Stable Function Research Articles

How justified is abandoning money from monetary policy? Evidence from dynamically simulated ARDL

The stable money demand function is a crucial policy tool of the monetary policy of any central bank, which links the monetary sector of an economy to its real sector. Notably, after the global financial crisis of 2007–08, the role of money has come to be envisaged as an essential issue while formulating and conducting the monetary policy, especially at zero lower bound. It is crucial to know whether money demand is stable for inferring a sound monetary policy. To this end, the present study examines the short- and long-run money demand relationship and its stability in India from 2006:Q3 to 2019:Q4. The study has employed a dynamically simulated autoregressive distributed lag (ARDL) cointegration approach, which shows a well-specified and stable money demand in India after incorporating the inflation forecast variable as one of the essential determinants along with other covariates. Furthermore, the dynamically simulated impulse response also supports the economic relationship among variables. The current finding of stable money demand implies a policy implication in terms of focusing on monetary aggregate, in the ongoing flexible inflation targeting framework, as one of the essential information or indicator variables, which acts as a long-term assessment of short-term interest rate setting behaviour to achieve the macroeconomic goals.

Commensal colonization reduces Pseudomonas aeruginosa burden and subsequent airway damage.

Pseudomonas aeruginosa dominates the complex polymicrobial cystic fibrosis (CF) airway and is a leading cause of death in persons with CF. Interestingly, oral streptococcal colonization has been associated with stable CF lung function. The most abundant streptococcal species found in stable patients, Streptococcus salivarius, has been shown to downregulate pro-inflammatory cytokines in multiple colonization models. However, no studies have demonstrated how S. salivarius potentially improves lung function. Our lab previously demonstrated that the P. aeruginosa exopolysaccharide Psl promotes S. salivarius biofilm formation in vitro, suggesting a possible mechanism by which S. salivarius is incorporated into the CF airway microbial community. In this study, we demonstrate that co-infection of rats leads to enhanced S. salivarius colonization and reduced P. aeruginosa colonization. Histological scores for tissue inflammation and damage are lower in dual-infected rats compared to P. aeruginosa infected rats. Additionally, pro-inflammatory cytokines IL-1β, IL-6, CXCL2, and TNF-α are downregulated during co-infection compared to P. aeruginosa single-infection. Lastly, RNA sequencing of cultures grown in synthetic CF sputum revealed that P. aeruginosa glucose metabolism genes are downregulated in the presence of S. salivarius, suggesting a potential alteration in P. aeruginosa fitness during co-culture. Overall, our data support a model in which S. salivarius colonization is promoted during co-infection with P. aeruginosa, whereas P. aeruginosa airway bacterial burden is reduced, leading to an attenuated host inflammatory response.

Metastatic xanthogranulomatous pyelonephritis managed with immunosuppression.

A male aged in his mid-60s was diagnosed with xanthogranulomatous pyelonephritis after a left nephrectomy for a renal mass that was detected during the investigation of weight loss and drenching night sweats. Past medical history includes type 2 diabetes mellitus, transient ischaemic attack, hypertension, non-alcoholic fatty liver disease, dyslipidaemia, osteoarthritis and active smoking. Three years after the initial diagnosis, the patient represented with abdominal pain. CT imaging demonstrated new pulmonary and pancreatic lesions, which were histologically confirmed to be xanthogranulomatous disease. The patient was too unstable for surgical intervention so was commenced on glucocorticoids with marked improvement in his clinical condition with resolution of inflammatory markers and radiographic improvement. Weaning of prednisolone led to a relapse of disease, which was managed with re-introduction of high-dose prednisolone and the initiation of azathioprine. The patient is now 2 years post initiation of immunosuppressive therapy with stable renal function and no active inflammation.

