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This multi-arm, randomized, double-blinded, controlled clinical trial was designed to evaluate the clinical efficacy of 0.5% Green Tea (GT), 0.2 % Chlorhexidine (CHX) and Aloe Vera (AV) mouthwash as compared to the control (CNT) group (scaling and polishing alone with no mouthwash) in the management of dental biofilm induced gingivitis among 18-40-year-old patients.Sixty patients with generalized dental biofilm-induced gingivitis) were randomly allocated to four study groups (n=15 each) for treatment, namely, Group GT, Group CHX, Group AV and Group CNT after scaling and polishing were administered to all the patients. Plaque index (PI), gingival index (GI) and sulcular bleeding index (SBI) were recorded at baseline, 14PI, GI and SBI at various time intervals (baseline, 14Green tea mouthwash displayed a significant reduction in plaque index, gingival index, and sulcular bleeding index. 0.5% Green tea catechin has equivalent anti-plaque efficacy as 0.2% Chlorhexidine gluconate and can be considered a potent alternative to prevent and treat gingival diseases.

Biodegradable magnesium has regained great attention due to its ability to temporarily offer mechanical strength and degrade completely once the injured pathological tissue is healed. A few clinical applications of Mg-based implants were reported in the last century. However, the knowledge and experience is being gained continuously by studying the host response and degradation behavior of Mg implant in animal models and clinical trials. This led to the development of commercial products emerging from Europe and Asia very recently. The potential of Mg implants in repairing fractures at upper and lower limb of large, small animal models and humans is compared and discussed in detail. In addition the possible future Mg implants that might treat problems concerning to urology and gynecology are reviewed.

The volume of the inferior turbinates (IT) and the lining of the maxillary sinuses are important parameters when assessing sino-nasal diseases. However, no radiographic studies have investigated the correlation between these parameters. The present study was conducted to analyze the association between IT volumes and thickness of maxillary sinus mucosal lining.A retrospective evaluation of the cone-beam computed tomography (CBCT) scans of 100 adult subjects was carried out by two radiologists. The scans were assigned to two groups (Group 12) based on the radiographic evidence of maxillary sinus lining in the CBCT scans. Group 1 consisted of 50 CBCT scans of subjects with no evidence of maxillary sinus mucosal lining, whereas Group 2 consisted of 50 subjects with evidence of maxillary sinus mucosal lining. The scans in the Group 2 were further sub-classified into five categories, based on the thickness of the maxillary sinus mucosal lining. Vesalius 3D software was used to evaluate the total volume of inferior nasal turbinates by the two radiologists and a mean volume was obtained for each study subject.The intraclass correlation coefficient (ICC) between the volumetric estimations performed by the two radiologist was 0.87. Analysis of the results revealed that there was no significant gender-based difference (Group 1, P = 0.67 and Group 2, P = 0.95) in the total turbinate volume in either of the study groups. The total turbinate volume did not show any significant correlation (Group 1, r = 0.24 and Group 2, r = 0.12) with the age. There was a significant increase (P = 0.001) in the total turbinate volume of the subjects in Group 2 compared to Group 1. Regression analysis revealed that the thickness of sinus lining correlated significantly (P = 0.001) with the total turbinate volume.An increase in the total turbinate volume has been associated with an increase in the thickness of the maxillary sinus mucosal lining. The data from this study will be useful for post-operative follow-up of inferior turbinates and maxillary sinus lining after the turbinate volume reduction procedures.

The semi-active vibration control of sandwich beams made of chopped strand mat glass fiber reinforced polyester resin polymer matrix composite (PMC) and magnetorheological fluid (MRF) core were experimentally investigated in this study. Two-, four- and six-layered glass fiber reinforced polyester resin polymer matrix composites were prepared using the hand-layup technique. The magnetorheological fluid was prepared in-house with 30% volume of carbonyl iron powder and 70% volume of silicone oil. Nine cantilever sandwich beams of varying thicknesses of the top and bottom layers glass fiber reinforced polyester resin polymer matrix composite beams and middle magnetorheological fluid core were prepared. The magnetorheological fluid core was activated with a non-homogeneous magnetic field using permanent magnets. The first three modes, natural frequencies and damping ratios of the glass fiber reinforced polyester resin polymer matrix composite-magnetorheological fluid core sandwich beams were determined through free vibration analysis using DEWESoft modal analysis software. The amplitude frequency response of the glass fiber reinforced polyester resin polymer matrix composite-magnetorheological fluid core sandwich beams through forced vibration analysis was determined using LabVIEW. The effect of various parameters such as magnetic flux density, thickness of glass fiber reinforced polyester resin polymer matrix composite layers and magnetorheological fluid core layer on the natural frequencies, damping ratio and vibration amplitude suppressions of the glass fiber reinforced polyester resin polymer matrix composite-magnetorheological fluid core sandwich beams was investigated. Based on the results obtained, 2 mm thickness top and bottom layers glass fiber reinforced polyester resin polymer matrix composite and 5 mm thickness magnetorheological fluid core sample have achieved a high shift in increased natural frequency, damping ratio and vibration amplitude suppression under the influence of magnetic flux density.

