bluuebunny/crossref_metadata_2025 huggingface dataset:
Weed species composition of different peat areas under pineapple plantation in Muar, Johor.
Authors: Noorsuliyana M N , Noor N M , Rahman S M A , Aani S N A
Published: June 2023

Weeds is the biggest challenge for pineapple production as competing for natural properties such as nutrient, water, sunlight, shelter and others which provided for the pineapple and also act as a host for pest attack. Improper weed management could cause severe weed infestation and reduce pineapple yield specifically in peat soils compared to mineral soils. Peat soils has excellent moisture holding, aeration and physical characteristics for weed germination. Since weed germination was influenced by agronomic changes, this study was conducted to examine weed species composition infested peat soils due to very limited study pertaining this issue. Study was carried out at three different peat areas of pineapple fields in Mukim Ayer Hitam, Muar, Johor. Experiment was done according to the quantitative survey method by using standardized quadrat. Surveying was done several weeks upon herbicides spraying. Broadleaves dominated peat areas compared to grasses, sedges and ferns at all sampling locations. Asystasia gangetica was found as most dominant weed species recorded more than 40% in peat soil regardless the surveyed locations. Asystasia gangetica adapted well in peat soil due to creeping root that remain robust. Proper documentation of dominant weed species infested pineapple plantation particularly in peat soil will be the key tool for sustainable weed management.
Techno-economic studies of threshing green beans (vigna radiata) using power thresher.
Authors: Yulianto K , Santosa  , Andasuryani  , Noviska E
Published: June 2023

Green bean threshing is one of the most important steps in the cultivation and processing of green beans. However, in practice, many problems are found that affect the level of economy and efficiency. This study aims to analyze the techno-economics of threshing green beans using a multipurpose threshing machine, namely the power thresher. The research method used involves a technical approach, economics, and statistics. The results showed that the green beans with a moisture content of 16.56% and an average feeding capacity of 388.88 kg/hour had an average threshing efficiency of 94.67% and a percentage of damaged green beans of 2.96%. Based on the results of research on parameter-technical parameters and statistics, it shows that there is an influence of moisture content on threshing green beans. In addition, for economic parameters, the basic cost for threshing green beans with a moisture content of 16.56% is Rp 255.30 per kg, with a break-even point of 21,076,738 kg per year. It can be concluded that, the lower the moisture content of green beans, the higher the economic value produced. In addition, the low moisture content makes the machine have a high level of efficiency.
Screening of antioxidant activities and their bioavailability of tropical plants
Authors: Pujiawati Y , Khotijah L , Wiryawan IKG
Published: June 2023

Indonesia has many types of plants that have the potential to be used as natural antioxidants. This study aims to characterize natural sources of antioxidants from five plants species: jackfruit leaves, turmeric, black tea, soursop peels, and aloe vera. The method used involved an analysis of phytochemicals in the form of polyphenols, tannins, and flavonoids. As well as analysis of antioxidant activity using the DPPH method. The data obtained were analyzed by ANOVA (Analysis of Variance) and Duncan’s test. Based on these data, the highest yields were found in jackfruit leaves, turmeric, black tea, and aloe vera (P<0.05), while the lowest yields were found in soursop peels. Based on phytochemical data, the highest total phenol was found in jackfruit leaves and soursop skin (P<0.05). While the highest flavonoid content was found in black tea and aloe vera (P<0.05), and the highest tannin content was found in black tea and soursop skin. Based on the method of measuring antioxidant activity, it was found that jackfruit leaves and black tea had the highest antioxidant activity.
Valorization of biomass using deep eutectic solvent: a short review
Authors: Onwucha C. N. , Talabi J. O. , Ajayi S. O. , Ehi-Eromosele C. O. , Ajanaku K. O.
Published: June 2023

The current rise in global energy demand has led to environmental concerns such as resource depletion and pollution. This has steered researchers towards exploring different renewable sources to achieve a sustainable circular bio-economy. Interestingly, the abundant nature of lignocellulose biomass (LCB) has attracted a lot of attention in the production of various specialty chemicals and fuels. The valorization of LCB requires that the recalcitrant structure of the biomass be broken down. However, the high capital cost, operating temperature, and several constraints that accompanythe pretreatment process make most of the pretreatment process economically unviable. Therefore, the quest for an environmentally benign pretreatment process led to the discovery of deep eutectic solvents (DES). They are classified as green solvents due to their biodegradable properties, lowcosts, eco-friendliness, enzyme compatibility, facile methods of synthesis, and recyclability. This review aims at giving information on LCB, Ionic liquids (ILs), and DES, the valorization of biomass to produce biofuel, and the recyclability of DES.
Impacts of Aerosol Scattering Attenuation on Free-Space Optical Communication in Owerri, Nigeria
Authors: Ayo-Akanbi O. A. , Akinwumi S. A. , Omotosho T.V. , A Arijaje T. , Ometan O. O. , Adewusi O. M.
Published: June 2023

In spite of the several benefits of using free-space optical (FSO) communication systems as complementary platforms for next-generation networks, the existence of atmospheric disturbances such fog and scintillations are key sources of signal impairment that affect system performance. Thus, it is crucial to learn about the specific weather patterns of the areas where FSO lines will be installed. The purpose of this work is to estimate the availability performance of FSO lines broadcasting at both 850 nm and 1550 nm by performing a statistical analysis of meteorological visibility data gathered for Owerri in Nigeria over a 21-year period (2000-2021). The results shows that the visibility during the most common fog events in Owerri is 100 meters. The probabilities of encountering and exceeding the scattering attenuations associated with Owerri’s most common fog event are 0.0002 and 0.0229, respectively. This research could be expanded in the future by exploring the effects of varying localized climatic conditions on the many forms of optical signals, such as plane, spherical, and Gaussian beam waves.
Groundwater occurrence and flow in varying geological formations
Authors: Ojoawo Ayobami Ismaila , Adagunodo Theophilus Aanuoluwa
Published: June 2023

