bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surface modification by superimposing piecewise shape function satisfying hull variation given by arbitrary characteristic curve on surface
Authors: Luong Quang-Phap , Nam Jong-Ho 
Published: May 2021

Abstract
The ship hull form is directly related to each design phase of a ship. This form is thus frequently designed based on a variation of a well-made parent ship to avoid new design risks. However, in hull form variation, satisfactory geometric preservation and good performance continuity of the parent ship are considered competing requirements. To effectively facilitate the variation, an appropriate compromise between these requirements should be achieved. Instead of altering hull form parameters, we propose a flexible and intuitive approach to interactively vary the hull surfaces with arbitrary curve constraints and to focus on preserving the properties of the original hull surface. The advantage of the superposition of the curve or surface is leveraged to modify the hull shape. An intermediate surface that satisfies an intermediate curve constraint and has a smooth shape is constructed and superimposed on the top of the original surface to yield the desired surface. A shape control mechanism using a shape function simplifies the control of the surface modification with a curve constraint. The developed method was applied to modify the characteristic curves and section curves situated on the stern part of a container vessel. The changes in the geometric shape and hydrodynamic performance due to the curve-constraint variation were assessed to demonstrate the practicality and efficiency of the proposed method. The results show that the proposed method produces a smooth shape and almost unchanging hydrodynamic patterns. The proposed variation provides an effective tool for varying the hull in a linear fashion.
Survival of chemo-naïve patients with EGFR mutation-positive advanced non-small cell lung cancer after treatment with afatinib and bevacizumab: updates from the Okayama Lung Cancer Study Group Trial 1404
Authors: Ninomiya Takashi , Nogami Naoyuki , Kozuki Toshiyuki , Harada Daijiro , Kubo Toshio , Ohashi Kadoaki , Ichihara Eiki , Kuyama Shoichi , Kudo Kenichiro , Bessho Akihiro , Sakugawa Makoto , Fujimoto Nobukazu , Aoe Keisuke , Minami Daisuke , Sugimoto Keisuke , Ochi Nobuaki , Takigawa Nagio , Hotta Katsuyuki , Maeda Yoshinobu , Kiura Katsuyuki 
Published: May 2021

Abstract

Background
In a phase I study, afatinib (30 mg/body daily) plus bevacizumab (15 mg/kg every 3 weeks) was well tolerated and showed favourable outcomes in patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small-cell lung cancer. Herein, we report the 2-year progression-free survival, overall survival and safety profile of these patients.

Methods
Chemo-naïve patients with EGFR-mutant advanced non-small-cell lung cancer were enrolled. One group of patients received 40 mg afatinib daily and 15 mg/kg bevacizumab every 3 weeks (level 0) until disease progression or severe toxicity. Another group of patients received 30 mg afatinib daily and the same dose of bevacizumab (level 1). Dose-limiting toxicity was the primary endpoint, whereas long-term progression-free survival, overall survival and tolerability were secondary endpoints. Survival rates were estimated using the Kaplan–Meier method.

Results
The study included 19 patients (level 0: 5; level − 1: 14). Until the data cut-off date, seven patients continued the treatment, whereas 12 discontinued due to disease progression (n = 5) or toxicity (n = 7). The median PFS was 24.2 months, while the median overall survival was not reached. All patients developed adverse effects. Diarrhoea and skin rash were frequently observed as severe adverse events (grade 3). A secondary EGFR mutation (T790M) was detected in two patients after progression.

Conclusions
Prolonged follow-up revealed that combination therapy with afatinib and bevacizumab might improve survival outcomes in EGFR-mutant advanced non-small-cell lung cancer patients and seems to be promising.