Background and Aims: In periodontics and other surgical disciplines, sutures play a detrimental role in healing of wound. The use of chemical adjuncts to boost healing has been experimented in recent years. The aim of this study was to evaluate the role of hyaluronic acid rinse in influencing the tensile strengths of commonly used sutures. Materials and Methods: Two commonly used nonabsorbable suture materials, silk and polyamide, were used for this in vitro study. Tensile strengths of the suture materials were determined by pre- and post-immersion in hyaluronic acid (test) and chlorhexidine (control). A Tinius Olsen Universal Testing Machine was used to assess the tensile strength of the samples. The variables were assessed for normality using the Kolmogorov–Smirnov test. The Wilcoxon signed rank test and Mann–Whitney U test (for quantitative data within two groups) were used for quantitative data comparison of all the clinical indicators. The level of significance was set at P ≤ 0.05. Results: Polyamide showed better stability in terms of tensile strength when compared to silk. Hyaluronic acid as a chemical adjunct did not alter the tensile strengths of both suture materials pre- and post-immersion. Conclusion: This in vitro study has shown a promising property of hyaluronic acid with relation to stabilization of tensile strength of suture materials, which needs to be evaluated in clinical settings.

Background: The accumulation and maturation of bacterial plaque at the gingival margin is widely recognized as the primary etiological factor in the development of chronic periodontitis. With the rise in bacterial resistance to antibiotics, there is considerable interest in the development of other classes of antimicrobials for the control of infection. Aim: The aim of this study was to evaluate the efficacy of Psidium guajava (guava) and Allium sativum (garlic) on Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. Materials and Methods: Aqueous guava extract (AGvE), ethanolic guava extract (EGvE), aqueous garlic extract (AGE), and ethanolic garlic extract (EGE) were prepared. The inhibitory effects of these extracts for the periodontal pathogens were tested by agar well diffusion method. Minimal inhibitory concentration (MIC) of the aqueous and ethanol extracts of guava and garlic was determined by macrobroth dilution method. Minimum bactericidal concentration (MBC) was done to observe the bactericidal effect of the guava and garlic extracts against the organisms. Results: Of the AGE, 25, 50, and 75 μL showed 16, 20, and 25 mm zone of inhibition, respectively, on P. gingivalis. The AGE showed greater bacteriostatic activity against the P. gingivalis with MIC determined at 16.6 μL/mL. MIC determined for AGvE and EGvE was at 75 μL/mL concentration for P. gingivalis, whereas EGvE showed the activity at 75 μL/mL on P. gingivalis. MIC determined for AGvE was at 50 μL/mL, whereas MIC determined for EGvE was at 3.12 μL/mL for A. actinomycetemcomitans. Conclusion: P. guajava and A. sativum displayed a significant antibacterial effect. A. sativum was found to be most effective against P. gingivalis, whereas P. guajava showed the highest efficacy on A. actinomycetemcomitans.

Dynamic characterization of silicon carbide particles reinforced Al6082 alloy metal matrix composite sandwich beam with magnetorheological fluid core is experimentally investigated. The study is focused on determining the effect of magnetorheological fluid core on the dynamic behavior of the sandwich structure. The magnetorheological fluid core is enclosed between the top and bottom metal matrix composite beams. The metal matrix composite beams are cast with silicon carbide particles in Al6082 alloy varying from 0 to 20 wt%. The magnetorheological fluid is prepared in-house and contains 30 vol.% carbonyl iron powder and 70 vol.% silicone oil. The free vibration test is conducted to determine the natural frequencies and damping ratio. It is found that the natural frequencies and damping ratio of the sandwich beams increased with an increase in the applied magnetic flux density. The experimental forced dynamic response of sandwich beams is carried out using sine sweep excitation. Vibration amplitude suppression capabilities of the sandwich beams subjected to varying magnetic flux densities are determined. The experimental forced vibration results reveal that metal matrix composite–magnetorheological fluid core sandwich beams have excellent vibration amplitude suppression capabilities.

Objective: To investigate the impact of “Brush Up” - a mobile application, on oral hygiene behaviours of 4-6-year-old children in Bangalore city. Methods: In this experimental study, 247 children aged 4-6, were randomly divided into three groups. Considering “Brush Up” is a mobile application, parents of the children in Group 1 (n=82) downloaded the application on their smartphones. Children in Group 2 (n=83) and Group 3 (n=82) received tooth brushing instructions by an educative video and manual demonstration, respectively. Effectiveness of tooth brushing was assessed with plaque scores, which were recorded for all the groups at baseline and one month using Visible Biofilm Index. Results: Wilcoxon signed rank test showed a significant improvement in the tooth brushing behaviour for the Brush Up group, which was indicated by a lower plaque score after a follow-up of one month. Kruskal-Wallis test followed by post-hoc test showed that the mean ranks of plaque scores of Brush Up group are consistently lower than those of video demonstration group and manual demonstration group. Conclusions: The lower plaque score in subsequent follow-up in Brush Up group suggests that using a smart system can enhance learning a correct tooth brushing method in young children and can also help in implementing the required reinforcement and motivation to brush and aid in better plaque control. RESUMO Objetivo: Investigar o impacto do “Brush Up”, um aplicativo móvel, sobre comportamentos de higiene bucal de crianças de 4 a 6 anos na cidade de Bangalore, na Índia. Métodos: Neste estudo experimental, 247 crianças de 4 a 6 anos foram divididas aleatoriamente em 3 grupos. Como “Brush Up” é um aplicativo móvel, os pais das crianças do Grupo 1 (n=82) baixaram o aplicativo em seus smartphones. As crianças do grupo 2 (n=83) e do grupo 3 (n=82) receberam instruções sobre escovação por meio de vídeo educativo e demonstração manual, respectivamente. A efetividade da escovação foi avaliada por meio de escores de placa bacteriana, registrados para todos os grupos antes da intervenção e um mês depois. Resultados: O teste de Wilcoxon sinalizou uma melhora significativa na escovação para o grupo “Brush Up”, com uma pontuação mais baixa na placa bacteriana após um mês de acompanhamento. O teste de Kruskal-Wallis, seguido do teste post hoc, mostrou que as classificações médias das pontuações do grupo “Brush Up” foram consistentemente mais baixas do que as do grupo com demonstração em vídeo e demonstração manual. Conclusões: Os resultados obtidos no grupo “Brush Up” sugerem que o uso de um sistema inteligente pode melhorar o aprendizado de um método correto de escovação em crianças pequenas e ajudar na implementação do reforço e motivação necessários para escovar e controlar melhor a placa bacteriana.

