bluuebunny/crossref_metadata_2025 huggingface dataset:
The Argentinian landscape of mycological diagnostic capacity and treatment accessibility
Authors: Riera Fernando , Caeiro Juan Pablo , Cornely Oliver A , Salmanton-García Jon ,   Argentinian IFI diagnostic and treatment capacity group, Reyes Nahir Daniela Anahí , Morales Adria , Oyola María Carolina , Messina Fernando A , Atorri Silvia , Bertone Juan Manuel , Lambert Sanra , Costantini Patricia , Cuello Alejandra , Stefanini Lucas , Arce Veronica , Alaniz Valeria , Cikman Fernando , Garzón María Isabel , Marianelli Leonardo , Bernachea Paula , Angélica Miriam , Castellano Farias , Lerman Damian , Bangher María , Frola María Soledad , Méndez Gustavo A , Morera Graciana , Raimondo Mariana Rodríguez , Lipari Flavio , Guerci Marcia , Maillard Diego Varela
Published: June 2023

Immunosuppressed patients, transplant recipients, and those with acute or chronic respiratory disease are at increased risk for invasive fungal infections in Argentina. Although the national public system guarantees universal access to health care for all citizens, little is known about the quality of available diagnostic and treatment armamentaria for invasive fungal infections in the country. Between June and August 2022, infectious disease clinicians from each of the 23 provinces and the Autonomous City of Buenos Aires were contacted to describe local access to fungal diagnostic tools and antifungal agents. The information collected included different aspects such as hospital characteristics, patients admitted and wards, access to diagnostic tools, estimated infection incidence, and treatment capacity. Thirty responses were collected from facilities throughout Argentina. Most institutions were governmental (77%). A mycology department was available in 83% of them. Histopathology was available in almost 93% of the sites, while automated methods and galactomannan tests were available in 57%, each; 53% of the sites had access to MALDI-TOF-MS through regional reference laboratories, and PCR was present in 20% of the sites. Susceptibility testing was available in 63% of the laboratories. Candida spp. (24%), Cryptococcus spp. (20%), Aspergillus spp. (18%), and Histoplasma spp. (16%) were described as the main pathogens. Fluconazole was the only antifungal agent available in all institutions. This was followed by amphotericin B deoxycholate (83%) and itraconazole (80%). If an antifungal agent was not available onsite, then 60% of the patients could receive adequate antifungal treatment within the first 48 h upon request. Although there are no significant differences in access to diagnostic and clinical management of invasive fungal infections among the Argentinean centres studied, national awareness-raising initiatives led by policymakers could help to improve their general availability.
Accreting neutron stars: composition of the upper layers of the inner crust
Authors: Shchechilin N N , Gusakov M E , Chugunov A I
Published: June 2023

We model the nuclear evolution of an accreted matter as it sinks toward the stellar center, in order to find its composition and equation of state. To this aim, we developed a simplified reaction network that allows for redistribution of free neutrons in the inner crust to satisfy the recently suggested neutron hydrostatic and diffusion equilibrium condition. We analyse the main reaction pathways for the three representative thermonuclear ash compositions: Superburst, Kepler, and Extreme rp. In contrast to the previous results, which neglect redistribution of free (unbound) neutrons in the inner crust, the most significant reactions in our calculations are neutron captures and electron emissions. The pycnonuclear fusion plays some role only for Kepler ashes. For the direct application of our results in astrophysical codes we present profiles of the average charge, 〈Z〉, impurity parameter, Qimp and equation of state for a set of models, parametrized by the pressure at the outer-inner crust interface. Typically, for Superburst ashes Qimp ≈ 1 − 4, while for Kepler ashes Qimp decreases from ≈23 at the outer-inner crust interface to ≈5 at the end of our simulation (the corresponding density equals ρdc ≈ 2 × 1012 g cm−3). At the same time, for Extreme rp ashes Qimp remains large ≈30 − 35 in the considered inner crust region. Our results are important for modeling the thermal relaxation of transiently accreting neutron stars after the end of the outburst.
Recent astrophysical observations reproduced by a short-range correlated van der Waals-type model?
Authors: Rodrigues E H , Dutra M , Lourenço O
Published: June 2023

We perform an improvement in a van der Waals-type model by including its effects of short-range correlations (SRCs). Attractive and repulsive parts of the nucleon–nucleon interaction are assumed to be density-dependent functions, more specifically, we adopt the Carnahan–Starling (CS) method for the latter, and a suitable expression for the former in order to reproduce the structure of the Clausius (C) real gas model. The parametrizations of the resulting model, named as Clausius-–Carnahan–Starling (CCS)-SRC model, are shown to be capable of reproducing the flow constraint at the high-density regime of symmetric nuclear matter for incompressibility values inside the range of K0 = (240 ± 20) MeV. In the context of stellar matter, our findings point out a good agreement of the CCS-SRC model with recent astrophysical observational data, namely, mass–radius contours and dimensionless tidal deformability regions and values, coming from gravitational waves data related to the GW170817 and GW190425 events, and from the NASA’s Neutron star Interior Composition Explorer mission. Furthermore, the values for the symmetry energy slope of the model (L0) are in agreement with a recent range found for this quantity, claimed to be consistent with results reported by the updated lead radius experiment (PREX-2) collaboration. In this case, higher values of L0 are favoured, while the opposite scenario does not allow simultaneous compatibility between the model and the astrophysical data.
3D Global climate model of an exo-Venus: a modern Venus-like atmosphere for the nearby super-Earth LP 890-9 c
Authors: Quirino Diogo , Gilli Gabriella , Kaltenegger Lisa , Navarro Thomas , Fauchez Thomas J , Turbet Martin , Leconte Jérémy , Lebonnois Sébastien , González-Galindo Francisco
Published: June 2023

