Ongoing Data Research Articles

Anaplastic sarcoma of the kidney (DICER1-sarcoma of the kidney): A report from the International Pleuropulmonary Blastoma/DICER1 Registry.

Anaplastic sarcoma of the kidney (ASK) is a DICER1-related neoplasm first identified as a distinctive tumor type through the evaluation of unusual cases of putative anaplastic Wilms tumors. Subsequent case reports identified the presence of biallelic DICER1 variants as well as progression from cystic nephroma, a benign DICER1-related neoplasm. Despite increasing recognition of ASK as a distinct entity, the optimal treatment remains unclear. Individuals with known or suspected DICER1-related tumors including ASK were enrolled in the International Pleuropulmonary Blastoma/DICER1 Registry. Additionally, a comprehensive review of reported cases of ASK was undertaken, and data were aggregated for analysis with the aim to identify prognostic factors and clinical characteristics to guide decisions regarding genetic testing, treatment, and surveillance. Ten cases of ASK were identified in the Registry along with 37 previously published cases. Staging data, per Children's Oncology Group guidelines, was available for 40 patients: 13 were stage I, 12 were stage II, 10 were stage III, and five were stage IV. Outcome data were available for 37 patients. Most (38 of 46) patients received upfront chemotherapy and 14 patients received upfront radiation. Two-year event-free survival (EFS) for stage I-II ASK was 81.8% (95% confidence interval [CI]: 67.2%-99.6%), compared with 46.6% EFS (95% CI: 24.7%-87.8%) for stage III-IV (p=.07). Two-year overall survival (OS) for stage I-II ASK was 88.9% (95% CI: 75.5%-100.0%), compared with 70.0% (95% CI: 46.7%-100.0%) for stage III-IV (p=.20). Chemotherapy was associated with improved EFS and OS with hazard ratios of 0.09 (95% CI: 0.02-0.31) and 0.08 (95% CI: 0.02-0.42), respectively. ASK is a rare DICER1-related renal neoplasm. In the current report, we identify clinical and treatment-related factors associated with outcome including the importance of chemotherapy in treating ASK. Ongoing data collection and genomic analysis are indicated to optimize outcomes for children and adults with these rare tumors.

Bystanders Saving Lives with Naloxone: A Scoping Review on Methods to Estimate Overdose Reversals.

People who use drugs in community settings are at risk of a fatal overdose, which can be mitigated by naloxone administered via bystanders. In this study we sought to investigate methods of estimating and tracking opioid overdose reversals by community members with take-home naloxone (THN) to coalesce possible ways of characterizing THN reach with a metric that is useful for guiding both distribution of naloxone and advocacy of its benefits. We conducted a scoping review of published literature on PubMed on August 15, 2022, using PRISMA-ScR protocol, for articles discussing methods to estimate THN reversals in the community. The following search terms were used: naloxone AND ("take home" OR kit OR "community distribution" OR "naloxone distribution"). We used backwards citation searching to potentially find additional studies. Overdose education and naloxone distribution program-based studies that analyzed only single programs were excluded. The database search captured 614 studies, of which 14 studies were relevant. Backwards citation searching of 765 references did not reveal additional relevant studies. Of the 14 relevant studies, 11 were mathematical models. Ten used Markov models, and one used a system dynamics model. Of the remaining three articles, one was a meta-analysis, and two used spatial analysis. Studies ranged in year of publication from 2013-2022 with mathematical modeling increasing in use over time. Only spatial analysis was used with a focus on characterizing local naloxone use at the level of a specific city. Of existing methods to estimate bystander administration of THN, mathematical models are most common, particularly Markov models. System dynamics modeling, meta-analysis, and spatial analysis have also been used. All methods are heavily dependent upon overdose education and naloxone distribution program data published in the literature or available as ongoing surveillance data. Overall, there is a paucity of literature describing methods of estimation and even fewer with methods applied to a local focus that would allow for more targeted distribution of naloxone.

Development and Acceptability of Web-based Module in Cookery

This study delves into the development and acceptance of a web-based cookery module, aiming to enhance culinary education, particularly in the face of challenges such as the pandemic. These modules offer promising avenues for effective learning experiences and the promotion of self-regulated learning among students. Employing a mixed-method approach utilizing the Input-Process-Output design model, the study involves the validation of the developed module by eight expert practitioners in cookery. Subsequently, its acceptability will be assessed among Senior High School (SHS) Technical-Vocational-Livelihood (TVL) students enrolled in cookery subjects during the academic year 2023-2024. Evaluation of the module by teacher experts utilizes a four-point rating scale, drawing from the Guidelines and Processes for Learning Resource Management and Development System (LRMDS) Assessment & Evaluation – Evaluation Rating Sheet for Non-Print Materials (DepEd, 2009), focusing on content quality, instructional quality, technical quality, and other pertinent factors. Similarly, student feedback is gathered through a five-point scale adapted from Venkatesh et al. (2003) and modified by Namoco, S. (2021) to align with the Unified Theory of Acceptance and Use of Technology (UTAUT) model, offering both rating scale responses and descriptive interpretations. Both teacher experts and student users are purposefully selected for their insights. Initial findings from the expert evaluation indicate a high recommendation for implementing the web-based module in cookery education. However, ongoing data collection and analysis are underway to gauge student-user acceptability comprehensively. This study underscores the significance of well-designed interactive learning modules in fostering self-regulated learning and enhancing student performance in cookery subjects, notwithstanding the challenges posed by the pandemic and economic constraints.

