bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Relative Unimportance of Aesthetic Value in Evaluating Visual Arts
Authors: Kulka Tomas
Published: April 2021

Contrary to the received view according to which the value of works of art consists exclusively or primarily in their aesthetic value I argue that the importance of aesthetic value has been grossly overrated. In earlier publications I have shown that the assumption stipulating that the value of artworks consists exclusively in their aesthetic value is demonstrably wrong. I have suggested a conceptual distinction between the aesthetic and the artistic value arguing that when it comes to evaluation the artistic value, which reflects the significance of innovations exemplified by the work, is no less important than the aesthetic value. Here I take the argument a step further by suggesting that the aesthetic value is considerably less important than the artistic value. To show this I draw attention to a neglected aspect of art evaluation, namely to the monetary value of artworks. Although there is no necessary connection between monetary value of works of art (determined by supply and demand) and their aesthetic value or their artistic value, it can nevertheless tell us something important not only about the overall value of works of art (as art) but also about the relative importance of the two component values. I show that the enormous differences between monetary values of different artworks cannot be accounted for by the corresponding differences in their aesthetic value but can be explained by the differences in their artistic value.
Hypothesis Generation During Foodborne-Illness Outbreak Investigations
Authors: White Alice E , Smith Kirk E , Booth Hillary , Medus Carlota , Tauxe Robert V , Gieraltowski Laura , Scallan Walter Elaine
Published: April 2021

Hypothesis generation is a critical, but challenging, step in a foodborne outbreak investigation. The pathogens that contaminate food have many diverse reservoirs, resulting in seemingly limitless potential vehicles. Identifying a vehicle is particularly challenging for clusters detected through national pathogen-specific surveillance, because cases can be geographically dispersed and lack an obvious epidemiologic link. Moreover, state and local health departments could have limited resources to dedicate to cluster and outbreak investigations. These challenges underscore the importance of hypothesis generation during an outbreak investigation. In this review, we present a framework for hypothesis generation focusing on 3 primary sources of information, typically used in combination: 1) known sources of the pathogen causing illness; 2) person, place, and time characteristics of cases associated with the outbreak (descriptive data); and 3) case exposure assessment. Hypothesis generation can narrow the list of potential food vehicles and focus subsequent epidemiologic, laboratory, environmental, and traceback efforts, ensuring that time and resources are used more efficiently and increasing the likelihood of rapidly and conclusively implicating the contaminated food vehicle.
Highly diverse and highly successful: invasive Australian acacias have not experienced genetic bottlenecks globally
Authors: Vicente Sara , Máguas Cristina , Richardson David M , Trindade Helena , Wilson John R U , Le Roux Johannes J
Published: April 2021

Background and Aims

Invasive species may undergo rapid evolution despite very limited standing genetic diversity. This so-called genetic paradox of biological invasions assumes that an invasive species has experienced (and survived) a genetic bottleneck and then underwent local adaptation in the new range. In this study, we test how often Australian acacias (genus Acacia), one of the world’s most problematic invasive tree groups, have experienced genetic bottlenecks and inbreeding.

Methods

We collated genetic data from 51 different genetic studies on Acacia species to compare genetic diversity between native and invasive populations. These studies analysed 37 different Acacia species, with genetic data from the invasive ranges of 11 species, and data from the native range for 36 species (14 of these 36 species are known to be invasive somewhere in the world, and the other 22 are not known to be invasive).

Key Results

Levels of genetic diversity are similar in native and invasive populations, and there is little evidence of invasive populations being extensively inbred. Levels of genetic diversity in native range populations also did not differ significantly between species that have and that do not have invasive populations.

Conclusion

We attribute our findings to the impressive movement, introduction effort and human usage of Australian acacias around the world.
Functional rice with tandemly repeated Cbl-b ubiquitin ligase inhibitory pentapeptide prevents denervation-induced muscle atrophy in vivo
Authors: Akama Kazuhito , Shimajiri Yasuka , Kainou Kumiko , Iwasaki Ryota , Nakao Reiko , Nikawa Takeshi , Nishikawa Akio
Published: April 2021

Ubiquitin ligase Casitas B-lineage lymphoma-b (Cbl-b) play a critical role in nonloading-mediated skeletal muscle atrophy: Cbl-b ubiquitinates insulin receptor substrate-1 (IRS-1), leading to its degradation and a resulting loss in muscle mass. We reported that intramuscular injection of a pentapeptide, DGpYMP, which acts as a mimic of the phosphorylation site in IRS-1, significantly inhibited denervation-induced skeletal muscle loss. In order to explore the possibility of the prevention of muscle atrophy by diet therapy, we examined the effects of oral administration of transgenic rice containing Cblin (Cbl-b inhibitor) peptide (DGYMP) on denervation-induced muscle mass loss in frogs. We generated transgenic rice seeds in which 15 repeats of Cblin peptides with a WQ spacer were inserted into the rice storage protein glutelin. A diet of the transgenic rice seeds had significant inhibitory effects on denervation-induced atrophy of the leg skeletal muscles in frogs, compared with those receiving a diet of wild-type rice.
Cloprostenol, a synthetic analog of prostaglandin F2α induces functional regression in cultured luteal cells of felids
Authors: Hryciuk Michał M , Jewgenow Katarina , Braun Beate C
Published: April 2021

