bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of the CFTR gene with asthma and airway mucus hypersecretion
Authors: Crespo-Lessmann Astrid , Bernal Sara , del Río Elisabeth , Rojas Ester , Martínez-Rivera Carlos , Marina Nuria , Pallarés-Sanmartín Abel , Pascual Silvia , García-Rivero Juan Luis , Padilla-Galo Alicia , Curto Elena , Cisneros Carolina , Serrano José , Baiget Montserrat , Plaza Vicente ,   Emerging Asthma Group
Published: June 2021

Introduction

Asthma with airway mucus hypersecretion is an inadequately characterized variant of asthma. While several studies have reported that hypersecreting patients may carry genetic variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, many of those studies have been questioned for their numerous limitations and contradictory results.

Objectives

(1) To determine the presence of genetic variants of theCFTRgene in patients with asthma with and without airway mucus hypersecretion. (2) To identify the clinical, inflammatory and functional characteristics of the asthma phenotype with airway mucus hypersecretion.

Method

Comparative multicentre cross-sectional descriptive study that included 100 patients with asthma (39 hypersecretors and 61 non-hypersecretors). Asthmatic hypersecretion was defined as the presence of cough productive of sputum on most days for at least 3 months in 2 successive years. The patients were tested for fractional exhaled nitric oxide, spirometry, induced sputum cell count, total immunoglobulin E (IgE), peripheral blood eosinophil count, C-reactive protein, blood fibrinogen and blood albumin and underwent a skin prick test. Asthma control and quality of life were assessed by the Asthma Control Test and Mini Asthma Quality of Life questionnaires, respectively. Blood DNA samples were collected from the patients and next-generation sequencing using a MiSeq sequencer and the Illumina platform was used for theCFTRgene analysis.

Results

Genetic differences were observed in the c.1680-870T>A polymorphism of theCFTRgene, significantly more evident in hypersecretors than in non-hypersecretors: 78.94% vs. 59.32% in the majority allele and 21.05% vs. 40.67% in the minority allele (p = 0.036). Clinically, asthma hypersecretors compared to non-hypersecretors were older (57.4 years vs. 49.4 years; p = 0.004); had greater asthma severity (58.9% vs. 23.7%; p = 0.005); experienced greater airway obstruction (FEV1/FVC% 64.3 vs. 69.5; p = 0.041); had poorer asthma control (60% vs. 29%; p = 0.021); had lower IgE levels (126.4 IU/mL vs. 407.6 IU/mL; p = 0.003); and were less likely to have a positive prick test (37.5% vs. 68.85%; p = 0.011).

Conclusion

The results suggest that patients with asthma and with mucus hypersecretion (1) may have a different phenotype and disease mechanism produced by an intronic polymorphism in theCFTRgene (NM_000492.3:c.1680-870T>A), and (2) may have a poorer clinical outcome characterized by severe disease and poorer asthma control with a non-allergic inflammatory phenotype.
An external telemetry system for recording resting heart rate variability and heart rate in free-ranging large wild mammals
Authors: Twiss Sean D. , Brannan Naomi , Shuert Courtney R. , Bishop Amanda M. , Pomeroy Patrick. P. , Moss Simon
Published: June 2021

Measures of heart rate variability (and heart rate more generally) are providing powerful insights into the physiological drivers of behaviour. Resting heart rate variability (HRV) can be used as an indicator of individual differences in temperament and reactivity to physical and psychological stress. There is increasing interest in deriving such measures from free ranging wild animals, where individuals are exposed to the natural and anthropogenic stressors of life. We describe a robust, externally mounted heart rate monitor for use in wild mammals, deployed here on wild breeding adult female grey seals (Halichoerus grypus), that delivers millisecond precise measures of inter beat intervals (IBIs), allowing computation of resting HRV parameters. Based on Firstbeat™ heart rate belts, our system allows for remote, continuous recording of IBI data from over 30 individuals simultaneously at ranges of up to 200m. We assessed the accuracy of the IBI data provided by the Firstbeat™ system using concurrent IBI data derived from in-field electrocardiogram (ECG) recordings. Bland-Altmann analyses demonstrated high correspondence between the two sets of IBI data, with a mean difference of 0.87±0.16ms. We used generalized additive mixed-effects models to examine the impact of the default Firstbeat™ software artefact correction procedure upon the generation of anomalous data (flats and stairs). Artefact correction and individual activity were major causes of flats and stairs. We used simulations and models to assess the impact of these errors on estimates of resting HRV and to inform criteria for subsampling relatively error free IBI traces. These analyses allowed us to establish stringent filtering procedures to remove traces with excessive numbers of artefacts, including flats and stairs. Even with strict criteria for removing potentially erroneous data, the abundance of data yielded by the Firstbeat™ system provides the potential to extract robust estimates of resting HRV. We discuss the advantages and limitations of our system for applications beyond the study system described here.
Dose- and time-dependent changes in viability and IL-6, CXCL8 and CCL2 production by HaCaT-cells exposed to cobalt. Effects of high and low calcium growth conditions
Authors: Klasson Maria , Lindberg Magnus , Särndahl Eva , Westberg Håkan , Bryngelsson Ing-Liss , Tuerxun Kedeye , Persson Alexander
Published: June 2021

Background

Sensitization requires exposure to an allergen with subsequent production of a “danger “signal. In the skin, keratinocytes are the main producers of these signals.