A Balancing Act: Data Protection Compliance of Artificial Intelligence

Abstract Neural network based generative artificial intelligence (GenAI) systems, in particular large language models (LLMs), hold huge potential for economic, scientific, and artistic progress. However, they are also the subject of ongoing fierce data protection debates. Some even doubt whether GenAI systems can, at least in principle, comply with the General Data Protection Regulation (EU) 2016/679 (GDPR). This issue was highlighted by a temporary ban of ChatGPT by the Italian data protection authority in March 2023. To answer the question of possible compliance with the GDPR, this paper will first illustrate relevant technical aspects and then examine the extent to which GenAI systems process personal data. A distinction will be made between training, use, and the system itself as stored on a hard drive. On this basis, this paper addresses the key question of the lawfulness of the respective processing activities, bearing in mind that each specific use case of any GenAI system requires a specific data protection assessment. While the issues discussed in this paper are relevant to GenAI systems in general, they are particularly relevant to LLMs trained on large amounts of text-based personal data. As one result, the analysis identifies serious challenges in the application of the GDPR to LLMs. However, with no significant updates to the relevant GDPR provisions in sight, this paper aims to show how pragmatic solutions are both necessary and largely possible even under the current legal framework. This includes practical guidance for developers and users on how to ensure compliance.

The Tasmanian Emergency Care Outcomes Registry (TECOR) Protocol

Emergency Departments (ED) play a vital role within the health system, representing the ‘front door’ to hospitals, the first point of hospital contact for patients who are undifferentiated and may be critically ill. They also serve as a safety net for the healthcare system. Together with ED overcrowding, this patient care environment is highly vulnerable to the provision of suboptimal care and breaches in patient safety. Government agencies in Australia currently collect data that are broad and administratively focused and are limited in capacity to identifying clinical quality. Clinical quality registries (CQR) help fill this gap but are often funded by not-for-profit organisations or research grants. There is no emergency care CQR in Tasmania, Australia. We propose the establishment of the Tasmanian Emergency Care Outcomes Registry (TECOR) to monitor emergency care processes and outcomes. The primary objective of TECOR is to monitor the unexpected 30-day mortality of patients who are cared for in the ED as well as 30-day safety events where emergency care was the primary contributor. The TECOR is expected to provide ongoing data on other important processes of emergency care in Tasmania such as length of stay in EDs, 28-day representation to EDs and hospital length of stay. The registry was designed to national standards and will meet the needs of the clinical community and have a positive impact on the communities it serves.

Testing meson portal dark sector solutions to the MiniBooNE anomaly at the Coherent CAPTAIN Mills experiment

A solution to the MiniBooNE excess invoking rare three-body decays of the charged pions and kaons to new states in the MeV mass scale was recently proposed as a dark-sector explanation. This class of solution illuminates the fact that, while the charged pions were focused in the target-mode run, their decay products were isotropically suppressed in the beam-dump-mode run in which no excess was observed. This suggests a new physics solution correlated to the mesonic sector. We investigate an extended set of phenomenological models that can explain the MiniBooNE excess as a dark sector solution, utilizing long-lived particles that might be produced in the three-body decays of the charged mesons and the two-body anomalous decays of the neutral mesons. Over a broad set of interactions with the long-lived particles, we show that these scenarios can be compatible with constraints from LSND, KARMEN, and MicroBooNE, and evaluate the sensitivity of the ongoing and future data taken by the Coherent CAPTAIN Mills experiment to a potential discovery in this parameter space. Published by the American Physical Society 2024

DETERMINANTS OF THE MORTALITY OF PATIN FISH IN TEMERLOH, PAHANG, MALAYSIA

This study explores the factors influencing Patin fish mortality in Malaysia's expanding aquaculture industry, which is crucial for meeting the rising global demand for fish and seafood. Analysing data from 135 fish farmers through SPSS Software, it finds significant correlations between mortality rates and variables like fish species, time until sale, and fish quantity per cage. At the same time, factors such as partnership numbers and feeding frequency have minimal impact. These results highlight the critical role of water quality management in fish health and production costs. The findings are vital for developing strategies to improve fish farming and water quality control in Malaysia, addressing the need to consider various factors to reduce fish mortality. Despite the significance of certain variables, the low adjusted R-squared value points to other yet unidentified factors affecting fish deaths, suggesting ongoing data collection and model refinement for stakeholders. This research contributes to understanding aquaculture costs and fish health, informing theories such as Interactive Governance Theory, Stress Response Theory, and Disease Ecology Theory and underscoring the importance of comprehensive strategies for sustainable aquaculture practices.

A Universal Indicator for Assessing the Ease of Humans Learning Wildlife Behavior

Understanding wildlife behavior is crucial for effective conservation and management. However, studying the behavior of diverse species presents challenges due to their complexity and the availability of data. To address this, we present a universal indicator for assessing the ease of humans learning wildlife behavior. This indicator incorporates species familiarity, behavioral complexity, and data availability, providing a standardized framework for evaluating learnability. Applying the indicator to a diverse range of species reveals insights into research priorities and knowledge gaps. The indicator enables researchers, educators, and policymakers to prioritize efforts, enhance conservation strategies, and facilitate effective wildlife management and education initiatives. Its application has the potential to contribute to a more comprehensive understanding of wildlife behavior on a global scale. While the indicator is a valuable tool, its limitations necessitate ongoing data collection and refinement. The universal indicator advances our understanding of wildlife behavior and informs evidence-based conservation and management strategies.

