Gene-editing systems have emerged as bioengineering tools in recent years. Classical gene-editing systems include zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats (CRISPR) with CRISPR-associated protein 9 (Cas9) (CRISPR/Cas9), and these tools allow specific sequences to be targeted and edited. Various modified gene-editing systems have been established based on classical gene-editing systems. Base editors (BEs) can accurately carry out base substitution on target sequences, while prime editors (PEs) can replace or insert sequences. CRISPR systems targeting mitochondrial genomes and RNA have also been explored and established. Multiple gene-editing techniques based on CRISPR/Cas9 have been established and applied to genome engineering. Modified gene-editing systems also make transgene-free plants more readily available. In this review, we discuss the modifications made to gene-editing systems in recent years and summarize the capabilities, deficiencies, and applications of these modified gene-editing systems. Finally, we discuss the future developmental direction and challenges of modified gene-editing systems. The world’s population is increasing rapidly, so food security has been greatly challenged. With the problem of climate change, the world’s arable land is also under threat. Therefore, increasing food production per unit of cultivated land area is a crucial strategy to maintain global food security.Improving crops is an important way of improving agricultural productivity. The traditional breeding method obtains crops with excellent agronomic traits through natural mutation and cross-breeding. This method has been widely used in human history, and many excellent crop resources have been obtained . Howeverarticle, the modification and characteristics of gene-editing systems are reviewed, and their application in crops is introduced.Unlike transgenesis, gene editing allows targeted gene manipulation at a specific locus, so traits do not depend on transgenic elements. This technique generates transgene-free crops with favorable traits and stable inheritance in actual agricultural production . CurrentPresently, various gene-editing tools are employed, among which ZFNs and TALENs were developed earlier.Zinc-finger nucleases are derived from a region containing multiple zinc finger structures that can bind to DNA and from a non-specific nuclease region. A single zinc finger recognizes three specific bases, so by combining zinc finger structures, the DNA binding domain can recognize specific sequences in multiples of three bases. TALENs are similar to ZFNs in that their DNA binding regions are composed of specific conservative repeats, each of which contains 34 amino acids, and the 12th and 13th amino acids form repeat variable di-residues (RVDs), where one RVD can only recognize specific bases . After tClustered regularly interspaced short palindromic repeats-CRISPR-associated protein 9 is essentially the immune mechanism of bacteria or archaea and is composed of three parts. The first is CRISPR RNA (crRNA) complementary to the targeted sequence. The second is trans-activating crRNA (tracrRNA), which binds both crRNA and Cas9. To make CRISPR-Cas9 easier to use in practical applications, CRISPR-Cas9 was modified at the molecular level. CrRNA and tracrRNA were linked by stem-loop, combining the two into a single guide RNA (sgRNA), which significantly reduced the structural complexity of the CRISPR-Cas9 gene-editing system . The thiCas12a is also used in CRISPR. The CRISPR-Cas12a (Cpf1) system uses crRNA to target sequences and has unique advantages. Firstly, Cas12a is smaller than standard Cas9, making it easier to enter the nucleus for editing. Secondly, CRISPR-Cas12a editing produces sticky ends, which is conducive to the deletion of larger fragments and the joining of foreign fragments. Thirdly, CRISPR-Cas12a can process pre-crRNA to form mature crRNA, making its multi-target editing system easier to construct and more efficient . MoreoveTo date, classical gene-editing techniques have been applied in many crops, including rice, corn, wheat, potato, tomato, grape, and citrus, providing technical support for crop quality improvement, resistance to biological stress, resistance to abiotic stress, and re-domestication .Many modifications to the classic gene-editing systems have been made to overcome their limitations. An example is CRISPR interference systems and CRISPR activation systems, which regulate gene expression rather than edit genes. Four strategies have a high potential for modifications with gene editing capability. The first strategy is to enable gene-editing systems to be applied to RNA, mitochondrial, or chloroplast genomes. The second strategy is to change the gene-editing ability so that the gene-editing system can accurately complete the replacement of bases or the replacement and insertion of long sequences. The third strategy is multi-target editing, which would make genome engineering possible. The fourth strategy is to integrate the system with other transgenic elements or change transformation strategies to make transgene-free crops more readily available.In classical gene-editing systems, Cas9 and Cas12a are both type II single-component effector proteins that target DNA. In the progressive exploration of immunity in prokaryotes, the Type VI system has been elucidated. This system