Objective

To compare dose- and time-effects of cobalt on the viability of and cytokine release from HaCaT cells cultured at low or high calcium.

Method

To model two separate states of differentiation of keratinocytes, HaCaT cells were cultured under low or high calcium conditions. HaCaT were exposed to different concentrations of cobalt chloride (10 μm to 5 mM) over time (30 minutes– 48 hours). Cell viability was measured with the Cell-Titer Blue Viability assay. Cytokine production was measured using a bead-based immunoassay and flow cytometry. Gene expression was quantified using qPCR. Data was analyzed by ANOVA and linear mixed model.

Results

Viability of the cells was dose- and time-dependent. A linear mixed statistical model showed that cobalt exposure induces increase in IL-6, CXCL8 and CCL2 production over time and whereas increase of IL-6 and a decrease of CCL2 was associated with increasing cobalt chloride concentrations. When comparing the cells incubated under high and low calcium conditions, the more differentiated cells in the high concentration were found to exert a stronger response in terms of IL-6 release.

Conclusions

Our data suggest that cobalt chloride triggered an alarm system in HaCaT cells, and proinflammatory cytokines/chemokines were secreted in a dose- and time-dependent manner. When high and low calcium incubations were compared, the difference was seen only for IL-6. These findings indicate that the effect of cobalt chloride on cell toxicity occurs throughout the living epidermis.
Heavy metals uptake by the global economic crop (Pisum sativum L.) grown in contaminated soils and its associated health risks
Authors: Galal Tarek M. , Hassan Loutfy M. , Ahmed Dalia A. , Alamri Saad A. M. , Alrumman Sulaiman A. , Eid Ebrahem M.
Published: June 2021

The aim of the present investigation was to determine the concentration of heavy metals in the different organs of Pisum sativum L. (garden pea) grown in contaminated soils in comparison to nonpolluted soils in the South Cairo and Giza provinces, Egypt, and their effect on consumers’ health. To collect soil and plant samples from two nonpolluted and two polluted farms, five quadrats, each of 1 m2, were collected per each farm and used for growth measurement and chemical analysis. The daily intake of metals (DIM) and its associated health risks (health risk index (HRI) were also assessed. The investigated heavy metals were cadmium (Cd), arsenic (As), chromium (Cr), copper (Cu), nickel (Ni), iron (Fe), manganese (Mn), zinc (Zn), silver (Ag), cobalt (Co) and vanadium (V). Significant differences in soil heavy metals, except As, between nonpolluted and polluted sites were recorded. Fresh and dry phytomass, photosynthetic pigments, fruit production, and organic and inorganic nutrients were reduced in the polluted sites, where there was a high concentration of heavy metals in the fruit. The bioaccumulation factor for all studied heavy metals exceeded 1 in the polluted sites and only Pb, Cu and Mn exceeded 1 in the nonpolluted sites. Except for Fe, the DIM of the studied heavy metals in both sites did not exceed 1 in either children or adults. However, the HRI of Pb, Cd, Fe, and Mn in the polluted plants and Pb in the nonpolluted ones exceeded 1, indicating significant potential health risks to consumers. The authors recommend not to eat garden peas grown in the polluted sites, and farmers should carefully grow heavy metals non-accumulating food crops or non-edible plants for other purposes such as animal forages.
Directly observed therapy at opioid substitution facilities using sofosbuvir/velpatasvir results in excellent SVR12 rates in PWIDs at high risk for non-adherence to DAA therapy
Authors: Schmidbauer Caroline , Schwarz Michael , Schütz Angelika , Schubert Raphael , Schwanke Cornelia , Gutic Enisa , Pirker Roxana , Lang Tobias , Reiberger Thomas , Haltmayer Hans , Gschwantler Michael
Published: June 2021

Background & aims

We evaluated the effectiveness of sofosbuvir/velpatasvir (SOF/VEL) in difficult-to-treat PWIDs with presumed high risk for non-adherence to antiviral therapy using an innovative concept involving their opioid agonist therapy (OAT) facility.

Methods

N = 221 patients (m/f: 168/53; median age: 44.7 years (IQR 16.9); HCV-genotype 3: 45.2%; cirrhosis: 33.9%) treated with SOF/VEL were included. PWIDs at high risk for non-adherence to DAA therapy (n = 122) received HCV treatment alongside OAT under the supervision of medical staff ("directly observed therapy", DOT). These patients were compared to patients with presumed excellent drug compliance, who were treated in a "standard setting" (SS) of SOF/VEL prescription at a tertiary care center (n = 99).

Results

DOT-patients (n = 122/221; 55.2%) were younger than SS-patients (median age: 41.3 vs. 53.0 years), all had psychiatric comorbidities and most had a poor socioeconomic status. 83/122 (68.0%) reported ongoing intravenous drug use. Within the DOT-group, SVR12 was achieved in 99.1% (95% CI: 95.0–100; n = 109/110) with one patient experiencing treatment failure, while n = 12/122 (9.8%) patients were excluded due to loss of follow-up (FU). 5 patients showed HCV reinfection after achieving SVR12. SS-patients achieved SVR in 96.6% (95% CI: 90.3–99.3%; n = 84/87) after exclusion of 10/99 (10.1%) patients who were lost to FU and 2 patients who died prior to SVR12 due to reasons not related to DAA therapy.

