bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of bone morphogenetic protein 10 and recurrent atrial fibrillation after catheter ablation
Authors: Hennings Elisa , Aeschbacher Stefanie , Coslovsky Michael , Paladini Rebecca E , Meyre Pascal B , Voellmin Gian , Blum Livia , Kastner Peter , Ziegler André , Conen David , Zuern Christine S , Krisai Philipp , Badertscher Patrick , Sticherling Christian , Osswald Stefan , Knecht Sven , Kühne Michael
Published: June 2023

Aims

Atrial remodelling, defined as a change in atrial structure, promotes atrial fibrillation (AF). Bone morphogenetic protein 10 (BMP10) is an atrial-specific biomarker released to blood during atrial development and structural changes. We aimed to validate whether BMP10 is associated with AF recurrence after catheter ablation (CA) in a large cohort of patients.

Methods and results

We measured baseline BMP10 plasma concentrations in AF patients who underwent a first elective CA in the prospective Swiss-AF-PVI cohort study. The primary outcome was AF recurrence lasting longer than 30 s during a follow-up of 12 months. We constructed multivariable Cox proportional hazard models to determine the association of BMP10 and AF recurrence. A total of 1112 patients with AF (age 61 ± 10 years, 74% male, 60% paroxysmal AF) was included in our analysis. During 12 months of follow-up, 374 patients (34%) experienced AF recurrence. The probability for AF recurrence increased with increasing BMP10 concentration. In an unadjusted Cox proportional hazard model, a per-unit increase in log-transformed BMP10 was associated with a hazard ratio (HR) of 2.28 (95% CI 1.43; 3.62, P < 0.001) for AF recurrence. After multivariable adjustment, the HR of BMP10 for AF recurrence was 1.98 (95% CI 1.14; 3.42, P = 0.01), and there was a linear trend across BMP10 quartiles (P = 0.02 for linear trend).

Conclusion

The novel atrial-specific biomarker BMP10 was strongly associated with AF recurrence in patients undergoing CA for AF.

ClinicalTrials.gov Identifier

NCT03718364; https://clinicaltrials.gov/ct2/show/NCT03718364
When does natural selection take place?
Authors: Vermeij Geerat J
Published: June 2023

Although many studies of form and function find a correlation between performance and adaptive specialization, others fail to discern such a tight link despite careful monitoring and observation. This inconsistency among studies raises the question of when, how often, and how effectively natural selection and the organism’s own activities operate to maintain or improve the adapted state. I suggest here that most organisms operate well within the limits of their capacities (safety factors) most of the time and that interactions and circumstances that cause natural selection and test the body’s limits come in discrete, intermittent events rather than as continuously present or chronic conditions. Everyday life without such events does not test performance limits and therefore does not usually result in natural selection. This perspective on selection as rare, intermittent testing by ecological agencies suggests that studies of selective processes and activity in the wild should focus on observing and measuring the intensity and frequency of selective events and responses, intense challenges stemming from agencies such as predators, competitors, mating-related rituals, and extreme weather.
The influence of age on the timber properties and grading of Scots pine and larch in Ireland
Authors: Gil-Moreno David , Manso Rubén , O’Ceallaigh Conan , Harte Annette M
Published: June 2023

Scots pine (Pinus sylvestris L.) and larch (Larix spp.) are two species that could contribute to diversifying Ireland’s timber supply. However, there is little knowledge about their properties as well as their variation with age. The aim of this study is to investigate the structural properties (modulus of elasticity, strength and density) of Irish-grown Scots pine and larch and the effect of cambial age on timber grading. Structural-sized pieces were used for this purpose, and the timber properties, knots and ring width were measured on 158 and 250 pieces of Scots pine and larch, respectively. Characteristic values of the properties and indicative yields for different strength classes were calculated. The age effect was assessed using an empirical approach, and a novel modelling approach that disaggregates the timber properties at the annual growth ring level. Yields above 90 per cent of C20 were achieved for Scots pine, whereas larch achieved a 100 per cent yield of C24 strength class. The effect of cambial age in the grading properties indicated that older boards increased the characteristic values of a timber population. In Scots pine, the empirical approach showed that the yields increased by up to 26 per cent when using pieces up to 50 years old compared with pieces up to 30 years old. In larch, the use of pieces up to 40 years old increased the yields by up to 16 per cent compared with using pieces up to 30 years old. The results of the modelling approach were consistent with the values obtained in the empirical analysis and can help to make informed decisions regarding rotation lengths for the production of structural timber. Our results found that cambial ages of 40 years in Scots pine produce high yields of structural timber, whereas 30 years are enough for larch.
Thermal insulation and mechanical properties of a specially improved insulation plaster under freezing–thawing and high-temperature conditions
Authors: Ustabas Ilker , Cuce Erdem
Published: June 2023

