The long shadow of socioeconomic deprivation over the modern management of acute myeloid leukemia – time to unravel the challenges

Abstract Biological and non-biological variables unrelated to acute myeloid leukemia (AML) preclude standard therapy in many settings, with “real world” patients under-represented in clinical trials and prognostic models. Here, using a case-based format, we illustrate the impact that socioeconomic and anthropogeographical constraints can have on optimally managing AML in 4 different healthcare systems. The granular details provided, emphasize the need for the development and targeting of socioeconomic interventions that are commensurate with the changing landscape of AML therapeutics, in order to avoid worsening the disparity in outcomes between patients with biologically similar disease

Bone seeking matrix metalloproteinase-2 inhibitors prevent bone metastatic breast cancer growth

Bone metastasis is common during breast cancer progression. Matrix metalloproteinase-2 (MMP-2) is significantly associated with aggressive breast cancer and poorer overall survival. In bone, tumor or host derived MMP-2 contributes to breast cancer growth and does so by processing substrates including type I collagen and transforming growth factorβ (TGFβ) latency proteins. These data provide strong rationale for the application of MMP-2 inhibitors to treat the disease. However, in vivo, MMP-2 is systemically expressed. Therefore, to overcome potential toxicities noted with previous broad-spectrum MMP inhibitors (MMPIs), we used highly selective bisphosphonic based MMP-2 inhibitors (BMMPIs) that allowed for specific bone targeting. In vitro, BMMPIs impacted the viability of breast cancer cell lines and osteoclast precursors but not osteoblasts. In vivo, we demonstrated using two bone metastatic models (PyMT-R221A and 4T1) that BMMPI treatment significantly reduced tumor growth and tumor associated bone destruction. Additionally, BMMPIs are superior in promoting tumor apoptosis compared to the standard of care bisphosphonate, zoledronate. We demonstrated MMP-2 selective inhibition in the bone microenvironment using specific and broad spectrum MMP probes. Further, compared to zoledronate, BMMPI treated mice had significantly lower levels of TGFβ signaling and MMP generated type I collagen carboxy-terminal (ICTP) fragments. Taken together, our data show the feasibility of selective inhibition of MMPs in the bone metastatic breast cancer microenvironment. We posit that BMMPIs could be easily translated to the clinical setting for the treatment of bone metastases given the well-tolerated nature of bisphosphonates

Giant cutaneous horn in an African woman: a case report

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Rehabilitation of Post-COVID Patients: A Virtual Reality Home-Based Intervention Including Cardio-Respiratory Fitness Training

The post-COVID syndrome is emerging as a new chronic condition, characterized by symptoms of breathlessness, fatigue, and decline of neurocognitive functions. Rehabilitation programs that include physical training seem to be beneficial to reduce such symptoms and improve patients' quality of life. Given this, and considering the limitations imposed by the pandemic on rehabilitation services, it emerged the need to integrate telerehabilitation programs into clinical practice. Some telerehabilitation solutions, also based on virtual reality (VR), are available in the market. Still, they mainly focus on rehabilitation of upper limbs, balance, and cognitive training, while exercises like cycling or walking are usually not considered. The presented work aims to fill this gap by integrating a VR application to provide cardio-respiratory fitness training to post-COVID patients in an existing telerehabilitation platform. The ARTEDIA application allows patients to perform a cycling exercise and a concurrent cognitive task. Patients can cycle in a virtual park while performing a "go/no-go" task by selecting only specific targets appearing along the way. The difficulty of the practice can be adjusted by the therapists, while the physiological response is continuously monitored through wearable sensors to ensure safety. The application has been integrated into the VRRS system by Khymeia. In the next months, a study to assess the feasibility of a complete telerehabilitation program based on physical and cognitive training will take place. Such a program will combine the existing VRRS exercises and the cardio-respiratory fitness exercise provided by the ARTEDIA application. Feasibility, acceptance, and usability will be assessed from both the patients' and the therapists' sides

The long shadow of socioeconomic deprivation over the modern management of acute myeloid leukemia: time to unravel the challenges

Biological and non-biological variables unrelated to acute myeloid leukemia (AML) preclude standard therapy in many settings, with “real world” patients under-represented in clinical trials and prognostic models. Here, using a case-based format, we illustrate the impact that socioeconomic and anthropogeographical constraints can have on optimally managing AML in 4 different healthcare systems. The granular details provided, emphasize the need for the development and targeting of socioeconomic interventions that are commensurate with the changing landscape of AML therapeutics, in order to avoid worsening the disparity in outcomes between patients with biologically similar disease

“Cape Fear”—A Hybrid Hillslope Plot for Monitoring Hydrological Processes

Innovative experimental field designs and methods are instrumental for dissecting hydrological processes in hillslopes. However, experimental studies at the catchment scale are rarely affordable to most research groups, and laboratory flumes are oversimplified to reproduce natural phenomena. In this work, we present the innovative “hybrid” experimental plot of Cape Fear, which features controllable water fluxes and boundary conditions, but it is directly exposed to external atmospheric agents. We demonstrate the suitability of Cape Fear to study hydrological phenomena through a feasibility test, whereby the response of the plot to a natural storm is in line with the well-known hydrological response of natural hillslopes. Future studies will address the influence of the plot geometry parameters on rill formation

An Evaluation of Image Velocimetry Techniques under Low Flow Conditions and High Seeding Densities Using Unmanned Aerial Systems

Image velocimetry has proven to be a promising technique for monitoring river flows using remotely operated platforms such as Unmanned Aerial Systems (UAS). However, the application of various image velocimetry algorithms has not been extensively assessed. Therefore, a sensitivity analysis has been conducted on five different image velocimetry algorithms including Large Scale Particle Image Velocimetry (LSPIV), Large-Scale Particle Tracking Velocimetry (LSPTV), Kanade−Lucas Tomasi Image Velocimetry (KLT-IV or KLT), Optical Tracking Velocimetry (OTV) and Surface Structure Image Velocimetry (SSIV), during low river flow conditions (average surface velocities of 0.12−0.14 m s - 1 , Q60) on the River Kolubara, Central Serbia. A DJI Phantom 4 Pro UAS was used to collect two 30-second videos of the surface flow. Artificial seeding material was distributed homogeneously across the rivers surface, to enhance the conditions for image velocimetry techniques. The sensitivity analysis was performed on comparable parameters between the different algorithms, including the particle identification area parameters (such as Interrogation Area (LSPIV, LSPTV and SSIV), Block Size (KLT-IV) and Trajectory Length (OTV)) and the feature extraction rate. Results highlighted that KLT and SSIV were sensitive to changing the feature extraction rate; however, changing the particle identification area did not affect the surface velocity results significantly. OTV and LSPTV, on the other hand, highlighted that changing the particle identification area presented higher variability in the results, while changing the feature extraction rate did not affect the surface velocity outputs. LSPIV proved to be sensitive to changing both the feature extraction rate and the particle identification area. This analysis has led to the conclusions that for surface velocities of approximately 0.12 m s - 1 image velocimetry techniques can provide results comparable to traditional techniques such as ADCPs. However, LSPIV, LSPTV and OTV require additional effort for calibration and selecting the appropriate parameters when compared to KLT-IV and SSIV. Despite the varying levels of sensitivity of each algorithm to changing parameters, all configuration image velocimetry algorithms provided results that were within 0.05 m s - 1 of the ADCP measurements, on average