The recently discovered super-Earth LP 890-9 c is an intriguing target for atmospheric studies as it transits a nearby, low-activity late-type M-dwarf star at the inner edge of the Habitable Zone. Its position at the runaway greenhouse limit makes it a natural laboratory to study the climate evolution of hot rocky planets. We present the first 3D-Global Climate Model exo-Venus model for a modern Venus-like atmosphere (92 bar surface pressure, realistic composition, and H2SO4 radiatively-active clouds), applied to the tidally-locked LP 890-9 c to inform observations by JWST and future instruments. If LP 890-9 c has developed into a modern exo-Venus, then the modelled temperatures suggest that H2SO4 clouds are possible even in the substellar region. Like on modern Venus, clouds on LP 890-9 c would create a flat spectrum. The strongest CO2 bands in transmission predicted by our model for LP 890-9 c are about 10 ppm, challenging detection, given JWST estimated noise floor. Estimated phase curve amplitudes are 0.9 and 2.4 ppm for continuum and CO2 bands, respectively. While pointing out the challenge to characterise modern exo-Venus analogues, these results provide new insights for JWST proposals and highlight the influence of clouds in the spectrum of hot rocky exoplanet spectra.
#4181 THE AUTOSOMAL RECESSIVE POLYCYSTIC KIDNEY DISEASE PROTEIN, FPC, RELEASES MITOCHONDRIA LOCALISING FRAGMENTS INVOLVED IN PREVENTING CYSTOGENESIS
Authors: Walker Rebecca , Xu Hangxue , Maranto Anthony , Outeda Patricia , Watnick Terry , Qian Feng
Published: June 2023

Background and Aims

Autosomal recessive polycystic kidney disease is caused by mutations in PKHD1 encoding FPC, and is characterized by severe renal cystogenesis in neonates, yet mouse models do not fully recapitulate the human phenotype. Indeed, even the Pkhd1 null allele does not cause renal cystogenesis in the mouse. Several cleavage products of FPC are reported yet their function remains unknown. The aim of this study was to determine the function of the FPC cleavage products and their effects on cyst development in ARPKD.

Method

Three Pkhd1 mutant mouse lines and the cystic Pkd1V mouse were crossed to produce digenic mice with which to study renal cystogenesis. Biochemical analysis was used to investigate FPC cleavage patterns using a panel of new antibodies. Cell models and electron microscopy revealed underlying mitochondrial defects in Pkhd1 Knockout mice.

Results

Pkhd1 mutation modifies a Pkd1 uncleavable mutant (Pkd1V), enhancing the cystic phenotype in both the kidney and pancreas. The hypomorphic Pkhd1 mutant and Pkhd1 KO both enhance the Pkd1V kidney phenotype, making distal tubule cysts more severe and initiating cystogenesis in the proximal tubules. FPC displays differential cleavage to produce fragments of unknown function. New antibodies were generated to interrogate FPC cleavage products. Three small C terminal cleavage fragments were identified which contain a mitochondrial targeting sequence and are recruited to mitochondria. Mitochondrial ultrastructural changes were evident after deletion of Pkhd1 including mitochondrial fragmentation and dilated cristae, suggesting disrupted mitochondrial function. Deletion of just the C-terminal fragment of FPC (ΔCT), the portion that directly corresponds to the portion that cleaves and localises to the mitochondria, is sufficient to enhance the renal cystic phenotype of the PC1 cleavage mutant. Unlike the other Pkhd1 mutants however, FPC (ΔCT) does not result in the pancreatic cystogenesis when combined with Pkd1V, suggesting that the FPC C terminus in not required to prevent pancreatic cyst development.

Conclusion

Our results suggest that the C-terminus of FPC plays an important role in preventing renal cystogenesis via a newly discovered mitochondria specific function. Our work reveal some aspects of FPC's function, in particular a previously unrecognised mitochondria function that is mediated through FPC cleavage products and is essential in the kidney to prevent the enhancement of cystogenesis in the digenic model.
#6225 MICROPLASTICS: FIRST EXTENDED PROTEOMIC ANALYSIS ON KIDNEY TUBULAR CELLS
Authors: Cervello Carla , Bruschi Maurizio , Candiano Giovanni , Kajana Xhuliana , Garbarino Andrea , Rumeo Noemi , Petretto Andrea , Cravedi Paolo , Gentile Micaela , Angeletti Andrea , Lugani Francesca , Ghiggeri Gian Marco , Verrina Enrico Eugenio , Bigatti Carolina , Giordano Paolo , Esposito Pasquale , Viazzi Francesca , Verzola Daniela , La Porta Edoardo
Published: June 2023

Background and Aims

Several studies have shown the ubiquitous presence of microplastics (plastic fragments between 5 mm and 1 μm in diameter) and nanoplastics (<1 μm) in the environment and their toxicity. Furthermore, microplastics (MPs) absorb a lot of environmental pollutants, such as bisphenol A (BPA), and release them into tissues increasing their toxicity; this is the so called “Trojan Horse” effect. Recent studies have also proved their presence in human blood and human tissues of healthy people, such as placenta and lung, and in cirrhotic liver. Most frequent biological effects of MPs are inflammation, oxidative stress and alteration of metabolic pathways. In this study proteomic analysis was performed to evaluate the toxicity of polyethylene (PE) and bisphenol-A (BPA) MPs on renal tubular cells (HK2) in vitro. This is the first extended proteomic study on human cells.

