A Federated Graph Neural Network Framework for Privacy-Preserving Personalization

Graph neural network (GNN) is effective in modeling high-order interactions and has been widely used in various personalized applications such as recommendation. However, mainstream personalization methods rely on centralized GNN learning on global graphs, which have considerable privacy risks due to the privacy-sensitive nature of user data. Here, we present a federated GNN framework named FedGNN for both effective and privacy-preserving personalization. Through a privacy-preserving model update method, we can collaboratively train GNN models based on decentralized graphs inferred from local data. To further exploit graph information beyond local interactions, we introduce a privacy-preserving graph expansion protocol to incorporate high-order information under privacy protection. Experimental results on six datasets for personalization in different scenarios show that FedGNN achieves 4.0%~9.6% lower errors than the state-of-the-art federated personalization methods under good privacy protection. FedGNN provides a novel direction to mining decentralized graph data in a privacy-preserving manner for responsible and intelligent personalization.

Success and complication rate of miniscrew assisted non-surgical palatal expansion in adults - a consecutive study using a novel force-controlled polycyclic activation protocol

Introduction Bone-borne miniscrew assisted palatal expansion (MAPE) is a common technique to improve maxillary transverse deficiency in young adolescents. Adult patients usually present a challenge, as they often require additional surgical assisted maxillary expansion (SARPE). There is still no clear statement about non-surgical expansion in adult patients using this technique. The aim of this study was to evaluate the success and complication rate of non-surgical palatal expansion in adults utilizing MAPE with a novel force-controlled polycyclic expansion protocol (FCPC). Methods This consecutive study consisted of 33 adult patients with an average age of 29.1 ± 10.2 years (min. 18 years, max. 58 years), including one dropout patient. First, four miniscrews were inserted and after 12-weeks latency, the expander was placed and the FCPC protocol was applied (MAPE group). In case of missing expansion, a SARPE was performed (SARPE group). After maximum expansion, a cone beam CT was made and widening of the midpalatal suture was measured. The outcome variables were successful non-surgical expansion and, with sample size power above 80%, the odds of failed non-surgical expansion and associated complications were evaluated. The primary predictor variable was age. Statistical analysis was performed using R (Version 3.1) to calculate power, to construct various models for measuring the odds of requiring surgical intervention/complications, and others. Results Successful non-surgical expansion was achieved in 27 patients (84.4%), ranging from 18 to 49 years. Mean age differed significantly between both groups (26.8 ± 8.2 years vs. 41.3 ± 9.9 years; p < 0.001). Mean expansion at the anterior and posterior palate for the MAPE group was 5.4 ± 1.5 mm and 2.5 ± 1.1 mm, respectively. Among these subjects’ complications were observed in 18.5%. Age significantly increased the odds of complications (p = 0.019). Conclusions 1. The success rate of MAPE among individuals aged 18 to 49 years was 84.4%. 2. A V-shaped expansion pattern in the antero-posterior dimension was mostly observed. 3. Complications were significantly associated with age. 4. A careful expansion protocol seems to be beneficial to prevent unfavorable results in adult patients. Trial registration Consecutive cohort study, Review Board No. EK-2-2014/0016.

Comparison of dentoskeletal and soft tissue changes between tooth-borne and tooth-bone-borne hybrid nonsurgical rapid maxillary expansions in adults: a retrospective observational study

