men and women but not with IS.

Conclusions:

Genetically predicted blood Lp(a) and hepatic
LPA
gene expression as well as serum Lp(a) levels predict the risk of CAD and CAVS in men and in women. Whether RNA interference therapies aiming at lowering Lp(a) levels could be useful in reducing cardiovascular disease risk in both men and women with high Lp(a) levels needs to be determined in large-scale cardiovascular outcomes trials.
Chance-Constrained Active Inference
Authors: van de Laar Thijs , Şenöz İsmail , Özçelikkale Ayça , Wymeersch Henk 
Published: July 2021

Abstract
Active inference (ActInf) is an emerging theory that explains perception and action in biological agents in terms of minimizing a free energy bound on Bayesian surprise. Goal-directed behavior is elicited by introducing prior beliefs on the underlying generative model. In contrast to prior beliefs, which constrain all realizations of a random variable, we propose an alternative approach through chance constraints, which allow for a (typically small) probability of constraint violation, and demonstrate how such constraints can be used as intrinsic drivers for goal-directed behavior in ActInf. We illustrate how chance-constrained ActInf weights all imposed (prior) constraints on the generative model, allowing, for example, for a trade-off between robust control and empirical chance constraint violation. Second, we interpret the proposed solution within a message passing framework. Interestingly, the message passing interpretation is not only relevant to the context of ActInf, but also provides a general-purpose approach that can account for chance constraints on graphical models. The chance constraint message updates can then be readily combined with other prederived message update rules without the need for custom derivations. The proposed chance-constrained message passing framework thus accelerates the search for workable models in general and can be used to complement message-passing formulations on generative neural models.
Retrospective Review of Multitarget Stool DNA as a Screening Test for Colorectal Cancer
Authors: Kleinschmidt Thomas K. , Clements Austin , Parker Mark A. , Scarcliff Steven D. 
Published: July 2021

Objectives To review the effectiveness of noninvasive multitarget stool DNA testing as a screening test for colorectal cancer. Methods We performed a retrospective review of patients referred to 2 high volume outpatient procedural centers for colonoscopy for positive Cologuard test. Positive findings for colorectal cancer based on pathologic findings and also advanced adenomas were recorded. Positive predictive value (PPV) was assessed. Results Of the 1585 patients evaluated and referred for colonoscopy from January 1, 2018 to November 1, 2019, for ICD-10 codes R19.5 (other fecal abnormalities) and K92.1 (melena), 84 were referred for a positive Cologuard test. Out of the 84, 6 were excluded based on family history of colon cancer in first degree relative or personal history of inflammatory bowel disease. Of the remaining 78 patients, 1 patient (1.3%) had colorectal cancer and 5 (6.4%) had advanced adenomas (>1 cm size, high grade dysplasia or villous). Postive predictive value for colorectal cancer was 1.3% and for precancerous lesions plus colorectal cancer was 7.7%. A total of 53 (68.0%) patients had either totally normal colonoscopy or hyperplastic polyps. Out of the 78 individuals in our study, 70 (89.7%) had normal findings, hyperplastic polyps, or non-advanced adenomas. Conclusions Multitarget stool DNA testing carries an unacceptably low PPV to be utilized as a screening test for colorectal cancer. The study fails to detect both adenomas and colon cancer at a higher rate than screening colonoscopy in selected studies. The advantage of being noninvasive has been noted to increase colorectal cancer screening in otherwise non-compliant Medicare patients.
COVID-19 disaster management plans for two laboratory animal facilities in South Africa
Authors: Chipangura John K , Naidoo Vinny , Coertze Nicolene , Mohr Bert 
Published: July 2021

Policies and guidelines are available for acute disasters such as earthquakes, fire and floods, however, little is available on how laboratory animal facilities should mitigate subacute disasters like the COVID-19 pandemic that imposed major restrictions on the free movement of people. As such, laboratory animal facilities had to find plausible mitigating measures to safeguard the welfare of animals in their care, to prevent animal suffering if staff could not reach the animals, albeit with limited time. The simplest approach was to stop active experiments and halt animal breeding, or to euthanize all animals. Challenges with such methods included the ethical debate regarding euthanasia of animals at the start of a pandemic and the need to perform a harm–benefit analysis while drafting the disaster plans, termination of studies at advanced stages with information loss or killing of genetically modified strains that would be difficult to replace. Two research animal facilities in South Africa addressed these challenges by implementing several changes such as allowing only essential studies to continue, maintaining small breeding colonies for essential strains, and providing staff with private transport for travelling to and from work to avoid public transport and risk of exposure to SARS-CoV-2. Engineering changes included redesigning working areas to cater for social distancing. The mitigating measures put in place by the two laboratory animal facilities were successful in ensuring the continued welfare of animals during the COVID-19 lockdown restrictions. These measures can be adopted in future pandemics that lead to restricted movement of staff. Plans de gestion en cas de catastrophes telles que le COVID-19 pour deux installations d’animaux de laboratoire en Afrique du Sud
Intelligent approach for optimal sizing in photovoltaic panel-battery system and optimizing smart grid energy
Authors: Naceur Ferdaws Ben , Salah Chokri Ben , Telmoudi Achraf Jabeur , Mahjoub Mohamed Ali 
Published: July 2021

Renewable energy plays a very important role in solving energy problems, and solar energy is one of the most important renewable sources, especially in sunny countries. This paper deals with two problems: The first one is about optimal sizing in a photovoltaic panel (PVP)-battery system, and the second consists in energy management in smart grids. To achieve the first objective, an adaptive neuro-fuzzy inference system (ANFIS) estimation algorithm is developed in order to estimate a database of instantaneous photovoltaic power. The estimated instantaneous photovoltaic power is used in an optimal algorithm to size a PVP-battery power station to supply a 1.5 kW AC load. For the second objective, a deep learning forecasting algorithm is realized to estimate the smart grid parameters so as to optimize the consumption energy. All results are checked carrying out Matlab simulation using real weather data. The simulation results give a good performance of our proposed sizing and management systems.