bluuebunny/crossref_metadata_2025 huggingface dataset:
In-hospital mortality predictors in patients with non-ST-segment elevation myocardial infarction
Authors: Paula S , Santos M , Santos H , Almeida I , Figueiredo M , Almeida S , Almeida L
Published: May 2022

Funding Acknowledgements

Type of funding sources: None.

Introduction

Ischemic heart disease is a leading cause of cardiovascular mortality. Non-ST-segment elevation myocardial infarction (NSTEMI) makes up for the majority of admissions to a cardiac unit.

Purpose

identify the predictors leading to in-hospital mortality in patients presenting with NSTEMI.

Methods

Based on a multicenter retrospective study, data collected from admissions between January 2013 and January 2020. Patients without data on previous cardiovascular history or uncompleted clinical data were excluded. Patients were divided in 2 groups (G): G1 – in-hospital death due to NSTEMI; G2 – patients with NSTEMI that survived. Logistic regression was performed.

Results

7453 patients were admitted with NSTEMI, 90 patients (1.2%) died during the in-hospital stay. Regarding epidemiological and past history, G1 was older (74±11 vs 66±12, p<0.001), had higher rates of arterial hypertension (83.9% vs 72.7%, p=0.02), renal insufficiency (19.3% vs 6.1%, p<0.001) and dementia (5.3% vs 0.7%, p<0.001). G1 had more patients taking diuretics (54.9% vs 25.7%, p<0.001) previously to the hospital admission, presented more frequently with fatigue (6.0% vs 0.6%, p=0.01) and Killip-Kimball class (KKC) > 1 (51.8% vs 11.5%, p<0.001), had higher rates of elevated brain natriuretic peptide (BNP) (61.8% vs 23.8%, p<0.001), multivessel disease (74.2% vs 50.5%, p<0.001) and had worse left ventricular systolic function <30% (27.0% vs 2.4%, p<0.001).

Logist regression confirmed that patients previously taking diuretics (p=0.01, OR 1.99, CI 1.16-3.42), presenting with fatigue (p=0.01, OR 5.75, CI 1.45-22.96) and KKC > 1 (p=0.001, OR 2.66, CI 1.51-4.66) and with severe left ventricular systolic dysfunction <30% (p=0.01, OR 2.57, CI 1.21-5.46) were predictors of in-hospital death in patients presenting with NSTEMI.

Conclusion

In-hospital mortality in the setting of NSTEMI was associated with patients taking diuretics previously to the admission, fatigue and Killip-Kimball class > 1 at admission and with poorer left ventricular systolic function.
A literature review of coping strategies and health-related quality of life among patients with heart failure
Authors: Alanazi Mohammed Owayrif , Given Charles W , Deka Pallav , Lehto Rebecca , Wyatt Gwen
Published: May 2022

Aims

To identify and provide clarity on factors that influence coping and the type of coping strategies used by patients with heart failure (HF) to improve health-related quality of life (HRQoL).

Methods and results

The Arksey and O’Malley template framed this scoping review guided by the stress and coping model. Five databases were explored: PubMed, Web of Science, Cochrane, CINAHL, and PsycINFO. Keywords included HF, quality of life, coping, and influencing factors. Eligibility criteria involved patients with HF, reported on coping strategies and HRQoL, and published in English. Thirty-five studies were included (4 randomized controlled trials, 27 cross-sectional, and 4 qualitative/mixed methods). Active emotional coping (e.g. acceptance) and problem-focused (e.g. seeking social support) coping strategies were linked to better HRQoL, while avoidant emotional coping (e.g. denial) was linked to worse HRQoL. In the presence of the stressor of HF severity, key factors that influenced the types of the coping strategy included sex, age, social support, income, education, spiritual beliefs, and illness duration. However, the evidence on the effectiveness of the type of coping on HRQoL remains inadequate due to the majority of studies being cross-sectional.

Conclusion

Problem-focused and active emotional coping strategies are associated with improved HRQoL. However, their effect is inconclusive due to the lack of experimental studies. Additional predictive studies will enhance the understanding of coping among HF patients.
CHD Chromatin Remodeling Protein Diversification Yields Novel Clades and Domains Absent in Classic Model Organisms
Authors: Trujillo Joshua T. , Long Jiaxin , Aboelnour Erin , Ogas Joseph , Wisecaver Jennifer H.
Published: May 2022

Chromatin remodelers play a fundamental role in the assembly of chromatin, regulation of transcription, and DNA repair. Biochemical and functional characterizations of the CHD family of chromatin remodelers from a variety of model organisms have shown that these remodelers participate in a wide range of activities. However, because the evolutionary history of CHD homologs is unclear, it is difficult to predict which of these activities are broadly conserved and which have evolved more recently in individual eukaryotic lineages. Here, we performed a comprehensive phylogenetic analysis of 8,042 CHD homologs from 1,894 species to create a model for the evolution of this family across eukaryotes with a particular focus on the timing of duplications that gave rise to the diverse copies observed in plants, animals, and fungi. Our analysis confirms that the three major subfamilies of CHD remodelers originated in the eukaryotic last common ancestor, and subsequent losses occurred independently in different lineages. Improved taxon sampling identified several subfamilies of CHD remodelers in plants that were absent or highly divergent in the model plant Arabidopsis thaliana. Whereas the timing of CHD subfamily expansions in vertebrates corresponds to whole genome duplication events, the mechanisms underlying CHD diversification in land plants appear more complicated. Analysis of protein domains reveals that CHD remodeler diversification has been accompanied by distinct transitions in domain architecture, contributing to the functional differences observed between these remodelers. This study demonstrates the importance of proper taxon sampling when studying ancient evolutionary events to prevent misinterpretation of subsequent lineage-specific changes and provides an evolutionary framework for functional and comparative analysis of this critical chromatin remodeler family across eukaryotes.
Increase of Diversity of Mumps Virus Genotype G SH Variants Circulating Among a Highly Immunized Population: Spain, 2007–2019
Authors: Gavilán A M , Díez-Fuertes F , Sanz J C , Castellanos A M , López-Perea N , Jiménez S M , Ruiz-Sopeña C , Masa-Calles J , García-Comas L , de Ory F , Pérez-Olmeda M , Fernández-García A , Echevarría J E
Published: May 2022

