bluuebunny/crossref_metadata_2025 huggingface dataset:
Left ventricular systolic function decreases in lamin a/c cardiomyopathy wihout concomitant ventricular dilatation
Authors: Eystein Skjolsvik ES , Oyvind Haugen Lie OL , Monica Chivulescu MC , Margareth Ribe MR , Anna Isotta Castrini AIC , Thor Edvardsen TE , Kristina Hermann Haugaa KHH
Published: February 2021

Funding Acknowledgements

Type of funding sources: Foundation. Main funding source(s): This work was supported by the Norwegian Research Council [203489/030]

onbehalf

Department of Cardiology, Research group for genetic cardiac diseases and sudden cardiac death, Oslo University Hospital, Rikshospitalet, Oslo, Norwa

Background

Lamin A/C disease is an inheritable cardiomyopathy characterized by conduction abnormalities, ventricular arrhythmias and end stage heart failure with complete age-related penetrance.

Purpose

To assess left ventricular structural and functional progression in patients with lamin A/C cardiomyopathy.

Methods

We included and followed consecutive lamin A/C genotype positive patients with clinical examination and echocardiography at every visit. We evaluated progression of left- ventricular size and function by mixed model statistics.

Results

We included 101 consecutive lamin A/C genotype positive patients (age 44 [29-54] years, 39% probands, 51%female) with 576 echocardiographic exams during 4.9 (IQR 2.5-8.1) years of follow-up. LV ejection fraction (LVEF) declined from 50 ± 12% to 47 ± 13%, p < 0.001 (rate -0.5%/year). LV end diastolic volumes (LVEDV) remained stationary with no significant dilatation in the total population (136 ± 45ml to 138 ± 43ml, p = 0.60), (Figure). In the subgroup of patients >58 years, we observed a decline in LV volumes 148, SE 9 ml to 140, SE 9 ml p < 0.001 (rate -2.7 ml/year) towards end stage heart failure.

Conclusions

LVEF deteriorated, while LV size remained unchanged during 4.9 years of follow-up in patients with lamin A/C cardiomyopathy. In patients <58 years, we observed a reduction in LV volumes. These findings represent loss of LV function without the necessary compensatory dilation to preserve stroke volume indicating high risk of decompensated end stage heart failure in lamin A/C.

Abstract Figure.
Cardiac remodelling and heart failure symptoms in patients with apical hypertrophic cardiomyopathy
Authors: Rosca M , Ciuperca D , Mandes L , Trofin M , Calin A , Beladan C , Enache R , Radu DN , Jurcut R , Ginghina C , Popescu BA
Published: February 2021

Funding Acknowledgements

Type of funding sources: None.

Background

Although earlier publications suggested a more benign clinical course for patients (pts) with apical hypertrophic cardiomyopathy (ApHCM), recent studies report increased morbidity and mortality, comparable to the prognosis of other HCM variants. Moreover, information regarding cardiac remodelling and its relationship with symptoms in pts with ApHCM is scarce. The aim of our study was to assess left ventricular (LV), right ventricular (RV) and left atrial (LA) remodelling in pts with ApHCM in comparison with non-apical variants of HCM (nonApHCM), and the impact of cardiac remodelling on heart failure symptoms.

Methods

One hundred fifty-one consecutive pts with HCM (52 ± 16 yrs, 47% men) in sinus rhythm and with preserved LV ejection fraction (16 pts with ApHCM and 135 pts with nonApHCM), were prospectively enrolled. Comprehensive echocardiography was performed in all, including the measurement of maximal LV wall thickness (LVWT), RV free wall thickness (RVWT) and maximal LA volume indexed to body surface area (LAVi). Global LV strain (ɛ), RVɛ, LAɛ and end-diastolic LA strain rate (ASr) were measured using speckle-tracking echocardiography (STE). The ratio of E to average e’ was used to estimate LV filling pressure. The degree of mitral regurgitation (1/2/3) has also been assessed. Heart failure symptoms were defined according to the New York Heart Association (NYHA) classification.

Results

Forty-eight pts in nonApHCM group had intraventricular obstruction. There were no significant differences between pts with and without ApHCM regarding: age (58 ± 20 vs 52 ± 16 yrs), gender distribution, RVWT, LVɛ (-14.9 ± 2.7 vs -13.9 ± 3.5 %), RVɛ (-19.6 ± 3.6 vs -10.0 ± 5.0%), LAɛ (19.2 ± 5.8 vs 16.4 ± 7.1%)(p > 0.05 for all). Pts with ApHCM had lower values for LVWT (17.2 ± 1.9 vs 21.4 ± 5.2 mm, p = 0.002), E/e’ (12.0 ± 5.8 vs 17.6 ± 8.5, p = 0.02) and LAVi (48 ± 16 vs 61 ± 25, p = 0.03) compared to pts with nonApHCM. Pts with ApHCM had slightly better LA contractile function as assessed by ASr (-1.23 ± 0.50 vs -0.97 ± 0.49 sec-1, p = 0.05). Mitral regurgitation was more often severe in nonApHCM pts (56/42/31 vs 10/4/0, p < 0.001). There was no significant difference between the percentage of symptomatic pts (NYHA class ≥2) in ApHCM vs nonApHCM group (p = 0.3). In the ApHCM group, symptomatic pts had significantly lower ASr compared to asymptomatic pts (-0.98 ± 0.35 vs -1.61 ± 0.46 sec-1, p = 0.01).

