Electrospun nanofibers have been exploited in multidisciplinary fields with numerous applications for decades. Owing to their interconnected ultrafine fibrous structure, high surface-to-volume ratio, tortuosity, permeability, and miniaturization ability along with the benefits of their lightweight, porous nanofibrous structure, they have been extensively utilized in various research fields for decades. Electrospun nanofiber technologies have paved unprecedented advancements with new innovations and discoveries in several fields of application including energy devices and biomedical and environmental appliances. This review article focused on providing a comprehensive overview related to the recent advancements in health care and energy devices while emphasizing on the importance and uniqueness of utilizing nanofibers. A brief description regarding the effect of electrospinning techniques, setup modifications, and parameters optimization on the nanofiber morphology was also provided. The article is concluded with a short discussion on current research challenges and future perspectives. The fourth industrial revolution has remodeled various technological domains including nanotechnology, biotechnology, new materials, artificial intelligence, and human-machine interfaces. This resulted in the conjugation of nanotechnology with medicine and has also driven a new wave into the energy sector ,2,3. TheThe ability to make large differences with micro/nano scale materials has been realized through nanotechnology ,8. The mOwing to their novel physical and chemical properties in providing high specific surface area, large surface-to-volume ratio, tunable porosity, and the ability of desired chemical functionalization, they are competent enough to overcome many limitations faced in their corresponding macroscales . There aBranched-out applications of the nanofibrous material are presented in Shredding some light on the environmental deterioration, climate change, and depleting fossil fuels, the dire importance of developing renewable and rechargeable energy devices is understood. Here, the nanofibers have been broadly utilized in various types of energy devices  includinOver the past few decades, the global market value of the health care sector, energy devices, and smart fabric technologies has been escalating while crossing the thousand-billion-dollar mark. Along with that, in the near future, market value with innovation is predicted to go far beyond. This review article provided a broad survey on the contribution of electrospun technology over the past 2–3 years in these application fields through discussing the most recent developments accompanied with current and future research trends. The role of nanofibers and associated device performance as well as advantages and disadvantages of each application were emphasized in detail. Here, we anticipated the future scope and direction through summarizing the drawbacks faced in the current research scenario. This article is organized as follows: in the first section, we discuss various aspects of the electrospinning process, including setup, spinning, solution, and environmental parameters. The following section of this article focuses on the most recent research, including the past 2 years of work while emphasizing the role of nanofibers, their structure, and device performance. Finally, we conclude by addressing existing challenges which should be addressed for future perspectives.Nanofiber materials, owing to their one-dimensional nanostructured morphology, are noticed to have superior properties when compared with bulk materials. Various unique properties such as their small size, higher carrier mobility, larger specific surface area, and high surface-to-volume ratio have helped in the emergence of nanofiber technology by introducing nanofibers as an appropriate active material for various applications in the fields of electronics, biomedicine, energy storage, healthcare, fabric technology, etc. . These nSeveral factors affect the nanofiber morphology and uniformity in the electrospinning process. These factors involve precursor solution parameters, process setup parameters, and environmental conditions.Concentration, molecular weight, surface tension, dielectric constant, viscosity, and conductivity of the solution are the affecting parameters of precursor solution towards nanofiber formation . StudiesIn the process setup parameters, applied voltage, flow rate, and solution output nozzle-to-collector distance play crucial roles in nanofiber formation. Electrostatic repulsion force is induced on the solution jet by application of external voltage . This faApart from solution and process conditions, environmental parameters such as humidity and temperature also influence the nanofiber morphology. Temperature changes the solution viscosity, which in turn affects the spinning process . WhereasA conventional electrospinning setup consists of a spinning electrode, solution holder, pushing pump, spinneret, high-voltage power supply, and a grounded collector. Since the development of the electrospinning process, several modification techniques have emerged in order to provide tailored morphology to the nanofibers. Some of these techniques involve coaxial, gas-assisted, porous hollow tube, multi-jet, self-bundling, and roller electrospinning ,74.Coaxial electrospinning is generally employed to fabricate core-shelled structured nanofibers. Here, two solutions are used, in which one acts as a sheath (shell) and the other acts as a core. Two syringes are used in the working with different solutions which are pushed simultaneously to release the material through their respective capillaries and facilitate formation of composite nanofibers, illustrated in Besides these, a few other application-specific electrospinning setups include the charge-injection method , near-fiThe evolution of electrospinning technology and the ability to fabricate tunable nanofibers have facilitated the development of advanced applications in the fields of health care, energy devices, the textile industry, environmental appliances, etc.Being a dominant and necessary sector, health care, or biomedical applications, is of the utmost importance and has become a highly explored area by researchers. As a potential solution to various challenges faced in the field of biomedicine, nanofiber technology is beneficial and has attractive properties. Resolutions such as organ repair, crucial vital monitoring, burns and wound dressing, blood purification, treatment for various diseases, and etc. have been offered by nanofiber technology .Biosensors are analytical tools that assist in the detection, quantification, and monitoring of various analytes such as enzymes, bacteria, cells, nucleic acids, antibodies, etc. present in human body . Such deIn this field, researchers have utilized dimension, porosity, and the surface-to-volume ratio of nanofibers to develop highly efficient antibody detectors .For example, in their recent work, Kim et al.  develope2 g−1 and 99.356 m2 g−1, respectively. Here, inclusion of ZIF-8 crystal within CA fiber network contributed in achieving higher porous structure and high absorption capacity. During cyclic voltammetry measurements, significant redox peaks were observed at ~0.39 V and ~0.51 V. These nanofiber membranes showed long-term stability up to 15 h. Recently, another glucose sensor was reported by Sapountzi et al. [In the field of glucose sensing, electrospun nanofiber-based biosensors are highly explored because of their high surface area, which provides a large immobilization site resulting in increased interaction with analytes, shorter detection time, and increased lifetime . A noveli et al. . Here, pi et al. .2) nanofiber. These were used for label-free detection of β-Amyloid (1–42) in early-stage diagnosis of Alzheimer’s Disease. This hormone-specific capture antibody was covalently immobilized on the carbon electrode modified by SnO2 nanofibers. SnO2 is an intrinsic n-type semiconductor containing a number of oxygen vacancies present at the grain boundaries. These vacancies enable absorption of external molecules which increases Schottky barrier height, resulting in a reduction of conductivity which in turn controls the electrical behavior of the sensor. This inherent heterogeneity of SnO2 can facilitate target analyte detection in fairly low concentrations of analyte. It has been noted that within the concentration range of 1 fg/mL−1 μg/mL, the sensing platform shows a sensitivity of 274.96 (kΩ/ng.mL−1)/cm2 and 0.146 fg/mL LOD.Another type of electrochemical sensor has been recently developed by Supraja et al.  using el2) nanosheet arrays/carbon nanofibers. These nanofibers were used as an electrode in a biosensor for detection of levodopa and uric acid. MoS2 nanosheet arrays are promising materials for sensing applications due to their large surface area, excellent conductivity, high catalytic efficiency, and biocompatibility. When combined with nanofibers, the composite material possessed high electronic conductivity with improved electrochemical active sites by increasing the specific surface area of CNFs network. These composite nanofibers facilitated in achieving stability, good repeatability, and higher sensitivity (0.91 μA μM−1 for levodopa and 0.73 μA μM−1 for uric acid) within the range of 1–60 μM.In another study Wang et al.  used Mol2O2) detection plays an important role for disease determination, as it is a common by-product of some biochemical processes, catalyzed by enzymes  and triggering cancer growth. Daemi et al. [2O2 detection with ZnO-CuO hybrid nanofiber that has a sensitive amperometric response and LOD of 2.4 µM. Though ZnO is a low-cost inorganic n-type semiconductor with a wide band gap of 3.37 eV, high mobility, and non-toxicity, it suffers from weak cycling performance when used as an electrode material. To address this issue, CuO (a p-type stable semiconductor with narrow band gap 1.2–1.9 eV) was incorporated to synthesize a hybrid nanostructure which provided synergetic electrochemical sensing properties due to the presence of binary metal oxides. This hybrid nanofiber exhibited the lowest charge transfer resistance and the highest electrocatalytic performance among other modified electrodes used for the detection of H2O2.In the field of biosensing, hydrogen peroxide ; direct mixing of PVA, SPI, sepiolite, and ketoprofen ; and mixing PVA, SPI, and ketoprofen-preloaded sepiolite . Experiments showed that incorporation of SPI and sepiolite into the PVA nanofibers increased the mechanical strength of the mats up to 40%, making them long lasting and easier to handle [A few of the current innovations in the field of drug delivery were detailed in this section. Recently, Thao et al.  preparedo handle .3)3, and vancomycin) where a biphasic scaffold served as the delivery agent for the eradication of mature biofilms on artificial wounds created on ex vivo human skin explants [A research team from the University of Nebraska fabricated biphasic scaffolds by integrating nanofiber mats with dissolvable microneedle arrays (with 100 to 150 needles on a 6 mm disk) through coaxial electrospinning for simultaneous drug delivery