In this study, the effects of heat preservation and the resistance to environmental conditions of ready-made insulating sludge used in the interior and exterior facades of the buildings were investigated. The insulation consists of lightweight aggregates, boron and steel fiber. Within the scope of the study, 1 L of water was mixed with 1 kg of insulating fluid as a proportion and a composite material was obtained. Thermal conductivity coefficient, resistance to high temperature, changes in ultrasound speed, resistance to frost and compressive strength tests were compared with respect to normal plaster consumption. At the same time, samples of 15 × 15 × 15 cm cube samples taken from fresh concrete were plated to be 1 and 2 cm on each surface, and the extent to which the mortar retained concrete under environmental conditions was investigated. One of the components of the insulating sludge, lightweight aggregate-derived perlite and pumice, was found to provide heat and sound insulation. The presence of boron in the components increased the binding and did not necessitate the use of cement during mortar. It has been observed that the presence of steel fibers minimizes the cracks in the mortar and increases the resistance of the mixture mortar. The unit weight of the insulation plaster mortar is about 0.5 g/cm3 owing to the remarkably lower density of light fine particles. Polymer fibers and boron additives yield a notably low thermal conductivity of 0.13 W/mK.
Could Fact-checks Intervene Directionally Motivated Reasoning and Mitigate Social Divisions? A Case Study in Hong Kong
Authors: Chia Stella C , Lu Fangcao , Gunther Albert C
Published: June 2023

This study examined the effectiveness of fact-checking in reducing misperceptions held by people of two opposing camps in the Anti-Extradition Bill Movement in Hong Kong. The experimental design mirrored the political rhetoric in the city’s media and exposed participants to erroneous information in news reports that cast protesters in a negative light or accused the police unfoundedly. We found that directional motivation persistently exerted a profound influence on people’s acceptance of misinformation. Exposure to fact-checks was found to have limited effects in combating the influence of misinformation and mitigating social division. The effects were contingent on the audiences’ attitude strength and fact-checkers. The findings suggest that the effectiveness of fact-checking is subject to the political and media contexts in which misinformation and fact-checks are circulated as well as the implications of those contexts on people’s trust in fact-checks.
3D quantitative assessment for nuclear morphology in osteocytic spheroid with optical clearing technique
Authors: Inagaki Takashi , Kim Jeonghyun , Tomida Kosei , Maeda Eijiro , Matsumoto Takeo
Published: June 2023

In recent years, three-dimensional (3D) cell culture has been attracting attention as a cell culture model that mimics an environment closer to that of a living organism. It is known that there is a close relationship between cell nuclear shape and cellular function, which highlights the importance of cell nucleus shape analysis in the 3D culture. On the other hand, it is difficult to observe the cell nuclei inside the 3D culture models because the penetration depth of the laser light under a microscope is limited. In this study, we adopted an aqueous iodixanol solution to the 3D osteocytic spheroids derived from mouse osteoblast precursor cells to make the spheroids transparent for 3D quantitative analysis. With a custom-made image analysis pipeline in Python, we found that the aspect ratio of the cell nuclei near the surface of the spheroid was significantly greater than that at the center, suggesting that the nuclei on the surface were deformed more than those at the center. The results also quantitatively showed that the orientation of nuclei in the center of the spheroid was randomly distributed, whereas those on the surface of the spheroid were oriented parallel to the surface of the spheroid. Our 3D quantitative method with an optical clearing technique will contribute to the 3D culture models including various organoid models to elucidate the nuclear deformation during the development of the organs.

Insight box Although 3D cell culture has been a powerful tool in the fields of fundamental biology and tissue engineering, it raises the demand for quantification techniques for cell nuclear morphology in the 3D culture model. In this study, we attempted to optically clear a 3D osteocytic spheroid model using iodixanol solution for the nuclear observation inside the spheroid. Moreover, using a custom-made image analysis pipeline in Python, we successfully quantified the nuclear morphology regarding aspect ratio and orientation. Our quantitative method with the optical clearing technique will contribute to the 3D culture models such as various organoid models to elucidate the nuclear deformation during the development of the organs.
P06 Improving antibiotic prescribing practice in a tertiary burns and plastic surgery department
Authors: Parente Cristina , Joseph Annie
Published: June 2023

Background

Antimicrobial resistance is an ever-emerging global public health issue. In the healthcare setting, it is essential to use antimicrobials appropriately and manage infections effectively to help tackle antimicrobial resistance.

Objectives

To review local antibiotic resistance data, update the plastic surgery infection guidelines based on this data, implement interventions to facilitate compliance with the guidelines and re-audit to assess if these interventions have been effective.

Methods

A review was undertaken of the previous 3 months of antibiotic susceptibility results for significant staphylococci and streptococci species isolated from blood cultures and wound swabs, and the microbiology results of all local cases of necrotizing fasciitis over a 5-year period. The plastic surgery infection guidelines were updated to reflect the changes in local antibiotic resistance rates. Following implementation of the new guideline, various interventions were undertaken including provision of departmental teaching sessions, ensuring availability of appropriate antibiotics in the burns and plastics theatres and redesigning the guideline to include all plastic surgery and infection guidelines within the one document (previously multiple specific guidelines). Between each intervention, compliance with the guideline was measured to establish if the intervention had made a difference.

Results

Changes to the guideline included using clindamycin rather than doxycycline for the treatment of cellulitis in penicillin allergic patients, as 44% of Group A Streptococcus isolates identified in wound swabs were resistant to doxycycline. Other changes included the introduction of linezolid if the patient had received a recent or failed course of clindamycin, and the use of cefazolin rather than clindamycin for patients with severe cellulitis with a penicillin allergy, due to the increase in rates of clindamycin resistance. After the three intervention cycles, prescriber compliance with the guideline increased from 50% to 71% demonstrating the need for ongoing intervention and re-evaluation.