Method

HK-2 cultures were exposed for 5-24-48 hours to BPA, PE Microspheres (PE-MP) and MP combined with BPA. Then it was performed a proteomic analysis by mass spectrometry (MS). MS data were obtain by Orbitrap Fusion Tribrid mass spectrometer (ThermoScientific). Analysis of data were performed using unsupervised hierarchical clustering using multidimensional scaling, non-linear support vector machine (SVM) learning, and partial least squares discriminant analysis. In SVM learning, a fourfold cross-validation approach was applied to estimate the prediction and classification accuracy.

Results

The proteomic analysis showed a clear differentiation of the HK2 proteome based on conditioning and identified a “core” of proteins, significant at ANOVA and above the 95th percentile for “fold increase” and significant at T-test compared with controls, highly discriminatory between groups. Finally, among these, a final set of 6 proteins was selected to be validated for distinguishing features: Nephronectin, GDF15, Vasorin, IGFBP7, Midkine, Tissue factor-F3. Nephronectin is a structural membrane's protein involved in cellular adhesion. GDF15, tissue factor F3 and midkine are markers of stress conditions, including inflammation and oxidative stress. IGFBP7 is a biomarker of acute kidney damage. Vasorin is a transmembrane glycoprotein that protects against apoptosis and fibrosis.

Conclusion

MP and BPA significantly modify the protein expression in renal tubular cells. These findings highlight the urgent need for additional research into the toxic effects of plastic debris on human kidneys and the eventual link to kidney diseases.
#2561 URINE PROTEOMICS FOR PREDICTION OF DISEASE PROGRESSION IN PATIENTS WITH IGA NEPHROPATHY
Authors: Peters Björn , Beige Joachim , Siwy Justyna , Rudnicki Michael , Wendt Ralph , Ortiz Alberto , Sanz Ana Belen , Mischak Harald , Reich Heather , Nasic Salmir , Mahmood Dana , Persson Anders , Fernström Anders , Weiner Maria , Stegmayr Bernd
Published: June 2023

Background and Aims

IgA nephropathy (IgAN) may lead to kidney failure. The urinary proteomics biomarker-based classifier (IgAN237) may predict progression at the time of kidney biopsy [1]. We now studied whether IgAN237 predicts disease progression not only at the time of biopsy but also later in the course of IgAN.

Method

Urine samples from 103 patients with biopsy-proven IgAN were analyzed using capillary electrophoresis-mass spectrometry at baseline (IgAN237 score-1) and 89 also at follow-up (IgAN237 score-2). Patients were grouped into ‘non-progressors’ (IgAN237 score ≤0.38 Units) and ‘progressors’ (IgAN237 score >0.38 Units). Historical and follow-up data included, e.g., estimated glomerular filtration rate (eGFR)-slopes, urinary albumin/creatinine ratio (UACR)-slopes and medication. Multiple logistic regression analysis, using a stepwise model, was done with progressors and non-progressors as dependent factors including explanatory variables age, sex, eGFR- and UACR-slopes.

Results

Median age at biopsy was 44 years (range 11-92); 63% were male. Median interval between biopsy and IgAN237 score-1 was 65 months (0-606), and between IgAN237 score-1 and score-2 was 258 days (71-531). IgAN237 score-1 and score-2 values did not differ significantly and were correlated (rho = 0.44, p<0.001). Twenty-eight and 26% of patients were classified as progressors based on IgAN237 score-1 and score-2, respectively. The IgAN237 score inversely correlated with the chronic eGFR slopes (rho = -0.278, p = 0.02 for score-1; rho = -0.409, p = 0.002 for score-2) and with ±180days eGFR slopes (rho = -0.31, p = 0.009 and rho = -0.439, p = 0.001, respectively) (Figure 1). The ±180days eGFR-slopes were more reduced for progressors than non-progressors (median -5.98 versus -1.22 mL/min/1.73m2 per year for score-1, p<0.001; -3.02 vs 1.08 mL/min/1.73m2 per year for score-2, p = 0.047) (Figure 2). The only significant variable maintained in a multiple logistic regression analysis for IgAN237 score-1 (progressor vs non-progressor) was ±180days eGFR slope (p<0.001) and for IgAN237 score-2 the UACR (p = 0.002) and age at baseline (p = 0.016).

Conclusion

The urinary IgAN237 classifier represents a risk stratification tool in IgAN not only at the time of biopsy but also later in the course of the disease. It may guide physicians in management and follow-up strategies in an individualized manner.
#3895 COMPARABLE RENO-CARDIAC PROTECTIVE EFFECTS OF SGLT2 INHIBITION VERSUS DPP-4 INHIBITION IN DIABETIC KIDNEY TRANSPLANT RECIPIENTS: KUWAIT EXPERIENCE
Authors: Alotaibi Torki , Gheith Osama Ashry Ahmed , Elsayed Zakaria , Yahya Ahmed , Shaker Mohamed , Khalid Mahmoud , Emam Mohamed , Hammad Muhammad , Nagib Ayman Maher , Mostafa Mohamed , Denewar Ahmed , Zahab Mohamed Ahmed Abdulkhalek , Nair Prasad , Elserwy Nashwa , Elserwy Nabil
Published: June 2023

Background and Aims

Diabetes is the most common cause of chronic kidney disease (CKD) globally. The renal and cardio-vascular benefits of the new anti-diabetic agents are not assessed comprehensively. We aimed to evaluate the short term renal and cardio-protective effects of Sodium-Glucose Cotransporter-2 Inhibition (SGLT2i) Vs. Dipeptidyl peptidase-4 Inhibition (DPP4i) among diabetic kidney transplant recipients.

