Letter: The Impact of the Coronavirus (COVID-19) Pandemic on Neurosurgeons Worldwide

This article is made available for unrestricted research re-use and secondary analysis in any form or be any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.The aim of our study was to explore the impact of this pandemic on neurosurgeons with the hope of improving preparedness for future crisis. We created a 20-question survey designed to explore demographics (nation, duration and scope of practice, and case-burden), knowledge (source of information), clinical impact (elective clinic/surgery cancellations), hospital preparedness (availability of personal protective equipment [PPE] and cost of the supplies), and personal factors (financial burden, workload, scientific and research activities). The survey was first piloted with 10 neurosurgeons and then revised. Surveys were distributed electronically in 7 languages (Chinese, English, French, German, Italian, Portuguese, and Spanish) between March 20 and April 3, 2020 using Google Forms, WeChat used to obtain responses, and Excel (Microsoft) and SPSS (IBM) used to analyze results. All responses were cross-verified by 2 members of our team. After obtaining results, we analyzed our data with histograms and standard statistical methods (Chi-square and Fisher's exact tests and logistic regression). Participants were first informed about the objectives of our survey and assured confidentiality after they agreed to participate (Helsinki declaration). We received 187 responses from 308 invitations (60.7%), and 474 additional responses were obtained from social media-based neurosurgery groups (total responses = 661). The respondents were from 96 countries representing 6 continents (Figure ​(Figure11A-​A-11C)

Impairing Proliferation of Glioblastoma Multiforme with CD44+ Selective Conjugated Polymer Nanoparticles

Glioblastoma is one of the most aggressive types of cancer with median survival of only 15 months. Successful therapy is hampered by the existence of treatment resistant populations of stem-like tumour initiating cells (TICs) and poor blood-brain barrier drug penetration. Therapies capable of effectively targeting the TIC population are in high demand. Here, we synthesize spherical diketopyrrolopyrrole (DPP)-based conjugated polymer nanoparticles (CPNs) with an average diameter of 109 nm. The CPN were designed to include fluorescein-conjugated hyaluronic acid (HA), a ligand for the CD44 receptor present on one population of TICs. We demonstrate blood-brain barrier permeability of this system and concentration and cell cycle phase-dependent selective uptake of HA-CPNs in CD44 positive GBM-patient derived cultures. Interestingly, we found that uptake alone decreases stemness, invasive properties and proliferation of the CD44-TIC population in zebrafish PDX models in vivo. This study is the first to show surface moiety-driven selectivity of conjugated polymer nanoparticles in targeting TIC populations in brain cancer

Impairing proliferation of glioblastoma multiforme with CD44+ selective conjugated polymer nanoparticles

Glioblastoma is one of the most aggressive types of cancer with success of therapy being hampered by the existence of treatment resistant populations of stem-like Tumour Initiating Cells (TICs) and poor blood–brain barrier drug penetration. Therapies capable of effectively targeting the TIC population are in high demand. Here, we synthesize spherical diketopyrrolopyrrole-based Conjugated Polymer Nanoparticles (CPNs) with an average diameter of 109 nm. CPNs were designed to include fluorescein-conjugated Hyaluronic Acid (HA), a ligand for the CD44 receptor present on one population of TICs. We demonstrate blood–brain barrier permeability of this system and concentration and cell cycle phase-dependent selective uptake of HA-CPNs in CD44 positive GBM-patient derived cultures. Interestingly, we found that uptake alone regulated the levels and signaling activity of the CD44 receptor, decreasing stemness, invasive properties and proliferation of the CD44-TIC populations in vitro and in a patient-derived xenograft zebrafish model. This work proposes a novel, CPN- based, and surface moiety-driven selective way of targeting of TIC populations in brain cancer