bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved quality of resistance spot welded joints for molybdenum sheets in lap configuration by adding titanium interlayer
Authors: Ning Jie , Zhang Lin-Jie , Yang Bai-Yu , Ma Ru-Yuan , Sun Yuan-Jun
Published: June 2021

Resistance spot welding (RSW) exhibits low heat input and high efficiency. However, because Mo exhibits low resistivity and high hot strength, it is difficult to effectively combine the resistance spot welded joints of Mo. The lap joint of 1-mm-thick Mo sheets was welded using RSW. Moreover, the welding parameters (current, welding duration, and electrode force) were optimised. Using Ti foil as the interlayer, the influence of the alloying element on the resistance spot welded joint of the Mo sheets was explored. The results indicate that the success rate of welding can be improved by utilising a high current and short welding duration, and increasing the electrode force causes reduced contact resistance and further failure of the welding. In addition, an excessively high electrode force may result in electrode adhesion. Here, a current of 20 kA, welding duration of 0.4 s, and electrode force of 3726 N were used as the optimised parameters. The joint obtained under the parameters can withstand the highest shear load (about 2.20 kN); the shear load of the joint obtained after adding the Ti interlayer (thickness: 0.03 mm) increases by approximately 54%. After adding the Ti foil, the heat input on the interface increased and Ti melted to form metallurgical bonding with Mo. Under these conditions, the interfacial strength increased significantly. During the tensile–shear test, the heat-affected zone of Mo is fractured, in which the shear fracture is subjected to brittle failure.
Neutrophil-to-lymphocyte ratio predicts delirium after stroke
Authors: Guldolf Kaat , Vandervorst Fenne , Gens Robin , Ourtani Anissa , Scheinok Thomas , De Raedt Sylvie
Published: May 2021

Background

Delirium is an underdiagnosed and possibly preventable complication in acute stroke and is linked to poor outcome. Neutrophil-to-lymphocyte ratio (NLR), a marker of systemic inflammation, is also associated with poor outcome after acute ischemic stroke.

Aim

To determine whether NLR is a predictor of post-stroke delirium (PSD).

Methods

We reviewed the UZ Brussel stroke database and included 514 patients with acute ischemic stroke within 24 hours from stroke onset between February 2009 and December 2014. The presence of delirium was evaluated by two raters based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria, using a retrospective chart review method. When no consensus was reached, a third evaluator was consulted. Patients were divided into two groups: those who developed delirium within the first week after stroke onset (n = 201; 39%) and those who did not (n = 313; 61%). Receiver operating characteristics (ROC) and multiple logistic regression analysis (MLRA) were used to identify predictors of PSD.

Results

MLRA showed that NLR (odds ratio (OR) 1.14; 95% confidence interval (CI) 1.04–1.26), age (OR 1.05; 95% CI 1.03–1.07), National Institutes of Health Stroke Scale (NIHSS; OR 1.14; 95% CI 1.10–1.18), premorbid modified Rankin Scale (mRS) (OR 1.35; 95% CI 1.05–1.74) and premorbid cognitive dysfunction (OR 3.16; 95% CI 1.26–7.92) predicted PSD. ROC curve of a prediction model including NLR, age, NIHSS and premorbid cognitive dysfunction showed an area under the curve of 0.84 (95% CI = 0.81–0.88).

Conclusions

Besides age, stroke severity, premorbid mRS and cognitive impairment, NLR is a predictor of PSD, even independent of the development of pneumonia or urinary tract infection.
Pythagorean Self-Awareness Intervention for Multiple Sclerosis Patients: A Quasi-Experimental Pragmatic Trial
Authors: Panagopoulou Zacharo , Artemiadis Artemios K , Chrousos George P , Darviri Christina , Anagnostouli Maria C
Published: May 2021

Objective

Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system affecting patients’ well-being and quality of life. Pythagorean Self-Awareness Intervention (PSAI) is a novel non-pharmaceutical intervention with significant benefits both in MS and other chronic diseases. In this study, the longstanding effectiveness of PSAI was investigated.

Method

This was a two-arm quasi-experimental pragmatic trial in relapsing–remitting MS patients (23 in the PSAI and 21 in the control group). PSAI patients received an 8-week training period and then they performed PSAI at home for another 16 weeks. Assessments took place at baseline, 8 weeks, and 24 weeks. These included cognition, fatigue, perceived stress, and hair cortisol.

Results

Significant group × time interactions favoring PSAI were found during the first 8-week period for information processing speed, fatigue, and perceived stress. However, only verbal memory was found to be significantly improved in the PSAI group during the 24-week follow-up period. There were no significant group × time differences with respect to hair cortisol. No side effects were noted and compliance was excellent.

Conclusions

PSAI was mostly effective during the first 8-week training period. Its benefits worn out during the non-training period, albeit we observed a delayed significant improvement of verbal memory. Our findings will help to further refine the technique, either by extending the training period and/or by including booster sessions, throughout the PSAI treatment. This study provided Class III evidence for PSAI.
Introduction to the Special Issue Forum “Digital Cultures of South Asia: Inequalities, Informatization, Infrastructures”
Authors: Chadha Kalyani , Kumar Sangeet , Parameswaran Radhika
Published: May 2021