Artificial pneumatic muscle actuator (PMA) is used to convert pneumatic power to mechanical force. These actuators are like biological muscles, hence its name. PMAs have a wide range of applications ranging from robotics, industrial to the medical applications, as a result of its high power-to-weight ratio, nonhazardous, and compliant nature. The PMA, like any other actuator, has to be tested and validated before using it in any real-world application. An experimental procedure is set up to allow the designer to predict, analyze, and optimize PMA performance before its use in sensitive applications. To achieve this, a rigid experimental test rig needs to be designed to test properties of PMA such as displacement, force, and load capacity. Result of the experiment conducted on the standard PMA by using developed test rig has 5% variation with the values of the manufacturer’s datasheet.

Objective: To define the subgingival microbial profile associated with Stage II generalized periodontitis using next-generation sequencing and to determine the relative abundance of novel periodontal pathogens and bacterial complexes. Methodology: Subgingival biofilm samples were collected from 80 subjects diagnosed with Stage II generalized periodontitis. Bacterial DNA was extracted, and 16S rRNA-based bacterial profiling via next-generation sequencing was carried out. The bacterial composition and diversity of microbial communities based on the age and sex of the patients were analyzed. The bacterial species were organized into groups: bacterial complexes (red, orange, purple, yellow, and green), novel periodontal pathogens, periodontal health-related species, and unclassified periodontal species. The results were analyzed and statistically evaluated. Results: The highest number of bacteria belonged to the phylum Bacteroidetes and Firmicutes. In terms of relative abundance, the orange complex represented 18.99%, novel bacterial species (Fretibacterium spp. and Saccharibacteria spp.) comprised 17.34%, periodontal health-related species accounted for 16.75% and unclassified periodontal species represented (Leptotrichia spp. and Selenomonas spp.) 15.61%. Novel periodontal pathogens had outweighed the periodontal disease-related red complex (5.3%). The one-sample z-test performed was statistically significant at p

Emergency surgical treatment has been challenging and the risk of blood contamination has been high, which is a concern among the medical and dental fraternity. The risk outweighs the benefits in these unprecedented times if proper screening and inactivation of blood products are not performed. Pathogen reduction technologies incorporate various modalities for the inactivation of blood products mainly related to blood transfusion. Oral surgical procedures and periodontal surgeries use platelet-rich fibrin for various regenerative procedures that amplify the prognosis positively. The use of blood products for various treatments could result in contamination, a factor which should be significant attention. The objective of this study was to review the role of pathogen reduction technology in inactivating pathogens in blood products and its use in oral and periodontal surgical procedures. The literature presented in the study is from original studies from a period of 2000 to 2020 which was sourced from Medline, PubMed, and Cochrane central databases. Relevant published papers and in-press papers that provided information were identified and selected. The studies presented have shown data related to implementation of pathogen reduction technologies in relation to the severe acute respiratory syndrome, Middle East respiratory syndrome, and its possible implementation in coronavirus disease-2019 (COVID-19). The paper reviews the various technologies offered and the possibility to eradicate pathogens found in routine blood products, used in oral and periodontal surgical procedures. In all probability, the use of pathogen reduction technology might offer a ray of light to contain the spread among dental treatment procedures

The aim of this study was to improve the life and performance of tungsten carbide turning tool inserts coated with TiN/AlN multilayer thin films using physical vapor deposition technique. Quality characteristics of the coating are evaluated using Calo and VDI 3198 tests. Thickness of the coating is found to be $$3.651 \,\upmu \hbox {m}$$ with adhesion quality of HF1. The performance of coated tool inserts is evaluated using cutting speed (59–118 m/min), feed rate (0.062–0.125 mm/rev) and depth of cut (0.2–0.4 mm) as process parameters in turning MDN431 steel. Experimental investigation has been carried out based on full factorial design, and regression analysis was used to analyze and build the mathematical models for cutting force and surface roughness. Multi-objective optimization of the process parameters has been done with the combination of desirability approach and MOPSO technique. Optimum machining condition for least cutting force and optimum surface roughness is found to be $${V}_{\mathrm{c}} =59\, \hbox {m/min}$$, $${f}=0.063\,\hbox {mm/rev}$$ and $${a}_{{p}} =0.2\,\hbox {mm}$$. Cutting force and surface roughness are reduced by 9% in TiN/AlN-coated tools compared with the uncoated tool. To improve the CoD and capability of predictive regression models, ANN modeling has been adopted. ANN trained model and mathematical regression models are used to predict the results and predict the responses, which follow the experimental data with minimum absolute error. The predicted results are validated using ANN and regression analysis found with minimum error, and developed models are adequate for further usage. Tool wear was reduced by 105% in TiN/AlN-coated tools compared with the uncoated tool.