is characterized by the effector protein C2c2, which contains a higher eukaryotic and prokaryotic nucleotide-binding (HEPN) domain. HEPN domains are characterized by RNA enzyme activity, so C2c2 has the ability to target and edit RNA, and was named Cas13a in subsequent studies .in vitro or in prokaryotic cells, which often leads to apoptosis, but is highly specific in eukaryotic cells. In plants, Cas13a is suitable for the modification of rice, with a maximal knockdown of 78%  degradation and inhibiting target genes at the transcriptional level . In addin of 78% .Tobacco mosaic virus in tobacco leaves, so Cas13 has a high breeding potential for disease resistance in crops  and Dicer-like (DCL) enzymes to form an RNA-induced silencing complex (RISC), thus completing the silencing of target genes. Therefore, RNAi or artificial microRNA cannot be used to study genes related to the silencing system. Cas13 can complete the silencing of target genes only by itself, without limitations from target genes. In addition, Cas13 can also be used for RNA virus inhibition. Studies have shown that Cas13 can significantly inhibit in crops .Cas13 can also be modified to perform more complex functions to meet production or research needs. dCas13 was obtained by inactivating Cas13 by mutating the HEPN conserved domain and fusing dCas13 with the human adenosine deaminase acting on RNA 2 (ADAR2) deaminase domain to obtain a BE for ssRNA in mammalian cells . CompareMitochondria are responsible for plant respiration and are associated with many secondary metabolites, so they could greatly improve crop yield and quality if they can be modified . ChloropORF79 and ORF125, which proved to be cytoplasmic male sterility genes  were produced by fusing half of the split-DddA transcription activator-like effector array protein with a uracil glycosylase inhibitor (UGI). In human mitochondria, this method can substitute C-G base pairs with A-T base pairs with high precision and efficiency .A. thaliana, RNA processing factor 2 (RPF2) was engineered to target NAD6 for cleavage, virtually eliminating NAD6 expression, leading to the accumulation and activity of complex I , preventing U from being repaired to C and reverting to a C-G base pair  and adenine BEs (ABEs). CBEs were developed first and can transform C into U. Thus, a U-G base pair can be converted into a T-A base pair during DNA repair and replication. CBEs edit bases by cytosine deaminase and contain UGIs. UGIs, derived from ase pair . The earase pair . In a laase pair .Adenine BEs replace A with I, converting I-T base pairs to C-G base pairs during DNA repair and replication. Unlike CBEs, DNA glycosylase inhibitors are not required in ABEs; however, natural adenine deaminases cannot accept DNA. With further understanding of base deaminases, the heterodimer formed by the fusion of RNA adenosine deaminase (TadA) and its mutant deoxyadenosine deaminase  was found to have a good catalytic capacity for adenine deaminase . A highlStreptococcus pyogenes Cas9 (spCas9), whose PAM sequence is NGG , watermelon , tomato , and potato ; transgene-free plants were obtained for watermelon, tomato, and potato , which both specifies the target site and encodes the desired editing sequence. After nCas9 cleaves the single strand of DNA, template RNA paired with the sequence near the editing site, and the pegRNA template complementary strand is resynthesized under the action of Moloney murine leukemia virus (M-MLV) to complete accurate editing . To datein vivo  to separate different sgRNAs and cut them into independent sgRNAs in vivo . At presin vivo .via gene editing sometimes fails to cause changes in the secondary structure of lncRNA, so there will be no functional changes. One way to avoid these disadvantages is to delete these long fragments so that the gene disappears completely. Although many large fragment deletion results have been reported, these cases are often random and difficult to apply in practice. A feasible approach is to design multiple targets with the expectation of achieving fragment deletion between the targets. This strategy has been successfully established in rice and soybean (Currently, gene editing mainly silences genes through early termination of the coding frameshift, but this method produces truncated proteins that, in some cases, are functional and can affect research and breeding . In addi soybean . Further soybean . HoweverCP12 and PPO1 exchanged positions through a 911 kb inversion, and a new expression box was formed between the promoter of Ubiquitin2 and HPPD through a 338 kb duplication. Due to the high expression levels of original CP12 and Ubiquitin2 in leaves, the change of promoter increased the expression levels of PPO1 and HPPD by tens of folds, which enabled rice to have sufficient herbicide resistance in field tests without adverse effects on other important agronomic traits (Multi-target editing can also cause the inversion of large segments of chromatin. In maize, by designing six targets, three on each side, 75.5 Mb were inverted on chromosome 2, simulating the mutation that occurs in nature in maize . In addic traits . This meIn summary, multi-target CRISPR/Cas9 has a high potential for chromatin engineering, both to simulate natural mutations and to make knockout results more reliable. However, chromatin engineering can only be applied to crops with