This short introductory essay first lays out the broader map of the digital media ecosystem in South Asia and then establishes the importance of this region in the global south--with its growing networked population--for understanding the future trajectories of global digital culture. Just as any other part of the world that is gradually getting on board the digital bandwagon, the South Asian digital landscape shows signs of both ingenuity, innovation and progressive potential as well as unchecked power, surveillance and exploitation. Our introduction uses the framework of digital culture's promises and its challenges to organize the collection of essays in this special forum.
Sustainable food systems: do agricultural economists have a role?
Authors: Fresco Louise O , Geerling-Eiff Floor , Hoes Anne-Charlotte , van Wassenaer Lan , Poppe Krijn J , van der Vorst Jack G A J
Published: May 2021

Are agricultural economists losing their relevance and significance in research on sustainable food systems? Could the world thrive without the contribution of agricultural economists? How could agricultural economists have more impact in addressing the grand challenges of our time? In this paper we address these questions by reflecting on the field of agricultural economics and re-examining the role and impact of agricultural economists. We argue that agricultural economists could raise their impact through better collaboration with other disciplines, stakeholder engagement and the adoption of a more systematic approach to the grand challenges, the innovation pathways and their disrupting developments in the data economy. We outline key topics in the economics of food systems on which agricultural economists could make major contributions and key areas in which methodological innovations are needed.
Daily Reciprocity and Well-Being: A Diary Study of Intergenerational Support Between Mothers and Adult Children During the COVID-19 Pandemic
Authors: Jiang Da , Fung Helene H
Published: May 2021

Objectives

Intergenerational support between aging parents and adult children is important to the well-being of both groups, especially during public health emergencies. However, few previous studies have examined the effects of daily support between parents and children on their well-being during public health emergencies. To fill in this gap, we examined the association between daily support and well-being in mothers and their adult children during the coronavirus disease 2019 pandemic.

Methods

Seventy-seven pairs of mothers (aged 44–80 years, M = 53.78, SD = 9.57) and adult children (aged 18–54 years, M = 26.61, SD = 9.46; 19% male) in mainland China participated in a 14-day daily diary study during a stay-at-home period. All of the participants reported the daily emotional and instrumental support they had given to and received from their mother/child each day for 14 consecutive days. Their daily positive affect and negative affect were also measured.

Results

Receiving more support on a given day was associated with providing more support on that day, suggesting a daily reciprocity. This finding was consistent across mothers and children. A lower level of being underbenefitted on a day was associated with better daily well-being of children, but not that of mothers. Providing support, but not receiving support, was positively associated with mothers’ daily well-being, whereas receiving support, but not providing support, was positively associated with children’s daily well-being.

Discussion

This study provides evidence of daily intergenerational support during a global public health emergency. The findings shed light on the importance of daily reciprocity and its implications for well-being.
Stress Responses across the Scales of Life: Toward a Universal Theory of Biological Stress
Authors: Wasserman Michael D , Wing Boswell , Bickford Nate , Hobbs Kimberly , Dijkstra Peter , Carr James A
Published: May 2021

Although biological systems are more complex and can actively respond to their environment, an effective entry point to the development of a universal theory of biological stress is the physical concepts of stress and strain. If you apply stress to the end of a beam of steel, the strain will accumulate within that steel beam. If the stress is weak then the strain will disappear when the force is removed and the beam will return to its original state of form and functionality. If the stress is more severe, then the strain becomes permanent and the beam will be deformed, potentially losing some degree of functionality. In extremely stressful situations, the beam will break and lose most or all of its original functional capabilities. Although this stress–strain theory applies to the abiotic, stress and strain are also rules of life and directly relate to the form and function of living organisms. The main difference is that life can react and adjust to stress and strain to maintain homeostasis within a range of limits. Here, we summarize the rules of stress and strain in living systems ranging from microbes to multicellular organisms to ecosystems with the goal to identify common features that may underlie a universal biological theory of stress. We then propose to establish a range of experimental, observational, and analytical approaches to study stress across scales, including synthetic microbial communities that mimic many of the essential characteristics of living systems, thereby enabling a universal theory of biological stress to be experimentally validated without the constraints of timescales, ethics, or cost found when studying other species or scales of life. Although the range of terminology, theory, and methodology used to study stress and strain across the scales of life presents a formidable challenge to creating a universal theory of biological stress, working toward such a theory that informs our understanding of the simultaneous and interconnected unicellular, multicellular, organismal, and ecosystem stress responses is critical as it will improve our ability to predict how living systems respond to change, thus informing solutions to current and future environmental and human health challenges.
Transparent Uniforms
Authors: Niv Ady
Published: May 2021

Reserve forces constitute an important component in most armies and play a crucial role in times of war. Notwithstanding, the legal status of reservists, when mobilized or demobilized, and their possible detention or classification as a military target according to international law has rarely been discussed. It is only in the last case before the International Criminal Tribunal for the former Yugoslavia, Prlić et al., that the Appeals Chamber had to assess whether the opposing party could detain men only because they were mobilized. The aim of this article is to remedy this lacuna, to discuss the status of reservists in international humanitarian law and to analyse the possible legal framework for detaining and targeting — both active and non-active — reservists.
Giant leiomyosarcoma of the inferior vena cava necessitating extended liver resection: A case report and review of the literature
Authors: Silverman Jacob , Pencovich Niv , Mayer Chen , Volkov Alexander , Eshkenazi Rony , Nachmany Ido
Published: June 2021