Conclusions

Co-amoxiclav and clindamycin were the most commonly prescribed antibiotics in those patients whose antibiotic prescriptions did not comply with the guidelines. The main reason for this is historical usage of these antibiotics within the specialty; this project demonstrates the challenges in changing established practices in individual clinicians. Interventions to ‘make it easy’ for prescribers to follow antibiotic guidelines (for example, the right antibiotic being easily available at the site of prescription), along with targeted education, can be effective but long-standing prescribing habits within specialist areas may be difficult to change.
P17 Aetiology of hospital-acquired Gram-negative bacteraemias over the COVID-19 pandemic: a single NHS Trust experience, UK
Authors: Dhillon Syra , Buchanan Oscar , Sargent Catherine
Published: June 2023

Background

Gram-negative bacteria (GNB) are the most common cause of healthcare-associated bacteraemias, most commonly caused by Escherichia coli, Klebsiella, and Pseudomonas.1 GNB carry significant mortality and morbidity; therefore, prompt and appropriate antibiotic therapy is important.2 However, there are also high rates of GNB resistance, posing a significant public health concern. Nationally, all NHS trusts are mandated to report their rates of GNB to the UK Health Security Agency as part of their plan to reduce incidence by 2025.3 The COVID-19 pandemic disrupted healthcare delivery from March 2020, with higher rates of GNB being recorded nationally.4

Methods

We retrospectively analysed 3 years of GNB data, using a 5-month sample of April to August each year, from University Sussex Hospital NHS Foundation Trust east hospitals. Looking at hospital-acquired data (defined as blood culture taking on or after ay 3 of admission), we analysed the demographics, incidence and resistance patterns of GNB using online medical and microbiology records. Data collection and analysis took place on Microsoft Excel.

Results

From 2019 to 2021, there were 29, 27 and 19 cases in each time 5-month sample, respectively. The median age of patients was 78, 64 and 73 years. Positive blood cultures were taken later into admission during 2020 (14 versus 8 and 9 days) with an increased length of median hospital stay (33 versus 23 and 24 days). The source of each GNB can be seen in Table 1 (created as per national record keeping guidelines), with 2020 attributing a higher proportion of cases to ‘other’, which includes iatrogenic procedures and surgical operations. Mortality rates were highest in 2020 (26.9 versus 21.4 and 21.1%), although not significantly, with transmission in neonates a risk factor. 2020 also carried the highest rate of multi-drug–resistant GNB (22%), both within and outside of an intensive care setting.

Conclusions

Our data shows an increase in the mortality rate and antibiotic resistance in GNB during the height of the COVID-19 pandemic that returned to baseline the following year, likely due to a reduction in elective activity and fewer bed days. Ongoing evaluation of GNB aetiology, particularly resistance patterns, is vital to improve health outcomes.
P33 Using the Australian National Antimicrobial Prescribing Survey (NAPS) portal to undertake an annual point prevalence survey (PPS)
Authors: Ng Bee Yean , Parsons Teig , O’Riordan Bernadette , Pill Gemma , Dunsmure Louise , Jones Nicola
Published: June 2023

Background

Annual point prevalence surveys (PPS) are cornerstones in antimicrobial stewardship (AMS). The National Antimicrobial Prescribing Survey (NAPS) is a web-based qualitative auditing platform that provides a standardized and validated tool to assist hospitals in assessing the appropriateness of antimicrobial prescribing.

Objectives

To evaluate the usefulness of NAPS in a UK tertiary hospital setting.

Methods

Permission to use the platform was given by NAPS on a pilot basis. NAPS e-learning was completed by the AMS team. All patients on antimicrobials on a single day were extracted using the Cerner electronic prescribing system. Indication, appropriateness and compliance to guidelines were reviewed, anonymized and uploaded by the trained individuals to NAPS. Ethical approval was not required.

Results

695 patients were audited. 35% (n = 241) of the patients were prescribed antimicrobials. The total number of antimicrobial prescriptions was 326, and 46% (n = 190) of antimicrobial prescriptions were under general medicine and geratology. The most common indications for antimicrobials were respiratory 27% (n = 87) followed by intra-abdominal infection 11% (n = 37), sepsis and bacteraemia 11% (n = 37), urinary tract infection 10% (n = 34) and skin and soft tissue infection 8% (n = 25). The most prescribed agent was co-amoxiclav 34% (n = 111). Compliance with guidelines was achieved in 84% (n = 273) of prescriptions, and 72% (n = 236) were deemed appropriate. Inappropriate prescriptions were more prevalent for co-amoxiclav (38%) and ceftriaxone (43%) compared with amoxicillin (6%) and doxycycline (8%) (Figure 1). The most common reasons for inappropriate prescription were incorrect (prolonged) duration (44%) and spectrum too broad (28%).