Method

In this observational trial, 222 diabetic kidney transplants recipients (NODAT or type 2 diabetes) were enrolled and were categorized into two groups. Group 1 (n = 99) received SGLT2i while group 2(n = 123) received DPP4i as an add on antidiabetic medications. All patients in the two groups were followed up for 12 months.

Results

Most patients in the two groups (1&2) were men (59.6 vs. 61.7%, p = 0.73) in their middle age (58.5±11.9 vs. 54.4±12.9, p = 0.016) years respectively. The two groups were matched regarding their demographics especially the type of donor, type of immunosuppression (induction or maintenance), number of cardiovascular events before enrollment in the study and the number of patients who were maintained on ACEi or ARB(p>0.05). The minority of patients were smokers (12.9 vs.8.7%), and chronic glomerulonephritis was the original disease in 36.4 vs. 35.4% in the two groups, respectively. Most of the enrolled patients (72.8 vs. 78.6%) underwent hemodialysis pre-transplant. During follow up period, patients in both groups were comparable regarding mean blood pressure, body weight, HbA1C, 24-hour urine protein, and graft function (represented by the mean serum creatinine) at different time intervals and compared to base line values(p>0.05). However, the mean HbA1C was significantly higher in group 1 during the whole follow up period of the study (p<0.05) but it did not drop significantly compared to baseline values (p>0.05). We did not report any macroangiopathic events (cerebral stroke, acute myocardial infection, or peripheral arterial disease) in the two groups during the study.

Conclusion

Both GLT2i and DPP-4 I are comparable regarding renal and cardio-vascular protection among diabetic kidney transplant recipients.
#4499 MATCHING-ADJUSTED INDIRECT COMPARISON OF SPARSENTAN VS DELAYED-RELEASE FORMULATION BUDESONIDE FOR PROTEINURIA REDUCTION IN ADULTS WITH IGA NEPHROPATHY
Authors: Chai Xinglei , Bensink Mark , Gao Sophie , Gong Wu , Diva Ulysses , Hendry Bruce , Mercer Alex , Zhou Jenny
Published: June 2023

Background and Aims

Immunoglobulin A (IgA) nephropathy is a rare kidney disorder characterized by deposition of IgA in the glomeruli and associated with a reduction in renal function and increased risk of kidney failure [1,2]. In the absence of head-to-head trials, this study used matching-adjusted indirect comparison (MAIC)[3] of randomized control trial data to compare 9-month efficacy outcomes between potential treatment options for IgA nephropathy, sparsentan and recently FDA and EMA approved delayed-release formulation budesonide [4,5].

Method

An unanchored MAIC was conducted using individual patient level data from the PROTECT trial for sparsentan and aggregate data from the NefIgArd trial for delayed-release formulation budesonide. Patients in the sparsentan arm of PROTECT were weighted to match the key baseline characteristics of patients in the budesonide delayed-release formulation arm of NefIgArd. After matching, the percentage reduction of urine protein-creatinine ratio (UPCR) at Month 9 relative to baseline were compared between sparsentan and delayed-release formulation budesonide. A two-tailed z-test was performed to estimate the p-value.

Results

Assessment of cross-trial heterogeneities suggested that PROTECT and NefIgArd trials were sufficiently similar in terms of patient population, key inclusion and exclusion criteria, and outcome definitions; however, due to differences in control arms (renin-angiotensin system blocker [RASB] optimization), an unanchored MAIC (comparing treatment arms directly) was selected. After matching, all matched baseline patient characteristics were well-balanced between corresponding treatment arms of the two trials. The comparative results showed that patients treated with sparsentan achieved a greater mean percentage reduction in UPCR at 9 months from baseline compared to budesonide-treated patients (p-value withheld pending FDA approval of sparsentan due to regulatory requirements).

Conclusion

The MAIC results showed that sparsentan was associated with a significantly larger percentage reduction in UPCR, a recognized surrogate of long-term kidney outcomes, from baseline to month 9 compared with delayed-release formulation budesonide.
#5414 CLINICAL UTILITY OF SEROLOGICAL TEST AT TIME OF BIOPSY
Authors: Segelmark Mårten , Weiner Maria , Peters Björn
Published: June 2023

Background and Aims

It is common practice to order serological tests at time of renal biopsy, but the diagnostic value in different clinical settings is largely unknown. We utilized data from the national Swedish Renal Biopsy Registry to analyze the positive and negative post-test likelihood of four common diagnoses depending on the results of frequently used serological tests.

Method

Data on all biopsies performed during the period 2015-01-01 – 2020-12-31 was retrieved from the Swedish Renal Biopsy Registry. All biopsies are classified into one of the following five biopsy indications: the nephrotic syndrome (nephrosis), acute/subacute nephritic syndrome (nephritis), other acute kidney injury (AKI), chronic kidney disease stage 1-2 (CKD 1-2), and CKD 3-5. Biopsy results are given as SNOMED codes by the pathologist and a clinical diagnosis using the ERA coding system by the nephrologist. Results from the following serological tests were analyzed: C3, C4, ANA, anti-dsDNA, ANCA (PR3 and/or MPO-ANCA) and anti-phospholipid antibodies. Pre-test likelihood, positive post-test (PPL) and negative post-test likelihood (NPL) for the diagnoses IgA nephropathy (IgAN), diabetic nephropathy (DN), ANCA-associated vasculitis (AAV) and lupus nephritis (LN) were analyzed. The diagnostic yield was defined as the ratio between the PPL and NPL.

