Global Challenges After a Global Challenge: Lessons Learned from the COVID-19 Pandemic.

Coronavirus disease 2019 (COVID-19) has affected not only individual lives but also the world and global systems, both natural and human-made. Besides millions of deaths and environmental challenges, the rapid spread of the infection and its very high socioeconomic impact have affected healthcare, economic status and wealth, and mental health across the globe. To better appreciate the pandemic's influence, multidisciplinary and interdisciplinary approaches are needed. In this chapter, world-leading scientists from different backgrounds share collectively their views about the pandemic's footprint and discuss challenges that face the international community.

A computational theoretical model for radiofrequency ablation of tumor with complex vascularization.

Radiofrequency ablation (RFA) for liver tumors is a minimally invasive procedure that uses electrical energy and heat to destroy cancer cells. One of the critical factors that impedes its successful outcome is the thermal heat sink effects from complex vascular systems that give rise to incomplete destruction of the target tumor tissue, resulting in therapy failure. To better understand the thermal influence of the complex vascular system during RFA, this work proposes the employment of two 3D fractal tree-like branched networks to investigate which key factors of the tree-like vascular system impact heating process. A three-dimensional finite difference analysis is employed to simulate the RFA treatment. Based on the data acquired from the measured experiments, the simulated results derived from combining the Pennes bioheat model and the boundary condition-enforced immersed boundary method (IBM) have demonstrated close agreement with experimental data with a maximum discrepancy of ±8.3%. We employed the orthogonal design approach to analyze 3 factors, namely, the blood vessel's volume, the average distance between probe center and the blood vessel system and the number of the selected part's branches at three different levels. Results have revealed that the distance between RFA probe and blood vessel plays a major role during the heating process compared with the other two factors. In addition, both the ablating rates and the volume of damaged tissue are slightly reduced with increasing number of blood vessel branches.

Molecular dynamics simulation of gas-phase ozone reactions with sabinene and benzene.

Gas-phase reactions of ozone (O3) with volatile organic compounds were investigated both by experiment and molecular simulations. From our experiments, it was found ozone readily reacts with VOC pure components and reduces it effectively. By introducing ozone intermittently, the reaction between VOC and ozone is markedly enhanced. In order to understand the relationship between intermediate reactions and end products, ozone reaction with benzene and alicyclic monoterpene sabinene were simulated via a novel hybrid quantum mechanical/molecular mechanics (QM/MM) algorithm that forced repeated bimolecular collisions. Molecular orbital (MO) rearrangements (manifested as bond dissociation or formation), resulting from the collisions, were computed by semi-empirical unrestricted Hartree-Fock methods (e.g., RM1). A minimum of 975 collisions between ozone and targeted organic species were performed to generate a distribution of reaction products. Results indicated that benzene and sabinene reacted with ozone to produce a range of stable products and intermediates, including carbocations, ring-scission products, as well as peroxy (HO2 and HO3) and hydroxyl (OH) radicals. Among the stable sabinene products observed included formaldehyde and sabina-ketone, which have been experimentally demonstrated in gas-phase ozonation reactions. Among the benzene ozonation products detected composed of oxygen mono-substituted aromatic C6H5O, which may undergo further transformation or rearrangement to phenol, benzene oxide or 2,4-cyclohexadienone; a phenomenon which has been experimentally observed in vapor-phase photocatalytic ozonation reactions.

Nano-assisted radiofrequency ablation of clinically extracted irregularly-shaped liver tumors.

Radiofrequency ablation (RFA) for liver tumors is a minimally invasive procedure that uses electrical energy and heat to destroy cancer cells. One of the critical factors that impedes its successful outcome is the use of inappropriate radiofrequency levels that will not completely destroy the target tumor tissues, resulting in therapy failure. Additionally, the surrounding healthy tissues may suffer from serious damage due to excessive ablation. To address these challenges, this work proposes the employment of injected nanoparticles to thermally promote the ablation efficacy of conventional RFA. A three-dimensional finite difference analysis is employed to simulate the RFA treatment. Based on the data acquired from measured experiments, the simulation results have demonstrated close agreement with experimental data with a maximum discrepancy of within ±8.7%. Several types of nanoparticles were selected to evaluate their influences on liver tissue's thermal and electrical properties. We analysed the effects of nanoparticles on liver RFA via a tumor rending process incorporating several clinically-extracted tumor profiles and vascular systems. Simulations were conducted to explore the temperature difference responses between conventional RFA treatment and one with the inclusion of assisted nanoparticles on several irregularly-shaped tumors. Results have indicated that applying selected nanoparticles with high thermal conductivity and electrical conductivity on the targeted tissue zone promotes heating rate while sustaining a similar ablation zone that experiences lower maximum temperature when compared with the conventional RFA treatment. In sum, incorporating thermally-enhancing nanoparticles promotes heat transfer during the RFA treatment, resulting in improved ablation efficiency.