Conclusions

SOF/VEL given as DOT along with OAT in PWIDs at high risk of non-adherence to antiviral therapy including those with ongoing intravenous drug use resulted in excellent SVR rates similar to patients with presumed “excellent compliance” under standard drug intake.
Glaucoma classification based on scanning laser ophthalmoscopic images using a deep learning ensemble method
Authors: Sułot Dominika , Alonso-Caneiro David , Ksieniewicz Paweł , Krzyzanowska-Berkowska Patrycja , Iskander D. Robert
Published: June 2021

This study aimed to assess the utility of optic nerve head (onh) en-face images, captured with scanning laser ophthalmoscopy (slo) during standard optical coherence tomography (oct) imaging of the posterior segment, and demonstrate the potential of deep learning (dl) ensemble method that operates in a low data regime to differentiate glaucoma patients from healthy controls. The two groups of subjects were initially categorized based on a range of clinical tests including measurements of intraocular pressure, visual fields, oct derived retinal nerve fiber layer (rnfl) thickness and dilated stereoscopic examination of onh. 227 slo images of 227 subjects (105 glaucoma patients and 122 controls) were used. A new task-specific convolutional neural network architecture was developed for slo image-based classification. To benchmark the results of the proposed method, a range of classifiers were tested including five machine learning methods to classify glaucoma based on rnfl thickness—a well-known biomarker in glaucoma diagnostics, ensemble classifier based on inception v3 architecture, and classifiers based on features extracted from the image. The study shows that cross-validation dl ensemble based on slo images achieved a good discrimination performance with up to 0.962 of balanced accuracy, outperforming all of the other tested classifiers.
Metabolomic profiling of microbial disease etiology in community-acquired pneumonia
Authors: den Hartog Ilona , Zwep Laura B. , Vestjens Stefan M. T. , Harms Amy C. , Voorn G. Paul , de Lange Dylan W. , Bos Willem J. W. , Hankemeier Thomas , van de Garde Ewoudt M. W. , van Hasselt J. G. Coen
Published: June 2021

Diagnosis of microbial disease etiology in community-acquired pneumonia (CAP) remains challenging. We undertook a large-scale metabolomics study of serum samples in hospitalized CAP patients to determine if host-response associated metabolites can enable diagnosis of microbial etiology, with a specific focus on discrimination between the major CAP pathogen groups S. pneumoniae, atypical bacteria, and respiratory viruses. Targeted metabolomic profiling of serum samples was performed for three groups of hospitalized CAP patients with confirmed microbial etiologies: S. pneumoniae (n = 48), atypical bacteria (n = 47), or viral infections (n = 30). A wide range of 347 metabolites was targeted, including amines, acylcarnitines, organic acids, and lipids. Single discriminating metabolites were selected using Student’s T-test and their predictive performance was analyzed using logistic regression. Elastic net regression models were employed to discover metabolite signatures with predictive value for discrimination between pathogen groups. Metabolites to discriminate S. pneumoniae or viral pathogens from the other groups showed poor predictive capability, whereas discrimination of atypical pathogens from the other groups was found to be possible. Classification of atypical pathogens using elastic net regression models was associated with a predictive performance of 61% sensitivity, 86% specificity, and an AUC of 0.81. Targeted profiling of the host metabolic response revealed metabolites that can support diagnosis of microbial etiology in CAP patients with atypical bacterial pathogens compared to patients with S. pneumoniae or viral infections.
Computer-aided identification of degenerative neuromuscular diseases based on gait dynamics and ensemble decision tree classifiers
Authors: Fraiwan Luay , Hassanin Omnia
Published: June 2021

This study proposes a reliable computer-aided framework to identify gait fluctuations associated with a wide range of degenerative neuromuscular disease (DNDs) and health conditions. Investigated DNDs included amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), and Huntington’s disease (HD). We further performed a statistical and classification comparison elucidating the discriminative capability of different gait signals, including vertical ground reaction force (VGRF), stride duration, stance duration, and swing duration. Feature representation of these gait signals was based on statistical amplitude quantification using the root mean square (RMS), variance, kurtosis, and skewness metrics. We investigated various decision tree (DT) based ensemble methods such as bagging, adaptive boosting (AdaBoost), random under-sampling boosting (RUSBoost), and random subspace to tackle the challenge of multi-class classification. Experimental results showed that AdaBoost ensembling provided a 6.49%, 0.78%, 2.31%, and 2.72% prediction rate improvement for the VGRF, stride, stance, and swing signals, respectively. The proposed approach achieved the highest classification accuracy of 99.17%, sensitivity of 98.23%, and specificity of 99.43%, using the VGRF-based features and the adaptive boosting classification model. This work demonstrates the effective capability of using simple gait fluctuation analysis and machine learning approaches to detect DNDs. Computer-aided analysis of gait fluctuations provides a promising advent to enhance clinical diagnosis of DNDs.
MicroRNA characteristics in epithelial ovarian cancer
Authors: Prahm Kira Philipsen , Høgdall Claus Kim , Karlsen Mona Aarenstrup , Christensen Ib Jarle , Novotny Guy Wayne , Høgdall Estrid
Published: June 2021