b. This texplants .Staphylococcus aureus is one of the main sources of infection, which can be treated using comprehensive drugs like vancomycin and imipenem. For controlled drug delivery, these drugs can be incorporated within the nanofiber matrix to reduce negative side effects and hazards like nephrotoxicity, cytotoxicity, and hypersensitivity reaction. In this work, a dual drug-loaded nanofiber was prepared using PEO, CS, and vancomycin as shell materials and PVP, gelatin, and imipenem/cilastatin as the core-forming matrix which can perform a simultaneous release of vancomycin and imipenem at different rates into the wound sites. The results showed significant antibacterial activity against methicillin-resistant Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa with no recorded cytotoxicity [A different study involved the production of dual drug delivery of vancomycin and imipenem/cilastatin through core-shell nanofibers composed of polyethylene oxide (PEO), chitosan, PVP, and gelatin (with average fiber diameter varying from 218 to 342 nm) for the treatment of diabetic foot ulcer infections. For such types of wounds, methicillin-resistant toxicity .Bai et al.  synthesi2) were synthesized and optimized through a single-nozzle electrospinning technique. Eudragit S-100 was chosen because of its polyanionic and biocompatible nature which can exhibit controlled swelling in a gastric environment, providing customized drug release. It is water insoluble, as well, as an acidic and is considered as a food-grade polymer due to its non-toxicity. The developed system showed superior thermal stability, tumor regression potential, and pharmacokinetic profile when compared with the plain drug with 90% release of encapsulated drug therapeutic after 12 h, making it a potential approach for localized treatment of gastric cancer. The roles of different nanofiber materials used in various drug delivery applications are summarized in Precise drug delivery to tumor sites in cancer treatment is crucial for improved therapeutic efficacy and minimizing adverse effects, which is an unmet clinical need . GastricWound dressing is a process of regenerating dermal and epidermal tissues and a vital step for rapid healing of the affected part while offering protection against infection due to environmental exposure. A number of biochemical actions/phases such as proliferation, homeostasis, inflammation, and remodeling are involved in this dynamic activity . For theArtemisia annua L. is a type of annual herb that has been used for various treatments and wound healing [Bombyx mori cocoon extract, has good cytocompatibility and biocompatibility in both in vivo or in vitro applications. SF possesses attractive characteristics such as cell adhesion and proliferation that promotes wound healing. The fabricated membrane showed breaking strength ranging from 4.0 ± 1.0 MPa to 7.4 ± 0.3 MPa and Young’s modulus from 215.3 ± 2.0 MPa to 394.9 ± 1.3 MPa with elongation at break from 34.0 ± 7.8% to 127.0 ± 7.0%. The study proved that the obtained mechanical and anti-inflammatory property was suitable for wound dressing, without cytotoxicity. This provided a new method for the development and application of ART for wound healing. healing . In thei healing  utilizedBlumea balsamifera (BB), which is also known as “Sambong”, is one of the essential oils which have been used for thousands of years in Southeast Asian countries. Ullah et al. [2/day), and good antibacterial and antioxidant properties. The inclusion of BB oil resulted in a decrease in tensile strength and increase in fiber diameter, reducing porosity of the materials. They were also observed to undergo first-order release kinetics immediately after biphasic release. Ciprofloxacin is another well-known antibacterial drug that has been utilized for healing a wide range of wound infections. A study involving in vitro and in vivo evaluations of ciprofloxacin -loaded chitosan/polyethylene oxide/silica nanofibers fabrication through electrospinning for treating cutaneous wounds of Balb/C mice was carried out by Hashemikia and coworkers  while efficiently preventing short circuits, respectively. Along with fulfilling the above requisites, nanofibers can also provide mechanical strength and high electrochemical stability with improved cycle life through well interconnected porous membranes ,164. SomIn battery technologies, Lithium-ion batteries (LIBs) are the most researched area due to their high volumetric, gravimetric energy density with light weight and good shape versatility, which has led to various miniaturized applications in electrotonic as well as electrical appliances. However, achieving high power capability along with high energy density along the way remains a challenge. Here, electrospun nanofibers are implemented to overcome these difficulties by enhancing electric and ionic conductivities of LIBs through utilizing high specific surface area, porosity, controllable fiber diameter, and well interconnected porous structure. Moreover, they can be functionalized to have controlling ability over properties like electrolyte affinity, pore size, and thermal stability to achieve enhanced cell performance .−5 S cm−1 and cycling stability of 135 mAh g−1 after 100 cycles at 0.4 C. Comprehensive upgradation of the electrolyte was observed through obtaining higher ion conductivity, mechanical and electrochemical stabilities, and interfacial resistance against Li dendrites. For portable, wearable electronics, development of flexible and foldable LIBs that provide shorter charge and longer discharge time have received increasing attention. Traditional LIBs usually lack in the area of flexibility due to their weight and rigid built-up characteristics. Hence, to address such an issue, a study involving free-standing and foldable vanadium oxide/multichannel carbon nanofibers (V2O3/MCCNFs) composites prepared via electrospinning  using a binder-free and self-supporting V2O5 nanofiber-based cathode with magnesium anode and dual-salt electrolyte containing both Mg2+ and Li+ [2O5 is a promising intercalation compound, as it can provide high storage capacities and energy densities owing to its redox chemistry. The presence of VO5 bilayer chains makes it a suitable cathode material for MLIBs. The space between the layers contain water molecules, which provides large vacancy to host intercalating ions and can facilitate ion insertion into intercalation sites. Here, V2O5 nanofiber cathode helped in achieving high energy densities by providing high intercalation potential. In this rechargeable electrochemical storage system, the cathode provided a high operating voltage of up to 1.5 V vs. Mg/Mg2+ while achieving storage capacities of around 386 mAh g−1, complemented with an energy density of 280 W h kg−1 and good cycling stability of 200 mA g−1 over 500 cycles.LIBs have pioneered battery technologies for decades with their high performance. However, there are still disadvantages such as toxicity and safety hazards due to their highly reactive properties and thermal runaway caused by dendrite formation, which has triggered research for mono and multivalent metal-ion battery systems. In past few years, magnesium-ion batteries (MIBs) have exhibited promising qualities due to the abundance in availability of magnesium and its ability to provide a volumetric capacity of 3832 mA h cm and Li+ . V2O5 isAnother hybrid battery study on a hygroelectric generator was carried out by Feng et al.  using an2 when in contact with liquid water, hence making it a potential candidate in water or vapor leakage detection, portable energy source, humidity sensors, etc. The fiber network in this study acted as a good water-absorbing material and could produce a high current density exceeding the reduction potential of magnesium by tuning the oxidation of the carbon nanofiber.The device could generate an open-circuit voltage up to 2.65 V and average peak short-circuit current density of ~6 mA/cm−1), easy conversion and storage, abundancy in nature, low cost, and environmental friendliness. Zang et al. [2O4 porous nanofibers by electrospinning to use as bifunctional catalysts in the rechargeable Zinc air battery. NiO has been proven to be an ideal electrocatalyst in oxygen evolution reaction (OER)/oxygen reduction reaction (ORR) due to its special eg orbitals, as the surface of nanoscale NiO is oxidized easily to active Ni3+ species. On the other hand, spinel structured NiCo2O4 has also been known as a promising OER, ORR electrocatalyst, as the cobalt and nickel ions can introduce various functions within the structure. In this engineered structure of NiO/NiCo2O4, chemical bonds that form at the interface facilitate a higher charge-transfer rate. In parallel, the heterostructure also promotes the intrinsic activity of OER/ORR through exposure of more electrocatalytic active sites. As a result, the interface engineering of NiO/NiCo2O4 with numerous mesopores synergistically provides sufficient oxygen transport, satisfactory intrinsic activity, and abundant electrocatalyst’ active sites. Here, NiO/NiCo2O4 porous nanofibers contributed to enhancing electron transfer rate and promoting the intrinsic activity through providing exposure to more electrocatalytic active sites. The synthesized catalyst exhibited superior electrocatalytic performance, lower overpotential of 357 mV at 10 mA cm−2, half-wave potential of 0.73 V, specific capacity of 814.4 mA h g−1, and cycling stability of 175 h.Other than Li and Mg batteries, Zn is another transition metal which has been highly explored in battery research for its high theoretical gravimetric energy  nanosheets. Here, NiGa2S4 nanosheets improved the electrochemical activity by promoting electrolyte-to-electrode diffusion. Along with this, superior electrical conductivity of the Ni@CNF provided electrochemical stability and also enhanced charge transfer that occurs in the electrode -derived electrospun polyacrylonitrile/cyclodextrin (CD) composite PMnCD(β) using β-CD phase, which exhibited a hierarchical porous structure. Hybrids of nano-sized MnO2 and carbon nanofibers have been declared as suitable candidates for supercapacitor electrodes, as they simultaneously exhibit high pseudo capacity and excellent electronic conductivity. The as fabricated PMnCD(β) electrode showed a large specific surface area for accumulation of ions and fast ion diffusion due to the mesopores and nitrogen groups. The β phase of CD nanofibers exhibited a hierarchical porous structure with a large specific surface area of 499 m2g−1, and 0.32 cm3g−1 total pore volume, that assisted in accumulation of hydrated molecules for double-layer formation by improving adsorption efficiency. Here. the electrode reported a maximum energy density of 25.3–16.0 Whkg−1 within the power density range of 400–10,000 Wkg−1, high specific capacitance of 228 Fg−1 at 1 mAcm−2, and excellent cycling stability of 94% after 10,000 cycles.The development of supercapacitors with high energy density and rate capability is extensively explored for energy storage applications in electric vehicles and in wearable portable electronic devices. However, the conventional supercapacitors lack flexibility. To address this issue, Kim