Conclusions

Using NAPS, we identified that general medicine and geratology are the major users of antimicrobials, and pneumonia is the leading indication for prescribing. Co-amoxiclav is the main antibiotic prescribed, and appropriateness of this and other antibiotics, such as ceftriaxone, are below the 90% target. Consequently, targeted AMS efforts can be designed. PPS results are feedback to the respective teams and have been used in teaching sessions to encourage teams to take ownership of their data and influence prescribing patterns. We have found NAPS to be user friendly and reliable. Reports are produced immediately on completion of the survey to allow timely feedback. We would recommend NAPS as a useful tool in performing PPS and as a potential way to benchmark NHS trusts.
Narrowing the gap: expected versus deployment performance
Authors: Zhou Alice X , Aczon Melissa D , Laksana Eugene , Ledbetter David R , Wetzel Randall C
Published: June 2023

Objectives

Successful model development requires both an accurate a priori understanding of future performance and high performance on deployment. Optimistic estimations of model performance that are unrealized in real-world clinical settings can contribute to nonuse of predictive models. This study used 2 tasks, predicting ICU mortality and Bi-Level Positive Airway Pressure failure, to quantify: (1) how well internal test performances derived from different methods of partitioning data into development and test sets estimate future deployment performance of Recurrent Neural Network models and (2) the effects of including older data in the training set on models’ performance.

Materials and Methods

The cohort consisted of patients admitted between 2010 and 2020 to the Pediatric Intensive Care Unit of a large quaternary children’s hospital. 2010–2018 data were partitioned into different development and test sets to measure internal test performance. Deployable models were trained on 2010–2018 data and assessed on 2019–2020 data, which was conceptualized to represent a real-world deployment scenario. Optimism, defined as the overestimation of the deployed performance by internal test performance, was measured. Performances of deployable models were also compared with each other to quantify the effect of including older data during training.

Results, Discussion, and Conclusion

Longitudinal partitioning methods, where models are tested on newer data than the development set, yielded the least optimism. Including older years in the training dataset did not degrade deployable model performance. Using all available data for model development fully leveraged longitudinal partitioning by measuring year-to-year performance.
Medicaid expansion and racial disparity in timely multidisciplinary treatment in muscle invasive bladder cancer
Authors: Jiang Changchuan , Perimbeti Stuthi , Deng Lei , Xing Jiazhang , Chatta Gurkamal S , Han Xuesong , Gopalakrishnan Dharmesh
Published: June 2023

Background

Multidisciplinary cancer care (neoadjuvant chemotherapy followed by radical cystectomy or trimodality therapy) is crucial for outcome of muscle-invasive bladder cancer (MIBC), a potentially curable illness. Medicaid expansion through Affordable Care Act (ACA) increased insurance coverage especially among patients of racial minorities. This study aims to investigate the association between Medicaid expansion and racial disparity in timely treatment in MIBC.

Methods

This quasi-experimental study analyzed Black and White individuals aged 18-64 years with stage II and III bladder cancer treated with neoadjuvant chemotherapy followed by radical cystectomy or trimodality therapy from National Cancer Database 2008-2018. Primary outcome was timely treatment started within 45 days following cancer diagnosis. Racial disparity is the percentage-point difference between Black and White patients. Patients in expansion and nonexpansion states were compared using difference-in-differences and difference-in-difference-in-differences analyses, controlling for age, sex, area-level income, clinical stage, comorbidity, metropolitan status, treatment type, and year of diagnosis.

Results

The study included 4991 (92.3% White, n = 4605; 7.7% Black, n = 386) patients. Percentage of Black patients who received timely care increased following the ACA in Medicaid expansion states (54.5% pre-ACA vs 57.4% post-ACA) but decreased in nonexpansion states (69.9% pre-ACA vs 53.7% post-ACA). After adjusting covariates, Medicaid expansion was associated with a net 13.7 percentage-point reduction of Black–White patient disparity in timely receipt of MIBC treatment (95% confidence interval = 0.5% to 26.8%; P < .01).

Conclusions

Medicaid expansion was associated with statically significant reduction in racial disparity between Black and White patients in timely multidisciplinary treatment for MIBC.
Optimizing machine learning methods to discover strong gravitational lenses in the deep lens survey
Authors: Keerthi Vasan G C , Sheng Stephen , Jones Tucker , Choi Chi Po , Sharpnack James
Published: June 2023

Machine learning models can greatly improve the search for strong gravitational lenses in imaging surveys by reducing the amount of human inspection required. In this work, we test the performance of supervised, semi-supervised, and unsupervised learning algorithms trained with the ResNetV2 neural network architecture on their ability to efficiently find strong gravitational lenses in the Deep Lens Survey (DLS). We use galaxy images from the survey, combined with simulated lensed sources, as labeled data in our training data sets. We find that models using semi-supervised learning along with data augmentations (transformations applied to an image during training, e.g. rotation) and Generative Adversarial Network (GAN) generated images yield the best performance. They offer 5 – 10 times better precision across all recall values compared to supervised algorithms. Applying the best performing models to the full 20 deg2 DLS survey, we find 3 Grade-A lens candidates within the top 17 image predictions from the model. This increases to 9 Grade-A and 13 Grade-B candidates when 1 per cent (∼2500 images) of the model predictions are visually inspected. This is ≳ 10 × the sky density of lens candidates compared to current shallower wide-area surveys (such as the Dark Energy Survey), indicating a trove of lenses awaiting discovery in upcoming deeper all-sky surveys. These results suggest that pipelines tasked with finding strong lens systems can be highly efficient, minimizing human effort. We additionally report spectroscopic confirmation of the lensing nature of two Grade-A candidates identified by our model, further validating our methods.
Probing the delay time of supermassive black hole binary mergers with gravitational waves
Authors: Fang Yun , Yang Huan
Published: June 2023