MuV caused three epidemic waves in Spain since genotype G emerged in 2005, despite high vaccination coverage. SH gene sequencing according to WHO protocols allowed the identification of seven relevant variants and 88 haplotypes. While the originally imported MuVi/Sheffield.GBR/1.05/-variant prevailed during the first two waves, it was subsequently replaced by other variants originated by either local evolution or importation, according to the additional analysis of hypervariable NCRs. The time of emergence of the MRCA of each MuV variant clade was concordant with the data of the earliest sequence. The analysis of Shannon entropy showed an accumulation of variability on six particular positions as the cause of the increase on the number of circulating SH variants. Consequently, SH gene sequencing needs to be complemented with other more variable markers for mumps surveillance immediately after the emergence of a new genotype, but the subsequent emergence of new SH variants turns it unnecessary.
Waning Immunity Against Respiratory Syncytial Virus During the Coronavirus Disease 2019 Pandemic
Authors: Reicherz Frederic , Xu Rui Yang , Abu-Raya Bahaa , Majdoubi Abdelilah , Michalski Christina , Golding Liam , Stojic Aleksandra , Vineta Marina , Granoski Madison , Cieslak Zenon , Chacko Anil , Desai Neil , Sekirov Inna , Marchant David J , Lavoie Pascal M
Published: May 2022

Health jurisdictions have seen a near-disappearance of respiratory syncytial virus (RSV) during the first year of the coronavirus disease 2019 (COVID-19) pandemic. Over this corresponding period, we report a reduction in RSV antibody levels and live virus neutralization in sera from women of childbearing age and infants between May to June 2020 and February to June 2021, in British Columbia (BC), Canada. This supports that antibody immunity against RSV is relatively short-lived and that maintaining optimal antibody levels in infants requires repeated maternal viral exposure. Waning immunity may explain the interseasonal resurgence of RSV cases observed in BC and other countries.
Leveraging resources and the impact of neglected tropical disease elimination programmes: getting (much) more than what you pay for
Authors: Jones Iain , Downs Philip
Published: May 2022

Partnerships have been key to significant progress in combating neglected tropical diseases (NTDs). Collaboration between a range of partners, each bringing different skills and resources, helps reach more people in need with greater efficiency. Some partners have contributed in-kind donations, including drugs and volunteer time. When making resource allocation decisions donors need to consider the significant leverage their investment in NTD programmes can have. This commentary estimates the value of the leverage that the Ascend programme achieved. It is clear that funding from UK aid to Ascend delivered (much) more than what they paid for.
Development of a quality assurance tool for intensive care units in Lebanon during the COVID-19 pandemic
Authors: Halmin Märit , Abou Mourad Ghada , Ghneim Adam , Rady Alissar , Baker Tim , Von Schreeb Johan
Published: May 2022

Background

During the coronavirus disease (COVID-19) pandemic, low- and middle-income countries have rapidly scaled up intensive care unit (ICU) capacities. Doing this without monitoring the quality of care poses risks to patient safety and may negatively affect patient outcomes. While monitoring the quality of care is routine in high-income countries, it is not systematically implemented in most low- and middle-income countries. In this resource-scarce context, there is a paucity of feasibly implementable tools to monitor the quality of ICU care. Lebanon is an upper middle-income country that, during the autumn and winter of 2020–1, has had increasing demands for ICU beds for COVID-19. The World Health Organization has supported the Ministry of Public Health to increase ICU beds at public hospitals by 300%, but no readily available tool to monitor the quality of ICU care was available.

Objective

The objective with this study was to describe the process of rapidly developing and implementing a tool to monitor the quality of ICU care at public hospitals in Lebanon.

Methods

In the midst of the escalating pandemic, we applied a systematic approach to develop a realistically implementable quality assurance tool. We conducted a literature review, held expert meetings and did a pilot study to select among identified quality indicators for ICU care that were feasible to collect during a 1-hour ICU visit. In addition, a limited set of the identified indicators that were quantifiable were specifically selected for a scoring protocol to allow comparison over time as well as between ICUs.

Results

A total of 44 quality indicators, which, using different methods, could be collected by an external person, were selected for the quality of care tool. Out of these, 33 were included for scoring. When tested, the scores showed a large difference between hospitals with low versus high resources, indicating considerable variation in the quality of care.