et al.  fabricatlectrode a. These g et al.  develope3O4/N-CNTs@CNFs for supercapacitors, exhibiting a promising performance through self-templated MOF-synthesized onto carbonized electrospun carbon nanofibers (CNF) mat. The composite supercapacitor exhibited a high specific capacity of 238 mA h g−1 at 1 A g−1 with a long lifespan and high rate capability. The assembled asymmetric supercapacitor could deliver 52.9 Whkg−1 specific energy at a specific power of 873.5 Wkg−1 outstanding lifetime  [2g−1 when ECNFMs were carbonized at 1000 °C. A symmetrical supercapacitor device was prepared by sandwiching PVA/(Sulfuric acid) H2SO4 hydrogel within two freestanding ECNFMs. The device exhibited a high specific capacitance of ~99.72% along with excellent capacitance retention of ~320 mF cm−2 at 0.25 mA cm−2 after 10,000 charge/discharge cycles. Along with that, a large energy density of ~11.1 μWh cm−2 was obtained for input power density of 500 mW m−2 [Nowadays, to further enhance the specific surface area, structural uniformity, porosity, functionality and diverse topology of supercapacitors, metal–organic frameworks (MOFs), and their derivatives are being integrated to the electrospun fibers network. Recently, Mukhiya and coworkers developed a 3D Co cycles) . Apart f0 mW m−2 .2SO4) as well as polymer gel electrolyte (using PVA-1M H2SO4 hydrogel). The solid-state electrolyte device could operate at higher voltages  compared with the aqueous electrolyte . Even after 10,000 cycles, the device exhibited 62.6 Wh/kg energy density and 1.25 kW/kg power density with 99.5% efficiency, providing futuristic energy storage applications of carbon nanofibers-based solid-state electrolyte [In another study, Singh et al. fabricated all-solid-state supercapacitors by kraft lignin-derived heat-treated carbon nanofibers. Although most of the studies use synthetic PAN polymer, its higher cost, non-renewable nature, and tendency to release toxic gases like HCN during heat treatment have promoted the usage of some renewable green precursors like Lignin, cellulose, etc. for synthesizing CNF. In this study, Lignin was selected for its abundancy in nature, non-toxicity, higher aromatic structure carbon content, and renewability. Higher specific capacitance 196.63 F/g was achieved for 1 A/g current density. For direct comparison, the device was tested in both aqueous  , triboel2 at a 100 MΩ load resistance [2 at a load resistance of 100 MΩ, which turned out to be about seven times greater than other nanofibers obtained from other setups.To produce a scalable energy harvester for human motion monitoring and powering various light-emitting diode, Huang and coworkers used a simple one-step-electrospinning technique. Here, TENG was developed by electrospinning ethyl cellulose/polyamide 6 and poly(vinylidene fluoride) (PVDF) polymers A. In thisistance . For comsistance . Both PI2 under a 30 MΩ load resistance. Due to their high energy conversion efficiency and ease of implementation, piezoelectric nanogenerators are extensively exploited as energy harvesting devices [2O4) (400 nm diameter) nanofiber films [2O4 within PVDF fiber resulted into transformation of microstructure from α-phase to β-phase by 68%. The fabricated device exhibited ferroelectric properties with a highest polarization value of 1.46 μC/cm2. In vibrational testing mode, the sample showed a maximum saturation magnetization value of 4.2 emu/cm3, open circuit voltage of 10 V, and 4.8 V output voltage under a weak AC magnetic field of 10 Oe at 50 Hz.Coaxial electrospinning is a technique mostly used for simultaneous electrospinning of solutions with poor dispersion and incompatibility. Zhang and group constructed a high-output-performance nanofiber TENG device comprising inorganic/organic hybrid materials to achieve synergic dielectric and dispersity modulation . In this devices . Designi devices  fabricater films . ElectroApart from nanogenerators, solar (photovoltaic) cells are also energy harvesting device that converts light energy into electric energy. As the demand for cleaner energy is growing, solar cells, capable of producing renewable energy have been widely explored for their portability, efficiency, durability, and low maintenance. Nanofibers have been extensively used for solar cell research to achieve improved efficiency with other advantages like large scale production, miniaturization, etc. There are mainly three types of photovoltaic devices: dye sensitized, perovskite, and organic cells which have been explored recently . A few o−1 with 78.5% optical transparency of (at 550 nm), which was comparable to the commercial polyethylene naphthalate/indium-tin-oxide substrate. The device was able to withstand 15 peeling cycles and 500 bending cycles, displaying its high mechanical stability and very low thermal expansion coefficient (3.37 × 10−6 K−1) that aided in obtaining a new perspective for the development of sustainable organic photovoltaics [Eco-friendly organic solar cells have several advantages, including biodegradability, safety, low-cost, lightweight properties, large surface areas, and nontoxic characteristics. Lin et al. successfully developed Ag NWs embedded TEMPO-oxidized eco-friendly cellulose nanofibers photovoltaic substrates using a facile, printable transfer method. In high-performance flexible OPVs, plastic flexible substrates like polyethylene terephthalate (PET) and polyethylene naphthalate (PEN) are mostly used, which have very high coefficients of thermal expansion that cause severe expansion or shrinkage, resulting in cracks. To avoid such damages, TEMPO-oxidized Cellulose NFs were used here. It was observed that the TEMPO-mediated oxidation largely improved mechanical strength of CNFs. Here, the nanofiber network enabled the formation of a homogeneous hybrid with Ag NWs and concurrently allowed a higher percentage of visible light. The device showed a low sheet resistance of 2.62 Ω sqvoltaics .2) nanofibers-based solar cell was conducted by Nien et al. [2 nanofibers acted as a barrier layer which reduced the charge transfer resistance by preventing recombination of photogenerated electrons and holes. As FePt nanoparticles exhibit high chemical stability and coercivity in addition to their excellent magnetic property, they can reduce the surface charge recombination rate of metal oxides. Hence, in this study, FePt nanoparticles were mixed with TiO2 nanofibers to modify the photoanodes. The device showed an output intensity of 100 mW/cm2 and a 16% increase in photoelectric conversion efficiency when compared with the TiO2 photoanode, which was 3.79%, and FePt/TiO2 nanofiber photoanode, which was 4.41%. In general, solar cell transparency is a crucial factor to capture and utilize the solar energy. In this direction, a study involving fabric-like transparent electrode for flexible perovskite solar cell was carried out by Zhai et al. [In spite of many advantages, there are few drawbacks such as low efficiency, stability, and strength, which triggered research interest in looking for other alternatives. A recent study on iron platinum (FePt)/Titanium dioxide (TiOn et al. . The devi et al. . In thisThe roles of different nanofiber materials used in various nanogenerator applications are summarized in This article was structured and presented in a format to provide an understanding of the state-of-the-art properties, characteristics, and advanced applications of nanofiber technology. Nanofibers with high surface area and tunable porosity, along with other novel properties like high conductivity, superior electrochemical activity, improved mechanical strength, structural integrity, etc., are being fabricated through the unique, simple, lucrative, and versatile technique of electrospinning. The ability to affect nanofiber morphology with respect to the electrospinning setup modifications, along with environmental, solution, and process parameters, was discussed in the review. Applications including biosensors, tissue engineering, wound healing, and drug delivery in health care sector and batteries, supercapacitors, solar cells, and nanogenerators in energy devices were elaborated in this article. Although electrospinning is the most versatile among existing techniques, there are a few drawbacks such as: requirement of high voltage and conducting targets; difficulty in achieving in situ deposition; scalability for mass production; requirement of specialized equipment and reproducible systems for commercialization; difficulty in obtaining long, continuous, and oriented nanofiber; avoiding beads formation during electrospinning caused by solution viscosity or net charge density that reduces effective surface area of fibers; becoming friable after calcination; and difficulty in fabricating nanofibers with diameters less than 10 nm, etc. Along with these, there are also application-specific shortcomings for each field. In health care applications, despite having unique properties, electrospun nanofibers show a low level of biodegradability, poor infiltration of cells or drugs into the scaffolds, and a consistency mismatch between the nanofibers and bone extracellular matrix, etc. Similarly, some challenges have also been faced in the applications of electrospun nanofibers-based energy devices. Some of these are inefficient inhibition, unavailability of efficient and durable redox activation and stability, limited theoretical specific capacity, the need of improved energy density, reproducibility, extended shelf life, and longer cycle life, etc.The drawbacks and challenges that are being faced currently have become the problem statement for future research works. Commercialization and meeting the demand of nanofiber technology have become prime focuses for future research which aim towards large-scale production for facilitating laboratory-to-market transition. The brittleness of electrospun nanofibers is also a major setback for various applications, which has become another triggering factor for upcoming research, especially on developing highly flexible continuous fibers. To obtain synergistic chemical as well as physical characteristics, the addition of nanofillers within the fiber matrix has become another key researched area for both biomedical and energy related applications. In the case of tissue engineering, wound dressing, and drug delivery, qualitative to quantitative analysis for cytocompatibility of the fibrous scaffolds for cell adhesion, proliferation, and differentiation is becoming an essential feature. Along with this, exploration through in vivo animal/human study with clinical trials for evaluating real-life practical applicability of the device or scaffold should also be emphasized. On the other hand, in energy devices, synthesizing nanofiber-based electrodes with optimized porosity and pore distance for improving ion carrying and storing capacity is one of the upcoming major goals which will subsequently enhance both voltammetric energy and power density. The aim of this review was to provide an overall insight on electrospun nanofibers and their advanced applications through understanding the direction of research that has been conducted in the past 2 years in the fields of health care and energy devices.