10025 Background: Encouraging responses to chemoimmunotherapy with I/T/DIN/GM-CSF have been observed in trials for patients (pts) with relapsed/refractory HR-NBL, but factors associated with response have not been identified and duration of response has not been assessed. We aimed to evaluate timing and duration of response among pts with relapsed HR-NBL treated with I/T/DIN/GM-CSF and identify factors associated with response. Methods: We performed a multicenter retrospective cohort study of pts treated with I/T/DIN/GM-CSF. Eligibility criteria included: diagnosis of relapsed HR-NBL prior to age 30; objective response [OR; complete, partial, or minor response (CR, PR, or MR) by International Neuroblastoma Response Criteria (INRC)] or stable disease (SD) after initial therapy; receipt of I/T/DIN/GM-CSF for relapse or progression outside a clinical trial from 1/1/15-6/1/20. Logistic regression was used to identify factors associated with OR. Kaplan Meier analysis was used to determine progression-free survival (PFS). Results: We enrolled 143 pts with a median age at diagnosis of 51 months. Tumors were MYCN amplified in 52 (36%) and ALK was wild type in 73/94 (78% of tumors in which ALK status was known). 79 (55%) had received prior anti-GD2 therapy. I/T/DIN/GM-CSF comprised first relapse therapy in 96 pts (67%), second relapse therapy in 23 (16%) and subsequent therapy in 24 (17%). 70 (49%) achieved OR following I/T/DIN/GM-CSF therapy [29% CR, 15% PR, 5% MR], 30 (21%) achieved SD and 43 (30%) progressed. Median cycles received was 5 (range 1-31). 121 patients (85%) had their best response upon first disease evaluation. Later disease evaluations showed improved INRC classification in 14% of pts with initial SD, 33% with MR, and 41% with PR. Median time to OR was 2 months (range 1-21). Of the 105 relapse/progression events after starting I/T/DIN/GM-CSF (73% of pts), 59 (56%) occurred during therapy. Of the 42 pts who achieved CR with I/T/DIN/GM-CSF, 5 (12%) relapsed during I/T/DIN/GM-CSF and 17 (40%) relapsed after discontinuation. I/T/DIN/GM-CSF was discontinued in 83 pts (58%) due to suboptimal response or PD, and in 19 (13%) for toxicity. Median PFS among objective responders was 15.5 months. Among those in CR, median PFS after discontinuation of I/T/DIN/GM-CSF was 11.8 months (range 0.7-70.6). Multivariable models did not identify clinical or biologic factors associated with OR. Conclusions: 49% of pts receiving I/T/DIN/GM-CSF for relapsed HR-NBL achieved OR. Among responders, median response duration was 15.5 months. Pts with SD on first disease evaluation were unlikely to achieve OR, but > 1/3 of pts with MR/PR on first evaluation ultimately achieved CR. No identifiable clinical or biologic factors were associated with OR.

10003 Background: The addition of dinutuximab (DIN) in the post-consolidation setting led to improved event-free survival rates for patients with high-risk neuroblastoma. Chemoimmunotherapy including irinotecan, temozolomide, DIN and sargramostim (GM-CSF) in patients with recurrent or refractory neuroblastoma results in robust objective clinical responses. Evaluation of chemoimmunotherapy in the induction setting for patients with newly-diagnosed high-risk neuroblastoma (HR-NBL) warrants investigation. Methods: Children’s Oncology Group (COG) ANBL17P1 is a prospective, single arm, limited institution pilot study to assess the tolerability and feasibility of administering DIN (17.5mg/m2/dose, IV Days 2-5) and GM-CSF (250mcg/m2/dose, subcutaneous Days 6-count recovery) with COG Induction chemotherapy Cycles 3-5 for patients with newly-diagnosed high-risk neuroblastoma. The primary endpoint of tolerability included the number of toxic deaths and number of patients experiencing predefined unacceptable toxicities during Induction Cycles 3-5. Unacceptable toxicities included: hypotension requiring pressors > 24 hours, respiratory toxicity requiring ventilatory support > 24 hours, Grade 4 neuropathy that did not resolve prior to the next cycle, and failure to recover the ANC to > 750 mm3 by day 35. Feasibility was assessed as being able to receive > 75% of planned DIN doses administered during Induction Cycles 3-5. Revised International Neuroblastoma Response Criteria (INRC) were used to assess end of Induction (EOI) response. Results: Forty-two eligible and evaluable patients with newly-diagnosed high-risk neuroblastoma enrolled at 8 sites (22 [52.4%] males; median age 3.3 years at diagnosis) from January 14, 2019 to June 4, 2020. The most common DIN related Grade >3 toxicities observed during Induction Cycles 3-5 included fever (31.0%) and pain (9.5%). None of the patients experienced a toxic death or unacceptable toxicity during Induction Cycles 3-5. Thus, the regimen was deemed tolerable. Patients received 97.4% - 101.8% of the total DIN dose expected to be administered during Induction Cycles 3-5. Therefore, the regimen was deemed feasible. Thirty-eight of 42 patients completed the EOI evaluations, including 11 with complete response, 22 with partial response, 0 with minor response, 3 with stable disease and 2 with progressive disease. The overall EOI objective response rate (CR+PR+MR) was 86.8%. Conclusions: The administration of DIN and GM-CSF to COG Induction Cycles 3-5 for patients with newly-diagnosed high-risk neuroblastoma was tolerable and feasible. The objective response rate at EOI appears encouraging. This therapeutic regimen will be studied in a randomized phase 3 trial to further evaluate the efficacy of Induction phase chemoimmunotherapy for high-risk neuroblastoma. Clinical trial information: NCT03786783.