In the present study, we investigated the effect of the synthetic analog of prostaglandin F2α (PGF2α)—cloprostenol—on cultured steroidogenic luteal cells of selected felid species over a 2-day culture period. The changes induced by cloprostenol were measured based on progesterone concentration and mRNA expression analysis of selected genes. Cloprostenol significantly reduced concentration of progesterone in cell culture medium of small luteal cells isolated from domestic cat corpora lutea (CL) at the development/maintenance stage (P < 0.05), but did not influence progesterone production in cultured cells from the regression stage. A decrease or complete silencing of progesterone production was also measured in cultured luteal cells of African lion (formation stage) and Javan leopard (development/maintenance stage). Gene-expression analysis by real-time PCR revealed that treatment with cloprostenol did not have an influence on expression of selected genes coding for enzymes of steroidogenesis (StAR, HSD3B, CYP11A1) or prostaglandin synthesis (PTGS2, PGES), nor did it effect hormone receptors (AR, ESR1, PGR, PTGER2), an anti-oxidative enzyme (SOD1) or factors of cell apoptosis (FAS, CASP3, TNFRSF1B, BCL2) over the studied period. Significant changes were measured only for expressions of luteinizing hormone (P < 0.05), prolactin (P < 0.05) and PGF2α receptors (P < 0.005) (LHCGR, PRLR, and PTGFR). The obtained results confirm that PGF2α/cloprostenol is a luteolytic agent in CL of felids and its impact on progesterone production depends on the developmental stage of the CL. Cloprostenol short-term treatment on luteal cells was associated only with functional but not structural changes related to luteal regression.
Widespread Positive Direct and Indirect Effects of Regular Physical Activity on the Developing Functional Connectome in Early Adolescence
Authors: Brooks Skylar J , Parks Sean M , Stamoulis Catherine
Published: April 2021

Adolescence is a period of profound but incompletely understood changes in the brain’s neural circuitry (the connectome), which is vulnerable to risk factors such as unhealthy weight, but may be protected by positive factors such as regular physical activity. In 5955 children (median age = 120 months; 50.86% females) from the Adolescent Brain Cognitive Development (ABCD) cohort, we investigated direct and indirect (through impact on body mass index [BMI]) effects of physical activity on resting-state networks, the backbone of the functional connectome that ubiquitously affects cognitive function. We estimated significant positive effects of regular physical activity on network connectivity, efficiency, robustness and stability (P ≤ 0.01), and on local topologies of attention, somatomotor, frontoparietal, limbic, and default-mode networks (P < 0.05), which support extensive processes, from memory and executive control to emotional processing. In contrast, we estimated widespread negative BMI effects in the same network properties and brain regions (P < 0.05). Additional mediation analyses suggested that physical activity could also modulate network topologies leading to better control of food intake, appetite and satiety, and ultimately lower BMI. Thus, regular physical activity may have extensive positive effects on the development of the functional connectome, and may be critical for improving the detrimental effects of unhealthy weight on cognitive health.
A Comparison of Less Invasive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Diagnostic Specimens in Nursing Home Residents—Arkansas, June–August 2020
Authors: Gable Paige , Huang Jennifer Y , Gilbert Sarah E , Bollinger Susan , Lyons Amanda K , Sabour Sarah , Surie Diya , Biedron Caitlin , Haney Tafarra , Beshearse Elizabeth , Gregory Christopher J , Seely Kathryn A , Clemmons Nakia S , Patil Naveen , Kothari Atul , Gulley Trent , Garner Kelley , Anderson Karen , Thornburg Natalie J , Halpin Alison L , McDonald L Clifford , Kutty Preeta K , Brown Allison C ,   Centers for Disease Control and Prevention COVID-19 Laboratory Task Force, Ramachandran Sumathi , Hughes Holly , Bohannon Caitlin , Sexton D Joseph , Lonsway David , Bhatnagar Amelia , Breaker Erin , Adamczyk Michelle , McAllister Gillian A , Campbell Davina , Houston Hollis , Perry-Dow K Allison , Reese Natashia , Paulick Ashley , Spicer Lori , Harcourt Jennifer L , Coughlin Melissa M , Tamin Azaibi , Whitaker Brett , Stumpf Megan M , Mills Lisa , Ata Ur Rasheed Mohammad
Published: April 2021

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing remains essential for early identification and clinical management of cases. We compared the diagnostic performance of 3 specimen types for characterizing SARS-CoV-2 in infected nursing home residents.

Methods

A convenience sample of 17 residents were enrolled within 15 days of first positive SARS-CoV-2 result by real-time reverse transcription polymerase chain reaction (RT-PCR) and prospectively followed for 42 days. Anterior nasal swabs (AN), oropharyngeal swabs (OP), and saliva specimens (SA) were collected on the day of enrollment, every 3 days for the first 21 days, and then weekly for 21 days. Specimens were tested for presence of SARS-CoV-2 RNA using RT-PCR and replication-competent virus by viral culture.

Results

Comparing the 3 specimen types collected from each participant at each time point, the concordance of paired RT-PCR results ranged from 80% to 88%. After the first positive result, SA and OP were RT-PCR-positive for ≤48 days; AN were RT-PCR–positive for ≤33 days. AN had the highest percentage of RT-PCR–positive results (21/26 [81%]) when collected ≤10 days of participants’ first positive result. Eleven specimens were positive by viral culture: 9 AN collected ≤19 days following first positive result and 2 OP collected ≤5 days following first positive result.

