bluuebunny/crossref_metadata_2025_split huggingface dataset:
Memories without Survival: Personal Identity and the Ascending Reticular Activating System
Authors: Meier Lukas J 
Published: June 2023

AbstractLockean views of personal identity maintain that we are essentially persons who persist diachronically by virtue of being psychologically continuous with our former selves. In this article, I present a novel objection to this variant of psychological accounts, which is based on neurophysiological characteristics of the brain. While the mental states that constitute said psychological continuity reside in the cerebral hemispheres, so that for the former to persist only the upper brain must remain intact, being conscious additionally requires that a structure originating in the brainstem—the ascending reticular activating system—be functional. Hence, there can be situations in which even small brainstem lesions render individuals irreversibly comatose and thus forever preclude access to their mental states, while the neural correlates of the states themselves are retained. In these situations, Lockeans are forced to regard as fulfilled their criterion of diachronic persistence since psychological continuity, as they construe it, is not disrupted. Deeming an entity that is never again going to have any mental experiences to be a person, however, is an untenable position for a psychological account to adopt. In their current form, Lockean views of personal identity are therefore incompatible with human neurophysiology.
Public Secrets: The Dynamics of Publicity and Secrecy in Offensive Cyber Operations
Authors: Baram Gil 
Published: June 2023

Abstract
Historically, offensive cyber operations (OCOs) have been considered a practice that states could carry out covertly, away from the public eye, with both perpetrators and defenders having incentives to remain silent. Over the past few years, however, perpetrators and defenders have publicly acknowledged their involvement in OCOs. How common is this strategic choice among states? What are its characteristics? In this research note I show that this is not a binary choice, and that there is variance in the strategies available to either side. I then examine what state behavior patterns can be identified by using compiled data of OCOs between 1996 and 2019. I show that this phenomenon of giving up secrecy is occurring and point out on states’ characteristics and probabilities of choosing each strategy. Initial findings show significant use of public strategies by perpetrators (20 percent) and more so by defenders (50 percent), and that democracies tend toward public credit claiming and attribution, while less democratic countries tend toward public denial. As governments increasingly engage in OCOs, the implications of this research note are of interest to scholars and practitioners alike.
Comparative network analysis as a new approach to the editorship profiling task: A case study of the Mishnah and Tosefta from Rabbinic literature
Authors: Zadok Avital , Zhitomirsky-Geffet Maayan , Schler Jonathan , Katzoff Binyamin 
Published: June 2023

AbstractSocial network analysis of characters in historical works is a popular research methodology in the study of historical literature. This article proposes using this methodology to characterize and comparatively analyze editing styles of similar historical literary works to determine whether they were edited by the same hand. To that end, the study proposes constructing a network of characters for each of the works being studied and to compute standard statistical measures for these networks, thus producing a network-based profile for the editing style of each work, which can be compared to the profiles of various other works. To determine the effectiveness of this new approach, it was tested on two similar works from the realm of Rabbinic literature—the Mishnah and the Tosefta. Our findings show that despite the abundant structural, thematic, and linguistic similarities of the works, their network-based profiles demonstrated clear differences between them with respect to various parameters, like the degree of connectivity, density, and centrality of the networks and their communities, and also with respect to the usage of different types of relationships in each network. These differences are reflected in the network features of the works, rather than in their texts, and so it would be difficult to identify them using direct stylometric analysis on the texts of the works, especially given the stylistic and thematic similarity between them. The approach presented in this article forms a basis for developing automatic classifiers to identify different editors and editing styles based on works’ network-based profiles.
A study of the high-inclination population in the Kuiper belt – IV. High-order mean-motion resonances in the classical region
Authors: Li Jian , Lawler S M , Lei Hanlun 
Published: June 2023