512 Background: Sacituzumab govitecan (SG), a novel antibody-drug conjugate in which the topoisomerase 1 inhibitor SN-38 (active metabolite of irinotecan) is linked to a humanized monoclonal antibody targeting the tumor antigen Trop2, is currently approved for treatment of patients (pts) with pre-treated metastatic triple negative breast cancer (TNBC). We conducted a phase 2 study evaluating neoadjuvant (NA) SG as upfront therapy for pts with localized TNBC (NCT04230109). The primary objective was to assess pathological complete response (pCR) rate in breast and lymph nodes (ypT0/isN0) with SG. Secondary objectives included assessment of radiological response rate, evaluation of the safety and tolerability (CTCAE v5.0) and event-free survival (EFS). Methods: Patients with localized TNBC (tumor size ≥1cm, or any size if node positive) with no prior treatment were eligible. SG was administered IV on Days 1, 8 of each 21-day cycle at a starting dose of 10 mg/kg for 4 cycles. After 4 cycles, patients with biopsy-proven residual disease, considered as no pCR for primary endpoint, had the option to receive additional NA therapy at the discretion of the treating physician. Radiologic response (US or MRI) was defined by RECIST version 1.1 using a composite response of CR & PR. Standard descriptive statistics were utilized, including 95% binomial confidence intervals for all rates estimated. Results: From 7/14/20 – 8/31/21, 50 pts were enrolled (median age = 48.5; 11 stage I disease, 24 stage II, 11 stage III, 4 unknown; 62% node negative). The majority (98%; n = 49) of pts completed 4 cycles of SG. Overall, the radiological response rate with SG alone was 62% (n = 31, 95% CI 48%, 77%). 26 pts proceeded directly to surgery after SG. Overall, the pCR rate with SG alone was 30% (n = 15/50, 95% CI 18%, 45%). The other 11 pts had RCB-1 (n = 3), RCB-2 (n = 5), and RCB-3 (n = 3) disease, respectively. Of the 24 pts who received additional NA therapy, 6 had a pCR (3 received anthracycline-based regimen, 2 carboplatin/taxane, and 1 docetaxel/cyclophosphamide). Among pts with a germline BRCA mutation (n = 8), 7 proceeded directly to surgery after SG and 6 had a pCR (86%, 95% CI 42%, 99%). The most common AEs with SG were nausea (82%, n = 41), fatigue (78%, n = 39), alopecia (76%, n = 38), neutropenia (58%, n = 29), anemia (36%, n = 18), and rash (48%, n = 24). 6% of pts required dose-reduction. No pts discontinued SG therapy due to disease progression or AEs; 1 discontinued due to minimal response per investigator preference. At the time of data cut-off (1/18/22), no pts experienced disease recurrence. Updated biomarker and EFS results will be presented at the meeting. Conclusions: In the first neoadjuvant trial in TNBC with an ADC, SG demonstrated single agent efficacy in localized TNBC. Further research on optimal duration of SG as well as NA combination strategies, including immunotherapy, are needed. Clinical trial information: NCT04230109.

10041 Background: Lorlatinib, a macrocyclic ATP-competitive ALK inhibitor, exerts potent activity against neuroblastoma (NB) xenograftsharboring the most common ALK mutations. We performed a first-in-child phase 1 study of lorlatinib for patients with refractory/relapsed (R/R) ALK aberrant high-risk NB. We previously reported on Part A of the study, where safety of single agent lorlatinib was determined, showing complete responses (CR) to lorlatinib at the recommended phase 2 dose (RP2D) of 115 mg/m2 in pts < 18 years and 150 mg in pts > 18 yrs. Part B of the study aimed to determine the safety, pharmacokinetics (PK), RP2D, and explore the anti-tumor activity of lorlatinib in combination with topotecan and cyclophosphamide in pts with R/R ALK-driven NB. Methods: Patients with R/R NB ages 1-17 years with ALK mutations or amplification were eligible; prior ALK inhibitor (ALKi) treatment was allowed. Lorlatinib was orally administered once daily on days 1-28 with topotecan (0.75 mg/m2/day) and cyclophosphamide (250 mg/m2/day) administered intravenously days 1-5 and GCSF starting day 6. Two lorlatinib dose levels (DL) of 95 mg/m2/day (DL4B) and 115 mg/m2/day (DL5B) were assessed using a 3+3 dose escalation design with the primary endpoint of dose limiting toxicity (DLT) in Course 1. We report lorlatinib safety, PK, and objective response rate (ORR) for patients enrolled on Part B. Results: Between 10FEB2020 and 03DEC2021,9 eligible pts enrolled on Part B with a median age of 6.7 years (3.7-12.7). Three pts were enrolled onto DL4B and six onto DL5B (2/3 pts on DL4B and 4/6 pts on DL5B had received prior ALKi therapy) with no DLT’s observed in course 1. One patient on DL5B experienced a neuropsychological DLT in Course 3. Most common treatment-related adverse events were hematological, febrile neutropenia, high cholesterol, hypertriglyceridemia, and neuropsychological effects. The median number of courses received was 6 with a range of 1-8 on DL4B and 1-7 on DL5B. Of the 8 patients evaluable for response, ORR was 50%: 2/3 pts on DL4B and 2/5 pts on DL5B. Preliminary PK data demonstrate comparable dose level-associated lorlatinib steady state exposure between Part B chemotherapy combination and Part A monotherapy cohorts, supporting that chemotherapy had no effect on lorlatinib exposure that there are no overlapping toxicities. Conclusions: Lorlatinib in combination with topotecan and cyclophosphamide is well tolerated, and early data suggest encouraging objective anti-tumor activity. These data support the current integration of lorlatinib into up-front high risk neuroblastoma therapy for patients with ALK-driven neuroblastoma. Clinical trial information: NCT03107988.