Results

Out of a total of 3165 individuals that had undergone kidney biopsy, there were 694 (21.9%) patients assigned a diagnosis of IgAN, 378 (11.9%) with DN, 342 (10.8%) with AAV and 117 (3.7%) with LN. The proportion of patients being tested varied from 17% for anti-phospholipid antibodies to 77% for ANCA. The highest diagnostic yield was found for ANCA in AAV were the PPL/NPL ratio was 154. In patients with nephrosis the ratio went up to 290 mainly because of a very low NPL (0.2%). The next best diagnostic yield was seen in SLE were both ANA and anti-dsDNA exhibited a PPL/NPL ratio of 26. The best yield for ANA was found when the biopsy indication was nephrosis where the PPL was 33% and the NPL 0.54% and the ratio 61. For anti-dsDNA the best yield was in AKI with a ratio of 46 (PPL 55%, NPL 1.1%). The best test to make a diagnosis less likely was anti-phospholipid antibodies in diabetic nephropathy. The test was never positive in any of the 42 patients with this diagnosis, however the same result slightly increased the likelihood of AAV. A positive result for C3(reduced levels) also reduced the likelihood av diabetic nephropathy, the PPL / NPL ratio was 13. C4 and ANCA being, on the other hand, reduced the likelihood for IgAN with a ratio in the same range.

Conclusion

While the utility of ANCA, ANA and anti-dsDNA is well known, it is less known when a positive test substantially reduced the likelihood of a disease. Here we present data showing that a positive test for C3 decreases the likelihood of DN, while the likelihood is much less affected by C4. The opposite Is seen for IgAN.
#5475 SAFETY OF NATIVE AND TRANSPLANT KIDNEY BIOPSY IN A NATIONAL COHORT
Authors: Mcquarrie Emily , Bell Samira , Campbell Jacqueline , Watters Chrissie , Lakey Joe , Metcalfe Wendy , Hunter Robert , Stevens Kate , Traynor Jamie , Cousland Zoe , Joss Nicola , Walbaum David , Kipgen David , Crosby Jana , Kelly Michael , Dey Vishal , Buck Kate , Methven Shona , Stewart Graham , Murugan Kiru , Conway Bryan , Geddes Colin C
Published: June 2023

Background and Aims

Safety of kidney biopsy is variably reported in different published series. Since 2014, all native kidney biopsies undertaken in the 9 adult renal units in Scotland have been recorded by the Scottish Renal Registry (SRR) and since 2015 all transplant kidney biopsies were included. In this complete national dataset, we report data on safety of kidney biopsy in a current real world setting.

Method

Major complications of kidney biopsy are recorded using pre-defined terms and include: arteriography and embolisation, arteriography no embolisation, clot retention, blood transfusion only, death within 28 days directly attributable to biopsy, nephrectomy and other. Biopsies are undertaken under ultrasound guidance using 16G or 18G spring loaded biopsy guns. All centres discontinue clopidogrel, DOACs and warfarin. Some centres continue aspirin. In some centres biopsy is performed by nephrologists and in others by radiologists

Results

In total, 6979 biopsies in 5755 patients were recorded between 2014 and 2021 (5095 native biopsies and 1884 transplant biopsies), with an adequacy for diagnosis of 98.1%. Table 1 describes the demographics, indications, operator and diagnoses made by biopsy type. Overall, in patients undergoing native kidney biopsy 2.4% suffered a major complication and 1.4% of patients undergoing transplant biopsy. The commonest complication was the requirement for arteriography, with or without embolisation. We included CT angiography in this group. There were 8 deaths within 28 days attributable to renal biopsy.

Conclusion

Kidney biopsy remains safe for the vast majority of patients and complications are less likely with transplant biopsy.
#5946 MULTICENTER STUDY EVALUATING THE FREQUENCY OF ADVERSE EVENTS ASSOCIATED WITH THE SARS-COV2 VACCINATION AMONG PATIENTS WITH GLOMERULAR DISEASES
Authors: Lionaki Sophia , Kriki Pelagia , Marinaki Smaragdi , Dounousi Evaggelia , Flouda Sophia , Fanouriakis Antonios , Liakopoulos Vasileios , Vaios Vasileios , Sardeli Angeliki , Kleinaki Zoe , Petrou Dimitra , Agoranou Marilena , Gkika-Zervou Louisa , Goumenos Dimitrios , Papasotiriou Marios , Venetsanopoulou Aliki , Voulgari Paraskevi , Grapsa Eirini , Andronikidi E , Stylianou Konstantinos , Panagoutsos Stylianos , Boletis Ioannis
Published: June 2023

Background and Aims

Development of SARS-CoV-2 vaccination has altered the natural course of the related infection and the pandemic. The present study aims to explore the frequency of adverse events in patients with glomerular diseases (GD).

Methods

Patients with biopsy-broven GD, who received at least one dose of the vaccine against SARS-CoV-2 were studied retrospectively. Patients who ended up in ESKD prior to vaccination were excluded. We recorded demographics, histopathological diagnosis, past medical history, immunosuppressive regimens which were given at diagnosis and thereafter, outcome of the GD and adverse events associated with the vaccine, both systemic and local. We also estimated the rate of GD relapse post vaccination in patients who were in remission of the primary diseases compared with patients who decided not to receive the vaccine.

Results

To date 280 patients with GD have been included in the study with a mean age of 47,6 (±17,8) years, of whom 111 (39,6%) are males. Patients received in total 3,0 (±0,9) vaccine doses with the mean time from the diagnostic kidney biopsy to the 1st dose of being 76,5 (±61,5) months. 47,1% of the patients were on immunosuppressive therapy at the time of vaccination. 27,1% of the patients reported systemic side effects (fever, arthralgias, myalgias) and 50,7% reported local side effects (pain, swelling, itching, edema). Renal function and 24-hour proteinuria remained stable after vaccination. Among patients who were in remission of the GD at the time of vaccination 19 (8,2%) patients experienced a relapse of the primary disease after vaccination, versus 5% of patients not vaccinated (p = 0,99).