Merging supermassive black hole binaries are expected as a consequence of galaxy mergers, yet the detailed evolution path and underlying merging mechanisms of these binaries are still subject to large theoretical uncertainties. In this work, we propose to combine the (future) gravitational wave measurements of supermassive black hole binary merger events with the galaxy merger rate distributions from galaxy surveys/cosmological simulations, to infer the delay time of binary mergers, as a function of binary mass. The delay time encodes key information about binary evolution, which can be used to test the predictions of various evolution models. With a Mock data set of supermassive black hole binary merger events, we discuss how to infer the distribution of delay time with hierarchical Bayesian inference and test evolution models with the Bayesian model selection method. The astrophysical model uncertainties are also considered in the hierarchical Bayesian inference and Bayesian model selection.
Accretion in the binary system GG Carinae and implications for B[e] supergiants
Authors: Kashi Amit
Published: June 2023

We simulate the hydrodynamics of the wind flow in the B[e] supergiant binary system GG Carinae and obtain the mass accretion rate on to the secondary and the observed light curve. We find an inhomogeneous Bondi–Hoyle–Lyttleton accretion into a curved accretion tail, and confirm that the accretion rate is modulated along the orbit, with a maximum close to periastron. We show that the accretion itself cannot account for the periodical variation in brightness. Instead, we explain the observed variation in the light curve with absorption by the accretion tail. Our results are in general agreement with previously derived stellar masses, orbital parameters, and the system orientation, but imply that the B[e] supergiant is more luminous. We find an effect related to the orbital motion of the two stars, in which the accretion tail is cut by the primary, and we term it the Lizard Autotomy Effect. As part of the effect, the primary is self accreting wind that it ejected earlier. The Lizard Autotomy Effect creates an outwardly expanding spiral shell made up of broken segments. We suggest that such a tail exists in other B[e] supergiant systems and can be the source of the circumstellar material observed in such systems. The accretion also forms a disc around the secondary near periastron that later vanishes. We suggest that the formation of such a disc can launch jets that account for the bipolar structure observed around some B[e] supergiants.
Topological data analysis reveals differences between simulated galaxies and dark matter haloes
Authors: Ouellette Aaron , Holder Gilbert , Kerman Ely
Published: June 2023

We use topological summaries based on Betti curves to characterize the large-scale spatial distribution of simulated dark matter haloes and galaxies. Using the IllustrisTNG and CAMELS-SAM simulations, we show that the topology of the galaxy distribution is significantly different from the topology of the dark matter halo distribution. Further, there are significant differences between the distributions of star-forming and quiescent galaxies. These topological differences are broadly consistent across all simulations, while at the same time there are noticeable differences when comparing between different models. Finally, using the CAMELS-SAM simulations, we show that the topology of the quiescent galaxies, in particular, depends strongly on the amount of supernova feedback. These results suggest that topological summary statistics could be used to help better understand the processes of galaxy formation and evolution.
The cosmic web in Lyman-alpha emission
Authors: Byrohl Chris , Nelson Dylan
Published: June 2023

We develop a comprehensive theoretical model for Lyman-alpha (Ly α) emission, from the scale of individual Ly α emitters (LAEs) to Ly α haloes (LAHs), Ly α blobs (LABs), and Ly α filaments (LAFs) of the diffuse cosmic web itself. To do so, we post-process the high-resolution TNG50 cosmological magnetohydrodynamical simulation with a Monte Carlo radiative transfer method to capture the resonant scattering process of Ly α photons. We build an emission model incorporating recombinations and collisions in diffuse gas, including radiative effects from nearby AGN, as well as emission sourced by stellar populations. Our treatment includes a physically motivated dust model, which we empirically calibrate to the observed LAE luminosity function. We then focus on the observability and physical origin of the z = 2 Ly α cosmic web, studying the dominant emission mechanisms and spatial origins. We find that diffuse Ly α filaments are, in fact, illuminated by photons that originate not only from the intergalactic medium itself but also from within galaxies and their gaseous haloes. In our model, this emission is primarily sourced by intermediate mass haloes (1010–1011 M⊙), principally due to collisional excitations in their circumgalactic media as well as central, young stellar populations. Observationally, we make predictions for the abundance, area, linear size, and embedded halo/emitter populations within filaments. Adopting an isophotal surface brightness threshold of 10−20 erg s−1 cm−2 arcsec−2, we predict a volume abundance of Ly α filaments of ∼10−3 cMpc−3 for lengths above 400 pkpc. Given sufficiently large survey footprints, detection of the Ly α cosmic web is within reach of modern integral field spectrographs, including MUSE, VIRUS, and KCWI.
#2640 SINGLE TUBULE RNASEQ FROM GITLEMAN SYNDROME MICE REVEALING MAGNESIUM HANDLING IN DISTAL RENAL TUBULES
Authors: Sung Chih-Chien , Hsu Yu-Juei , Lin Chien-Ming , Lin Shih-Hua
Published: June 2023

Background and Aims

Gitelman syndrome (GS) is characterized by salt-losing hypotension, hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria caused by a specific mutation in the thiazide-sensitive sodium chloride co-transporter (NCC) gene SLC12A3. However, magnesium (Mg2+) associated gene in the distal renal tubules remains unclear.