Groundwater includes water that is formed within the unsaturated zone (soil), above the water table (capillary fringe) and below the water table. Its occurrence is everywhere, and it is restricted to a maximum of 750 m depth in the near surface. Groundwater availability within the subsurface formation has become a primary concern to the geoscientists because the dependency of surface water has been limited and declined due to it inadequate yield during the period of a year and also the surface contaminant which affect its quality and potential. The investigation of groundwater in the near surface has been a major principal discovery which has served both the domestic, commercial, agricultural and industrial purposes and to understand the continuity of groundwater availability within the subsurface, a study on occurrence and flow of groundwater is highly significant. Understanding the flow pattern is a major constituent in productive groundwater exploitation and exploration. Therefore, this review has been design to place emphasis on the occurrence and flow of groundwater in the near surface, which is one of the agenda of the Sustainable Development Goals.
Retrograde Assemblages of Gneisses at Arigidi and Erusu Areas of Southwestern Nigeria
Authors: Oziegbe E. J. , Oziegbe O.
Published: June 2023

The study is aimed to unravel the presence of low-grade minerals in the migmatite terrain of Southwestern Nigeria. Mineral and textural relationship of mineral assemblages were determined using a petrographic microscope, while chemical composition was analyzed using XRF and LA-ICP-MS. Petrographic studies show the mineral assemblage, biotite + plagioclase + chlorite + epidote + quartz + muscovite + ilmenite ± calcite. There is intense alteration of both biotite and plagioclase. Textural evidence shows chloritization of biotite and epidotization of both biotite and plagioclase. Epidotization of biotite is basically at the edges of biotite while that of plagioclase in more intense at the core of grains. Primary foliation is defined by mineralogical banding of quartzo-feldspathic and mafic minerals, while secondary foliation is defined by both biotite and chlorite. SiO2 contents are high in both gneisses (> 60 wt %), while there is a high depletion of REE. The results from field observations, mineral assemblages and textural relationship suggests that deformation due to shearing could have enhanced the retrograde chloritization of gneisses. Shearing could have created a path for the influx of fluid (H2O & CO2) thus triggering alteration of both biotite and plagioclase. Hydrothermal fluids containing K+ can be said to have initiated the retrograde process which gave rise to reactions that produces secondary low grade minerals; chlorite, epidote and muscovite.
Investigation of subsurface contaminants leachate within Ansaru-Islam Secondary School, Ilorin, Nigeria
Authors: Suleman K. O. , Adagunodo T. A. , Ogunmola O. L. , Adeoye T. O. , Sunmonu L. A. , Alagbe G. A. , Agboola R. O. , Usikalu M. R. , Isibor P. O. , Akinwumi S. A. , Olawole O. C. , Babarimisa I. O.
Published: June 2023

This study adopts the use of Vertical Electrical Sounding (VES) and 2-D resistivity imaging (employing Schlumberger and Wenner array configurations) to investigate and map the extent of leachate’s migration and its possible impacts on groundwater within Abata Asunkere dumpsite, Ilorin, Kwara State. This study was inspired by the unrestrained manner of garbage dumping in the area over time, which poses great threat to the availability of clean water for the increasing populace. To delineate the subsurface, 2-D resistivity imaging data were acquired along two traverses, while the VES data were randomly acquired along the established traverses. The 2-D resistivity imaging and VES data were processed using Res2D and IPI2Win software respectively. The results of the 2-D and VES revealed five (5) geoelectric sections, which correspond to the topsoil, clayey sand, weathered basement, fractured basement and fresh basement rocks with H, QH and KH sounding signature curve types. The topsoil has layer thickness of 0.5 - 1.7 m and resistivity values ranging from 11.9 - 165 Ωm. The clayey sand has layer thicknesses between 0.7 - 2.8 m and resistivity values ranging from 20.1 - 56 Ωm. The weathered basement has thickness of 0.9 - 16.3 m and resistivity values ranging from 2.09 - 5.25 Ωm. The fractured to fresh basement has resistivity values ranging from 26.8 - 3000 Ωm with thickness ranging from 5.3 m to infinity. The third layer with low resistivity values of 2.09 - 3.52 Ωm at depth range 0.9 - 10 m is suggestive of leachate contamination. The outcome of this study indicates that some regions around the dumpsite are susceptible to leachate’s contamination, which has tendencies to permeate the unconfined aquifers in the study area if not properly monitored and controlled.
Low regularity estimates for CutFEM approximations of an elliptic problem with mixed boundary conditions
Authors: Burman Erik , Hansbo Peter , Larson Mats
Published: June 2023

We show error estimates for a cut finite element approximation of a second order elliptic problem with mixed boundary conditions. The error estimates are of low regularity type where we consider the case when the exact solution

u
∈

H
s

u \in H^s

with

s
∈
(
1
,
3

/

2
]

s\in (1,3/2]

. For Nitsche type methods this case requires special handling of the terms involving the normal flux of the exact solution at the the boundary. For Dirichlet boundary conditions the estimates are optimal, whereas in the case of mixed Dirichlet-Neumann boundary conditions they are suboptimal by a logarithmic factor.
Gaussian quadrature rules for composite highly oscillatory integrals
Authors: Wu Menghan , Wang Haiyong
Published: June 2023