Trial registration
UMIN000015944.
Digital Communication at the Time of COVID-19: Relieve the Refugees’ Psychosocial Burden and Protect Their Wellbeing
Authors: Mancini Tiziana , Imperato Chiara , Vesco Silvia , Rossi Michele 
Published: May 2021

AbstractThe study aims to evaluate the usefulness and effectiveness of digital communication tools implemented by an Italian NGO during the coronavirus disease 2019 (COVID-19) emergency period, considering their relations with perception of health-related risk, sense of belonging to host community, psychological distress, and wellbeing of the refugees taken in charge by the association. The study was conducted through an anonymous questionnaire proposed to a group of 102 refugees. The results confirmed that by increasing the sense of belonging to the Italian community, the time refugees spent on digital communication negatively associated with their psychological distress and positively associated with their wellbeing. Refugees’ access to digital communication also increased their health-related risk perception that in turn raised their psychological distress. It specifically occurred when digital communication has been perceived as less affordable, i.e. as less clear, easy and reassuring. The results will be used to improve digital communication for health, educational, and proximity services dedicated to refugees.
Adenosine 5′ phosphosulfate reductase and sulfite oxidase regulate sulfite-induced water loss in Arabidopsis
Authors: Bekturova Aizat , Oshanova Dinara , Tiwari Poonam , Nurbekova Zhadyrassyn , Kurmanbayeva Assylay , Soltabayeva Aigerim , Yarmolinsky Dmitry , Srivastava Sudhakar , Turecková Veronika , Strnad Miroslav , Sagi Moshe 
Published: May 2021

Abstract
Chloroplast-localized adenosine-5’-phosphosulphate reductase (APR) generates sulfite and plays a pivotal role in reduction of sulfate to cysteine. The peroxisome-localized sulfite oxidase (SO) oxidizes excess sulfite to sulfate. Arabidopsis wild type, SO RNA-interference (SO Ri) and SO overexpression (SO OE) transgenic lines infiltrated with sulfite showed increased water loss in SO Ri plants, and smaller stomatal apertures in SO OE plants compared with wild-type plants. Sulfite application also limited sulfate and abscisic acid-induced stomatal closure in wild type and SO Ri. The increases in APR activity in response to sulfite infiltration into wild type and SO Ri leaves resulted in an increase in endogenous sulfite, indicating that APR has an important role in sulfite-induced increases in stomatal aperture. Sulfite-induced H2O2 generation by NADPH oxidase led to enhanced APR expression and sulfite production. Suppression of APR by inhibiting NADPH oxidase and glutathione reductase2 (GR2), or mutation in APR2 or GR2, resulted in a decrease in sulfite production and stomatal apertures. The importance of APR and SO and the significance of sulfite concentrations in water loss were further demonstrated during rapid, harsh drought stress in root-detached wild-type, gr2 and SO transgenic plants. Our results demonstrate the role of SO in sulfite homeostasis in relation to water consumption in well-watered plants.
Magnetohydrodynamic stability of magnetars in the ultrastrong field regime I: the core
Authors: Rau Peter B , Wasserman Ira 
Published: May 2021

ABSTRACT
We study magnetohydrodynamic stability of neutron star core matter composed of neutrons, protons, and leptons threaded by a magnetar-strength magnetic field 1014–1017 G, where quantum electrodynamical effects and Landau quantization of fermions are important. Stability is determined using the Friedman–Schutz formalism for the canonical energy of fluid perturbations, which we calculate for a magnetizable fluid with H ≠ B. Using this and the Euler–Heisenberg–Fermi–Dirac Lagrangian for a strongly magnetized fluid of Landau-quantized charged fermions, we calculate the local stability criteria for a neutron star core with a spherical axisymmetric geometry threaded by a toroidal field, accounting for magnetic and composition gradient buoyancy. We find that, for sufficiently strong fields B ≳ 1015 G, the magnetized fluid is unstable to a magnetosonic-type instability with growth times of the order of 10−3 s. The instability is triggered by sharp changes in the second-order field derivative of the Euler–Heisenberg–Fermi–Dirac Lagrangian that occur where additional Landau levels start being populated. These sharp changes are divergent at zero temperature, but are finite for non-zero temperature, so realistic neutron star core temperatures 5 × 107 K &lt; T &lt; 5 × 108 K are used. We conjecture that this mechanism could promote the formation of magnetic domains as predicted by Blandford and Hernquist and Suh and Mathews.
MO001THE EUROPEAN DRTA REGISTRY: AN INITIAL DATA ANALYSIS*
Authors: Bockenhauer Detlef , Emma Francesco , Talhi Amina , Papizh Svetlana , Atmis Bahriye , Homan Nakisa , Aksu Bagdagul , Santos Fernando , Boyer Olivia , Fila Marc , Bayrakci Umut Selda , Ouda Eid Loai Akram , VanDyck Maria , Moguel Carlos , Yüksel Selçuk , Canpolat Nur , Schaefer Franz , Oh Jun , Liebau Max , Ariceta Iraola Maria Gema , Vargas-Poussou Rosa , Levtchenko Elena , Lopez-Garcia Sergio Camilo , Wlodkowski Tanja , Topologlu Rezan 
Published: May 2021