The area detector 320‐row CT scanner, which can cover the whole heart in one rotation, can aid in reducing radiation exposure during electrocardiography (ECG)‐gated coronary CT angiography (CCTA). Recently, researchers have proposed dose‐modulated dynamic CCTA with a 320‐row scanner for the detection of functional myocardial ischemia. In the present study, we compared and validated the radiation dose of this method with that of the standard CCTA method and the latest diagnostic reference levels (DRLs).The study included a total of 164 consecutive patients with suspected or known coronary artery disease (CAD) who underwent CCTA with a 320‐row scanner. The patients were randomly divided into dynamic and standard CCTA groups, and the CT dose index (CTDIvol) and dose length product (DLP) calculated by the CT system were compared between the two protocols and with the latest DRL.p = 0.0014). DLP was also significantly higher for standard CCTA than for dynamic CCTA . For standard scans, CTDIvol and DLP exceeded the 2020 DRL in Japan in 16% (12/77) and 17% (13/77) of cases, respectively. In contrast, rates for the dynamic scan were only 1% (1/87) for CTDIvol and 0% (0/87) for DLP.Standard and dynamic CCTA scans were performed in 77 and 87 patients, respectively. CTDIvol was significantly higher for standard CCTA than for dynamic CCTA (41 ± 35 mGy vs. 22 ± 7 mGy, The dose of radiation exposure during dynamic CCTA with a 320‐row scanner does not exceed that of standard CCTA and is sufficient to meet the latest DRL. Thus, our results suggest that the method is safe from the perspective of radiation exposure. It is estimated that approximately 60% of medical exposure occurs during CT examinations.With the advent of a 64‐row CT scanner in 2004, it is now possible to perform noninvasive imaging of the coronary arteries.Functional coronary stenosis, rather than anatomic coronary stenosis, is key in determining whether to perform coronary interventions such as revascularization therapy.22.1The study included a total of 186 consecutive patients with suspected or known CAD who underwent CCTA using a 320‐row CT scanner  at our institution between May 2020 and November 2020. Of the 186 patients, 22 patients with a body weight of <40 kg or >80 kg were excluded. A total of 164 patients were finally included. Patients with a history of arrhythmia or previous treatment were scanned using the standard CCTA protocol, while the others were randomly divided into dynamic CCTA and standard CCTA protocols. Age, sex, height, and body weight were collected from the patients’ medical records. CTDIvol and DLP were collected from the dose recordings of the CT equipment.2.2metoprolol (20 mg) was administered to patients with a heart rate of ≥65 beats/min. Immediately before image acquisition, all patients received sublingual nitroglycerine (0.2 mg). First, the test‐bolus examination was performed using non‐electrocardiography (ECG)‐gated axial scans at the ascending aorta to determine the optimal scan timing. Next, dynamic CCTA was continuously performed in mid‐diastole for 8–12 cardiac cycles with prospective ECG‐gating scans after a 10‐s injection of contrast medium . One scan of the dynamic CCTA was performed as a boost scan for standard CCTA at the peak phase of the ascending aorta .Data are expressed as the mean ±standard deviation (SD) for continuous variables and as a number  for categorical variables. To examine differences in demographic data between the normal coronary CT group and the dynamic CT group, we used the unpaired Student's t‐test for continuous variables and the Chi‐square test for categorical variables. The differences in CTDIvol and DLP between the standard and dynamic CCTA groups were analyzed using the Mann–Whitney U‐test. Statistical significance was established using a two‐tailed 3The 164 patients  ranged in age from 21 to 89 years, with an average age of 62 years. Dynamic CCTA and standard CCTA were performed in 87 and 77 patients, respectively. Weight and heart rate were significantly higher in patients who underwent standard CCTA than in those who underwent dynamic CCTA. There were no significant differences in age or sex between the two groups (Table p < .0001). CTDIvol for standard CCTA was significantly higher than that for dynamic CCTA . The DLP for standard CCTA was significantly higher than that for dynamic CCTA   and 17% (13/77) of cases, respectively. In contrast, rates for the dynamic scan were only 1% (1/87) for CTDIvol and 0% (0/87) for DLP  and 0% (0/87) of cases, respectively. These rates were also lower than those for the standard CCTA protocol . Recently, Kojima et al. reported a DLP of approximately 330 mGy × cm, estimated based on the standard chest k‐factor of 0.026 mSv ×mGy−1 cm−1 in a similar protocol.The mean DLP for the original dynamic CCTA reported by Nagao et al.We acknowledge the limitation that CTDIvol and DLP in this study are not dosimetric measurements. However, we measure CTDIvol and DLP one a year using a human phantom and a dosimeter. We have confirmed that these dosimetric measurements are consistent with the values estimated from the CT system. Furthermore, the values of CTDIvol and DLP estimated from 320‐row scanner are reported to be stable and less variable in large facilities such as ours.5The dose of radiation exposure during dynamic CCTA with a 320‐row scanner does not exceed that of standard CCTA and is sufficient to meet the latest DRL. Dynamic CCTA with a 320‐row scanner was able to reduce radiation exposure by 50% of the DLP compared to standard CCTA. If functional coronary stenosis can be detected using dynamic CCTA, our results suggest that the method is safe from the perspective of radiation exposure.This work was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI (19K08209).All authors declare no relationships with any companies whose products or services may be related to the subject matter of the article.All authors contributed to the study conception and design. Material preparation, and data collection and analysis were performed by Yukako Izoe, Michinobu Nagao, Mei Tokai, Hiroyuki Hashimoto, and Isao Tanaka. The first draft of the manuscript was written by Yukako Izoe, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.


Background: Concerns with problematic research are primarily attributed to statistics and methods used to support data. Language, as an extended component of problematic research in published work, is rarely given the same attention despite language's equally important role in shaping the discussion and framings of presented data.Purpose: This study uses a topic modeling approach to study language as a predictor of potential bias among collected publication histories of several health research areas.Methods: We applied Latent Dirichlet Allocation (LDA) topic models to dissect publication histories disaggregated by three factors commonly cited as language influencers: (1) time, to study ADHD pharmacotherapy; (2) funding source, to study sugar consumption; and (3) nation of origin, to study Pediatric Highly-Active Anti-Retroviral Therapy (P-HAART).Results: We found that, for each factor, there were notable differences in language among each corpus when disaggregated by each factor. For time, article content changed to reflect new trends and research practices for the commonly prescribed ADHD medication, Ritalin. For funding source, industry and federally funded studies had differing foci, despite testing the same hypothesis. For nation of origin, regulatory structures between the United States and Europe seemingly influenced the direction of research.Conclusion: This work presents two contributions to ethics research: (1) language and language framing should be studied as carefully as numeric data among studies of rigor, reproducibility, and transparency; and (2) the scientific community should continue to apply topic models as mediums to answer hypothesis-driven research questions. Peer-reviewed research is facing unprecedented retraction rates for published work  identify and discuss how language is easily influenced by external factors; and (2) demonstrate how tools such as topic models can detect language variability in a less subjective manner by analyzing the publication histories of various health-related fields. Together, we hope to promote dialogues in the academia that emphasize language's role in shaping or framing scientific discussions. Importantly, we intend to validate this area of study—language framing—as equally important to investigations of bias.and sensationalizing findings (linguistic) to create mainstream appeal of his science  that led to increased scrutiny of his data and methods employed to generate his findings.Readers of all published materials, generally, hold an implicit assumption that the communication is objective and written in clear, unequivocal terms. In practice, however, the manner in which language is written and contextualized  may bias how the message is understood. This practice is known as framing, which, in communication literature, generally refers to how messages are strategically crafted to convey a message in a specific way  to identify commonly occurring themes across documents .LDA uses Bayesian inferencing and Gibbs sampling to compare each word (x) with all other words (y) across the entire corpus to identify which words, and groups of words, are most probabilistically associated with one another  as a tool for reducing unintentional reviewer bias in systematic literature reviewing, (2) for practical thematic exploration of qualitative data and thematic analysis validation, and (3) for comparing similar corpora to explore semantic similarities and differences. .Indeed, current exploratory topic modeling applications only seek to consolidate large collections of text and identify overall themes. The analytic capabilities of topic modeling, however, extend beyond this exploratory lens. With regard to the subjectivity of challenging linguistic framing, approaches that include topic models to consolidate and map themes among text could provide a more objective framework with which to detect linguistic biases. Specifically, by using a machine to consolidate and thematically map scientific literature—i.e., archives of published research—one could compare these corpora for semantic differences when disaggregated by factors that are historically known for introducing bias into the science. This could, in turn, uncover important nuances across corpora that may demonstrate how these factors may intentionally or unintentionally be influencing language patterns.A language-altering (or influencing) factor is defined here as any decision, action, or contribution to the research process that carries the potential to influence specific word choices McArdle, . Though This study is a machine-learning-based content analysis of abstracts from published studies collected via online repositories, including PubMed, EbscoHost, and Web of Science.Our aim is to highlight how language used to frame these scientific reports may change when they are disaggregated, and compared, by various factors: time, funding source, and nation of origin. Our intent with this paper is not to scrutinize one, or any, area of research but, rather, to call attention to linguistic framing broadly. Therefore, to compare corpora by time, funding source, and nation of origin we purposefully collected three groups of abstracts from mutually exclusive research areas: ADHD pharmacotherapy (to test language changes over time), sugar consumption (to test language differences by funding source), and pediatric Highly Active Anti-retroviral Therapy (P-HAART) (to assess language differences between the United States and European Union). See all health research, they still embody distinct heuristic examples with which to catch differences in linguistic framing within this small-scale study.We selected these specific content areas for several reasons. First, each of these areas  is a prolific area of study, meaning there is a high volume of scientific output per each area. As such, these fields provide a rich library of language data to generate clear topic models for each language-altering factor  for analysis. We generated one topic