Leiomyosarcoma of the inferior vena cava (IVC) is a rare malignant tumour of smooth muscle origin. It commonly presents with non-specific symptoms including abdominal pain, distention, and lower extremity edema. Surgical resection with macroscopically clear margins is the only potential curative treatment for the disease. Here we present the case of a previously healthy 38-year-old woman with a subacute one-month increase of a four-year slowly progressive right sided abdominal pain and back pain. Imaging revealed a 14.5x12x15cm mass in the right hepatic lobe causing mass effect on adjacent abdominal and retroperitoneal organs, and involving the retrohepatic IVC. En-bloc resection of the right hemi-liver, most of segment four, the caudate lobe, and approximately a 10 cm section of the retrohepatic IVC, along with IVC reconstruction, was performed. Histologic examination revealed the diagnosis of a high grade leiomyosarcoma.
Morphological classification of galaxies with deep learning: comparing 3-way and 4-way CNNs
Authors: Cavanagh Mitchell K , Bekki Kenji , Groves Brent A
Published: May 2021

Classifying the morphologies of galaxies is an important step in understanding their physical properties and evolutionary histories. The advent of large-scale surveys has hastened the need to develop techniques for automated morphological classification. We train and test several convolutional neural network (CNN) architectures to classify the morphologies of galaxies in both a 3-class (elliptical, lenticular, and spiral) and a 4-class (+irregular/miscellaneous) schema with a data set of 14 034 visually classified SDSS images. We develop a new CNN architecture that outperforms existing models in both 3-way and 4-way classifications, with overall classification accuracies of 83 and 81 per cent, respectively. We also compare the accuracies of 2-way/binary classifications between all four classes, showing that ellipticals and spirals are most easily distinguished (>98 per cent accuracy), while spirals and irregulars are hardest to differentiate (78 per cent accuracy). Through an analysis of all classified samples, we find tentative evidence that misclassifications are physically meaningful, with lenticulars misclassified as ellipticals tending to be more massive, among other trends. We further combine our binary CNN classifiers to perform a hierarchical classification of samples, obtaining comparable accuracies (81 per cent) to the direct 3-class CNN, but considerably worse accuracies in the 4-way case (65 per cent). As an additional verification, we apply our networks to a small sample of Galaxy Zoo images, obtaining accuracies of 92, 82, and 77 per cent for the binary, 3-way, and 4-way classifications, respectively.
Predicting exoplanet mass from radius and incident flux: a Bayesian mixture model
Authors: Ma Qi , Ghosh Sujit K
Published: May 2021

The relationship between mass and radius (M–R relation) is the key for inferring the planetary compositions and thus valuable for the studies of formation and migration models. However, the M–R relation alone is not enough for planetary characterization due to the dependence of it on other confounding variables. This paper provides a non-trivial extension of the M–R relation by including the incident flux as an additional variable. By using Bayesian hierarchical modelling (BHM) that leverages the flexibility of finite mixture models, a probabilistic mass–radius–flux relationship (M–R–F relation) is obtained based on a sample of 319 exoplanets. We find that the flux has non-negligible impact on the M–R relation, while such impact is strongest for hot Jupiters. On the population level, the planets with higher level of flux tend to be denser, and high flux could trigger significant mass loss for plants with radii larger than 13R⊕. As a result, failing to account for the flux in mass prediction would cause systematic over- or underestimation. With the recent advent of computing power, although a lot of complex statistical models can be fitted using Monte Carlo methods, it has largely remained illusive how to validate these complex models when the data are observed with large measurement errors. We present two novel methods to examine model assumptions, which can be used not only for the models we present in this paper but can also be adapted for other statistical models.
MO075KLF11 DEFICIENCY ENHANCES CHEMOKINE GENERATION AND INJURY IN MURINE UNILATERAL URETERIC OBSTRUCTION
Authors: DeLorenzo Silvana , Grande Joseph
Published: May 2021

Background and Aims

Kruppel-like factors (KLFs) comprise a family of zinc-finger transcription factors that play a critical role in development, proliferation, and regeneration following injury. There are over 17 members of this family; recent studies have shown that KLF family members regulate podocyte differentiation, preservation of the glomerular filtration barrier, and regulation of mitochondrial function. However, a role for KLF11 in renal pathophysiology has not been previously established.

Method

Wild-type (WT) and KLF11 knockout (KO) mice were subjected to unilateral ureteric obstruction (UUO), a well-established model of renal inflammation and fibrosis; controls included mice subjected to manipulation of the ureter without ligation. Kidneys were harvested after 9 days (n=8 animals per group). Semiquantitative histopathologic analysis of renal atrophy, fibrosis, and inflammation was performed in a blinded fashion. Gene expression analysis was performed on renal cortex employing the Pathway Detect RNA array and RNASeq.

Results

In UUO, renal atrophy was more severe in KLF11 KO mice than WT mice (p<0.001). Deposition of collagen, as assessed by quantitative analysis of Sirus Red stained sections, was greater in KLF11 KO mice, compared to WT mice subjected to UUO; COL3A1 expression was also increased (p<0.05). Atrophy was associated with an increase in F4/80+ (p<0.01) and CD206+ macrophages (p<0.05), but not CD3+ T cells in KLF11 KO vs. WT mice. Induction of CC chemokines, including CCL2, CCL5, CCL7, CCL12, and CCL2 as well as CCR2 was significantly higher in KLF11 KO versus WT mice subjected to UUO (all p<0.001). Expression of NF-kB (p<0.01) and TNF alpha (p<0.01), but not IL-1 beta, IL-6, or IL-10 were significantly higher in KLF11 KO than WT mice with UUO. Expression of TGF-beta 1, Smad2, and Smad3 were also higher in KLF11 KO mice than WT mice with UUO (p<0.05).