Abstract

Background and Aims
Distal renal tubular acidosis (dRTA) is a rare disorder characterised by an inability of the distal tubule to secrete acid, leading to metabolic acidosis. Clinical consequences typically include hypokalaemia, hypercalciuria with nephrocalcinosis and/or urolithiasis, as well as bone disease. Treatment with adequate alkali supplementation corrects the acidosis and hypercalciuria, but there are few data on long-term outcome. In 2018, a registry for dRTA was established by the European Society for Paediatric Nephrology, hosted by the European Rare Kidney Disease Reference Network. Here, we present an initial analysis of data in the registry.

Method
Analysis of data entered into the registry by the cut-off data of 18/11/2020.

Results
A total of 135 patients had been entered, of which 106 had additional data from an annual follow-up visit. Median age at last visit was 10 years (range 0-54), including 16 adults (&gt;17y). Genetic testing had been performed in 91 subjects and causative variants were reported in 74 (81%). Pertinent clinical details according to genetic group are listed in table 1.
Treatment was provided with at least 15 different preparations, containing citrate or bicarbonate, given in 1-10 (median 3) daily doses.
Adequate treatment at last follow-up, as judged by a plasma bicarbonate level &gt;21 mmol/l and a urine calcium-creatinine ratio in the age-specific normal range was present in 46% of subjects.
There was a trend for higher eGFR and height SDS in subjects with adequate treatment compared to those without, but this was not statistically significant.

Conclusion
Currently available data demonstrate the difficulties in treating dRTA, with less than half of subjects achieving adequate control of their acidosis. By collecting long-term data, the registry will provide important information on the prognosis and complications of dRTA and to what degree these can be prevented with treatment. Enrollment of further, especially adult patients will contribute to our understanding of this rare disorder.
MO004PRIMARY BILIARY CHOLANGITIS PRESENTING WITH RENAL FANCONI SYNDROME: A FORGOTTEN PHENOTYPE
Authors: Er Chaoxui , Sayer John 
Published: May 2021

Abstract

Background and Aims
Primary biliary cholangitits (PBC) is an autoimmune liver disease, leading to liver fibrosis and cirrhosis. It is a rare disease affecting 1 in 3-4000 people and is more common in females. Symptoms may go unnoticed and include itch and fatigue. Most patients have anti-mitochondrial antibodies (AMA) as well as raised gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) levels. First line treatment for PBC is ursodeoxycholic acid and is usually continued lifelong. It improves liver biochemistry, histological progression of liver disease and liver transplant-free survival. Renal complications of PBC include distal renal tubular acidosis (RTA), tubule-interstitial nephritis (TIN) and renal Fanconi syndrome.

Method
We reviewed a case of PBC presenting with renal Fanconi syndrome.

