A Secure Transportation System (STS) improves traffic safety and enables vehicles to pass through non-congested routes. However, none of the prevailing works concentrated on protecting the data used for authorization in STS. Therefore, the secure authorization and Traffic Congestion Prediction (TCP) model is proposed. Initially, the user registers into blockchain and a key is generated using Koblitz Torus Curve Cryptography (KTCC). Then, the network is initialized and vehicle information is sensed, and then using KTCC, the data are secured. From the sensed data, the hash code is generated using Entropy Davies-Meyer Streebog (EDM-Streebog). Meanwhile, the vehicle's number-plates are detected using You Only Look Once-Version 8 (YOLOV8). Now, in the number-plate image, the watermarking is done to protect the hash code through R-squared Regression Discrete Wavelet Transform (R3-DWT). Next, the hash code is retrieved in the blockchain and the verification is processed. For the verified hash, the secured data are decrypted and TCP is done. To train the TCP model, the high traffic video data are collected and pre-processed. Then, the day/night frame is identified. Then, the image conversion of the night frame is done and along with the day frame, the vehicle detection in the frame is done by YOLOV8. From the vehicle detected image, the vehicle tracking is done and then using Elliott Deep Identity Convolutional Neural Network (EDICNN), the TCP is made. Thus, the congestion details are notified to users for secure transportation. The proposed work thus predicted the traffic congestion effectively with an accuracy of 98.0213%, and recall of 98.3024%.
Radioligand therapies have emerged as promising treatment modality for certain cancers. This therapeutic approach relies on a suitable tumor-targeting moiety labelled with a radioactive payload to allow the delivery of the radionuclide to cancer cells with high specificity. Due to its expression profile in tumor vs healthy tissues, MSLN is an attractive protein for targeted therapies. MSLN is a GPI-anchored membrane protein which is overexpressed in many tumor types, including ovarian cancer and pancreatic adenocarcinoma. Therapeutic approaches targeting MSLN have encountered obstacles due to the high levels of its proteolytically cleaved soluble form (sMSLN), which can sequester anti-MSLN therapeutics and potentially diminish their efficacy. To circumvent this caveat, we sought to generate a Designed Ankyrin Repeat Protein (DARPin) that binds to a membrane proximal epitope of MSLN and therefore avoids binding to sMSLN. Thanks to their small size and high affinity, DARPins are ideal vectors for targeted radiotherapies, dubbed as Radio-DARPin therapies (RDT). As radioactive payload we used 212Pb, an alpha particle-emitting radionuclide with a short half-life and a favorable decay profile which allows high energy deposition on tumor in a short time frame. Herein we report for the first time the development and initial preclinical characterization of our anti-MSLN 212Pb-RDT approach. In vitro assays revealed that the membrane proximal MSLN targeting DARPin specifically interacts with MSLN expressed on cancer cells with high affinity, and cell binding was not affected by the presence of sMSLN. The DARPin was then labelled with 212Pb and its preclinical pharmacokinetic and biodistribution profile was evaluated in MSLN-expressing xenograft tumor models. In these tumor bearing mice, the anti-MSLN 212Pb Radio-DARPin demonstrated substantial uptake into MSLN-positive tumors, while other organs only showed limited accumulation. We designed an approach to specifically target MSLN expressed on cancer cells employing DARPin technology combined with 212Pb. Our early preclinical results indicative of a favorable biodistribution profile of the 212Pb labelled MSLN DARPin motivate further development of this RDT for the treatment of patients with MSLN-positive solid tumors. Stephan Wullschleger,Amal Saidi,Delphine Buffet,Tania Stallons,Stefanie Riesenberg,Amy Wong,Maria Paladino,Federico Rojas,Mischa Müller,Christel Herzog,Justin Walter,Denis Villemagne,Yvonne Kaufmann,Nicole Pina,Henri Fernandez,Tamara Lekishvili,Eleni Tselempi,Jacqueline Blunschi,Liridon Abduli, Chloe Iss,Amelie Croset,Clara Domke,Aaron Schatzmann,Anne Goubier,Julien Torgue,Daniel Steiner. Development of 212Pb-based Radio-DARPin therapy (RDT) for the treatment of mesothelin (MSLN)-positive solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 339.
