bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure of the PCBP2/stem–loop IV complex underlying translation initiation mediated by the poliovirus type I IRES
Authors: Beckham Simone A , Matak Mehdi Y , Belousoff Matthew J , Venugopal Hariprasad , Shah Neelam , Vankadari Naveen , Elmlund Hans , Nguyen Joseph H C , Semler Bert L , Wilce Matthew C J , Wilce Jacqueline A 
Published: June 2020

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

Abstract

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

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

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

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

Abstract

Background and Aims
Critically ill patients undergo important muscle wasting during ICU stay, and a significant loss of muscle mass still occurs in the first few days of hospital stay. This may delay both functional recovery and weaning from mechanical ventilation, being also a well-known predictor of mortality. Quite often, muscle wasting is masked by fluid overload, increasing the risk for underestimating the presence of malnutrition, as frequently occurs in critically ill patients with AKI.
An important concern in this clinical setting is the lack of adequate tools for routine bedside evaluation of the skeletal muscle mass. Lately, the use of ultrasound (US) for the assessment of muscle mass has aroused considerable interest. It is a non-invasive technique, applicable at the bedside and even in non-collaborative patients, it is economically viable, safe and do not require specialized staff. Recently, its reliability and validity have been demonstrated in critically ill patients with AKI. On this premise, in the present study, we aimed to evaluate the clinical application of US for both evaluation and monitoring of quadriceps muscle thickness in critically ill patients with AKI.

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

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

Abstract

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

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

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

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

Abstract

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

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

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

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

Abstract

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

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

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

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

Abstract

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

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

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

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

Abstract

Background and Aims
Hypertension (AH) is an early complication of autosomal dominant polycystic kidney disease (ADPKD), which significantly increases the risk of decline of kidney function and impacts cardiovascular risk. The diagnosis of AH is often delayed and the optimal control of blood pressure (BP) is difficult to achieve in this group of patients. Of note, the optimal treatment of AH in ADPKD is yet to be established.
Aim of the study was to diagnose AH (including the prevalence of masked hypertension) and to evaluate the control of BP with the use of ABPM in a cohort of ADPKD patients.

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

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

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

Abstract

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

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

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

Conclusion
Our somatic mutation data from single genomes support the existence of two different populations of proliferating tubule cells in healthy, human kidney. One is protected from mutagen exposure, similar to stem cells from other organs. The other population is derived from damaged proximal tubule cells and shows a high mutation rate between 30 and 70 years of age. Mutations are enriched in transcribed genes and regulatory regions, thus enhancing the chances of tumorigenic transformation and suggesting conditions that predispose to cancer in the kidney proximal tubule.
SO044ALPHA LIPOIC ACID COMPARED TO SELENIUM IN MITOCHONDRIAL RESUSCITATION AND MI RNA-126 EXPRESSION IN HEMODIALYSIS PATIENTS
Authors: ElSharkawy Magdy , Al Kasaby Zainab , A. Elewa Hosny , Abdelrahman Maha 
Published: June 2020

Abstract

Background and Aims
anti-oxidants may decrease the risk of cardiovascular complications (CVC) in HD patients. We aimed to study antioxidant effect of Alpha lipoic acid and selenium on oxidative stress, endothelial repair, and mitochondrial functions in HD patients by evaluating the serum level of reactive oxygen species (ROS), miRNA-126, and CoQ10.

Method
60 individuals were enrolled and randomized into 3 groups, G1; 22 HD patients as control, G2; 20 HD patients received Selenium, and G3;18 HD patients received. Serum levels of ROS, CoQ10, and miRNA-126 were assessed at base line and after three months treatment for all patients.

Results
At baseline, all groups were matched regarding their demographic data and target parameters.
After three months, in G1; the serum level of ROS increased significantly (P &lt; 0.05), CoQ10 didn't change significantly (P &gt; 0.05), while the fold expression of miRNA-126 decreased significantly (P &lt; 0.05). In G2,3; there were statistical significant changes in target parameters after the treatment, ROS level decreased significantly by 34%, and by 79%, CoQ10 mean levels increased significantly from 13.21 to 28.35, and from 13.46 to 36.43 ng/ml, mean fold expression of miRNA126, increased significantly by 6.94, and 10.54 folds, in Selenium and, Thiotacid groups respectively. The results showed that Thiotacid was better than Selenium in ROS level reduction, and CoQ10 level improvement, while no statistical significant difference between two drugs regarding miRNA126 level (P &gt; 0.05).

Conclusion
Selenium and, Thiotacid reduce oxidative stress and also they enhancing the endothelial repairing, and improve mitochondrial functions and thus may reduce risk of CVC.