Results
A 48-year-old female was referred to the renal clinic due to progressive decline in renal function since she was diagnosed with type 2 diabetes in 2007. She was also known to have AMA (&gt;1:640) and previously had transient transaminitis. She was clinically well with no major symptoms but reported that she had had a few episodes of urinary tract infection in the previous year. Her diabetes was managed with lifestyle modifications in the past until a few months ago when Metformin was introduced. However, her HbA1c level had never been greater than 55 mmol/mol. Urine dipstick in the clinic showed pH of 6, blood+, glucose+++, protein+++ and ketone trace. The severity of glycosuria was inconsistent with her glycaemic control. There was a disparity between her urine albumin/creatinine ration (ACR) of 18.8g/mol and protein/creatinine ratio (PCR) of 124mg/mmol. Myeloma screen was negative and further urine analysis showed generalised aminoaciduria. She also had hypouricaemia, intermittent hypophosphataemia and non-anion gap metabolic acidosis. These results are in keeping with renal Fanconi syndrome. Her eGFR was 48 ml/min/1.72m2 in 2007 and was 21 ml/min/1.72m at the time of review. A renal biopsy was undertaken, and the appearances were suggestive of mild tubulo-interstitial nephritis; the glomeruli were unremarkable; there was mild chronic tubulo-interstitial damage. She was started on oral steroid, sodium bicarbonate and ursodeoxycholic acid. The course of steroid had a slight transitory beneficial effect on the renal function.

Conclusion
Distal RTA is the usual renal feature of PBC, occurring in 1/3 of cases with advanced disease. In contrast, proximal RTA associating with renal Fanconi syndrome occurs rarely. Like our case, the cases that have been previously reported show that Fanconi syndrome occurred during the early phase of PBC in the absence of marked hepatic abnormalities, and were associated with CKD.
Fanconi syndrome and TIN are renal features of mitochondrial cytopathies and are perhaps a forgotten association of PBC. Antimitochondrial antibodies may play a role in the onset of tubulo-interstitial nephritis and Fanconi syndrome.
MO078DEEP LEARNING DIAGNOSIS OF ANTIBODY-MEDIATED REJECTION (AMR) ON GLOMERULAR TRANSECTIONS
Authors: Cicalese Pietro A , Rizvi Syed A , Roufosse Candice , Batal Ibrahim , Hellmich Martin , Ernst Angela , Moos Katharina , Clahsen-van Groningen Marian , Weidemann Alexander , Mohan Chandra , Nguyen Hien V , Becker Jan Ulrich 
Published: May 2021

Abstract

Background and Aims
Antibody-mediated rejection (AMR) is among the most common causes for kidney transplant loss. The histological diagnosis is hampered by significant intra- and interobserver variability. Training a deep learning classifier for the recognition of AMR on glomerular transections as the most decisive compartment could establish a reliable and perfectly reproducible diagnostic method.

Method
We identified 48 biopsies with AMR (all positive for donor-specific antibody) and 38 biopsies without AMR according to Banff 2017 from our archive. Photographs were taken from all non-globally sclerosed glomeruli on two PAS-stained level sections, yielding a total of 1,655 images as a training set. 1,503 images could be labeled by three experienced nephropathologists conclusively as AMR or non-AMR in a blinded fashion. We trained a DenseNet-121 classifier (pre-trained on ImageNet) with basic online augmentation. In addition, we implemented StyPath++, a data augmentation algorithm that leverages a style transfer mechanism, addressing significant domain shifts in histopathology. Each sample was assigned a consensus label generated by the pathologists.

Results
Five-fold cross validation schemes produced a weighted glomerular level performance of 88.1%, exceeding the baseline performance by 5%. The improved generalization ability of the StyPath++ augmented model shows that it is possible to construct reliable glomerular classification algorithms with scarce datasets.