e22015 Background: GSK-3β overexpression is associated with aggressive malignancies, treatment resistance and poor prognosis. The GSK-3β inhibitor Elraglusib induces apoptosis via NFΚB and p53 pathways and has potent anti-fibrotic and immunomodulatory activity. Adult studies of elraglusib demonstrate clinical activity in pancreatic cancer, melanoma, lymphoma and sarcoma as a single agent or in combination with cytotoxic chemotherapy. Elraglusib is active in in vivo models of neuroblastoma (NBL) and malignant glioma. This first-in-pediatrics study (NCT04239092) is evaluating the safety, pharmacokinetics (PK), and efficacy of elraglusib monotherapy and in combination with chemotherapy in patients with refractory malignancies. Methods: Elraglusib is given intravenously (IV) twice-weekly at 3 dose levels (DL) (9.3, 12.4 and 15 mg/kg) as a single agent or in combination with irinotecan, cyclophosphamide/topotecan or temozolomide/irinotecan in 21-day cycles. A cohort of pts with refractory NBL will be treated at the recommended phase 2 dose (RP2D) of elraglusib with temozolomide/irinotecan. Results: As of January 2022, 23 pts (n = 7 female, median age 14.2 years) have received at least one dose of elraglusib. Tumor types: 5 NBL, 3 diffuse midline glioma (DMG), 3 osteosarcoma (OS), 3 ependymoma (EP), 2 alveolar rhabdomyosarcoma (aRMS), 1 angiosarcoma (AS), 1 Ewing sarcoma (ES), 1 glioblastoma (GBM), 1 hepatoblastoma (HB), 1 embryonal CNS tumor NOS, 1 NUT midline carcinoma, 1 pineoblastoma (PB). Median time from diagnosis is 26 months (range: 6.7 – 156.3) and median number of lines of prior systemic therapy is 2 (range 0-14). Two DLs of single agent (6 pts) have been completed (9.3 and 12.4 mg/kg) without elraglusib-attributable severe adverse events (SAEs). Of the 15 patients on the combination arm with irinotecan or cyclophosphamide/topotecan, a single adverse event (Grade 4 hypotension/infusion reaction) was reported. Grade 1/2 elraglusib attributable-AEs include: transient visual change (n = 10), nausea (n = 7), vomiting (n = 6), fatigue (n = 2), hypotension (n = 2) and infusion reaction (n = 1). One pt with recurrent ES had a radiographic and pathologic CR after 3 cycles of elraglusib/cyclophosphamide/topotecan. 6 pts (26.1%) had SD (2 NBL, 1 aRMS, 1 EP, 1 OS, 1 GBM). 8 pts (35%) remained on study treatment ≥ 3 months (2 NBL, 2 EP, 1 OS, 1 aRMS, 1 ES, 1 PB). Median treatment duration was 40 days (range 1 - 126). 4 pts remain on therapy. Conclusions: Elraglusib is well tolerated as a single agent and with several chemotherapy regimens in this heavily pretreated pediatric population with refractory cancers. It has encouraging antitumor activity, with 1 CR in a patient with recurrent ES. Enrollment is ongoing; a RPD2 has not been reached. Clinical trial information: NCT04239092.

10038 Background: 131I-metaiodobenzylguanidine (MIBG) is one of the most active salvage therapies for patients with relapsed or refractory (R/R) high-risk neuroblastoma (HRNB). Preclinical neuroblastoma studies show cooperative effects when radiation is combined with anti-GD2 monoclonal antibody (mAb). We hypothesized that MIBG would synergize with the anti-GD2 mAb dinutuximab to provide improved anti-tumor responses. The primary aims of Part A of this study were to determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of MIBG administered with dinutuximab in children with R/R HRNB and to define and describe the toxicities. Methods: Patients 1-29 years of age with R/R HRNB who had MIBG uptake in ≥ 1 site were eligible. Prior anti-GD2 mAb therapy was allowed provided it was not administered with MIBG and not permanently discontinued due to toxicity. One prior MIBG therapy was allowed. MIBG was administered on day 1 at one of three dose levels (DLs): 12, 15, and 18 mCi/kg (DL1-DL3, respectively) with an expansion cohort at the RP2D. Doses were escalated using a rolling six design starting at DL1. The primary endpoint was dose-limiting toxicity (DLT) during course 1. Dinutuximab (17.5 mg/m2/dose) was administered intravenously on days 8-11 and 29-32 and GM-CSF (250 mcg/m2/dose) subcutaneously on days 8-17 and 29-38. Autologous peripheral blood stem cells were infused to all patients on day 15 (+/- 2 days). A maximum of 2 courses per patient were allowed. Response rate was defined as the proportion of patients with a complete or partial response. Results: Thirty-one patients were enrolled. Fourteen were evaluable for dose escalation (4 on DL1, 4 on DL2, and 6 on DL3); 5 evaluable patients were treated in the DL3 expansion. The median age was 7.4 years (range: 3.1 – 22.0) and 20 (65%) were male. Twenty-seven (87%) patients had previously received a median of 8.5 cycles of chemoimmunotherapy (range: 2 – 21). Eight patients previously progressed while receiving anti-GD2 mAb including 7 in DL3. Five (16%) patients had previously received MIBG. No patient at any dose level experienced DLT. Common grade 3/4 treatment-related toxicities were expected hematologic toxicities attributable to MIBG and non-hematologic toxicities attributable to dinutuximab or GM-CSF. Among 26 response-evaluable patients, the centrally-confirmed response rate was 31% across all dose levels: 2/6 (33%) in DL1, 3/5 (60%) in DL2, and 3/15 (20%) in DL3. There were 3 minor responses, 1 in DL2 and 2 in DL3. Conclusions: The RP2D of MIBG in combination with standard doses of dinutuximab and GM-CSF is 18 mCi/kg. This radioimmunotherapy regimen is well-tolerated without additive toxicity. Preliminary efficacy data are encouraging in this heavily pre-treated patient population. A phase 2 trial of this regimen is planned in patients with R/R HRNB. Clinical trial information: NCT03332667.

