bluuebunny/crossref_metadata_2025 huggingface dataset:
Analytical Validation of HEARTBiT: A Blood-Based Multiplex Gene Expression Profiling Assay for Exclusionary Diagnosis of Acute Cellular Rejection in Heart Transplant Patients
Authors: Kim Ji-Young V , Lee Brandon , Koitsopoulos Pavlos , Shannon Casey P , Chen Virginia , Hollander Zsuzsanna , Assadian Sara , Lam Karen , Ritchie Gordon , McManus Janet , McMaster W Robert , Ng Raymond T , McManus Bruce M , Tebbutt Scott J
Published: June 2020

Background

HEARTBiT is a whole blood-based gene profiling assay using the nucleic acid counting NanoString technology for the exclusionary diagnosis of acute cellular rejection in heart transplant patients. The HEARTBiT score measures the risk of acute cellular rejection in the first year following heart transplant, distinguishing patients with stable grafts from those at risk for acute cellular rejection. Here, we provide the analytical performance characteristics of the HEARTBiT assay and the results on pilot clinical validation.

Methods

We used purified RNA collected from PAXgene blood samples to evaluate the characteristics of a 12-gene panel HEARTBiT assay, for its linearity range, quantitative bias, precision, and reproducibility. These parameters were estimated either from serial dilutions of individual samples or from repeated runs on pooled samples.

Results

We found that all 12 genes showed linear behavior within the recommended assay input range of 125 ng to 500 ng of purified RNA, with most genes showing 3% or lower quantitative bias and around 5% coefficient of variation. Total variation resulting from unique operators, reagent lots, and runs was less than 0.02 units standard deviation (SD). The performance of the analytically validated assay (AUC = 0.75) was equivalent to what we observed in the signature development dataset.

Conclusion

The analytical performance of the assay within the specification input range demonstrated reliable quantification of the HEARTBiT score within 0.02 SD units, measured on a 0 to 1 unit scale. This assay may therefore be of high utility in clinical validation of HEARTBiT in future biomarker observational trials.
Colonization by Biological Control Agents on Post-Fire Regrowth of Invasive Lygodium microphyllum (Lygodiaceae)
Authors: David Aaron S , Sebesta Nicole , Abdel-Kader Anwar A , Lake Ellen C
Published: June 2020

Integration of biological control with other management tactics such as prescribed burning is often important for successful invasive weed control. A critical step in this integration is determining whether the agent can colonize postburn growth of the weed. Here, we investigated postburn colonization by biological control agents on regrowth of the invasive vine Lygodium microphyllum (Cav.) R. Br. (Lygodiaceae, Old World climbing fern) in Florida. We monitored regrowth and subsequent colonization of two agents already established in Florida—the gall-inducing mite Floracarus perrepae Knihinicki and Boczek (Acariformes: Eriophyidae) and the foliage-feeding moth Neomusotima conspurcatalis Warren (Lepidoptera: Crambidae)—following three prescribed burns. We provide the first report of natural colonization by the F. perrepae mite and N. conspurcatalis moth on postburn L. microphyllum regrowth, and this colonization typically began 5–9 mo postburn. Furthermore, we report that L. microphyllum can recover to prefire levels of percent cover in as little as 5 mo. Our findings indicate that biological control of L. microphyllum has the potential to be integrated with prescribed burns.
Soil microbial succession following surface mining is governed primarily by deterministic factors
Authors: Kane Jennifer L , Morrissey Ember M , Skousen Jeffrey G , Freedman Zachary B
Published: June 2020

Understanding the successional dynamics governing soil microbial community assembly following disturbance can aid in developing remediation strategies for disturbed land. However, the influences shaping microbial communities during succession following soil disturbance remain only partially understood. One example of a severe disturbance to soil is surface mining for natural resources, which displaces communities and changes the physical and chemical soil environment. These changes may alter community composition through selective pressure on microbial taxa (i.e. deterministic processes). Dispersal and ecological drift may also shape communities following disturbance (i.e. stochastic processes). Here, the relative influence of stochastic and deterministic processes on microbial community succession was investigated using a chronosequence of reclaimed surface mines ranging from 2–32 years post-reclamation. Sequencing of bacterial and fungal ribosomal gene amplicons coupled with a linear modeling approach revealed that following mine reclamation, while bacterial communities are modestly influenced by stochastic factors, the influence of deterministic factors was ∼7 × greater. Fungal communities were influenced only by deterministic factors. Soil organic matter, texture, and pH emerged as the most influential environmental factors on both bacterial and fungal communities. Our results suggest that management of deterministic soil characteristics over a sufficient time period could increase the microbial diversity and productivity of mine soils.
The Press-safety Paradox of Democracies: Regime-type Duration and Journalist Killings
Authors: Solis Jonathan A
Published: June 2020

Previous research finds that journalist killings are more likely to occur in democracies rather than non-democracies. While these results provide an important first step in exploring regime type’s effect on journalist’s safety, they assume no variation in how long countries have remained a regime type. In this paper, I argue that as a country’s regime type endures, the likelihood of seeing journalists killed for their work will decrease. My theory also examines the process in different regime types and argues that this effect should hold for autocracies and anocracies, but not democracies|though democratic consolidation should decrease journalist killings there. Using an original sample of journalists killed for their professional work in countries worldwide from 1992 to 2014, I evaluate my theory using regression and survival analyses and find evidence that as regime types endure, journalist killings decrease, on average. As expected, the result holds for autocracies and anocracies but not democracies. However, the data show democratic consolidation does decrease journalist killings. The results provide a broader understanding of the working dynamics between regime type and journalists’ safety in a country’s media system.
The Changing Adoption of Culture Change Practices in U.S. Nursing Homes
Authors: Lima Julie C , Schwartz Margot L , Clark Melissa A , Miller Susan C
Published: June 2020

Background and Objectives

The study aimed to: (i) describe whether culture change (CC) practice implementation related to physical environment, resident-centered care, and staff empowerment increased within the same nursing homes (NHs) over time; and (ii) identify factors associated with observed increases.