Conclusions

AN, OP, and SA were effective methods for repeated testing in this population. More AN than OP were positive by viral culture. SA and OP remained RT-PCR-positive longer than AN, which could lead to unnecessary interventions if RT-PCR detection occurred after viral shedding has likely ceased.
Estimating Population-Level Effects of the Acellular Pertussis Vaccine Using Routinely Collected Immunization Data
Authors: Rane Madhura S , Halloran M Elizabeth
Published: April 2021

Background

Measuring and reporting the different population-level effects of the acellular pertussis vaccine on pertussis disease in addition to direct effects can increase the cost-effectiveness of a vaccine.

Methods

We conducted a retrospective cohort study of children born between 1 January 2008 and 31 December 2017, in King County, Washington, who were enrolled in the Washington State Immunization Information System. Diphtheria, tetanus toxoids, and acellular pertussis (DTaP) vaccination data from in the Washington State Immunization Information System was linked with pertussis case data from Public Health Seattle and King County. Census-level vaccination coverage was estimated as proportion of age-appropriately vaccinated children residing in it. Direct vaccine effectiveness was estimated by comparing pertussis risk in fully vaccinated and undervaccinated children. Population-level vaccine effectiveness (VE) measures were estimated by comparing pertussis risk in census tracts in the highest quartile for vaccination coverage with that in the lowest quartile.

Results

For direct protection, estimated VE was 76% (95% confidence interval, 63%–84%) in low-vaccination-coverage clusters, and it decreased to 47% (13%–68%) in high-coverage clusters, after adjustment for potential confounders. The estimated indirect VE was 45.0% (95% confidence interval, 1%–70%), the total VE 93.9% (91%–96%), and the overall VE 42.2% (19%–60%).

Conclusion

Our findings suggest that DTaP vaccination provided direct as well as indirect protection in the highly immunized King County, Washington. Routine DTaP vaccination programs may have the potential to provide not only protection for vaccinated individuals but also for the undervaccinated individuals living in the same area.
Cis-epistasis at the LPA locus and risk of cardiovascular diseases
Authors: Zeng Lingyao , Moser Sylvain , Mirza-Schreiber Nazanin , Lamina Claudia , Coassin Stefan , Nelson Christopher P , Annilo Tarmo , Franzén Oscar , Kleber Marcus E , Mack Salome , Andlauer Till F M , Jiang Beibei , Stiller Barbara , Li Ling , Willenborg Christina , Munz Matthias , Kessler Thorsten , Kastrati Adnan , Laugwitz Karl-Ludwig , Erdmann Jeanette , Moebus Susanne , Nöthen Markus M , Peters Annette , Strauch Konstantin , Müller-Nurasyid Martina , Gieger Christian , Meitinger Thomas , Steinhagen-Thiessen Elisabeth , März Winfried , Metspalu Andres , Björkegren Johan L M , Samani Nilesh J , Kronenberg Florian , Müller-Myhsok Bertram , Schunkert Heribert
Published: April 2021

Aims

Coronary artery disease (CAD) has a strong genetic predisposition. However, despite substantial discoveries made by genome-wide association studies (GWAS), a large proportion of heritability awaits identification. Non-additive genetic effects might be responsible for part of the unaccounted genetic variance. Here, we attempted a proof-of-concept study to identify non-additive genetic effects, namely epistatic interactions, associated with CAD.

Methods and results

We tested for epistatic interactions in 10 CAD case–control studies and UK Biobank with focus on 8068 SNPs at 56 loci with known associations with CAD risk. We identified a SNP pair located in cis at the LPA locus, rs1800769 and rs9458001, to be jointly associated with risk for CAD [odds ratio (OR) = 1.37, P = 1.07 × 10−11], peripheral arterial disease (OR = 1.22, P = 2.32 × 10−4), aortic stenosis (OR = 1.47, P = 6.95 × 10−7), hepatic lipoprotein(a) (Lp(a)) transcript levels (beta = 0.39, P = 1.41 × 10−8), and Lp(a) serum levels (beta = 0.58, P = 8.7 × 10−32), while individual SNPs displayed no association. Further exploration of the LPA locus revealed a strong dependency of these associations on a rare variant, rs140570886, that was previously associated with Lp(a) levels. We confirmed increased CAD risk for heterozygous (relative OR = 1.46, P = 9.97 × 10−32) and individuals homozygous for the minor allele (relative OR = 1.77, P = 0.09) of rs140570886. Using forward model selection, we also show that epistatic interactions between rs140570886, rs9458001, and rs1800769 modulate the effects of the rs140570886 risk allele.

Conclusions

These results demonstrate the feasibility of a large-scale knowledge-based epistasis scan and provide rare evidence of an epistatic interaction in a complex human disease. We were directed to a variant (rs140570886) influencing risk through additive genetic as well as epistatic effects. In summary, this study provides deeper insights into the genetic architecture of a locus important for cardiovascular diseases.
Increasing metadata coverage of SRA BioSample entries using deep learning–based named entity recognition
Authors: Klie Adam , Tsui Brian Y , Mollah Shamim , Skola Dylan , Dow Michelle , Hsu Chun-Nan , Carter Hannah
Published: April 2021

High-quality metadata annotations for data hosted in large public repositories are essential for research reproducibility and for conducting fast, powerful and scalable meta-analyses. Currently, a majority of sequencing samples in the National Center for Biotechnology Information’s Sequence Read Archive (SRA) are missing metadata across several categories. In an effort to improve the metadata coverage of these samples, we leveraged almost 44 million attribute–value pairs from SRA BioSample to train a scalable, recurrent neural network that predicts missing metadata via named entity recognition (NER). The network was first trained to classify short text phrases according to 11 metadata categories and achieved an overall accuracy and area under the receiver operating characteristic curve of 85.2% and 0.977, respectively. We then applied our classifier to predict 11 metadata categories from the longer TITLE attribute of samples, evaluating performance on a set of samples withheld from model training. Prediction accuracies were high when extracting sample Genus/Species (94.85%), Condition/Disease (95.65%) and Strain (82.03%) from TITLEs, with lower accuracies and lack of predictions for other categories highlighting multiple issues with the current metadata annotations in BioSample. These results indicate the utility of recurrent neural networks for NER-based metadata prediction and the potential for models such as the one presented here to increase metadata coverage in BioSample while minimizing the need for manual curation.