Conclusion

Renal injury in UUO is exacerbated in KLF11 KO mice, compared to WT mice. Injury is associated with increased macrophage influx and production of pro-inflammatory chemokines. Future studies will determine how KLF11 deficiency directs transcription of pro-inflammatory and pro-fibrotic genes.
MO076REGULATION OF DIFFERENTIAL CELLULAR RESPONSE TO OXIDATIVE STIMULI IN SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: Ene Corina-Daniela , Penescu Mircea , Georgescu Simona Roxana , Tampa Mircea , Nicolae Ilinca
Published: May 2021

Background and Aims

Interaction of reactive oxygen species (ROS) with lipids, proteins, nucleic acids and hydro carbonates promotes acute and chronic tissue damage, mediates immunomodulation and triggers autoimmunity in systemic lupus erythematous (SLE) patients. The aim of the study was to determine the pathophysiological mechanisms of the oxidative stress-related damage and molecular mechanisms to counteract oxidative stimuli in lupus nephritis.

Method

Our study included 82 volunteers with SLE: 38 SLE volunteers with lupus nephritis (LN group) and 44 SLE volunteers without renal impairment (non-LN group) and a control group of 40 healthy volunteers. LN was diagnosed by histological exam (optic microscopy, electronic microscopy and immunofluorescence). Disease activity was measured by systemic SLE disease activity index (SLEDAI), urinary protein/creatinine ration, anti-dsDNA, C3, C4 and urinary β2-microglobulin.

In the present paper, we evaluated in serum:

Results

We detected high lipid peroxidation, elevated oxidative DNA damage, excess accumulation of reactive carbonylic compounds, important oxidation of carbohydrates, disulphide bonds formation and high nitrotyrosination with statistically significant differences between groups, when compared LN and non-LN groups with control group.

When compared LN and non-LN groups, our results showed:

3-Nitrotyrosine levels, the decrease of total and native serum thiols, pentosidine levels, sRAGE level and OGG1 activity correlated with disease activity markers in both LN and non-LN groups, while AGE correlated with disease activity only in non-LN group.

Conclusion

The cellular response to oxidative stimuli in SLE is concreted in the amplification of oxidative degradation of lipids, proteins, nucleic acid, hydro carbonates and in alteration of endogenous strategies for suppression /modulating oxidative stress. The defective DNA repair mechanism via OGG1 and the reduced regulatory effect of sRAGE in activation AGE-RAGE axis in LN group versus non-LN could explain alteration of renal architecture and development of renal injury.
MO077AUTOMATIC SEGMENTATION OF ARTERIES, ARTERIOLES AND GLOMERULI IN NATIVE BIOPSIES WITH THROMBOTIC MICROANGIOPATHY AND OTHER VASCULAR DISEASES
Authors: Lutnick Brendon , Moos Katharina , Seshan Surya V , Kers Jesper , Roelofs Joris , Hellmich Martin , Sciascia Savino , Cicalese Pietro Antonio , Ginley Brandon , Sarder Pinaki , Becker Jan Ulrich
Published: May 2021

Background and Aims

Thrombotic microangiopathies (TMAs) manifest themselves in arteries, arterioles and glomeruli. Nephropathologists need to differentiate TMAs from mimickers like hypertensive nephropathy and vasculitis which can be problematic due to interobserver disagreement and poorly defined diagnostic criteria over a wide spectrum of morphological changes with partial overlap.

As a first step towards a machine learning analysis of TMAs, we developed a computer vision model for segmenting arteries, arterioles and glomeruli in TMA and mimickers.

Method

We manually segmented n=939 arteries, n=6,023 arterioles, n=4,507 glomeruli on whole slide images (WSIs) of 34 renal biopsies and their HE, PAS, trichrome and Jones sections (19 TMA, 11 hypertensive nephropathy, 4 vasculitis with preglomerular involvement). As a segmentation model we used DeepLab V3, pretrained on 61,734 segmented glomeruli from 768 WSIs. 58 randomly chosen WSIs served as the intrainstitutional holdout testing set after training of the model on the remaining slides. Automatic segmentation accuracies were reported as Cohen’s kappa, intersection over union (IoU) and Matthews correlation coefficient (MCC) against the nephropathologist’s segmentation as ground truth.

Results

Over all classes (artery, arteriole, glomerulus) Cohen’s kappa was 0.86.

IoU was 0.716 for artery, 0.491 for arteriole and 0.829 for glomerulus.

MCC was 0.837 for artery, 0.664 for arteriole and 0.907 for glomerulus.

Conclusion

We achieved good automatic segmentation of arteries, arterioles and glomeruli, even with severe pathological distortion on routine histopathological slides. We will further improve this segmentation technology in order to enable the bulk analysis of these descisive tissue compartments in large clinicopathological repositories of native kidney biopsies with TMA using supervised and unsupervised machine learning algorithms.
MO079SOY PROTEINS PREVENT HEART REMODELING IN WISTAR RATS ON HIGH SODIUM CHLORIDE DIET
Authors: Beresneva Olga , Parastaeva Marina , Ivanova Galina , Kulikov Aleksander , Kucher Anatoly , Smirnov Kirill , Khasun Mokhamad , Kayukov, Ivan
Published: May 2021

Background and Aims

Increased salt intake has been linked to a number of poor effects, such as myocardial remodeling [1], independently of blood pressure level. Yet, many aspects of this remodeling are not well understood. The aim of the study was to find echocardiographic myocardial changes in Wistar rats on high sodium chloride (NaCl) diet, as well as to prove protective effects of diet, containing soy proteins.