Method

We performed small samples RNA-seq from manual microdissection of distal convoluted tubules (DCT1s) in nonsense Ncc Ser707X (S707X) homozygous knockin mice (NccS707X/S707X mice) (n = 4) and wild-type (WT, n = 4). Cortical thick ascending limbs of Henle (cTALs), connecting tubule (CNT), cortical collecting duct (CCD) were also microdissected.

Results

Among DCT makers, Slc12a3 (NCC) and Pvalb (Parabumin) were significantly downregulated (Log2TPMS707X/WT: −4.45, P = 0.0003; −6.888258295, P = 0.0003, respectively). Mg2+ transporters of Trpm6 gene expression were significantly downregulated. In addition, Egf and Cnnm2 have been reported to increase TRPM6 trafficking or activity, were also decreased in DCT segment. Rack1 was also decreased in DCT1. Claudins including Cldn10, Cldn16, and Cldn19, involving paracellularly reabsorption of Ca2+and Mg2+, were not changed in cTALs. All findings indicate chronic hypokalemia may mediate DCT1 remodeling and affect development.

Conclusion

Our small samples RNA-Seq from dissected DCT highlight the possible molecular pathway of hypomagnesemia in GS. Chronic hypokalemia caused by inactivation of Slc12A3 gene may affect the DCT development causing loss of Mg2+ associated transporters.
#3973 EXCELLENT EFFICACY AND BENEFICIAL SAFETY DURING FIVE YEAR FOLLOW-UP OF RAPID STEROID WITHDRAWAL AFTER RENAL TRANSPLANTATION (HARMONY STUDY)
Authors: Stumpf Julian , Thomusch Oliver , Opgenoorth Mirian , Wiesener Michael , Pascher Andreas , Woitas Rainer , Suwelack Barbara , Rentsch Markus , Witzke Oliver , Rath Thomas , Banas Bernhard , Benck Urs , Sommerer Claudia , Kurschat Christine , Lopau Kai , Weinmann-Menke Julia , Jänigen Bernd , Trips Evelyn , Hugo Christian
Published: June 2023

Background and Aims

We previously reported excellent efficacy and improved safety aspects of rapid steroid withdrawal in the randomized controlled one year “Harmony” trial with 587 predominantly deceased-donor kidney transplant recipients randomized either to basiliximab or rabbit antithymocyte globulin induction therapy and compared to standard immunosuppressive therapy consisting of basiliximab, low tacrolimus once daily, mycophenolate mofetil, and corticosteroids. The five-year post-trial follow-up (FU) data reported here were obtained in an observational manner to evaluate, how these excellent short-term surrogate parameters will translate into hard long-term outcome parameters like patient death/graft loss.

Method

The five-year post-trial follow-up data were obtained in an observational manner at a three and a five-year visit for patients who consented to participate and covered clinical events that occurred from the second year onwards.

Results

Biopsy-proven acute rejection and death-censored graft loss rates remained low and independent of rapid steroid withdrawal (see Figure 1). Rapid steroid withdrawal was an independent positive factor for patient survival (adjusted hazard ratio 0.554, 95 % confidence interval 0.314 to 0.976; p = 0.041, see Table 1). The reduced incidence of post-transplantation diabetes mellitus in rapid steroid withdrawal patients during the original one-year study period was not compensated by later incidences during follow-up. Incidences of other important outcome parameters such as opportunistic infections, malignancies, cardiovascular morbidity/risk factors, donor specific antibody formation, or kidney function did not differ during follow-up period.

Conclusion

The Harmony follow-up trial confirms excellent efficacy and beneficial safety aspects of rapid steroid withdrawal under modern immunosuppressive therapy demonstrating for the first time increased patient survival in an immunologically low-risk, elderly population of Caucasian kidney transplant recipients.
#4088 IMPACT OF DYSMAGNESEMIA ON ATRIAL FIBRILLATION IN MAINTENANCE HAEMODIALYSIS PATIENTS: A NATIONWIDE STUDY
Authors: Toida Tatsunori , Kurita Noriaki , Masanori Abe , Hanafusa Norio , Joki Nobuhiko
Published: June 2023

Background and Aims

The dose-response relationship between serum magnesium (sMg) and atrial fibrillation (AF) and the contribution of dysmagnesemia to AF remain unknown among haemodialysis patients.

Method

This was a nationwide cross-sectional study on the Japanese Society for Dialysis Therapy registry as of the end of 2019. Eligible participants were adult patients undergoing haemodialysis thrice a week. The main exposure was sMg, categorised into seven categories (≤1.5, >1.5-≤2, >2-≤2.5, >2.5-≤3, >3-≤3.5, >3.5-≤4, and ≥4.0 mg/dL). The outcome was AF reported by dialysis facilities. The independent contribution to AF was assessed via logistic regression to generate population-attributable fractions, assuming a causal relationship between sMg and AF.

Results

A total of 165,926 patients from 2,549 facilities were analyzed. The prevalence of AF was 7.9%. Compared with the reference (>2.5-≤3 mg/dL), lower sMg was associated with increased AF (adjusted ORs [95%CI] of 1.49 [1.19-1.85], 1.24 [1.17-1.32], and 1.11 [1.06-1.16] for sMg of ≤1.5, >1.5-≤2.0, and >2.0-≤2.5 mg/dl categories, respectively). The slightly high sMg was associated with fewer AF (adjusted OR 0.87 [95%CI 0.79-0.96] for sMg of >3.0-≤3.5 mg/dl). The adjusted population-attributable fraction of lower sMg and higher and lower sMg for AF was 7.4% and 6.9%, respectively.