Database URL: https://github.com/cartercompbio/PredictMEE
The Impact of Vedolizumab on COVID-19 Outcomes Among Adult IBD Patients in the SECURE-IBD Registry
Authors: Agrawal Manasi , Zhang Xian , Brenner Erica J , Ungaro Ryan C , Kappelman Michael D , Colombel Jean-Frederic
Published: April 2021

Background

The impact of immune-modifying therapies on outcomes of coronavirus disease 2019 [COVID-19] is variable. The purpose of this study was to determine the impact of vedolizumab [VDZ], a gut-selective anti-integrin, on COVID-19 outcomes in inflammatory bowel disease [IBD] patients.

Methods

Using data from the Surveillance of Coronavirus Under Research Exclusion for IBD [SECURE-IBD], an international registry of IBD patients with confirmed COVID-19, we studied the impact of VDZ on COVID-19 hospitalization and severe COVID-19 [intensive care unit stay, mechanical ventilation and/or death].

Results

Of 3647 adult patients on any IBD medication in the registry, 457 [12.5%] patients were on VDZ. On multivariable analyses using backward selection of covariates, VDZ use was not associated with hospitalization or severe COVID-19 when compared with patients on all other medications (adjusted odds ratio [aOR] 0.87; 95% confidence interval [CI] 0.71, 1.1 and aOR 0.95; 95% CI 0.53, 1.73, respectively). On comparing VDZ monotherapy to anti-tumour necrosis factor [anti-TNF] monotherapy, the odds for hospitalization, but not severe COVID-19, were higher [aOR CI 1.39; 95% CI 1.001, 1.90 and aOR 2.92; 95% CI 0.98, 8.71, respectively]. In an exploratory analysis, VDZ monotherapy, compared to anti-TNF monotherapy, was associated with new-onset gastrointestinal symptoms at the time of COVID-19, especially among patients whose IBD was in remission.

Conclusions

COVID-19 outcomes among IBD patients on VDZ are comparable to those on all other therapies. Hospitalization, but not severe COVID-19, is more likely with VDZ monotherapy than with anti-TNF monotherapy. Overall, VDZ appears to be safe in IBD patients with COVID-19.
Predictors of reoperation and mortality after complete atrioventricular septal defect repair
Authors: Fong Laura S , Betts Kim , Ayer Julian , Andrews David , Nicholson Ian A , Winlaw David S , Orr Yishay ,   the Australian CAVSD study group, Alphonso Nelson , Bell Douglas , Hu Thomas , Konstantinov Igor E , Radford Dorothy
Published: April 2021

OBJECTIVES

Previous studies investigating risk factors associated with reoperation or mortality after repair of complete atrioventricular septal defect (CAVSD) often have not included sizeable cohorts undergoing modified single-patch repair. Both double patch and modified single-patch techniques have been widely used in Australia since the 1990s. Using a large multi-institutional cohort, we aimed to identify risk factors associated with reoperation or mortality following CAVSD repair.

METHODS

Between January 1990 and December 2015, a total of 829 patients underwent biventricular surgical repair of CAVSD in Australia at 4 centres. Patients with associated tetralogy of Fallot and other conotruncal abnormalities were excluded. Demographic details, postoperative outcomes including reoperation and survival, and associated risk factors were analysed.

RESULTS

Fifty-six patients (6.8%) required early reoperation (≤30 days) for significant left atrioventricular valve regurgitation or residual septal defects. Freedom from reoperation at 10, 15 and 20 years was 82.7%, 81.1% and 77%, respectively. Patients without Down syndrome and moderate left atrioventricular valve regurgitation on postoperative echocardiogram were found to be independent risk factors for reoperation. Operative mortality was 3.3%. Overall survival at 10, 15 and 20 years was 91.7%, 90.7% and 88.7%, respectively. Prior pulmonary artery banding was a predictor for mortality, while later surgical era (2010–2015) was associated with a reduction in mortality risk.

CONCLUSIONS

Improved survival in the contemporary era is in keeping with improvements in surgical management and higher rates of primary CAVSD repair over time. The presence of residual moderate left atrioventricular valve regurgitation on postoperative echocardiography is an important factor associated with reoperation and close surveillance is essential to allow timely reintervention. Primary CAVSD repair at age <3 months should be preferenced to palliation with pulmonary artery banding due to the association of pulmonary artery banding with mortality in the long-term.
Intermediate-term neurodevelopmental outcomes and quality of life after arterial switch operation beyond early neonatal period
Authors: Ramanan Sowmya , Sundaram Soumya , Gopalakrishnan Arun , Anija D V , Sandhya P , Jose Dhiya Susan , Baruah Sudip Dutta , Menon Sabarinath , Dharan Baiju S
Published: April 2021

OBJECTIVES

The study objective was to evaluate the cardiac, neurodevelopmental, psycho-social and health-related quality of life (HRQOL) outcomes of children who underwent an arterial switch operation (ASO).