Method

28 male Wistar rats (age of 2.5-3.0 months) were enrolled in the observational prospective study (4 month) and subdivided into several groups. 1) Standard diet-Control group (C, n = 8, 20.16% protein of animal origin and 0.34% NaCl); 2) High salt diet (n = 10, 8% NaCl); 3) Low-protein diet (n=10, 10% soy protein (SUPRO 760) and 8% NaCl).

Tail systolic blood pressure (BP) measurement, as well as echocardiographic examination were performed in anesthetized rats. Statistical analysis was performed with STATISTICA 10 software package. Fisher's LSD test was used. The significance level was <0.05. All data are presented as mean ± SEM.

Results

Keeping rats on a diet with 8% NaCl did not lead to significant changes in blood pressure (group 2 - 138.0 + 5.0, group 3 - 134.0 + 5.0 mm Hg), compared to C (135.0 + 5.0 mm Hg). On the contrary, left ventricle back wall width in rats of group 2 was significantly higher (1.83 ± 0.09 mm, p <0.02), than in C (1.49 ± 0.10 mm) or animals from group 3 (1, 47 ± 0.09mm).

The values of end systolic left ventricle size, interventricular septum width, mitral valve systolic movement and tricuspid valve systolic movement in group 3 were significantly lower (1.67 ± 0.08 mm, 2.18 ± 0.13 mm, 2.70 ± 0.23 mm), than in group 2 (3.26 ± 0.33mm, p <0.037; 2.00 ± 0.12mm, p <0.043; 2.67mm ± 0.15, p <0.0124; 3.56 ± 0.34mm , p <0.0148, respectively). At the same time, left ventricular chamber size and thickness of interventricular septum did not differ significantly. In C animals, mitral valve movement (1.96 ± 0.09 mm; p <0.0008) and tricuspid valve movement (2.35 ± 0.07 mm; p<0.0012) were significantly lower than in rats of group 2 but not differed much from the values found in group 3.

Conclusion

High sodium containing diet does not necessarily lead to the development of arterial hypertension in Wistar rats, but may cause heart remodeling, while soy proteins counteracts the development of left ventricle hypertrophy, even in case of high sodium consumption.
MO081THE INFLUENCE OF VITAMIN D3 ON PODOCYTE DIFFERENTIATION IN SITU AND IN VITRO
Authors: Lange Tim , Kuhn Laura , Böttcher Marie-Christin , Simm Stefan , Hammer Elke , Kaderali Lars , Völker Uwe , Weber Claudia , Endlich Karlhans , Endlich Nicole
Published: May 2021

Background and Aims

Dedifferentiation of podocytes affects their complex 3 D morphology and is the main initiator for the development of chronic kidney disease (CKD). Unfortunately, there is no causal therapy for CKD until today. Thus, inadequate and late treatment lead to end-stage renal disease which subsequently makes renal replacement therapy inevitable. To address this, new treatment options are of high significance for CKD patients. Recently, vitamin D3 (VitD) became a promising candidate, but it is controversially discussed. In the present study, we investigated the influence of VitD on podocyte differentiation and the related pathways in situ and in vitro.

Method

We combined a podocyte dedifferentiation model (GlomAssay) with an automated imaging procedure (Aquifer Imaging Machine). We analyzed cultured glomeruli from transgenic mice expressing cyan-fluorescent protein (CFP) under the control of the nephrin promoter which were treated with VitD and its` analogue (calcipotriol). In this model, the decreasing CFP fluorescence is as a read out for podocyte (de)differentiation. Additionally, VitD-, calcipotriol- and VitD receptor (VDR) inhibitor (PS121912)-treated glomeruli were investigated by RNA-Seq and LC-MS/MS to reveal the molecular effects of VitD on podocyte differentiation. Furthermore, we treated cultured murine podocytes with VitD, calcipotriol and PS121912 to elucidate the morphological and molecular changes by immunofluorescence staining, RT-qPCR and Western blot.

Results

VitD- and calcipotriol-treated glomeruli showed a significantly higher intensity of CFP fluorescence after 9 days, indicating higher level of nephrin compared to the control. This was verified by RT-qPCR and Western blot for nephrin and CFP. Additionally, we found an upregulation of VDR in VitD- and calcipotriol-treated glomeruli compared to controls. By transcriptomic and proteomic analysis, we identified molecular patterns that are specific for the different treated groups. Thus, we observed differential gene expression in VitD- and Wnt-signaling pathway as well as regulated genes that are essential for the actin cytoskeleton, focal adhesion formation and the slit membrane. Beside this, cultured podocytes showed a significant upregulation of the slit membrane protein nephrin, VDR and CYP24A1 by VitD. This is accompanied by an altered morphology of the podocytes due to a reorganization of the actin cytoskeleton.

Conclusion

Our results show that VitD influences podocyte differentiation in situ and in vitro by the regulation of specific signaling pathways.
MO083SYSTEMATIC HISTOLOGICAL SCORING OF TUBULOINTERSTITIAL LESIONS CORRELATE WITH CLINICAL PARAMETERS IN ANCA-ASSOCIATED GLOMERULONEPHRITIS
Authors: Tampe Björn , Hakroush Samy
Published: May 2021

Background and Aims

Renal involvement is a common and severe complication of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We have previously reported that severe deterioration of kidney function is associated with necrotizing and crescentic ANCA glomerulonephritis (GN), classified into Berden’s crescentic class or ANCA renal risk score (ARRS) high risk. However, tubulointerstitial inflammation associated with either histopathological subgrouping or ARRS remains elusive. Furthermore, clinical and laboratory markers of AAV disease severity or deterioration of kidney function in association with inflammatory findings in the kidney have not been described yet. Since aggressive immunosuppressive therapy is recommended for remission induction especially in severe cases of AAV, we here aimed to expand our current knowledge with regard to histopathological classification of tubulointerstitial injury and inflammatory findings analogous to the Banff classification.

