Magnetic hyperthermia (MH) is a nanotechnology-driven therapy that seizes the heat release of magnetic nanoparticles when exposed to an alternating magnetic field. It has already been and is currently trialed in clinical settings as adjuvant of chemotherapy and radiotherapy to successfully treat several types of tumors [1, 2]. In silico testing (computer simulations) allows us to mimic several clinical situations and to evaluate the treatment safety in terms of dosimetry and temperature rise, including possible hot spots due to eddy currents, in a cheap and fast way. MH has taken advantages of this virtual testing in its way towards personalized therapy. The versatility of the simulations to evaluate many clinical setups allows us to study the actual risks of the current exclusion criteria [1, 3]. Nowadays, bearing any kind of metallic object, orthopedic implants for example, constitutes a contraindication for the treatment. This is based on the knowledge obtained from MRI related studies, but there is an important lack in the literature about the quantification of these risks in the context of clinical MH. In this work, we use computer simulations to study the actual risks of potential MH patients carrying different orthopedic prosthesis, as well as the influence of the presence of this metallic object in the effective magnetic field reaching the nanoparticles site. We have considered different treatment setups varying tumor locations, implant types and materials to evaluate the temperature increase and the dosimetric values in the major tissue groups. These safety parameters have been included in a multi-criteria decision analysis to asses a risk index for each tissue group in every clinical situation analyzed [4]. Acknowledgements We acknowledge COST Action MyWave (CA 17115), NoCanTher project (grant agreement No 685795), Regional Government of Madrid under contract PEJD-2017-PRE/IND-3663, Spanish Ministry of Economy and Competitiveness through the grants MAT2017-85617-R, Ramón y Cajal RYC2018-025253-I, the “Severo Ochoa” Program for Centers of Excellence in R&D (SEV-2016-0686) and the support of NVIDIA Corporation through the GPU Grant Program with the donation of the Quadro P6000 GPU used in this work.

![](https://assets.underline.io/uploads/markdown_image/1/image/5b88302d4b166afa56c0e9833b44c1ec.jpg)

In Silico Safety Analysis of Magnetic Hyperthermia Treatments of Implant-Bearing Patients

Achieving homogeneous tumour heating is one of the most long-standing challenges in magnetic hyperthermia for cancer therapy. Clinical studies must meet strict safety regulations that require knowledge and control over the physical properties of the chosen magnetic nanoparticles [1]. Whereas it is well-established that the heat released by magnetic nanostructures is influenced by interparticle interactions, as of today there is no method to analyze heat exchange at single-particle level in interacting systems at nonzero temperature. This gap needs to be bridged so to harness nanoparticle magnetization dynamics for the sake of biomedical applications. Building on previous theoretical work [2], we present an equation to estimate the heat dissipation of individual, interacting particles at nonzero temperature that perform both field-induced and thermal switching. After validating this equation, we use the macrospin simulation tool Vinamax [3], to investigate a system of interacting particles with different anisotropies, as we showed in this contribution [4]. Our preliminary results indicate (see figure) that the generated heat becomes more homogeneously distributed at larger fields. We believe that this homogenization of the particle heating will help to achieve a more homogenized heating of tumors during hyperthermia treatments. The use of the proposed equation would simplify the selection process of optimum nanoparticle distributions leading to optimal tumour heating. Its simplicity and flexibility also allow it to be integrated into multi-scale, multi-physics simulations to accurately assess the magnetic hyperthermia therapy without impacting the overall computational time.

![](https://assets.underline.io/uploads/markdown_image/1/image/cd66b63a757f78697365ef1ca41b5bd1.jpg)

Figure: Heat generated in a system consisting of two interacting nanoparticles with different anisotropies. Both particles show switching behavior as soon as the excitation field amplitude overcomes their anisotropy barrier. The heat generation tends to become more uniform with increasing excitation fields.