Highly oscillatory integrals of composite type arise in electronic engineering and their calculations are a challenging problem. In this paper, we propose two Gaussian quadrature rules for computing such integrals. The first one is constructed based on the classical theory of orthogonal polynomials and its nodes and weights can be computed efficiently by using tools of numerical linear algebra. An interesting connection between the quadrature nodes and the Legendre points is proved and it is shown that the rate of convergence of this rule depends solely on the regularity of the non-oscillatory part of the integrand. The second one is constructed with respect to a sign-changing function and the classical theory of Gaussian quadrature cannot be used anymore. We explore theoretical properties of this Gaussian quadrature, including the trajectories of the quadrature nodes and the convergence rate of these nodes to the endpoints of the integration interval, and prove its asymptotic error estimate under suitable hypotheses. Numerical experiments are presented to demonstrate the performance of the proposed methods.
Hiding among colors: background color diversity impedes detection time
Authors: Sadiq Akhil , Kodandaramaiah Ullasa
Published: June 2023

Avoiding detection is vital for the survival of many animals. Factors extrinsic to animals, such as the visual complexity of the background, have been shown to impede the detection of animals. Studies using artificial and natural backgrounds have attributed background complexity to various visual features of the background. One feature that has received less attention is the diversity of color (hue) in the background. We used chickens and artificial backgrounds containing perceptually distinct elements in experiments to test whether color and luminance diversity affect detection time. We found that color diversity in the background impeded detection, while color diversity in prey and luminance diversity in the background did not impede detection. We also did not find an effect of luminance contrast on detection time. Our study suggests a prey animal can benefit in terms of increased detection times by predators when resting on backgrounds with enhanced color diversity.
Permissiveness and competition within and between Neurospora crassa syncytia
Authors: Mela Alexander P , Glass N Louise
Published: June 2023

A multinucleate syncytium is a common growth form in filamentous fungi. Comprehensive functions of the syncytial state remain unknown, but it likely allows for a wide range of adaptations to enable filamentous fungi to coordinate growth, reproduction, responses to the environment, and to distribute nuclear and cytoplasmic elements across a colony. Indeed, the underlying mechanistic details of how syncytia regulate cellular and molecular processes spatiotemporally across a colony are largely unexplored. Here, we implemented a strategy to analyze the relative fitness of different nuclear populations in syncytia of Neurospora crassa, including nuclei with loss-of-function mutations in essential genes, based on production of multinucleate asexual spores using flow cytometry of pairings between strains with differentially fluorescently tagged nuclear histones. The distribution of homokaryotic and heterokaryotic asexual spores in pairings was assessed between different auxotrophic and morphological mutants, as well as with strains that were defective in somatic cell fusion or were heterokaryon incompatible. Mutant nuclei were compartmentalized into both homokaryotic and heterokaryotic asexual spores, a type of bet hedging for maintenance and evolution of mutational events, despite disadvantages to the syncytium. However, in pairings between strains that were blocked in somatic cell fusion or were heterokaryon incompatible, we observed a “winner-takes-all” phenotype, where asexual spores originating from paired strains were predominantly one genotype. These data indicate that syncytial fungal cells are permissive and tolerate a wide array of nuclear functionality, but that cells/colonies that are unable to cooperate via syncytia formation actively compete for resources.
Physiological Dysregulation Proceeds and Predicts Health Outcomes Similarly in Chinese and Western Populations
Authors: Li Qing , Legault Véronique , Hermann Honfo Sewanou , Milot Emmanuel , Jia Qingzhou , Wang Fuqing , Ferrucci Luigi , Bandinelli Stefania , Cohen Alan A
Published: June 2023

Background

A decade ago, we proposed an index of physiological dysregulation based on Mahalanobis distance (DM) that measures how far from the norm an individual biomarker profile is. While extensive validation has been performed, focus was mostly on Western populations with little comparison to developing countries, particularly at a physiological system level. The degree to which the approach would work in other sociocultural contexts and the similarity of dysregulation signatures across diverse populations are still open questions.

Methods

Using 2 data sets from China and 3 from Western countries (United States, United Kingdom, and Italy), we calculated DM globally and per physiological system. We assessed pairwise correlations among systems, difference with age, prediction of mortality and age-related diseases, and sensitivity to interchanging data sets with one another as the reference in DM calculation.

Results

Overall, results were comparable across all data sets. Different physiological systems showed distinct dysregulation processes. Association with age was moderate and often nonlinear, similarly for all populations. Mahalanobis distance predicted most health outcomes, although differently by physiological system. Using a Chinese population as the reference when calculating DM for Western populations, or vice versa, led to similar associations with health outcomes, with a few exceptions.

Conclusions

While small differences were noticeable, they did not systematically emerge between Chinese and Western populations, but rather diffusively across all data sets. These findings suggest that DM presents similar properties, notwithstanding sociocultural backgrounds, and that it is equally effective in capturing the loss of homeostasis that occurs during aging in diverse industrial human populations.
Constitutional framings of the right to abortion: A global view
Authors: Śledzińska-Simon Anna
Published: June 2023