Conclusion
We created a deep learning classifier with excellent performance and reproducibility for the diagnosis of AMR on glomerular transections. We plan to expand the training set, including challenging cases of differential diagnoses like glomerulonephritis or other glomerulopathies. We are also interested in external clinicopathological datasets to further validate our results.
MO082THE EFFECTS OF DIFFERENT MICROMOLAR CONCENTRATIONS OF CADMIUM IONS ON THE PERITUBULAR MEMBRANE POTENTIAL OF PROXIMAL TUBULAR CELLS IN PERFUSED FROG KIDNEYS
Authors: Kovacevic Sanjin , Spasic Svetolik , Lopicic Srdjan , Todorovic Jasna , Dincic Marko , Stanojevic Marija , Nesovic - Ostojic Jelena 
Published: May 2021

Abstract

Background and Aims
Cadmium (Cd2+) is toxic metal and environmental pollutant. Accumulation of cadmium in the kidney results initially in proximal tubule dysfunction. Although Cd2+ toxicity is well documented, all mechanisms that are involved in the early stages of nephrotoxicity, especially considering low micromolar concentrations of Cd2+ ions are still unknown. The Aim of this study was to investigate the effects acute exposure to different peritubular micromolar concentrations of cadmium (0.25, 0.50, 1.0, 2.0, 3.0, 5.0 μmol/L) on the peritubular cell membrane potential in proximal tubular cells of frog kidney.

Method
The experiments were performed on isolated, doubly perfused kidneys of Rana esculenta of both sexes. Aortic and portal vein were cannulated in order to perfusate luminal and peritubular cell membraine. In controled conditions, Ringer solution was simultaneously used to perfusate both cell membraines. Cadmium chloride (different concentrations: 0.25, 0.50, 1.0, 2.0, 3.0, 5.0 μmol/L) were added to the peritubular perfusate separately, by switching the peritubular perfusate from the control Ringer solution to Ringer solution with addition of cadmium ions. Peritubular cell membrane potentials (PD) were measured with conventional 3 mol/L KCl microelectrodes.

Results
The peritubular application of different micromolar Cd2+ concentrations led to a rapid, sustained, reversible hyperpolarization of the peritubular cell membrane: 0.25 µmol/L, by −3.3±0.4 mV (n=8, p&lt;0.001); 0.50 µmol/L, by −3.0±0.5 mV (n=11, p&lt;0.001); 1.0 µmol/L, by −2.9±0.6 mV (n=8, p&lt;0.01); 2.0 µmol/L, by −4.2±0.4 mV (n=13, p&lt;0.01); 3.0 µmol/L, by −3.4±0.3 mV (n=14, p&lt;0.001); 5.0 µmol/L, by −3.0±0.4 mV (n=10, p&lt;0.001). After switching the perfusion from Ringer solution with addition of cadmium ions to control Ringer, the peritubular membraine potential returned to the average values that were maintained before the peritubular Cd2+ application (p&gt;0.05). Comparing the effect of different Cd2+ concentrations, there was no difference in the hyperpolarization of the peritubular cell membrane (p&gt;0.05).Each cell served as its own control.

Conclusion
Different low micromolar concentrations of Cd2+ provoked rapid and sustained hyperpolarization of peritubular membrane potential that did not show concentration-dependent response.
MO087PLASMALEMMAL VESICLE-ASSOCIATED PROTEIN-1 (PLVAP) INDICATES THE FORMATION OF DIAPHRAGM-BRIDGED FENESTRATIONS OF GLOMERULAR ENDOTHELIAL CELLS IN KIDNEY DISEASE
Authors: Tampe Björn , Schridde Laura , Hakroush Samy 
Published: May 2021

Abstract

Background and Aims
Plasmalemmal vesicle-associated protein-1 (PLVAP or PV-1) is a major protein of diaphragm-bridged fenestrated endothelial cells found in capillaries of neuroendocrine glands and peritubular capillaries. In contrast to peritubular capillaries, the glomerulus is known for its unique fenestrated endothelium without any diaphragm formation thereby ensuring free filtration. Here we aimed to investigate whether PLVAP is expressed in glomerular endothelial cells in various glomerular diseases and whether PLVAP expression is associated with the formation of diaphragm-bridged endothelial cells.

Method
A total number of 114 biopsy samples of glomerular diseases including diabetic nephropathy, FSGS, IgA-Nephritis, ANCA-GN and Lupus–Nephritis were analyzed immunohistochemistically for glomerular PLVAP expression. A fraction of PLVAP positive cases was subsequently investigated ultrastrucurally for the formation of diaphragm-bridged glomerular endothelial cells.