Conclusions

The proposed tool is a promising way to systematically assess and monitor the quality of care in ICUs in the absence of more advanced and resource-demanding systems. It is currently in use in Lebanon. The proposed tool may help identifying quality gaps to be targeted and can monitor progress. More studies to validate the tool are needed.
Robustness scores in fattening pigs based on routinely collected phenotypes: determination and genetic parameters
Authors: Lenoir Guillaume , Flatres-Grall Loïc , Friggens Nicolas C , David Ingrid
Published: May 2022

The objective was to determine operational proxies for robustness based on data collected routinely on farm that allow phenotyping of these traits in fattening pigs, and to estimate their genetic parameters. A total of 7,256 pigs, from two Piétrain paternal lines (Pie and Pie NN), were tested at the AXIOM boar testing station (Azay-sur-Indre, France) from 2019 to 2021. During the fattening period (from 75 to 150 d of age), individual performance indicators were recorded (growth, backfat, loin depth, feed intake, and feed conversion ratio [FCR]) together with indicators such as insufficient growth, observable defect, symptoms of diseases, and antibiotic and anti-inflammatory injections. These indicators were combined into three categorical robustness scores: R1, R2, and R3. Genetic parameters were estimated using an animal linear model. The robustness score R2 (selectable or not selectable animal) that combined information from status at testing and mortality had the highest heritability estimates of 0.08 ± 0.03 for Pie NN line and a value of 0.09 ± 0.02 for Pie line, compared with traits R1 and R3. The score R3 that combines information from the score R2 with antibiotic and anti-inflammatory injections presented slightly lower heritability estimates (0.05 ± 0.02 to 0.07 ± 0.03). Genetic correlations between R2 and R3 were high and favorable (0.93 ± 0.04 to 0.95 ± 0.03) and R2 and R3 can be considered identical with regard to the confidence interval. These two robustness scores were also highly and favorably genetically correlated with initial body weight and average daily gain, and unfavorably correlated with daily feed intake (ranging from 0.73 ± 0.06 to 0.90 ± 0.08). Estimates of genetic correlations of R2 and R3 with backfat depth and raw FCR (not standardized between starting and finishing weights) were moderate and unfavorable (0.20 ± 0.13 to 0.46 ± 0.20). A part of these genetic correlations, that are of low precision due to the number of data available, have to be confirmed on larger datasets. The results showed the interest of using routine phenotypes collected on farm to build simple robustness indicators that can be applied in breeding.
Potential effect of twoBacillusprobiotic strains on performance and fecal microbiota of breeding sows and their piglets
Authors: Saladrigas-García Mireia , Solà-Oriol David , López-Vergé Sergi , D’Angelo Matilde , Collado Maria Carmen , Nielsen Bea , Faldyna Martin , Pérez José Francisco , Martín-Orúe Susana M
Published: May 2022

The effect of long-term administration of two Bacillus strains was tested on 98 breeding sows and their litters allotted into three treatments: a control group (CON); supplemented with 5 × 108 cfu/kg B. subtilis − 541 (BSU); or with 5 × 108 cfu/kg B. amyloliquefaciens − 516 (BAM). Reproductive and performance variables were recorded over three cycles with 56 dams remaining through the third lactation. Blood and fecal samples were taken longitudinally from 12 sows per treatment on days 8 and 21 of the third lactation and milk samples were taken on day 21. Feces from one piglet per litter was sampled on days 21 and 33 and jejunal gene expression was assessed in two piglets on day 21. Changes in fecal microbiota were assessed by 16S rRNA gene sequencing (Illumina MiSeq) and gene expression by Open-Array technology. Metabolomic responses were analyzed in milk by NMR and Ig-G and Ig-A specific antibodies were determined by ELISA. No significant differences were observed on feed intake, body weight, or fat mobilization of the sows. However, a significant increase in the total number of piglets born was observed in supplemented sows. Although the increase was seen from the first cycle with BAM, improvements were not seen with BSU until the third cycle. BAM also increased the number of born-alive and weaned piglets. NMR analysis showed an impact of BAM on milk composition. No differences were found in milk or blood immunoglobulins. A different structure of the fecal microbiota was found in supplemented sows, with changes across phylum, family, and genus. These changes were greater at day 8, suggesting a relevant role of probiotics establishing a new intestinal balance after labor. Shifts in the microbiota were also seen in the piglets, with a clearer impact post-weaning than in suckling. In this regard, correlations between microbial groups of sows and piglets showed a higher link with weaned (d33) than with suckling pigs (d21), reinforcing the idea of an early maternal carry-over. No changes due to treatment in jejunal gene expression were detected; however, piglet size had a clear impact on different genes. In summary, the addition of both probiotics, and particularly Bacillus amyloliquefaciens, demonstrated potential benefits on the prolificacy of sows. Daily feeding of Bacillus amyloliquefaciens resulted in an increase in the number of weaned piglets. The high correlations between the compositions of the microbiota of sows and their piglets are evidence of maternal imprinting, with effects lasting beyond weaning.
Factors Associated With Endowed Chair Allocation in Medical Oncology in the United States
Authors: Jia Lena , Rooney Michael Kevin , Jacobson Clare E , Griffith Kent A , Mangurian Christina , Jagsi Reshma , Markham Merry Jennifer
Published: May 2022

To explore persisting gender disparities across leadership roles in medicine, we examined factors associated with holding endowed chairs in US oncology divisions. In 2019, we identified 95 academic oncology divisions, using the Oncology Division Chiefs and Department Chairs listing in the American Society of Clinical Oncology myConnection forum. We collected public information on gender, degree, total National Institutes of Health funding as principal investigator, H-indices, publication and citation numbers, and graduation year and constructed a multivariable logistic regression model. All statistical tests were 2-sided. We identified 1087 oncology full professors. Of these, 287 (26.4%) held endowed chairs: 60 of 269 women (22.3%) vs 227 of 818 men (27.8%) (P = .08). On multivariable analysis, greater research productivity and National Institutes of Health funding were associated with having an endowed chair (P < .001), whereas gender was not (P = .45). Though sample size was limited, if gender differences are in fact smaller in certain subspecialties than other fields of internal medicine, insights might emerge to guide efforts to promote equity.
Phonetic Variance of /d/ and /r/ in Hebrew in Late Antiquity
Authors: Howard Jonathan
Published: May 2022