At the present time, no national constitution expressly guarantees access to abortion as a human right. Yet, despite the absence of explicit constitutional provisions, a growing body of case law from countries’ highest courts recognizes abortion as a fundamental, natural right. Judicial interpretations of the right to abortion are evolving, with courts considering it a derivative of the constitutional guarantees of liberty, equality, dignity, or, more recently, the protection of health. Conversely, some courts, notably in the United States and Poland, have ruled out the possibility of such a right having constitutional status. This Reflection outlines current constitutional approaches to the right to abortion. It highlights an important paradigm shift in constitutional law toward framing abortion as part of the right to reproductive health, as already affirmed in international human rights law. Reproductive rights are now defined in relation to the state’s obligation, on the one hand, not to interfere with reproductive choices and, on the other hand, to provide women and girls with conditions ensuring freedom of choice, but also to determine the limits of their choices.
Impact of robotic-assisted and video-assisted sympathetic nerve reconstruction on quality of life for severe compensatory hyperhidrosis after thoracic sympathectomy
Authors: Rojas Dorian , Duggan Simon M , Mauduit Marion , Anselmi Amedeo , Verhoye Jean-Philippe , Rouze Simon , Valla Jean , Richard De Latour Bertrand
Published: June 2023

OBJECTIVES

Severe compensatory hyperhidrosis (CH) is a disabling complication following thoracic sympathectomy. Our study was to establish valid patient selection criteria and determine outcomes of nerve reconstructive surgery. Furthermore, we assessed the clinical feasibility and safety of a robotic-assisted approach compared to video-assisted thoracoscopic surgery.

METHODS

Adults with severe CH following bilateral sympathectomy for primary hyperhidrosis were enrolled. We performed 2 questionnaires: the Hyperhidrosis Disease Severity Scale and the Dermatology Life Quality Index before and 6 months after nerve reconstructive surgery. A one-time evaluation of healthy volunteers (controls) was undertaken to validate the quality of life measures.

RESULTS

Fourteen patients (mean age 34.1 ± 11.5 years) underwent sympathetic nerve reconstruction. None of the patients had a recurrence of primary hyperhidrosis. Improvement in quality of life was reported in 50% of patients. Both mean Hyperhidrosis Disease Severity Scale and mean Dermatology Life Quality Index were significantly reduced compared to preoperative assessments. In 10 patients, a video-assisted approach and in 4 patients robotic assistance was utilized. There was no significant difference in outcomes between approaches.

CONCLUSIONS

Somatic–autonomic nerve reconstructive surgery offers a reversal in the debilitating symptoms in some patients with severe CH. Proper patient selection, preoperative counselling and management of expectation are of paramount importance. Robot-assisted thoracic surgery is an alternative method to conventional video-assisted surgery. Our study provides a practical approach and benchmark for future clinical practice and research.
Prayer and Buddhism? The Supreme Offering
Authors: Teiser Stephen F
Published: June 2023

How can comparative categories be used with vigorous attention to historical context and cultural variation? My example is the concept of prayer applied to various forms of premodern Buddhism. After analyzing past attempts to square theocentric notions with Buddhism, I propose a more circumspect mode of comparison. Adopting a performative approach to the study of religious language, I stipulate prayer as “speech acts directed toward seen and unseen sentient beings.” This strategy broadens the addressees in prayer discourse to include Buddhas, bodhisattvas, minor gods, ghosts, spirits, and other beings. It also covers a wide range of Buddhist practice and focuses on exchange, morality, and bodily engagement. The article then analyzes a specific ritual, the supreme offering, found in many articulations across Buddhist cultures. The conclusion argues that this approach offers several insights. Engaging a wide range of beings in the cosmos, the supreme offering envisages a hierarchical moral community. The different steps in prayer highlight the importance of karma in Buddhist ritual. As a regimen of practice, the supreme offering aims at forming ethical dispositions and cultivating character.
#2647 MENOPAUSAL HORMONE THERAPY AND RISK OF DEMENTIA IN WOMEN WITH PRE-DIALYSIS CKD: A NATIONWIDE OBSERVATIONAL COHORT STUDY
Authors: Huh Hyuk , Kim Dong Ki , Cho Semin , Kim Jung-Hyun , Joo Kwon Wook
Published: June 2023

Background and Aims

The risk of dementia is increased in postmenopausal women. The incidences of premature menopause and dementia are increased in patients with chronic kidney disease (CKD). Therefore, the potential benefit of hormone replacement therapy (HRT) for cognitive function may be a more critical issue in CKD patients.

Method

Menopausal women over 40 years with or without HRT were identified through the National Health Screening questionnaire in 2009. Among the subjects, those newly diagnosed with CKD between 2009 and 2013 were enrolled. HRT was used as an exposure variable and was followed from the day when CKD was diagnosed to December 2019. The hazard ratio (HR) of dementia was evaluated using a Cox proportional hazards regression analysis.

Results

We included 755,426 postmenopausal women with CKD. The median follow-up period was 7.3 (IQR, 5.8-8.7) years. All-cause dementia occurred in 107,848 (14.3%), Alzheimer's disease in 87,833 (11.6%), and vascular dementia in 10,245 (1.4%). HRT was significantly associated with a lower risk of dementia in the adjusted Cox regression model (all-cause dementia: hazard ratio [HR] 0.796, 95% confidence interval [95% CI] 0.776-0.816, P < 0.001; Alzheimer's disease: HR 0.795, 95% CI 0.773-0.818, P < 0.001; vascular dementia: HR 0.803, 95% CI 0.743-0.868, P < 0.001).