Research Design and Methods

This was a nationally representative panel study of 1,584 U.S. NHs surveyed in 2009/2010 and 2016/2017. Survey data were merged with administrative, NH, and market-level data. Physical environment, staff empowerment, and resident-centered care domain scores were calculated at both time points. Multivariate logistic regression models examined factors associated with domain score increases.

Results

Overall, 22% of NHs increased their physical environment scores over time, 32% their staff empowerment scores, and 44% their resident-centered care scores. However, 32%–68% of NHs with below median baseline scores improved their domain scores over time compared with only 11%–21% of NHs with baseline scores at or above the median. Overall, NHs in states with Medicaid pay-for-performance (with CC components), in community care retirement communities, with special care units and higher occupancy had significantly higher odds of increases in physical environment scores. Only baseline domain scores were associated with increases in staff empowerment and resident-centered care scores.

Discussion and Implications

This is the first nationally representative panel study to assess NH CC adoption. Many NHs increased their CC practices, though numerous others did not. While financial incentives and indicators of financial resources were associated with increase in physical environment scores, factors associated with staff empowerment and resident-centered care improvements remain unclear. Studies are needed to assess whether the observed increases in CC adoption are associated with greater quality of life and care gains for residents and whether there is a threshold effect beyond which the efficacy of additional practice implementation may be less impactful.
Patterns of (Dis)similarity in the Design of Regional Organizations: The Regional Organizations Similarity Index (ROSI)
Authors: Jetschke Anja , Münch Sören , Cardozo-Silva Adriana Rocío , Theiner Patrick
Published: June 2020

How similar are the institutional designs of regional organizations (ROs)? Is there a trend toward particular designs such as the European Union's, or is there greater institutional variety as more regions have created an increasing number of ROs? Which designs have spread through the system, and which remain idiosyncratic? To answer these questions, the Comparative Regional Organizations Project has assembled the most detailed dataset on ROs to date, with more than 80 organizations and their 276 founding and amending treaties being coded on more than 300 institutional design features. From these data, the project has generated the Regional Organizations Similarity Index (ROSI), a dyadic measure of the similarity between any two ROs at various points during their existence. We outline the rationale for ROSI and detail its construction, and show that it captures previously unstudied patterns of variation in the RO universe across time and space. In addition to generalizations about the case universe, ROSI allows us to estimate which institutional designs constitute deviations and which tend to follow established models. We demonstrate the validity of ROSI with the help of brief case studies exploring which institutional design features led to the identified scores.
Replacing cottonseed meal and sorghum grain with corn dried distillers’ grains with solubles in lamb feedlot diets: carcass, trained sensory panel, and volatile aroma compounds traits
Authors: Hodges Kade M , Kerth Chris R , Whitney Travis R , Wall Kayley R , Miller Rhonda K , Ramsey W Shawn , Woerner Dale R
Published: June 2020

In a randomized design study, lambs were individually fed with ad libitum access to 70.9% concentrate diets for 56 d in individual pens. The positive control diet (CNTL) contained cottonseed meal (CSM), sorghum grain, and cottonseed hulls, but no dried distillers’ grains with solubles (DDGS). Four treatment diets were similar to CNTL but did not contain CSM. Corn DDGS replaced 0% (0DDGS), 33% (33DDGS), 66% (66DDGS), or 100% (100DDGS) of the sorghum grain in the treatment diets. At 48-h postmortem, the longissimus muscle (LM) was removed from the carcass, cut into chops, frozen, thawed, cooked, and evaluated by a trained sensory panel. Lambs fed CNTL were compared with 0DDGS using contrasts and linear and quadratic effects were evaluated among the four DDGS diets. Lambs fed CNTL had greater (P ≤ 0.03) hot carcass weight (HCW) and LM area than lambs fed 0DDGS. As DDGS incrementally replaced sorghum grain, marbling linearly decreased (P = 0.03), LM area tended to linearly increase (P = 0.06), and skeletal maturity tended to linearly decrease (P = 0.06). As DDGS incrementally replaced sorghum grain, flavor attributes quadratically increased to 33DDGS then decreased (brown, roasted, umami; P ≤ 0.03), quadratically decreased to 33DDGS then increased (metallic; P = 0.004), or linearly decreased (lamb flavor identity; P = 0.03). Volatile aroma compounds 2-(hexyloxy)-ethanol decreased and 2,3-octanedione and methyl pyrazine increased quadratically with an increase in DDGS (P < 0.05). Additionally, 2-heptenal, heptanal, and 2-pentyl furan increased linearly, while 2-butanone decreased linearly as DDGS increased in the diet (P < 0.05). Results indicate that carcass and sensory characteristics and volatile aroma compounds are not negatively affected, in fact brown, roasted, and umami flavors are enhanced, when 33% DDGS replaces CSM and sorghum grain in Dorper lamb feedlot diets.
The Predictive Applicability of Liberal vs Restrictive Intubation Criteria in Adult Patients With Suspected Inhalation Injury—A Retrospective Cohort Study
Authors: Chotalia Minesh , Pirrone Christine , Mangham Thomas , Torlinska Barbara , Mullhi Randeep , England Kaye , Torlinski Tomasz
Published: June 2020