Conclusion

An association does indeed exist between lower sMg and AF, with the fewest percentages of AF at sMg levels above the reference range for the general population. Dysmagnesemia may be an important contributor to AF among adult haemodialysis patients. Further longitudinal studies are warranted to determine whether correction of sMg reduces the incidence of AF.
#4110 BIO-CONDUCTIVITY MEASUREMENTS ENABLE PORTABLE AND SELF-ADMINISTRATED CHRONIC KIDNEY DISEASE SCREENING AND MONITORING
Authors: Cheung Pak To , Zouari Fedi , Touboul Adrien , Ho Cheuk Man , Sin Venice , Wong Eddie C , Zhou Iris , Yap Desmond , Chan Russell
Published: June 2023

Background and Aims

Chronic kidney disease (CKD) is an escalating health concern. The identification of CKD during mass public screening by laboratory tests constitutes important resource implications. Home-based and self-administrated approach to screen and monitor disease severity in both healthy and CKD subjects are eagerly awaited. Frequency-difference electrical impedance tomography (fdEIT) reconstructs the interior of a body by measuring the electrical responses to a small alternating current applied at the surface of the subject at various frequencies. Kidney fibrosis is a cardinal feature of CKD, which is associated with alterations in renal molecular composition and hence electrical conductivity. Therefore, this study aims to investigate the feasibility of a portable, self-administrated approach to assess CKD severity using fdEIT in the kidney region.

Method

Clinical subjects are recruited at Queen Mary Hospital, Hong Kong. EIT data was collected via a PVC belt acting as an electrode holder placed circumferentially on the upper abdominal region of the subject. The belt was connected to a portable console to collect EIT data. 24 frequencies ranging from 10KHz to 300KHz are used to stimulate electrical responses in the body. (Figure 1A) Paired blood and urine samples were collected for measured of eGFR. Group source separation was implemented to extract the kidney region of interest (ROI) and extract conductivity features (Figure 1A); these features, together with the age of the subject, are then input into a regression model to estimate the eGFR and the CKD stage of the subject according to the following classification scheme: stage 1 CKD (eGFR > 90) as healthy subjects, stages 3, 4, 5 CKD (eGFR < 60) as unhealthy subjects, stage 2 CKD (60 < eGFR < 90) as borderline cases.

Results

75 subjects were recruited (54 with CKD and 21 were healthy volunteers). We obtained an eGFR estimation model with R2 score of 0.40. We also obtained a CKD stage classifier with sensitivity of 87.5% and specificity of more than 99.9%. (Figure 1C) The mean conductivity in the extracted kidney signal comprises 40% weighting in the regression model (Figure 1B), showing comparable importance as the age in predicting the eGFR.

Conclusion

The results demonstrate that measuring bio-conductivity anomalies through fdEIT is highly accurate and non-invasive, and can be developed into a portable and self-administrable device to screen and monitor CKD
#4534 FINERENONE ADDED TO RAS/SGLT2 BLOCKADE FOR NON-DIABETIC CHRONIC KIDNEY DISEASE: RESULTS OF A PRECLINICAL DOUBLE-BLINDED RANDOMIZED CONTROLLED TRIAL
Authors: Zhu Zhihui , Kusunoki Yoshihiro , Rosenkranz Karoline , LI Chenyu , Klaus Martin , Gross Oliver , Angelotti Maria Lucia , Cirillo Luigi , Romagnani Paola , Bülow Roman David , Boor Peter , Anders Hans-Joachim
Published: June 2023

Background and Aims

Inhibitors of the renin-angiotensin system (RAS), sodium-glucose transporter (SGLT)-2, and the mineralocorticoid receptor (MR) have all demonstrated renoprotective effects in large clinical trials of diabetes-related CKD. Furthermore, dual RAS/SGLT2 blockade showed additive renoprotective effects also in non-diabetic CKD. We hypothesized that triple RAS/SGLT2/MR blockade would be even superior to dual RAS/SGLT2 blockade in non-diabetic CKD.

Method

We performed a “no touch” preclinical randomized controlled trial in Col4a3-deficient mice with spontaneous and progressive CKD (registry ID: PCTE0000266). Treatments were administered as food admix from 6-14 weeks of age at the following estimated doses: 10 mg/kg ramipril, 30 mg/kg empagliflozin, 10 mg/kg finerenone. The prespecified primary endpoint was total lifespan up to uremic death. Ancillary studies addressed baseline histology, and mechanistic studies on a subset of mice after 2.5 weeks of treatment.

Results

At the time of randomization, Col4a3-/- mice had albuminuria, elevated serum creatinine, glomerulosclerosis, tubular atrophy, and interstitial fibrosis. Total lifespan was 63.7 ± 9.99 days (vehicle), 77.25 ± 5.34 days (ramipril), 80.3 ± 10.98 days (ramipril+empagliflozin), and 103.05 ± 20.28 days (triple therapy), respectively. Artificial intelligence-based histopathology and RNA sequencing analysis documented a potent anti-sclerotic, -inflammation and -fibrotic effect of the triple combination.