Conclusions

Despite of lower LVWT values, less severe MR and no obstruction, pts with apical HCM have similar prevalence of heart failure symptoms, and similar LV, RV and LA dysfunction compared to pts with non-apical HCM. Symptomatic pts with apical HCM have worse LA contractile function compared to asymptomatic pts.
Pulmonary pressure-to-longitudinal strain ratio by echocardiography: a rapid surrogate to magnetic resonance for right ventricular failure assessment
Authors: Li A , Poon J WL , Ching S , Chan K , Chung TS , Yue CS , Ha S CN , Chang HC , Ng MY
Published: February 2021

Funding Acknowledgements

Type of funding sources: Public hospital(s). Main funding source(s): United Christian Hospital Ruttonjee and Tang Siu Kin Hospitals

Background

Better risk stratification in pulmonary hypertension (PH) by echocardiography (echo) to detect ventricular vascular uncoupling may act as gate-keeper for downstream management, such as MRI and expensive therapies. Studies showed modest correlation found between RV peak global longitudinal strain (RVGLS), which is afterload dependent, and right ventricular ejection fraction (RVEF)

Purpose

To test the accuracy and optimal cut-off of echo derived mean PA pressure-to-RVGLS ratio against MRI detected severe RV dysfunction (defined as RVEF< 35%), RV dilatation (defined as RVEDVi >87ml), and correlate native T1-values (nT1)

Method

Strain analyses by echo and volumetric assessment by 1.5 tesla MRI were performed in all patients. Contoured MRI short axis images provided RVEF. In a subgroup of pulmonary arterial hypertension (PAH), right heart catheterization and MRI non-contrast native T1 mapping were performed (Figure 1). Using previous study data, to identify a difference of 1.8 pressure-to-strain ratio between mild and severe PH with a variance  of 2.2 , power of 80% and a significance level of 0.05, a total of 11 participants per group were needed

Result

Thirty-one PH patients (13 female, age 60 ± 14y, 13 had PAH) were recruited prospectively. Strong correlation was demonstrated between the mean PA pressure-to-RVGLS ratio to MRI derived RVEF (r = 0.80, p < 0.01), and to catheterization derived pulmonary vascular resistance and indexed cardiac output (r = -0.80, p= 0.001; r= -0.75, p = 0.003 respectively). The cut-off value of -2.5 had best accuracy in ROC analyses (Table 1)

In PAH patients, this ratio correlated with global nT1 at basal short-axis level (r= -0.91, p = 0.004), but not at the mid short-axis level. Their basal posterior interventricular insertion regions had significantly higher nT1 than those of age-matched normal controls at the same region on the same scanner (1256 ± 217 ms vs. 932 ± 25 ms, p = 0.04)

Conclusion

In terms of detection of severe right ventricular dysfunction by echocardiography, mean PA pressure-to-RVGLS ratio performed better than RVGLS alone, and a ratio cutoff of -2.5 predicts MRI determined ventricular vascular uncoupling in pulmonary hypertension

Table 1 Echo detect MRI AUC standard error 95% CI sens (%) spec (%) p Mean PA pressure -to-RVGLS ratio RVEF < 35% 0.86 0.073 0.71-1.00 72 83 0.007 RVEDVi > 87ml 0.81 0.081 0.65-0.97 83 70 0.004 RVGLS RVEF < 35% 0.76 0.100 0.57-0.96 60 83 0.048 RVEDVi > 87ml 0.73 0.090 0.55-0.91 67 70 0.032 PA pulmonary artery; RVGLS: RV global longitudinal strain; RVEDVi: indexed RV end-diastolic volume Abstract Figure 1
Genome sequence of the oyster mushroom Pleurotus ostreatus strain PC9
Authors: Lee Yi-Yun , Vidal-Diez de Ulzurrun Guillermo , Schwarz Erich M , Stajich Jason E , Hsueh Yen-Ping
Published: February 2021

The oyster mushroom Pleurotus ostreatus is a basidiomycete commonly found in the rotten wood and it is one of the most cultivated edible mushrooms globally. Pleurotus ostreatus is also a carnivorous fungus, which can paralyze and kill nematodes within minutes. However, the molecular mechanisms of the predator–prey interactions between P. ostreatus and nematodes remain unclear. PC9 and PC15 are two model strains of P. ostreatus and the genomes of both strains have been sequenced and deposited at the Joint Genome Institute (JGI). These two monokaryotic strains exhibit dramatic differences in growth, but because PC9 grows more robustly in laboratory conditions, it has become the strain of choice for many studies. Despite the fact that PC9 is the common strain for investigation, its genome is fragmentary and incomplete relative to that of PC15. To overcome this problem, we used PacBio long reads and Illumina sequencing to assemble and polish a more integrated genome for PC9. Our PC9 genome assembly, distributed across 17 scaffolds, is highly contiguous and includes five telomere-to-telomere scaffolds, dramatically improving the genome quality. We believe that our PC9 genome resource will be useful to the fungal research community investigating various aspects of P. ostreatus biology.
Prey sensing and response in a nematode-trapping fungus is governed by the MAPK pheromone response pathway
Authors: Chen Sheng-An , Lin Hung-Che , Schroeder Frank C , Hsueh Yen-Ping
Published: February 2021