Background Despite the gradual increase in the use of rapid maxillary expansion (RME), specifically RME with the aid of skeletal anchorage in adults, there have been no reports comparing dentoskeletal and soft tissue changes between nonsurgical tooth-borne and tooth-bone-borne RMEs in adults. This study aimed to analyse differences in dentoskeletal and soft tissue changes between tooth-borne and tooth-bone-borne RMEs using a similar appliance design and the same expansion protocol in adult patients. Methods Twenty-one patients with tooth-borne expansion (a conventional expansion screw with two premolars and two molar bands for dental anchorage [T-RME]) and the same number of patients with tooth-bone-borne hybrid expansion (a conventional expansion screw with two premolar and two molar bands for dental anchorage and four mini-implants in the palate for skeletal anchorage [H-RME]) were included. Dentoskeletal and soft tissue variables at pretreatment (T1) and after expansion (T2) were measured using posteroanterior and lateral cephalograms and frontal photographs. The sex distribution of the two groups was analysed using the chi-square test, and the change after RME in each group was evaluated using the Wilcoxon signed-rank test. Differences in pretreatment age, expansion duration, post-expansion duration, and dentoskeletal and soft tissue changes after RME between the two groups were determined using the Mann–Whitney U test. Results There were no significant differences in the expansion protocol, pretreatment conditions, and sex distribution between the two groups. Despite similar degrees of dental expansion at the crown level between the two groups, H-RME induced increased skeletal and parallel expansion of the maxilla compared to T-RME. After expansion, H-RME demonstrated increased forward displacement of the maxilla without significant changes in the vertical dimension, while T-RME exhibited increased backward displacement of the mandible, increased vertical dimension, and decreased overbite. Both groups showed significant retroclination and extrusion of the maxillary incisors without significant intergroup differences. There were no significant soft tissue changes between the two groups. Conclusion This study suggests that using skeletal anchorage in RME may induce increased skeletal and parallel expansion of the maxilla without significant effects on the vertical dimension.

Comparison of Dentoskeletal and Soft Tissue Changes Between Tooth-Borne and Tooth-Bone-Borne Hybrid Nonsurgical Rapid Maxillary Expansions in Adults: A Retrospective Observational Study

Background Despite the gradual increase in the use of rapid maxillary expansion (RME), specifically RME with the aid of skeletal anchorage in adults, there have been no reports comparing dentoskeletal and soft tissue changes between nonsurgical tooth-borne and tooth-bone-borne RMEs in adults. This study aimed to analyse differences in dentoskeletal and soft tissue changes between tooth-borne and tooth-bone-borne RMEs using a similar appliance design and the same expansion protocol in adult patients. Methods Twenty-one patients with tooth-borne expansion (a conventional expansion screw with two premolars and two molar bands for dental anchorage [T-RME]) and the same number of patients with tooth-bone-borne hybrid expansion (a conventional expansion screw with two premolar and two molar bands for dental anchorage and four mini-implants in the palate for skeletal anchorage [H-RME]) were included. Dentoskeletal and soft tissue variables at pretreatment (T1) and after expansion (T2) were measured using posteroanterior and lateral cephalograms and frontal photographs. The sex distribution of the two groups was analysed using the chi-square test, and the change after RME in each group was evaluated using the Wilcoxon signed-rank test. Differences in pretreatment age, expansion duration, post-expansion duration, and dentoskeletal and soft tissue changes after RME between the two groups were determined using the Mann–Whitney U test. Results There were no significant differences in the expansion protocol, pretreatment conditions, and sex distribution between the two groups. Despite similar degrees of dental expansion at the crown level between the two groups, H-RME induced increased skeletal and parallel expansion of the maxilla compared to T-RME. After expansion, H-RME demonstrated increased forward displacement of the maxilla without significant changes in the vertical dimension, while T-RME exhibited increased backward displacement of the mandible, increased vertical dimension, and decreased overbite. Both groups showed significant retroclination and extrusion of the maxillary incisors without significant intergroup differences. There were no significant soft tissue changes between the two groups. Conclusion This study suggests that using skeletal anchorage in RME may induce increased skeletal and parallel expansion of the maxilla without significant effects on the vertical dimension.

178 Expansion of Tumor-Infiltrating Lymphocytes and Marrow-Infiltrating Lymphocytes from Pediatric Malignant Solid Tumors