A common type of textual variant in Hebrew is the alternation of ד and ר. Such variance has traditionally been attributed to scribes and confined to the written layer of transmission. However, given the articulatory proximity of /d/ and /r/, orally-induced variance should also be considered. I present several instances in Hebrew and Aramaic, where the context suggests that the two letters were confused in speech. This in turn sheds light on two other matters: first, it offers a new point of view for examining the question of the two allophones of /r/ reported in the Tiberian Masoretic tradition, seemingly in support of Aron Dotan’s view on the matter; second, it removes one of the difficulties raised against Yaacov Sussman’s theory about the orality of the Mishna in the Amoraic period, by reducing a scribal variant (צוערי/סועדי) to a phonetic one.
Travel-associated SARS-CoV-2 transmission documented with whole genome sequencing following a long-haul international flight
Authors: Ngeh Sera , Vogt Florian , Sikazwe Chisha T , Levy Avram , Pingault Nevada M , Smith David W , Effler Paul V
Published: May 2022

Background

Multiple instances of flight-associated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission during long-haul flights have been reported during the COVID-19 pandemic. However, comprehensive investigations of passenger risk behaviours, before, during and after the flight, are scarce.

Methods

To investigate suspected SARS-CoV-2 transmission during a flight from United Arab Emirates to Australia in July 2020, systematic, repeated polymerase chain reaction (PCR) testing of passengers in hotel quarantine was linked to whole genome sequencing. Epidemiological analyses of in-depth interviews covering behaviours during the flight and activities pre- and post-boarding were used to identify risk factors for infection.

Results

Seventeen of the 95 passengers from four different travel origins had PCR-confirmed infection yielding indistinguishable genomic sequences. Two of the 17 passengers were symptomatic within 2 days of the flight, and classified as co-primary cases. Seven secondary cases were seated within two rows of the co-primary cases, but five economy passengers seated further away and three business class passengers were also infected (attack rate = 16% [15/93]). In multivariable analysis, being seated within two rows of a primary case [odds ratio (OR) 7.16; 95% confidence interval (CI) 1.66–30.85] and spending more than an hour in the arrival airport (OR 4.96; 95% CI 1.04–23.60) were independent predictors of secondary infection, suggesting travel-associated SARS-CoV-2 transmission likely occurred both during and after the flight. Self-reported increased hand hygiene, frequent aisle walking and using the bathroom on the plane did not independently affect the risk of SARS-CoV-2 acquisition.

Conclusions

This investigation identified substantial in-flight transmission among passengers seated both within and beyond two rows of the primary cases. Infection of passengers in separate cabin classes also suggests transmission occurred outside the cabin environment, likely at the arrival airport. Recognizing that transmission may occur pre- and post-boarding may inform contact tracing advice and improve efforts to prevent future travel-associated outbreaks.
Hemispheric asymmetry of long-term sunspot activity: sunspot relative numbers for 1939–2019
Authors: Zhang X J , Deng L H , Fei Y , Li C , Tian X A , Wan Z J
Published: May 2022

Hemispheric asymmetry of solar magnetic structures is an important feature of solar cycles, and it involves dynamical processes in the interior of the Sun. For the first time, the data of the monthly sunspot relative numbers derived from the National Astronomical Observatory of Japan (NAOJ) is used to perform a long-term study (1939 March–2019 November) of the north–south asymmetry. The results show the following: (1) the sunspot relative numbers derived from NAOJ/Mitaka observatory are highly correlated with the international sunspot numbers obtained from the World Data Center Sunspot Index and Long-term Solar Observations, which justifies the use of Mitaka sunspot time series for hemispheric variation; (2) the change in the signs of the slopes of the regression lines fitted to the absolute asymmetry index suggest a kind of periodic variation in the hemispheric asymmetry, but the time interval of the current data base is not long enough to derive 8 or 12 cycles periodicity; and (3) for mid-term periods, there are enhanced powers for the period ranges around 3.7 yr, around 9 yr, between 30 and 50 yr. Our analysis results implicate a possible mechanism responsible for the generation and variation of the hemispheric coupling in the Sun.
Diagnostics for PopIII galaxies and direct collapse black holes in the early universe
Authors: Nakajima K , Maiolino R
Published: May 2022