Detection of surrounding organisms in the environment plays a major role in the evolution of interspecies interactions, such as predator–prey relationships. Nematode-trapping fungi (NTF) are predators that develop specialized trap structures to capture, kill, and consume nematodes when food sources are limited. Despite the identification of various factors that induce trap morphogenesis, the mechanisms underlying the differentiation process have remained largely unclear. Here, we demonstrate that the highly conserved pheromone-response MAPK pathway is essential for sensing ascarosides, a conserved molecular signature of nemaotdes, and is required for the predatory lifestyle switch in the NTF Arthrobotrys oligospora. Gene deletion of STE7 (MAPKK) and FUS3 (MAPK) abolished nematode-induced trap morphogenesis and conidiation and impaired the growth of hyphae. The conserved transcription factor Ste12 acting downstream of the pheromone-response pathway also plays a vital role in the predation of A. oligospora. Transcriptional profiling of a ste12 mutant identified a small subset of genes with diverse functions that are Ste12 dependent and could trigger trap differentiation. Our work has revealed that A. oligospora perceives and interprets the ascarosides produced by nematodes via the conserved pheromone signaling pathway in fungi, providing molecular insights into the mechanisms of communication between a fungal predator and its nematode prey.
Repeated horizontal gene transfer of GALactose metabolism genes violates Dollo’s law of irreversible loss
Authors: Haase Max A B , Kominek Jacek , Opulente Dana A , Shen Xing-Xing , LaBella Abigail L , Zhou Xiaofan , DeVirgilio Jeremy , Hulfachor Amanda Beth , Kurtzman Cletus P , Rokas Antonis , Hittinger Chris Todd
Published: February 2021

Dollo’s law posits that evolutionary losses are irreversible, thereby narrowing the potential paths of evolutionary change. While phenotypic reversals to ancestral states have been observed, little is known about their underlying genetic causes. The genomes of budding yeasts have been shaped by extensive reductive evolution, such as reduced genome sizes and the losses of metabolic capabilities. However, the extent and mechanisms of trait reacquisition after gene loss in yeasts have not been thoroughly studied. Here, through phylogenomic analyses, we reconstructed the evolutionary history of the yeast galactose utilization pathway and observed widespread and repeated losses of the ability to utilize galactose, which occurred concurrently with the losses of GALactose (GAL) utilization genes. Unexpectedly, we detected multiple galactose-utilizing lineages that were deeply embedded within clades that underwent ancient losses of galactose utilization. We show that at least two, and possibly three, lineages reacquired the GAL pathway via yeast-to-yeast horizontal gene transfer. Our results show how trait reacquisition can occur tens of millions of years after an initial loss via horizontal gene transfer from distant relatives. These findings demonstrate that the losses of complex traits and even whole pathways are not always evolutionary dead-ends, highlighting how reversals to ancestral states can occur.
Tolerance to oxidative stress is associated with both oxidative stress response and inherent growth in a fungal wheat pathogen
Authors: Zhong Ziming , McDonald Bruce A , Palma-Guerrero Javier
Published: February 2021

Reactive oxygen species are toxic byproducts of aerobic respiration that are also important in mediating a diversity of cellular functions. Reactive oxygen species form an important component of plant defenses to inhibit microbial pathogens during pathogen–plant interactions. Tolerance to oxidative stress is likely to make a significant contribution to the viability and pathogenicity of plant pathogens, but the complex network of oxidative stress responses hinders identification of the genes contributing to this trait. Here, we employed a forward genetic approach to investigate the genetic architecture of oxidative stress tolerance in the fungal wheat pathogen Zymoseptoria tritici. We used quantitative trait locus (QTL) mapping of growth and melanization under axenic conditions in two cross-populations to identify genomic regions associated with tolerance to oxidative stress. We found that QTLs associated with growth under oxidative stress as well as inherent growth can affect oxidative stress tolerance, and we identified two uncharacterized genes in a major QTL associated with this trait. Our data suggest that melanization does not affect tolerance to oxidative stress, which differs from what was found for animal pathogens. This study provides a whole-genome perspective on the genetic basis of oxidative stress tolerance in a plant pathogen.
Links Between Inflammation, Mood, and Physical Function Among Older Adults With HIV
Authors: Derry Heather M , Johnston Carrie D , Burchett Chelsie O , Brennan-Ing Mark , Karpiak Stephen , Zhu Yuan-Shan , Siegler Eugenia L , Glesby Marshall J
Published: February 2021

Objectives

People living with human immunodeficiency virus (PLWH) treated with antiretrovirals have life spans similar to their HIV-negative peers. Yet, they experience elevated inflammation-related multimorbidity. Drawing on biopsychosocial determinants of health may inform interventions, but these links are understudied in older PLWH. We investigated cross-sectional relationships between psychosocial factors (mood, loneliness, and stigma), inflammatory markers, and age-related health outcomes among 143 PLWH aged 54–78 years.

Method

Participants provided blood samples for serum cytokine and C-reactive protein (CRP) analyses, completed surveys assessing psychosocial factors and health, and completed frailty assessments. Regression models tested relationships between key psychosocial-, inflammation, and age-related health variables, adjusting for relevant sociodemographic and clinical factors.

Results

Participants with more depressive symptoms had higher composite cytokine levels than those with fewer depressive symptoms (β = 0.22, t(126) = 2.71, p = .008). Those with higher cytokine levels were more likely to be prefrail or frail (adjusted odds ratio = 1.72, 95% confidence interval = 1.01–2.93) and reported worse physical function (β = −0.23, t(129) = −2.64, p = .009) and more cognitive complaints (β = −0.20, t(129) = −2.16, p = .03) than those with lower cytokine levels. CRP was not significantly related to these outcomes; 6-month fall history was not significantly related to inflammatory markers.