METHODS

Children who underwent ASO were evaluated on follow-up at 3–5 years with cardiovascular, neurodevelopmental and HRQOL assessment using validated tools. Children with developmental delay, attention-deficit hyperactivity disorder, autism spectrum disorder, neuromotor and speech and language impairment were considered to have neurodevelopmental disorder (NDD). The impact of socioeconomic status (Kuppuswamy classification), perioperative cardiac, nutritional and psycho-social factors on outcomes was analysed.

RESULTS

There were 61 (89.7%) survivors at a mean follow-up of 50.9 ± 7.6 months. The median age at surgery was 41 days (22–74.5). One-third of patients had growth restriction. Two children had residual cardiovascular lesions requiring intervention. The mean HRQOL score was >90 in all scales of the Paediatric Quality of Life Inventory™ 3.0 Cardiac Module. Neurological abnormalities were seen in 19 patients (31.1%) of whom 17 (27.9%) patients had NDD and 12 had developmental delay. Speech and language impairment, attention-deficit hyperactivity disorder, and neuromotor impairment were found in 16.4%, 3.3% and 6.7% patients, respectively. On multivariate analysis, increasing time to lactate normalization and low socioeconomic status were associated with developmental delay after ASO.

CONCLUSIONS

While intermediate-term cardiac outcomes and HRQOL after ASO were fairly satisfactory, NDD was identified in one-fourth of these children. Increasing time to lactate normalization after ASO and low socioeconomic status were associated with suboptimal intermediate neurodevelopment outcomes after ASO.
Serial right ventricular assessment in patients with hypoplastic left heart syndrome: a multiparametric cardiovascular magnetic resonance study
Authors: Sobh Mohamed , Freitag-Wolf Sandra , Scheewe Jens , Kanngiesser Luca M , Uebing Anselm S , Gabbert Dominik D , Voges Inga
Published: April 2021

OBJECTIVES

The aim of this study was to assess single right ventricular (RV) function in a large cohort of hypoplastic left heart syndrome (HLHS) patients after the completion of total cavopulmonary connection by analysing serial cardiovascular magnetic resonance (CMR) studies.

METHODS

CMR studies from 95 HLHS patients were analysed. RV end-diastolic and end-systolic volumes (RVEDV, RVESV), ejection fraction (RVEF) and long-axis strain (LAS) were measured from cine images.

RESULTS

All 95 patients had at least 2 CMR scans and 35 patients had 3 CMR scans. The median age (first quartile–third quartile) at the 3 examinations was 4.2 (3.3–6.1), 9.4 (6.1–11.4) and 14.6 (11.8–16.8) years. RV indexed volumes (RVEDVi and RVESVi) increased from first to the second and from the first and second examination to the third examination in patients with >10 years of age (P < 0.05). There was a slight decrease in RVEF and LAS throughout the examinations, but this was not statistically significant. Correlations were found between RVEF and LAS (r = −0.23; P < 0.01). Both RVEF and LAS correlated with RVEDVi and RVESVi (r = −0.17 to 0.43; P < 0.05).

CONCLUSIONS

Serial assessment of CMR studies in HLHS patients after total cavopulmonary connection completion demonstrate an increase in indexed RV volumes in older HLHS patients but only mild reduction in RVEF and LAS. The correlation of indexed RV volumes with RVEF and LAS together with the significant increase in RV volumes over time suggests that indexed RV volumes might be superior to RV functional markers to monitor the RV in HLHS patients.
Morphological alterations, activity, mRNA fold changes, and aging changes before and after orthodontic force application in young and adult human-derived periodontal ligament cells
Authors: Mohanakumar Aravind , Vijay Geethu L , Vijayaraghavan Nandakumar , Rajendran Rahul S , Chandran Madhav B , Thulasidharan Midhun U , Damodaran Deepak R , Sreekumar Chandrima , Krishnan Vinod
Published: April 2021

Background

The response of periodontal ligament cells (PDLC) from adult subjects in comparison to those obtained from younger ones to mechanical forces has been a matter of interest recently because of induced senescent changes. This study evaluated and compared cell surface changes and activity, integrin beta 1, and β-actin mRNA fold changes as well as klotho protein secretion capabilities of PDLC from young and adult donors before and after subjecting to orthodontic forces.

Methods

A total of 40 subjects with bimaxillary dentoalveolar protrusion requiring extraction of first premolars for orthodontic treatment were selected and divided into two groups. Force ranging from 80 to 90 g was applied to maxillary first premolars and extraction was carried out at two different time periods—pre-treatment (control group) and 28 days after force application (experimental group). Periodontal ligament was obtained, and cell surface changes and activity were observed with atomic force microscopy (AFM) and fluorescent tagging. mRNA fold change of integrin beta-1 and β-actin mRNA, as well as beta-galactosidase assay, was performed, and levels of klotho protein were evaluated.

Results

AFM nanoindentation and fluorescent tagging indicated increased surface morphological changes in younger cells compared to adult ones. We observed a decrease in integrin beta 1 but an increase in β-actin mRNA levels in PDLC obtained from younger subjects compared to adults, while an increase was observed in SA-β-GAL from adult cells. The level of klotho protein was lower in adult cells in comparison to younger ones.

Limitations

Large sample studies are required to find out a variation in aging characteristics between young and adult PDLC.