BackgroundHigh-risk non-CNS pediatric malignant solid tumors (pMST) have unsatisfactory outcomes, and novel therapies are warranted. Adoptive cellular therapy (ACT) using tumor-infiltrating lymphocytes (TIL) has produced durable responses in melanoma, and improvements in TIL expansion have made ACT-TIL feasible for other solid tumors.1–3 Preclinical mouse models suggest that T-cells from bone marrow (marrow-infiltrating lymphocytes, MIL) have antitumor reactivity offering another source for ACT.4 5 To demonstrate feasibility of ACT in pMST we hypothesized that TIL/MIL can be expanded from these patients.MethodsPatients ≤21 years old undergoing standard-of-care pMST resection were enrolled on an IRB approved protocol. Fresh tumor (≥1 cm3) was collected and bone marrow (10 mL) was obtained when accessible from standard of care procedures. TIL/MIL were cultured in media containing IL-2 (6000 IU/mL). TIL were expanded from tumor fragment cultures (TFC, >1 mm3) or tumor digest. Select TIL samples were further expanded using a rapid expansion protocol (REP). Phenotype of expanded TIL (CD3, CD4, CD8 and CD56) was evaluated using flow cytometry. IFN- γ secretion, measured by ELISA assay, measured tumor-specific reactivity after co-culture with autologous tumor and TIL.ResultsTwenty samples were obtained between March 2019-May 2021. Two samples were ineligible (final pathology not pMST), leaving 18 samples for analysis. Five marrow samples were collected. TIL were expanded from 14/18 samples (78%) through TFC with median 5.17 x 10^6 cells (range 1.86 x 10^6–3.21 x 10^8). Average phenotype (%) of TFC-TIL were CD3 (63.17), CD4 (21.46), CD8 (46.19) and CD56 (32.68). 9/10 (90%) of samples successfully underwent REP with median 9.35 x 10^7 cells(range 2.49 x 10^7–5.86 x 10^8) final viable TIL and average fold-change 718.6 (median 458.6). Average phenotype (%) of post-REP TIL were CD3 (96.04), CD4 (75.04), CD8 (19.17) and CD56 (0.43). TIL were expanded from TFC of therapy-naïve (8/10, 80%) and pretreated (chemotherapy and checkpoint immunotherapy) samples (5/8, 63%). Seven samples had sufficient tissue to test tumor-specific reactivity; all were non-reactive. MIL pre-REP was expanded from four samples with median 9.55 x 10^6 cells (range 8.00 x 10^5–1.00 x 10^7). Average phenotype of expanded MIL (%) were CD3 (45.17), CD4 (24.46), CD8 (36.15) and CD56 (28.21) (table 1).Results of TIL and MIL expansion from 18 pMST samples. Abbreviations: Dx: diagnosis, pre-REP: pre-rapid expansion protocol, post-REP: post-rapid expansion protocol, PBMC: peripheral blood mononuclear cells, GNB: ganglioneuroblastoma, WT: Wilms tumor, OS: osteosarcoma, NB: neuroblastoma, IMT: inflammatory myofibroblastic tumor; ASPS: alveolar soft part sarcoma, SS: synovial sarcoma, ERMS: embryonal rhabdomyosarcoma, N: no systemic therapy, C: chemotherapy, I: immunotherapy, DNG: did not grow, N/A: not applicable, NR: non-reactiveAbstract 178 Table 1Expansion of TIL from pMSTConclusionsThis study demonstrates feasibility of pMST TIL expansion ex vivo. Due to tissue volume constraints inherent in pMST sampling, anti-tumor reactivity testing was not feasible for most patients. Determining optimal strategy for TIL-ACT in pMST will require further investigation regarding techniques for expanding tumor-specific TIL.AcknowledgementsThe authors would like to thank Swim Across America (www.swimacrossamerica.org) and the Ocala Royal Dames (www.ocalaroyaldames.org) for their generous support of this work.ReferencesRosenberg SA, Restifo NP. Adoptive cell transfer as personalized immunotherapy for human cancer. Science 2015;348(6230):62–68.Hall M, Mullinax JE, Royster E, et al. Expansion and characterization of tumor-infiltrating lymphocytes from human sarcoma. Journal of Immunotherapy of Cancer 2015;3(Suppl. 2):19.Mullinax JE, Hall M, Beatty M, et al. Expanded tumor-infiltrating lymphocytes from soft tissue sarcoma have tumor-specific function. J Immunother 2021;44(2):63–70.Feuerer M, Beckhove P, Bai L, et al. Therapy of human tumors in NOD/SCID mice with patient-derived reactivated memory T cells from bone marrow. Nat Med 2001;7(4):452–458.Feuerer M, Rocha M, Bai L, et al. Enrichment of memory T cells and other profound immunological changes in the bone marrow from untreated breast cancer patients. Int J Cancer 2001;92(1):96–105.Ethics ApprovalThis study was approved by the Johns Hopkins All Children’s Hospital IRB (#IRB00193453). Consent was obtained from the patient or parent, as appropriate for age, prior to participating in this study.