Discussion

Novel approaches are needed to manage comorbidities and maximize quality of life among older PLWH. Illustrating key expected biopsychosocial links, our findings highlight several factors (e.g., depressive symptoms, poorer physical function) that may share bidirectional relationships with chronic inflammation, a key factor driving morbidity. These links may be leveraged to modify factors that drive excessive health risk among older PLWH.
Growth and reproductive responses of the seagrass Zostera marina to sediment nutrient enrichment
Authors: Qin Le-Zheng , Suonan Zhaxi , Kim Seung Hyeon , Lee Kun-Seop
Published: February 2021

Nutrient loading into coastal sediments is increasing due to anthropogenic activity and climate change. We examined the effects of sediment nutrient enrichment on the growth and reproduction of Zostera marina by adding nitrogen (N) and phosphorus (P) fertilizers into sediments. Areal productivity and shoot density increased by ca. 60% in N and N + P enrichment plots and by ca. 20% in the P enrichment plots. Biomass and shoot height were also higher in the N and N + P enrichment plots than in the P enrichment and control plots. These results suggest that sediment N availability was more important than P availability in stimulating the vegetative growth of Z. marina . The density and morphology of reproductive shoots and seed production increased in only the N enrichment plots. The sediment N enrichment stimulated both the vegetative growth and sexual reproduction, improving the meadow resilience through both sexual and asexual mechanisms. The P enrichment slightly increased only the vegetative growth and might have limited influence on seagrass reproduction. According to these results, the alteration of the sediment nutrient regimes might shift the balance between the vegetative growth and sexual reproduction of Z. marina. These findings may have important implications for the management of seagrass meadows under fluctuations in sediment nutrients caused by anthropogenic activity and climate change.
Factors associated with the utilisation of skilled delivery services in Papua New Guinea: evidence from the 2016–2018 Demographic and Health Survey
Authors: Seidu Abdul-Aziz , Ahinkorah Bright Opoku , Agbaglo Ebenezer , Oduro Joseph Kojo , Amoah Abigail , Yaya Sanni
Published: February 2021

Background

We sought to determine the prevalence and factors associated with the use of skilled assistance during delivery in Papua New Guinea.

Methods

We analysed nationally representative data from 5210 women in Papua New Guinea using the 2016–2018 Demographic and Health survey. Both bivariate and multivariable analyses were performed. Statistical significance was set at p<0.05.

Results

The prevalence of skilled assistance during delivery was 57.6%. The richest women (adjusted OR [AOR]=3.503, 95% CI 2.477 to 4.954), working women (AOR=1.221, 95% CI 1.037 to 1.439), women with primary (AOR=1.342, 95% CI 1.099 to 1.639), secondary or higher education (AOR=2.030, 95% CI 1.529 to 2.695), women whose partners had a secondary or higher level of education (AOR=1.712, 95% CI 1.343 to 2.181], women who indicated distance was not a big problem in terms of healthcare (AOR=1.424, 95% CI 1.181 to 1.718), women who had ≥4 antenatal care (ANC) visits (AOR=10.63, 95% CI 8.608 to 13.140), women from the Islands region (AOR=1.305, 95% CI 1.045 to 1.628), those who read newspapers or magazines (AOR=1.310, 95% CI 1.027 to 1.669) and women who watched television (AOR=1.477, 95% CI 1.054 to 2.069) less than once a week had higher odds of utilising skilled attendants during delivery. On the contrary, women in the Momase region (AOR=0.543, 95% CI 0.438 to 0.672), women in rural areas (AOR=0.409, 95% CI 0.306 to 0.546), as well as women with a parity of 3 (AOR=0.666, 95% CI 0.505 to 0.878) or ≥4 (AOR=0.645, 95% CI 0.490 to 0.850) had lower odds of utilising skilled attendance during delivery.

Conclusion

There is relatively low use of skilled delivery services in Papua New Guinea. Wealth, employment status, educational level, parity and number of ANC visits, as well as access to healthcare and place of residence, influence the utilisation of skilled delivery services.
International medical electives for medical students at a German university: a secondary analysis of longitudinal data
Authors: Weigel Ralf , Wiegand Lara , Balzereit Stefanie , Galatsch Michael
Published: February 2021

Background

International medical electives (IMEs) are entry points to global health opportunities. IME uptake at German universities is unclear. We analyse 14 y of IME.

Methods

Student registry data were collected. Univariate linear regression examined relationships between enrolment year and IMEs.

Results

The median (IQR) number of IMEs of all enrolment years was 54 (32–80) and 51 (38–67)% of all students took an IME. Enrolment year significantly predicted IME frequency and the proportion of students taking IMEs.

Conclusions

Student interest in IMEs is increasing. Universities should invest more broadly in IME opportunities for student, faculty and university enrichment.
Designing and testing a blockchain application for patient identity management in healthcare
Authors: Khurshid Anjum , Holan Cole , Cowley Cody , Alexander Jeremiah , Harrell Daniel Toshio , Usman Muhammad , Desai Ishav , Bautista John Robert , Meyer Eric
Published: February 2021

Objective

Healthcare systems suffer from a lack of interoperability that creates “data silos,” causing patient linkage and data sharing problems. Blockchain technology’s unique architecture provides individuals greater control over their information and may help address some of the problems related to health data. A multidisciplinary team designed and tested a blockchain application, MediLinker, as a patient-centric identity management system.

Methods

The study used simulated data of “avatars” representing different types of patients. Thirty study participants were enrolled to visit simulated clinics, and perform various activities using MediLinker. Evaluation was based on Bouras’ criteria for patient-centric identity management and on the number of errors in entry and sharing of data by participants.