Method

A total number of 50 renal biopsies with confirmed renal involvement of AAV were retrospectively included between 2015 till 2020 in a single-center observational study. Renal biopsies were evaluated for either focal, crescentic, mixed or sclerotic class (according to Berden et al.) and ARRS low, intermediate or high risk (according to Brix et al.). Inflammatory and fibrotic tubulointerstital alterations were evaluated analogous to Banff scoring system for allograft pathology.

Results

We here show that distinct inflammatory lesions are associated with glomerular findings classified into either histopathological subgrouping or ARRS. Furthermore, interstitial inflammation and tubulitis correlate with disease severity and decline of kidney function in AAV. Finally, we provide data that tubulointerstitial injury and inflammatory findings correlate with short-term outcome in response to aggressive immunosuppression and remission induction therapy.

Conclusion

In summary, we here provide evidence that a systematic scoring of inflammatory and degenerative tubulointerstitial lesions correlate with severe renal impairment and short-term response to remission induction therapy. Since aggressive immunosuppressive therapy is recommended for remission induction especially in severe cases of AAV, systematic histopathological scoring of tubuloinsterstital lesions could further improve our current knowledge of ANCA GN progression.
MO084THE INFLUENCE OF INTRAVENOUS CORTICOSTEROIDS ON PLASMA SIRTUIN-1 AND SCLEROSTIN LEVELS IN PATIENTS WITH PRIMARY GLOMERULAR DISEASE
Authors: Peczek Katarzyna , Nowicki Michal
Published: May 2021

Background and Aims

SIRT-1 is member of seven protein family that are involved in the cellular response to inflammatory, metabolic, and oxidative stress. The sirtuin family is a group of class III histone deacetylases. The best known of the family is SIRT-1. It may induce organ protection through inactivation of apoptosis and anti-inflammatory action.

Sclerostin is a glycoprotein produced by the osteocytes and an inhibitor of Wnt signaling. Increased activity of sclerostin increases the resorption of bone tissue and inhibits osteogenesis. It has been hypothesized that by deacetylating histones SIRT-1 could negatively regulate sclerostin gene. That mechanism requires a confirmation in clinical setting.

This exploratory study was designed to assess the influence of high doses of intravenous methylprednisolone on plasma SIRT-1 and sclerostin levels in patients with primary glomerular disease.

Method

The study included 40 patients (25 M, 15 F; mean age 53.1±14 years, mean eGFR 58.9±31.3 ml/min) in different stages of chronic kidney disease. 20 patients had eGFR below the median value of 46 ml/min. The main inclusion criterion was the clinical and histopathological diagnosis of primary glomerular disease and urine protein excretion >2.0 g/24h. The main biopsy-proven diagnoses were IgA nephropathy (13 patients) and focal segmental glomerulonephritis (FSGS) (13 patients). The patients were hospitalized to receive scheduled intravenous pulses of methylprednisolone 20-30 mg/kg/day for three consecutive days followed by oral prednisone 0.8-1.0 mg/kg/day.

The blood was taken before the administration of methylprednisolone to assess SIRT-1, sclerostin, calcium, phosphate and PTH and urine for was taken for the measurement of calcium, phosphate and albumin to creatinine ratio. The same laboratory tests were repeated after 4, 7 and 30 days of steroid therapy.

Results

Plasma SIRT-1 during increased significantly during steroid administration (Fig.1). Plasma sclerostin did not change significantly during the study however a statistically significant correlation between the changes of SIRT-1 levels and sclerostin was found. In a multiple regression model the changes of plasma sclerotin induced by steroid therapy explained the largest part of the variance of the respective changes of plasma SIRT-1.

Conclusion

Plasma SIRT-1 increases during high-dose corticosteroids therapy. The negative relation between the changes of plasma SIRT-1 and plasma sclerostin may suggest a protective role of SIRT-1 against the rapid bone loss induced by corticosteroids.
MO085MONOCLONAL GAMMOPATHY OF UNKNOWN SIGNIFICANCE AMONG MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS PATIENTS
Authors: Kovala Marja , Seppala Minna , Kaartinen Kati , Meri Seppo , Honkanen Eero Olavi , Räisänen-Sokolowski Anne
Published: May 2021

Background and Aims

Monoclonal gammopathy is an entity where a B-cell or plasma cell clone produces monoclonal immunoglobulin. When paraproteinemia and a kidney disease is discovered without criteria for treatment of haematological malignangy, the entity is called monoclonal gammopathy of unknown significance (MGUS) or of renal significance (MGRS). It can cause variable histology, among which membranoproliferative glomerulonephritis (MPGN) has been described. Direct entrapment of paraprotein in glomeruli/tubules can be observed by immunofluorescence (IF), but IF can also be negative as paraprotein can cause complement-associated disease by acting as an activator of the classical pathway or as a dysregulator of the alternative pathway. Electron microscopy (EM) is needed to differentiate possible organized deposits.

Method

We investigated the prevalence, clinical parameters, histology, and the type of monoclonal gammopathy in biopsy-proven MPGN between 2006-2017. A total of 15 adult patients with a detected urine and/or serum paraprotein with concurrent biopsy-proven diagnosis were discovered among 60 patients (Figure 1). Two diagnostic biopsies were from transplants.