Homogenization of Heating in Magnetic Hyperthermia Through Exploitation of Magnetisation Dynamics of Interacting Particles

Novel magnetic nanostructures (MNS) present a unique spin arrangement in the magnetic ground state, namely spin-vortex or synthetic antiferromagnetic state. MNS showed promising results in cell separation, as a contrast enhancing agents in MRI and in magneto-mechanically induced cell annihilation. The main advantages of magneto-mechanically induced cell annihilation are the usage of weaker magnetic fields with lower frequencies, as well as the need for a lower concentration of particles [1,2]. In this work, we developed one subset of biocompatible magnetic nanostructures that exhibit a spin-vortex state. First, micromagnetic simulations, using mumax3 of sub-micron iron discs, were performed for different interdot distance and aspect-ratio (thickness/diameter). By analysing the nucleation and annihilation fields, as well as the magnetic susceptibility, it was found that the (ideal) discs could be considered as isolated for interdot distances greater than twice the radius of the disc (2R) [3]. We also found that discs with an aspect ratio between 5 and 15 should sustain the vortex state in remanence [4]. Iron nano-discs in a vortex state, with a diameter of about 500 nm, were fabricated by electron beam evaporation on a Si substrate pre-patterned by interference lithography. Then, the magnetic vortex nano-discs were released from the substrate by chemical etching of a sacrificial layer. Subsequently, cell viability and uptake assays were performed in a human leukaemia monocyte cell line (THP-1) [5]. Several concentrations of nano-discs were studied by flow cytometry. As a result, the discs were internalized by the cells and found to be innocuous to them, in the absence of an external magnetic field.

Vortex nano-discs: from micromagnetic simulations to cancer cells internalization for magneto-mechanically induced damage applications.

Transcranial magnetic stimulation (TMS)1,2 is clinically used in patients with depression2,3, while the effects of TMS-like magnetic fields on extracranial tissues are almost unknown4. Here, we explored effects of TMS-like repetitive magnetic stimulation (RMS) on metabolic activity of human hepatocellular carcinoma (HCC) and colorectal cancer (CRC) cells. The HuH7 (HCC) and HCT116 (CRC) cell cultures were treated using a TMS device “Magstim Rapid2” with an AFC70 coil. Intermittent RMS (iRMS) modes (4 trains of 150 pulses with frequency f=1, 5, 10, 20 or 40 Hz and equal intertrain intervals) and burst RMS (600 pulses delivered in trains, f=40 Hz/ bursts, f=3 Hz). The coil power output /magnetic field strength was (100% or 50%, B=0.8 T or 0.4 T, respectively) in burst modes or 100% in iRMS. The activity of SDG, an enzyme essential for energy production, was measured by MTT colorimetric assay in 24 h post-RMS. The control groups included: (1) untreated cells, (2) 20 min room temperature control, and (3) strong metabolic suppression by 100% DMSO solution. The main results are shown in Figures 1 and 2. Dashed red lines are CI95% for mean absorbance in the untreated control group; Abs is MTT assay product absorbance, a.u. In HuH7 cells, the tested protocols of RMS either did not change or stimulated the metabolic activity. However, correlation analysis indicated that the modes with higher frequency, burst pattern, and shorter cycles are more probable as suppressors of the liver cancer cells’ metabolism. In HCT116 cells, an iRMS mode 1B100 (f=1 Hz) induced a statistically significant decrease of metabolic activity, while high-frequency iRMS and burst modes stimulated it. In CRC, correlation analysis revealed the opposite to HCC trend of reduction of the metabolic rate at lower frequencies, intermittent PRMS, and the increase of it at high frequencies and burst modes. Our pioneering findings demonstrate the tumour-specific and mode-specific effects of re-purposed TMS technology on hepatic and colorectal cancer cells. The potential of RMS as adjuvant anti-cancer treatment will be discussed. We thank Medilink Australia for providing the “Magstim”.

![](https://assets.underline.io/uploads/markdown_image/1/image/3328edd15f9c1f201697574351fdeb65.jpg)

Figure 1. Effect of RMS on HuH7 cells.

![](https://assets.underline.io/uploads/markdown_image/1/image/181596c78a02d0fe7e97c8ea95446c42.jpg)

Figure 2. Effect of RMS on HCT116 cells.