Conclusion

HRT was significantly associated with a lower risk of CKD-related cognitive dysfunction in postmenopausal women. Prospective studies on whether HRT lowers the risk of dementia in menopausal women with CKD are needed.
#3382 REASONS FOR DIALYSIS INITIATION AND SAFETY OF DAPAGLIFLOZIN AMONG DIALYSIS PARTICIPANTS: NEW INSIGHTS FROM DAPA-CKD
Authors: Heerspink Hiddo Lambers , Wheeler David C , Jong Niels , Correa-Rotter Ricardo , Rossing Peter , Gansevoort Ronald , Mcmurray John , Langkilde Anna Maria , Toto Robert , Chertow Glenn
Published: June 2023

Background and Aims

The DAPA-CKD trial demonstrated that dapagliflozin reduced the risk of kidney failure in patients with chronic kidney disease (CKD) with or without type 2 diabetes. In contrast to most other trials, participants who reached dialysis were allowed to continue study medication with dapagliflozin or placebo. In this pre-specified analysis of the DAPA-CKD trial, we assessed reasons for dialysis initiation and serious adverse events (SAEs) among participants who initiated dialysis and continued the study medication.

Method

The DAPA-CKD trial randomized 4304 patients with CKD (estimated glomerular filtration rate [eGFR] 25−75 mL/min/1.73m2) and albuminuria (urinary albumin-to-creatinine ratio 200−5000 mg/g) to dapagliflozin 10 mg daily or placebo in addition to standard of care. Chronic dialysis was defined as the need for dialysis for at least 28 days. Investigator reported reasons for dialysis and SAEs were summarized by treatment groups.

Results

During median 2.4 years follow-up, 68/2152 (3.2%) and 99/2152 (4.6%) participants in the dapaglifozin and placebo groups respectively required chronic dialysis. Reasons for dialysis initiation are shown in the Table below, with volume overload being the most frequently reported. Roughly one-third of patients in both groups had discontinued study drug in advance of dialysis initiation; in the dapagliflozin and placebo groups, 25/68 (37%) and 41/99 (41%) continued the blinded study medication while receiving chronic dialysis. Among these, SAEs were reported in 8/25 (32%) and 11/41 (27%), respectively.

Conclusion

Participants who continued dapagliflozin or placebo after dialysis initiation experienced similar rates of SAEs. To determine whether dapagliflozin provides cardiovascular or other benefits to patients with kidney failure on chronic dialysis, will require a dedicated prospective trial. Based on our prespecified exploratory analysis, we observed no safety concerns that might discourage the conduct of such a trial.

Funding

This study was funded by AstraZeneca
#3440 TOCILIZUMAB INDUCTION THERAPY IN KIDNEY TRANSPLANTATION
Authors: Abdullaev Sherzod , Sharapov Olimkhon
Published: June 2023

Background and Aims

Antibody induction therapy is frequently used as an adjunct to the maintenance immunosuppression in adult kidney transplant recipients (KTRs). There are few comparisons of antibody induction therapy allowing early glucocorticoid withdrawal in KTRs. The purpose of the present study was to compare induction therapy involving tocilizumab with the most commonly used induction regimens in patient populations at either high immunologic risk or low immunologic risk.

Method

In this prospective study, we randomly assigned patients to receive tocilizumab or conventional induction therapy such as basiliximab. Patients were stratified according to acute rejection risk, with a high risk defined by a repeat transplant, a peak or current value of panel-reactive antibodies of 30% or more. The 102 high-risk patients received tocilizumab (one dose of 8 mg/kg, in 52 patients) or basiliximab (a total of 40 mg over 4 days, in 50 patients). The 113 low-risk patients received tocilizumab (one dose of 8 mg/kg, in 62 patients) or basiliximab (a total of 40 mg over 4 days, in 51 patients). All patients received tacrolimus and mycophenolate mofetil and underwent a 10-days glucocorticoid (prednisone) taper in a regimen of early steroid withdrawal. The primary end point was biopsy-confirmed acute rejection at 6 months and 12 months. Patients were followed for 2 years for safety and efficacy end points.

Results

The rate of biopsy-confirmed acute rejection was significantly lower in the tocilizumab group than in the basiliximab group at both 6 months (5.3% vs. 10.9%, P<0.01) and 12 months (7.9% vs. 12.9%, P<0.01). At 2 years, the rate of biopsy-confirmed acute rejection in low-risk patients was lower with tocilizumab than with basiliximab (9.7% vs. 17.7%, P<0.05), but among high-risk patients, no significant difference was seen between tocilizumab and basiliximab (19.2% vs. 16.0%, P = 0.68). Adverse-event rates were similar among all four treatment groups.

Conclusion

By the first year after transplantation, biopsy-confirmed acute rejection was less frequent with tocilizumab than with conventional therapy. The apparent superiority of tocilizumab with respect to early biopsy-confirmed acute rejection was restricted to patients at low risk for transplant rejection; among high-risk patients, tocilizumab and basiliximab had similar efficacy. Further randomized and controlled studies are needed to support these results.
#4139 EFFECTS OF EMPAGLIFLOZIN ON FLUID OVERLOAD IN CHRONIC KIDNEY DISEASE: AN EMPA-KIDNEY BIOIMPEDANCE SUBSTUDY
Authors: Mayne Kaitlin
Published: June 2023

Background and Aims

The EMPA-KIDNEY trial showed that, compared to placebo, empagliflozin 10 mg once daily reduced the risk of kidney disease progression or cardiovascular death in 6609 patients with chronic kidney disease at risk of progression. We aimed to assess effects of empagliflozin on bioimpedance-measured fluid overload and adiposity in a subset to better understand the mechanisms of cardiovascular benefits of sodium glucose co-transporter-2 inhibitors.