Abstract PO2-06-13: Promising clinical performance of 89Zirconium-labelled Girentuximab PET-CT for imaging metastatic triple negative breast cancer patients (OPALESCENCE)

Abstract Aim: Triple Negative Breast Cancer (TNBC) is aggressive, often with a metastatic evolution and drug-resistant with limited therapeutic options. Evaluating new markers is an unmet need. Recently, the combination of anti-angiogenic and targeted hypoxia effectors agents proved to enhance therapy response. Indeed, anhydrase Carbonic-IX (CA-IX), a hypoxia-mediated breast tumor growth regulator, is important for the BC stem cells maintenance within hypoxic region and is highly overexpressed in TNBC. This pilot prospective study “OPALESCENCE” (NCT04758780) aimed at assessing PET/CT with 89Zr-labeled girentuximab (89Zr-TLX250) targeting CA-IX in 12 metastatic TNBC patients. Methods: Patients underwent FDG and 89Zr-TLX250 PET-CT and conventional imaging (CI) if needed (CT, US, mammography, brain MRI). Without any premedication or dietary preparation, patients received a single slow intravenous administration of 37±10% MBq 89Zr-TLX250 (10 mg). Day 3 or 5 post injection, a skull to mid-thigh PET/CT was acquired with 10 minutes acquisition time per bed position. The gold standard was determined by FDG PET/CT, CI and follow-up; lesion detected at least by 2 modalities was considered as true positive. Immunohistochemistry (IHC) was performed with Bond RX fully automated research stainer with CA-IX antibody (Leica, clone TH22). Staining was evaluated with semi-quantitative analysis (percentage and intensity of tumor cells expression). Human anti-chimeric antibody (HACA) were sampled but will be determined at study end. Results: Enrolment has been completed, a total of 273 lesions confirmed by gold standard as shown on table 1 were detected in 12 patients (231 by 89Zr-TLX250 and 264 by FDG PET/CT). Overall sensitivity of 89Zr-TLX250 PET/CT was 87.5%, with 100% sensitivity for breast, skin, adrenal gland and brain and 88.0%, 91.9% for nodes and bone respectively. Overall sensitivity for FDG-PET/CT was 96.7%. According to table 2, 6 patients had 100% of their lesions highlighted by 89Zr-TLX250 PET. In addition, for 2 other patients only one of the lesions was not detected by immunoPET. 89Zr-TLX250 PET therefore detected almost all of the metastatic lesions in 67% of the patients. For 8/12 patients, IHC was analysed and for 6 patients, CA-IX expression lesions was from 100% to 10% with an intensity from 3+ to 2+, whereas two patients presented no Ca-IX expression on tumour lesions. No 89Zr-TLX250 safety issue was reported. Conclusion: 89Zr-TLX250 PET/CT seems very promising because it allows the CA IX status lesions knowledge on whole body scale with a minimally invasive way, unlike the information provided by biopsies corresponding to only 1 or 2 lesions studied. Moreover, these results illustrated interest of 89Zr-TLX250 PET/CT as targeting agent for TNBC patients leading above all to a theranostic approach possibility. Study analysis (specially IHC, HACA and semi-quantitative PET/CT analysis) is ongoing and supplementary data will be presented during the congress. This is an investigator initiated trial. Investigational medicinal product was provided by Telix Pharmaceuticals. Table 1: Sensitivity of 89Zr-TLX250 PET, FDG PET, and conventional imaging (US, brain MRI and Mammography). Table 2: Number of confirmed lesions according to Gold Standard detected by 89Zr-TLX250 PET/CT (iPET), FDG PET/CT and CI for each patients. Citation Format: Caroline Rousseau, Marie Francoise Heymann, Jean Sebastien FRENEL, Elise Picot-Dilly, Maelle Le Thiec, Manon Taupin, Alexis Mouton, Emmanuelle Bourbouloux, Agnès Morel, Nadia Allam, Amélie Mallet, Mario Campone, Ludovic Ferrer, Françoise Kraeber-Bodéré. Promising clinical performance of 89Zirconium-labelled Girentuximab PET-CT for imaging metastatic triple negative breast cancer patients (OPALESCENCE) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-06-13.

Genetic counseling access and service delivery in New York State is variable for parents of infants with complex CFTR genotypes conferring uncertain phenotypes.