This study compares the ability of liberal vs restrictive intubation criteria to detect prolonged intubation and inhalation injury in burn patients with suspected inhalation injury. Emerging evidence suggests that using liberal criteria may lead to unnecessary intubation in some patients. A single-center retrospective cohort study was conducted in adult patients with suspected inhalation injury admitted to intensive care at Queen Elizabeth Hospital, Birmingham between April 2016 and July 2019. Liberal intubation criteria, as reflected in local guidelines, were compared to restrictive intubation criteria, as outlined in the American Burn Association guidelines. The number of patients displaying positive characteristics from either guideline was compared to the number of patients who had prolonged intubation (more than 48 hours) and inhalation injury. In detecting a need for prolonged intubation (n = 85), the liberal criteria had greater sensitivity (liberal = 0.98 [0.94–1.00] vs restrictive = 0.84 [0.75–0.93]; P = .013). However, the restrictive criteria had greater specificity (restrictive = 0.96 [0.89–1.00] vs liberal = 0.48 [0.29–0.67]; P < .001). In detecting inhalation injury (n = 72), the restrictive criteria were equally sensitive (restrictive = 0.94 [0.87–1.00] vs liberal = 0.98 [0.84–1.00]; P = .48) and had greater specificity (restrictive = 0.86 [0.72–1.00] vs liberal = 0.04 [0.00–0.13]; P < .001). In patients who met liberal but not restrictive criteria, 65% were extubated within 48 hours and 90% did not have inhalation injury. Liberal intubation criteria were more sensitive at detecting a need for prolonged intubation, while restrictive criteria were more specific. Most patients intubated based on liberal criteria alone were extubated within 48 hours. Restrictive criteria were highly sensitive and specific at detecting inhalation injury.
Lessons Learned From Implementation and Management of Skin Allograft Banking Programs in Low- and Middle-Income Countries: A Systematic Review
Authors: Roberson Jeffrey L , Pham Julie , Shen Jolie , Stewart Kelly , Hoyte-Williams Paa Ekow , Mehta Kajal , Rai Shankar , Pedraza Jorge Morales , Allorto Nikki , Pham Tam N , Stewart Barclay T
Published: June 2020

Wound excision and temporary coverage with a biologic dressing can improve survival for patients with large burns. Healthcare systems in low- and middle-income countries (LMICs) rarely have access to allografts, which may contribute to the limited survival of patients with large burns in these settings. Therefore, we aimed to describe the lessons learned from the implementation and maintenance of tissue banks in LMICs to guide system planning and organization. PubMed, MEDLINE, CINAHL, and World Health Organization Catalog were systematically searched with database-specific language to represent a priori terms (eg, skin, allograft, and tissue bank) and all LMICs as defined by the World Bank. Data regarding tissue banking programs were extracted and described in a narrative synthesis. The search returned 3346 records, and 33 reports from 17 countries were analyzed. Commonly reported barriers to ideal or planned implementation included high capital costs and operational costs per graft, insufficient training opportunities, opt-in donation schemes, and sociocultural stigma around donation and transplantation. Many lessons were learned from the implementation and management of tissue banks around the world. The availability of skin allografts can be improved through strategic investments in governance and regulatory structures, international cooperation initiatives, training programs, standardized protocols, and inclusive public awareness campaigns. Furthermore, capacity-building efforts that involve key stakeholders may increase rates of pledges, donations, and transplantations. Some issues were ubiquitously reported and could be addressed by current and future tissue banking programs to ensure allograft availability for patients living in countries of all income levels.
Essential Oil Components in Superabsorbent Polymer Gel Modify Reproduction ofBlattella germanica(Blattodea: Ectobiidae)
Authors: Oladipupo S O , Hu X P , Appel A G
Published: June 2020

The use of essential oil components (EOCs) against the German cockroach, Blattella germanica (L.), has increasingly received attention from researchers. However, the determination of lethal doses/concentrations alone does not provide enough information on the range of biological effects of these EOCs. To improve our understanding of the potential effects of EOCs, we examined biological parameters of B. germanica exposed to sublethal EOCs formulated in gels. This study employed superabsorbent polymer (SAP) gel to prolong bioavailability of limonene, carvacrol, and β-thujaplicin, and evaluated how these EOCs shape biological parameters of B. germanica. Overall, median survival days ranged from 57 to 69.5 d for males and 73 to 99 d for females. The survival day ranking for the EOCs was limonene > β-thujaplicin > carvacrol. Carvacrol and β-thujaplicin gels reduced male longevity by at least 34 and 39%, respectively, while limonene had no effect. The longevity of females was reduced by limonene, but not by carvacrol and β-thujaplicin gels. EOCs significantly suppressed overall adult females’ reproductive period, oothecal hatchability, reduced fecundity, and interoothecal period, but not the number of oothecae formed and egg incubation period. The preoviposition period (mean: 2–25 d) ranking was limonene < carvacrol < β-thujaplicin. Based on these results, limonene, carvacrol, and β-thujaplicin in SAP gels show promising potential to reduce adult male survival/longevity, suppress egg hatchability and female fecundity, and delay the interoothecal period. These findings may represent the basis for the practical use of EOCs as a tactic in integrated pest management systems for B. germanica.
Impact of Full-Field Digital Mammography Versus Film-Screen Mammography in Population Screening: A Meta-Analysis
Authors: Farber Rachel , Houssami Nehmat , Wortley Sally , Jacklyn Gemma , Marinovich Michael L , McGeechan Kevin , Barratt Alexandra , Bell Katy
Published: June 2020

Background

Breast screening programs replaced film mammography with digital mammography, and the effects of this practice shift in population screening on health outcomes can be measured through examination of cancer detection and interval cancer rates.

