In this study, we synergistically integrate Ro5's target evaluation (SpectraView) and deep-learning-driven virtual screening (HydraScreen) tools with Strateos automated robotic cloud lab optimized for ultra high-throughput screening, to experimentally validate Ro5's tools. This integrated approach leads to a significant acceleration in the processes of target identification and hit discovery. By using SpectraView to select IRAK1 as the focal point of our investigation, we prospectively validate HydraScreen structure-based deep learning model. We can achieve the identification of an 23.8% of all IRAK1 hits within the top 1% of ranked compounds. HydraScreen also outperforms traditional virtual screening techniques and offers advanced features such as ligand pose confidence scoring. Simultaneously, we identify three potent (nanomolar) scaffolds from our compound library, two of which represent novel candidates for IRAK1 and hold potential for future development. Our platforms and innovative tools promise to expedite the early stages of drug discovery.
76 Background: Oncoplastic surgery has helped improve outcomes following partial mastectomy. However, in most cases, patients still require post-operative radiotherapy, which can cause significant complications. While recent advances have made it feasible to perform external beam radiation in a more targeted and accelerated fashion, these methods are not commonly used in the treatment of breast cancer. This is due to the difficulty in identifying the margins of the surgical site, and can be particularly challenging with oncoplastic surgery (OPS). In this pilot study, we evaluated a new method for marking the margins of the surgical cavity when using oncoplastic techniques. Methods: 15 patients were selected to have a 3-D tissue marker implanted at the time of lumpectomy. All patients were candidates for partial mastectomy, sentinel lymph node biopsy and breast reconstruction using OPS. Post-operative treatment plans including radiation and/or adjuvant chemotherapy were completed as recommended. Patients were followed and imaged with standard breast imaging following completion of their treatment. Results: The marker was easily identified and clearly delineated the margins of the lumpectomy cavity. It allowed for 3-D characterization of the borders surrounding the cavity, and it was easily distinguishable from the seroma and other surgical tissue changes. Respiratory motion was easily tracked using the device making it possible to apply advanced radiation treatment methods such as IMRT and accelerated protocols. When compared to conventional methods of determining the target area, use of the marker resulted in treatment volumes that were reduced by >60%. In appropriate patients, the marker also facilitated the use of an accelerated protocol, decreasing total treatment time from 6 weeks to 5 days. No complications were reported. Conclusions: This novel 3-D marker was consistently visualized, was readily incorporated into standard and advanced dose planning methods, and had appreciable benefits when designing optimal treatment plans. Its unique features were also helpful when using oncoplastic techniques, and proved valuable for long-term follow-up using standard methods of breast imaging.
To demonstrate a seasonal variation in the detection of breast cancer in women diagnosed at St Marks Breast Centre, Auckland.Data on women diagnosed with breast cancer at St Marks Breast Centre from January 1992 till December 2001 were obtained from the computerised database.A total of 1760 women were diagnosed with breast cancer; 1584 were referred by their general practitioner and 176 self referred. The peak incidence of seasonal diagnosis was in spring (September, October, November) with 521 cases. The lowest incidence was in summer (December, January, February) with 375 cases. These findings were consistent annually from 1992 to 2001.There is a seasonal variation in the incidence of breast cancer similar to that noted in other studies. Our findings suggest that temporal factors and possible behavioural patterns may have a role in this seasonal variation.
The term breast physician was coined in Australia in 1990 to describe a female medical practitioner who is skilled in interpreting screening mammograms and the diagnostic work-up of women with symptomatic breast problems. The Australian Society of Breast Physicians was formed in 1990, and in 1995 became the Australasian Society to incorporate the New Zealand breast physicians. There is now a network of breast physicians throughout Australia who are involved in breast screening clinics or breast diagnostic centres. Thirty women doctors in the United Kingdom work in a similar role. The role of the breast physician is a new, exciting and challenging career option for women doctors. The authors believe that breast physicians have an important role in the diagnosis, treatment and follow up of women with symptomatic breast problems.