New York State (NYS) utilizes a three-tiered cystic fibrosis newborn screening (CFNBS) algorithm that includes cystic fibrosis transmembrane conductance regulator (CFTR) gene sequencing. Infants with >1 CFTR variant of potential clinical relevance, including variants of uncertain significance or varying clinical consequence are referred for diagnostic evaluation at NYS cystic fibrosis(CF) Specialty Care Centers (SCCs). As part of ongoing quality improvement efforts, demographic, screening, diagnostic, and clinical data were evaluated for 289 CFNBS-positive infants identified in NYS between December 2017 and November 2020 who did not meet diagnostic criteria for CF and were classified as either: CFTR-related metabolic syndrome/CF screen positive, inconclusive diagnosis (CRMS/CFSPID) or CF carriers. Overall, 194/289 (67.1%) had CFTR phasing to confirm whether the infant's CFTR variants were in cis or in trans. Eighteen complex alleles were identified in cis; known haplotypes (p.R117H+5T, p.F508del+p.L467F, and p.R74W+p.D1270N) were the most common identified. Thirty-twoinfants (16.5%) with all variants in cis were reclassified as CF carriers rather than CRMS/CFSPID. Among 263 infants evaluated at anNYS SCC, 70.3% were reported as having received genetic counseling about their results by any provider, with 96/263 (36.5%) counseled by a certified genetic counselor. Given the particularly complex genetic interpretation of results generated by CFNBS algorithms including sequencing analysis, additional efforts are needed to ensure families of infants with a positive CFNBS result have CFTR phasing when needed to distinguish carriers from infants with CRMS/CFSPID, and access to genetic counseling to address implications of CFNBS results.

Abstract PS12-09: Capivasertib plus cyclin-dependent kinase 4/6 inhibitor and fulvestrant in hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: updated Phase 1b analysis from CAPItello-292

Abstract Background AKT pathway activation is implicated in endocrine therapy (ET) and cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) resistance in patients (pts) with HR+/HER2– advanced breast cancer (ABC). In CAPItello-291, capivasertib (C, a potent inhibitor of all 3 AKT isoforms) + fulvestrant (F) significantly improved PFS versus placebo F in pts with aromatase inhibitor-resistant HR+/HER2– ABC. Simultaneous inhibition of AKT and CDK4/6 pathways may delay CDK4/6i resistance or re-sensitize tumors to ET plus CDK4/6i, leading to improved clinical outcomes. CAPItello-292 (NCT04862663) is an ongoing Phase 1b/3 study examining the efficacy and safety of C + CDK4/6i (palbociclib [P], ribociclib [R]) + F in HR+/HER2– ABC. The recommended Phase 3 dose (RP3D) of C+P+F has been determined (C 400 mg BID, 4 days on/3 days off, P 125 mg, F 500 mg). Here we report ongoing Phase 1b data on C+P+F and C+R+F. Methods: Phase 1b of CAPItello-292 uses a keyboard design (mTPI-2) with the following planned doses: C 200 mg, 320 mg, 400 mg; P 75 mg, 100 mg, 125 mg; R 200 mg, 400 mg, 600 mg; F is fixed at 500 mg every 28 days + loading dose on cycle 1 day 15. Starting doses for C+P+F were C 320 mg BID, 4 days on/3 days off, P 125 mg QD) for 21 days of each 28-day cycle. Starting doses for C+R+F (ongoing) are C 400 mg BID, 4 days on/3 days off, R 400 mg QD for 21 days of each 28-day cycle. Eligible pts have HR+/HER2− ABC and ≥1 prior ET in the advanced setting or disease recurrence within 12 months of completing (neo)adjuvant ET (HER2− defined as immunohistochemistry [IHC] 0, or 1-positive or IHC2-positive/in situ hybridization-negative). Prior use of CDK4/6i, selective estrogen receptor degraders, and chemotherapy is permitted in Phase 1b. Phase 1b primary objectives: assess safety/tolerability; confirm RP3D. Objective response and clinical benefit rates (24 weeks; RECIST v1.1) were also assessed. Results: At data cut-off (Apr 21, 2023), 40 pts (median age: 58.5 years [range 38–82]) who were heavily pre-treated (as follows: 82.5% [33/40] prior CDK4/6i; 47.5% [19/40] prior F; 70.0% [28/40] prior chemotherapy [median 1.5 lines]) were treated with C+P+F. No new dose-limiting toxicities (DLTs) were observed since determination of RP3D. The most frequent adverse events (AEs) occurring in >40% of pts were diarrhea (70.0% [28/40]; 1/28 grade [G] ≥3), neutropenia (55.0% [22/40]; 20/22 G≥3), fatigue, and nausea (both 42.5% [17/40]; all G1/2). Hyperglycemia occurred in 17.5% (7/40) pts (1/7 G3). No treatment-related deaths or new safety risks were identified. At the RP3D, the median (range) duration of exposure to C was 8.6 months (1.7–14.1); 5/8 pts with measurable disease at baseline had confirmed partial response (objective response rate: 62.5%, 95% confidence interval [CI] 24.5–91.5). Two additional pts had stable disease ≥7 weeks as a best objective response. At 24 weeks, the clinical benefit rate was 53.8% (7/13; 95% CI 25.1–80.8).Enrollment into C+R+F is ongoing: as of May 05, 2023, 8 pts had been dosed (6/8 pts had completed cycle 1). Based on clinical and safety review, the safety review committee has endorsed dose escalation to the highest dose level of R; no DLTs have been reported so far, although data are preliminary.Preliminary ctDNA analyses of pts treated with C+P/R+F will be presented. Conclusions: C+P+F was tolerable in heavily pre-treated pts with HR+/HER2– ABC at all dose levels; AEs were as expected, given the known safety profile of the individual treatments. Evidence of clinical activity has been observed in pts treated with the RP3D; data collection is ongoing. Preliminary safety analysis of C+R+F suggests no critical tolerability concerns; more pts and longer follow-up is required to characterize the safety of the combination. Updated data will be presented. Funding: AstraZeneca Capivasertib was discovered by AstraZeneca subsequent to a collaboration with Astex Therapeutics (and its collaboration with the Institute of Cancer Research and Cancer Research Technology Limited) Citation Format: Erika Hamilton, Patrick Neven, Barbara Pistilli, Muralidhar Beeram, Virginia Borges, Mario Campone, José Luiz Miranda Guimarães, Theodoros Foukakis, Annette Raskov Kodahl, Peter Lau, Elgene Lim, Iwona Ługowska, Greg Rychlik, Christopher Gresty, Claire Miller, Roberto Sommavilla, Dhivya Sudhan, Hope Rugo. Capivasertib plus cyclin-dependent kinase 4/6 inhibitor and fulvestrant in hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: updated Phase 1b analysis from CAPItello-292 [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS12-09.