Postoperative Renal Complications Adversely Impact Late Survival Following Open Juxtarenal Aortic Aneurysm Repair

Preoperative renal function is a predictor of morbidity and mortality after the repair of juxtarenal aortic aneurysms. However, the impact of postoperative renal failure on late outcomes after repair are poorly understood. Therefore, our objective was to assess the impact of postoperative renal dysfunction on long-term outcomes after juxtarenal aortic aneurysm repair. We identified all open repairs of juxtarenal aortic aneurysms in the Vascular Quality Initiative from 2011 to 2018 with linkage to Medicare claims data. Juxtarenal aortic aneurysm repair was defined as the placement of proximal clamp above at least one renal artery during open repair. Postoperative renal function was categorized as stable renal function, acute kidney injury (AKI; ≥0.5 mg/dL serum creatinine increase) or new renal replacement therapy (RRT). Kaplan-Meier estimates and Cox regression were used to identify the effect of AKI or RRT on 5-year mortality, rupture, and reintervention. Of 1643 open repairs, 29% experienced postoperative AKI, and 6.5% required RRT. Renal visceral ischemia time >25 minutes was higher in the AKI and RRT cohorts (stable: 52% vs AKI 65% vs RRT 67%; P < .001). Postoperative mortality was higher with increasing severity of postoperative renal dysfunction (2.5% vs 9.5% vs 31%; P < .001). Increasing renal dysfunction severity was also associated with higher risk of 5-year mortality (14% vs 25% vs 57%; AKI: adjusted hazard ratio [aHR], 1.7 [1.3-2.4]; P < .001/RRT: aHR, 4.6 [3.1-7.0]; P < .001) (Fig). In addition, RRT was associated with higher risk of late rupture (3.1% vs 6.8% vs 10%; AKI: aHR, 1.1 [0.3-3.7]; P < .788/RRT: aHR, 5.5 [1.2-25]; P < .026) and late reintervention (15% vs 20% vs 55%; AKI: aHR, 1.4 [0.9-2.2]; P = .114/RRT: aHR, 3.4 [1.7-7.0]; P = .001). Postoperative renal dysfunction adversely impacts late mortality, rupture, and reintervention. In addition increasing severity of postoperative renal dysfunction has a dose-dependent effect on perioperative and late outcomes after repair. Preoperative and intraoperative care should be taken to prevent renal complications after repair. Furthermore, these patients may benefit from closer follow-up after repair.

Evaluation of Renal Function Recovery After Holmium Laser Enucleation of the Prostate in Patients with Chronic Kidney Disease.

Introduction: Holmium laser enucleation of the prostate (HoLEP) has become a new surgical gold standard treatment for benign prostatic hyperplasia (BPH). It is known that untreated BPH can lead to bladder outlet obstruction (BOO). A positive correlation exists between BOO and chronic kidney disease (CKD), but stability or recovery of renal function after HoLEP remains unknown. We sought to describe changes in renal function after HoLEP in men with CKD. Methods: A retrospective study was conducted of patients who underwent HoLEP with glomerular filtration rates (GFRs) <60, CKD stages III to V. Pre- and postoperative GFRs were selected within 3 months before the operation and within 1 year postoperatively. The presence of an indwelling catheter, preoperative hydronephrosis, history of kidney stones, and prostate size were also reviewed. Data were analyzed in accordance with preoperative CKD stage. Results: Of the reviewed patients, 138 met inclusion criteria with CKD stages III to V. Each CKD group was without significant postoperative complications. There was a significant increase between pre- and postoperative GFR for patients in CKD stages III (n = 116) and IV (n = 17) (p < 0.0001 and p = 0.010, respectively). The mean increase between pre- and postoperative GFR for the CKD stages III and IV patients were 6.4 and 6.49, respectively. There was no correlation between presence of preoperative hydronephrosis, history of kidney stones, catheter dependency, nor prostate size on change in postoperative GFR (p > 0.05). Conclusion: These findings suggest that patients in CKD stages III or IV undergoing HoLEP experience an increase in GFR. It is noteworthy that there appears to be no decline in renal function postoperatively in any group. HoLEP represents an excellent surgical option for patients with preoperative CKD and may prevent further renal decline.