Conclusions

According to our findings the vaccine against SARS-CoV-2 appears safe for patients with GD with no significant impact in renal function or the probability for relapse.
#4646 CT-DERIVED RADIOMICS ANALYSIS OF DIABETIC NEPHROPATHY BY MACHINE LEARNING MODELS
Authors: Chung Eui Seok , Lee Eun Ji , Yoon Jongjin , Lee Haekyung , Kim Hyoungnae , Noh Hyunjin , Kwon Soon Hyo , Jeon Jin Seok
Published: June 2023

Background and Aims

Kidney radiomics has been used to develop more accurate diagnostic tools of renal tumor and predict outcomes. However, radiomics studies for diabetic kidney disease (DKD) remain few. In this light, we hypothesized that computed tomography (CT) radiomics features could differentiate DKD from normal kidneys and assess the severity of DKD.

Method

This retrospective study included 343 subjects with type 2 diabetes mellitus (T2DM) (male 65.5%, mean age 63.6±14.8) and 90 healthy controls (HC) (male 34.4%, mean age 41.9±8.5) who underwent abdominal CT. Whole volumetric CT data of both kidneys were automatically extracted using a deep-learning based model and radiomics features were extracted. T2DM were categorized into three groups according to eGFR (mL/min/1.73 m^2) (group 1, eGFR > 60; group 2, 15 ≤ eGFR ≤ 60; and group 3, eGFR <15). The capability of CT radiomics features to distinguish not only DKD from HC but also various DKD groups based on eGFR, was evaluated using machine learning models.

Results

A total of 1,723 radiomics features were extracted from the volumetric CT data of both kidneys. A combination of LASSO filter and random forest showed best performance in differentiating between HC and DKD, with an area under curve (AUC) of 0.98 and accuracy of 95.7%. It also showed an excellent performance in differentiating between HC and DKD group 1 with AUC of 0.97 and accuracy of 91.7%, and also it was able to differentiate between DKD groups (AUCs > 0.78). CT radiomics features and eGFR had a moderate degree of correlation (R=-0.50 to R=0.63, all P<.00).

Conclusion

CT-derived radiomics analysis of kidneys using machine learning models can be useful in differentiating DKD from normal kidneys as well as assessing the severity of DKD.
#6794 CALCIUM/MAGNESIUM RATIO IN PATIENTS WITH DIABETES AND CHRONIC KIDNEY DISEASE: A RISK FACTOR FOR CARDIOVASCULAR DISEASE
Authors: Borges Henrique , Afonso Rita , Marques Roberto Calças , Jerónimo Teresa , Silva Ana
Published: June 2023

Background and Aims

Chronic Kidney Disease (CKD) and Diabetes Mellitus (DM) are significant risk factors for Cardiovascular (CV) Disease. Patients with CKD and/or DM exhibit higher incidence and prevalence of CV events compared to the general population. Hypomagnesemia and elevated calcium-magnesium (Ca:Mg) ratios have been identified as independent risk factors for CV-related deaths. The aim of this study is to determine the relationship between Ca:Mg and the prognosis of CV disease in patients with CKD and DM.

Method

This cross-sectional study enrolled patients with DM and CKD followed at Diabetic Nephrology appointments in a hospital. The study population was divided into two groups: Group 1 (G1) - patients who had a previous hospitalization due to a CV event, and Group 2 (G2) - patients without CV-related hospitalizations. A logistic regression model was employed to evaluate the predictive factors for CV hospitalization for the variables studied.

Results

A total of 223 patients were included in the study, 92 females and 131 males, with an estimated glomerular filtration rate of 38.4±22 mL/min/1.73 m2 and 41% had been hospitalized due to a CV event. G1 had higher age (P = .02), higher serum phosphate (p<0.01), parathormone (p<0.01), interleukin-6 (p<0.01), FGF-23 (p<0.01), oxidized-LDL (p<0.01), Ca:Mg (p<0.01), and pulse pressure (p<0.01), as well as lower eGFR (p<0.01) and magnesium serum levels (p<0.01). The multivariate logistic regression model revealed that higher FGF-23 levels (OR=3.44, 95% CI 1.192-9.954, P = .02), Ca:Mg (OR=1.204, 95% CI 2.072-59.040, P = .01), oxidized LDL (OR=9.746, 95% CI 3.277-29.020, p<0.01), and an eGFR <30 mL/min/1.73 m2 (OR=8.685, 95% CI 1.277-59.040, P = .03) were predictors of CV morbidity.

Conclusion

In this population, Ca:Mg and FGF-23 were predictors of CV morbidity. Further studies are necessary to fully understand the relationship between serum magnesium and calcium levels and CV events. Monitoring these parameters may be valuable in clinical practice to identify high-risk patients.
Determinants of cervical spine disorders in military pilots: a systematic review
Authors: Al Rumaithi M , Al Qubaisi M , Al Suwaidi M , Al Zaabi F , Campos L A , Baltatu O C , Al Tunaiji H
Published: June 2023

Background

Neck pain and cervical spine disorders are widespread among military cockpit aircrew pilots and are often recognized as occupational stressors.

Aims

This systematic review aimed to identify significant determinants for military pilot neck pain and cervical spine disorders determined through multivariable logistic regression studies.