Results

Twenty-nine of the 30 participants completed all study activities. MediLinker fulfilled all of Bouras’ criteria except for one which was not testable. A majority of data errors were due to user error, such as wrong formatting and misspellings. Generally, the number of errors decreased with time. Due to COVID-19, sprint 2 was completed using “virtual” clinic visits. The number of user errors were less in virtual visits than in personal visits.

Discussion

The evaluation of MediLinker provides some evidence of the potential of a patient-centric identity management system using blockchain technology. The results showed a working system where patients have greater control over their information and can also easily provide consent for use of their data.

Conclusion

Blockchain applications for identity management hold great promise for use in healthcare but further research is needed before real-world adoption.
A Pareto-Improving Compensation Rule for Investment Treaties
Authors: Aisbett Emma , Bonnitcha Jonathan
Published: February 2021

Investment treaties grant foreign investors legal rights to compensation for losses caused by certain host state conduct. Many states are reconsidering their involvement in these treaties because they perceive the risks to outweigh the benefits. We start from the normative premise that participation in investment treaties should benefit both ‘host’ and ‘home’ states. Using a law and economics approach, we model a variety of common fact scenarios that arise in investment treaty arbitration. Our modelling demonstrates that being party to an investment treaty does not necessarily benefit a host state. The objective of mutual benefits would be achieved if investment treaties were modified to provide only the minimum protection necessary to solve time inconsistency problems for the host state and, thereby, deter opportunistic conduct. The treaties should not place wider constraints on legal and policy change. Our specific proposal is that a state should only have to compensate the investor if it breaches or modifies the domestic legal regime governing the investment and that compensation should be the lesser of the investor’s loss and the host state’s gain from the host state not having had the new legal regime in place when the investment was made.
Volatility Estimation and Forecasts Based on Price Durations
Authors: Hong Seok Young , Nolte Ingmar , Taylor Stephen J , Zhao Xiaolu
Published: February 2021

We investigate price duration variance estimators that have long been neglected in the literature. In particular, we consider simple-to-construct non-parametric duration estimators, and parametric price duration estimators using autoregressive conditional duration specifications. This paper shows (i) how price duration estimators can be used for the estimation and forecasting of the integrated variance of an underlying semi-martingale price process and (ii) how they are affected by discrete and irregular spacing of observations, market microstructure noise, and finite price jumps. Specifically, we contribute to the literature by constructing the asymptotic theory for the non-parametric estimator with and without the presence of bid/ask spread and time discreteness. Further, we provide guidance about how our estimators can best be implemented in practice by appropriately selecting a threshold parameter that defines a price duration event, or by averaging over a range of non-parametric duration estimators. We also provide simulation and forecasting evidence that price duration estimators can extract relevant information from high-frequency data better and produce more accurate forecasts than competing realized volatility and option-implied variance estimators, when considered in isolation or as part of a forecasting combination setting.
Facsimile narratives: Researching the past in the age of digital reproduction
Authors: Fafinski Mateusz
Published: February 2021

Taking a cue from the reflections and contributions made by manuscript, archival and historical studies, this paper proposes a new approach to the methodology of digital facsimiles. It asks how we research the past in the age of digital facsimiles and what are our biggest challenges and opportunities. By broadening the definition of what digital facsimiles are and re-evaluating their relationship with databases seeing databases as primarily aggregations of digital facsimiles the paper argues that the key methodological challenge lies in acknowledging the narrative within them. This can only be achieved if we incorporate the existing humanities methodologies in any data-related pursuits. The article demonstrates how notions of objective thresholds in data aggregations are in reality failures to notice and acknowledge the inherent narratives within the digital facsimiles that constitute them. At the same time, while deeply connected, digital facsimiles have to be recognised as ontologically separate from their exemplars. This influences greatly the way we research the past and a failure to recognize both the inherent narrativity and the cognitive gap will always lead to questionable results.
BRCA1-BARD1 regulates transcription through BRD4 in Xenopus nucleoplasmic extract
Authors: Barrows John K , Fullbright George , Long David T
Published: February 2021

The tumor suppressor BRCA1 is considered a master regulator of genome integrity. Although widely recognized for its DNA repair functions, BRCA1 has also been implicated in various mechanisms of chromatin remodeling and transcription regulation. However, the precise role that BRCA1 plays in these processes has been difficult to establish due to the widespread consequences of its cellular dysfunction. Here, we use nucleoplasmic extract derived from the eggs of Xenopus laevis to investigate the role of BRCA1 in a cell-free transcription system. We report that BRCA1-BARD1 suppresses transcription initiation independent of DNA damage signaling and its established role in histone H2A ubiquitination. BRCA1-BARD1 acts through a histone intermediate, altering acetylation of histone H4K8 and recruitment of the chromatin reader and oncogene regulator BRD4. Together, these results establish a functional relationship between an established (BRCA1) and emerging (BRD4) regulator of genome integrity.
The branched-chain amino acid aminotransferase TaBCAT1 modulates amino acid metabolism and positively regulates wheat rust susceptibility
Authors: Corredor-Moreno Pilar , Minter Francesca , Davey Phoebe E , Wegel Eva , Kular Baldeep , Brett Paul , Lewis Clare M , Morgan Yvie M L , Macías Pérez Luis A , Korolev Andrey V , Hill Lionel , Saunders Diane G O
Published: February 2021