Forthcoming observational facilities will make the exploration of the early universe routine, likely probing large populations of galaxies at very low metallicities. It will therefore be important to have diagnostics that can solidly identify and distinguish different classes of objects in such low metallicity regimes. We use new photoionization models to develop diagnostic diagrams involving various nebular lines. We show that combinations of these diagrams allow the identification and discrimination of the following classes of objects in the early universe: PopIII and direct collapse black holes (DCBH) in pristine environments, PopIII and DCBH embedded in slightly enriched interstellar medium (ISM; $\rm Z\sim 10^{-5}-10^{-4}$), and (metal poor) PopII and active galactic nucleus in enriched ISM. Diagnostics involving rest-frame optical lines (that will be accessible by James Webb Space Telescope) have a better discriminatory power but also rest-frame ultraviolet diagnostics can provide very useful information. Interestingly, we find that metal lines such as [O iii]λ5007 and C ivλ1549 can remain relatively strong (about a factor of 0.1–1 relative H β and He iiλ1640, respectively), even in extremely metal poor environments ($\rm Z\sim 10^{-5}-10^{-4}$), which could be embedding PopIII galaxies and DCBH.
Optical variability of quasars with 20-yr photometric light curves
Authors: Stone Zachary , Shen Yue , Burke Colin J , Chen Yu-Ching , Yang Qian , Liu Xin , Gruendl R A , Adamów M , Andrade-Oliveira F , Annis J , Bacon D , Bertin E , Bocquet S , Brooks D , Burke D L , Carnero Rosell A , Carrasco Kind M , Carretero J , da Costa L N , Pereira M E S , De Vicente J , Desai S , Diehl H T , Doel P , Ferrero I , Friedel D N , Frieman J , García-Bellido J , Gaztanaga E , Gruen D , Gutierrez G , Hinton S R , Hollowood D L , Honscheid K , James D J , Kuehn K , Kuropatkin N , Lidman C , Maia M A G , Menanteau F , Miquel R , Morgan R , Paz-Chinchón F , Pieres A , Plazas Malagón A A , Rodriguez-Monroy M , Sanchez E , Scarpine V , Serrano S , Sevilla-Noarbe I , Smith M , Suchyta E , Swanson M E C , Tarlé G , To C ,   (DES Collaboration)
Published: May 2022

We study the optical gri photometric variability of a sample of 190 quasars within the SDSS Stripe 82 region that have long-term photometric coverage during ∼1998−2020 with SDSS, PanSTARRS-1, the Dark Energy Survey, and dedicated follow-up monitoring with Blanco 4m/DECam. With on average ∼200 nightly epochs per quasar per filter band, we improve the parameter constraints from a Damped Random Walk (DRW) model fit to the light curves over previous studies with 10–15 yr baselines and ≲ 100 epochs. We find that the average damping time-scale τDRW continues to rise with increased baseline, reaching a median value of ∼750 d (g band) in the rest frame of these quasars using the 20-yr light curves. Some quasars may have gradual, long-term trends in their light curves, suggesting that either the DRW fit requires very long baselines to converge, or that the underlying variability is more complex than a single DRW process for these quasars. Using a subset of quasars with better-constrained τDRW (less than 20 per cent of the baseline), we confirm a weak wavelength dependence of τDRW∝λ0.51 ± 0.20. We further quantify optical variability of these quasars over days to decades time-scales using structure function (SF) and power spectrum density (PSD) analyses. The SF and PSD measurements qualitatively confirm the measured (hundreds of days) damping time-scales from the DRW fits. However, the ensemble PSD is steeper than that of a DRW on time-scales less than ∼ a month for these luminous quasars, and this second break point correlates with the longer DRW damping time-scale.
A fast and reliable method for the comparison of covariance matrices
Authors: Ferreira Tassia , Marra Valerio
Published: May 2022

Covariance matrices are important tools for obtaining reliable parameter constraints. Advancements in cosmological surveys lead to larger data vectors and, consequently, increasingly complex covariance matrices, whose number of elements grows as the square of the size of the data vector. The most straightforward way of comparing these matrices, in terms of their ability to produce parameter constraints, involves a full cosmological analysis, which can be very computationally expensive. Using the concept and construction of compression schemes, which have become increasingly popular, we propose a fast and reliable way of comparing covariance matrices. The basic idea is to focus only on the portion of the covariance matrix that is relevant for the parameter constraints and quantify, via a fast Monte Carlo simulation, the difference of a second candidate matrix from the baseline one. To test this method, we apply it to two covariance matrices that were used to analyse the cosmic shear measurements for the Dark Energy Survey Year 1. We found that the uncertainties on the parameters change by 2.6%, a figure in agreement with the full cosmological analysis. While our approximate method cannot replace a full analysis, it may be useful during the development and validation of codes that estimate covariance matrices. Our method takes roughly 100 times less CPUh than a full cosmological analysis.
MO008: Patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD) without a Clear Family History have Rapid Progression and Poor Prognosis
Authors: Gkika Vasiliki , Louka Michaela , Fokas Stavros , Tigka Eirini , Drakopoulos Angelos , Markou Niki , Kanellopoulou Konstantina , Kostopoulou Myrto , Tsagkatakis Mihail , Tsirpanlis George
Published: May 2022

BACKGROUND AND AIMS

A small percentage of patients with autosomal dominant polycystic kidney disease (ADPKD) have no clear family history. The clinical course and prognosis of the disease in this subgroup of patients may be different. The present study investigates the progression and prognostication of end-stage renal disease (ESRD) in a large cohort of patients with and without a family history of ADPKD.

METHOD

This study enrolled 291 patients who were being followed in a specialized outpatient ADPKD clinic. Patients having a total of more than 10 kidney cysts in a recent magnetic resonance imaging (MRI) scan were included in the study even if they had no clear family history or confirmatory genetic test. At enrollment, total kidney volume was calculated by MRI, and the Mayo Clinic Imagining Category (MCIC) was determined. The prediction of ESRD (future estimated-glomerular filtration rate [e-GFR < 10 mL/min] based on the Mayo Clinic formula (which takes into consideration age, TKV, e-GFR, gender, race and MCIC) was also calculated. Demographics, medical and laboratory data were recorded using a standardized form. T-test, x2 and Mann–Whitney test were used for statistical analysis.

