Printing of 3D biomimetic structures for the study of bone metastasis: A review.

Bone metastasis primarily occurs when breast, prostate, or lung cancers disseminate tumoral cells into bone tissue, leading to a range of complications in skeletal tissues and, in severe cases, paralysis resulting from spinal cord compression. Unfortunately, our understanding of pathophysiological mechanisms is incomplete and the translation of bone metastasis research into the clinic has been slow, mainly due to the lack of credible ex vivo and in vivo models to study the disease progression. Development of reliable and rational models to study how tumor cells become circulating cells and then invade and sequentially colonize the bone are in great need. Advances in tissue engineering technologies offers reliable 3D tissue alternatives which answer relevant research questions towards the understanding of cancer evolution and key functional properties of metastasis progression as well as prognosis of therapeutic approach. Here we performed an overview of cellular mechanisms involved in bone metastasis including a short summary of normal bone physiology and metastasis initiation and progression. Also, we comprehensively summarized current advances and methodologies in fabrication of reliable bone tumor models based on state-of-the-art printing technologies which recapitulate structural and biological features of native tissue. STATEMENT OF SIGNIFICANCE: This review provides a comprehensive summary of the collective findings in relation to various printed bone metastasis models utilized for investigating specific bone metastasis diseases, related characteristic functions and chemotherapeutic drug screening. These tumoral models are comprehensively evaluated and compared, in terms of their ability to recapitulate physiological metastasis microenvironment. Various biomaterials (natural and synthetic polymers and ceramic based substrates) and printing strategies and design architecture of models used for printing of 3D bone metastasis models are discussed here. This review clearly out-lines current challenges and prospects for 3D printing technologies in bone metastasis research by focusing on the required perspective models for clinical application of these technologies in chemotherapeutic drug screening.

Understanding functional brain reorganization for naturalistic piano playing in novice pianists.

Learning to play the piano is a unique complex task, integrating multiple sensory modalities and higher order cognitive functions. Longitudinal neuroimaging studies on adult novice musicians show training-related functional changes in music perception tasks. The reorganization of brain activity while actually playing an instrument was studied only on a very short time frame of a single fMRI session, and longer interventions have not yet been performed. Thus, our aim was to investigate the dynamic complexity of functional brain reorganization while playing the piano within the first half year of musical training. We scanned 24 novice keyboard learners (female, 18-23 years old) using fMRI while they played increasingly complex musical pieces after 1, 6, 13, and 26 weeks of training. Playing music evoked responses bilaterally in the auditory, inferior frontal, and supplementary motor areas, and the left sensorimotor cortex. The effect of training over time, however, invoked widespread changes encompassing the right sensorimotor cortex, cerebellum, superior parietal cortex, anterior insula and hippocampus, among others. As the training progressed, the activation of these regions decreased while playing music. Post hoc analysis revealed region-specific time-courses for independent auditory and motor regions of interest. These results suggest that while the primary sensory, motor, and frontal regions are associated with playing music, the training decreases the involvement of higher order cognitive control and integrative regions, and basal ganglia. Moreover, training might affect distinct brain regions in different ways, providing evidence in favor of the dynamic nature of brain plasticity.

Tuning Physical Properties of GelMA Hydrogels through Microarchitecture for Engineering Osteoid Tissue.

Gelatin methacryloyl (GelMA) hydrogels have gained significant attention due to their biocompatibility and tunable properties. Here, a new approach to engineer GelMA-based matrices to mimic the osteoid matrix is provided. Two cross-linking methods were employed to mimic the tissue stiffness: standard cross-linking (SC) based on visible light exposure (VL) and dual cross-linking (DC) involving physical gelation, followed by VL. It was demonstrated that by reducing the GelMA concentration from 10% (G10) to 5% (G5), the dual-cross-linked G5 achieved a compressive modulus of ∼17 kPa and showed the ability to support bone formation, as evidenced by alkaline phosphatase detection over 3 weeks of incubation in osteogenic medium. Moreover, incorporating poly(ethylene) oxide (PEO) into the G5 and G10 samples was found to hinder the fabrication of highly porous hydrogels, leading to compromised cell survival and reduced osteogenic differentiation, as a consequence of incomplete PEO removal.

Interoception and the musical brain: Evidence from cross-sectional and longitudinal behavioral and resting-state fMRI study.

