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Chimeric antigen receptor T cell (CAR-T) therapy is an emerging strategy to improve treatment outcomes for recurrent high-grade glioma, a cancer that responds poorly to current therapies. Here we report a completed phase I trial evaluating IL-13Rα2-targeted CAR-T cells in 65 patients with recurrent high-grade glioma, the majority being recurrent glioblastoma (rGBM). Primary objectives were safety and feasibility, maximum tolerated dose/maximum feasible dose and a recommended phase 2 dose plan. Secondary objectives included overall survival, disease response, cytokine dynamics and tumor immune contexture biomarkers. This trial evolved to evaluate three routes of locoregional T cell administration (intratumoral (ICT), intraventricular (ICV) and dual ICT/ICV) and two manufacturing platforms, culminating in arm 5, which utilized dual ICT/ICV delivery and an optimized manufacturing process. Locoregional CAR-T cell administration was feasible and well tolerated, and as there were no dose-limiting toxicities across all arms, a maximum tolerated dose was not determined. Probable treatment-related grade 3+ toxicities were one grade 3 encephalopathy and one grade 3 ataxia. A clinical maximum feasible dose of 200 × 106 CAR-T cells per infusion cycle was achieved for arm 5; however, other arms either did not test or achieve this dose due to manufacturing feasibility. A recommended phase 2 dose will be refined in future studies based on data from this trial. Stable disease or better was achieved in 50% (29/58) of patients, with two partial responses, one complete response and a second complete response after additional CAR-T cycles off protocol. For rGBM, median overall survival for all patients was 7.7 months and for arm 5 was 10.2 months. Central nervous system increases in inflammatory cytokines, including IFNγ, CXCL9 and CXCL10, were associated with CAR-T cell administration and bioactivity. Pretreatment intratumoral CD3 T cell levels were positively associated with survival. These findings demonstrate that locoregional IL-13Rα2-targeted CAR-T therapy is safe with promising clinical activity in a subset of patients. ClinicalTrials.gov Identifier: NCT02208362 .

BackgroundThe prevalence of maxillary lateral incisor agenesis ranges from 1% to 3%, with slight global variability. The unilateral agenesis of the maxillary lateral incisor is often associated with a contralateral tooth with microdontia or a peg shape and can have esthetic, functional, and psychosocial implications for patients. The aim of the present survey was to assess the perceptions of smile aesthetics among orthodontists, general dentists and laypeople on different treatment choices, modifying the initial condition of the right maxillary lateral incisor agenesis and the contralateral peg-shaped tooth.MethodsA series of 6 photographs of different smile simulations were presented to 109 orthodontic specialists, 109 general dentists and 141 laypeople through an online survey. Each photograph was duplicated and judged from 1 to 10 for 2 different bipolar adjectives.ResultsStatistically significant results were found for all the groups investigated. All three groups preferred the photo that maintained the typical symmetrical ‘high-low-high gingival contour. Moreover, both orthodontic specialists and general dentists preferred unilateral mesialization of the canine and conservative rehabilitation of the peg-shaped incisor. In contrast, the laypeople preferred bilateral mesialization of the canines with peg-shaped incisor avulsion.ConclusionThe normal symmetrical array of the central incisor, lateral incisor and canine had the best aesthetic results for all subjects. Laypeople were more attracted to a symmetrical smile than were the groups of orthodontic specialists and general dentists.

This 1:30,000 scale geological map describes Oxia Planum, Mars, the landing site for the ExoMars Rosalind Franklin rover mission. The map represents our current understanding of bedrock units and their relationships prior to Rosalind Franklin’s exploration of this location. The map details 15 bedrock units organised into 6 groups and 7 textural and surficial units. The bedrock units were identified using visible and near-infrared remote sensing datasets. The objectives of this map are (i) to identify where the most astrobiologically relevant rocks are likely to be found, (ii) to show where hypotheses about their geological context (within Oxia Planum and in the wider geological history of Mars) can be tested, (iii) to inform both the long-term (hundreds of metres to ∼1 km) and the short-term (tens of metres) activity planning for rover exploration, and (iv) to allow the samples analysed by the rover to be interpreted within their regional geological context.

High-grade (WHO grades III-IV) glioma remains one of the most lethal human cancers. Adoptive transfer of tumor-targeting chimeric antigen receptor (CAR)-redirected T cells for high-grade glioma has revealed promising indications of anti-tumor activity, but objective clinical responses remain elusive for most patients. A significant challenge to effective immunotherapy is the highly heterogeneous structure of these tumors, including large variations in the magnitudes and distributions of target antigen expression, observed both within individual tumors and between patients. To obtain a more detailed understanding of immunotherapy target antigens within patient tumors, we immunochemically mapped at single cell resolution three clinically-relevant targets, IL13Rα2, HER2 and EGFR, on tumor samples drawn from a 43-patient cohort. We observed that within individual tumor samples, expression of these antigens was neither random nor uniform, but rather that they mapped into local neighborhoods - phenotypically similar cells within regions of cellular tumor - reflecting not well understood properties of tumor cells and their milieu. Notably, tumor cell neighborhoods of high antigen expression were not arranged independently within regions. For example, in cellular tumor regions, neighborhoods of high IL13Rα2 and HER2 expression appeared to be reciprocal to those of EGFR, while in areas of pseudopalisading necrosis, expression of IL13Rα2 and HER2, but not EGFR, appeared to reflect the radial organization of tumor cells around hypoxic cores. Other structural features affecting expression of immunotherapy target antigens remain to be elucidated. This structured but heterogeneous organization of antigen expression in high grade glioma is highly permissive for antigen escape, and combinatorial antigen targeting is a commonly suggested potential mitigating strategy. Deeper understanding of antigen expression within and between patient tumors will enhance optimization of combination immunotherapies, the most immediate clinical application of the observations presented here being the importance of including (wild-type) EGFR as a target antigen.