model for each 5 year increment, then compared those models, respectively.This corpus, comprised of articles testing the link between sugar consumption and poor health-related outcomes, sought to evaluate linguistic framing in studies with different funding mechanisms. To compose this corpus, we searched PubMed, EbscoHost, Web of Science, and Medline, using various combinations of the terms “sugar” and “diet,” which, after excluding duplicates, yielded 828 unique abstracts. We then narrowed these abstracts further by removing articles that did not expressly indicate either federal funding  or industry funding  as the primary benefactor of the study. Our final abstracts included for analysis were 212 federally funded studies and 71 industry studies published from 2014 to 2018. We generated two topic models, one for federal and one for industry funding, and compared those models, respectively.This corpus, composed of articles testing the efficacy of Pediatric HAART, sought to evaluate the linguistic framing of studies originating from either the United States or Europe. We intentionally selected this comparison to compliment the extended history of comparative EU/US medical research , (2) stemming the document , and (3) creating a document term matrix, which is an aggregate calculation of how many times every word is used in a corpus, or sub-corpus.All analyses, which included generating various LDA topic models for each language altering factor, were conducted using R version 3.4.2 and the following downloadable R packages: (1) topicmodels (sic), (2) tm, and (3) tidyR (sic). These packages—which are specialized program extensions for R—run text data through a multi-step process to prepare for analysis, including: (1) removing punctuation, numbers, special symbols  topics in each decade changed gradually over time. In the 1970s and 1980s, children and boy were common terms, potentially reflecting the populations most frequently addressed in the studies. Beginning in the 1990s, however, terms reflecting ADHD pharmacotherapy among other populations began to emerge often enough to appear within other latent topics, such as parent, human (in place of child), rodent and, in the 2010–18 sub-corpus, adult. Other words, such as abuse, toxic, and addict, begin appearing in the 1990s and beyond but remained entirely absent from older models. Bolded columns represent the computer-identified most salient topic in the corpus. Of note, words in the most salient topic across all decades remained fairly consistent: boy, reflected the only population being tested— girl, adolescent, and adult did not appear in that decade's sub-corpus at all. Subsequent decades saw diversification regarding who was tested, eventually including girls, adults, and adolescents. Beginning in the late 90s, and extending into the 2010–2018 decade, the terms adult and adolescent became more important  than the original 1970s term “boy.” Further, words such as abuse, adverse, and side (as in “side-effect”) also gained importance and became much more visible over time.In the 1970s, for example, the 79th most used word, This analysis sought to determine if funding source  for studies testing the link between table sugar and health comorbidities influenced language patterns. As shown in diet, food, sugar, intake, increase, weight, high, consumption, energy, and risk. Topics 2, 4, and 5 centered on outcomes related to sugar consumption , and topic 3 centered on interventions and cost .Within the federally funded topic model, the most important topic contained the words intake, sugar, diet, cosum, food, energy, beverage, consumpt, dietary, and pattern. Diet, as in food consumed daily, was a recurrent theme in the majority of the remaining topics, especially observable in topics 2, 3, and 4. In those topics, food related words such as calori, effect, baseline, promote, breakfast, fruit, juice, eat, among others, were also common. Topic 1 in the industry-funded topic model, was notably different from topics 2, 3, 4, and 5. Rather than emphasize diet— as in food consumption—Topic 1 uniquely discussed outcomes of sugar consumption such as increased adiposity and heart function .The industry-funded topic model seemed to have a different emphasis altogether. The most salient theme, Topic 5, contained the following words: This analysis sought to determine if P-HAART studies conducted, funded, and published in the United States and in other European nations would influence language patterns. As with the previous analyses, there were indications of language differences between domestic and international studies see .HIV, infect, children, pediatr, health, report, care, youth, infant, and disease. Topics 2 and 3 in the US-based model focused on HIV transmission and pharmacotherapy applications: drug, medic, birth, issue, viral, test, aid, born, recommend, high, dose, exposure, matern, among others. Topics 4 and 5 used slightly different words to convey a focus on general recommendations and federal guidelines, such as regimin, factor, cdc, human, research evalu, adult, and patient.Language in US-based studies focused on prescribing and administering of P-HAART to infants upon birth. The most-salient theme for US-based studies contained the following words: art, parent, manage, status, diagnos, drug, screen, europ, hundred. Topic 3 reflects guidelines using the words guideline, health, recommend, provid, migrant, aid, adolescent, and disease. Topic 1, on the other hand, addresses national reports of HIV infection: year, present, patient, country, and report. Topic 5 can further be interpreted as care for children living with HIV: HIV, children, infect, paediatri, care, age, women, clinic, follow, European.Similarly, the European studies also focused on medication adherence. However, these studies focused more on management of HIV rather than HAART uptake. The most-important theme contained the following words: For each of the three language altering factors, the resultant topic models uncovered various linguistic differences that may be partially explained by the factors discussed above. We note that it is not our intent to accuse authors of being linguistically biased, we simply aim to highlight how the factors outlined up above can, and often do, play a role in shaping the direction of linguistic patterns and framing of published research. Below, we situate our findings within the context of their respective literatures to explain many of the differences identified in the topic models.As noted, we observed linguistic changes in ADHD pharmacotherapy language between 1970 and 2018. Part of those changes may be partially explained by the growth of ADHD pharmacotherapy as a publishable research field over time. In the 1970s—roughly the start of the ADHD pharmacotherapy era—we collected fewer than 100 scientific publications on Ritalin and other ADHD-related medications. In the 2010 decade we collected nearly 3,000 unique abstracts from diverse fields, including psychology, sociology, biology, epidemiology, and others.girl, adolescent, and adult eventually emerge as components in emergent topics. While this drug was initially intended to primarily treat children , the shift in demographics prompted new clinical trials to determine if Ritalin regimens were safe long term   there were two major changes to reflect updated positions on ADHD and ADHD pharmacotherapies: first, ADHD was reclassified from a psychological disorder to a chronic condition, and second, the appropriate ages to administer Ritalin were changed to include children as young as 4 and adults 18 and over  differences in industry vs. federally funded sugar studies.However, those accusations may also be misguided without carefully reviewing industry funded studies further. When the UK's Academy of Medical Royal Colleges argued 30 min of moderate exercise five times weekly was more powerful than any drug at preventing chronic disease, Malhotra et al.  who discbirth, issue, virus, transmiss, infant, hiv, children). More evident was the sense of urgency in administering P-HAART at the time of birth: birth, issue antiretrovir, prophylaxi, receive. In the EU model, however, the target population was not as clear, as there were more emergent groups throughout the corpus and final topic model: provid, migrant, aid, adolesc, women, children. Absent altogether from the European model was the word infant despite this corpus being composed of studies regarding pediatric HAART.Regarding nation of origin, the US topic model was clear regarding the targeted population: infants and children . Simply, any infant is to begin P-HAART even before diagnosis is confirmed.”“The uses of anti-retroviral (ARV) in infants include: “one or more ARV drugs to a newborn [immediately] without confirmed HIV infection to reduce the risk of HIV acquisition HIV older children/adolescents and not pre-diagnosed infants: “PENTA guidelines seek to optimize treatment for children…particularly during adolescence, [when] care may need to be individualized…[additional]consideration of ART initiation in all children aged 1–3 years [is needed] in order to minimize risks of disease progression or death”  influenced language patterns presented in published, peer-reviewed research. Our findings illustrate that, through topic modeling, we successfully identified linguistic differences by each language influencing factor, including shifts in the intended demographic populations of a research field, and foci of the studies. In particular, these differences clearly demonstrate how scientific language aligns itself with the larger narratives within which it is embedded, meaning that external factors inevitably influence the direction of a research field. Given that our findings underscore the vulnerability of language to such factors, we argue that language framing in scientific reporting should be an equally important consideration  when evaluating the merit of scientific work. Even if, through this study, we could not objectively declare instances of bias within collections of abstracts, the linguistic differences identified for each factor warrant pause for concern and evidence that further evaluations are needed to rigorously examine science from a linguistics perspective.Importantly, our findings also situate topic modeling as a valid, more-objective public health tool with which to evaluate language and text, whether that be from published peer-reviewed literature, industry-based promotional advertising, public policy documents, and/or social media and internet content. Though this approach is still a novel in some fields, including health, tools such as topic modeling have been widely used in other fields to identify nuance within language amongst large collections of text. Thus, health promotion, public health practitioners, and other types of research should leverage this useful tool to further advance studies of bias—both numeric and language based—and ultimately improve health and well-being and the integrity of science within our fields.All studies are subject to limitations, inclusive of this investigation. First, we acknowledge that despite online databases such as PubMed and EbscoHost containing full-text access to many published articles included in our study, we intentionally only selected abstracts for review. This was strategically done for two reasons. First, topic models are a means to consolidate language into manageable themes. Abstracts of scientific papers represent, “information that is the most important for the reader and is often used as a proxy for the content of an article” (Ermakova et al., Because the lay public often cannot differentiate between good and bad quality science, the obligation falls on scientists to uphold the credibility of their scientific endeavors by being transparent with the outcomes of their work (Wallach et al., The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation, to any qualified researcher.DV was the primary author and facilitated all aspects of this study, including conception, data collection, data analysis, and presentation of findings as part of a doctoral dissertation. PG oversaw the logic and framing of this study, in addition to providing assistance with writing. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Antimicrobial resistance (AMR) is a global healthcare problem and therefore raising awareness within young learners is imperative. An AMR roadshow was designed to take key stage 4 students' learning ‘out of the classroom’, assess pre-existing knowledge of AMR and determine the impact of the roadshow on knowledge retention. Knowledge and subsequent retention were measured pre- and post-event through a standardised questionnaire. The roadshow significantly improved knowledge and understanding of AMR, which was retained for a minimum of twelve weeks. Engaging and interactive strategies addressing key health issues provide a positive learning experience which contributes to retained knowledge in young learners. Antimicrobial resistance (AMR) is a significant world-wide public health problem.  It is crTheatre performance is an alternative educational campaign for increasing public awareness of health issues such as HIV/AIDS  and smokThe aim of this current investigation was to add to our previous Educational Theatre study  and deveThree academies participated in the AMR roadshow: Wood Green Academy , Walsall Academy  and Aston University Engineering Academy (AUEA), .Staphylococcus aureus (MRSA); (3) Antibiotics; (4) Molecules to Man. KS4 students from the Birmingham region were invited to the AMR roadshow. Participants' pre-existing knowledge of antibiotics and AMR was assessed through a standardised questionnaire. Each questionnaire was assigned with a unique code identifier. The pre-event questionnaire was issued to all participants on attendance at the AMR Roadshow for completion in workshop (1). Post-event questionnaires were issued for completion and collection following the AMR Roadshow at the end of the event. To determine retention of AMR knowledge over an extended period post-event, identical questionnaires containing the unique code identifiers were issued to academies for subsequent distribution to their students at 6 and 12 weeks. Students within the academies completed the questionnaires independently during a designated tutorial period.The AMR roadshow was a one-day event delivered at Aston University, Birmingham, UK, in the fields of Microbiology, Pharmacy and Biochemical Engineering. The event comprised 4 interactive workshops: (1) Introduction to Microbiology and AMR; (2) Infection and the Superbug Methicillin Resistant (1)Determining pre-existing knowledge of Microbiology and AMR.In this introductory session, students completed the pre-event questionnaire which collated demographic information  and existing knowledge and understanding of antibiotics and AMR. The questionnaire comprised sixteen questions; eleven multiple choice (4 options with single correct answer) which were corrected to binary (correct/incorrect) for analysis, and 5 using standard 5-point Likert scales where 1="very unlikely/not important” and 5="very likely/very important”. The content of the questionnaire related to aspects of antibiotics and AMR that the student may (a) already know (b) be acquired through the subsequent interactive workshops.Staphylococcus aureus (MRSA).(2) Infection and the Superbug Methicillin Resistant (3)AntibioticsAn interactive session on MRSA was delivered which included: the epidemiological aspects; acquisition of resistance; the chain of infection and breaking the chain of infection . For the practical interactive component, students practiced the World Health Organisation hand washing technique to demonstrate effective handwashing using ‘Glitter Bug Cream’ (UV disclosing lotion) for hand contamination and UV boxes to highlight results post-handwashing. This aspect of the workshop was an engaging activity and valuable exercise used to demonstrate effective hand washing technique; a key element in infection control procedures and ‘breaking the chain of infection'.Staphylococcus aureus ATCC 6538. To raise awareness of the potential antimicrobial efficacy of naturally occurring substances, students examined agar diffusion plates inoculated with S. aureus ATCC 6538 and measured the ZOI of: Manuka honey, garlic, ginger and lemon and compared them to the ZOI achieved for the antibiotics tested.(4)Molecules to ManAn interactive session was delivered comprising the history of antibiotics, how antibiotics work, AMR on a global scale, the 5 mechanisms through which bacteria become resistant to antibiotics and measures that can be undertaken to help prevent AMR. For the practical aspect, students examined antibiotic disk diffusion assays and measured zones of inhibition (ZOI) of Ampicillin (10μg), Gentamicin (10 μg), Ciprofloxacin (1 μg) and Trimethoprim (2.5 μg) against This workshop focused on new drug discovery , pre-clinical and clinical development of antimicrobials, and manufacturing issues. This was illustrated with the discovery of penicillin and the processes involved in producing large quantities of the drug. The interactive component comprised two main activities: the production challenges following drug discovery (i.e. creation of robust processes within short time limits) through the construction, within 30 minutes, of an accurate 3D molecular model of penicillin, and secondly, the role of pharmacokinetics in drug design. Students were asked to make coloured beads using alginate, a component employed in drug formulation. The disposition of a pharmaceutical compound within the body ) was then demonstrated using standard chemistry lab ware.The non-parametric Wilcoxon matched-pairs test was used to compare the Likert scores for pre- and post-performance responses for each question .The AMR roadshow was attended by 159 KS4 students: Wood Green Academy (n=30), Walsall Academy (n=52), AUEA (n=77). The gender split was male (n=110) and female (n =49). Participants were aged 15 (n=60) or 16 (n=99). Participant ethnicity included: UK and Ireland (n= 62): Asia (n=64); Africa (n=24) Caribbean (n=5); Middle East (n=4). Student questionnaire responses relating to knowledge and understanding of AMR through Likert Scale and MCQ questions over time are shown in Regarding the MCQ responses, prior to the roadshow, 3 out of 11 (27%) were answered correctly by 50% or more of the KS4 cohort, whilst directly after the AMR roadshow 9 out of 11 (82%) were answered correctly by 50% or more of the students. Directly post-AMR event, a positive increase in knowledge was demonstrated in 91% of the MCQ with only Q14 see  demonstrPre-AMR roadshow MCQ questionnaire responses demonstrated that participants had an existing knowledge  of MRSA, stages of handwashing and what antibiotic resistance means. Initial knowledge regarding issues including: minimum time for effective handwashing, natural antimicrobials, antibiotic production and preventing the spread of antimicrobial resistant microorganisms was less embedded, with correct responses ranging from 10% to 42%. Q2 (Penicillin was purified by …. ?) was answered incorrectly by 90% of the participants prior to the AMR roadshow alongside Q14 (antibiotic resistance is caused by …. ?) which was answered incorrectly by 81% of the students.Regarding the Likert Scale questions, a good level (mean response >4) of pre-existing knowledge relating to the importance of handwashing in preventing the spread of AMR (Q11), washing your hands properly (Q6) and following potential exposure to microorganisms (Q5) was demonstrated. Less knowledge (mean response <3.5) was demonstrated relating to the 6-stages of handwashing (Q3) and the potential use of natural products to treat infection.There was no significant difference in responses based on academy or gender (p> 0.05). Furthermore, ethnicity was not significantly associated with the participants' questionnaire responses; participants from Europe and mixed ethnic backgrounds demonstrated an increased knowledge of AMR across the study period, whilst those from Asia and the Caribbean displayed a similar trend but with an increased retained knowledge at twelve weeks. The AMR roadshow improved knowledge and understanding of AMR  across the KS4 student cohort. Increased accuracy to 91% MCQ questionnaire responses and 100% positive change in response to Likert Scale questions was demonstrated at 12 weeks post event.The AMR roadshow provided an interactive LOtC platform to determine existing knowledge and understanding of AMR amongst KS4 students and also the impact of the roadshow in knowledge enhancement and retention over a 12-week period. It has been shown in previous studies that adopting a variety of different ‘teaching’ platforms to engage the public and young learners is central to raising awareness of important healthcare issues. .In our previous report,  it was det al. (2013) [et al. [The findings from this study demonstrated that the level of pre-existing knowledge and awareness amongst the KS4 academy cohort with regards to antibiotics and AMR varied considerably. This was not entirely surprising considering the differences in curriculum between academies, triple science or combined science studies students, and natural variation in learning ability amongst the cohort. Indeed, other factors relating to learning ability, which were not investigated in this current study, may include aspects such as attention disorder (diagnosed or undiagnosed), support at home from parents and family and general mental health and wellbeing. All of these factors are likely to contribute to some extent to the broad range of pre-existing AMR knowledge and overall learning. Furthermore, this current study included only KS4 students from academies; the study may have benefitted from inclusion of KS4 students from non-academy institutions to compare learning, knowledge enhancement and retention. Nonetheless, through the use of inspirational educational platforms, such as the Aston AMR roadshow, whereby students undertake LOtC and engage through active learning with a hands-on interactive approach, this study has demonstrated that knowledge is clearly enhanced and retained over a 12 week period. Our findings are in line with those of Freeman . (2013)  who demo. (2013) ,9 In theWhat is clear from our findings is that young learners are aware of basic AMR issues, including MRSA and the importance of handwashing, but are less aware of ‘how’ to wash hands properly or ‘how’ AMR occurs. Many students thought that ‘people’ become resistant to antibiotics, which is a common misconception and were not familiar with the potential use of natural products, e.g. Manuka Honey in treatment of infection. Currently, there is little known about the most effective mechanism to raise awareness of important healthcare issues, including AMR, within the public, but the body of research and evidence is increasing and includes platforms such as performing arts, educational theatre, theatre production and LOtC.  DifferenAn application was submitted to the University Research & Ethics Committee and considered by the Life & Health Sciences (LHS) Ethics Committee under application #1107. The committee granted that the study, as an evaluation of an educational resource, was eligible for self-certification. Consent from parents of KS4 participants was sought prior to the event.Not applicable.The datasets used and analysed during the current study are available from the corresponding author on reasonable request. The AMR roadshow information and workshop booklet is available upon request. On-line video links which provide underpinning and additional information to support the AMR roadshow can be found at:https://www.youtube.com/watch?v=qRIR-X7N2VIhttps://www.youtube.com/watch?v=eQ0Z1gzhndghttps://www.youtube.com/watch?v=00RvoJSBn1Ahttps://www.youtube.com/watch?v=zeRmpaCeAmUThe authors declare they have no competing interests.UK Engineering and Physical Sciences Research Council: Bridging the Gaps between Engineering and Physical Sciences in Antimicrobial Resistance, as part of the UK cross-Research Council Initiative on Antimicrobial Resistance (AMR) Grant number EP/M02735X/1.The work was supported by the RA, AB, JC, AH, SJ, ET and TW authored the AMR roadshow and contributed to the event expert panel. JB contributed to the development and analysis of the event evaluation materials. All authors contributed to, read and approved the final manuscript.