Methods

A systematic review and random effects meta-analysis were undertaken. Seven databases were searched for publications that compared film with digital mammography within the same population of asymptomatic women and reported cancer detection and/or interval cancer rates.

Results

The analysis included 24 studies with 16 583 743 screening examinations (10 968 843 film and 5 614 900 digital). The pooled difference in the cancer detection rate showed an increase of 0.51 per 1000 screens (95% confidence interval [CI] = 0.19 to 0.83), greater relative increase for ductal carcinoma in situ (25.2%, 95% CI = 17.4% to 33.5%) than invasive (4%, 95% CI = −3% to 13%), and a recall rate increase of 6.95 (95% CI = 3.47 to 10.42) per 1000 screens after the transition from film to digital mammography. Seven studies (80.8% of screens) reported interval cancers: the pooled difference showed no change in the interval cancer rate with −0.02 per 1000 screens (95% CI = −0.06 to 0.03). Restricting analysis to studies at low risk of bias resulted in findings consistent with the overall pooled results for all outcomes.

Conclusions

The increase in cancer detection following the practice shift to digital mammography did not translate into a reduction in the interval cancer rate. Recall rates were increased. These results suggest the transition from film to digital mammography did not result in health benefits for screened women. This analysis reinforces the need to carefully evaluate effects of future changes in technology, such as tomosynthesis, to ensure new technology leads to improved health outcomes and beyond technical gains.
‘Physically sheltered but existentially homeless’: Losing home in the aftermath of conflict and displacement
Authors: Perez Murcia Luis Eduardo
Published: June 2020

This article explores the interplay between conflict-induced displacement and home. Inspired by Arendt’s discussion on home for those European refugees who were forced to move and deported to Nazi concentration camps during the Second World War, the article argues that displacement results in the loss of a place called home. Drawing on the narratives of those who in the aftermath of conflict have fled within national borders in Colombia, the article shows that displacement consistently results in the loss of home and it is experienced as the loss of people’s place in the world. Their loss of home was not only experienced as the loss of a physical shelter and its financial value but primarily as the loss of a place in which their lives were fulfilled with existential meaning. Despite the fact that the displaced found a new place for dwelling, most of them stressed the feeling of being out of place within their own country. The empirical findings challenge internal displacement research which rather than looking at how displacement disrupts one’s sense of home, has tended to focus on the loss of material assets and the subsequent risk of being trapped by poverty as the most salient impacts of displacement. The article ends by suggesting that the use of a notion of home which is material and symbolic, may provide internal displacement research with new venues for understanding both the very meaning of being displaced and how displacement is experienced.
Optical variability of three extreme TeV blazars
Authors: Pandey Ashwani , Gupta Alok C , Damljanovic G , Wiita P J , Vince O , Jovanovic M D
Published: June 2020

We present the results of optical photometric observations of three extreme TeV blazars, 1ES 0229+200, 1ES 0414+009, and 1ES 2344+514, taken with two telescopes (1.3 m Devasthal Fast Optical Telescope, and 1.04 m Sampuranand Telescope) in India and two (1.4 m Milanković telescope and 60 cm Nedeljković telescope) in Serbia during 2013–2019. We investigated their flux and spectral variability on diverse time-scales. We examined a total of 36 intraday R-band light curves of these blazars for flux variations using the power-enhanced F-test and the nested ANOVA test. No significant intraday variation was detected on 35 nights, and during the one positive detection the amplitude of variability was only 2.26 per cent. On yearly time-scales, all three blazars showed clear flux variations in all optical wavebands. The weighted mean optical spectral index (αBR), calculated using B − R colour indices, for 1ES 0229+200 was 2.09 ± 0.01. We also estimated the weighted mean optical spectral indices of 0.67 ± 0.01 and 1.37 ± 0.01 for 1ES 0414+009, and 1ES 2344+514, respectively, by fitting a single power law (Fν ∝ ν−α) in their optical (VRI) spectral energy distributions. A bluer-when-brighter trend was only detected in the blazar 1ES 0414+009. We briefly discuss different possible physical mechanisms responsible for the observed flux and spectral changes in these blazars on diverse time-scales.
The well correlated diffuse interstellar bands at λλ 6196, 6614 Å and their possible companions
Authors: Bondar A
Published: June 2020

Considered here is the interrelation between five diffuse interstellar bands (DIBs), λλ 5545, 6113, 6196, 6445 and 6614 Å. Two DIBs (λλ 6196 and 6614 Å) are already known as being well correlated with each other; their relation with three other weaker bands is investigated for the first time. To accomplish this task, high-resolution spectra (λ/δλ ≈100 000) with high signal-to-noise ratios (S/N) of 54 hot O–B stars with reddening 0.12–1.45 mag were used. Analysis of measured equivalent widths has allowed us to establish linear dependences and evaluate linear correlation coefficients as high as 0.968–0.988 between the intensities of these five DIBs. Such a degree of correlation may indicate their common origin. Several spacings in wavenumbers found between these DIBs correspond to the energies of vibrational transitions in some polycyclic aromatic hydrocarbons resulting in IR emissions at λλ 16.4, 11.3, 7.7, 6.2 and 3.3 μm.
Modified Hermite integrators of arbitrary order
Authors: Dittmann Alexander J
Published: June 2020