Method

This EMPA-KIDNEY substudy added Body Composition Monitor (BCM) measurements at randomization and the 2 and 18 month follow-up visits to the trial's main protocol-specified procedures. The primary outcome was Absolute Fluid Overload (a parameter reflecting overhydration, derived from extracellular and intracellular resistance). Pre-specified subgroup analyses of the primary outcome were by sex, diabetes status, estimated glomerular filtration rate (eGFR) and N-terminal pro-brain-type natriuretic peptide (NT-proBNP) at baseline. The key secondary analysis was a composite of death from heart failure, heart failure hospitalisation or development of new moderate (>7%, ≤15%) or severe (>15%) BCM-measured Relative Fluid Overload. Tertiary outcomes included weight, anthropometry, and other BCM-measurements of body water and adiposity. The primary outcome was analysed used mixed-model repeated measures (MMRM) methods. The key secondary outcome used time-to-first event methods.

Results

A total of 660 EMPA-KIDNEY participants were recruited into this substudy. Mean age was 64 years, 205 (31%) were female and 245 (37%) had diabetes. Mean (SD) eGFR was 36 (12) ml/min/1.73m2 and median (Q1-Q3) NTpro-BNP was 211 (93-581) ng/L. Mean (SD) Absolute Fluid Overload at baseline was 0.4 (1.6) L, 19% had moderate fluid overload and 5% fulfilled criteria for severe fluid overload at baseline. Compared to placebo, the mean study average absolute difference in Absolute Fluid Overload was -0.24L (95% CI -0.38, -0.11), with similar differences at 2 months and 18 months (Figure 1). This difference was similar in men and women, in people with and without diabetes, and across the spectrum of eGFR and NT-proBNP studied (Figure 2). The number of key secondary outcomes was low and there was no significant difference in the risk of this outcome between treatment groups (35/332 [10%] vs 38/328 [12%], hazard ratio 0.91 [95% CI 0.57, 1.45], p = 0.69).

Conclusion

In patients with chronic kidney disease, empagliflozin reduced bioimpedance-measured fluid overload irrespective of diabetes status or level of eGFR. This effect persisted for at least 18 months with no evidence of attenuation over time.

Funding

Boehringer Ingelheim, Eli Lilly and others; Clinicaltrials.gov:NCT03594110.
#4572 EFFECTS OF EMPAGLIFLOZIN ON KIDNEY AND CARDIAC MRI MEASURES IN PATIENTS WITH CHRONIC KIDNEY DISEASE
Authors: Judge Parminder , EMPA-KIDNEY collaborative group on behalf of the
Published: June 2023

Background and Aims

EMPA-KIDNEY demonstrated empagliflozin reduced the risk of kidney disease progression or cardiovascular death in patients with CKD at risk of progression, but the mechanisms of benefit are uncertain. MRI was used to assess whether empagliflozin modified the structure and function of the kidneys and heart at around 18 months after randomization.

Method

Randomized participants from 8 sites in UK and Germany without a contraindication to MRI scanning, were eligible and invited to participate in this substudy. MRI scans were performed using a standardized protocol. Renal T1 mapping (MOLLI 5[3]3 scheme which measures fibrosis and inflammation) was computed by first segmenting MOLLI data using a U-net and then applying the masks to both kidneys. Cardiac MRI included cine steady-state free precession imaging to assess biventricular volumes, mass and function, and T1 mapping to assess myocardial inflammation and fibrosis. The primary outcome was kidney cortical T1 mapping measured by MOLLI. Secondary outcomes included LV ejection fraction, myocardial T1 MOLLI and LV mass index. Differences in MRI measurements between treatment groups were analysed using linear regression adjusted for baseline age, sex, eGFR, UACR and diabetes status. 172 participants were required to provide 90% power at 2p = 0.05 to detect a 50 ms difference in T1.

Results

172 participants had an MRI scan around 18 months after randomization. 93 (54%) were allocated empagliflozin and 79 (46%) placebo. Mean (SD) age was 60 (15) years, 26% were female and 23% had diabetes. Mean eGFR was 37 (13) mL/min/1.73m2 and geometric mean (95% CI) UACR was 242 (182-322) mg/g (Table 1). Adjusted mean (SE) cortical T1 mapping by MOLLI was 1623 (10) ms in those allocated empagliflozin versus 1634 (11) ms in those allocated placebo, difference in means (95% CI) −11 (−41 to 18), P = 0.45 (Table 2). Medullary T1 MOLLI scores were similar. Empagliflozin had no significant effect on cardiac MRI measures: difference (95% CI) in LV ejection fraction 1% (−1 to 4); myocardial T1 MOLLI −3 ms (−16 to 10); LV mass index −3 g/m2 (−5 to 0) (Table 2).

Conclusion

Empagliflozin had no significant effect on MRI-based measures of fibrosis within the kidney cortex or myocardium in people with CKD at risk of progression. There was no effect of treatment on measures of cardiac structure or function. Further MRI measures will be available for presentation by the time of the ERA congress.

Funding

Boehringer Ingelheim, Eli Lilly and others; Clinicaltrials.gov:NCT03594110.
#4989 FIRST INTERIM ANALYSIS OF THE INTERNATIONAL DISTAL RENAL TUBULAR ACIDOSIS REGISTRY
Authors: Giaccari Marta , Haffner Dieter , Schaefer Franz , Ariceta Gema , Bockenhauer Detlef , Emma Francesco
Published: June 2023

Background and Aims

Primary Distal Renal Tubular Acidosis (dRTA) is a rare genetic condition characterized by impaired capacity of A-type intercalated cells to excrete excess of H+ ions. The disease is caused primarily by pathogenic variants in the SLC4A1 gene encoding for the basolateral anion exchanger 1 (AE1) or the ATP6V1B1 and ATP6V0A4 genes encoding for two subunits of the apical proton ATPase. The latter also cause variable degrees of sensorineural hearing loss (SNHL). Additional genes include WDR72 that is associated with amelogenesis imperfecta and FOXI1 that also causes SNHL. To understand better the impact of alkali treatment on the natural history of dRTA, a European prospective registry has been created in collaboration with the ERKNet European Reference Network.