Conclusions

The study observed significant differences between PDLC obtained from younger and adult subjects in response to orthodontic force application.
Contingent valuation of landowner demand for forest amenities: application in Andalusia, Spain
Authors: Oviedo José L , Campos Pablo , Caparrós Alejandro
Published: April 2021

We applied discrete choice contingent valuation to the amenities consumed by non-industrial private forest owners in Andalusia (Spain) in a survey of 765 landowners. The landowners’ median willingness to accept compensation from an alternative investment for giving up land amenity consumption is EUR 387.8 per hectare yearly. The preferred model shows diminishing marginal values of amenity consumption with property size, negative effects of eucalyptus and Aleppo pine presence and positive effects of distance to urban centres. We discuss the performance of the question formats and models employed and recommend the single-bounded format in this valuation context.
Effects of environmental factors on sensitivity of Cryptococcus neoformans to fluconazole and amphotericin B
Authors: Carlson Tyler , Lupinacci Emily , Moseley Katie , Chandrasekaran Srikripa
Published: April 2021

Cryptococcus neoformans is a leading cause of fungal meningitis in immunocompromized populations. Amphotericin B (AMB) and fluconazole (FLC) are common anticryptococcal agents. AMB treatment leads to severe side-effects. In contrast, FLC-based therapy is relatively safe, although C. neoformans often develops resistance to this drug. C. neoformans must adapt to the challenging environment of the human host. Environmental effects on potency of AMB and FLC and development of drug resistance remain poorly characterized. Here, the effects of nutrients, temperature and antioxidants on susceptibility of C. neoformans towards FLC and AMB were investigated. Limited nutrients led to a decrease and an increase of sensitivity towards FLC and AMB, respectively. Co-treatment with various antioxidants also demonstrated reciprocal effects on susceptibility towards FLC and AMB. In contrast, elevated temperature increased the efficacy of both drugs, although the effect on FLC was more drastic as compared to that of AMB. In addition, temperatures of 37°C and above prevented development of FLC resistance. Our study pointed to a critical role of the environment on susceptibility towards AMB and FLC and revealed reciprocal effects towards these antifungal drugs, reflecting contrasting modes of action of AMB and FLC.
Screening of probiotic candidates in a simulated piglet small intestine in vitro model
Authors: Hansen L H B , Cieplak T , Nielsen B , Zhang Y , Lauridsen C , Canibe N
Published: April 2021

The CoMiniGut in vitro model mimicking the small intestine of piglets was used to evaluate four probiotic strains for their potential as a preventive measure against development of diarrhea in weaned pigs. In the in vitro system, piglet digesta was inoculated with pathogenic enterotoxigenic Escherichia coli F4 (ETEC F4), and the short-chain fatty acid profile and the gut microbiota composition were assessed. A total of four probiotic strains were evaluated: Enterococcus faecium (CHCC 10669), Lactobacillus rhamnosus (CHCC 11994), Bifidobacterium breve (CHCC 15268) and Faecalibacterium prausnitzii (CHCC 28556). The significant differences observed in metabolite concetration and bacterial enumeration were attributed to variation in inoculating material or pathogen challenge rather than probiotic treatment. Probiotic administration influenced the microbiota composition to a small extend. Learnings from the present study indicate that the experimental setup, including incubation time and choice of inoculating material, should be chosen with care.
Independent and Joint Associations Between Leisure Time Physical Activity and Strength Activities With Mortality Outcomes in Older Adults At least 65 Years of Age: A Prospective Cohort Study
Authors: Nie Jing , Haberstroh Michelle , Acosta Tania , Huang Wentao , Wang Yafeng , Barengo Noël C
Published: April 2021

Scientific evidence regarding the combined effect of both aerobic leisure-time physical activity (LTPA) and muscle-strengthening activities on all-cause, cardiovascular disease (CVD), or cancer mortality in older adults is scant. The aim of the study was to investigate the associations between recommended physical activity and mortality in adults 65 years or older. This prospective cohort study used data from the National Health Interview Surveys from 1997 to 2013 linked with mortality files through December 31, 2015 (n = 89 962). The main outcomes included all-cause, CVD, and cancer mortality. The main exposure variables were aerobic LTPA and guideline-concordant strength training during leisure time. Cox regression models were used to calculate the hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs). Muscle-strengthening activity at least twice per week were associated with lower hazards of all-cause mortality (HR 0.92; 95% CI 0.88–0.96), CVD mortality (HR 0.90; 95% CI 0.81–0.99), and cancer mortality (HR 0.87; 95% CI 0.79–0.96). Those who reached the recommended weekly amount of LTPA had a lower hazard of all-cause mortality by 35% (HR 0.66; 95% CI 0.63–0.67), the hazard of CVD by 38% (HR 0.62; 95% CI 0.58–0.67), and cancer mortality by 22% (HR 0.78; 95% CI 0.73–0.84). The hazard of death among those who were physically active in both leisure time and engaged in muscle-strengthening activities was 0.57 (95% CI 0.54–0.60) for all-cause mortality, 0.53 (95% CI 0.47–0.61) for CVD mortality, and 0.66 (95% CI 0.58–0.75) for cancer mortality. Thus, engaging in muscle-strengthening activity at least 2 times/week may provide additional benefits among physically active older adults.
Lower Risk for Dementia Following Adult Tetanus, Diphtheria, and Pertussis (Tdap) Vaccination
Authors: Scherrer Jeffrey F , Salas Joanne , Wiemken Timothy L , Jacobs Christine , Morley John E , Hoft Daniel F
Published: April 2021

Background

Adult vaccinations may reduce risk for dementia. However, it has not been established whether tetanus, diphtheria, pertussis (Tdap) vaccination is associated with incident dementia.