Z to E isomerization of the doubly-protonated switch, transporting cargo in one direction (arbitrarily defined as ‘forward’) in up to 85% yield, while polar solvent mixtures were unexpectedly found to favour E to Z isomerization enabling transport in the reverse (‘backward’) direction in >98% yield. Transport of the substrates proceeded in a matter of hours  without the peptides at any time dissociating from the machine nor exchanging with others in the bulk. Under the new operating conditions, key intermediates of the switch are sufficiently stabilized within the macrocycle formed between switch, arm, substrate and platform that they can be identified and structurally characterized by 1H NMR. The size of the peptide cargo has no significant effect on the rate or efficiency of transport in either direction. The new operating conditions allow detailed physical organic chemistry of the ratcheted transport mechanism to be uncovered, improve efficiency, and enable the transport of more complex cargoes than was previously possible.Peptides attached to a cysteine hydrazide ‘transporter module’ are transported selectively in either direction between two chemically similar sites on a molecular platform, enabled by the discovery of new operating methods for a molecular transporter that functions through ratcheting. Substrate repositioning is achieved using a small-molecule robotic arm controlled by a protonation-mediated rotary switch and attachment/release dynamic covalent chemistry. A polar solvent mixtures were found to favour  Peptides are transported in either direction between chemically similar sites on a molecular platform, substrate repositioning is achieved using a cysteine hydrazide transporter module and a small-molecule robotic arm controlled by a rotary switch. In doing so the substrate is prevented from exchanging with others in the bulk enabling the controlled synthesis of complex natural products.4–6 Such physical manipulation is reminiscent of the way robots position and process parts on factory assembly lines. A key feature of assembly line robots, shared by some biological molecular machines, is the ability to deliver different outcomes in response to different programed commands .The manipulation of matter with molecular machines has intrigued scientists since it was proposed by Feynman over 60 years ago.7–16 include examples that combine building blocks in a defined sequence11–15 or move gold nanoparticles.16 Small-molecule artificial molecular machines17–23 have been developed that can transport macroscopic droplets along a surface24 and perform other mechanical tasks,25–29 and that can carry out sequence-specific30–33 and programable34–40 chemical synthesis. Here we demonstrate that a molecular ‘robotic arm’40–42 can be programed to transport cysteine-containing peptide derivatives, rapidly and with good efficiency in either direction, between two chemically similar sites 2 nm apart on a molecular platform.A step towards the long-term vision of using small-molecule robots to perform useful tasks by passing building blocks and other cargoes between machines and along polymer chains and across surfaces, is to develop molecules that can pick up, reposition and put down substrates at specific sites. Programable DNA devices41 The gripper picks up/releases the cargo by formation/breakage of a disulfide bond, while dynamic hydrazone chemistry modulates binding of the cargo to the platform.43 Transport is achieved by selectively inducing configurational  scale" fill="currentColor" stroke="none"><path d="M0 440 l0 -40 320 0 320 0 0 40 0 40 -320 0 -320 0 0 -40z M0 280 l0 -40 320 0 320 0 0 40 0 40 -320 0 -320 0 0 -40z"/></g></svg>N double bond) and conformational (rotation about a C–N single bond) changes of an embedded bidirectional hydrazone-based rotary switch44,45 that steers the arm. In a three-stage operation, 3-mercaptopropanehydrazide could be transported in either (chosen) direction between the two platform sites. The machine-induced transport is processive: the 3-mercaptopropanehydrazide does not at any time fully dissociate from the machine nor exchange with other molecules in the bulk, ensuring that substrate transport arises solely from the change in position of the robotic arm.A programable artificial molecular machine has been developed that is able to pick up, reposition, and set down 3-mercaptopropanehydrazide at either one of two different sites through judicious control of a robotic arm and ‘gripper’.Limitations of these demonstrations included: (i) experiments were only carried out with a single, simple, molecular cargo; (ii) transport in one direction was slow, as the acid-catalyzed hydrazone exchange takes up to six days to equilibrate at the low concentrations of acid necessary for the mechanism used; and (iii) some steps in the transport process proceed in modest yield. We decided to investigate alternative operation mechanisms for the prototypical molecular robotic system while exploring its application for the site-to-site platform transport of more complex molecular substrates, in particular peptides.E-to-Z (backward transport) experiments with molecular machine 1 were originally carried out using 5 equivalents of CF3CO2H.41 Selective protonation of the pyridine nitrogen of the hydrazone switch induced transport of 3-mercaptopropanehydrazide from the green site  to the blue site . Although transport was achieved in good yield (91%), the process took six days to achieve this level of conversion. Consideration of the intermediates in the transportation pathway suggested the rate-limiting step to be acyl hydrazone exchange of the cargo between the two platform sites, presumably the rate limited by the low concentration of acid  used. However, higher acid concentrations favour a different switch configuration, preventing transport in the desired direction.E-1 and Z-1 in C2D2Cl4 (2.5 mM) with increasing amounts of CF3CO2H  and determined the E-1 : Z-1 ratio by 1H NMR spectroscopy once a steady state had been reached  equivalents of CF3CO2H.High acid concentrations had a detrimental effect on Z-1-H33+-right and Z-1-H33+-left (via rotation about the C–N (quinoline) bond of the transient acyl hydrazides. This type of conformational change was originally described by Aprahamian,44 in which a large excess of CF3CO2H leads to protonation of both the pyridine and quinoline nitrogens resulting in the doubly-protonated Z-isomer of the rotary switch , forward transport could be achieved with an improved 83% conversion by treating Z-1 with 80 equivalents of CF3CO2H to generate 83 : 17 Z-1-H33+-right : Z-1-H33+-left 2SO, CD3CN and CD3OD, little or no conversion to E-1 was observed (Z-1-H33+-left (hydrazone exchange is still dynamic under these reaction conditions). In CD2Cl2, 10% E-1 was formed  was observed . We hypothesized that faster and higher conversions of E-1 to Z-1 might be possible using 80 equivalents of CF3CO2H in polar solvents that favour intermediate Z-1-H33+-left. The molecular machine operation was followed by 1H NMR (see ESI Section S53CO2H to E-1 in C2D2Cl4 : CD3CN (2 : 1) led to Z-1-H33+-right, which converts to Z-1-H33+-left (identified by 1H NMR) over an 8 hour period. The 1H NMR spectrum of the product after workup showed >98% conversion to Z-1. This is a significant improvement in speed and efficiency of operation  compared to the previously reported system . The findings demonstrate that the direction of cargo transport can be controlled solely by adjusting the polarity of the solvent while keeping other factors (e.g. acid concentration) unchanged. Polar solvent mixtures favour E-1 to Z-1 conversion; apolar solvent mixtures favour Z-1 to E-1 conversion.We next turned our attention to improving A significant aspect of the architecture of molecular machine 1 is that binding of the substrate simultaneously to both the gripper of the machine arm and to the platform, forms a macrocycle. The results in A potential useful feature of molecular machine 1 is that the structure of the 3-mercaptopropanehydrazide cargo can be elaborated upon without changing its interaction points with the platform and the arm. This could allow this unit to be used as a ‘transporter module’ for other small-molecules attached to it. 3-Mercaptopropanehydrazide is the hydrazide derivative of the amino acid cysteine, missing the amino group. Accordingly, we explored the site-to-site transport of a series of peptidic cysteine derivatives in both forward and backward directions to investigate whether the modified cargo would have an effect on the transportation process.via silver-mediated disulfide formation.49,50 Deprotection of the trityl group was achieved with silver nitrate, generating the silver thiolate intermediate which reacts with the 2-pyridyl disulfide moiety of E/Z-2 to afford E/Z-6–8 in 63–79% yield , whereas with the tri-peptide, Z-11 (R = Phe-Ala-Piv), the trans isomer dominates (90%). The larger E-9–11 macrocycles strongly favour the cis rotamer of the acyl hydrazone irrespective of the size of the peptide cargo: the trans rotamer is not observed in E-9 and only a small amount is present in E-10 and E-11 .copy e.g. shows thR = Piv, , the cisE to Z) using CF3CO2H (80 equiv.) in C2D2Cl4 : CD3CN (2 : 1). Conversion of E-9 to Z-9 (transport of a single amino acid) was achieved in >98% conversion in line with the results obtained with 3-mercaptopropanehydrazide (1H NMR spectra of the operations to form E-11 and Z-11 are shown in E-11 to Z-11) is evident from the characteristic shift of the imine proton H1 into the aldehyde region (from 7.94 ppm to 10.16 ppm). The upfield shift of the hydrazone NH proton H22 from 16.30 ppm to 13.26 ppm, and the downfield shift of the hydrazone ester group indicate E to Z isomerization of the rotary switch (Z-11 to E-11) was carried out with CF3CO2H (80 equiv.) in C2D2Cl4 : C6D5CD3 (1 : 2). Conversion of Z-11 to E-11 proceeded in 63% yield with the outcome of the operation analyzed by 1H NMR spectroscopy in a similar fashion  was found for Z-9, Z-10 and Z-11 . Nevertheless, successful site-to-site transport of the series of peptide-derived cargoes indicates that the size of the cargo does not prevent transport, nor does the size of the peptide affect the efficiency of transport.Site-to-site transport of the peptides was carried out in the backward direction  direction with >98% conversion in one direction and 63–85% conversion (depending on the substrate) in the other. The direction of transport can be reversed by changing the polarity of the medium rather than control of the protonation level of the switch. The new operation conditions allow key interconvertible intermediates involved in the process to be identified and characterized. Cysteine hydrazide can act as a ‘transporter module’ through which to attach and transport mono, di- and tripeptide cargoes between different sites on a molecular scaffold within reach of the robotic arm and gripper. The size of the peptide does not affect the effectiveness of programable transport in either direction. The ability to pass a substrate selectively in either direction between chemically similar sites through a ratchet mechanism, without the substrate ever being able to exchange with others in the bulk, is a rare feature for a synthetic molecular machine. The use of a cysteine transporter module for programable repositioning is a significant step towards the vision of complex molecular substrates being manipulated with atomic precision between multiple sites by robotic molecular machines.The authors declare no conflicts of interests.SC-012-D0SC05906D-s001