P330 MANAGEMENT OF HYPERKALEMIA IN A PATIENT WITH HFREF

Abstract Hyperkalimia (HK) is a condition that occurs very frequently in patients with heart failure (HF). HK often limits and discourages the implementation and optimization of RAASI therapy in patients with HFrEF. The introduction of the new K–binders drugs has made it possible to overcome this obstacle by allowing optimization of therapy even in patients with persistent hyperkalemia. Mr. AB aged 83 years cognitively intact and autonomous ( Katz‘s BADL and Lawton‘s IADL preserved; MMSE 29/30). February 2022 accessed DEA for aggravating exertional dyspnea; at that time echocardiogram finding reduced left ventricular systolic function, FE 35%. March 2022 performed elective coronarography: coronary tree free of critical lesions, confirmed on echocardiogram reduced FE. Post indication to undertake Sacubitril/Valsartan, beta blocker and SGLT2i therapy. For moderate CKD (eGFR 33 ml/min) with tendency to hyperkalemia not initiated MRA. April 2022 the patient was taken to our Heart Failure Outpatient Clinic–UTIG– AOU Careggi. June 2022 considered improvement in renal function and Kaliemia in optimized range GDMTs therapy with Potassium Canreonate 25 mg/day. At control EEs in July 2022 found hyperKalemia with K values 5.5 mEq/L but stability of renal function. Reduced therefore the dosage of Potassium Canreonate (25 mg every other day) with indication to repeat blood tests soon. September 2022 despite reduction in MRA dosage further increase in Kaliemia values to 5.8 mEq/L. Suspended Potassium Canreonate and started Sodium Zirconium Cyclosilicate therapy initially at loading dosage of 10 g three times daily for two days then continued with maintenance dosage of 5 g. At follow–up performed the following week K 4.5 mEq/L. Re–introduced Potassium Canreonate 25 mg/day with initial tight control of potassium values that remained stably at optimal values. Hyperkalemia is an obstacle in titrating HFrEF, especially in elderly patients with CKD. However, we have new drugs available that may allow the implementation of guideline–recommended treatments by controlling potassium values.

LCP-tacrolimus in long-term kidney graft recipients: Dosing and adherence

IntroductionThe new LCP-formulation of tacrolimus (Tac) has shown pharmacokinetic advantages in patients after liver transplantation that are associated with better adherence. The influence of prolonged release Tac on adherence, trough levels and dosing of Tac remains unclear. MethodsA prospective study was performed in 62 patients from two centers, who were switched to LCP-Tac after kidney transplantation, to assess adherence as defined by the Tac trough level coefficient of variation (CoV) (primary endpoint) and BAASIS© Score, as well as kidney function, Tac trough level and tacrolimus dose. ResultsBAASIS© Score and Tac trough level CoV demonstrated good adherence over the study period, with no difference between the study timepoints (0.26 ± 0.16 at study start and 0.26 ± 0.11 at study end, p = 0.976, paired t-test). Graft function and Tac trough levels remained stable, and Tac dose could be reduced. ConclusionsA switch to LCP-Tac is feasible and leads to stable adherence, graft function and Tac trough levels, in combination with lower Tac doses.

Asymptotic subadditivity/superadditivity of Value‐at‐Risk under tail dependence

AbstractThis paper presents a new method for discussing the asymptotic subadditivity/superadditivity of Value‐at‐Risk (VaR) for multiple risks. We consider the asymptotic subadditivity and superadditivity properties of VaR for multiple risks whose copula admits a stable tail dependence function (STDF). For the purpose, a marginal region is defined by the marginal distributions of the multiple risks, and a stochastic order named tail concave order is presented for comparing individual tail risks. We prove that asymptotic subadditivity of VaR holds when individual risks are smaller than regularly varying (RV) random variables with index −1 under the tail concave order. We also provide sufficient conditions for VaR being asymptotically superadditive. For two multiple risks sharing the same copula function and satisfying the tail concave order, a comparison result on the asymptotic subadditivity/superadditivity of VaR is given. Asymptotic diversification ratios for RV and log regularly varying (LRV) margins with specific copula structures are obtained. Empirical analysis on financial data is provided for highlighting our results.

Safety and Efficacy of Conversion to Once-Daily Tacrolimus from Twice-Daily Tacrolimus in Pediatric Liver Transplant Recipients