Methods

Hypotheses were tested in a Veterans Health Affairs (VHA) cohort and replicated in a MarketScan medical claims cohort. Patients were at least 65 years of age and free of dementia for 2 years prior to index date. Patients either had or did not have a Tdap vaccination by the start of either of the 2 index periods (2011 or 2012). Follow-up continued through 2018. Controls had no Tdap vaccination for the duration of follow-up. Confounding was controlled using entropy balancing. Competing risk (VHA) and Cox proportional hazard (MarketScan) models estimated the association between Tdap vaccination and incident dementia in all patients and age subgroups (65–69, 70–74, and ≥75 years).

Results

VHA patients were, on average, 75.6 (SD ± 7.5) years of age, 4% female, and 91.2% were White. MarketScan patients were 69.8 (SD ± 5.6) years of age, on average and 65.4% were female. After controlling for confounding, patients with, compared to without, Tdap vaccination had a significantly lower risk for dementia in both cohorts (VHA: hazard ratio [HR] = 0.58; 95% confidence interval [CI]:0.54–0.63 and MarketScan: HR = 0.58; 95% CI:0.48–0.70).

Conclusions

Tdap vaccination was associated with a 42% lower dementia risk in 2 cohorts with different clinical and sociodemographic characteristics. Several vaccine types are linked to decreased dementia risk, suggesting that these associations are due to nonspecific effects on inflammation rather than vaccine-induced pathogen-specific protective effects.
Geomagnetic semblance and dipolar–multipolar transition in top-heavy double-diffusive geodynamo models
Authors: Tassin Théo , Gastine Thomas , Fournier Alexandre
Published: April 2021

Convection in the liquid outer core of the Earth is driven by thermal and chemical perturbations. The main purpose of this study is to examine the impact of double-diffusive convection on magnetic field generation by means of 3-D global geodynamo models, in the so-called ‘top-heavy’ regime of double-diffusive convection, when both thermal and compositional background gradients are destabilizing. Using a linear eigensolver, we begin by confirming that, compared to the standard single-diffusive configuration, the onset of convection is facilitated by the addition of a second buoyancy source. We next carry out a systematic parameter survey by performing 79 numerical dynamo simulations. We show that a good agreement between simulated magnetic fields and the geomagnetic field can be attained for any partitioning of the convective input power between its thermal and chemical components. On the contrary, the transition between dipole-dominated and multipolar dynamos is found to strongly depend on the nature of the buoyancy forcing. Classical parameters expected to govern this transition, such as the local Rossby number—a proxy of the ratio of inertial to Coriolis forces—or the degree of equatorial symmetry of the flow, fail to capture the dipole breakdown. A scale-dependent analysis of the force balance instead reveals that the transition occurs when the ratio of inertial to Lorentz forces at the dominant length scale reaches 0.5, regardless of the partitioning of the buoyancy power. The ratio of integrated kinetic to magnetic energy Ek/Em provides a reasonable proxy of this force ratio. Given that Ek/Em ≈ 10−4 − 10−3 in the Earth’s core, the geodynamo is expected to operate far from the dipole–multipole transition. It hence appears that the occurrence of geomagnetic reversals is unlikely related to dramatic and punctual changes of the amplitude of inertial forces in the Earth’s core, and that another mechanism must be sought.
Cross-ancestry genome-wide association studies identified heterogeneous loci associated with differences of allele frequency and regulome tagging between participants of European descent and other ancestry groups from the UK Biobank
Authors: De Lillo Antonella , D'Antona Salvatore , Pathak Gita A , Wendt Frank R , De Angelis Flavio , Fuciarelli Maria , Polimanti Renato
Published: April 2021

To investigate cross-ancestry genetics of complex traits, we conducted a phenome-wide analysis of loci with heterogeneous effects across African, Admixed-American, Central/South Asian, East Asian, European and Middle Eastern participants of the UK Biobank (N = 441 331). Testing 843 phenotypes, we identified 82 independent genomic regions mapping variants showing genome-wide significant (GWS) associations (P < 5 × 10−8) in the trans-ancestry meta-analysis and GWS heterogeneity among the ancestry-specific effects. These included (i) loci with GWS association in one ancestry and concordant but heterogeneous effects among the other ancestries and (ii) loci with a GWS association in one ancestry group and an experiment-wide significant discordant effect (P < 6.1 × 10−4) in at least another ancestry. Since the trans-ancestry GWS associations were mostly driven by the European ancestry sample size, we investigated the differences of the allele frequency (ΔAF) and linkage disequilibrium regulome tagging (ΔLD) between European populations and the other ancestries. Within loci with concordant effects, the degree of heterogeneity was associated with European–Middle Eastern ΔAF (P = 9.04 × 10−6) and ΔLD of European populations with respect to African, Admixed-American and Central/South Asian groups (P = 8.21 × 10−4, P = 7.17 × 10−4 and P = 2.16 × 10−3, respectively). Within loci with discordant effects, ΔAF and ΔLD of European populations with respect to African and Central/South Asian ancestries were associated with the degree of heterogeneity (ΔAF: P = 7.69 × 10−3 and P = 5.31 × 10−3, ΔLD: P = 0.016 and P = 2.65 × 10−4, respectively). Considering the traits associated with cross-ancestry heterogeneous loci, we observed enrichments for blood biomarkers (P = 5.7 × 10−35) and physical appearance (P = 1.38 × 10−4). This suggests that these specific phenotypic classes may present considerable cross-ancestry heterogeneity owing to large allele frequency and LD variation among worldwide populations.
Comparative analysis of zooplankton diversities and compositions estimated from complement DNA and genomic DNA amplicons, metatranscriptomics, and morphological identifications
Authors: Machida Ryuji J , Kurihara Haruko , Nakajima Ryota , Sakamaki Takashi , Lin Ya-Ying , Furusawa Kazushi
Published: April 2021