Results

MGUS was diagnosed in 15/60 (25%) of patients. Clinical variables are summarized in Table 1. The mean age at presentation was 59 years (37-79), 47-% were males. Smoldering myeloma was diagnosed in 2 (13%) patients and overt malignancy in 3 (20%) patients.

Histological features are summarized in Table 2. There were 7 (47%) with dominant staining for C3 (6 with C3 glomerulonephritis, 1 Dense Deposition Disease) and 8 (53%) with dominant staining for Ig, of which 4 (31%) had mesangioproliferative, 4 (31%) membranoproliferative, 3 (23%) minimal change, 2 (15%) crescentic and 1 (8%) exudative pattern in light microscopy (LM). Seven (47%) biopsies, which did not stain for kappa or lambda light chains. The most common EM deposit location was subendothelial (69%).

Conclusion

MPGN was associated with a significant risk of underlying monoclonal gammopathy, as many (25%) patients were diagnosed with concurrent MGUS. When MPGN is observed, it should prompt investigations of the possible underlying monoclonal gammopathy and possibly, hematological neoplasm.
MO086THE EFFECT OF HIGH SODIUM CHLORIDE INTAKE ON CARDIOVASCULAR SYSTEM AND KIDNEYS IN SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Kayukov, Ivan , Beresneva Olga , Parastaeva Marina , Ivanova Galina , Zaraiski Mikhail , Kucher Anatoly , Smirnov Kirill , Khasun Mokhamad , Smirnov Alexei
Published: May 2021

Background and Aims

It is believed that high consumption of sodium chloride (NaCl) leads to the development of arterial hypertension, which result in heart remodeling, however, NaCl can probably cause direct heart damage. We aimed to evaluate the effects of high and normal NaCl containing diets on blood pressure (BP), myocardial remodeling, as well as on the level of nuclear transcription factor κB (NFκB) expression in myocardium and kidneys.

Method

49 spontaneously hypertensive rats (SHR) were enrolled and subdivided into 2 groups: Group 1 (n=24) received standard diet (NaCl=0,34%); Group 2 (n=25) was on high sodium diet (NaCl=8%). In 2 months, systolic BP, myocardial and renal mass indices, morphological changes, as well as NFκB expression in heart and kidneys were assessed. Results are presented as mean ± SD.

Results

BP in group 2 did not change significantly (190 ± 10 mm Hg, p> 0.05) compared to group 1, yet left ventricle muscle mass indices as well as, right and left kidney mass indices were higher. Hypertrophy of cardiomyocytes (CMC) was found in group2: (area of the nucleus- 43.55 ± 17.39 μm2 (p <0.001); area of CMC-21799.31 ± 579.89 μm2 (p <0.001), compared to group 1: (area of the nucleus- 36.14 ± 4.67 μm2 (p <0.001); area of CMC-19011.13 ± 571.8 μm2 (p <0.001). Also, perivascular fibrosis was found in group2 (area of perivascular connective tissue(APCT)- 4038.96 ± 28.58 μm2 (p <0.001), compared to group1 (APCT-3718.36 ± 91.8 μm2, p <0.001). An increase in arterial wall thickness was noted in group 2 (15.71 ± 6.28 μm, p<0,001), compared to group 1 (13.51 ± 8 ,68 μm, p<0,001). The expression level of NFκB in myocardial tissue (n = 7) in group 2 was 33 times higher, and in kidney tissue (n = 5) 12 times higher than in group 1 (n = 8).

Conclusion

High consumption of NaCl induces NFκB activation in kidneys and myocardium, and may cause myocardial remodeling, probably via NFκB - associated signaling pathways.
MO088CLINICOPATHOLOGICAL FEATURES OF THROMBOTIC MICROANGIOPATHY
Authors: Menezes Maria Do Mar , Soares Elsa , Viana Helena , Góis Mário , Nolasco Fernando
Published: May 2021

Background and Aims

TMA is a rare and severe endothelial lesion with thrombus formation and vascular occlusion with organ damage. It can be a complication of several clinical conditions. The aim of this study was to characterize clinical and pathological findings of patients with confirmed kidney TMA.

Method

We performed a retrospective observational descriptive study that analyzed all patients with TMA diagnosed by kidney biopsy, in two hospital centers, from January 2015 until December 2020. Clinical, laboratorial, pathologic characteristics were analyzed as also therapeutic performed and kidney and patient outcomes.

Results

Our sample had 14 patients, the majority female (n=11, 78%) with a mean age of 45±10 years-old and 12 (80%) were Caucasian. Six (40%) had past medical history of HTA, 2 (13%) had Multiple Myeloma, 4 (26%) transplant (3 kidney, 1 lung) and none had positive viral serology’s. Prodromal symptoms included diarrhea in 2 (13%) patients, neurological in 3 (20%) and previous infection in 3 (20%).

Mean laboratorial values were: Hemoglobin 7.8 g/dL, platelets 161.000/uL; LDH 586 UL; bilirubin 1.38 mg/dL, haptoglobin 1,55 g/L. Only 5 had schistocytes. ADAMTS13 activity was >10% in all performed and in all, Coombs test were negative.

C3 was consumed in 3 (20%) patients and C4 in 2 (13%) but complement phenotypic study was normal in all performed patients. Auto-immune study revealed: 1 positive ANA, dsDNA negative in all but one with positive c1q antibody. One had positive antiphospholipid syndrome (AFS) antibodies and one scleroderma antibodies.

Main kidney presentation was acute kidney injury in 8 (53%) patients, with mean eGFR 14ml/min/1,73m2. Mean proteinuria was 2,5 g/24h and half (50%) had hematuria.