TMS-like Magnetic Fields Modulate Metabolic Activity of Hepatic and Colorectal Cancer Cells

Pre-trained language models (LMs) have become ubiquitous in solving various natural language processing (NLP) tasks. There has been increasing interest in what knowledge these LMs contain and how we can extract that knowledge, treating LMs as knowledge bases (KBs). While there has been much work on probing LMs in the general domain, there has been little attention to whether these powerful LMs can be used as domain-specific KBs. To this end, we create the BioLAMA benchmark, which is comprised of 49K biomedical factual knowledge triples for probing biomedical LMs. We find that biomedical LMs with recently proposed probing methods can achieve up to 18.51% Acc@5 on retrieving biomedical knowledge. Although this seems promising given the task difficulty, our detailed analyses reveal that most predictions are highly correlated with prompt templates without any subjects, hence producing similar results on each relation and hindering their capabilities to be used as domain-specific KBs. We hope that BioLAMA can serve as a challenging benchmark for biomedical factual probing.

Can Language Models be Biomedical Knowledge Bases?

Introduction: Sarcoidosis is a granulomatous disease that can affect any organ. Diagnosis can be challenging and often requires tissue sampling; a non-invasive diagnostic method is lacking. Electronic nose (eNose) analysis is an emerging method for profiling exhaled volatile organic compounds. We aimed to evaluate whether eNose data could distinguish between sarcoidosis, other interstitial lung diseases (ILDs) and healthy controls, and between different phenotypes or clinical characteristics of sarcoidosis patients.
Methods: In this cross-sectional single centre study, exhaled breath of outpatients with sarcoidosis was analysed using an eNose (SpiroNose). Clinical characteristics were collected from medical files. eNose sensor data were analysed with partial least square discriminant and ROC analysis. Regression analysis was conducted to correlate sIL-2R values with the main principal component.
Results: 569 patients were included (252 with sarcoidosis, 317 with ILD) and 48 healthy controls. The mean age of sarcoidosis patients was 53.1±11.4 years, 53.2% was male, 61% never smoked, and 88.9% had pulmonary involvement. eNose data could distinguish sarcoidosis patients from healthy controls (AUC 1.00; Figure 1) and ILD patients (AUC 0.89). There were no differences in eNose data between sarcoidosis patients with or without fibrosis (AUC 0.60), immunosuppressive treatment (AUC 0.59), or pulmonary involvement (AUC 0.64). eNose data did differentiate the 1st and 4th sIL-2R quartiles (AUC 0.83; Figure 2). A moderate correlation of eNose data with individual sIL-2R values (r=0.32, p<0.05) was found.
Conclusion: Exhaled breath analysis using eNose technology may be a novel diagnostic tool for sarcoidosis. No differences were found between different phenotypes of sarcoidosis.

Use of electronic nose technology in sarcoidosis

We describe two accessible and successful microfluidic strategies to expose human pluripotent stem cells to spatial gradients of differentiation-inducing extracellular signals in vitro. In addition, coupling with a fluorescent reporter and live-cell imaging allowed us to characterize the spatiotemporal dynamics of differentiation of our spatially patterned cell colonies.

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In Silico Safety Analysis of Magnetic Hyperthermia Treatments of Implant-Bearing Patients

Homogenization of Heating in Magnetic Hyperthermia Through Exploitation of Magnetisation Dynamics of Interacting Particles

Vortex nano-discs: from micromagnetic simulations to cancer cells internalization for magneto-mechanically induced damage applications.

TMS-like Magnetic Fields Modulate Metabolic Activity of Hepatic and Colorectal Cancer Cells

Can Language Models be Biomedical Knowledge Bases?

Use of electronic nose technology in sarcoidosis

Spatially controlled stem cell differentiation via morphogen gradients: comparing static and dynamic microfluidic platforms

Hormonal Signaling and Metabolic Tissue Microenvironment in Health and Disease

Adipose Tissue Plasticity in Obesity

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