ENHANCING ELECTIVE SURGERY MANAGEMENT WITH OPENPREDICTOR: VALIDATION OF A CLINICAL DECISION AID FOR OPTIMIZING ELECTIVE PATHWAYS

OpenPredictor, a machine learning-enabled clinical decision aid, has been developed to manage backlogs in elective surgeries. It aims to optimise the use of high volume, low complexity surgical pathways by accurately stratifying patient risk, thereby facilitating the allocation of patients to the most suitable surgical sites. The tool augments elective surgical pathways by providing automated secondary opinions for perioperative risk assessments, enhancing decision-making. Its primary application is in elective sites utilising lighter pre-assessment methods, identifying patients with minimal complication risks and those high-risk individuals who may benefit from early pre-assessment.The Phase 1 clinical evaluation of OpenPredictor entailed a prospective analysis of 156 patient records from elective hip and knee joint replacement surgeries. Using a polynomial logistic regression model, patients were categorised into high, moderate, and low-risk groups. This categorisation incorporated data from various sources, including patient demographics, co-morbidities, blood tests, and overall health status.In identifying patients at risk of postoperative complications, OpenPredictor demonstrated parity with consultant-led preoperative assessments. It accurately flagged 70% of patients who later experienced complications as moderate or high risk. The tool's efficiency in risk prediction was evidenced by its balanced accuracy (75.6%), sensitivity (70% with a 95% confidence interval of 62.05% to 76.91%), and a high negative predictive value (96.7%).OpenPredictor presents a scalable and consistent solution for managing elective surgery pathways, comparable in performance to secondary consultant opinions. Its integration into pre-assessment workflows assists in efficient patient categorisation, reduces late surgery cancellations, and optimises resource allocation. The Phase 1 evaluation of OpenPredictor underscores its potential for broader clinical application and highlights the need for ongoing data refinement and system integration to enhance its performance.

Abstract PO1-20-08: Primary breast implant-associated squamous cell carcinoma with subsequent TEMPUS testing and failure of immunotherapy

Abstract Primary squamous cell carcinoma of the breast is a rare entity, and there are a limited number of cases in the literature describing squamous cell carcinoma arising from breast implants. It has been hypothesized that these implant-associated cancers may arise from epithelialization of the implant capsule followed by chronic inflammation. None of the cases in the literature were treated with immunotherapy. We present a case of an aggressive, primary sarcomatoid squamous cell carcinoma of the breast arising from a breast implant that was treated unsuccessfully with simultaneous chemotherapy and immunotherapy following TEMPUS testing. Introduction: Breast augmentation is the most common plastic surgery procedure performed worldwide, with more than 300,000 done in the United States every year. While breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is extensively discussed in recent literature, other breast implant-associated cancers are rarer and less studied. Breast implant-associated squamous cell carcinoma (BIA-SCC) specifically is an extremely rare complication of breast augmentation and no guidelines for treatment exist. The American Society of Plastic Surgeons (ASPS) released a statement on BIA-SCC on 9/2022 following a safety communication from the FDA, and it is recommended health care providers submit case reports of BIA-SCC to a patient registry. Case study: We present the case of a female patient who underwent bilateral breast augmentation in 2006 with Mcghan textured, pre-pectoral, areolar saline implants. In 2022, she presented with swelling and a lump in her breast and underwent bilateral breast implant removal with capsulectomy. Pathology showed triple negative sarcomatoid squamous cell carcinoma of the right breast capsule. TEMPUS testing on the breast biopsy revealed a PIK3CA mutation and PD-L1 negative status. Her case was discussed with a multi-disciplinary team including plastic surgery, multiple oncologists, and radiation oncology and her clinical picture was determined to be most consistent with BIA-SCC. Based on the KEYNOTE-522 study, she was determined to be a candidate for neoadjuvant therapy with pembrolizumab and chemotherapy as she was newly diagnosed, previously untreated, nonmetastatic, and had a triple negative tumor. She received two cycles of carboplatin, paclitaxel, and pembrolizumab but unfortunately rapidly progressed with chest wall extension, multiple new pulmonary nodules, worsening lymphadenopathy, right ventricular tumor thrombus, and new malignant pleural effusion and was transitioned to hospice. Discussion: Seven cases of BIA-SCC, one case of squamous cell carcinoma (SCC) after liquid silicone injection augmentation, one case of squamous metaplasia on the breast implant capsule, and one case of epithelization of the breast implant capsule have been previously described in the literature (Table 1). None of the available cases of BIA-SCC report TEMPUS testing, and none of the patients were treated with immunotherapy. The origin of BIA-SCC is unclear, but several theories have been described including chronic inflammation leading to conversion of epithelial tissue on the capsule to SCC. It is unknown how the breast implant capsule might become epithelialized to begin with – introduction of epithelium intraoperatively during augmentation, rupture of epidermal cysts, existence of epithelium in the area from a childhood injury or from birth, or epithelization from chronic shear forces from the augmentation or leakage of the implant are all possibilities. With the ongoing data gathering through the FDA patient registry, we will continue to learn more about these rare cancers and potentially get further insight into their origins. Table 1 An overview of cases of BIA-SCC in the literature Citation Format: Emily Podany, Katherine Clifton. Primary breast implant-associated squamous cell carcinoma with subsequent TEMPUS testing and failure of immunotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-20-08.