The purpose of the current study was to clarify differences in microRNA expression according to clinicopathological characteristics, and to investigate if miRNA profiles could predict cytoreductive outcome in patients with FIGO stage IIIC and IV ovarian cancer. Patients enrolled in the Pelvic Mass study between 2004 and 2010, diagnosed and surgically treated for epithelial ovarian cancer, were used for investigation. MicroRNA was profiled from tumour tissue with global microRNA microarray analysis. Differences in miRNA expression profiles were analysed according to histologic subtype, FIGO stage, tumour grade, type I or II tumours and result of primary cytoreductive surgery. One microRNA, miR-130a, which was found to be associated with serous histology and advanced FIGO stage, was also validated using data from external cohorts. Another seven microRNAs (miR-34a, miR-455-3p, miR-595, miR-1301, miR-146-5p, 193a-5p, miR-939) were found to be significantly associated with the clinicopathological characteristics (p ≤ 0.001), in our data, but mere not similarly significant when tested against external cohorts. Further validation in comparable cohorts, with microRNA profiled using newest and similar methods are warranted.
A behavioural model of minority language shift: Theory and empirical evidence
Authors: Uriarte José Ramón , Sperlich Stefan
Published: June 2021

Natural languages with their speech communities tend to compete for speakers, very much like firms compete for market shares. As a result, some languages suffer a shifting pressure which might lead them to their extinction. This work studies the dynamics of language shift in the context of modern bilingual societies like the Basque Country, Ireland and Wales. They all have two official languages, linguistically distant: A, spoken by all, and B, spoken by a bilingual minority. They also have a bilingual education system that ensures a steady flow of new bilinguals. However, a decay in the use of B is observed, signalling that shift processes are at work. To investigate this apparent paradox, we use a novel approach in the literature of language competition. We build a behavioural game model with which bilinguals choose either language A or B for each interaction. Thus, they play repeatedly the game. We present a theorem predicting that under reasonable assumptions, any given population of bilinguals will converge into a linguistic convention, namely into an evolutionary stable equilibrium of the game, that always embeds a proportion of bilinguals shifting to A. We validate this result by means of an empirical version of the model, showing that the predictions fit well the observed data of street use of Basque and daily use of Irish and Welsh.
Chronic heat stress delays immune system development and alters serotonin signaling in pre-weaned dairy calves
Authors: Marrero Marcela G. , Dado-Senn Bethany , Field Sena L. , Yang Guan , Driver John P. , Laporta Jimena
Published: June 2021

Exposure to heat stress can alter the development and immune system function in dairy calves. Serotonin is an immunomodulatory biogenic amine that functions as a neurotransmitter and as a stress-response mediator. Our objectives were to characterize the patterns of serum serotonin concentrations and the pattern of serotonin-related genes expressed by immune cells of calves exposed to chronic heat stress or heat stress abatement during early life, and to explore whether these might relate to immune system development. Dairy calves were exposed to chronic heat stress (HS; n = 6) or heat stress abatement (cooling, CL; n = 6) across the prenatal (late gestation, last 46 d) and postnatal (from birth to weaning, 56 d) developmental windows. Blood samples were collected to harvest serum (weekly, from d 1 to 49), to isolate of circulating leukocyte mRNA (at 1, 21 and 42 d of age) and characterize immune cell populations by flow cytometry (at 21 and 47 d of age). Calves exposed to chronic heat stress pre- and postnatally had lower red blood cell counts and lower circulating serotonin, immunoglobulin G, and B-lymphocytes compared to CL calves. Circulating blood leukocyte mRNA expression of serotonin receptors -1A,-1F,-4and-5was greater, while heat shock protein 70 and immune-related genes (i.e.,TBX21,TLR4, andTGFβ) were lower in HS relative to CL calves. Peripheral blood leukocytes from all calves secreted serotonin and interleukin-6 afterin-vitrolipopolysaccharide stimulation. However, the HS calves produced more serotonin and less interleukin-6 than CL calves when activatedin-vitro. Together, our data suggest that providing heat stress abatement to dairy calves across prenatal and postnatal developmental windows might modulate the serotonin synthesis pathway in ways that may benefit humoral immunity against microbial pathogens.
Accounting for the spread of vaccination behavior to optimize influenza vaccination programs
Authors: Kahana Dor , Yamin Dan
Published: June 2021

Vaccination is the most efficient means of preventing influenza infection and its complications. While previous studies have considered the externalities of vaccination that arise from indirect protection against influenza infection, they have often neglected another key factor–the spread of vaccination behavior among social contacts. We modeled influenza vaccination as a socially contagious process. Our model uses a contact network that we developed based on aggregated and anonymized mobility data from the cellphone devices of ~1.8 million users in Israel. We calibrated the model to high-quality longitudinal data of weekly influenza vaccination uptake and influenza diagnoses over seven years. We demonstrate how a simple coupled-transmission model accurately captures the spatiotemporal patterns of both influenza vaccination uptake and influenza incidence. Taking the identified complex underlying dynamics of these two processes into account, our model determined the optimal timing of influenza vaccination programs. Our simulation shows that in regions where high vaccination coverage is anticipated, vaccination uptake would be more rapid. Thus, our model suggests that vaccination programs should be initiated later in the season, to mitigate the effect of waning immunity from the vaccine. Our simulations further show that optimally timed vaccination programs can substantially reduce disease transmission without increasing vaccination uptake.
Factors associated with gynaecological morbidities and treatment-seeking behaviour among adolescent girls residing in Bihar and Uttar Pradesh, India
Authors: Kumar Pradeep , Srivastava Shobhit , Chauhan Shekhar , Patel Ratna , Marbaniang Strong P. , Dhillon Preeti
Published: June 2021