Success And Complication Rate of Miniscrew Assisted Non-Surgical Palatal Expansion In Adults - A Consecutive Study Using A Novel Force-Controlled Polycyclic Activation Protocol

Introduction: Bone-borne miniscrew assisted palatal expansion (MAPE) is a common technique to improve maxillary transverse deficiency in young adolescents. Adult patients usually present a challenge, as they often require additional surgical assisted maxillary expansion (SARPE). There is still no clear statement about non-surgical expansion in adult patients using this technique. The aim of this study was to evaluate the success and complication rate of non-surgical palatal expansion in adults utilizing MAPE with a novel force-controlled polycyclic expansion protocol (FCPC).Methods: This consecutive study consisted of 33 adult patients with an average age of 29.1 ± 10.2 years (min. 18 years, max. 58 years), including one dropout patient. First, four miniscrews were inserted and after 12-weeks latency, the expander was placed and the FCPC protocol was applied (MAPE group). In case of missing expansion, a SARPE was performed (SARPE group). After maximum expansion, a cone beam CT was made and widening of the midpalatal suture was measured. The outcome variables were successful non-surgical expansion and, with sample size power above 80%, the odds of failed non-surgical expansion and associated complications were evaluated. The primary predictor variable was age. Statistical analysis was performed using R (Version 3.1) to calculate power, to construct various models for measuring the odds of requiring surgical intervention/complications, and others.Results: Successful non-surgical expansion was achieved in 27 patients (84.4%), ranging from 18 to 49 years. Mean age differed significantly between both groups (26.8 ± 8.2 years vs. 41.3 ± 9.9 years; p < 0.001). Mean expansion at the anterior and posterior palate for the MAPE group was 5.4 ± 1.5 mm and 2.5 ± 1.1 mm, respectively. Among these subjects' complications were observed in 18.5%. Age significantly increased the odds of complications (p = 0.019).Conclusions:1. The success rate of MAPE among individuals aged 18 to 49 years was 84.4%.2. A V-shaped expansion pattern in the antero-posterior dimension was mostly observed.3. Complications were significantly associated with age.4. A careful expansion protocol seems to be beneficial to prevent unfavorable results in adult patients.Trial registration: consecutive cohort study, Review Board No. EK-2-2014/0016

SARS-CoV-2 spike glycoprotein-reactive T cells can be readily expanded from COVID-19 vaccinated donors

Introduction: The COVID-19 vaccine was designed to provide protection against infection by the severe respiratory coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19). However, the vaccine's efficacy can be compromised in patients with immunodeficiencies or the vaccine-induced immunoprotection suppressed by other comorbidity treatments, such as chemotherapy or immunotherapy. To enhance the protective role of the COVID-19 vaccine, we have investigated a combination of the COVID-19 vaccination with ex vivo enrichment and large-scale expansion of SARS-CoV-2 spike glycoprotein-reactive CD4+ and CD8+ T cells. Methods: SARS-CoV-2-unexposed donors were vaccinated with two doses of the BNT162b2 SARS-CoV-2 vaccine. The peripheral blood mononuclear cells of the vaccinated donors were cell culture-enriched with T cells reactive to peptides derived from SARS-CoV-2 spike glycoprotein. The enriched cell cultures were large-scale expanded using the rapid expansion protocol (REP) and the peptide-reactive T cells evaluated. Results: We show that vaccination with the SARS-CoV-2 spike glycoprotein-based mRNA COVID-19 vaccine induced humoral response against SARS-CoV-2 spike glycoprotein in all tested healthy SARS-CoV-2-unexposed donors. This humoral response was found to correlate with the ability of the donors' PBMCs to become enriched with SARS-CoV-2 spike glycoprotein-reactive CD4+ and CD8+ T cells. Using an 11-day rapid expansion protocol, the enriched cell cultures were expanded nearly a thousand fold, and the proportions of the SARS-CoV-2 spike glycoprotein-reactive T cells increased. Conclusions: These findings show for the first time that the combination of the COVID-19 vaccination and ex vivo T cell large-scale expansion of SARS-CoV-2-reactive T cells could be a powerful tool for developing T cell-based adoptive cellular immunotherapy of COVID-19.