Childhood internalizing, externalizing and attention symptoms predict changes in social and nonsocial screen time.

While accumulating research has tested the hypothesis that screen time causes psychiatric symptoms in children, less attention has been paid to the hypothesis that children with psychiatric symptoms change their patterns of screen time and digital media use. We aimed to test whether children with psychiatric symptoms subsequently change their patterns of screen time and digital media use. N = 9,066 children primarily aged 9-10 in the Adolescent Brain Cognitive Development Study at baseline and 1-year later. Psychiatric symptoms included internalizing, attention, and externalizing symptoms. Screen time was measured as ordinally defined weekday and weekend time on social and nonsocial [e.g., YouTube] digital media). Models assessed psychiatric symptoms as predictors of screen time, and screen time as predictors of psychiatric symptoms, controlled for baseline measures of each, sex, age, race/ethnicity, and income. Children with psychiatric symptoms spent more time on non-social media one year later compared with peers. Considering total psychiatric problems, clinical levels of problems predicted higher levels of weekday (OR = 1.22, 95% CI 1.22-1.23) and weekend (OR = 1.10, 95% CI 1.09-1.11) nonsocial screen time. For nearly all analyses of psychiatric symptoms predicting screen time, associations were highest for a non-social screen time outcome rather than a social screen time outcome (Highest OR = 1.65, 95% CI 1.63-1.67, clinical rule breaking predicting weekday nonsocial screen time). Comparable magnitude associations were observed for social and nonsocial media use predicting future psychiatric symptoms, suggesting bidirectionality. Children with psychiatric symptoms have different subsequent media use patterns, including higher rates of subsequent nonsocial engagement. Ensuring that ongoing data collection and analysis efforts attend to temporality and transitions in the relation between media use and psychiatric symptoms will accelerate progress in the field.

The potential of classroom video recordings in detecting the TA-to-pupil, teacher-to-TA and peer interactions: An overview

Technology in the classroom comes in many shapes to differentiate instruction, create meaningful learning experiences, actively engage the learners, or inform about classroom exchanges. Video recordings are no exception. They facilitate the investigation of classroom interactions and the collection of audio-visual data that provide further insights into the teaching practice and classroom dynamics. Previous education research has almost turned a blind eye to uncovering the intricacies of elementary classroom behavior and interactions through the medium of modern technologies. Only scattered attempts have brought to bear the issue. To this end, this paper presents an overview of the salient role of digital technologies, mainly video materials, in clarifying the different interactions that take place within the confines of the classroom, including teacher-to-teaching assistant (TA) relationships, teacher-aide-to-pupil interactions, and peer-to-peer interaction drawing on an ongoing data collection from elementary schools around Hradec Králové (HK) region in the Czech Republic. Classroom recordings might be a fountainhead for detailed, reflective analysis, enhanced communication among all participants, and better teaching-learning practice if used properly. The first part of the paper reviews some related definitions based on several previous theoretical grounds. Then, it highlights the peculiar classroom interactions aided by various analytic angles. Deeply rooted in education research, these dynamics are indebted to the presence of audio and visual records. Most importantly, the paper is built around the research endeavor by researchers at the University of HK, mainly the Faculty of Education, that aims at getting down to brass tacks of TAs interactions by means of technological intervention in data collection (video recordings) and measurement (Flanders et al. – FIAS). Keywords: Video recordings, TA-to-Pupil interaction, Teacher-to-TA interaction, elementary schools, Flanders Interaction Analysis System

An Empirical Study on Cybersecurity Awareness, Cybersecurity Concern, and Vulnerability to Cyber-attacks