Musical training has been linked to enhanced interoceptive abilities and increased resting-state (RS) functional connectivity (FC) within the interoceptive brain network. We aimed to replicate and extend these findings with a unique cross-sectional and longitudinal study design. Professional musicians and matched individuals with no prior musical experience (training group) were recruited. Participants underwent RS fMRI scans and completed heartbeat counting and discrimination tasks outside of the scanner (time point 1). The training group additionally had RS scans and interoception tests repeated after a 6-month-long keyboard course training (time point 2). We found no evidence for increased interoceptive abilities in professional musicians relative to non-musicians, nor did we observe any improvements in interoception over the course of musical training. RS FC analysis revealed increased FC within the sensorimotor network in professional musicians compared to the training group at the first time point with no change in FC over time in the Training group. These findings challenge the view that musical training may improve interoceptive abilities. Yet, the results suggest that musical training is related to increased communication within the sensorimotor RS network, which consists of some hubs important for interoceptive processing (namely pre- and postcentral gyri and supplementary motor area).

Unlocking the musical brain: A proof-of-concept study on playing the piano in MRI scanner with naturalistic stimuli.

Music is a universal human phenomenon, and can be studied for itself or as a window into the understanding of the brain. Few neuroimaging studies investigate actual playing in the MRI scanner, likely because of the lack of available experimental hardware and analysis tools. Here, we offer an innovative paradigm that addresses this issue in neuromusicology using naturalistic, polyphonic musical stimuli, presents a commercially available MRI-compatible piano, and a flexible approach to quantify participant's performance. We show how making errors while playing can be investigated using an altered auditory feedback paradigm. In the spirit of open science, we make our experimental paradigms and analysis tools available to other researchers studying pianists in MRI. Altogether, we present a proof-of-concept study which shows the feasibility of playing the novel piano in MRI, and a step towards using more naturalistic stimuli.

How Musical Training Shapes the Adult Brain: Predispositions and Neuroplasticity.

Learning to play a musical instrument is a complex task that integrates multiple sensory modalities and higher-order cognitive functions. Therefore, musical training is considered a useful framework for the research on training-induced neuroplasticity. However, the classical nature-or-nurture question remains, whether the differences observed between musicians and non-musicians are due to predispositions or result from the training itself. Here we present a review of recent publications with strong focus on experimental designs to better understand both brain reorganization and the neuronal markers of predispositions when learning to play a musical instrument. Cross-sectional studies identified structural and functional differences between the brains of musicians and non-musicians, especially in regions related to motor control and auditory processing. A few longitudinal studies showed functional changes related to training while listening to and producing music, in the motor network and its connectivity with the auditory system, in line with the outcomes of cross-sectional studies. Parallel changes within the motor system and between the motor and auditory systems were revealed for structural connectivity. In addition, potential predictors of musical learning success were found including increased brain activation in the auditory and motor systems during listening, the microstructure of the arcuate fasciculus, and the functional connectivity between the auditory and the motor systems. We show that "the musical brain" is a product of both the natural human neurodiversity and the training practice.

New insight into defining the lakes of the southern Baltic coastal zone.

There exist many classification systems of hydrographic entities such as lakes found along the coastlines of seas and oceans. Each system has its advantages and can be used with some success in the area of protection and management. This paper aims to evaluate whether the studied lakes are only coastal lakes or rather bodies of water of a completely different hydrological and hydrochemical nature. The attempt to create a new classification system of Polish coastal lakes is related to the incompleteness of lake information in existing classifications. Thus far, the most frequently used are classifications based solely on lake basin morphogenesis or hydrochemical properties. The classifications in this paper are based not only on the magnitude of lake water salinity or hydrochemical analysis but also on isolation from the Baltic Sea and other sources of water. The key element of the new classification system for coastal bodies of water is a departure from the existing system used to classify lakes in Poland and the introduction of ion-"tracking" methods designed to identify anion and cation distributions in each body of water of interest. As a result of the work, a new classification of lakes of the southern Baltic Sea coastal zone was created. Featured objects such as permanently brackish lakes, brackish lakes that may turn into freshwater lakes from time to time, freshwater lakes that may turn into brackish lakes from time to time, freshwater lakes that experience low levels of salinity due to specific incidents, and permanently freshwater lakes. The authors have adopted 200 mg Cl- dm-3 as a maximum value of lake water salinity. There are many conditions that determine the membership of a lake to a particular group, but the most important is the isolation lakes from the Baltic Sea. Changing a condition may change the classification of a lake.