ABSTRACT
In our previous study of Neptune’s 4:7 mean-motion resonance (MMR), we discovered that its resonant angle can only librate within a specific eccentricity (e) versus inclination (i) region, determined by a theoretical limiting curve. This ‘permissible region’ is independent of time and encompasses the entire possible stable region. We now generalize this theory to investigate all high-order MMRs embedded in the main classical Kuiper belt (MCKB). We first consider the second-order 3:5 MMR in the framework of planet migration and resonance capture, and have further validated our limiting curve theory for both captured and observed 3:5 resonators. It suggests that only the (e, i) pairs inside the individual permissible regions should be chosen as initial conditions for studying the in situ evolution of high-order resonators. With such a new setting, we proceed to explore the long-term stability (for 4 Gyr) of different resonant populations, and our simulations predict that (1) the 3:5 and 4:7 resonators are comparable in number, and they could have inclinations up to 40°, (2) the populations of objects in the higher order 5:9, 6:11, 7:12, and 7:13 resonances are about 1/10 of the 3:5 (or 4:7) resonator population, and nearly all of them are found on the less inclined orbits with i &lt; 10°, and (3) for these high-order resonances, almost all resonators reside in their individual permissible regions. In summary, our results make predictions for the number and orbital distributions of potential resonant objects that will be discovered in the future throughout the MCKB.
#3295 RAPIDLY PROGRESSIVE AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE : RISK FACTORS FOR DISEASE SEVERITY DURING CHILDHOOD AND EARLY ADULTHOOD
Authors: Wigerinck Stijn , Schellekens Pieter , Dachy Angélique , Chedid Maroun , Hanna Christian , Jouret François , Harris Peter , Bammens Bert , Chebib Fouad , Mekahli Djalila 
Published: June 2023

Abstract

Background and Aims
Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease and is characterized by genetic complexity and phenotypic variability. The age of reaching kidney failure (KF) is variable and covers the complete age-spectrum. There is an unmet need for early biomarkers to differentiate between rapid and slow progressors. The PROPKD score identified hypertension before the age of 35 years as a risk factor for rapid kidney function decline. We aim to identify earlier risk factors for rapid disease progression by studying a population of ADPKD patients who reached kidney failure (KF) before the age of 40y.

Method
This multicentric retrospective study focusses on a unique population (n = 200) of ADPKD patients who reached KF before 40y. Kidney failure (KF) was defined as CKD5 or start of Kidney Replacement Therapy (KRT), whichever came first. Longitudinal data on childhood history, comorbidities and kidney function were collected. Life table and Proportional Hazards analysis were used to assess associations between clinical parameters and time to KF.

Results
Median age of ADPKD diagnosis was 22.3 (16.5 – 28.6) and median age of KF onset was 36.2 years (32.9-38.7 years). Fourty-seven patients were genotyped (23.5%) of which 38 patients (81.0%) were PKD1T and 8 (17.0%) were PKD1NTand only 1 patient (2.1%) was PKD2. Median age at first urological event was 27.0 (20.7 – 32.0) years. 71 patients (35.5%) had history of UTI's, 67 patients (33.5%) had hemorrhagic cysts on abdominal imaging, 66 patients (33.0%) presented with gross hematuria and 40 patients (25.0%) presented with kidney stones. There was a high prevalence of hypertension (N = 128, 64.0%). Four patients (N = 4/128, 3.1%) had a very early diagnosis of hypertension before the age of 10 years. Hypertension-onset before the age of 18 years correlated with a significantly faster progression (UV HR: 2.07 (1.32 – 3.25)).

Conclusion
This study describes a unique cohort of ADPKD patients with rapid disease progression. Hypertension at young age (&lt;18) correlated with rapid disease progression, suggesting that ambulatory blood pressure in children might be useful to identify patients at risk for rapidly progressive ADPKD.
#5528 FIBROBLAST GROWTH FACTOR 21 PREDICTS ARTERIOVENOUS FISTULA FUNCTIONAL PATENCY LOSS AND MORTALITY IN PATIENTS UNDERGOING MAINTENANCE HEMODIALYSIS
Authors: Hu Xinhui , Wei Qing , Wang Bin , Liu Hong 
Published: June 2023

Abstract

Background and Aims
Arteriovenous fistula (AVF) dysfunction is a common complication in patients undergoing maintenance hemodialysis (MHD). Elevated serum level of fibroblast growth factor 21 (FGF21) was associated with atherosclerosis and cardiovascular mortality. However, its association with vascular access outcomes remains elusive. In this study, we aimed to evaluate the relationship of serum FGF21 levels with AVF dysfunction and all-cause mortality in patients undergoing MHD.

Method
We performed a study of patients undergoing MHD who received AVF creation at a tertiary medical center in China from January 2018 to December 2019. Serum FGF21 concentration was detected by enzyme-linked immunosorbent assay (ELISA). Patients were followed-up to record two clinical outcomes, including AVF functional patency loss and all-cause mortality. The follow-up period ended at April 30, 2022. Kaplan-Meier curves were used to analyze AVF dysfunction events and mortality. Univariate and multivariate Cox proportional risk model analyses were used to calculate risk ratios (HR) and 95% CI and independent prognostic factors. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to analyze the predictive value of FGF21 in AVF functional patency loss and all-cause mortality.