The research aimed to delve into the landscape of cybersecurity awareness and concern levels within Punjab, India, shedding light on the specific demographic groups most susceptible to cyber-attacks. Through meticulous survey administration and data analysis, the study pinpointed a noteworthy vulnerability: young adult females aged 18 to 29 residing in rural Punjab, particularly those either engaged in student pursuits or currently unemployed. This demographic emerged as disproportionately prone to cyber threats. Highlighting the gravity of this finding, the research underscores the urgency for tailored interventions to fortify the cyber defenses of this vulnerable population segment. A crucial facet of this approach involves the development of a prototype aimed at augmenting cybersecurity awareness and fostering ethical online conduct among the identified demographic. This prototype seeks to serve as a platform for delivering enhanced training modules tailored to the unique needs and challenges faced by young females in rural Punjab. Moreover, the paper delineates a comprehensive roadmap for the implementation and evaluation of these recommendations. Central to this plan is the deployment of an application based on the proposed prototype, designed to facilitate the delivery of targeted cybersecurity education and gauge its efficacy in bolstering cyber resilience among the identified demographic. This research not only illuminates the cybersecurity landscape in Punjab but also charts a proactive course of action aimed at mitigating vulnerabilities and empowering at-risk populations through informed intervention strategies. Through ongoing data collection and evaluation efforts, the efficacy of these interventions will be rigorously assessed, driving iterative refinement and optimization of cybersecurity initiatives tailored to the unique needs of Punjab's populace.

Standardizing eligibility and patient selection for Pressurized Intraperitoneal Aerosol Chemotherapy: A Delphi consensus statement

IntroductionPressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is a procedure for minimally invasive drug administration in patients with peritoneal metastasis. Previous studies have emphasized the importance of uniformity in treatment protocols and standardization of this practice. This study aimed to reach a consensus on eligibility, patient selection, and choice of chemotherapy for PIPAC. MethodsA three-round modified Delphi study was conducted. A steering group formulated a list of baseline statements, addressing the objectives. The steering group consisted of seven expert surgical and medical oncologists. Available evidence and published key opinions were critically reviewed. An international expert panel scored those statements on a 4-point Likert scale. The statements were submitted electronically and anonymously. Consensus was reached if the agreement rate was ≥75%. A minimum Cronbach's alpha of >0.8 was set. ResultsForty-five (45/58; 77.6%) experts participated and completed all rounds. Experts were digestive surgeons (n = 28), surgical oncologists (n = 7), gynecologists (n = 5), medical oncologists (n = 4), and one clinical researcher. Their assessment of 81 preliminary statements in the first round resulted in 41 consolidated statements. In round two, consensus was reached on 40 statements (40/41; 97.6%) with a consensus of ≥80% for each individual statement. In the third round, 40 statements were unanimously approved as definitive. The choice of first- and second-line chemotherapy remained controversial and could not reach consensus. ConclusionsThis International Delphi study provides practical guidance on eligibility and patient selection for PIPAC. Ongoing trial data and long-term results that could contribute to the further standardization of PIPAC are eagerly awaited.

A Comprehensive Review of Security Measures and Implementation Challenges in Cloud Computing

Cloud computing has emerged as a cornerstone technology in the IT industry, transforming industries by providing flexible, scalable computing resources but the widespread adoption of cloud services has raised serious data security and privacy concerns. Cybercriminals always pose a threat by targeting sensitive information stored on cloud servers. To mitigate these risks, cloud encryption has emerged as an important safeguard, aiming to protect users data from unauthorized service providers against them and against unauthorized malicious hackers This paper examines the ongoing data security issues associated with cloud computing and analyzes the features and structures of cloud encryption. By examining complex approaches to cloud cryptography including encryption, key management and access control, this paper aims to provide insights into how these technologies can shape the security level of cloud-based systems confidentiality, integrity and availability are maintained, ensuring trust and confidence in cloud computing ecosystems

Abstract CT099: NGM707 in combination with pembrolizumab in advanced or metastatic solid tumors: Preliminary results from dose escalation

Abstract BACKGROUND: NGM707-IO-101 (NCT04913337) is a Phase 1/2, dose escalation/expansion study evaluating NGM707, a humanized monoclonal antibody that blocks ILT2 and ILT4 receptors, as monotherapy or in combination with pembrolizumab. Here we report data from the combination part of the study. METHODS: Eligible patients (pts) with advanced/metastatic solid tumors were enrolled into escalating dose cohorts of 200-1800 mg NGM707 combined with 200 mg pembrolizumab, administered Q3W iv. Assessment of safety and tolerability and recommended expansion doses for NGM707 in combination with pembrolizumab were the primary objectives of the study. Secondary and exploratory objectives included assessment of pharmacokinetics/receptor occupancy (RO), immunogenicity, biomarkers, and preliminary antitumor activity per RECIST v1.1. RESULTS: As of 06 Nov 2023, 46 pts have been enrolled in the combination escalation at dose levels up to 1800 mg; 5 pts crossed over from monotherapy. Median age 58.5 yrs [28-81]; ECOG PS 0 (19.6%), 1 (80.4%). Pts had received a median of 3 prior therapies (range 1-6) and all pts had metastatic disease. Overall, 20/45 pts had prior exposure to anti-PD1/anti-PD-L1. Treatment-related adverse events (any grade/grade ≥3) occurred in 41.3%/4.4% of pts. The most common treatment-related adverse events were fatigue (17.4%), diarrhea (6.5%), myalgia (4.3%), arthralgia (4.3%), and nausea (4.3%). No dose-limiting toxicities were observed. A maximum tolerated dose was not reached, and the maximum administered dose was 1800 mg NGM707 in combination with 200 mg pembrolizumab. Peripheral immune cells showed dose-dependent RO, with doses ≥ 200 mg maintaining ILT2 and ILT4 RO for the entire dosing interval. PK of NGM707 was typical for monoclonal antibodies, with a half-life of 12.8 days. Gene expression changes associated with myeloid cell and T cell activation were observed in tumor biopsies post-treatment. Of 37 response-evaluable pts, best overall responses to date are PR (confirmed) in 4 pts, SD in 12 pts, representing a DCR of ~43%. Nine pts had reduced target lesion (TL) size with a maximum reduction of 100%. Out of the 4 patients who had PR, 3 patients were pre-treated with anti-PD1/anti-PD-L1. Two subjects with MSS CRC achieved confirmed PR, one of them with TL reduction that allowed subsequent surgical resection of all gross residual disease and confirmed pathological CR with no active tumor cells and ctDNA below detection. CONCLUSIONS: NGM707 in combination with pembrolizumab appears to be safe and well tolerated at all dose levels. In this advanced and metastatic solid tumor cohort, early efficacy signals have been observed. Preliminary evidence of myeloid cell reprogramming was observed in paired tumor biopsies. Trial enrollment for the expansion part of the study is ongoing and updated data will be presented in the future. Citation Format: Judy S. Wang, Manish R. Sharma, William J. Edenfield, Kartik Sehgal, Do-Youn Oh, Yixing Jiang, Joel Michalski, Jeeyun Lee, Hans Hammers, Li-Yuan Bai, Chih-Hung Hsu, Brenda Dampier, Kefei Zhou, Li Yan, Lisa K. Blum, Joanne Sloan-Lancaster, Daniel D. Kaplan, Dhiraj Abhyankar, Hsiao D. Lieu, Vladimir Hanes, Aung Naing. NGM707 in combination with pembrolizumab in advanced or metastatic solid tumors: Preliminary results from dose escalation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT099.