We present a family of modified Hermite integrators of arbitrary order possessing superior behaviour for the integration of Keplerian and near-Keplerian orbits. After recounting the derivation of Hermite N-body integrators of arbitrary order, we derive a corrector expression that minimizes integrated errors in the argument of periapsis for any such integrator. In addition to providing an alternate derivation of the modified corrector for the fourth-order Hermite integrator, we focus on improved correctors for the sixth- and eighth-order integrators previously featured in the literature. We present a set of numerical examples and find that the higher order schemes improve performance, even when considering their slightly higher cost in floating point operations. The algorithms presented herein hold promise for systems dominated by central potentials, such as planetary systems and the centres of galaxies. Existing Hermite integrators of any order can be modified to use the expressions presented here with minimal effort. Accordingly, the schemes presented herein can be easily implemented on massively parallel architectures.
Structure of the PCBP2/stem–loop IV complex underlying translation initiation mediated by the poliovirus type I IRES
Authors: Beckham Simone A , Matak Mehdi Y , Belousoff Matthew J , Venugopal Hariprasad , Shah Neelam , Vankadari Naveen , Elmlund Hans , Nguyen Joseph H C , Semler Bert L , Wilce Matthew C J , Wilce Jacqueline A
Published: June 2020

The poliovirus type I IRES is able to recruit ribosomal machinery only in the presence of host factor PCBP2 that binds to stem–loop IV of the IRES. When PCBP2 is cleaved in its linker region by viral proteinase 3CD, translation initiation ceases allowing the next stage of replication to commence. Here, we investigate the interaction of PCBP2 with the apical region of stem–loop IV (SLIVm) of poliovirus RNA in its full-length and truncated form. CryoEM structure reconstruction of the full-length PCBP2 in complex with SLIVm solved to 6.1 Å resolution reveals a compact globular complex of PCBP2 interacting with the cruciform RNA via KH domains and featuring a prominent GNRA tetraloop. SEC-SAXS, SHAPE and hydroxyl-radical cleavage establish that PCBP2 stabilizes the SLIVm structure, but upon cleavage in the linker domain the complex becomes more flexible and base accessible. Limited proteolysis and REMSA demonstrate the accessibility of the linker region in the PCBP2/SLIVm complex and consequent loss of affinity of PCBP2 for the SLIVm upon cleavage. Together this study sheds light on the structural features of the PCBP2/SLIV complex vital for ribosomal docking, and the way in which this key functional interaction is regulated following translation of the poliovirus genome.
SO006DIPEPTIDYL PEPTIDASE-4 INHIBITOR PROTECTS FROM PERITONEAL FIBROSIS--- A TRANSLATIONAL RESEARCH FROM CLINICAL OBSERVATION TO ANIMAL STUDY
Authors: Li Yi-Chen , Yang Chihchao , Sung Pei-Hsun , Yip Hon-Kan
Published: June 2020

Background and Aims

The increasing prevalence rate of end-stage renal disease (ESRD) has emerged as a global health burden. Peritoneal dialysis (PD) possesses the survival and convenient advantage for ESRD during the first 2 years of dialysis treatment. However, long-term PD and hyperglycemia have been identified to frequently result in peritoneal fibrosis (PF) as subsequently to lead the failure of peritoneal function. Therefore, how to prevent PF is an important issue, especially in diabetic ESRD patients.

Method

To explore the effective protection in PD patients, Taiwan National Health Insurance Research Database was utilized to conduct the retrospective population-based cohort study from 1997 to 2013. A total of 19,828 diabetic ESRD patients with PD were analyzed the incidence of PD failure in the user and nonuser of dipeptidyl peptidase-4 (DPP4) inhibitors. On the other hand, the pathological role of DPP4 was further verified by cellular model and animal model of PF induced by chlorhexidine gluconate (CG).

Results

The rate of PD failure was significantly lower in diabetic ESRD patients with than without receiving DPP4 inhibitors (p<0.0001). Among all collected types of antidiabetic drugs, diabetic ESRD patients with DPP4 inhibitors treatment had the lowest rate of PD failure. In cellular study, the high concentration of glucose induced the increase of DPP4 protein levels, accumulating with the epithelial–mesenchymal transition (EMT), inflammation and the generation of oxidative stress in the mesothelial cells. However, sitagliptin treatment remarkably suppressed high concentration of glucose-inducing cellular damage. Additionally, in vivo study, sitagliptin treatment significantly decreased DPP4 activity, reversed EMT process via attenuating TGF-β/ Smad3 axil, ameliorated angiogenesis, reduced oxidative stress generation and inflammation through inhibiting NF-κB/ MyD88 signaling, followed by protected peritoneal integrity and function against CG-inducing PF in rats.

Conclusion

DPP4 contributed to the peritoneal fibrosis and functional impairment, whereas DPP4 inhibitors were suggested as a clinical protective strategy for extending PD. Figure:
SO018NON-INVASIVE ASSESSMENT AND MONITORING OF SKELETAL MUSCLE MASS IN CRITICALLY ILL PATIENTS WITH AKI BY QUADRICEPS MUSCLE ULTRASOUND
Authors: Sabatino Alice , Regolisti Giuseppe , Cantarelli Chiara , Palladini Andrea , Di motta Tommaso , Maggiore Umberto , Fiaccadori Enrico
Published: June 2020

Background and Aims

Critically ill patients undergo important muscle wasting during ICU stay, and a significant loss of muscle mass still occurs in the first few days of hospital stay. This may delay both functional recovery and weaning from mechanical ventilation, being also a well-known predictor of mortality. Quite often, muscle wasting is masked by fluid overload, increasing the risk for underestimating the presence of malnutrition, as frequently occurs in critically ill patients with AKI.