Community-based diversity analyses, such as metabarcoding, are increasingly popular in the field of metazoan zooplankton community ecology. However, some of the methodological uncertainties remain, such as the potential inflation of diversity estimates resulting from contamination by pseudogene sequences. Furthermore, primer affinity to specific taxonomic groups might skew community composition and structure during PCR. In this study, we estimated OTU (operational taxonomic unit) richness, Shannon’s H’, and the phylum-level community composition of samples from a coastal zooplankton community using four approaches: complement DNA (cDNA) and genomic DNA (gDNA) mitochondrial COI (Cytochrome oxidase subunit I) gene amplicon, metatranscriptome sequencing, and morphological identification. Results of mismatch distribution demonstrated that 90% is good threshold percentage to differentiate intra- and inter-species. Moderate level of correlations appeared upon comparing the species/OTU richness estimated from the different methods. Results strongly indicated that diversity inflation occurred in the samples amplified from gDNA because of mitochondrial pseudogene contamination (overall, gDNA produced two times more richness compared with cDNA amplicons). The unique community compositions observed in the PCR-based methods indicated that taxonomic amplification bias had occurred during the PCR. Therefore, it is recommended that PCR-free approaches be used whenever resolving community structure represents an essential aspect of the analysis.
A pooled analysis of pacemaker implantation after Perceval sutureless aortic valve replacement
Authors: Moscarelli Marco , Santarpino Giuseppe , Athanasiou Thanos , Mastroroberto Pasquale , Fattouch Khalil , Nasso Giuseppe , Speziale Giuseppe
Published: April 2021

OBJECTIVES

We performed a literature meta-analysis to estimate the rate of pacemaker implantation after Perceval sutureless aortic valve replacement.

METHODS

Pertinent articles were identified from the PubMed, Google Scholar, Ovid MEDLINE and Ovid EMBASE databases. Eligible studies reported the de novo incidence of postoperative pacemaker implantation after Perceval valve surgery. Among 394 articles retrieved, 26 studies including 9492 patients met the inclusion criteria.

RESULTS

The pooled event rate for postoperative pacemaker implantation was 7% [95% confidence interval (CI) 6–9%]; however, significant heterogeneity was observed across studies. In a sub-analysis, there was no difference between the rates of pacemaker implantation calculated from multicentre and registry studies (8 studies, 6845 patients; 7%, 95% CI 5–10%) and single-centre studies (18 studies, 2647 patients; 7%, 95% CI 5–9%; P = 0.75). Implantation rates were similar in high-volume studies (16 studies, 9121 patients; 7%, 95% CI 5–8%) than in low-volume studies (10 studies, 371 patients; pooled rate: 7%, 95% CI 4–14%; P = 0.5). Postoperative pacemaker implantation rates tended to decrease over time.

CONCLUSIONS

With a pooled event rate of 7%, postoperative pacemaker implantation remains an important limitation of Perceval sutureless valve surgery, although we observed a degree of variability across included studies. The resultant findings provide a useful estimate for physicians and patients and can serve as a benchmark for future comparative studies.

PROSPERO registration number

CRD42020188397.
An ex vivo evaluation of two different suture techniques for the Ozaki aortic neocuspidization procedure
Authors: Saisho Hiroyuki , Scharfschwerdt Michael , Schaller Tim , Reil Jan Christian , Ensminger Stephan , Fujita Buntaro , Aboud Anas
Published: April 2021

OBJECTIVES

We investigated the Ozaki procedure using a single interrupted suture technique (SST) and compared this with the standard continuous suture technique (CST) with regard to hydrodynamic valve performance. In addition, both techniques were compared with the native aortic valve (NAV).

METHODS

Effective orifice area, mean pressure gradient and leakage volume were evaluated in the NAV as well as after an Ozaki procedure using SST or CST in fresh swine aortic roots using a mock circulation loop. The NAV, SST and CST were evaluated under 4 defined hydrodynamic conditions.

RESULTS

Both suture techniques resulted in a similar effective orifice area under all conditions [for stroke volume of 70 ml: SST: 1.50 (1.35–1.87) vs CST: 1.57 (1.41–1.72) cm2, P = 0.8] and there were no significant differences between both suture techniques and the NAV (P > 0.05). Regarding mean pressure gradient, the Ozaki procedure with SST and CST showed no significant differences [7.23 (5.53–8.91) vs 7.04 (6.65–7.60) mmHg, P = 0.72] and there was no significant difference between both suture techniques and the NAV (P > 0.1). In leakage volume, there was no significant difference between SST and CST [4.49 (3.91–4.99) vs CST: 4.23 (3.58–4.87) ml/stroke, P = 0.34].

CONCLUSIONS

The Ozaki procedure with SST performed similarly to that with CST with regard to hydrodynamic performance. Our results suggest that the Ozaki procedure can be performed with SST instead of CST, which may be useful in patients with limited surgical exposure, such as a small annulus.