BackgroundNonadherence to immunosuppression is the most common cause of late acute rejection in pediatric liver transplant (LT) recipients. A prolonged-release once-daily tacrolimus formulation was developed to improve adherence and long-term allograft survival. MethodsWe screened 179 pediatric LT recipients who converted from twice-daily tacrolimus (TD-TAC) to once-daily tacrolimus (OD-TAC) between February 2011 and September 2019. ResultsOne hundred seventy-nine recipients converted to OD-TAC and were followed for 18 months. 152 OD-TAC-converted recipients (84.9%) experienced uneventful follow-up, while 21 recipients showed LFT elevation. Four recipients had biopsy-proven acute rejection within six months of conversion, all of which were successfully treated with steroid pulse. 166 recipients (92.7%) remain on OD-TAC and 13 (7.3%) were switched back to TD-TAC. The mean tacrolimus trough level significantly decreased three months following conversion (3.14 ± 1.9 ng/mL) compared with pre-conversion levels (3.69 ± 1.98 ng/mL). Mean tacrolimus trough levels remained unchanged from 3 months to 12 months following conversion. Percent coefficient of variation of tacrolimus trough levels decreased significantly from 32.5 ± 16.4 ng/mL to 27.5 ± 15.6 ng/mL after conversion to OD-TAC, reflecting a decrease in variation of tacrolimus trough levels following conversion. ConclusionsConversion to OD-TAC in pediatric LT recipients with stable graft function is safe and effective. Level of evidenceLevel IV.

Development and validation of urinary exosomal microRNA biomarkers for the diagnosis of acute rejection in kidney transplant recipients.

Acute rejection (AR) continues to be a significant obstacle for short- and long-term graft survival in kidney transplant recipients. Herein, we aimed to examine urinary exosomal microRNAs with the objective of identifying novel biomarkers of AR. Candidate microRNAs were selected using NanoString-based urinary exosomal microRNA profiling, meta-analysis of web-based, public microRNA database, and literature review. The expression levels of these selected microRNAs were measured in the urinary exosomes of 108 recipients of the discovery cohort using quantitative real-time polymerase chain reaction (qPCR). Based on the differential microRNA expressions, AR signatures were generated, and their diagnostic powers were determined by assessing the urinary exosomes of 260 recipients in an independent validation cohort. We identified 29 urinary exosomal microRNAs as candidate biomarkers of AR, of which 7 microRNAs were differentially expressed in recipients with AR, as confirmed by qPCR analysis. A three-microRNA AR signature, composed of hsa-miR-21-5p, hsa-miR-31-5p, and hsa-miR-4532, could discriminate recipients with AR from those maintaining stable graft function (area under the curve [AUC] = 0.85). This signature exhibited a fair discriminative power in the identification of AR in the validation cohort (AUC = 0.77). We have successfully demonstrated that urinary exosomal microRNA signatures may form potential biomarkers for the diagnosis of AR in kidney transplantation recipients.

Assessing Head Check Crack Growth by Eddy-Current Testing

Managing head checks is a crucial task for an infrastructure manager as in case of deep cracks, rails can break and, thus, accidents might be the consequence. Many infrastructure managers use vehicle-mounted eddy-current testing for detecting cracks. This is sufficient for guaranteeing safe railway operation in applying a reactive maintenance regime removing cracks of a pre-defined depth. Moving this towards a predictive maintenance regime is only possible through assessing the crack growth. Establishing a stable deterioration function needs a sound data basis including a proper re-positioning of the test results of consecutive testing campaigns. This paper presents the results achieved from analysing the eddy-current testing campaigns of 10 years on a main line of the Austrian railway network and calculating a crack growth function as regression to field data. While it is possible to derive stable functions, the testing frequency needs to be shortened in order to move further to predictive maintenance.

Performance of Bayesian Area Under the Concentration-Time Curve-Based Pharmacokinetic Dosing Based on a One-Compartment Model and Trough-Only Monitoring for Vancomycin.