Background

Gynaecological morbidities are more common than reproductive and contraceptive morbidities and constitute a substantial proportion of disease burden in women. This study aimed to examine the prevalence and factors associated with gynaecological morbidities and the treatment-seeking behaviour among adolescent girls residing in Bihar and Uttar Pradesh, India.

Methodology

The study utilized data from the Understanding the Lives of Adolescents and Young Adults (UDAYA) survey with a sample size of 14,625 adolescents girls aged 10–19 years. We defined gynaecological morbidity in dichotomous form, created from five questions on different morbidities. Further, the treatment-seeking behaviour was assessed for reported gynaecological morbidities three months prior to the survey. Univariate and bivariate analysis was used to perform analysis to carve out the preliminary results. Additionally, the study employed the heckprobit selection model, a two-equation model, to identify the determinants of outcome variables.

Results

Overall, about one-fourth (23.6%) of the adolescent girls reported suffering from gynaecological morbidities, and only one-third of them went for treatment. Non-Scheduled Caste/Scheduled Tribe (Non-SC/ST) adolescents were significantly less likely to have gynaecological morbidities (β: -0.12; CI: -0.18, -0.06) compared to SC/ST counterparts; however, they were more likely to go for the treatment (β: 0.09; CI: 0.00, 0.19). The adolescents who had 8–9 (β: 0.17; CI: 0.05, 0.29) or ten and above years of education (β: 0.21; CI: 0.09, 0.34) had a higher likelihood of going for the treatment than adolescents with no education. Moreover, adolescents who belonged to rural areas were less likely to go for the treatment of gynaecological morbidities (β: -0.09; CI: -0.17, -0.01) than urban counterparts.

Conclusion

Multi-pronged interventions are the need of the hour to raise awareness about the healthcare-seeking behaviour for gynaecological morbidities, especially in rural areas. Adolescent girls shall be prioritized as they may lack the knowledge for gynaecological morbidities, and such morbidities may go unnoticed for years. Mobile clinics may be used to disseminate appropriate knowledge among adolescents and screen asymptomatic adolescents for any possible gynaecological morbidity.
Limitations and perceived delays for diagnosis and staging of lung cancer in Portugal: A nationwide survey analysis
Authors: Barata Fernando , Fidalgo Paula , Figueiredo Sara , Tonin Fernanda S. , Duarte-Ramos Filipa
Published: June 2021

Background

We aimed to identify the perception of physicians on the limitations and delays for diagnosing, staging and treatment of lung cancer in Portugal.

Methods

Portuguese physicians were invited to participate an electronic survey (Feb-Apr-2020). Descriptive statistical analyses were performed, with categorical variables reported as absolute and relative frequencies, and continuous variables with non-normal distribution as median and interquartile range (IQR). The association between categorical variables was assessed through Pearson’s chi-square test. Mann-Whitney test was used to compare categorical and continuous variables (Stata v.15.0).

Results

Sixty-one physicians participated in the study (45 pulmonologists, 16 oncologists), with n = 26 exclusively assisting lung cancer patients. Most experts work in public hospitals (90.16%) in Lisbon (36.07%). During the last semester of 2019, responders performed a median of 85 (IQR 55–140) diagnoses of lung cancer. Factors preventing faster referral to the specialty included poor articulation between services (60.0%) and patients low economic/cultural level (44.26%). Obtaining National Drugs Authority authorization was one of the main reasons (75.41%) for delaying the begin of treatment. The cumulative lag-time from patients’ admission until treatment ranged from 42–61 days. Experts believe that the time to diagnosis could be optimized in around 11.05 days [IQR 9.61–12.50]. Most physicians (88.52%) started treatment before biomarkers results motivated by performance status deterioration (65.57%) or high tumor burden (52.46%). Clinicians exclusively assisting lung cancer cases reported fewer delays for obtaining authorization for biomarkers analysis (p = 0.023). Higher waiting times for surgery (p = 0.001), radiotherapy (p = 0.004), immunotherapy (p = 0.003) were reported by professionals from public hospitals.