Methods

This systematic review was conducted according to the recommendations of the Statement of Systematic Review and Meta-analysis Protocols (Preferred Reporting Items for Systematic Reviews and Meta-Analyses [PRISMA]-P). The following databases were searched for literature: Medline and Embase. We included studies that studied neck pain, cervical spine disorders, and/or radiological abnormalities and associated exposures (adjusted odds ratios, ORadj) in military cockpit aircrew. The trustworthiness, relevance and results of the published papers were evaluated using the Joanna Briggs Institute critical checklist.

Results

A total of three studies quantified the strength of the correlations between exposures and outcomes. Significant determinants/risk factors of neck pain, cervical spine disorders and radiological abnormalities were identified as age (ORadj: 1.092 [95% CI 1.054, 1.132]), fighter type (ORadj: 3.9 [95% CI 1.1, 13.9]) and absolute rotation angle of C2-7 (ARA) (ORadj: 0.91 [CI 0.85, 0.98]). The following variables were unable to demonstrate statistical significance: flying hours, body height and body mass index.

Conclusions

Military cockpit aircrew’s frequent neck pain after a flight raises concerns about cervical spine disorders. Age, fighter type and ARA C2-7 are strong predictors of neck pain and cervical spine disorders. More research is needed on occupational determinants and risk factors for neck pain and cervical spine disorders in military cockpit aircrew.
Genetic factors for differentiated thyroid cancer in French Polynesia: new candidate loci
Authors: Zidane Monia , Haber Marc , Truong Thérèse , Rachédi Frédérique , Ory Catherine , Chevillard Sylvie , Blanché Hélène , Olaso Robert , Boland Anne , Conte Éric , Karimi Mojgan , Ren Yan , Xhaard Constance , Souchard Vincent , Gardon Jacques , Taquet Marc , Bouville André , Deleuze Jean-François , Drozdovitch Vladimir , de Vathaire Florent , Cazier Jean-Baptiste
Published: June 2023

Background

Populations of French Polynesia (FP), where France performed atmospheric tests between 1966 and 1974, experience a high incidence of differentiated thyroid cancer (DTC). However, up to now, no sufficiently large study of DTC genetic factors in this population has been performed to reach definitive conclusion. This research aimed to analyze the genetic factors of DTC risk among the native FP populations.

Methods

We analyzed more than 300 000 single nucleotide polymorphisms (SNPs) genotyped in 283 DTC cases and 418 matched controls born in FP, most being younger than 15 years old at the time of the first nuclear tests. We analyzed the genetic profile of our cohort to identify population subgroups. We then completed a genome-wide analysis study on the whole population.

Results

We identified a specific genetic structure in the FP population reflecting admixture from Asian and European populations. We identified three regions associated with increased DTC risk at 6q24.3, 10p12.2, and 17q21.32. The lead SNPs at these loci showed respective p-values of 1.66 × 10−7, 2.39 × 10−7, and 7.19 × 10−7 and corresponding odds ratios of 2.02, 1.89, and 2.37.

Conclusion

Our study results suggest a role of the loci 6q24.3, 10p12.2 and 17q21.32 in DTC risk. However, a whole genome sequencing approach would be better suited to characterize these factors than genotyping with microarray chip designed for the Caucasian population. Moreover, the functional impact of these three new loci needs to be further explored and validated.
Temporal and vertical dynamics of diatoms and dinoflagellates in the southeastern Mediterranean Sea
Authors: Rahav Eyal , Berman-Frank Ilana
Published: June 2023

The temporal distributions of microphytoplankton were studied monthly over 2 years in the shelf and the offshore waters of the “low nutrients low chlorophyll” (LNLC) southeastern (SE) Mediterranean Sea. The microphytoplankton were comprised mostly of diatoms (0–542 cells L−1, ~4 × 106–44 × 106 cells m−2) of the genera Rhizosolenia, Thalassionema, Chaetoceros, Leptocylindrus and Pseudo-nitzschia, and dinoflagellates (1–89 cells L−1, ~1 × 106–10 × 106 cells m−2) of the genera Tripos (formally known as Ceratium), Ornithocercus, Protoperidinium, Ceratocorys and Dinophysis. During the winter mixing, microphytoplankton abundance was ~2-fold higher than during the stratified summer months, in accordance with the higher inorganic nutrient levels. Diatoms were mostly found in the upper illuminated layers (0–100 m), while dinoflagellate distribution was patchy and spread from surface down to 200 m. We also calculated that diatoms and dinoflagellates contribute negligibly (~4%) to the total vertical carbon flux in the offshore water, suggesting fast recycling of organic matter at the photic layer. Our results provide a baseline to better understand carbon and biogenic silica fluxes at the LNLC SE Mediterranean Sea.
Genome-wide high-throughput chromosome conformation capture analysis reveals hierarchical chromatin interactions during early somatic embryogenesis
Authors: Chen Yan , Xie Dejian , Ma Xiangwei , Xue Xiaodong , Liu Mengyu , Xiao Xuechen , Lai Chunwang , Xu Xiaoping , Chen Xiaohui , Chen Yukun , Zhang Zihao , XuHan Xu , Lai Zhongxiong , Lin Yuling
Published: June 2023