Plant pathogens suppress defense responses to evade recognition and promote successful colonization. Although identifying the genes essential for pathogen ingress has traditionally relied on screening mutant populations, the post-genomic era provides an opportunity to develop novel approaches that accelerate identification. Here, RNA-seq analysis of 68 pathogen-infected bread wheat (Triticum aestivum) varieties, including three (Oakley, Solstice and Santiago) with variable levels of susceptibility, uncovered a branched-chain amino acid aminotransferase (termed TaBCAT1) as a positive regulator of wheat rust susceptibility. We show that TaBCAT1 is required for yellow and stem rust infection and likely functions in branched-chain amino acid (BCAA) metabolism, as TaBCAT1 disruption mutants had elevated BCAA levels. TaBCAT1 mutants also exhibited increased levels of salicylic acid (SA) and enhanced expression of associated defense genes, indicating that BCAA regulation, via TaBCAT1, has a key role in SA-dependent defense activation. We also identified an association between the levels of BCAAs and resistance to yellow rust infection in wheat. These findings provide insight into SA-mediated defense responses in wheat and highlight the role of BCAA metabolism in the defense response. Furthermore, TaBCAT1 could be manipulated to potentially provide resistance to two of the most economically damaging diseases of wheat worldwide.
Spatiotemporal control of miR398 biogenesis, via chromatin remodeling and kinase signaling, ensures proper ovule development
Authors: Cai Hanyang , Liu Liping , Zhang Man , Chai Mengnan , Huang Youmei , Chen Fangqian , Yan Maokai , Su Zhenxia , Henderson Ian , Palanivelu Ravishankar , Chen Xuemei , Qin Yuan
Published: February 2021

The coordinated development of sporophytic and gametophytic tissues is essential for proper ovule patterning and fertility. However, the mechanisms regulating their integrated development remain poorly understood. Here, we report that the Swi2/Snf2-Related1 (SWR1) chromatin-remodeling complex acts with the ERECTA receptor kinase-signaling pathway to control female gametophyte and integument growth in Arabidopsis thaliana by inhibiting transcription of the microRNA gene MIR398c in early-stage megagametogenesis. Moreover, pri-miR398c is transcribed in the female gametophyte but is then translocated to and processed in the ovule sporophytic tissues. Together, SWR1 and ERECTA also activate ARGONAUTE10 (AGO10) expression in the chalaza; AGO10 sequesters miR398, thereby ensuring the expression of three AGAMOUS-LIKE (AGL) genes (AGL51, AGL52, and AGL78) in the female gametophyte. In the context of sexual organ morphogenesis, these findings suggest that the spatiotemporal control of miRNA biogenesis, resulting from coordination between chromatin remodeling and cell signaling, is essential for proper ovule development in Arabidopsis.
STUDY ON A SPECIFIC TEST METHOD FOR DOSIMETRIC CHARACTERIZATION OF ULTRA-WIDE DETECTOR COMPUTED TOMOGRAPHY
Authors: Lu Heqing , Ye Xiangqun , Zhang Haowei , Sun Si
Published: February 2021

The purpose of this study was to establish a specific test method for dosimetric characterization of wide-beam computed tomography (CT). For a wide beam, the dose distribution curve and the area of the curve were obtained by using pencil-like ionization chamber, a long CT dose profiler probe, a head phantom and a body phantom. The absolute dose conversion coefficient was multiplied to obtain the total integration integral of the absolute dose distribution, and then the computed tomography dose index (CTDI) value under any wide beam condition was obtained by dividing the collimation width. It was calculated that the absolute dose conversion coefficient was 1.135 under the narrow beam of 8 mm. To a 160 mm-wide beam, the value of CTDI was 7.57 mGy/100mAs after normalized in the head 80 kV CT scanning, and it was 9.80 mGy/100mAs after normalized in the body 120 kV CT scanning. The specific test method solves the problem that the previous measurement method underestimates the CTDI value.
The Impact of Employment on Immigrant Mental Health: Results from a National Survey
Authors: Disney Lindsey
Published: February 2021

Mental illness and unemployment are both well documented in the literature as potentially having harmful and even detrimental impacts on individuals’ lives. However, less is known about the intersections of mental illness and unemployment in the U.S. immigrant population. This study examined whether unemployment is a predictor of mental illness in a sample of immigrants in the United States (N = 3,732). Data were from the National Epidemiologic Survey on Alcohol and Related Conditions, a three-wave, nationally representative dataset. Multivariate logistical regression analysis examined whether the main effects of a negative employment status were associated with a mental health diagnosis at Wave 2. Negative employment status was a significant predictor of all mental health diagnoses in the multivariate logistic regression models. The results from this study indicate that unemployment is associated with mental health problems among immigrants. This article presents discussion and implications for social work practice, policy, and research.
LAMP Detection and Identification of the Blackleg Pathogen Leptosphaeria biglobosa ‘brassicae’
Authors: Du Ran , Huang Yongju , Zhang Jing , Yang Long , Wu Mingde , Li Guo-qing
Published: February 2021

Blackleg of oilseed rape is a damaging invasive disease caused by the species complex Leptosphaeria maculans (Lm)/L. biglobosa (Lb), which is composed of at least two and seven phylogenetic subclades, respectively. Generally, Lm is more virulent than Lb, but under certain conditions, Lb can cause a significant yield loss in oilseed rape. Lb ‘brassicae’ (Lbb) has been found to be the causal agent for blackleg of oilseed rape in China, whereas Lm and Lb ‘canadensis’ (Lbc) were frequently detected in imported seeds of oilseed rape, posing a risk of spread into China. To monitor the blackleg-pathogen populations, a diagnostic tool based on loop-mediated isothermal amplification (LAMP) was developed using a 615-bp–long DNA sequence from Lbb that was derived from a randomly amplified polymorphic DNA assay. The LAMP was optimized for temperature and time, and tested for specificity and sensitivity using the DNA extracted from Lbb, Lbc, Lm, and 10 other fungi. The results showed that the optimal temperature and time were 65°C and 40 min, respectively. The LAMP primer set was specific to Lbb and highly sensitive as it detected the Lbb DNA as low as 132 fg per reaction. The LAMP assay was validated using the DNA extracted from mycelia and conidia of a well-characterized Lbb isolate, and its utility was evaluated using the DNA extracted from leaves, stems, pods, and seeds of oilseed rape. The LAMP assay developed herein will help for monitoring populations of the blackleg pathogens in China and in developing strategies for management of the blackleg disease.
Effects of Spore Density and Interaction With Heterodera glycines on Soybean Root Rot Caused by Fusarium solani and F. tricinctum
Authors: Yan Hui , Nelson Berlin
Published: February 2021