An important concern in this clinical setting is the lack of adequate tools for routine bedside evaluation of the skeletal muscle mass. Lately, the use of ultrasound (US) for the assessment of muscle mass has aroused considerable interest. It is a non-invasive technique, applicable at the bedside and even in non-collaborative patients, it is economically viable, safe and do not require specialized staff. Recently, its reliability and validity have been demonstrated in critically ill patients with AKI. On this premise, in the present study, we aimed to evaluate the clinical application of US for both evaluation and monitoring of quadriceps muscle thickness in critically ill patients with AKI.

Method

This is an observational study, conducted in the renal ICU of the Parma University Hospital. All adult patients with AKI, with no distinction regarding the severity of AKI, admitted in the renal ICU from 15/03/2017 to 15/03/2018, with previous hospital stay less than 72h, with a likely ICU stay of at least 5 days were eligible for entering the study. The diagnosis of AKI was made according to KDIGO. Quadriceps rectus femoris and vastus intermedius thickness (QRFT and QVIT) were measured at the midpoint and at the border between the upper third and lower two-thirds between the anterior superior iliac spine (ASIS) and the upper pole of the patella. US was performed twice during ICU stay, i.e., at baseline (within 72h from admission) and after 5 days since the first measurement.

Results

We enrolled 30 patients, 70% (n= 21/30) were male, mean age ± SD age 74±11 years, APACHE II mean ± SD, 22 ± 5. Ultrasonography took less than 10 minutes to set up and complete image acquisition and less than 10 minutes per image to complete measurement analysis in all patients. A total of 472 images were analyzed across the 30 subjects.
SO020NEPHROLOGY INTERVENTION IN PATIENTS AWAITING CARDIAC SURGERY: A RANDOMISED CONTROLLED TRIAL
Authors: Codina Sergi , Coloma Ana , Sbraga Fabrizio , Boza Enric , Vazquez-Reveron Jose Maria , Ferreiro Eva , Cruzado Josep , Montero Nuria
Published: June 2020

Background and Aims

Acute kidney injury (AKI) is a frequent complication after cardiac surgery. Its incidence ranges from 19 to 44% depending on the study and which definition is used. There are some well-known risk factors associated with AKI, including baseline patient characteristics (age and comorbidities), need of perioperative blood transfusion or presence of previous chronic kidney disease. We wanted to evaluate if a nephrologist management and control of potential risk factors of renal disease can be used to prevent AKI, thereby minimizing the risk of need RRT, reducing costs and improving survival in these patients. It will be the first study focused on this intervention. The aim of this study is to assess if a nephrology intervention before cardiac surgery can reduce the postoperative incidence of AKI.

Method

Unicentric prospective randomized controlled trial of 298 participants from 2015 to 2019. The inclusion criteria was patients undergoing scheduled cardiac surgery of > 18 years old. The exclusion criteria was a requirement for renal replacement therapy before surgery. Clinical Research Ethics Committee of Bellvitge has approved the study before initiation. All patients have given written informed consent. We have done an intention-to-treat analysis, continuous variables have been compared between groups using Student's t test and categorical variables using X2.

Results

Nephrology intervention before surgery, included a preoperative study done minimum 1 month before the surgery to optimize the patient’ s overall condition by optimization of hydration state, remove or minimize dose of drugs that potentially deteriorate kidney function and correct metabolic disorders. No differences in the characteristics of the patients between groups was found (Table 1). The number of patients with AKI were 49 without differences between groups (0.112), with most of them presenting a stage 1 AKI, only 3 patients present a stage 3 AKI, but none of them required renal replacement therapy (Table 2). We found 1.3% of mortality (1 participant in the intervention group and 3 in control group). Data at 1 year follow-up (n= 144) showed low incidence of kidney disease (creatinine in intervention arm 91.87±30.79μmol/L and in control arm 87.08±23.58, p=0.292) without differences in albuminuria.

Conclusion

In summary, we did not find any difference in acute kidney injury and death when a nephrology intervention is done to cardiac surgery patients, probably it would be necessary to increase the sample size to make conclusions. The results at 1 year follow-up showed no kidney disease in these patients.
SO026HUMAN KIDNEY PROXIMAL TUBULAR 3D SPHEROIDS TO STUDY THE ROLE OF ADAM17 IN DIABETIC NEPHROPATHY
Authors: Palau Vanesa , Nugraha Bramasta , Emmert Maximilian , Hoerstrup Simon , Pascual Santos Julio , Soler Romeo Maria Jose , Riera Marta
Published: June 2020

Background and Aims

ADAM17 is a disintegrin and metalloproteinase initially described to cleave the tumor necrosis factor α (TNFα). Currently, it is known that it can also release ectodomains of a diverse variety of molecules such as, transforming growth factor α (TGFα), L-selectin, and angiotensin-converting enzyme 2 (ACE2). It has been shown that ADAM17 protein expression increases in kidney mesangial cells after incubation with high glucose media mimicking what has been observed in diabetic patients and experimental models of diabetic nephropathy. We now studied the effect ADAM17 deletion on human kidney cells (HKC-8) in a 3D spheroids in vitro cell culture incubated with high glucose, low glucose and mannitol medium resembling the in vivo human kidney diabetic environment.