Somatic embryogenesis (SE), like zygotic embryo development, is a progressive process. Early SE is the beginning of a switch from a somatic to an embryogenic state and is an important stage for initiating chromatin reprogramming of SE. Previous studies suggest that changes in chromatin accessibility occur during early SE, although information on the 3D structure of chromatin is not yet available. Here, we present a chromosome-level genome assembly of longan (Dimocarpus longan) using PacBio combined with high-through chromosome conformation capture scaffolding, which resulted in a 446 Mb genome assembly anchored onto 15 scaffolds. During early SE, chromatin was concentrated and then decondensed, and a large number of long terminal repeat retrotransposons (LTR-RTs) were enriched in the local chromatin interaction region, suggesting LTR-RTs were involved in chromatin reorganization. Early SE was accompanied by the transformation from A to B compartments, and the interactions between B compartments were enhanced. Results from chromatin accessibility, monomethylation of histone H3 at lysine 4 (H3K4me1) modification, and transcription analyses further revealed a gene regulatory network for cell wall thickening during SE. Particularly, we found that the H3K4me1 differential peak binding motif showed abnormal activation of ethylene response factor transcription factors and participation in SE. The chromosome-level genomic and multiomics analyses revealed the 3D conformation of chromatin during early SE, providing insight into the molecular mechanisms underlying cell wall thickening and the potential regulatory networks of TFs during early SE in D. longan. These results provide additional clues for revealing the molecular mechanisms of plant SE.
Autophagy in maternal tissues contributes to Arabidopsis seed development
Authors: Erlichman Ori Avraham , Weiss Shahar , Abu Arkia Maria , Ankary-Khaner Moria , Soroka Yoram , Jasinska Weronika , Rosental Leah , Brotman Yariv , Avin-Wittenberg Tamar
Published: June 2023

Seeds are an essential food source, providing nutrients for germination and early seedling growth. Degradation events in the seed and the mother plant accompany seed development, including autophagy, which facilitates cellular component breakdown in the lytic organelle. Autophagy influences various aspects of plant physiology, specifically nutrient availability and remobilization, suggesting its involvement in source–sink interactions. During seed development, autophagy affects nutrient remobilization from mother plants and functions in the embryo. However, it is impossible to distinguish between the contribution of autophagy in the source (i.e. the mother plant) and the sink tissue (i.e. the embryo) when using autophagy knockout (atg mutant) plants. To address this, we employed an approach to differentiate between autophagy in source and sink tissues. We investigated how autophagy in the maternal tissue affects seed development by performing reciprocal crosses between wild type and atg mutant Arabidopsis (Arabidopsis thaliana) plants. Although F1 seedlings possessed a functional autophagy mechanism, etiolated F1 plants from maternal atg mutants displayed reduced growth. This was attributed to altered protein but not lipid accumulation in the seeds, suggesting autophagy differentially regulates carbon and nitrogen remobilization. Surprisingly, F1 seeds of maternal atg mutants exhibited faster germination, resulting from altered seed coat development. Our study emphasizes the importance of examining autophagy in a tissue-specific manner, revealing valuable insights into the interplay between different tissues during seed development. It also sheds light on the tissue-specific functions of autophagy, offering potential for research into the underlying mechanisms governing seed development and crop yield.
The social context of burning mouth syndrome: an exploratory pilot study of stigma, discrimination, and pain
Authors: Mathur Vani A , Payano Sosa Janell S , Keaser Michael L , Meiller Timothy F , Seminowicz David A
Published: June 2023

Background

The social context of burning mouth syndrome (BMS) has received little attention in the scientific literature. However, social psychological theory and insights from those with lived experiences suggest that people living with BMS experience compounding effects of stigma related to their pain, diagnosis (or lack thereof), and intersectional identities.

Objective

Our aim is to provide initial evidence and to motivate new directions for research on BMS. Here, we present the results of an exploratory pilot study (n = 16) of women living with BMS in the United States.

Methods

Participants completed self-report measures of stigma, discrimination, and pain, as well as laboratory assessments of pain through quantitative sensory testing.

Results

Results indicate a high prevalence of internalized BMS stigma, experience of BMS-related discrimination from clinicians, and gender stigma consciousness in this population. Moreover, results provide initial evidence that these experiences are related to pain outcomes. The most robust pattern of findings is that internalized BMS stigma was related to greater clinical pain severity, interference, intensity, and unpleasantness.

Conclusion

Given the prevalence and pain-relevance of intersectional stigma and discrimination identified in this pilot study, lived experience and social context should be incorporated into future research on BMS.
Joint tenderness at 3 months follow-up better predicts long-term pain than baseline characteristics in early rheumatoid arthritis patients
Authors: Eberhard Anna , Bergman Stefan , Mandl Thomas , Olofsson Tor , Sharma Ankita , Turesson Carl
Published: June 2023

Objective

To investigate pain course over time and to identify baseline and 3-month predictors of unacceptable pain with or without low inflammation in early RA.

Methods

A cohort of 275 patients with early RA, recruited in 2012–2016, was investigated and followed for 2 years. Pain was assessed using a visual analogue scale (VAS; 0–100 mm). Unacceptable pain was defined as VAS pain >40, and low inflammation as CRP <10 mg/l. Baseline and 3-month predictors of unacceptable pain were evaluated using logistic regression analysis.

Results

After 2 years, 32% of patients reported unacceptable pain. Among those, 81% had low inflammation. Unacceptable pain, and unacceptable pain with low inflammation, at 1 and 2 years was significantly associated with several factors at 3 months, but not at baseline. Three-month predictors of these pain states at 1 and 2 years were higher scores for pain, patient global assessment, and the health assessment questionnaire, and more extensive joint tenderness compared with the number of swollen joints. No significant associations were found for objective inflammatory measures.

Conclusion

A substantial proportion of patients had unacceptable pain with low inflammation after 2 years. Three months after diagnosis seems to be a good time-point for assessing the risk of long-term pain. The associations between patient reported outcomes and pain, and the lack of association with objective inflammatory measures, supports the uncoupling between pain and inflammation in RA. Having many tender joints, but more limited synovitis, may be predictive of long-term pain despite low inflammation in early RA.