RESULTS

Of the 291 patients included in the study, 34 (11.68%) had no clear family history of ADPKD, and 257 (88.32%) had a clear family history. Age, gender, presence or not, and age at diagnosis of hypertension as well as BMI were similar in the two groups (P = 0.369, 0.398, 0.170, 0.295, 0.597, respectively). The age at diagnosis of ADPKD was similar between patients with and without a clear family history (P = 0.125) as well as, the e-GFR, the stage of chronic kidney disease and albuminuria (P = NS). The TKV tended to be higher in patients without a clear family history (median, [range]), 2210.3 (440.7–9137.5) mL versus 1649.9 (215.7–10 425.9) mL in those with a family history of ADPKD (P = 0.09), and the same was valid for the height-adjusted TKV (P = 0.08). In MCIC 1C, 1D and 1E, more patients without a known family history of ADPKD were classified than patients with a family history of ADPKD (88.89% versus 70.14%), and vice versa in MCIC 1A and 1B (11.11% versus 29.86%; P = 0.04). Finally, the ESRD prediction was (median, [range]) 15.66 (1–42) years for the patients without a clear family history and 34.1 (1–346) years for those with a clear family history of ADPKD (P = 0.025).

CONCLUSION

Patients with ADPKD without a clear family history tend to have a more rapid progression and a worse renal prognosis than those with a clear family history of the same disease.
MO020: Rare mutation of the IQGAP1 protein in an Algerian family with corticosteroid-resistant nephrotic syndrome
Authors: Azouaou Leila , Oukrif Lamia , Bensnouci Abdelhani , Benabadji Mohamed , Seba Atmane
Published: May 2022

BACKGROUND AND AIMS

There is podocyte involvement in corticosteroid-resistant nephrotic syndrome. A certain number of proteins play an essential role in the biology of the podocyte; the mutation of these proteins generates the aforementioned pathology. The aim of this work is the determination of the rare mutation of the IQGAP1 protein, which is a protein involved in the remodeling of the actin cytoskeleton of the podocyte.

METHOD

We identified six patients in our family with corticosteroid-resistant nephrotic syndrome, including one death with four adults and two children from a consanguineous marriage with autosomal recessive transmission. It was noted that three deaths of unknown etiologies were reported at a very young age.

RESULTS

The patients had corticosteroid-resistant nephrotic syndrome. Nephrotic syndrome is discovered at the age of 4 years on average for two children and 20 years for four adults. Kidney biopsy showed minimal glomerular damage at 19%, mesangial proliferation at 6% and segmental and focal hyalinosis at 71%. The extra-renal manifestations observed were linked to complications of chronic renal failure. Alteration of the expression of IQGAP1 or of its cellular location, as well as structural or functional alterations of the protein could lead to abnormal interactions between the different complexes of the podocyte and the cytoskeleton; the specificity of the study is the discovery of an SNCRF in patients where they have only one mutation of the IQGAP1 gene without mutation of the other IQGAPs (2 and 3).

CONCLUSION

We have a very high consanguineous marriage rate, which explains why the transmission of recessive diseases is very important. The mutation of the IQGAP1 protein is inherited in an autosomal recessive fashion. A genetic investigation is essential. IQGAP1 can therefore be considered to be a factor influencing the progression of glomerulopathies.
MO062: Pan-Disease Segmentation and Feature Extraction for Large-Scale Digital Nephropathology
Authors: Hölscher David , Bouteldja Nassim , Lan Yu-Chia , von Stillfried Saskia , David Bülow Roman , Boor Peter
Published: May 2022

BACKGROUND AND AIMS

Nephropathology is essential for the diagnosis of kidney diseases. Deep learning-based image analyses, including segmentation of kidney histology, open new possibilities for reproducible quantitative precision pathology. Current segmentation approaches in kidney histology focused on specific use cases. Here, we developed a framework for automated segmentation and quantification of a wide spectrum of non-neoplastic kidney diseases.

METHOD

We trained U-Net Convolutional Neural Networks (CNNs) for two streamlined tasks: (i) detection of kidney tissue and (ii) instance segmentation of relevant histological structures, i.e. glomeruli, tubules and arteries. These were used to segment 1103 Whole-Slide-Images (WSIs) from four cohorts, including two external datasets for multi-center validation. In total, 35 features from 51 445 glomeruli, 4016 792 tubules and 362 471 arteries were extracted, generating 30 million morphometric data points. Morphometry data were associated with clinical and pathology data.

RESULTS

Kidney tissue was precisely outlined by the tissue segmentation CNN. The structure segmentation CNN for histology provided accurate results on WSI-level despite difficult histopathological morphologies such as crescents, segmental sclerosis, tubular casts or arteriosclerosis. Quantitative analyses of morphological alterations of glomeruli revealed, for example, an increased glomerular area in membranous glomerulonephritis and all cases characterized with nephrotic range proteinuria independent of the underlying disease, and decrease in glomerular tuft circularity in pauci-immune glomerulonephritis, especially in cases with severe loss of kidney function. Principal component analysis of multiple glomerular, tubular and interstitial features stratified based on estimated glomerular filtration rate identified CKD-relevant morphological alterations of glomeruli and the tubulointerstitium. Image extraction of morphometric outliers enabled fast-track visual assessment of severe lesions.

CONCLUSION

Segmentation and large-scale quantitative feature extraction enable reproducible quantitative analysis of kidney morphology, opening new possibilities for digital precision nephropathology.
MO066: The Role of Platelet-Derived Growth Factor in Focal Segmental Glomerulosclerosis
Authors: Jia Ting , Xu Tong , Smeets Bart , Johannes Moeller Marcus , Floege Jürgen , Mara Klinkhammer* Barbara , Boor* Peter
Published: May 2022

BACKGROUND AND AIMS

Focal segmental glomerulosclerosis (FSGS) describes a primary disease of podocytes (podocytopathy) and a secondary consequence of severe or progressive glomerular damage. No specific treatment options exist for FSGS, with many patients progressing to end-stage kidney disease. While podocyte injury is considered to initiate FSGS, parietal epithelial cells (PECs) were shown to be one of the main effector cells forming FSGS. Given the involvement of platelet-derived growth factor (PDGF) in fibrotic processes, we hypothesized that PDGF signaling is involved in the formation and progression of FSGS.

