Towards a Visual-Language Foundation Model for Computational Pathology

The accelerated adoption of digital pathology and advances in deep learning have enabled the development of powerful models for various pathology tasks across a diverse array of diseases and patient cohorts. However, model training is often difficult due to label scarcity in the medical domain and the model's usage is limited by the specific task and disease for which it is trained. Additionally, most models in histopathology leverage only image data, a stark contrast to how humans teach each other and reason about histopathologic entities. We introduce CONtrastive learning from Captions for Histopathology (CONCH), a visual-language foundation model developed using diverse sources of histopathology images, biomedical text, and notably over 1.17 million image-caption pairs via task-agnostic pretraining. Evaluated on a suite of 13 diverse benchmarks, CONCH can be transferred to a wide range of downstream tasks involving either or both histopathology images and text, achieving state-of-the-art performance on histology image classification, segmentation, captioning, text-to-image and image-to-text retrieval. CONCH represents a substantial leap over concurrent visual-language pretrained systems for histopathology, with the potential to directly facilitate a wide array of machine learning-based workflows requiring minimal or no further supervised fine-tuning

Влияние анизотропии на транспортные свойства слоистого высокотемпературного сверхпроводника с магнитными и немагнитными протяженными дефектами

Transport properties of anisotropic superconductor with point, columnar and columnar tilted defects have been analyzed using Monte-Carlo method. It was shown that for columnar tilted defects the critical current dependence on anisotropy weakens as increases and vanishes at certain . The S-type nonlinearity of current-voltage characteristics has been shown for three-dimensional vortex system in presence of ferromagnetic defects.Методом Монте-Карло проанализированы транспортные свойства анизотропного сверхпроводника с точечными, колумнарными и колумнарными наклонными дефектами. Показано, что в случае колумнарных наклонных дефектов зависимость критического тока от анизотропии ослабевает с ростом и при определенном исчезает совсем. Показано наличие S-образной нелинейности вольт-амперной характеристики для трехмерной вихревой системы с ферромагнитными дефектами

Влияние анизотропии на транспортные свойства слоистого высокотемпературного сверхпроводника с магнитными и немагнитными протяженными дефектами

Transport properties of anisotropic superconductor with point, columnar and columnar tilted defects have been analyzed using Monte-Carlo method. It was shown that for columnar tilted defects the critical current dependence on anisotropy weakens as increases and vanishes at certain . The S-type nonlinearity of current-voltage characteristics has been shown for three-dimensional vortex system in presence of ferromagnetic defects.Методом Монте-Карло проанализированы транспортные свойства анизотропного сверхпроводника с точечными, колумнарными и колумнарными наклонными дефектами. Показано, что в случае колумнарных наклонных дефектов зависимость критического тока от анизотропии ослабевает с ростом и при определенном исчезает совсем. Показано наличие S-образной нелинейности вольт-амперной характеристики для трехмерной вихревой системы с ферромагнитными дефектами

Vepafestinib is a pharmacologically advanced RET-selective inhibitor with high CNS penetration and inhibitory activity against RET solvent front mutations

Acknowledgements: This work was supported by funding from Helsinn Healthcare (to R.S. and M.L.) and grants from the National Institutes of Health to E.d.S. (U54 D020355) and the MSKCC (Cancer Center Support grant P30 CA008748 and Summer Research Experiences Supervised by Faculty Mentors grant 5R25CA020449).Funder: Helsinn Healthcare, SARET receptor tyrosine kinase is activated in various cancers (lung, thyroid, colon and pancreatic, among others) through oncogenic fusions or gain-of-function single-nucleotide variants. Small-molecule RET kinase inhibitors became standard-of-care therapy for advanced malignancies driven by RET. The therapeutic benefit of RET inhibitors is limited, however, by acquired mutations in the drug target as well as brain metastasis, presumably due to inadequate brain penetration. Here, we perform preclinical characterization of vepafestinib (TAS0953/HM06), a next-generation RET inhibitor with a unique binding mode. We demonstrate that vepafestinib has best-in-class selectivity against RET, while exerting activity against commonly reported on-target resistance mutations (variants in RETL730, RETV804 and RETG810), and shows superior pharmacokinetic properties in the brain when compared to currently approved RET drugs. We further show that these properties translate into improved tumor control in an intracranial model of RET-driven cancer. Our results underscore the clinical potential of vepafestinib in treating RET-driven cancers

Vepafestinib is a pharmacologically advanced RET-selective inhibitor with high CNS penetration and inhibitory activity against RET solvent front mutations.

RET receptor tyrosine kinase is activated in various cancers (lung, thyroid, colon and pancreatic, among others) through oncogenic fusions or gain-of-function single-nucleotide variants. Small-molecule RET kinase inhibitors became standard-of-care therapy for advanced malignancies driven by RET. The therapeutic benefit of RET inhibitors is limited, however, by acquired mutations in the drug target as well as brain metastasis, presumably due to inadequate brain penetration. Here, we perform preclinical characterization of vepafestinib (TAS0953/HM06), a next-generation RET inhibitor with a unique binding mode. We demonstrate that vepafestinib has best-in-class selectivity against RET, while exerting activity against commonly reported on-target resistance mutations (variants in RETL730, RETV804 and RETG810), and shows superior pharmacokinetic properties in the brain when compared to currently approved RET drugs. We further show that these properties translate into improved tumor control in an intracranial model of RET-driven cancer. Our results underscore the clinical potential of vepafestinib in treating RET-driven cancers

Vepafestinib is a pharmacologically advanced RET-selective inhibitor with high CNS penetration and inhibitory activity against RET solvent front mutations

Acknowledgements: This work was supported by funding from Helsinn Healthcare (to R.S. and M.L.) and grants from the National Institutes of Health to E.d.S. (U54 D020355) and the MSKCC (Cancer Center Support grant P30 CA008748 and Summer Research Experiences Supervised by Faculty Mentors grant 5R25CA020449).Funder: Helsinn Healthcare, SARET receptor tyrosine kinase is activated in various cancers (lung, thyroid, colon and pancreatic, among others) through oncogenic fusions or gain-of-function single-nucleotide variants. Small-molecule RET kinase inhibitors became standard-of-care therapy for advanced malignancies driven by RET. The therapeutic benefit of RET inhibitors is limited, however, by acquired mutations in the drug target as well as brain metastasis, presumably due to inadequate brain penetration. Here, we perform preclinical characterization of vepafestinib (TAS0953/HM06), a next-generation RET inhibitor with a unique binding mode. We demonstrate that vepafestinib has best-in-class selectivity against RET, while exerting activity against commonly reported on-target resistance mutations (variants in RETL730, RETV804 and RETG810), and shows superior pharmacokinetic properties in the brain when compared to currently approved RET drugs. We further show that these properties translate into improved tumor control in an intracranial model of RET-driven cancer. Our results underscore the clinical potential of vepafestinib in treating RET-driven cancers