89 Background: Most women in New Zealand undergo partial mastectomy (PM) and 6 weeks of whole breast irradiation for early breast cancer. Oncoplastic surgery (OPS) is common, however, reconstruction of the breast during partial mastectomy presents challenges for radiation targeting since tissues have been extensively rearranged. Further complicating matters, the seroma cavity is often absent, and many patients travel to different cities for radiation without much communication between the surgeon and radiation oncologist prior to treatment. Throughout the country there is interest in promoting hypofractionated or accelerated radiotherapy, however, these techniques cannot be popularized without accurate targeting to minimize complications. In this series of patients we studied a new method of breast reconstruction using a bioabsorbable implant that serves as a surgical site marker as well. Methods: Following informed consent, 15 women were studied in a prospective manner. The bioabsorbable implant was sutured into the tumor resection site, and tissue flaps were directly attached. Radiation treatment protocols followed ASTRO guidelines. Results: The implant provided volume replacement and acted as a scaffolding for the breast tissue flaps providing local reconstruction. Cosmetic outcomes were excellent in all patients, no device related or radiation complications occurred. One patient had a post-operative hematoma that resolved without intervention, there were no post-operative infections. 3 year follow up shows no tumor recurrences, and no untoward effects. When compared to conventional radiation targeting, use of the implant showed a > 50% reduction in treatment volume is possible. 3 year mammograms show normal regrowth of tissue without artifact and with minimal fibrosis. Conclusions: Three year follow-up shows this "mini" breast implant assists with oncoplastic breast reconstruction, while at the same time clearly marks the surgical site of tumor excision. Patients tolerated it well, and radiotherapy planning, positioning and treatment were all facilitated by the implant. Excellent patient outcomes in this pilot study have resulted in a national evaluation of this method in the public healthcare sector.
The best advice available at this time is that annual mammographic screening and annual clinical examination is beneficial to all women, irrespective of individual risk. All women with a breast change require review and referral when appropriate. Clinical breast and bimanual pelvic examination should be part of the routine annual physical review. The general practitioner is in the ideal position to identify women at risk and manage them appropriately. Genetic testing is available and continually developing. (author abstract)
Background: Target identification and hit identification can be transformed through the application of biomedical knowledge analysis, AI-driven virtual screening and robotic cloud lab systems. However there are few prospective studies that evaluate the efficacy of such integrated approaches. Results: We synergistically integrate our in-house-developed target evaluation (SpectraView) and deep-learning-driven virtual screening (HydraScreen) tools with an automated robotic cloud lab designed explicitly for ultra-high-throughput screening, enabling us to validate these platforms experimentally. By employing our target evaluation tool to select IRAK1 as the focal point of our investigation, we prospectively validate our structure-based deep learning model. We can identify 23.8% of all IRAK1 hits within the top 1% of ranked compounds. The model outperforms traditional virtual screening techniques and offers advanced features such as ligand pose confidence scoring. Simultaneously, we identify three potent (nanomolar) scaffolds from our compound library, 2 of which represent novel candidates for IRAK1 and hold promise for future development. Conclusion: This study provides compelling evidence for SpectraView and HydraScreen to provide a significant acceleration in the processes of target identification and hit discovery. By leveraging Ro5's HydraScreen and Strateos' automated labs in hit identification for IRAK1, we show how AI-driven virtual screening with HydraScreen could offer high hit discovery rates and reduce experimental costs. Scientific contribution: We present an innovative platform that leverages Knowledge graph-based biomedical data analytics and AI-driven virtual screening integrated with robotic cloud labs. Through an unbiased, prospective evaluation we show the reliability and robustness of HydraScreen in virtual and high-throughput screening for hit identification in IRAK1. Our platforms and innovative tools can expedite the early stages of drug discovery.
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