Fusarium root rot, caused by Fusarium solani and F. tricinctum, is a major soybean disease in the North Central United States. This study investigated the effects of the macroconidia density and the additive effects of soybean cyst nematode (SCN), Heterodera glycines, on the severity of Fusarium root rot. To determine the effect of spore density on severity, experiments were conducted in La Prairie silt loam soil in a greenhouse using conidial suspensions ranging from 101 to 106 macroconidia/ml soil. Root discoloration and lesion lengths on taproots increased as spore numbers increased, with significant effects of spore densities starting at 104 and 105 macroconidia/ml soil for F. solani and F. tricinctum, respectively. A nonlinear sigmoid model was fitted to root discoloration against density, whereas a linear regression model was fitted to root lesion length against density. The interaction between the nematode at different egg densities with the two Fusarium spp. at 105 macroconidia/ml soil was investigated. In the greenhouse, root discoloration and lesion length were significantly greater in plants inoculated with Fusarium spp. and H. glycines at 10 eggs/ml soil or greater, compared with Fusarium spp. alone. In field trials, coinfestation of soil with the two Fusarium spp. and H. glycines significantly increased root rot severity at an egg density of 16.7 eggs/ml soil. The results indicated that the presence of SCN can increase severity of root rot caused by F. solani and F. tricinctum and egg density in the soil is an important factor in the interaction.
Circular RNA circ_0000372 contributes to the proliferation, migration and invasion of colorectal cancer by elevating IL6 expression via sponging miR-495
Authors: Liu Xing , Qin Yixiang , Tang Xiuqi , Wang Yan , Bian Chao , Zhong Jiguang
Published: February 2021

Circular RNAs are thought to play a vital function in the progression of various cancers, including colorectal cancer (CRC). However, the biological function and mechanism of circ_0000372 in CRC are still not clear. The expression of circ_0000372 and microRNA (miR)-495 was examined by quantitative real-time PCR. Cell proliferation was evaluated using cell counting kit 8 and colony formation assays. Further, cell migration and invasion were assessed using transwell assay. Additionally, western blot analysis was used to detect the expression of proteins associated with proliferation, metastasis, Janus kinase 2 (JAK2)/signal transducers and activators of transcription (STAT3) signaling pathway and interleukin 6 (IL6). Dual-luciferase reporter assay and RNA immunoprecipitation assay were employed to verify the interaction between miR-495 and circ_0000372 or IL6. Furthermore, the effect of circ_0000372 on CRC tumor growth in vivo was explored using the mice xenograft models. Circ_0000372 was markedly upregulated in CRC, and its high expression was associated with the poor prognosis of CRC patients. Silenced circ_0000372 was able to suppress CRC cell proliferation, migration and invasion in vitro and CRC tumor growth in vivo. Bioinformatics prediction and experimental verification proposed that circ_0000372 could sponge miR-495, and miR-495 could target IL6. Besides, the JAK2/STAT3 signaling pathway activation could be regulated by circ_0000372, miR-495 and IL6. Rescue assay results confirmed that the inhibition effect of circ_0000372 knockdown on the proliferation and metastasis of CRC could be reversed by miR-495 inhibitor or IL6 overexpression. In short, we concluded that circ_0000372 promoted CRC progression by regulating the miR-495/IL6 axis, suggesting that circ_0000372 could be used as a new prognostic biomarker and therapeutic target for CRC.
Egress of non-enveloped enteric RNA viruses
Authors: Owusu Irene A. , Quaye Osbourne , Passalacqua Karla D. , Wobus Christiane E.
Published: February 2021

A long-standing paradigm in virology was that non-enveloped viruses induce cell lysis to release progeny virions. However, emerging evidence indicates that some non-enveloped viruses exit cells without inducing cell lysis, while others engage both lytic and non-lytic egress mechanisms. Enteric viruses are transmitted via the faecal–oral route and are important causes of a wide range of human infections, both gastrointestinal and extra-intestinal. Virus cellular egress, when fully understood, may be a relevant target for antiviral therapies, which could minimize the public health impact of these infections. In this review, we outline lytic and non-lytic cell egress mechanisms of non-enveloped enteric RNA viruses belonging to five families: Picornaviridae, Reoviridae, Caliciviridae, Astroviridae and Hepeviridae. We discuss factors that contribute to egress mechanisms and the relevance of these mechanisms to virion stability, infectivity and transmission. Since most data were obtained in traditional two-dimensional cell cultures, we will further attempt to place them into the context of polarized cultures and in vivo pathogenesis. Throughout the review, we highlight numerous knowledge gaps to stimulate future research into the egress mechanisms of these highly prevalent but largely understudied viruses.
Circular functional analysis of OCT data for precise identification of structural phenotypes in the eye
Authors: Ali Md. Hasnat , Wainwright Brian , Petersen Alexander , Jonnadula Ganesh B. , Aruru Meghana , Rao Harsha L. , Srinivas M. B. , Jammalamadaka S. Rao , Senthil Sirisha , Pyne Saumyadipta
Published: February 2021

Progressive optic neuropathies such as glaucoma are major causes of blindness globally. Multiple sources of subjectivity and analytical challenges are often encountered by the clinicians in the process of early diagnosis and clinical management of these diseases. In glaucoma, the structural damage is often characterized by neuroretinal rim (NRR) thinning of the optic nerve head, and other clinical parameters. Optical coherence tomography (OCT) is a popular and quantitative eye imaging platform for precise and reproducible measurement of such parameters in the clinic.