Radioligand therapy has shown strong clinical potential for the treatment of certain neuroendocrine and prostate tumors. Nevertheless, effective strategies in various cancer types are currently restricted by the lack of appropriate targeting agents for suitable tumor-associated antigens. Not expressed in healthy tissue, DLL3 is one of these promising targets highly upregulated in SCLC and other high-grade neuroendocrine tumors. Herein we present preclinical results of our DLL3-targeting 212Pb-based Radio-DARPin Therapeutic (RDT) combining the advantages of a small protein-based delivery vector and the short-lived alpha particle-emitting radioisotope 212Pb. Designed Ankyrin Repeat Proteins (DARPins) are a class of binding proteins with high specificity and affinity that can be generated against a broad range of tumor targets. Leveraging the learnings from our DARPin platform optimization allowed us to achieve efficient tumor uptake and penetration, while limiting exposure of healthy tissues. Our Radio-DARPin platform was optimized to effectively reduce DARPin uptake to kidneys, a major drawback of all small-size polypeptide vectors. This can be addressed by engineering the DARPin scaffold surface in conjunction with half-life extension (HLE) through serum albumin binding. 212Pb is a radioisotope with a short half-life of 11h and a favorable decay chain, allowing high energy deposition on tumor in a short time frame. By combining 212Pb with a HLE anti-DLL3 DARPin candidate, we aimed to generate a targeted RDT with high efficacy and a favorable safety profile. After several screening rounds of anti-DLL3-binding DARPins combined with HLE in mice, MP0712 was selected as lead candidate for further development. This molecule showed specific binding to lung cancer cells in vitro (∼2nM on NCI-H82 ± HSA) and high affinity to human DLL3 (0.2nM by Surface Plasmon Resonance). MP0712 biodistributions were assessed in different mouse xenograft tumor models, matching clinically relevant DLL3 expression levels or overexpression of DLL3, and reached tumor:kidney ratios >2. Double xenografted mouse models showed selective uptake in DLL3-expressing tumors compared with tumors not expressing DLL3, confirming high target specificity of MP0712. The anti-tumor activity of MP0712 in different mouse xenograft tumor models showed promising efficacy. MP0712 led to tumor stabilization and significant effects on tumor versus necrotic tissue. In NCI-H82 tumors, median survival duration increased up to 3-fold with MP0317 compared with the buffer control. MP0712 also showed a favorable safety profile in vivo up to 30µCi. These preclinical results support our 212Pb-based RDT against DLL3 as a promising treatment option for SCLC, with encouraging in vivo antitumor activity and a good safety profile for our first DLL3-targeting 212Pb-RDT candidate for further development into the clinic. Amelie Croset, Amal Saidi, Francesca Malvezzi, Tania Stallons, Madlaina Mettier, Amy Wong, Jitka Rantanen, Federico Rojas, Stephan Wullschleger, Eleni Tselempi, Yvonne Kaufmann, Tamar Lekishvili, Stefanie Riesenberg, Nicole Pina, Jacqueline Blunschi, Liridon Abduli, Christian Reichen, Christian Lizak, Aaron Schatzmann, Anne Goubier, Julien Torgue, Daniel Steiner. MP0712, the first anti-DLL3 212Pb radio-DARPin (RDT) candidate for targeted radiotherapy of small cell lung cancer (SCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 346.