Method

ADAM17 deletion was performed using the CRISPR/Cas9 technology. HKC8 cells grew inside a RGD-functionalized dextran hydrogel to obtain 3D spheroids. 13 days post-seeding, the spheroids were incubated with 35mM of D-glucose (HG), 5mM of D-glucose (LG) or 35mM of mannitol as osmotic control for 6h, 24h or 72h. The quality of the established 3D cell culture of mature HKC-8 spheroids was assessed by Aquoporin-1 and Glut-1 staining. After incubations quantitative-PCR analyses were performed for fibrotic and inflammatory markers. Immunofluorescence for fibrotic markers was performed on HKC-8 spheroids incubated for 72h.

Results

High glucose (HG) medium induced CCL5 gene expression on wild-type HKC-8 spheroids after 6h and 24h of incubation in comparison with the control group. Interestingly, in the ADAM17-deleted spheroids, CCL5 gene expression maintained similar to control after 6h of incubation with HG medium and tended to decrease after 24h of incubation in comparison with the wild-type. Collagen IV gene expression was increased in the wild-type spheroids incubated with HG in comparison with the control group. In ADAM17-deleted spheroids, Collagen IV gene expression was significantly decreased in the cells incubated with HG in comparison with the wild-type cells incubated with HG. HG increased the expression of α-SMA, fibronectin and Collagen IV in wild-type spheroids. Adam17 deletion blocked the increase of α-SMA, fibronectin and Collagen IV expression compared with wild-type cells after 72h of incubation.

Conclusion

ADAM17 blockade protects against fibrosis and inflammation in human kidney tubular spheroids under high glucose.
SO027ASSOCIATIONS OF MUSCLE SODIUM DEPOSITION WITH SODIUM-23 MRI IN HEMODIALYSIS PATIENTS
Authors: Salerno Fabio , Akbari Alireza , Lemoine Sandrine , Dorie Justin , Tamasi Tanya , McIntyre Christopher
Published: June 2020

Background and Aims

The development of sodium-23 magnetic resonance imaging (23Na MRI) allows the clinical quantification of tissue sodium. Recent studies have shown that hemodialysis (HD) patients have a tendency to retain tissue sodium due to impaired mechanisms in local tissue sodium clearance. However, the clinical significance of tissue sodium deposition in the HD patient population is unclear yet. The aim of this study was to investigate the association of tissue sodium deposition with well-established biomarkers of clinical outcomes.

Method

Chronic, thrice weekly HD patients underwent 23Na MRI of the leg on a non-dialysis day, during either the long or short interdialytic interval. Blood samples were also taken for the measurement of standard blood-based biomarkers. A multinuclear-capable 3.0-T MRI (GE Healthcare, Milwaukee WI) was used to acquire proton and sodium images. Maps of tissue 23Na concentration were generated using an in-house software developed within MATLAB (Mathworks, Natick, USA, R2018a). 23Na concentration maps were superimposed with the proton-anatomy images to delineate the regions of interest. Using the Horos (The Horos Project, Version 4.0.0) software, the soleus muscle was segmented (Figure, Panel A) and the sodium concentration in the region of interest was recorded for analysis.

Results

28 HD patients completed both 23Na MRI and bloodwork; 7/28 (25%) patients were females; mean±SD age was 66.1±8.3 years, mean body mass index was 30.9±6.5 kg/m2, and mean HD vintage was 30.2±34.9 months. Soleus muscle sodium concentration showed a strong, negative correlation with serum albumin (Figure, Panel B; r=-0.66, p<0.0001). Furthermore, soleus muscle sodium concentration showed a minor association with plasma hemoglobin (r=-0.46, p=0.01).

Conclusion

Serum albumin is a recognized, powerful predictor of mortality in the hemodialysis patient population. The strong relationship between muscle sodium concentration and serum albumin levels suggests that tissue sodium deposition may be a relevant biomarker of clinical outcomes. In addition, muscle sodium deposition may be involved in the development of anemia. These findings warrant further studies investigating the consequences of sodium removal on these biomarkers.
SO029FIRST YEAR RENAL OUTCOME OF TRANSPLANTATIONS OF KIDNEYS FROM HEPATITIS C INFECTED DONORS TO HEPATITIS C NEGATIVE RECIPIENTS
Authors: Molnar Miklos Zsolt , Talwar Manish , Balaraman Vasanthi , Bhalla Anshul , Azhar Ambreen , Yazawa Masahiko , Tsujita Makoto , Podila Pradeep , Nair Satheesh , Eason James
Published: June 2020

Background and Aims

Transplant centers in US are increasingly willing to transplant kidneys from hepatitis C infected donors to hepatitis C negative recipients. Long-term renal outcome data from non-prophylactic treatment approach outside clinical trials is missing.

Method

We compared kidney graft function of 132 hepatitis C negative recipients, who received HCV infected (NAT+ and antibody+/-; HCV+) versus HCV negative (NAT- and antibody-; HCV-) in 2018, in a single center, retrospective, observational study. Categorical variables were compared using χ2 tests and continuous variables were compared using t-tests or Mann–Whitney U-tests, as appropriate. Linear regression was applied to assess independent association between graft function and HCV viremic status.