Baseline structural heterogeneity in the eyes can play a key role in the progression of optic neuropathies, and thus present challenges to clinical decision-making. To address this, large and diverse normative OCT databases with mathematically precise description of phenotypes can help with early detection and characterization of the different phenotypes that are encountered in the clinic. In this study, we generated a new large dataset of OCT generated high-resolution circular data on NRR phenotypes, along with other clinical covariates, of nearly 4,000 healthy eyes as part of a well-established clinical cohort (LVPEI-GLEAMS) of Asian Indian participants.

In this study, we (1) generated high-resolution circular OCT measurements of NRR thickness in a given eye, (2) introduced CIFU, a new computational pipeline for CIrcular FUnctional data modeling and analysis that is demonstrated using the OCT dataset, and (3) addressed the disparity of representation of the Asian Indian population in normative OCT databases. We demonstrated CIFU by unsupervised circular functional clustering of the OCT NRR data, meta-clustering to characterize the clustering output using clinical covariates, and presenting a circular visualization of the results. Upon stratification by age, we identified a healthy NRR phenotype cluster in the age group 40-49 years with predictive potential for glaucoma.
The Construction and Analysis of ceRNA Network and Immune Infiltration in Kidney Renal Clear Cell Carcinoma
Authors: Deng Lugang , Qu Zhi , Wang Peixi , Liu Nan
Published: February 2021

Background

Kidney renal clear cell carcinoma (KIRC) has the highest invasion, mortality and metastasis of the renal cell carcinomas and seriously affects patients’ quality of life. However, the composition of the immune microenvironment and regulatory mechanisms at transcriptomic level such as ceRNA of KIRC are still unclear.

Methods

We constructed a ceRNA network associated with KIRC by analyzing the long noncoding RNA (lncRNA), miRNA and mRNA expression data of 506 tumor tissue samples and 71 normal adjacent tissue samples downloaded from the Cancer Genome Atlas (TCGA) database. In addition, we estimated the proportion of 22 immune cell types in these samples through “The Cell Type Identification by Estimating Relative Subsets of RNA Transcripts”. Based on the ceRNA network and immune cells screened by univariate Cox analysis and Lasso regression, two nomograms were constructed to predict the prognosis of patients with KIRC. Receiver operating characteristic curves (ROC) and calibration curves were employed to assess the discrimination and accuracy of the nomograms. Consequently, co-expression analysis was carried out to explore the relationship between each prognostic gene in a Cox proportional hazards regression model of ceRNA and each survival-related immune cell in a Cox proportional hazards regression model of immune cell types to reveal the potential regulatory mechanism.

Results

We established a ceRNA network consisting of 12 lncRNAs, 25 miRNAs and 136 mRNAs. Two nomograms containing seven prognostic genes and two immune cells, respectively, were successfully constructed. Both ROC [Area Under Curves (AUCs) of 1, 3 and 5-year survival in the nomogram based on ceRNA network: 0.779, 0.747 and 0.772; AUCs of 1, 3 and 5-year survivals in nomogram based on immune cells: 0.603, 0.642 and 0.607] and calibration curves indicated good accuracy and clinical application value of both models. Through co-correlation analysis between ceRNA and immune cells, we found both LINC00894 and KIAA1324 were positively correlated with follicular helper T (Tfh) cells and negatively correlated with resting mast cells.

Conclusions

Based on the ceRNA network and tumor-infiltrating immune cells, we constructed two nomograms to predict the survival of KIRC patients and demonstrated their value in improving the personalized management of KIRC.
Identification of endothelial-derived proteins in plasma associated with cardiovascular risk factors
Authors: Iglesias MJ , Kruse LD , Sanchez-Rivera L , Enge L , Dusart P , Hong MG , Uhlén M , Renné T , Schwenk JM , Bergstrom G , Odeberg J , Butler LM
Published: February 2021

Endothelial cell (EC) dysfunction is a well-established response to cardiovascular disease (CVD) risk factors, such as smoking and obesity. Risk factor exposure can modify EC signalling and behaviour, leading to arterial and venous disease development. Biomarker panels to assess EC dysfunction are lacking, but could be useful for risk stratification and to monitor treatment response. Here, we used affinity proteomics to identify EC-derived proteins circulating in plasma that were associated with CVD risk factor exposure. 216 proteins, known to be expressed in ECs across vascular beds, were measured in plasma samples (n=1005) from the population-basedSwedish CArdioPulmonary bioImage Study(SCAPIS) pilot. We identified 38 EC-derived proteins that were associated with body mass index, total cholesterol, low density lipoprotein, smoking, hypertension or diabetes. Sex-specific analysis revealed female- and male-only associations were most frequently observed with BMI, or total cholesterol, respectively. We showed a relationship between individual CVD risk, calculated with the Framingham risk score, and the corresponding biomarker profiles; presenting the concept of measuring EC-derived proteins in plasma to infer vascular status.