Conclusions

Physicians believe that is possible to reduce delays in all stages of lung cancer diagnosis with further efforts from multidisciplinary teams and hospital administration.
The function of the south-Levantine Late Chalcolithic and Early Bronze Age basalt vessels bearing circumferential depressions: Insights from use-wear analyses
Authors: Hruby Karolina , Cendrowska Marzena , Chasan Rivka , Groman-Yaroslavski Iris , Rosenberg Danny
Published: June 2021

One of the most characteristic aspects of the Late Chalcolithic and Early Bronze Age periods in the southern Levant is the appearance of large assemblages of basalt vessels. These vessels, frequently meticulously made, appear sometimes a considerable distance from the raw material sources and are found mainly at habitation sites. While these and their prestigious value have been widely discussed in the past, their function is still obscure. In the current paper, we address their functionality through microscopic use-wear analysis. Emphasis was placed on basalt vessels with a distinct wear pattern–circumferential depressions, which appear along the perimeter of their interior bases. The documented traces were compared to results of an experimental study we conducted to characterize the effects of abrasion, grinding, and lubrication on basalt surfaces. The results of the comparative experimental study suggest that the circumferential depression was formed from a repetitive rotational activity using a narrow-ended tool. Further, it seems that two material types acted in combination as the circling device and processed material. One was hard and abrasive, such as stone, and the other was semi-resilient, such as wood or mineral powder. Water was likely used as a lubricant in the rotational process. While the actual function of the bowls bearing the circumferential depressions is not entirely clear, the use-wear analyses suggest that they may have been devices involved in craft industries, used for processing materials unrelated to food (minerals in particular). Whatever the exact function was, it clear that this use continued from the Chalcolithic through the Early Bronze Age, providing evidence for functional continuity between these two periods.
Meta-analysis comparing direct oral anticoagulants versus vitamin K antagonists in patients with left ventricular thrombus
Authors: Kido Kazuhiko , Ghaffar Yasir Abdul , Lee James C. , Bianco Christopher , Shimizu Mikiko , Shiga Tsuyoshi , Hashiguchi Masayuki
Published: June 2021

Current American College of Cardiology/American Heart Association guidelines for stroke or ST-elevation myocardial infarction recommend the use of oral vitamin K antagonists (VKAs) as a first-line anticoagulant. Although several studies have compared the use of direct oral anticoagulants (DOACs) to VKAs for left ventricular thrombus (LVT) anticoagulation therapy, they are small scale and have produced conflicting results. Thus, this meta-analysis was performed to aggregate these studies to better compare the efficacy and safety of DOACs with VKAs in patients with LVT. Cochrane Library, Google Scholar, MEDLINE, and Web of Science database searches through January 10, 2021 were performed. Eight studies evaluating stroke or systemic embolism (SSE), six studies for LVT resolution, and five studies for bleeding were included. There were no statistically significant differences in SSE (OR 0.89; 95% CI 0.46, 1.71; p = 0.73; I2 = 45%) and LVT resolution (OR 1.13; 95% CI 0.75, 1.71; p = 0.56; I2 = 1%) between DOAC and VKA (reference group) therapy. DOAC use was significantly associated with lower bleeding event rates compared to VKA use (OR 0.61; 95% CI 0.40, 0.93; p = 0.02; I2 = 0%). DOACs may be feasible alternative anticoagulants to vitamin K antagonists for LV thrombus treatment. Randomized controlled trials directly comparing DOACs with VKAs are needed.
Predictors for carotid and femoral artery intima-media thickness in a non-diabetic sleep clinic cohort
Authors: Lambeth Christopher , Perri Rita , Lee Sharon , Verma Manisha , Campbell-Rogers Nicole , Larcos George , Byth Karen , Kairaitis Kristina , Amis Terence , Wheatley John
Published: June 2021

Introduction

The impact of sleep disordered breathing (SDB) on arterial intima-media thickness (IMT), a surrogate measure for cardiovascular disease, remains uncertain, in part because of the potential for non-SDB vascular risk factor interactions. In the present study, we determined predictors for common carotid (CCA) and femoral (CFA) artery IMT in an adult, sleep clinic cohort where non-SDB vascular risk factors (particularly diabetes) were eliminated or controlled.

Methods

We recruited 296 participants for polysomnography (standard SDB severity metrics) and CCA/CFA ultrasound examinations, followed by a 12 month vascular risk factor minimisation (RFM) and continuous positive pressure (CPAP) intervention for participants with a range of SDB severity (RFM Sub-Group, n = 157; apnea hyponea index [AHI]: 14.7 (7.2–33.2), median [IQR]). Univariable and multivariable linear regression models determined independent predictors for IMT. Linear mixed effects modelling determined independent predictors for IMT change across the intervention study. P<0.05 was considered significant.

Results

Age, systolic blood pressure and waist:hip ratio were identified as non-SDB predictive factors for CCA IMT and age, weight and total cholesterol:HDL ratio for CFA IMT. No SDB severity metric emerged as an independent predictor for either CCA or CFA IMT, except in the RFM Sub-Group, where a 2-fold increase in AHI predicted a 2.4% increase in CFA IMT. Across the intervention study, CCA IMT decreased in those who lost weight, but there was no CPAP use interaction. CFA IMT, however, decreased by 12.9% (95%CI 6.8, 18.7%, p = 0.001) in those participants who both lost weight and used CPAP > = 4hours/night.

Conclusion

We conclude that SDB severity has little impact on CCA IMT values when non-SDB vascular risk factors are minimised or not present. This is the first study, however, to suggest a potential linkage between SDB severity and CFA IMT values.