Results
One third of all cases showed at least one glomerulus with one single circumferential PLVAP staining. Interestingly, the most prominent staining, affecting the entire glomerular tuft, was observed in diabetic nephropathy and ANCA-GN. Ultrastructurally, such cases exhibited injured endothelium with focal detachment from the glomerular basement membrane, loss of pore formation and frequently diaphragm-bridged fenestrations reminiscent of peritubular capillaries.

Conclusion
Our data show that injured glomerular endothelium is capable of forming true diaphragm-bridged fenestrations, suggesting a possible role in preventing glomerular protein leakage and limiting its detachment from the GBM.
MO067DELETION AND BLOCKAGE OF KININ B1 RECEPTOR EXACERBATES CISPLATIN-INDUCED CKD
Authors: Estrela Gabriel , Budu Alexandre , Freitas-Lima Leandro , Arruda Adriano , Perilhão Mauro , Barrera-Chimal Jonatan , Araujo Ronaldo 
Published: May 2021

Abstract

Background and Aims
Kinins plays a major role in immune response, where kinin B2 receptor is constitutively expressed and kinin B1 receptor is induced under inflammatory stimuli. Kinin B1 receptor deletion and blockage has been shown to have beneficial effects in some models of renal diseases. Multiple acute renal insults, even if followed by renal recovery, is a risk factor for the future development of chronic kidney disease (CKD) and end-stage renal disease (ESRD). Our main objective was to determine the importance of kinin B1 receptor in tubulointerstitial fibrosis induced by ongoing cisplatin treatment.

Method
Male C57/Bl6 mice were divided in 3 groups, vehicle, cisplatin, cisplatin + R715 (kinin B1 receptor antagonist). Animals has been treated with multiple doses of cisplatin (7mg/kg i.p) once a week during 4 weeks and R715 (0.8mg/kg i.p) 48, 24 and 1 hour prior to cisplatin injections. We also used B1KO mice (C57Bl6 background) and WT mice (littermates). Mice were euthanized after 30 days of last cisplatin injection. Renal parameters, histology, real time PCR were performed to investigate renal injury, inflammation and fibrosis.

Results
Cisplatin treatment increases most of renal parameters, renal injury and fibrosis markers. Deletion of B1 receptor exacerbates significantly creatinine (WT CIS 0,60+0,03 B1KO 0,76+0,01 mg/dL), urea (WT CIS 111,8+5,638 B1KO CIS 240,8+28,60 mg/dL), and protein excretion (WT CIS 0,0058+0,0011 B1KO CIS 0,0121+0,0007 mg/24h). Association of cisplatin with R715 increased creatinine levels (veh 0,43+0,03 cis+R715 0,64+0,04 mg/dL), exacerbates urea (cis 95,51 + 3,926 cis+R715 158,9+14,40 mg/dL) and protein excretion (cis 0,012+0,002 cis+R715 0,018+0,003 mg/24h). Renal injury markers such as KIM-1 and TNF-a showed no significant differences. NGAL expression exacerbates (cis 2,53+0,44 cis+R715 5,66+1,34) and tubular injury score (cis 0,130+0,021 cis+R715 0,191+0,020) is higher in cisplatin+R715 group. Fibrosis markers a-SMA (cis 2,56+0,43 cis+R715 4,67+0,99), Col4 (cis 2,57+0,39 cis+R715 5,14+1,01) and Vimentin (2,69+0,31 cis+R715 4,62+0,98) were exacerbated in cisplatin treatment associated with R715. Picrosirius red staining were used to asses tubulointerstitial fibrosis, and we confirmed that R715 treatment here also exacerbates fibrosis (cis 0,225+0,025 cis+R715 0,345+0,042).

Conclusion
Here we show that both deletion and blockage of kinin B1 receptor has deleterious effects in renal injury and fibrosis induced by ongoing cisplatin treatment.