Whole-ExM: Expansion microscopy imaging of all anatomical structures of whole larval zebrafish

Nanoscale imaging of all anatomical structures over whole vertebrates is needed for a systematic understanding of human diseases, but this has not yet been achieved. Here, we demonstrate whole-ExM, which enables nanoscale imaging of all anatomical structures of whole zebrafish larvae by labeling the proteins of the larvae with fluorophores and expanding them four-fold. We first optimize the fluorophore selection and labeling procedure to visualize a broader range of anatomical structures. We then develop an expansion protocol for zebrafish larvae having calcified body parts. Through this process, we visualize the nanoscale details of diverse larvae organs, which have corresponding organ counterparts in humans, over the intact larvae. We show that whole-ExM retains the fluorescence signals of fluorescent proteins, and its resolution is high enough to visualize various structures that can be imaged only with electron microscopy. Whole-ExM would enable the nanoscale study of the molecular mechanisms of human diseases.

Comparison of Transversal Effects of Different Expansion Protocols: Alt-RAMEC versus RME

Objectives The aim of this study is evaluate the transversal effects of the Alt-RAMEC(Alternate Rapid Maxillary Expansion and Constriction) protocol on both craniofacial and dentoalveolar structures and to compare the transversal effects of the RME(Rapid Maxillary Expansion) protocol. Materials and Methods In our archive, selected patients were divided into two groups. Group 1 included 22 patients(12boys,10girls, mean age 11.61±2.11years) who had been treated with 5 weeks of Alt-RAMEC. Group 2 comprised 21 patients(11boys,10girls, mean age 11.66±1.23years) who had been treated with 1 week of RME. Transversal measurements were also performed on the study models pre-(T0) and post-treatment(T1) with digital caliper. Internasal, interzygomatic, interjugular and intergonial width measurements were made on posteroanterior radiographs. The initial measurements and the mean changes within the groups were analysed using a student’s t test. Results According to the results of the study, there was no statistically significant difference between the groups in terms of chronological age, gender distribution and initial values. The expansion protocols showed a statistically significant increase in the widths of intercanine, interpremolar, intermolar and alveolar base widths in the maxilla(p<0.05). No statistically significant changes were observed in both groups(p>0.05) in mandible. The changes in maxillary intercanine, interpremolar widths between the two groups were statistically significant(p<0.05). In the posteroanterior measurements, only statistically significant difference was found between the groups in internasal width(p<0.05). Conclusions Alt-RAMEC and RME protocols are effective treatment protocols for correction of transverse deficiency in growing patients. 5-weeks Alt-RAMEC protocol significantly increased intercanine and interpremolar widths compared to 1-week RME. Clinical Relevance Since there are no studies in the literature comparing the effects of two different expansion protocols in the transverse direction, this is both the first. Most importantly, clinicians will see which of these two protocols is more singular in the treatment of transversal problems. Keywords: RME, Alt-RAMEC, tranversal measurements

Loss of Nupr1 promotes engraftment by tuning the quiescence threshold of hematopoietic stem cell repository via regulating p53-checkpoint pathway

Hematopoietic stem cells (HSCs) are dominantly quiescent under homeostasis, which is a key mechanism of maintaining the HSC pool for life-long hematopoiesis. Dormant HSCs poise to be immediately activated on urgent conditions and can return to quiescence after regaining homeostasis. To date, the molecular networks of regulating the threshold of HSC dormancy, if exist, remain largely unknown. Here, we unveiled that deletion of Nupr1, a gene preferentially expressed in HSCs, activated the quiescence HSCs under homeostatic status, which conferred engraftment competitive advantage on HSCs without compromising their stemness and multi-lineage differentiation abilities in serial transplantation settings. Following an expansion protocol, the Nupr1-/- HSCs proliferate more robustly than their wild type counterparts in vitro. Nupr1 inhibits the expression of p53 and the rescue of which offsets the engraftment advantage. Our data unveil the de novo role of Nupr1 as an HSC quiescence-regulator, which provides insights into accelerating the engraftment efficacy of HSC transplantation by targeting the HSC quiescence-controlling network.