Conclusion

Adding finereone to dual RAS/SGLT2 blockade significantly prolongs uremia-free lifespan even when started at an advanced stage of Alport nephropathy. Triple RAS/SGLT2/MR blockade could be a potent treatment strategy to prolong uremia-free lifespan in patients with CKD related to Alport syndrome and possibly other progressive kidney disorders.
#5127 COMBINED ACTIVITY AND CHRONICITY SCORE FOR PROGNOSTIC ASSESSMENT IN ANCA-ASSOCIATED VASCULITIS WITH GLOMERULONEPHRITIS
Authors: Moura Marta Casal , Fervenza Fernando Custodio , Warrington Kenneth , Specks Ulrich , Sethi Sanjeev
Published: June 2023

Background and Aims

Previous studies have shown that chronic changes on kidney biopsy are useful for stratifying the risk of kidney failure in patients with AAV-GN. We aimed to evaluate the impact of inflammatory activity for the prediction of renal outcomes.

Method

A retrospective cohort study of MPO- or PR3-ANCA positive patients with AAV and active renal disease. Inflammatory activity was assessed by the Activity Index (AI): a ratio between the number of crescents and/or necrosis and the total number of glomeruli (in percent). We calculated the AI score: 0-5 = 0; 6-10 = 1; 11-15 = 2; 16-20 = 3; 21-25 = 4; 26-37.5 = 5; 37.6-50 = 6; 51-65 = 7; 66-80 = 8; 80-90 = 9; 90-100 = 10. Chronicity was evaluated with the Mayo Clinic Chronicity Score (MCCS). For the combined score, we summed the MCCS and the AI.

Results

Results. We analyzed 326 patients with kidney biopsies available to score. The biopsies had in median (IQR), 13 glomeruli (9-20), 4 crescents (2-6) and an AI of 28.6% (15.3-47.6). The population was classified according with the risk of progression to kidney failure (KF) in 3 classes as (i) low (0-6) – 114 (35.0%), (ii) intermediate (7-11) – 152 (46.6%), and (iii) high (≥12) – 60 (18.4%). Median eGFR at baseline correlated with the overall risk categories: 42.2 vs. 22.1 vs. 13.4 mL/min/1.73 m2, p<0.0001. The proportion of patients with eGFR< 30 mL/min/1.73 m2 was increased in patients classified as high: 88.3% vs. 66.4% vs. 36.0%, p<0.0001. Renal recovery was more frequent in patients at low risk of progression: 87.7% vs. 64.6% vs. 36.6%, p<0.0001, whereas kidney failure at 12 months and dialysis were more frequent in patients at higher risk (36.7% vs. 12.4% vs. 3.8%, p<0.0001; 35.6% vs. 13.0% vs. 2.9%, p<0.0001, respectively). The combination of AI with MCCS independently predicted the risk of KF at 12 months (HR 1.916, 95%CI 1.210 - 3.033, p = 0.006), particularly increased in patients classified as high risk (HR 3.124, 95%CI 1.224 – 7.970, p = 0.017) and in patients with PR3-ANCA (HR 1.896, 95%CI 1.012 - 3.551, p = 0.046) independently of eGFR at AAV-GN diagnosis and adjusted for severity of renal involvement and age.

Conclusion

The combined assessment of acute inflammatory activity and chronic changes on kidney histology independently predicted renal outcomes in patients with AAV-GN. The impact of the inflammatory activity is cumulative to the chronic changes.
#5319 ACCURACY OF PLATELET INDICES AS PREDICTOR OF IN-HOSPITAL MORTALITY IN PATIENTS WITH ACUTE KIDNEY INJURY REQUIRING RENAL REPLACEMENT THERAPY
Authors: Balasa Melvy June
Published: June 2023

Background and Aims

Acute kidney injury (AKI) is a major medical complication associated with a markedly increased risk of death, particularly in patients admitted to the ICU where in-hospital mortality exceeds 50%1. This study aimed to determine the accuracy of MPV, platelet count, and PDW as predictors of adverse outcomes in patients with AKI who received initiation renal replacement therapy (RRT).

Method

A retrospective cohort single-center study was done in a local private tertiary hospital in Cebu. Four hundred ninety-one patients with AKI who underwent RRT between January 2018 and December 2021 were enrolled. A retrieval of data on demographic and clinical parameters during the initiation of RRT was done. The impact of mortality-related factors were identified using univariate and multivariate logistic regression analysis. Determination of optimal cut-off values of platelet indices for in-hospital mortality was done.

Results

This study showed that the in-hospital mortality of patients was 58.45%, with a mean age of 68.6 ± 16.28 years among non-survivors. Among the platelet indices, platelet count and PDW were good predictors of in-hospital mortality in patients who received initiation renal replacement therapy. The optimal cut-off value of platelet count was 173 × 103/uL (sensitivity 56.45%, specificity 62.25%, PPV 67.78%, NPV 50.40%, AUC 0.604). The optimal cut-off value of PDW was 16.45% (sensitivity 50.87%, specificity 71.57%, PPV 71.57%, NPV 50.87%, AUC 0.611).

Conclusion

Platelet indices are feasible parameters that can be used as prognostic markers for mortality in patients with AKI requiring RRT. The in-hospital mortality of patients with AKI requiring initiation RRT is high (58.45%). Low platelet counts, high MPV values, and high PDW values are associated with poorer outcomes and higher mortality risk as compared to patients with normal indices.