A novel Bayesian method was developed to interpret serum vancomycin concentrations (SVCs) following the administration of one or more vancomycin doses with potential varying doses and intervals based on superposition principles. The method was evaluated using retrospective data from 442 subjects from three hospitals. The patients were required to receive vancomycin for more than 3 days, have stable renal function (fluctuation in serum creatinine of ≤0.3 mg/dL), and have at least 2 trough concentrations reported. Pharmacokinetic parameters were predicted using the first SVC, and the fitted parameters were then used to predict subsequent SVCs. Using only covariate-adjusted population prior estimates, the first two SVC prediction errors were 47.3 to 54.7% for the scaled mean absolute error (sMAE) and 62.1 to 67.8% for the scaled root mean squared error (sRMSE). "Scaled" refers to the division of the MAE or RMSE by the mean value. The Bayesian method had minimal errors for the first SVC (by design), and for the second SVC, the sMAE was 8.95%, and the sRMSE was 36.5%. The predictive performance of the Bayesian method did degrade with subsequent SVCs, which we attributed to time-dependent pharmacokinetics. The 24-h area under the concentration-time curve (AUC) was determined from simulated concentrations before and after the first SVC was reported. Prior to the first SVC, 170 (38.4%) patients had a 24-h AUC of <400 mg · h/L, 186 (42.1%) had a 24-h AUC within the target range, and 86 (19.5%) had a 24-h AUC of >600 mg · h/L. After the first SVC was reported, 322 (72.9%) had a 24-h AUC within the target range, 68 (15.4%) had low values, and 52 (11.8%) had high values based on the model simulation. Target attainments were 38% before the first SVC and 73% after the first SVC. The hospitals had no policies or procedures in place for targeting 24-h AUCs, although the trough target was typically 13 to 17 mg/L. Our data provide evidence of time-dependent pharmacokinetics, which will require regular therapeutic drug monitoring regardless of the method used to interpret SVCs.

Optimizing Arteriovenous Fistula Care in Kidney Transplant Recipients: A Complex Task.

Optimizing Arteriovenous Fistula Care in Kidney Transplant Recipients: A Complex Task.

The Revised Starling Hypothesis: Modeling the impact of the glycocalyx on vascular refilling during ultrafiltration in humans

The glycocalyx lines systemic capillaries and influences the distribution of osmotic forces across the capillary between the intravascular and interstitial compartments. By creating a pericapillary space between the capillary and the interstitium with a low osmotic pressure, the predicted and measured water flux at the distal end of systemic capillaries is outward under physiological conditions – contrary to the prediction of the traditional Starling model of capillary fluid transport. This has led to a ‘revised’ Starling model in which the predicted the movement of water from the capillary into the interstitium is consistently outward, and the return of water from the interstitial compartment necessary to maintain intravascular volume occurs nearly exclusively through the lymphatic system. We developed a methematicl model of the revised Starling Hypothesis that is applicable to the whole body in the special circumstance of hemodialysis, where the contributions of renal function to blood volume regulation may be ignored, and the total input and output of water and solutes are controlled and measured as part of the process of hemodialysis. We created a revised, two compartment (vascular+interstitial space), Starling model using the quantitative model of Facchini et al. (Microvasc. Res. 94:52-63, 2014) that describes capillary transport through the glycocalyx (albeit as normalized dimensionless values). We modelled the return of interstitial water to the vascular space through lymphatic flow based on the interstitial pressure (Possenti et al., Micro. Vasc. Res. 122:101-110, 2019), and we estimated the interstitial pressure based upon the formulation of Chapple et al. (Comp. Meth, and Prog. In Biomed. 41: 33-54,1993). We used the two-compartment model (intravascular and extravascular spaces) developed by de los Reyes et al. (J. Theoret. Biol. 390:146-155, 2016) to analyze transcapillary fluxes based on the traditional Starling model, and we embedded the description of fluxes across glycocalyx developed by Facchini et al. to decribe the fluxes of solutes and water across the glycocalyx and peri-glycocalyx/sub-capillary space and added control of lymphatic function within this two-compartment model to create a revised Starling model. The traditional and revised models were evaluated using data from periods of ultrafiltration in which the hematocrit (Crit-line), body weight and measured fluid input or ultrafiltrate removed were measured, and we compared the predicted fluxes of solvent and solutes across the capillary and through the lymphatic system between the traditional and revised Starling models. The two models lead to dramatically different predictions—all of the fluid transported out of the capillary must come back via the lymphatics according to the revised Starling model. This places vital importance upon the lymphatic flow during vascular refilling when blood volume is reduced and must be repleted to maintain stable cardiac function. Partially funded by the Renal Research Institute This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Efficacy and safety of rituximab for primary membranous nephropathy with different clinical presentations: a retrospective study.