Results
Among 147 patients, the mean age was 58.49±14.41 years, and 58.50% of them were males. The median serum level of FGF21 was 150.15 (70.57-318.01) pg/ml. During median follow-up period of 40.83 months, the serum level of FGF21 was an independent predictor for AVF functional patency loss (per 1 pg/mL increase, HR 1.002 [95% CI: 1.001-1.003, P = 0.003]. Besides, patients with higher serum level of FGF21 was more likely to suffer from all-cause mortality (per 1 pg/mL increase, HR 1.002 [95% CI: 1.000-1.003, P = 0.014]. The optimal cutoffs for FGF21 to predict AVF functional patency loss and all-cause mortality in patients undergoing MHD were 149.98 pg/ml and 146.43 pg/ml, with an AUC of 0.701 (95% CI 0.606-0.796, P = 0.001) and 0.677 (95% CI 0.566-0.788, P = 0.006), respectively.

Conclusion
Serum FGF21 level was an independent risk factor and predictor for AVF functional patency loss and all-cause mortality in patients undergoing MHD.
#6257 PROGNOSTIC VALUE OF A POSITIVE CROSSMATCH BEFORE DESENSITIZATION IN A COHORT OF HIGHLY-SENSITIZED PATIENTS
Authors: Noble Johan , Malvezzi Paolo , Jouve Thomas , Bardy Beatrice , Rostaing Lionel , Dard Celine 
Published: June 2023

Abstract

Background and Aims
Human Leukocyte antigen (HLA) sensitization in patients is a barrier for Kidney Transplantation (KT) access, and highly-sensitized patients remain on the waiting list longer than other patients which results in a higher morbidity and mortality. Desensitization may be an option to increase their access to KT. All patients transplanted in this context have a negative Complement-Dependent Cytotoxicity crossmatch (CDC-CM) the day of KT. However, the stratification of the long-term risk of graft loss according to flow cytometry crossmatch (FC-CM) and to CDC-CM during the desensitization period remains unknown.

Method
In this retrospective study, all highly-sensitized patients (Panel Reactive Antigen (PRA) ≥ 85) in our center were included. CDC-CM and FC-CM were performed on samples before and during the desensitization period and clinical follow-up data were retrieved. Pre-KT desensitization strategy consisted in two Rituximab infusions (375mg/m2) and a variable number of apheresis (mostly semi-specific immunoadsorption) associated with a classical immunosuppression-based regimen (tacrolimus, mycophenolate and steroids).

Results
A total of 183 highly-sensitized recipients received a KT between 2014 and 2022. Of these, 23 were desensitized prior to KT and among them 18 had a positive FC-CM before KT and 5 had no positive FC-CM on all assessed serums. Mean age was 52.9 ± 13 years. Mean follow-up was 5.2±4 and 3±2 years for non-desensitized and desensitized patients respectively. PRA before desensitization was higher in desensitized patients (98%) versus non-desensitized patients (95%) and the mean time on the waiting list was 5.8±4 versus 7.5±4 years respectively. Death-censored graft survival and patient's raw survival, using cox-survival analysis, were not statistically different between the desensitized kidney transplanted patients and the highly-sensitized patients without desensitization (p = 0.77 and p = 0.57 respectively). In sub-group analyses, the positivity of FC and/or CDC-CM did not add an additional risk of graft loss or patient mortality.

Conclusion
Desensitization allows highly-sensitized patients to access KT with an HLA-incompatible graft (with a positive CDC or FC-CM on the serum collected prior to desensitization), with the same graft survival as similarly sensitized patients transplanted with an HLA-compatible graft without desensitization.
#6496 CYCLIN D1 AMELIORATES ACUTE KIDNEY INJURY BY IMPROVING FATTY ACID OXIDATION VIA AMPK PATHWAY
Authors: Huang Yuliang , Chen Junzhe , Shao Xiaofei , LI Jinxiang , Tang Ying 
Published: June 2023

Abstract

Background and Aims
Acute Kidney Injury (AKI) is a critical condition that is caused by the absence of oxygen during the acute ischemic phase, leading to energy metabolism disturbance and kidney tubular epithelial cell damage. Fatty Acid Oxidation (FAO) is the main source of energy production of renal proximal tubular epithelial cells. Timely promoting FAO, increasing supplies of energy, and promoting cell proliferation are essential to improve kidney injury. However, there is no clinically recognized effective treatment for this. Cyclin D1(CCND1), a member of the cell cycle family, plays a vital role in cell proliferation. Our previous study showed that CCND1 improved AKI by increasing FAO. This study aimed to investigate the role and molecular basis of CCND1 involvement in fatty acid oxidation of AKI.