Results

The mean±SD age of recipients was 52±11 years, 44% were female, 20% and 79% of recipients were Caucasian and African-American, respectively. Baseline characteristics were similar between HCV+ vs HCV- groups, except dialysis duration, donors race, KDPI and cold ischemic time (Table). The DGF rate, estimated GFRs at post-transplant 3, 6, 9 and 12 months was similar between HCV+ and HCV- groups (Table). HCV viremic status was not a predictor of 3, 6, 9 and 12 months eGFR in our unadjusted model and after adjustment for donor and recipient characteristics.

Conclusion

Recipients of HCV-viremic kidneys have similar renal allograft function in the first year after transplantation compared to those who received from HCV-non-viremic kidneys.
SO037AMBULATORY BLOOD PRESSURE IN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE - IMPROVING DIAGNOSIS AND OPTIMIZING THERAPY
Authors: Jankowska Magdalena , Aniserowicz Marek , Nowak Piotr , Szyndler Anna , Hoffmann Michal , Narkiewicz Krzysztof , Debska-Slizien Alicja
Published: June 2020

Background and Aims

Hypertension (AH) is an early complication of autosomal dominant polycystic kidney disease (ADPKD), which significantly increases the risk of decline of kidney function and impacts cardiovascular risk. The diagnosis of AH is often delayed and the optimal control of blood pressure (BP) is difficult to achieve in this group of patients. Of note, the optimal treatment of AH in ADPKD is yet to be established.

Aim of the study was to diagnose AH (including the prevalence of masked hypertension) and to evaluate the control of BP with the use of ABPM in a cohort of ADPKD patients.

Method

ABPMs were performed in 163 consecutive patients, with ADPKD according to Pei criteria, appointed for the first outpatient visit. Prior to the ABPM, the diagnosis based on office BP or current AH treatment was established as well as age, sex, medication intake, and eGFR (CKD-EPI formula) were recorded. The study had a cross-sectional design.

Results

Out of 163 performed ABPMs, 143 were eligible for further analysis. The study group consisted of 93 females and 50 males, median age was 40 (18-87) years and median eGFR was 79.5(13-90) ml/min/1.73m2. 68% of patients had CKD G1 or 2. Median systolic blood pressure (SBP) was 127 (101-157) mmHg with blood pressure variability (BPV) 12 (7.8-23); median diastolic blood pressure (DBP) was 79 (58-98) mmHg, BPV 10.8 (6.2-17.4). 35% of patients were non-dippers, 2.7% extreme dippers and 4.9% reverse-dippers. In 31 (55%), out of 56 patients without previous diagnosis of AH, masked hypertension was found. Among 87 diagnosed with AH before the measurement, 49% were treated with 1 drug, and 29% with 2, 13% with 3, and 2% with 4. The most prevalent medication was ACE-inhibitor. Among treated, only 5.5% had all ABPM values within the target.

Conclusion

55% of patients previously not diagnosed with AH on the basis of office BP proved to suffer from masked hypertension. The night DBP was the most suboptimally controlled value in ADPKD patients. Whether this is a consequence of nonadherence or suboptimal treatment, needs further investigation. ABPM is an indispensable tool in managing patients inflicted with ADPKD.
SO042WHOLE GENOME SEQUENCING OF HUMAN KIDNEY PROGENITORS IDENTIFIES A MUTATION-PRONE CELL TYPE IN THE PROXIMAL TUBULE
Authors: Franco Irene , Helgadottir Hafdis , Moggio Aldo , Larsson Malin , Vrtacnik Peter , Johansson Anna , Norgren Nina , Lundin Pär , Mas-Ponte David , Nordstrom Johan , Lundgren Torbjörn , Stenvinkel Peter , Wennberg Lars , Supek Fran , Eriksson Maria
Published: June 2020

Background and Aims

The genome of every cell accumulates somatic mutations while aging. Somatic mutation data can be used to track a cell´s exposure to mutagens, thereby allowing the discovery of cell types that are more susceptible to mutate and become cancer and the underling mechanisms.

Method

To detect somatic mutations in healthy, human kidney, we set up a protocol for whole genome DNA sequencing of single non-cancer cells. The protocol requires in vitro clonal expansion prior to sequencing, a step that restricts the analysis to cells able to proliferate in vitro (progenitors), but allows a gene expression analysis in addition to genome sequencing. Cells were obtained from six living kidney donors undergoing surgery. In addition to the kidney cortex biopsy, multiple control tissues (skin, subcutaneous fata and visceral fat) were obtained from each donor, allowing a well-controlled comparison of mutation landscapes in different cell types. Donors´ age spanned from 30 to 69.

Results

Somatic mutation and gene expression data showed that we were able to culture two different populations of CD133/CD24 positive, tubular cells. One population showed a low amount of somatic mutations and a mutation profile similar to progenitors from other tissues (fat, skeletal muscle and blood), consistent with a lack of exposure to mutagens. Conversely, the other population showed high mutation burden and a unique mutation landscape, characterized by mutation enrichment in active chromatin, regulatory, and transcribed regions. Accumulation of potential, cancer-driver mutations was 6-fold faster in these compared to control cells. The mutation profile was similar to that of the most common kidney cancer subtypes (clear cell- and papillary cell-carcinoma) and indicated that these cells originated from the proximal tubule, in agreement with gene expression data.

Conclusion

Our somatic mutation data from single genomes support the existence of two different populations of proliferating tubule cells in healthy, human kidney. One is protected from mutagen exposure, similar to stem cells from other organs. The other population is derived from damaged proximal tubule cells and shows a high mutation rate between 30 and 70 years of age. Mutations are enriched in transcribed genes and regulatory regions, thus enhancing the chances of tumorigenic transformation and suggesting conditions that predispose to cancer in the kidney proximal tubule.