Rituximab (RTX) is gaining increasing clinical acceptance in the treatment of primary membranous nephropathy (PMN), with demonstrated efficacy and safety. However, there are few clinical studies on RTX for PMN in Asian populations, especially in China. To observe and analyse the efficacy and safety of RTX treatment, 81 patients with PMN suffering from nephrotic syndrome (NS) were enrolled and divided into an initial therapy group, a conventional immunosuppressive therapy relapse group, and a conventional immunosuppressive therapy ineffective group according to their pre-RTX treatment background. Patients in each group were followed up for 12 months. The primary outcome was clinical remission at 12 months, and the secondary outcomes were safety and the occurrence of adverse events. At 12 months, 65 of 81 (80.2%) patients achieved complete (n=21, 25.9%) or partial (n=44, 54.3%) remission after rituximab treatment. Thirty-two of 36 (88.9%) patients in the initial therapy group, 11 of 12 (91.7%) patients in the relapse group and 22 of 33 (66.7%) patients in the ineffective group achieved clinical remission. All 59 patients with positive anti-PLA2R antibodies showed a decreasing trend in antibody levels after RTX treatment, and 55 (93.2%) of them achieved antibody clearance (<20 U/mL). Logistic regression analysis showed that a high anti-PLA2R antibody titer (OR=0.993, P=0.032) was an independent risk factor for nonremission. Adverse events occurred in 18 (22.2%) patients, of which 5 (6.2%) were serious adverse events, and none were malignant or otherwise fatal. RTX alone can effectively induce remission PMN and maintain stable renal function. It is recommended as the first choice of treatment and is also effective in patients who relapse and have poor responses to conventional immunosuppressive therapy. Anti-PLA2R antibodies can be used as a marker for RTX treatment monitoring, and antibody clearance is necessary to achieve and improve the rates of clinical remission.

The case for treatment of monogenic SRNS with calcineurin inhibitors

Currently, no evidence-based guidelines exist for treatment of children with monogenic steroid-resistant nephrotic syndrome. A retrospective study on 141 patients from Malakasioti etal. revealed that 27.6% responded to calcineurin inhibitor (CNI) treatment, and 75% of responders maintained stable kidney function. Virtually all CNI nonresponders developed progressive loss of kidney function. This study emphasized roles for CNIs in patients with monogenic steroid-resistant nephrotic syndrome, and the need for future studies to identify CNI response biomarkers.

Abstract LB027: In vivo delivery of novel CD89 fusion receptor to myeloid cells by mRNA activates anti-tumor immunity

Abstract Despite the revolution provided by immunotherapy, sustained clinical benefit has yet to be achieved for most of patients with advanced solid tumors. Myeloid cells readily accumulate in tumors, in some cases contributing up to 75% of the tumor mass. While supporting tumor growth and being associated with unfavorable prognosis, myeloid cells can mediate phagocytosis of cancer cells and cytotoxic tumor killing and promote adaptive immune responses through antigen presentation and co-stimulation, therefore representing promising targets in cancer therapy. The ability to engineer circulating and tumor associated myeloid cells to activate their ability to elicit anti-tumor adaptive immunity is an attractive approach to harness systemic anti-tumor immunity. However, it remains challenging to specifically target and activate myeloid cells in vivo. To overcome this hurdle, we have developed a novel in vivo myeloid cell engineering platform in which a chimeric antigen receptor (CAR) is generated by fusing a tumor recognition scFv with the alpha chain of human Fc receptors (CD89). The stable expression and function of these receptors requires the endogenously expressed common Fc receptor gamma chain (FcRγ), which expression is mostly restricted to myeloid cells. For in vivo engineering, the construct is encapsulated and delivered in lipid nanoparticles (LNP). Trophoblast cell surface antigen 2 (TROP2) is overexpressed in most human solid epithelial cancers, as compared to low expression in corresponding normal tissue. Increased TROP2 expression has been linked to increased tumor growth and has been implicated as a prognostic marker in these cancers, supporting the development of therapies targeting TROP2. Intravenous infusion of LNP encapsulating mRNA encoding the anti-TROP2-CD89 fusion protein results in the uptake of the LNPs and expression of the chimeric receptor fusion protein in myeloid cells. In immunodeficient xenograft models of hepatocellular carcinoma and triple negative breast cancer, delivery of LNP mRNA encoding GPC3-CD89 or TROP2-CD89 fusion proteins resulted in anti-tumor efficacy, confirming the ability of this approach to program myeloid cells. Repeat dosing studies showed significant anti-tumor efficacy following bi-weekly administration of TROP2-CD89. Furthermore, in the B16/10 syngeneic melanoma model, treatment with the melanoma antigen gp75-CD89 fusion protein was also associated with the initiation of broad systemic immune responses, characterized by tumor infiltration by activated CD8+ T cells, reduced tumor-associated Tregs and activation of antigen presenting cells in spleen. When infused in cynomolgus monkeys, TROP2-CD89 LNP led to cell surface expression of anti-TROP2 CAR in myeloid cells. Together these studies highlight the potential of in vivo delivery of CD89 fusion proteins to program myeloid cells to recognize and kill cancer. Citation Format: Thomas E. Prod'homme, Shannon Argueta, Hongyun Zhao, Michael Gorgievski, Neha Diwangi, Edward Cochran, Bruce McCreedy, Yuxiao Wang, Daniel Getts. In vivo delivery of novel CD89 fusion receptor to myeloid cells by mRNA activates anti-tumor immunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB027.