Abstract CT129: A phase 1 dose escalation study of a novel coupled CAR T cell therapy, GCC19CART, for patients with metastatic colorectal cancer

Abstract Background: GCC19CART, the first clinical candidate from the CoupledCAR solid tumor platform, is designed to overcome the limitations of conventional CAR T-cells in solid tumor malignancies by pairing solid tumor CAR T-cells with CD19-targeting CAR T-cells to amplify the proliferation and activation of the solid tumor CAR T component. GCC19CART targets guanylate cyclase-C (GCC), which is reported to be expressed in the metastatic lesions of 70%-80% of subjects with colorectal cancers and largely restricted to the intestinal tract. A Phase 1 investigator-initiated clinical trial conducted in China showed preliminary efficacy with an overall response rate (ORR) at dose level 1 (1x106 CAR T-cells/kg) of 15.4% ORR (2/13) and 50% ORR (4/8) in dose level 2 (2x106 CAR T-cells/kg). Common side effects included cytokine release syndrome (CRS) and diarrhea/colitis. Immune effector cell-associated neurotoxicity syndrome (ICANS) was seen in a smaller proportion of patients. A phase 1 study was initiated in the United States in August 2022 for patients with metastatic colorectal cancer refractory to standard of care chemotherapy. As of a data cutoff on ​November 1, 2023, 4 subjects have been treated in the initial dose level. Methods: Subjects were initially screened for GCC expression; this requirement was later discontinued when immunohistochemistry studies revealed that the frequency of positive GCC expression exceeded 95%. Eligible subjects underwent leukapheresis, a single dose of lymphodepleting chemotherapy (fludarabine 30mg/m2 and cyclophosphamide 300mg/m2) 3 days prior to infusion, and then administration of a single infusion of GCC19CART. Responses were assessed by RECIST v1.1 by site investigator review and an independent third-party imaging contract research organization. Results: 4 subjects have been dosed at level 1 (1x106 cells/kg) and completed the DLT period at the time of data cutoff. The most common adverse events were CRS in 4/4 subjects (Grade 1: 2/4 (50%) or Grade 2: 2/4 (50%)) and diarrhea in 3/4 subjects (Grade 1: 1/4 (25%), Grade 2: 1/4 (25%), or Grade 3: 1/4 (25%)). Three out of four patients had a mild tremor (Grade 1) that resolved with corticosteroids and no other evidence of neurotoxicity. The combined overall response rate (ORR) was 50% (2/4) by independent review. Two subjects demonstrated a partial response (PR) while 1 additional subject had partial metabolic response (PMR) on PET/CT with stable disease (SD) and 1 patient had progressive disease per RECIST 1.1. Per site investigator review, the ORR was 25%, with 1 confirmed PR and 3 SD assessed as best response. The median PFS was 3.8 months in the dose level 1 group. Conclusions: Preliminary results demonstrate that GCC19CART has meaningful clinical activity and an acceptable safety profile in refractory metastatic colorectal cancer. This trial is ongoing and updated data will be presented, including from patients treated at dose level 2 (2x106 CAR T-cells/kg). Clinical trial information: NCT05319314. Citation Format: Bridget P. Keenan, Christopher H. Lieu, Marwan Fakih, Dongqi Chen, Lucy Lu, Eric Rowinsky, Victor Lu, Lei Xiao, Alan P. Venook, Benjamin Schlechter. A phase 1 dose escalation study of a novel coupled CAR T cell therapy, GCC19CART, for patients with metastatic colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT129.