Incorporating an immersed boundary method to study thermal effects of vascular systems during tissue cryo-freezing.

In this paper, the three-dimensional thermal effects of a clinically-extracted vascular tissue undergoing cryo-freezing are numerically investigated. Based on the measured experimental temperature field, the numerical results of the Pennes bioheat model combined with the boundary condition-enforced immersed boundary method (IBM) agreed well with experimental data with a maximum temperature discrepancy of 2.9°C. For simulating the temperature profile of a tumor sited in a dominantly vascularized tissue, our model is able to capture with ease the thermal effects at specified junctions of the blood vessels. The vascular complexity and the ice-ball shape irregularity which cannot be easily quantified via clinical experiments are also analyzed and compared for both two-dimensional and three-dimensional settings with different vessel configurations and developments. For the three-dimensional numerical simulations, a n-furcated liver vessels model from a three-dimensional segmented volume using hole-making and subdivision methods is applied. A specific study revealed that the structure and complexity of the vascular network can markedly affect the tissue's freezing configuration with increasing ice-ball irregularity for greater blood vessel complexity.

Studying the performance of bifurcate cryoprobes based on shape factor of cryoablative zones.

Conventional cryosurgical process employs extremely low temperatures to kill tumor cells within a closely defined region. However, its efficacy can be markedly compromised if the same treatment method is administrated for highly irregularly shaped tumors. Inadequate controls of freezing may induce tumor recurrence or undesirable over-freezing of surrounding healthy tissue. To address the cryosurgical complexity of irregularly shaped tumors, an analytical treatment on irregularly-shaped tumors has been performed and the degree of tumor irregularities is quantified. A novel cryoprobe coined the bifurcate cryoprobe with the capability to generate irregularly shaped cryo-lesions is proposed. The bifurcate cryoprobe, incorporating shape memory alloy functionality, enables the cryoprobe to regulate its physical configuration. To evaluate the probe's performance, a bioheat transfer model has been developed and validated with in vitro data. We compared the ablative cryo-lesions induced by different bifurcate cryoprobes with those produced by conventional cryoprobes. Key results have indicated that the proposed bifurcate cryoprobes were able to significantly promote targeted tissue destruction while catering to the shape profiles of solid tumors. This study forms an on-going framework to provide clinicians with alternative versatile devices for the treatment of complex tumors.

Regulating the cryo-freezing region of biological tissue with a controlled thermal device.

Cryoablation is a minimally invasive technique that kills tissue in situ through freezing and is used to destroy unresectable benign and malignant tumors. A key objective of this therapeutic technique is to kill cells within a closely defined malignant region while inflicting minimal thermal injury to the surrounding healthy tissue. The extremely low temperatures used in cryoablation inevitably cause varying degrees of damage to the surrounding healthy tissue. Thus, we proposed a simple, effective, and non-invasive heating device that can be easily incorporated into the existing cryosurgical technology. The chief aim of this device is to reduce the over-freezing of neighboring healthy tissue. A model was developed to study the performance of the proposed device during cryo-freezing of a biological tissue, for example porcine liver. The model, validated with the in vitro experimental data, demonstrated good agreement of up to 6.3%. The performance of the proposed device was evaluated using a dimensionless parameter termed the heating coil coefficient. Results demonstrated that the implementation of a heating coil is instrumental for reducing the size of undesired boundary lesions. The adoption of a 50-mm-diameter heating coil reduced the freezing of neighboring tissue by up to 56% within a freezing time of 10 min. This study establishes a framework for the selection of a correctly sized heating device to reduce the over-freezing of neighboring healthy tissue optimally.

Investigating the cryoablative efficacy of a hybrid cryoprobe operating under freeze-thaw cycles.

Cryoprobes are minimally invasive tools that apply extremely low temperatures to eradicate undesirable cancerous tissue during cryosurgery. At times, they may generate thermal injury to neighboring good tissue leading to the case of over-ablation. The magnitude of this problem becomes significant when tumors are complex, large size and irregular in shape. In this work, we propose a simple yet pragmatic hybrid cryoprobe which can potentially promote better surgical efficacy by improving tumor ablation while reducing undesired thermal injury to the neighboring tissue. To evaluate the performance of the proposed probe operating under cyclic freeze-thaw conditions, a detailed bioheat transfer model incorporating tissue death functions was developed. In-vitro experiments conducted to validate the model yielded a good agreement of 6.7%. We numerically studied the thermal impact of employing the hybrid cryoprobe on tissue temperature distributions. Evaluating the hybrid cryoprobe's control ability, we showed that the proposed device was able to regulate the growth of the ice front while sustaining an excellent coverage of the ablation zone. We also noted the existence of a diminishing temperature effect when alternate freeze-thaw cycles were applied. The performance of the hybrid cryoprobe could potentially lead to a portable and cost-effective device that may prove hugely beneficial for the purposes of surgical planning, rehearsal and control.