Method

We present a first interim descriptive analysis of first 182 patients that have been collected from 2019 to 2022. Treatment data are under analysis and are not included.

Results

To date, mostly paediatric patients (79%) have been included in the registry. A genetic diagnosis was available in 111/182 (61%) of patients and showed the following distribution of underlying genes: ATP6V0A4: 45%, ATP6V1B1: 41%, SLC4A1: 14%. Variants in WDR72 and FOXI1 were reported in one patient each. Overall, we observed no major differences in blood pressure and in urinary/blood parameters, when comparing children vs adults or proton ATPase vs AE1 defects (partially shown in tables 1 and 2). Adult patients were on average diagnosed later, had more frequently nephrolithiasis and higher BMI. In part, differences may reflect selections biases that will be assessed with the collection of longitudinal data. As expected, patients with proton pump defects were diagnosed earlier and had more frequently SNHL. The degree of nephrocalcinosis and the estimated glomerular filtration rates were similar when comparing all groups. None of the patients had developed end stage kidney disease.

Conclusion

This first report demonstrates successful enrolment of a cohort of patients with dRTA. Enrolment is still ongoing. Longitudinal data will allow assessing the impact of alkali therapy on the long-term outcome.
#5419 INVESTIGATING THE ROLE OF CFH VARIANTS AND HAPLOTYPES AS A RISK FACTOR OF IGA NEPHROPATHY IN A FRENCH COHORT
Authors: Duval Anna , Maillard Nicolas , Limou Sophie , Mariat Christophe , Ohlmann Sophie , Bacchi Veronique Fremeaux
Published: June 2023

Background and Aims

Excessive complement activation is particularly important in the pathogenesis of IgAN nephropathy (IgAN). The relationship of complement CFH gene genetics and IgAN phenotype has not been clearly established in IgAN.

Method

We performed a genetic analysis of 234 French IgAN patients by next generation sequencing and Sanger. CFH polymorphisms were combined into haplotypes using the Michigan imputation Server1. CFH rare variants (MAF<0.1%) and haplotypes frequencies were compared to the 1k genome population of European ancestry. Recombinant full-length FH rare variants were produced and studied functionally in vitro.

Results

Genetic analysis revealed an enrichment in CFH non synonymous rare variants in IgAN patients (n = 234) compared to the reference population (n = 503) (5.1 versus 1.8%, p = 0.010). Interestingly, the identified variants preferentially located in FH functional domains. In vitro functional studies based on new functional Luminex® assays showed a decrease in C3b-binding, C3bBb decay-accelerating activity and/or FI-cofactor activity for 4 variants, classifying a newly identified variant as a pathogenic variant. CFH haplotypes distribution differed between the IgAN patients and controls (p<0.001), with a higher prevalence of the H3 haplotype (rs80029 c.184G>A, rs1061170 c.1204T>C, rs7542235 chr1:196854483 A>G, GTA) in IgAN patients (28.2 versus 21.1%, p = 0.0029), but this haplotype was not associated with renal survival.

Conclusion

In our series of French IgAN patients, CFH rare variants and haplotypes are associated with disease's susceptibility. Our results support the hypothesis of a complement dysregulation underlying the IgAN pathogenesis.
#5773 URINARY OROSOMUCOID IS ASSOCIATED WITH ALL-CAUSE MORTALITY IN THE GENERAL POPULATION
Authors: Andreassen Runa Marie , Brobak Karl Marius , Melsom Toralf , Eriksen Bjørn Odvar , Solbu Marit Dahl
Published: June 2023

Background and Aims

Urinary albumin excretion (UAE) is considered a risk factor for cardiovascular (CV) disease and all-cause mortality, but the pathophysiological mechanisms are not known, and studies are not consistent with regards to the effect of pharmacological UAE reduction on endpoints. Another protein, orosomucoid (41-43kDa), is a non-specific acute inflammatory protein and is a part of the glycolax that covers the endothelium. Under normal conditions the concentration in urine is low, but a marked increase is demonstrated under both acute and chronic inflammation and in cardiovascular disease. In patients with diabetes urinary orosomucoid excretion (UOE), was an independent predictor of all-cause and cardiovascular mortality even in normoalbuminuric patients. In this longitudinal study, our aim was to study both UAE and UOE in a middle-aged cohort from the general population. We hypothesized that UOE, but not UAE, is an independent predictor for all-cause mortality.

Method

The Tromsø Study is a population-based, prospective study with repeated health surveys of inhabitants of Tromsø (Northern Norway), and the first took place in 1974. From the sixth wave (Tromsø6, 2007/2008) we included all participants with urinary samples. Follow-up time was assigned from the attendance date of Tromsø6 until 31.08.2022. The associations between urinary markers and all-cause mortality were assessed by Cox regression analysis.

Results

The cohort included 7180 subjects (4094 women and 3086 men) with a mean (SD) age 63.5 (±9.2) years. Median urinary orosomucoid to creatinine ratio (UOCR) was 0.44 g/g, median albumin to creatinine ratio (UACR) was 0.36 mg/mmol, mean (SD) eGFR was 88.1 (±14.0) ml/min/1.73m² and 1689 died during follow-up. UOCR was independently associated with all-cause mortality (hazard ratio (HR) per g/g increase 1.02, 95% CI 1.01,1.03, p<0.001) adjusted for sex, age, UACR, eGFR and CV risk factors (diabetes, hypertension, smoke, cholesterol, BMI). The HR for UOCR above vs. below median adjusted for the same variables was 1.13 (95% CI 1.01, 1.27, p = 0.032). UACR above median with the same adjustments was not associated to all-cause mortality (hazard ratio 1.04, 95%CI 0.93, 1.15, p = 0.484).