Discovery of cellular and genetic signatures of immune tolerance in kidney transplant recipients through single cell RNA sequencing analysis.

The objective of this study was to uncover distinct cellular and genetic signatures of transplant operational tolerance (TOT) in kidney transplant recipients (KTRs) through single cell RNA sequencing (scRNA-seq) using peripheral blood mononuclear cells (PBMCs). PBMCs were isolated from 12 KTRs, including those with TOT (TOT, n = 4), stable allograft function on maintenance immunosuppression (STA, n = 4) and biopsy-proven allograft rejection (BPAR, n = 4). ScRNA-seq of PBMCs was analyzed using 20 cell surface marker antibody sequencing to annotate clusters and 399 immune response panel to identify gene expression. Differences in cellular distribution and gene expression were compared among the three groups. Heatmap hierarchical clustering showed that overall cellular distribution pattern was distinct in TOT in comparison with those in the other two groups, with the proportion of B cells being higher in TOT, attributed to immature B cell fraction (TOT vs. STA vs. BPAR: 4.61% vs. 1.27% vs. 2.53%, p = 0.01). Transcript analysis of B cells revealed that genes involved in allo-immune pathway were downregulated in TOT. In T cell subset analysis, the proportion of naïve T cells and regulatory T cells (Tregs) was increased. In transcript analysis, genes associated with inflammation were decreased, while expression levels of CCR6 in Tregs were increased in TOT. Proportions of NKT and NK cells were increased in TOT than in the other two groups. This study showed that TOT has distinct cellular and genetic signatures such as increases of immature B cells, naïve T cells and Tregs and high expression levels of CCR6 in Tregs.

Renal function in patients with chronic kidney disease and hypertension degree 1–2 against the background of SARS-CoV-2

Renal function in patients with chronic kidney disease and hypertension degree 1–2 against the background of SARS-CoV-2

Path-Following Control of Small Fixed-Wing UAVs under Wind Disturbance

Aiming at the problems of low following accuracy and weak anti-disturbance ability in the three-dimensional path-following control of small fixed-wing Unmanned Aerial Vehicles (UAV), a Globally Stable Integral Sliding Mode Radial Basis Function S-Plane (GSISM+RBF S-Plane) controller is designed. The controller adopts the inner and outer loop mode, the outer loop adopts the Globally Stable Integral Sliding Mode (GSISM) control, and the inner loop adopts the S-Plane control. At the same time, the unknown disturbance in the model is estimated via an RBF neural network. Firstly, the outer loop controller is designed based on the GSISM, and its stability is proved using the Lyapunov theory. Then, the S-Plane controller is designed for the instruction signal of the inner loop. Considering the complexity of the derivation in the S-Plane controller, a second-order differentiator is introduced. Finally, considering the problem of external wind disturbance, the controller is modeled, studied, and processed in order to better reflect the impact of real external wind on UAV path following. Finally, the Globally Stable Sliding Mode (GSSM) control and Globally Stable Integral Sliding Mode S-Plane (GSISM S-Plane) control are used for a comparative experiment. The simulation results show that the designed GSISM+RBF S-Plane controller can accurately track the ideal path compared with the GSSM and GSISM S-Plane controller, and it has good control performance and anti-disturbance performance.