Method
CCND1 was evaluated in human kidney proximal tubular epithelial cells (HK-2 cells) and in male C57BL/6J mice (wild type). We investigated the protective role of CCND1 in AKI using a mouse model of ischemia-reperfusion injury, which was treated by transferring CCND1-expressing plasmids in male C57BL/6J mice (wild type) by ultrasound and microbubble-mediated delivery. Eight-week-old male C57BL/6J mice (wild type) were subjected to bilateral renal artery occlusion for 30min followed by 24h of reperfusion. We evaluated FAO, proliferation, and autophagy in vitro and in vivo. In addition, we evaluated the concentrations of blood urea nitrogen and creatinine, evaluated kidney ultrastructure and so on.

Results
In vivo studies showed that activation of CCND1 prevented AKI-induced lipid accumulation, kidney tubule injury and kidney function declined after ischemia-reperfusion injury. Compared to test control, the treatment significantly (p&lt;0.05) reduced the concentrations of blood urea nitrogen and creatinine. Kidney-specific overexpression of CCND1 increased FAO, promoted proliferation and reduced apoptosis. Mechanistically, CCND1 activated the AMPK pathway, which increased the expression of phosphorylation AMP activated protein kinase (p-AMPK) and upregulated FAO. On the other hand, inhibiting the expression of CCND1 worsened the impairment of FAO and disturbed energy metabolism.

Conclusion
CCND1 improved FAO and reduced lipid accumulation through the active AMPK pathway in kidney proximal tubular epithelial cells (PTECs). Hence, restoring of the expression of CCND1 may offer a novel therapeutic strategy for treating AKI.
#6709 DONOR-DERIVED CELL-FREE DNA (DD-CDNA) AS A NON-INVASIVE BIOMARKER OF KIDNEY ALLOGRAFT REJECTION IN PEDIATRIC KIDNEY TRANSPLANTATION
Authors: Hogan Julien , George Roshan , Winterberg Pamela , Hayes Carissa , Fan Chris , Kamel Margret , Garro Rouba 
Published: June 2023

Abstract

Background and Aims
Rejection remains the first cause of allograft loss in pediatric kidney transplant (pkTx) recipients. Detection of rejection currently relies on kTx biopsies performed either because of allograft dysfunction with the risk of late diagnosis or per surveillance protocols allowing early detection of subclinical rejection but resulting in many unnecessary biopsies. Dd-cfDNA was reported as a new non-invasive biomarker with the potential to improve rejection detection and guide biopsy indications. We aim to assess the association of dd-cfDNA levels with biopsy results in a large cohort of pediatric kTx recipients.

Method
All pediatric kTx patients with at least one dd-cfDNA assessment at the time of a biopsy at a single pediatric transplant center were included. Clinical, biological and histological data were collected from medical reports. Dd-cfDNA were retrospectively measured from plasma samples biobanked at the time of allograft biopsy between 2015 and 2020 or collected in patients who received regular dd-cfDNA testing as part as clinical care between 2021 and 2022.

Results
170 cfDNA measurements in 132 pkTx recipients were available at the time of a biopsy, including 100 performed for surveillance. Mean age at biopsy was 16 years with a median time from kTx of 21 [11;38] months. Median eGFR was 62 [48;83] mL/min/1.73 m2, median UPCR 0,21 [0,14;0,36] g/g, and 20% had DSA at the time of the biopsy. Biopsy findings included: 109 normal, 30 borderline, 15 TCMR, 11 AMR and 5 mixed rejections. Median cfDNA level was 0,64 [0,31;1,80] %. We found a strong association between cfDNA levels and active tubule-interstitial and microvascular Banff lesions (Figure 1). cfDNA levels were significantly increased in cases with rejection (Figure 2). Using the proposed cut-off of 0.5%, performances of the test to detect rejection were Se 84%, Spe 51%, PPV 33%, NPV 92%. Among the borderline cases, 17 (57%) had cfDNA&gt;0.5%.

Conclusion
We confirm in the largest pediatric kTx cohort to date, the association of dd-cfDNA levels with allograft rejection and its potential interest as a non-invasive biomarker in children. Further studies are needed to assess the added value of dd-cfDNA monitoring to the current standard of care and its ability to reduce unnecessary surveillance biopsies and improve outcomes.
#2837 ANGIOTENSIN II TYPE 1A RECEPTOR IN KIDNEY PERICYTES MEDIATES TERTIARY LYMPHOID TISSUE FORMATION AFTER ACUTE KIDNEY INJURY
Authors: Chou Yu-Hsiang , Shao Yu-Han , Chen Yung-Ming , Lin Shuei-Liong 
Published: June 2023

Abstract

Background and Aims
Tertiary lymphoid tissues (TLTs) have been demonstrated as a major cause of sustained inflammation after acute kidney injury (AKI), indicating a possible contribution of ensuing chronic kidney disease (CKD). And heterogeneous fibroblasts play the crucial role of induction of TLT by secretion of chemokines. Angiotensin II receptors also express on fibroblasts including pericytes. Our study aimed to investigate whether the blockade of angiotensin II receptor could attenuate TLT formation and ensuing CKD after AKI.