Computer simulations on multiprobe freezing of irregularly shaped tumors.

Cryosurgery is particularly suitable for the treatment of unresectable liver tumors. However, a major bottleneck is encountered during the treatment of large-sized irregularly shaped tumors. Large and complex liver tumors have varying degree of shape irregularity. Adopting a multiprobe freezing model, simulations for an irregularly shaped liver tumor were conducted. The model, validated with both in-vitro data from an experimental setup, showed good agreement of up to 5.8%. The chosen mathematical treatment and simulation technique permit the study of employing multiple cryoprobes to destroy cancer cells in irregularly shaped tumors. Results from our study indicated that multiple cryoprobes can be strategically positioned to form ice-fronts with various contours that adhere to the shape and size of the tumor. The amount of cell-deaths within the tumor after the -50°C ice-front can be quantitatively calculated to determine the efficacy of different multiprobe arrangements in order to maximize cell destruction. The paper also underlines a piecewise approach of using several cryoprobes to quickly 'sculpt' the desired shape of the ice-front based on the physical morphology of an irregular-shaped tumor. This numerical study forms an essential framework in allowing surgeons to make informed decisions on the most effective surgical protocol based on the degree of irregularity in shape and size of tumor.

An analytical study on the thermal effects of cryosurgery on selective cell destruction.

The aim of cryosurgery is to kill cells within a closely defined region maintained at a predetermined low temperature. To effectively kill cells, it is important to be able to predict and control the cooling rate over some critical range of temperatures and freezing states in order to regulate the spatial extent of injury during any freeze-thaw protocol. The objective of manipulating the freezing parameters is to maximize the destruction of cancer cells within a defined spatial domain while minimizing cryoinjury to the surrounding healthy tissue. An analytical model has been developed to study the rate of cell destruction within a liver tumor undergoing a freeze-thaw cryosurgical process. Temperature transients in the tumor undergoing cryosurgery have been quantitatively investigated. The simulation is based on solving the transient bioheat equation using the finite volume scheme for a single or multiple-probe geometry. Simulated results show good agreement with experimental data obtained from in vivo clinical study. The calibrated model has been employed to study the effects of different freezing rates, freeze-thaw cycle(s), and multi-probe freezing on cell damage in a liver tumor. The effectiveness of each treatment protocol is estimated by generating the cell survival-volume signature and comparing the percentage of cell damaged within the ice-ball. Results from the model show that employing freeze-thaw cycles has the potential to enhance cell destruction within the cancerous tissue. Results from this study provide the basis for designing an optimized cryosurgical protocol which incorporates thermal effects and the extent of cell destruction within tumors.

Intermittent drying of bioproducts--an overview.

Unlike the conventional practice of supplying energy for batch drying processes at a constant rate, newly developed intermittent drying processes employ time-varying heat input tailored to match the drying kinetics of the material being dried. The energy required may be supplied by combining different modes of heat transfer (e.g. convection coupled with conduction or radiation or dielectric heating simultaneously or in a pre-selected sequence) in a time-varying fashion so as to provide optimal drying kinetics as well as quality of the bioproduct. This is especially important for drying of heat-sensitive materials (such as foods, pharmaceutical, neutraceutical substances, herbs, spices and herbal medicines). Intermittent heat supply is beneficial only for materials which dry primarily in the falling rate period where internal diffusion of heat and moisture controls the overall drying rate. Periods when little or no heat is supplied for drying allow the tempering period needed for the moisture and heat to diffuse within the material. As the moisture content increases at the surface of the biomaterial during the tempering period, the rate of drying is higher when heat input is resumed. It is possible to control the heat input such that the surface temperature of the product does not exceed a pre-determined value beyond which thermal damage of the material may occur. This process results in reduction in the use of thermal energy as well as the mass of air used in convective drying. Thus, the thermal efficiency of such a process is higher. The quality of the product, as such color and ascorbic acid content, is also typically superior to that obtained with a continuous supply of heat. However, in some cases, there will be a nominal increase in drying time. In the case of microwave-assisted and heat pump drying, for example, the capital cost of the drying system can also be reduced by drying in the intermittent mode. This paper provides an overview of the basic process, selected results from experiments and mathematical models for a variety of biomaterials dried in a wide assortment of dryers. It begins with a classification of intermittent drying processes that may be applied e.g. time-varying temperature, air flow rate, operating pressure as well as heat input by different modes and in different temporal variations. The beneficial effects of improving the quality of dried bioproducts by different intermittent processes are also included and discussed.