METHOD

We analyzed the role of PDGF in FSGS development and progression using a murine Thy1.1 trangenic FSGS model, patient kidney biopsies and primary murine PECs. In a second step, we therapeutically treated mice with FSGS with a neutralizing anti-PDGF-B antibody.

RESULTS

The podocyte-specific Thy1.1 transgenic mice 3 weeks after anti-Thy1.1 antibody injection showed reduced kidney function due to FSGS development. In this model, compared with control mice, PECs were progressively activated (63.3-fold increase in CD44 expression), showed a significantly increased proliferation (14-fold increase in Ki67 expression), followed by glomerular extracellular matrix deposition (2.6-fold increase in collagen 4) and FSGS development. Fluorescence in situ hybridization showed that mRNA of Pdgfb and Pdgfd was elevated in podocytes and Pdgfrb was upregulated in PECs during the time course of the disease. Similarly, in human FSGS biopsies, gene expression of both ligands, PDGFB and PDGFD, was elevated in podocytes and PDGFRB was increased in PECs compared with healthy glomeruli. Stimulation of primary mouse PECs with PDGF-B and PDGF-D in vitro led to significant activation (1.37- and 1.44-fold increase in CD44 expression, respectively), proliferation (1.46- and 1.36-fold increase, respectively), migration and extracellular matrix production (1.40-fold increase in fibronectin after PDGF-D stimulation) which could be inhibited by imatinib or a neutralizing PDGF-B antibody. In mice with FSGS, both a short- and long-term treatment with PDGF-B neutralizing antibody improved kidney function and reduced FSGS, PEC proliferation and profibrotic activation.

CONCLUSION

PDGFR-β and its ligands PDGF-B and PDGF-D were upregulated in experimental and clinical samples with FSGS in PECs and podocytes, respectively, and the inhibition of PDGF-B reduced PEC proliferation and FSGS development. This suggests paracrine cross-talk between injured podocytes and PECs, leading to PECs activation toward a profibrotic (pro-FSGS) phenotype and FSGS development. Thus, PDGF represents a novel molecular pathway in FSGS pathogenesis and potential target for therapy.
MO072: PST3.1A, An Inhibitor of MGAT5 Decreases Renal Fibrosis in a Rat Model of Chronic Kidney Disease
Authors: Muyor Karen , Laget Jonas , Duranton Flore , Jover Bernard , Cortijo Irene , Loiseau Séverine , Chorro Karine , Jacquard Carine , Pau Bernard , Clarion Ludovic , Argiles Ciscart Angel , Gayrard Nathalie
Published: May 2022

BACKGROUND AND AIMS

Renal fibrosis is a main feature of chronic kidney disease (CKD) that participates in its progression to the end stage.(1) N-acetylglucosaminyltransferase 5 (MGAT5) adds N-acetylglucosamines to newly synthesized glycoproteins and is overexpressed in tumors participating in epithelial–mesenchymal transition (EMT), invasion and cell migration, some of the features observed in fibrosis.(2) PST3.1a is an inhibitor of MGAT5 that has already been shown to be beneficial in the treatment of brain tumors.(3) We presently evaluated the use of PST3.1a on renal fibrosis in CKD.

METHOD

Six-week-old Sprague-Dawley rats underwent 5/6th subtotal nephrectomy (SNx) (n = 16) or no surgery (Control) (n = 14). PST3.1a (0.2 mg/mL) or placebo was administered in the drinking water from the day of surgery for the entire protocol. Animals were sacrificed 4 weeks after surgery and the kidney was taken to evaluate fibrosis, MGAT5 expression and activity. Fibrosis was determined both by Sirius red staining and by immunohistochemistry (IHC) staining of three types of collagen (I, III and IV). To measure the activity of MGAT5 immunohistochemistry staining of Phaseolus Vulgaris Leucoagglutinine (PHA-L) and galectin 3 were carried out.

RESULTS

MGAT5 expression (12.2% ± 1.2 control versus 26.7% ± 2.6 SNx) and renal fibrosis (11.5% ± 0.7 control versus 26.9% ± 1.9 SNx) increased significantly in SNx animals in a preliminary study.

In the present study, PST3.1atreatment significantly decreased the expression of collagen 1 (col1) (2.1% ± 0.2 SNx versus 1.3% ± 0.2 SNx + PST3.1a; P < 0.05) and collagen 4 (col4) (9.4% ± 1.01 SNx versus 6.4% ± 0.3SNx + PST3.1a; P < 0.05) in kidneys of SNx animals (Fig. 1). Collagen 3 also had a trend to decrease. Sirius red staining showed a decrease in the PST3.1a treated group although it did not reach statistical significance (8.4% ± 1.7SNx versus 6.7% ± 0.2 SNx + PST3.1a). PHA-L and galectin 3 expressions were increased in SNx animals, and the overexpression was blunted in PST3.1a treated animals (9.4% ± 1.5 SNx versus 5.7% ± 0.2 SNx + PST3.1a; P < 0.05 for galectin 3) (Fig. 2).