Trial registration

Australian New Zealand Clinical Trials Registry, ACTRN12611000250932 and ACTRN12620000694910.
Comparative analysis of neuroinvasion by Japanese encephalitis virulent and vaccine viral strains in an in vitro model of human blood-brain barrier
Authors: Khou Cécile , Díaz-Salinas Marco Aurelio , da Costa Anaelle , Préhaud Christophe , Jeannin Patricia , Afonso Philippe V. , Vignuzzi Marco , Lafon Monique , Pardigon Nathalie
Published: June 2021

Japanese encephalitis virus (JEV) is the major cause of viral encephalitis in South East Asia. It has been suggested that, as a consequence of the inflammatory process during JEV infection, there is disruption of the blood-brain barrier (BBB) tight junctions that in turn allows the virus access to the central nervous system (CNS). However, what happens at early times of JEV contact with the BBB is poorly understood. In the present work, we evaluated the ability of both a virulent and a vaccine strain of JEV (JEV RP9 and SA14-14-2, respectively) to cross an in vitro human BBB model. Using this system, we demonstrated that both JEV RP9 and SA14-14-2 are able to cross the BBB without disrupting it at early times post viral addition. Furthermore, we find that almost 10 times more RP9 infectious particles than SA14-14 cross the model BBB, indicating this BBB model discriminates between the virulent RP9 and the vaccine SA14-14-2 strains of JEV. Beyond contributing to the understanding of early events in JEV neuroinvasion, we demonstrate this in vitro BBB model can be used as a system to study the viral determinants of JEV neuroinvasiveness and the molecular mechanisms by which this flavivirus crosses the BBB during early times of neuroinvasion.
High school science fair: Experiences of two groups of undergraduate bioscience students
Authors: Grinnell Frederick , Dalley Simon , Reisch Joan
Published: June 2021

Science fairs offer potential opportunities for students to learn first-hand about the practices of science. Over the past six years we have been carrying out voluntary and anonymous surveys with regional and national groups of high school and post high school students to learn about their high school science fair experiences regarding help received, obstacles encountered, and opinions about the value and impact of science fair. Understanding what students think about science fairs will help educators make science fairs more effective learning opportunities. In this paper, we focus on the findings with two national groups of post high school students–undergraduate research fellows (SURF students) who did research at UT Southwestern Medical Center during 2014–2019 and undergraduates biology students attending the 2019 Howard Hughes Medical Institute Science Education Alliance (SEA) summer symposium. About 25% of the students who completed surveys indicated that they had participated in high school science fair, but more than half attended high schools where science fairs were unavailable. Effectively, 6 out of every 10 students participated in science fair if available. Students who could have participated in high school science fair but chose not to do so identified not enough time and coming up with their project idea as major reasons why not. About half the SURF students favored requiring non-competitive science fair regardless whether they themselves had participated in science fair. On the other hand, less than 1 in 5 thought that competitive science fair should be required. Introduction to the scientific process and general learning were mentioned most frequently as the reasons to require non-competitive science fair; these reasons were mentioned rarely in connection with competitive science fair. Unlike the national cohort of high school students we surveyed previously, who mostly did science fair in 9th and 10th grades, SURF students participated in science fair throughout high school and were twice as likely as high school students to have carried out science fair more than once. In conclusion, our findings suggest that participation of the undergraduate bioscience majors in high school science fairs occurs far more frequently than recognized previously and provide insights into how these successful college students (gauged by the fact that they are doing summer science research) view science fairs. The findings emphasize further the importance of incentivizing rather than requiring science fair participation, especially in 9th and 10th grades, and the potential value of developing non-competitive science fairs.
Long-term medical and productivity costs of severe trauma: Results from a prospective cohort study
Authors: van der Vlegel Marjolein , Haagsma Juanita A. , Havermans Roos J. M. , de Munter Leonie , de Jongh Mariska A. C. , Polinder Suzanne
Published: June 2021

Background

Through improvements in trauma care there has been a decline in injury mortality, as more people survive severe trauma. Patients who survive severe trauma are at risk of long-term disabilities which may place a high economic burden on society. The purpose of this study was to estimate the health care and productivity costs of severe trauma patients up to 24 months after sustaining the injury. Furthermore, we investigated the impact of injury severity level on health care utilization and costs and determined predictors for health care and productivity costs.

Methods

This prospective cohort study included adult trauma patients with severe injury (ISS≥16). Data on in-hospital health care use, 24-month post-hospital health care use and productivity loss were obtained from hospital registry data and collected with the iMTA Medical Consumption and Productivity Cost Questionnaire. The questionnaires were completed 1 week and 1, 3, 6, 12 and 24 months after injury. Log-linked gamma generalized linear models were used to investigate the drivers of health care and productivity costs.

Results

In total, 174 severe injury patients were included in this study. The median age of participants was 55 years and the majority were male (66.1%). The mean hospital stay was 14.2 (SD = 13.5) days. Patients with paid employment returned to work 21 weeks after injury. In total, the mean costs per patient were €24,760 with in-hospital costs of €11,930, post-hospital costs of €7,770 and productivity costs of €8,800. Having an ISS ≥25 and lower health status were predictors of high health care costs and male sex was associated with higher productivity costs.