In recent years, the near net shape metal injection molding process combines desirable features of plastic injection molding and powder metallurgy processes to gain high strength-to-weight ratio for manufacturing complex-shaped parts. The metal injection molding process consists of mixing, molding, debinding, and sintering. Microwave processing has attracted much attention in global research because of its unique features such as its ability to heat and sinter a wide variety of metals and its significant advantages in energy efficiency, processing speed, and compatibility. Also, it presents few environmental risks and can produce refined microstructures. The injected samples to be sintered are composed of fine tool steel metal powder and binders, stearic acid, paraffin wax, low-density polyethylene, and polyethylene glycol (600). In recent years, microwave-assisted post-treatment is considered a novel method for processing green parts. In this work, the green parts are subjected to high-intensity microwave fields which operate at a frequency of 2.45 GHz. Metal injection molding compacts were sintered using multi-mode microwave radiation. The sintering of a metal injection molding compact by microwaves has hardly been reported. The metal injection molding compact showed better results than those produced by sintering with conventional heating. This study evaluates the effect of conventional sintering and microwave sintering on mechanical properties. By optimizing the sintering process, increased sintered hardness, a more homogeneous microstructure, and greater shrinkage were obtained using microwave-assisted sintering.

This paper investigates cyclic hot corrosion of plasma sprayed CoCrAlY + Al2O3 + YSZ (C1) and CoCrAlY + CeO2 (C2) composite coatings on MDN 321 and Superni 76 substrates in molten salt (Na2SO4-60%V2O5) environment exposed to 700 °C. Weight change technique is used to evaluate the corrosion performance. Both C1 and C2 coatings showed better corrosion resistance than uncoated alloy. Both the coatings showed linear weight gain during the initial cycles and parabolic weight gain nature with subsequent hot corrosion cycles. The parabolic rate constant (Kp) of C1 and C2 coating was observed to be in the range 0.29–0.32 × 10−10 g2 cm−4 s−1 and 1.0–1.13 × 10−10 g2 cm−4 s−1 respectively. In C1 coating, the globular and continuously packed structure on the corroded surface having CoO, Cr2O3, CoCr2O4 and CoAl2O4 spinel oxides provided superior hot corrosion resistance. While in case of C2 coating, the outward growth of CeVO4 irregular crystals as a corrosion product of CeO2 and V2O5 salt deteriorated the oxide scales resulting in higher corrosion rate.

Metal injection moulding (MIM) is a near-net shape manufacturing technology for producing intricate parts, cost-effectively. MIM comprises combined techniques of plastic injection moulding and powder metallurgy. The present study focused on the development of the binder and fabrication of defect free MIM component. A wax-based binder system consisting of paraffin wax (PW), low density polyethylene (LDPE), polyethylene glycol (PEG-600) and stearic acid was established for MIM of NiCrSiB (70% Wt.) + Cr3C2-NiCr (30% Wt.) nickel based metal matrix composite (NMMC) powder. The feedstock was characterised through rheological properties at different temperatures. Injection temperature was determined from the rheological investigation of the feedstock having the 56% powder loading and 44% binder by volume. Sintering process was carried out with the temperature cycle in the range of 1250–1300 ∘C under hydrogen purged atmosphere. The MIM components showed good and acceptable shrinkage in linear dimensions. The mechanical properties and wear behaviour of NMMC was studied using a pin-on-disc apparatus with alumina disc.Tests were performed under dry sliding conditions at room temperature and elevated temperatures of 200 and 400 ∘C. Results shows that wear rate is maximum at 400 ∘C for 40 N and lowest at room temperature for 10 N. Further wear mechanism was analysed using scanning electron microscope (SEM).

Highly alloyed steel are widely used in manufacturing of turbine materials because of its high resistance to corrosion and oxidation. MDN 431 is one of such material manufactured by Midhani. It’s having high hardness and strength which makes it hard-to-machine steel. DLC coating provide solution to this problem. DLC coating are developed using state of art PVD technique on the HSS tool. Turning process carried out on MDN431 steel using coated and uncoated HSS tool insert in both wet and dry condition. During the present investigation, speed, feed, and depth of cut varied according to full factorial design with level 3, consequently cutting forces, surface roughness (Ra) and tool wear were measured. The obtained results are optimized using factorial method for cutting forces and surface roughness. Using FFD method second order regression analysis carried out for each input variable and same compared with experimental values and found the developed model is with minimal error which supported by proof trials. Speed and depth of cut are inversely dependent on the cutting force and surface roughness whereas feed is opposite to it. Effect of DLC coating during machining of MDN431 is studied using optical profilometry in comparison with uncoated tool.

Metal injection moulding (MIM) is large scale manufacturing method, for creation of complex shapes and miniature parts by a combination of plastic injection moulding with the flexibility in sintering of metal particulates. In current investigation binder comprised of paraffin wax, polyethylene glycol, stearic acid and low-density polyethylene are developed for moulding of composite powders of SS316L+WC-CrC-Ni, and sintered at 1200°C under hydrogen purged atmosphere. Composites are characterised with respect to rheological, thermal properties and microstructure by scanning electron microscopy, microhardness and density. Properties of sintering temperature and heating rate on the above properties have been evaluated to obtain a defect-free composite.