Method
Ischemia-reperfusion injury (IRI) was used as AKI model. In vivo, systemic angiotensin II receptor blockade was performed by administration of an angiotensin II receptor antagonists called losartan after the recovery of AKI. Cell-specific angiotensin II receptor blockade was performed using Gli1-CreERT2;AT1Rfl/fl mice to knockout angiotensin II type 1a receptor in pericytes. We also investigated the effect of angiotensin II receptor blockade using 3T3 fibroblasts cell line.

Results
During the 8-month follow-up period after IRI, the activity of intra-renal renin–angiotensin system (RAS) elevated without treatment of losartan. We also displayed that multiple TLTs developed in ensuing CKD after IRI both in a CD-1 and C57BL/6J mice model, which were confirmed by staining of CD3 and B220 representing T and B lymphocytes, respectively. Notably, losartan could not only reduce the size and number of TLT, but also downregulate proinflammatory cytokines such as CXCL13, CCL21 and CCL19 which trigger the initiation of TLT. In vitro, using 3T3 fibroblasts cell line and primary pericytes isolated from kidney after IRI, angiotensin II administration could induce the development of fibroblasts with distinct phenotypes and stimulate production of aforementioned proinflammatory cytokines, particularly CCL19. Additionally, we discovered that angiotensin II-stimulated fibroblasts induced migration of lymphocytes via CCL19 production. Using Gli1-CreERT2;AT1Rfl/fl mice, we found that TLT formation decreased after IRI compared to control groups.

Conclusion
Losartan can reduce ensuing CKD and TLT formation. Distinctive pericytes inhibition by losartan is the plausible mechanism of amelioration of TLT formation. As a result, losartan might be the promising therapeutic agent to prevent AKI-CKD continuum.
#5215 OFATUMUMAB AS A RESCUE THERAPY FOR PATIENTS WITH MEMBRANOUS NEPHROPATHY
Authors: Podesta Manuel Alfredo , Portalupi Valentina , Gennarini Alessia , Tomatis Federica , Villa Alessandro , Rubis Nadia , Remuzzi Giuseppe , Ruggenenti Piero 
Published: June 2023

Abstract

Background and Aims
Rituximab is the first-line treatment for patients with primary membranous nephropathy (MN) and nephrotic syndrome (NS) at high risk of progression to end-stage kidney disease. However, this drug is effective only in approximately two thirds of treated patients, and repeated rituximab infusions may be complicated by hypersensitivity reactions, which contraindicate retreatment. Ofatumumab, a fully human anti-CD20 antibody, could overcome these limitations.

Method
We retrospectively evaluated the response to a single 50–300 mg dose of intravenous ofatumumab in 17 MN patients referred to our institution who either experienced hypersensitivity reactions (rituximab-intolerant, n = 5) or failed to achieve NS remission after rituximab infusion (rituximab-resistant, n = 12).

Results
Over a median [IQR] follow-up of 5.0 [3.0-9.8] months, ten (58.8%) patients—five rituximab-resistant (41.7%) and all five rituximab-intolerant—achieved complete or partial NS remission, defined as proteinuria &lt;0.3 g/day or proteinuria &lt;3.5 g/day with ≥50% reduction from baseline, respectively. Ofatumumab infusion induced a progressive reduction in 24-hour urinary protein and IgG excretion, and a sharp increase in serum albumin and IgG levels. Peripheral B cells were depleted in all patients and started reconstituting by 3 months from baseline. Seven of the 12 subjects with PLA2R-related disease (i.e. with baseline anti-PLA2R antibody levels &gt;2.7 RU/mL by ELISA) achieved antibody depletion during the follow-up (half of rituximab-resistant and all rituximab-intolerant). There were 14 non-serious infusion-related adverse events in nine patients, all of which completely resolved with temporary interruption of ofatumumab infusion.

Conclusion
Ofatumumab may be an effective and safe treatment option for all rituximab-intolerant and a substantial proportion of rituximab-resistant MN patients.