Conclusions

Both health care and productivity costs increased with injury severity, although large differences were observed between patients. It is important for decision-makers to consider not only in-hospital health care utilization but also the long-term consequences and associated costs related to rehabilitation and productivity loss.
End-stage kidney disease and COVID-19 in an urban safety-net hospital in Boston, Massachusetts
Authors: Kamel Mohamed Hassan , Mahmoud Hassan , Zhen Aileen , Liu Jing , Bielick Catherine G. , Mostaghim Anahita , Lin Nina , Chitalia Vipul , Ilori Titilayo , Waikar Sushrut S. , Upadhyay Ashish
Published: June 2021

Introduction

End-stage kidney disease (ESKD) patients are at a high risk for Coronavirus Disease 2019 (COVID-19). In this study, we compared characteristics and outcomes of ESKD and non-ESKD patients admitted with COVID-19 to a large safety-net hospital.

Methods

We evaluated 759 adults (45 with ESKD) hospitalized with COVID-19 in Spring of 2020. We examined clinical characteristics, laboratory measures and clinical outcomes. Logistic regression analyses were performed to investigate the associations between ESKD status and outcomes.

Results

73% of ESKD and 47% of non-ESKD patients identified as Black (p = 0.002). ESKD patients were older and had higher rates of comorbidities. Admission ferritin was approximately 6-fold higher in ESKD patients. During hospitalization, the rise in white blood cell count, lactate dehydrogenase, ferritin and C-reactive protein, and the decrease in platelet count and serum albumin were all significantly greater in ESKD patients. The in-hospital mortality was higher for ESKD [18% vs. 10%; multivariable adjusted odds ratio 1.5 (95% CI, 0.48–4.70)], but this did not reach statistical significance.

Conclusions

Among hospitalized COVID-19 patients, ESKD patients had more co-morbidities and more robust inflammatory response than non-ESKD patients. The odds ratio point estimate for death was higher in ESKD patients, but the difference did not reach statistical significance.
Governance quality indicators for organ procurement policies
Authors: Rodríguez-Arias David , Molina-Pérez Alberto , Hannikainen Ivar R. , Delgado Janet , Söchtig Benjamin , Wöhlke Sabine , Schicktanz Silke
Published: June 2021

Background

Consent policies forpost-mortemorgan procurement (OP) vary throughout Europe, and yet no studies have empirically evaluated the ethical implications of contrasting consent models. To fill this gap, we introduce a novel indicator of governance quality based on the ideal ofinformed support, and examine national differences on this measure through a quantitative survey of OP policy informedness and preferences in seven European countries.

Methods

Between 2017–2019, we conducted a convenience sample survey of students (n= 2006) in Austria (AT), Belgium (BE), Denmark (DK), Germany (DE), Greece (GR), Slovenia (SI) and Spain (ES), asking participants about their donation preferences, as well as their beliefs and views about the policy in place. From these measures, we computed indices of informedness, policy support, and fulfilment of unexpressed preferences, which we compared across countries and consent systems.

Results

Our study introduces a tool for analyzing policy governance in the context of OP. Wide variation in policy awareness was observed: Most respondents in DK, DE, AT and BE correctly identified the policy in place, while those in SI, GR and ES did not. Respondents in opt-out countries (AT, BE, ES and GR) tended to support the policy in place (with one exception, i.e., SI), whereas those in opt-in countries (DE and DK) overwhelmingly opposed it. These results reveal stark differences in governance quality across countries and consent policies: We found a preponderance of informed opposition in opt-in countries and a general tendency towards support–either informed or uninformed–in opt-out countries. We also found informed divergence in opt-in countries and a tendency for convergence–either informed or uninformed–among opt-out countries.

Conclusion

Our study offers a novel tool for analyzing governance quality and illustrates, in the context of OP, how the strengths and weaknesses of different policy implementations can be estimated and compared using quantitative survey data.
Industrialization as a source of heavy metals and antibiotics which can enhance the antibiotic resistance in wastewater, sewage sludge and river water
Authors: Hubeny Jakub , Harnisz Monika , Korzeniewska Ewa , Buta Martyna , Zieliński Wiktor , Rolbiecki Damian , Giebułtowicz Joanna , Nałęcz-Jawecki Grzegorz , Płaza Grażyna
Published: June 2021

The spread of antibiotic resistance is closely related with selective pressure in the environment. Wastewater from industrialized regions is characterized by higher concentrations of these pollutants than sewage from less industrialized areas. The aim of this study was to compare the concentrations of contaminants such as antibiotics and heavy metals (HMs), and to evaluate their impact on the spread of genes encoding resistance to antimicrobial drugs in samples of wastewater, sewage sludge and river water in two regions with different levels of industrialization. The factors exerting selective pressure, which significantly contributed to the occurrence of the examined antibiotic resistance genes (ARGs), were identified. The concentrations of selected gene copy numbers conferring resistance to four groups of antibiotics as well as class 1 and 2 integron-integrase genes were determined in the analyzed samples. The concentrations of six HMs and antibiotics corresponding to genes mediated resistance from 3 classes were determined. Based on network analysis, only some of the analyzed antibiotics correlated with ARGs, while HM levels were correlated with ARG concentrations, which can confirm the important role of HMs in promoting drug resistance. The samples from a wastewater treatment plant (WWTP) located an industrialized region were characterized by higher HM contamination and a higher number of significant correlations between the analyzed variables than the samples collected from a WWTP located in a less industrialized region. These results indicated that treated wastewater released into the natural environment can pose a continuous threat to human health by transferring ARGs, antibiotics and HMs to the environment. These findings shed light on the impact of industrialization on antibiotic resistance dissemination.