Pneumatic muscle actuators (PMA) are a class of soft actuators known for their high power to weight ratio and inherent compliance. The pneumatic muscle's inherent properties make them very favorable for assistive applications (e.g., medical exoskeletons). This study presents a novel end-fitting design that makes the developed pneumatic muscle actuator lightweight, cost-effective, and modular, thus simplifying the process of assembly and maintenance. The pneumatic muscle actuator assembled using the novel end fittings achieves a shorter overall length without compromising its contraction. The pneumatic muscle actuator has been assembled using a commercial bladder and a braided sleeve alongside a pair of 3D printed novel end-fittings. The paper also details the developed actuator's characterization for force and deflection parameters at various operating pressures. A total of four muscle actuators of varying diameters with constant actuation length (100 mm) were developed and tested to showcase the effect of size on the muscle actuator's behavior. The study presented here also involved comparing three mathematical models developed for pneumatic muscles in order to find a model which closely resembles the developed muscle actuator. Finally, the developed pneumatic muscle actuator's behavior is compared with a commercially available muscle to determine the efficacy of the developed muscle's design. The tests showed that the muscle using a bladder of smaller volume but higher tensile modulus had a higher accuracy and stable performance. As the muscle is intended for medical applications, it was also put through an endurance test with realistic loading and pressure conditions, which revealed very promising results.

In this paper, investigation into solid particle erosion behavior of atmospheric plasma-sprayed composite coating of CoCrAlY reinforced with Al2O3 and CeO2 oxides on Superni 76 at elevated temperature of 600 °C is presented. Alumina particles are used as erodent at two impact angles of 30° and 90°. The microstructure, porosity, hardness, toughness and adhesion properties of the as-sprayed coatings are studied. The effects of temperature and phase transformation in the coatings during erosion process are analyzed using XRD and EDS techniques. Optical profilometer is used for accurate elucidation of erosion volume loss. CoCrAlY/CeO2 coating showed better erosion resistance with a volume loss of about 50% of what was observed in case of CoCrAlY/Al2O3/YSZ coating. Lower erosion loss is observed at 90° as compared to 30° impact angle. The erosion mechanism evaluated using SEM micrograph revealed that the coatings experienced ductile fracture exhibiting severe deformation with unusual oxide cracks. Reinforced metal oxides provide shielding effect for erodent impact, enabling better erosion resistance. The oxidation of the coating due to high-temperature exposure reforms erosion process into oxidation-modified erosion process.

Tungsten carbide tool places in are coated by customized composition of Ti/TiCN/TiN/TiCN/TiN for multilayer and monolayer TiC-C using PVD assisted CAE technique. Quality physiognomies of coatings are evaluated using VDI3198 and Calo tests. Thickness of the coatings for Ti-multilayer and monolayer are found to be 1.837 and 1.198 µm respectively and adhesion quality of HF1 attained. Highly alloyed steel MDN431 is used as machining material to evaluate the performance of coatings. The coated tool insert performance has been evaluated at the machining parameters cutting speed in the range of 59-118 m/min, feed rate is 0.062-0.125 mm/rev and depth of cut is ap 0.2-0.4 mm during machining of MDN431 steel. Experiments are conducted based on L27 full factorial design. Cutting forces and surface roughness are analysed using regression analysis. Desirability approach as well as PSO technique is used to optimize the process parameters. Least cutting force and surface roughness are obtained at the condition of Vc−118 m/min, f-0.063 mm/rev, ap−0.2 mm and Vc−59 m/min, f-0.63 mm/rev, ap − 0.2 mm for Ti-multilayer and TiC-C coatings respectively. To augment the capability of predictive regression models and coefficients of determination (COD), ANN modelling has been adopted. Cutting forces and surface roughness are predicted using ANN and mathematical regression models, predicted data follows the experimental data with minimum absolute error. Tool wear was reduced by 65.7% in Ti-multilayer and TiC-C coated tools compared to uncoated tool.Tungsten carbide tool places in are coated by customized composition of Ti/TiCN/TiN/TiCN/TiN for multilayer and monolayer TiC-C using PVD assisted CAE technique. Quality physiognomies of coatings are evaluated using VDI3198 and Calo tests. Thickness of the coatings for Ti-multilayer and monolayer are found to be 1.837 and 1.198 µm respectively and adhesion quality of HF1 attained. Highly alloyed steel MDN431 is used as machining material to evaluate the performance of coatings. The coated tool insert performance has been evaluated at the machining parameters cutting speed in the range of 59-118 m/min, feed rate is 0.062-0.125 mm/rev and depth of cut is ap 0.2-0.4 mm during machining of MDN431 steel. Experiments are conducted based on L27 full factorial design. Cutting forces and surface roughness are analysed using regression analysis. Desirability approach as well as PSO technique is used to optimize the process parameters. Least cutting force and surface roughness are obtained at the condition of Vc−118...

BACKGROUND GD2 is a ganglioside that is ubiquitously expressed in the plasma membrane of neuroblastoma and is shed into the circulation. PROCEDURE GD2 was measured with a high-pressure liquid chromatography/tandem mass spectrometry assay in serum or plasma from 40 children without cancer (controls) and in biobanked samples from 128 (73 high-risk) children with neuroblastic tumors at diagnosis, 56 children with relapsed neuroblastoma, 14 children with high-risk neuroblastoma after treatment, and 8 to 12 children each with 10 other common childhood cancers at diagnosis. RESULTS The C18 (18 carbon fatty acid) lipoform was the predominant circulating form of GD2 in controls and in patients with neuroblastoma. The median concentration of GD2 in children with high-risk neuroblastoma at diagnosis was 167 nM (range, 16.1-1060 nM), which was 30-fold higher than the median concentration (5.6 nM) in controls. GD2 was not elevated in serum from children with the differentiated neuroblastic tumors, ganglioneuroma (n = 10) and ganglioneuroblastoma-intermixed subtype (n = 12), and in children with 10 other childhood cancers. GD2 concentrations were significantly higher in serum from children with MYCN-amplified tumors (P = 0.0088), high-risk tumors (P