Federated learning enables big data for rare cancer boundary detection.

Although machine learning (ML) has shown promise across disciplines, out-of-sample generalizability is concerning. This is currently addressed by sharing multi-site data, but such centralization is challenging/infeasible to scale due to various limitations. Federated ML (FL) provides an alternative paradigm for accurate and generalizable ML, by only sharing numerical model updates. Here we present the largest FL study to-date, involving data from 71 sites across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, reporting the largest such dataset in the literature (n = 6, 314). We demonstrate a 33% delineation improvement for the surgically targetable tumor, and 23% for the complete tumor extent, over a publicly trained model. We anticipate our study to: 1) enable more healthcare studies informed by large diverse data, ensuring meaningful results for rare diseases and underrepresented populations, 2) facilitate further analyses for glioblastoma by releasing our consensus model, and 3) demonstrate the FL effectiveness at such scale and task-complexity as a paradigm shift for multi-site collaborations, alleviating the need for data-sharing

Author Correction: Federated learning enables big data for rare cancer boundary detection.

10.1038/s41467-023-36188-7NATURE COMMUNICATIONS14

Federated Learning Enables Big Data for Rare Cancer Boundary Detection

Although machine learning (ML) has shown promise across disciplines, out-of-sample generalizability is concerning. This is currently addressed by sharing multi-site data, but such centralization is challenging/infeasible to scale due to various limitations. Federated ML (FL) provides an alternative paradigm for accurate and generalizable ML, by only sharing numerical model updates. Here we present the largest FL study to-date, involving data from 71 sites across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, reporting the largest such dataset in the literature (n = 6, 314). We demonstrate a 33% delineation improvement for the surgically targetable tumor, and 23% for the complete tumor extent, over a publicly trained model. We anticipate our study to: 1) enable more healthcare studies informed by large diverse data, ensuring meaningful results for rare diseases and underrepresented populations, 2) facilitate further analyses for glioblastoma by releasing our consensus model, and 3) demonstrate the FL effectiveness at such scale and task-complexity as a paradigm shift for multi-site collaborations, alleviating the need for data-sharing

False-positive serum botulism bioassay in Miller-Fisher Syndrome

We describe a patient with acute progressive weakness and areflexia. Both botulism and Miller-Fisher variant of Guillain-Barré syndrome were initial diagnostic considerations, and she was treated with intravenous immunoglobulin and botulinum antitoxin. A mouse bioassay was positive for botulinum toxin A, although her clinical course, electrodiagnostic studies, and cerebrospinal fluid findings supported Miller-Fisher syndrome. This patient\u27s atypical features offer points of discussion regarding the evaluation of patients with acute neuromuscular weakness and emphasize the limitations of the botulism bioassay

Influence of particle properties on powder bulk behaviour and processability

Understanding interparticle interactions in powder systems is crucial to pharmaceutical powder processing. Nevertheless, there remains a great challenge in identifying the key factors affecting interparticle interactions. Factors affecting interparticle interactions can be classified in three different broad categories: powder properties, environmental conditions, and powder processing methods and parameters. Although, each of these three categories listed is known to affect interparticle interactions, the challenge remains in developing a mechanistic understanding on how combination of these three categories affect interparticle interactions. This review focuses on the recent advances on understanding the effect of powder properties, particularly particle properties, its effect on interparticle interactions and ultimately on powder bulk behaviour. Furthermore, this review also highlights how particle properties are affected by the particle processing route and parameters. Recent advances in developing a particle processing route to prepare particles with desired properties allowing desired interparticle interaction to deliver favoured powder bulk behaviour are also discussed. Perspectives for the development of potential particle processing approaches to control interparticle interaction are presented.by Umang V. Shah, Vikram Karde, Chinmay Ghoroi and Jerry Y. Y. Hen

Selective Crystallization of Proteins Using Engineered Nanonucleants

This study reports for the first time a detailed experimental investigation of protein crystallization in engineered nanoconfined spaces with both controlled pore diameters and narrow pore size distributions. We propose a systematic approach for controlling the nucleation and crystallization of biological macromolecules based on a relationship between the protein radius of gyration (<i>R</i>_g) and specific pore diameter. A series of nanonucleants with ordered mesopores having narrow pore size distributions were prepared. The templates were tested for proteins ranging in molecular weight from 14 to 450 kDa. Well-formed protein crystals were obtained on only one of the five presented nanonucleants for all protein cases tested, highlighting the unique template selectivity exhibited by these nucleants. In addition, concanavalin A and catalase were both crystallized at ∼2 times lower supersaturation levels than previously reported by any known method. Our observations fully support theoretical studies that predict the enhanced thermodynamic stability of proteins in nanoconfined cavities, including specifically the importance of nucleant pore diameter with respect to protein radius of gyration. The nucleants described here could have major industrial applications for downstream separation and purification of biopharmaceuticals, as well as improved opportunities for the crystallization of complex proteins for structural determination

Crystallization of Proteins at Ultralow Supersaturations Using Novel Three-Dimensional Nanotemplates

A series of novel three-dimensional (3D) nanotemplates which have tuned surface mesoporosity and surface chemistry based on the protein of interest have been developed to facilitate protein crystallization. The crystallization of five model proteins systems is reported at hereto the lowest reported protein or precipitant concentrations. These improvements were only possible due to the combined use of optimum pore sizes with appropriate surface chemistries in the preparation of the 3D nanotemplates. The success of this strategy can be ascribed to the specific design of the ordered nanotemplates which are based on known physicochemical properties of the protein and offer an alternate targeted strategy for protein crystallization in contrast to previous methods based on the use of universal nucleants. The use of protein tuned nanotemplates will potentially open up new opportunities for the crystallization and structure determination of high value proteins, as well as opportunities for their separation and purification in downstream bioprocessing

Infusion of autologous adipose tissue derived neuronal differentiated mesenchymal stem cells and hematopoietic stem cells in post-traumatic paraplegia offers a viable therapeutic approach

Background: Spinal cord injury (SCI) is not likely to recover by current therapeutic modalities. Stem cell (SC) therapy (SCT) has promising results in regenerative medicine. We present our experience of co-infusion of autologous adipose tissue derived mesenchymal SC differentiated neuronal cells (N-Ad-MSC) and hematopoietic SCs (HSCs) in a set of patients with posttraumatic paraplegia. Materials and Methods: Ten patients with posttraumatic paraplegia of mean age 3.42 years were volunteered for SCT. Their mean age was 28 years, and they had variable associated complications. They were subjected to adipose tissue resection for in vitro generation of N-Ad-MSC and bone marrow aspiration for generation of HSC. Generated SCs were infused into the cerebrospinal fluid (CSF) below injury site in all patients. Results: Total mean quantum of SC infused was 4.04 ml with a mean nucleated cell count of 4.5 × 104/μL and mean CD34+ of 0.35%, CD45−/90+ and CD45−/73+ of 41.4%, and 10.04%, respectively. All of them expressed transcription factors beta-3 tubulin and glial fibrillary acid protein. No untoward effect of SCT was noted. Variable and sustained improvement in Hauser's index and American Spinal Injury Association score was noted in all patients over a mean follow-up of 2.95 years. Mean injury duration was 3.42 years against the period of approximately 1-year required for natural recovery, suggesting a positive role of SCs. Conclusion: Co-infusion of N-Ad-MSC and HSC in CSF is safe and viable therapeutic approach for SCIs