Introduction The immunological etiology of the itch-related dermatoses, chronic spontaneous urticaria (CSU), atopic dermatitis (AD), and prurigo nodularis (PN), has led to the development of several targeted therapeutic strategies. This has created the need for dermatology clinicians to stay abreast of evolving care approaches. To meet this educational need, CMEsquared® developed a year-long curriculum encompassing educational initiatives on CSU, AD, and PN management. These initiatives were supported by independent medical educational grants from Genentech, a member of the Roche Group, Novartis Pharmaceuticals Corporation, and Sanofi and Regeneron Pharmaceuticals, Inc. Methods: Nine educational initiatives (5 CSU, 4 AD/PN) were launched between October 2024 and March 2025. The live, expert-led symposia occurred at the 2024 Fall Clinical Dermatology Conference® and 2025 Winter Clinical Dermatology Conferences®- Miami and Hawaii and were endured on Dermsquared.org for 12 months. Aggregate data on learner demographics, intended practice changes, and practice barriers were evaluated. Qualitative, thematic analysis of learner questions was performed using ChatGPT (OpenAI) and verified/adapted by the researchers. Results As of August 2025, 5,383 clinician learners participated in the live and endured activities. Across all activities, ‘Treatment’ changes were the top intended practice change, and subsequent qualitative, thematic analysis of learner questions related to CSU and AD/PN treatment revealed differences in clinician interests. CSU learners were most interested in stepwise treatment algorithms that clarify integration of standard-of-care antihistamines with novel systemic therapies, while AD/PN learners were primarily focused on appropriate selection of systemic therapies. In CSU, diagnosis, pathophysiology and comorbidities were also a priority. In AD/PN, learners were interested in differentiating both disorders, safety of systemic therapies, and patient counseling to address psychosocial burden. Conclusion Clinician education must be tailored to current clinical gaps for each dermatosis. The increasing role of dermatology clinicians as front-line treaters of CSU necessitates education on foundational knowledge and the place of systemic therapies in the current treatment paradigm. Conversely, clinicians’ longer-standing familiarity with AD and PN necessitates education about patient-centered approaches to care that are focused on improving quality of life.
Burnout is one of many contributing factors that lead to nurses and other medical staff leaving the bedside resulting in high turnover rates. In 2017, 31.5% of nurses who left bedside, left due to burnout. Additionally, over half of healthcare providers report burnout, which can impact stress, attendance, mood, productivity, and work quality. Animal-assisted support programs can assist in the reduction of burnout in providers. In previous studies, all patients and staff reported improved mood after interacting with a therapy dog. Currently there is limited research in the effect of animal-assisted support programs in the hospital setting specifically regarding burn providers and burnout. A voluntary study was sent out to the staff members on the Burn Trauma Intensive Care Unit and the Ortho/Trauma Unit. These units were selected due to the large number of burn patients who are admitted in these areas. The study collected basic demographic data and asked the providers to rate their mood at that time using a visual analog scale. Additionally, the providers were asked to complete the Copenhagen Burnout Inventory (CBI). The CBI scores burnout in three categories: personal burnout, work-related burnout, and client-related burnout. The survey was available for two weeks and. Following the survey, the therapy dog and handler completed 30-minute weekly visits to each unit. The visits occurred during day shift and the participants were asked to rate their mood prior to and after interacting with the therapy dog. Weekly visits continued for three months. The initial survey received 42 responses. At the time of data collection, 34 interactions had been completed and the providers mood increased by an average of 76%. A paired t-test determined statistical significance with a p value < 0.001. At the conclusion of the study, an additional survey will be sent out to the participants. This survey will collect the same data as the pre-survey along with the approximate number of interactions the staff member had with the therapy dog, and if they felt their mood would be increased if they knew a therapy dog would be available during their shift. Thus far the study has shown the staff’s mood improved immediately following the visit with the therapy dog. However, data is yet to be finalized to see if the therapy dog helps to decrease the burnout rates over time as indicated from the final CBI results. Scheduled visits with a therapy dog should be considered in burn units to improve staff mood and reduce caregiver burnout. N/A