Kidney biopsies had a mean of 11,85 glomerulus, of which 14% sclerotic, mean interstitial fibrosis and tubular atrophy score 1,7. Acute tubular necrosis was present in 7 (46%) and inflammatory infiltrate in all, endotheliosis in 13 (86%), mesangiolysis in 3 (20%), arteriolar thrombus in 10 (66%), glomerular thrombus in 6 (40%), ischemic glomerulus in 12 (80%) and double-contour appearance in 7 (46%).

TMA etiologies were the following: 2 malignant hypertension, 2 proteasome inhibitor (PI), 1 scleroderma, 1 lupus, 1 AFS, 2 calcineurin and mammalian target of rapamycin inhibitors, 2 antibody mediated rejection (AMR), 1 methylmalonic acidemia and 2 undetermined.

Treatment performed encompassed: hypertension management, withdrawal od PI, changing immunosuppression, AMR treatment, cyanocobalamin, lupus induction treatment and eculizumab.

Kidney recovery was observed in 8 patients (53%). Patient survival at 6 months was 73%.

Conclusion

These study results highlight the vast context of conditions that TMA can appear. Most of them had only with mild or even absent clinical and laboratory features. Therefore, a high index of suspicion is required to diagnose TMA, allowing targeted treatment to preserve of kidney function.
MO089HISTOMORPHOMETRIC ANALYSIS OF GLOMERULI AND CAPILLARIES DENSITY IN THE INTERSTITIUM IN PREIMPLANTATION NEEDLE BIOPSIES OF PAIRED KIDNEYS HARVESTED FROM ADULT CADAVERIC DONORS
Authors: Adamczak Marcin , Kwiecien Katarzyna , Karkoszka Henryk , Krol Robert , Wiecek Andrzej Jan
Published: May 2021

Background and Aims

Preimplantation needle biopsy of kidney allows more precise interpretation of subsequent kidney biopsies performed after transplantation and potentially also may predict kidney graft survival. It is unknown, whether it is justified to perform the biopsy of one kidney only and then to transmit obtained results also to the second kidney or biopsies of both kidneys are mandatory. The aim of the study was to assess differences regarding glomerular volume, glomerular density and capillary density in the interstitium of both kidneys harvested from the same deceased donor.

Method

The study involved 40 pairs of kidneys (all together 80 kidneys) in which preimplantation kidney biopsies were performed. Kidneys were harvested from 40 deceased donors (17 females and 23 males; mean age 42.3 [37.6-47.0] years old) died because of intracranial haemorrhage (17 donors) or cerebral trauma due to accident (23 donors). Histomorphometric analysis was performed using “Olympus BX51” microscope (Olympus, Tokyo, Japan) coupled with “Olympus BX50” camera and the “cellSens Standard” software (Olympus, Tokyo, Japan). Weibel-Gomez formula was adapted to calculate glomerular volume.

Results

No significant differences were found between mean kidneys length [115.8 (112.4-119.1) vs.115.5 (112.5-118.5) mm], glomerular volume [2.59 (2.24-2.93) vs 2.49 (2.15-2.84) μm3 x106 ], glomerular density [3.43 (3.07-3.80) vs 3.24 (2.87-3.61) n/mm2] and interstitial capillaries density [233.58 (211.26) vs 217.80 (199.45-236.47) n/mm2] of both kidneys harvested from the same deceased donor.

Conclusions

1. Both kidneys harvested from the same deceased donor did not differ significantly in kidney length, glomerular volume, glomerular density and capillary density. 2. Our results justify to preimplantation biopsy of only one kidney and the results from the histomorphometric analysis may be used in the future also for assessment of the second kidney.
MO071PROTEINS LINKED TO ATHEROSCLEROSIS AND CELL PROLIFERATION ARE ASSOCIATED WITH SHRUNKEN PORE SYNDROME IN HEART FAILURE PATIENTS
Authors: Xhakollari Liana , Jujic Amra , Molvin John , Nilsson Peter M , Holm Hannes , Bachus Erasmus , Leosdottir Margret , Grubb Anders , Christensson Anders , Magnusson Martin
Published: May 2021

Background and Aims

The “Shrunken pore syndrome” is characterized by a difference in renal filtration between cystatin C and creatinine resulting in a low eGFRcystatinC/eGFRcreatinine-ratio, and studies have demonstrated a high risk for cardiovascular morbidity and mortality for patients with shrunken pore syndrome. In this observational study, we explored associations between shrunken pore syndrome and proteins implicated in cardiovascular disease and inflammation in patients with heart failure.

Method

Plasma samples from 300 individuals HARVEST-Malmö trial hospitalized for the diagnosis of heart failure (mean age 75 years; 30% female), were analyzed with a proximity extension assay consisting of 92 proteins, to identify proteins associated with shrunken pore syndrome. Shrunken pore syndrome was defined as eGFRcystatinC ≤60% of eGFRcreatinine. Proteins associated with shrunken pore syndrome in the initial age and sex-adjusted analyses (Bonferroni-corrected p≤ 5.4x10-4) were further adjusted for relevant covariates.

Results

In multivariate analyses, Shrunken pore syndrome was associated with elevated levels of six proteins; scavenger receptor cysteine-rich type 1 protein M130, tumor necrosis factor receptor 1, tumor necrosis factor receptor 2, osteoprotegerin, interleukin-2 receptor subunit alpha, and tyrosine-protein kinase receptor UFO (p<0.05).

Conclusion

In heart failure patients, shrunken pore syndrome was independently associated with proteins linked to atherosclerosis and cell proliferation.