To determine the cost effectiveness of molecular monitoring in patients with chronic myeloid leukemia in the chronic phase (CML-CP) compared to no molecular monitoring from a Chinese payer perspective.Analyses were conducted using a semi-Markov model with a 50-year time horizon. Population data from multicenter registry-based studies of Chinese patients with CML-CP informed the model. Transition probabilities were based on time-to-event data from the literature. Utility values were obtained from published studies and were assumed to be the same for patients with and without molecular monitoring. Costs were based on values commonly used in the Chinese healthcare system, including drug acquisition, drug administration, follow-up, treatment for disease progression, molecular monitoring, and terminal care costs, and were in the local currency (2020 Chinese Yuan RMB [¥]). Outcomes were total life-years (LYs) and quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratio.Molecular monitoring was dominant to no molecular monitoring, with increased LYs (1.52) and QALYs (1.90) and costs savings  over a lifetime compared to no monitoring in discounted analyses. The opportunity of patients that receive molecular monitoring to discontinue treatment during treatment-free remission, an opportunity not afforded to those without molecular monitoring, was the principle driver of this result. Results were similar across multiple clinical scenarios. Particularly, molecular monitoring remained dominant even if the proportion of patients achieving deep molecular response (DMR) was reduced by 10%-30%, or the proportion of patients maintaining DMR for 1 year was reduced by 10%-30% or increased by 10%. Cost savings in these scenarios ranged from ¥62,230 to ¥103,964.Overall, this analysis demonstrates that adherence to guideline recommendations of regular molecular monitoring of patients with CML-CP treated with TKIs provides significant clinical benefit that leads to substantial cost savings compared to no molecular monitoring from the perspective of a Chinese payer. In a time where healthcare systems have limited resources to allocate to optimal patient care, investment in molecular monitoring is an ideal choice for improving patient benefits at a reduced cost. BCR-ABL1 gene  . All patWithout regular monitoring, physicians cannot identify if the patient has achieved DMR and hence are not eligible for treatment discontinuation/TFR . As suchAll patients included in our model were newly diagnosed with CML-CP. Population data used to inform the model were derived from multicenter registry-based studies of Chinese patients with CML-CP ,38,39 T. The meaProbabilities for transitioning from imatinib to nilotinib and dasatinib were 50% each, and those for transitioning from nilotinib to dasatinib and from dasatinib to BSC were 100% . TransitUtility values were obtained from published studies and importantly were assumed to be the same for patients with and without molecular monitoring –49 Tabl. FrequenCost inputs are summarized in  and wereMultiple analyses were conducted to evaluate the impact of plausible clinical scenarios on model results . ScenariOne-way deterministic sensitivity analyses were performed to evaluate uncertainty of key parameters and to test model robustness. Key model input parameters were varied individually by ±25% of the base case value. Parameters examined in the sensitivity analyses included the utility values for patients in the CML-CP and AP/BC health states (with and without molecular monitoring), utility values for the TFR and DMR health state (with monitoring), probability of maintaining DMR for a year with dasatanib and nilotinib, mean age, and discount rates for benefits.Undiscounted and discounted results showed increased LYs and QALYs and reduced costs with implementation of molecular monitoring compared to no molecular monitoring . In the Incremental LYs, incremental QALYs, and incremental costs varied by health state and follow-up treatment in undiscounted and discounted analyses . In the In the DMR health state, molecular monitoring had greater LYs , QALYs , and costs  than no molecular monitoring. Since molecular response status was not available for those patients who are not monitored with molecular monitoring, no patients moved to the DMR or TFR health states . Hence no costs were incurred in the DMR or TFR health states. Likewise, in the TFR health state, molecular monitoring had greater LYs  and QALYs  than no molecular monitoring. Although no drug costs were associated with the TFR state, TFR was associated with monitoring and follow-up costs. In the AP/BC health state, molecular monitoring resulted lower LYs , QALYs , and costs  than no molecular monitoring. Terminal care costs were lower with molecular monitoring than without  and follow-up costs were slightly lower with molecular monitoring that without . Costs for molecular monitoring were ¥13,292 (undiscounted) and ¥9,399 (discounted).Analyses investigating the impact of different clinical scenarios showed that molecular monitoring was the dominant strategy when compared to no molecular monitoring, with greater LYs and QALYs gained and lower costs across all scenarios . NotablySensitivity analysis showed that for QALYs, the model was most sensitive to changes in utility values for CML-CP . RegardiThe introduction of TKIs has led to a shift in the management of CML, and is associated with a marked improvement in patient survival . CML is Molecular monitoring has been associated with improved clinical outcomes in several studies. A large, retrospective chart review of patients with CML-CP receiving first-line imatinib therapy (N = 402) reported that regular molecular monitoring resulted in a statistically significantly lower risk of progression and improved PFS compared to no molecular monitoring . SimilarEvidence from several studies has shown that molecular monitoring is associated with overall cost savings despite the additional monitoring related costs. A study of 901 Japanese patients eligible for TFR after first- or second-line TKI reported a total cost savings of ¥2,577,451,775, ¥2,589,441,684 and ¥2,458,281,181 during years 1, 2 and 3  with 100% compliance to molecular monitoring . These cIn this study, achieving DMR and the probability of maintaining DMR for 1 year represented substantial drivers in the savings associated with monitoring. In addition to the added cost of molecular monitoring, increased costs were observed for the DMR health state in patients with molecular monitoring. These additional costs were offset by cost savings in the CML-CP health state, as well as cost savings in the AP/BC health state, in terminal care costs, and in follow-up costs. Furthermore, reductions in the proportion of patients who achieved DMR or in the probability of maintaining DMR for 1 year did not impact results, with molecular monitoring continuing to have improved clinical benefits and lower costs compared to no molecular monitoring. Results were consistent even when these parameters were reduced by 30%. Additionally, when the frequency of molecular monitoring was increased to align with the ELN guidelines, overall cost effectiveness remained the same.The sources of data used to inform the model represent a significant strength of this study. Characteristics of the hypothetical cohort were informed by Chinese registry studies, monitoring frequencies were based on input from key opinion leaders, utilities were informed by previously-published cost-effectiveness analyses, cost inputs were derived from Chinese medical service databanks and health states and transition probabilities were based on published clinical trials. The resource utilization for follow-up costs and terminal care costs used in this study, however, were not based on data from the Chinese population, but rather from the National Institute for Health and Care Excellence and from published literature. Despite accumulating evidence demonstrating that molecular monitoring is associated with increased benefit, our model also conservatively assumed that molecular monitoring did not impact the TTD or PFS curves used to drive transition between health states. The assumptions that patients receiving molecular monitoring at different frequencies incurred similar benefits and the linear treatment algorithm in which flumatinib/dasatinib was considered for first-, second-, or third-line treatment represent the primary limitations of this study. In China, for instance, treatment guidelines recommend flumatinib as a first-line therapy. As such, certain treatment pathways like flumatinib (first line) to nilotinib (second line) were not included. The assumption that all patients eligible for treatment discontinuation agreed to enter TFR also represents a potential limitation of this study. Lastly, the AE costs associated with exposure to TKIs were not considered in this analysis. Given that monitoring leads to treatment discontinuation and reduced risk of AEs, this limitation may also have contributed to an underestimation of the benefits and cost savings incurred by monitoring.Overall, this analysis demonstrates that adherence to guideline recommendations for regular molecular monitoring of patients with CML-CP treated with TKIs provides significant clinical benefit that leads to substantial cost savings during the lifetime of a patient compared to no molecular monitoring from the perspective of a Chinese payer. The availability of the low-cost TFR health state to patients that received molecular monitoring was the overarching driver of this result. In a time where healthcare systems have limited resources to allocate for optimal patient care, investment in molecular monitoring is an ideal choice for improving patient benefits at a reduced cost and should go hand in hand with investment in TKIs.S1 Fig(TIF)Click here for additional data file.S1 Table(TIF)Click here for additional data file.