Conclusion

In this study, we showed for the first time that UOE, but not UAE, was an independent predictor of all-cause mortality in a large cohort from the general population. Thus, UOE may be an earlier marker of vascular damage than UAE. Whether UOE is clinically useful as an early marker of CV disease should be further studied.
#6402 IMPACT OF DARATUMUMAB AND BELATACEPT ON HLA ANTIBODIES IN KIDNEY TRANSPLANT CANDIDATES WITH 100% CPRA: EARLY RESULTS OF ATTAIN (ITN090ST)
Authors: Vincenti Flavio , Chandran Sindhu , Raja Rajalingam , Mason Kristen , Mall Shreya , Maruthamuthu Stalinraja , Martin Thomas , Breeden Cynthia , Silva Juliete
Published: June 2023

Background and Aims

Despite high allocation priority, <10% of kidney transplant candidates with cPRA 100% can find a compatible donor. Current desensitization strategies are ineffective due to antibody rebound. Adding costimulation blockade to plasma cell (PC) depletion prevents antibody rebound in nonhuman primates by countering nodal B cell and Tfh expansion.

Method

ATTAIN is a pilot, phase I/II trial of daratumumab, a CD38 mAb used in multiple myeloma, plus belatacept, a high affinity CTLA4-Ig, to desensitize kidney transplant candidates with cPRA ≥99.9%. Enrolled subjects receive daratumumab (6 doses: 8 mg/kg) and belatacept (4 doses: 10 mg/kg) over 10 weeks with bone marrow and blood assessments pre-and post-treatment. The primary efficacy endpoint (PE) is a composite of (1) elimination of ≥1 HLA antibody specificity, (2) ≥50% reduction in the MFI of ≥3 HLA antibody specificities, or (3) kidney transplant from a previously incompatible donor. Target accrual is 15, enrolled in 2 cohorts (5+10).

Results

Cohort 1 (n = 5, mean age 44, 60% with previous transplant) has been enrolled and treated, with 5-31 weeks follow-up to date. The treatment was tolerated well in all 5 patients who showed a significant reduction in most HLA antibodies after treatment without manifestation of rebound. 3 of 5 participants reached the PE and 5 of 5 had >50% bone marrow (BM) PC depletion. One patient received a kidney transplant from a previously incompatible deceased donor and is doing well at 7 months post-transplant without rejection or rebound of HLA antibody. Treatment was temporarily paused in 3 subjects due to AEs (acute cholecystitis and COVID, upper GI bleed, fevers); no cases of opportunistic infection or malignancy occurred.

Conclusion

A novel HLA desensitization regimen consisting of PC depletion with Daratumumab and costimulatory blockade with Belatacept appears safe and successful in the ongoing ATTAIN clinical trial. In the initial subject, this regimen led to transplant without HLA antibody rebound or acute rejection. Longer follow-up and additional subjects are needed to confirm these promising results. ATTAIN (NCT04827979) is a trial conducted by the Immune Tolerance Network and sponsored by NIAID (award UM1AI109565).
#3248 COMPARATIVE EFFECTIVENESS OF DIURETICS AND CALCIUM CHANNEL BLOCKERS ON TOP OF RASI ON CKD PROGRESSION AND MORTALITY: A NATIONWIDE COHORT STUDY
Authors: Faucon Anne-Laure , Fu Edouard , Stengel Benedicte , Mazhar Faizan , Evans Marie , Carrero Juan Jesus
Published: June 2023

Background and Aims

It is unknown whether initiating diuretics on top of renin-angiotensin system inhibitors (RASi) is superior to alternative antihypertensive agents such as calcium channel blockers (CCBs) in persons with CKD.

Method

We emulated a target trial in the Swedish Renal Registry 2007–2022, enrolling patients with moderate-advanced CKD under nephrology care who had good adherence to RASi and initiated antihypertensive therapy with either diuretics or CCB. Using propensity score-weighted cause-specific Cox regression, we compared risks of major adverse renal events (MAKE, including kidney replacement therapy [KRT], ≥40% decline in eGFR, eGFR<15 mL/min per 1.73 m²), major cardiovascular events (MACE, including CV death, myocardial infarction, stroke) and death.

Results

We identified 5875 patients (median age 71 years, 64% men, eGFR 26 mL/min per 1.73 m²), of whom 3165 started diuretics and 2710 CCB. After a median follow-up of 6.3 [3.2-9.7] years, 2558 MAKE and 1178 MACE occurred, and 2299 deaths (Figure). Compared to CCB, diuretic use was associated with a lower risk of MAKE (adjusted HR: 0.87 [95%CI: 0.77-0.97]), consistent across single components (KRT: 0.77[0.67-0.88], ≥40% eGFR decline: 0.81[0.72-0.91], and eGFR <15mL/min/1.73 m²: 0.85[0.75-0.97]). The risks of MACE (1.15 [0.96-1.36]), all-cause (1.07 [0.94-1.22]), CV- (1.20 [0.95-1.51]) and non-CV death (1.01 [0.86-1.19]) did not differ between therapies. Results were consistent across subgroups and robust to competing risks.

Conclusion

Our findings provide evidence from real-world clinical practice that in patients with moderate-advanced CKD, add-on antihypertensive therapy to RASi with diuretics may confer further kidney benefits and similar cardioprotection compared with CCBs.