CONCLUSION

Fibrosis was observed in SNx animals 4 weeks after surgery. PST3.1a significantly decreased MGAT5 activity. Treatment with PST3.1a decreased fibrosis and significantly downregulated col1 and col4. These data show that PST3.1a treatment through MGAT5 inhibition may be a new treatment for fibrosis in the context of CKD.
MO111: Hyperuricaemia and Risk of Simple Renal Cysts
Authors: Valentinova Monova Daniela , Kamenov Assen , Milenova Vladislava , Shumnalieva Russka , Monov Simeon
Published: May 2022

BACKGROUND AND AIMS

The relationship between hyperuricaemia and renal cysts is still insufficient. Simple renal cysts (SRCs) are the most common non-hereditary type of benign renal cysts in adults. The prevalence of SRC varies by population, geographic region and the imaging modality used. The overall prevalence of SRC is 4–12% in general populations. Most SRCs are asymptomatic, being accidentally detected by abdominal ultrasonography or computed tomography during a medical check-up. However, some cysts tend to increase in size and can be sufficiently large to cause pain, haematuria and/or urinary obstruction.

The aim of this study is to compare the risk of SRC in patients with and without hyperuricaemia.

METHOD

We retrospectively collected data on 246 non-smoking males (age 30–70 years) with SRC without hypertension, obesity and renal stones. In this study, patients with previous therapy with uric acid-lowering medication; patients with current acute complications of diabetes or urinary tract infections; and patients with cancer, blood disease, polycystic kidney disease, solitary kidney, urinary tract stenosis or kidney diseases were excluded. Albuminuria was defined as 24-h urine microalbuminuria of 30 mg and higher. SRCs were detected by ultrasonography. The sonographic criteria for the diagnosis of SRC included absent internal echoes, a smooth, sharply defined wall and posterior acoustic enhancement, indicating posterior through transmission that was not suspicious for a malignant renal mass. SPSS 22 for windows was used for analysing the study data. Chi-square and exact Fisher's tests were utilized, while continuous variables were assessed by Student's t-test. A P value of less than .05 was considered statistically significant.

RESULTS

SRC prevalence was significantly higher in hyperuricaemic (174 patients) than normouricemic subjects. Age (OR 1042, 95% CI 1032–1061, P < .001) and albuminuria (OR 1189, 95% CI 1176–1892, P < 05) are independent risk factors for SRC development. Patients with SRC and hyperuricaemia were more likely to be elderly males, and exhibited a longer duration of lower eGFR and higher serum uric acid, γ-glutamyl transferase, low-density lipoprotein cholesterol and plasma glucose level compared with those without SRC. The risk of SRC increased when the serum uric acid is more 460 μmol/L.

CONCLUSION

Of the 246 non-smoking males with SRC, 176 have hyperuricaemia. Patients who had a SRC were significantly older than patients without SRC (mean 58.27 versus 43.18 years), with lower glomerular filtration rate, more often suffer from coronary heart disease. Therefore, even asymptomatic hyperuricaemia requires standardized uric acid-lowering treatment to prevent the occurrence of SRC. According to our results, SRC patients should be careful to use uricosuric drugs.
MO171: Chronic Inflammation Might Protect Haemodialysis Patients from Severe COVID-19
Authors: Prietl Barbara , Odler Balazs , Kirsch Alexander H , Artinger Katharina , Eigner Manfred , Schmaldienst Sabine , Pfeifer Verena , Stanzer Stefanie , Eberl Anita , Raml Reingard , Rosenkranz Alexander , Brodmann Marianne , Eller Philipp , Pieber Thomas , Eller Kathrin
Published: May 2022

BACKGROUND AND AIMS

Patients on haemodialysis (HD) are expected to have excess mortality in coronavirus disease 2019 (COVID-19). This was challenged by a recent study reporting HD patients to have comparable mortality and decreased ICU admissions when hospitalized with COVID-19. It was speculated that an altered immune system due to chronic inflammation might protect HD patients from severe COVID-19. Therefore, we designed a study to describe the peripheral blood immune phenotype in HD patients and respective controls with COVID-19.

METHOD

Sixty-four patients (31 HD, 33 non-HD) with PCR-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and 16 control patients (10 HD, 6 non-HD) were prospectively included. According to symptoms, COVID-19 patients were categorized as asymptomatic/mild and moderate/severe COVID-19 phenotypes. Cytokine profiling and immune phenotyping were performed.

RESULTS

Th1 and Th17 plasma cytokine levels were highly increased in HD patients without SARS-CoV-2 infection and were not significantly regulated during COVID-19. In non-HD COVID-19 patients, these cytokines increased significantly with disease severity. While all patients with moderate/severe COVID-19 showed hallmarks of COVID-19 such as decreased CD3+ CD4+ and CD8+ and CD4+CD25hiFoxP3+ regulatory T cells, significantly increased CD38+CD8+ effector memory and CD38+CD8+ TEMRA T cells were detected in HD compared to non-HD patients with moderate/severe COVID-19. Furthermore, CD161+CD8+ T cells decreased significantly in non-HD COVID-19 patients dependent on disease severity, but not in HD patients. Dynamics of B cells and subtypes were comparable in HD and non-HD COVID-19 patients. Significantly fewer moderate/severe COVID-19 HD patients needed ICU treatment [1/13 (7.7%) HD, 12/24 (50%) non-HD], whereas no difference in mortality was observed [4/31 (12.9%) HD, 6/33 non-HD (18.2%)].

CONCLUSION

HD patients might be protected from severe COVID-19 due to their chronic inflammatory state with increased CD38+CD8+ effector memory and TEMRA T cells as well as CD161+CD8+ T cells.