Abstract Background The occurrence of mandibular canine impaction and/ or transmigration is a rare clinical entity but diagnosis and treatment planning is of clinical significance. The associated etiological factors and the clinical guidelines for the management are still not clear. The aim of this systematic review was to summarize the available data to report the prevalence and identify the etiological factors, clinical features, and various treatment outcomes in patients with mandibular canine impaction and/or transmigration. Methods The review protocol was registered in PROSPERO (CRD42021222566) and was conducted and reported according to the PRISMA and Cochrane Handbook / Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. A computerized search of studies published up to April 30, 2023, was conducted using the following databases: Medline, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Scopus, Web of Science, and Latin American and Caribbean Health Sciences Literature. A manual search of the reference and citation lists of eligible articles and existing systematic reviews for any additions were also conducted. The Newcastle–Ottawa Scale quality assessment tool was used to assess the studies' quality. Results After removing 6 duplicates, 3700 articles were identified. For the final analysis, 19 studies published between 1985 and 2023 met all the eligibility criteria and were included. A total of 7 studies presented as good and 12 studies presented as satisfactory. Patients were screened in ten studies and diagnostic records from archives were retrieved in nine studies. The total number of diagnostic records screened was 138.394, and the total number of patients from the included studies was 43.127. Conclusions Based on the findings from this systematic review, the prevalence of mandibular canine impaction ranged from 0.008% to 1.29% while canine transmigration from 0.12% to 0.98%. Crowding of the mandibular arch, the presence of a retained deciduous canine, and odontoma or cyst are the etiological factors more commonly associated with mandibular canine impaction and or transmigration. Surgical extraction and surgical exposure followed by orthodontic traction are the two most frequently carried out treatment modalities in the management of mandibular canine impaction and or transmigration.

Objective:Compliance is critical for successful outcomes in orthodontics, and personality traits may play a role in determining patient adherence. This study aimed to monitor compliance during treatment with removable clear aligners (CA) [Align Technology Inc, San José, Calif ], and evaluate the influence of motivational techniques and the patient’s profiles assessed through the psychological wellbeing (PWB) questionnaire on clinical outcomes.Methods:Thirty-nine consecutive patients in permanent dentition seeking treatment with CA were recruited from two universities. Casts were obtained before treatment and after 3, 6, and 12 months and the corresponding digital Clincheck©.STL files were used to calculate the discrepancy index to check for differences between virtual and real treatment stages. Patients were divided into two groups: the Case group, which received motivational techniques at each appointment, and the control group which received instructions only at the beginning. Psychological profiles were evaluated before treatment (T0) and after 3 (T1), 6 (T2), and 12 (T3) months.Results:There were no differences between the Case and Control groups regarding the use of motivational reminders. The analysis of the PWB showed that almost all values increased, and there was a strong correlation between dental casts and correspondent. STL files at every time point. The PWB showed increased values from T0 to T3 in the sample.Conclusion:Motivational techniques did not affect patient compliance, and treatment outcomes were achieved as planned. The PWB of all patients improved throughout the treatment with CA.

Objective To estimate the prevalence of overweight at 12 months in an Italian birth cohort and to identify factors related to an increased likelihood of being overweight.Methods The Italian NASCITA birth cohort was analysed. Infants were classified as underweight (

The integration of 3D printing technology in maxillofacial surgery in Iran represents a significant advancement in medical practice, offering unprecedented precision and efficiency in surgical procedures. Employing the Non-Adoption, Abandonment, Scale-Up, Spread, and Sustainability (NASSS) framework and the WHO Health Systems Framework, this study analyzes the complex impact and challenges of 3D printing adoption within the Iranian healthcare sector. Maxillofacial surgery has seen transformative progress with 3D printing’s ability to produce accurate surgical models and customized implants. The results indicate a notable improvement in surgical precision and patient recovery times, alongside combatting identified barriers including technological access, cost, and skill acquisition. This conclusion underscores the critical need for targeted educational programs, policy support, and infrastructure development to overcome these obstacles. This paper highlights 3D printing’s potential to revolutionize maxillofacial surgery in Iran, provided that comprehensive strategies are implemented to address the current limitations and fully leverage this innovative technology’s benefits.