high editing efficiency, such as rice. Application in other crops requires optimization of editing efficiency or interference with DSB repair.Obtaining transgene-free plants can be of great value for the commercialization of crops; in addition, transgene-free plants can be more easily used for other gene function studies in scientific research. Currently, CRISPR transgenic plants are obtained using Agrobacterium-mediated transformation. The Cas9-expression cassette and sgRNA-expression cassette with resistance screening genes are transferred into the plant genome, resulting in transgenic plants expressing Cas9 and sgRNA, allowing complete editing on the genome. Thus, the majority of T0 plants contain transgenic elements. Traditionally, the acquisition of transgene-free plants relies mainly on the genetic segregation of plants after self-fertilization. If only one copy of the CRISPR transgene is inserted into the genome in the T0 plants, 25% of transgene-free plants can be obtained in the T1 generation according to Mendelian genetics. However, transgenes often result in multiple copies of insertions that may be distributed on different chromosomes, making it extremely difficult to obtain transgene-free plants by self-fertilization . CrossinA. thaliana, by adding the mCherry fluorescent marker gene into the transgenic elements, the red fluorescence of mCherry can be used to identify and isolate transgene-free seeds (In the isolation of transgene-free plants, the most time-consuming and labor-intensive work is planting, sampling, DNA extraction, and identification. Therefore, a method to identify or screen whether the seeds are genetically modified would avoid much unnecessary labor. An effective way to reduce the workload is to marker transgenic plants by fluorescence. In ee seeds . This meee seeds . In addiee seeds .REG2 was found to be specifically expressed in early rice embryos, while the rice male gametophyte-specific lethal protein CMS2 can disrupt mitochondrial function during the development of male gametophytes, leading to male sterility. By adding a REG2: BARNASE and 35S: CMS2 expression cassette into the transgenic element, the transgenic male gametes and embryos were directly killed, thus ensuring that the seeds obtained were non-transgenic (Direct transgene-free seeds can also be obtained by self-elimination. The BARNASE gene encodes a toxic protein with nuclease activity, whose expression can kill plant cells. The promoter of ansgenic . CompareAgrobacterium mediates transient transgene expression when transgenic elements enter plant cells . With thin vitro transcribed sgRNA to form cas9-sgRNA RNP complex in vitro and deliver the complex in vivo with gene gun or microinjection (In animal cells, the most commonly used method is to combine purified recombinant Cas9 with njection . RNP cannjection . Edited njection . HoweverThe low efficiency of RNP may be because most cells are not transformed when bombarding calli with RNP owing to the structure of calli. It is possible to improve this efficiency if a new RNP conversion method is established. In animal cells, one potential strategy is to encapsulate RNP by adenovirus proteins and use viral mechanisms to transform RNP into cells. A large amount of RNP can be wrapped in the virus, significantly improving the transformation efficiency. The efficiency of both Cas9 knockout and base editing can be significantly improved by this method . At presTraditional breeding methods are no longer able to meet the food security challenges posed by population growth owing to their highly laborious and time-consuming techniques. Compared with traditional breeding, molecular breeding, especially gene-editing systems, has the advantages of being highly efficient and safe. At present, classical gene-editing systems have been successfully applied to improve disease resistance, stress resistance, and quality traits of crops . Gene-edHowever, classical gene-editing systems have their limitations. They often rely on NHEJ to make editing random, which results in poor performance when studying lethal genes . Also, cLike classical gene-editing systems, many modified systems are limited by species. The vast majority of systems performed well in rice but poorly in other species. On the one hand, as the main grain, rice is of high research value, so is often selected as the research target. But on the other hand, the same gene-editing system tends to be more efficient in rice and significantly less efficient in other crops, showing species-specificity. Therefore, the optimization of gene-editing systems for different species has high research value and will be an important research direction in the future. In addition to promoter and codon preference, a possible cause of the inefficiency is crop culture temperature, which is lower for most crops than rice. There is evidence that both Cas9 and Cas12a are temperature sensitive. Therefore, lifting the temperature limit may be helpful for the optimization of gene-editing systems.The combination of different CRISPR modifications can also significantly increase the power of gene-editing systems. For example, paired pegRNAs PEs obtained by combining multi-target editing with PEs can modify longer sequences than classical PEs. BEs have excellent performance in mitochondrial and chloroplast editing owing to the defect in DSB repairability. PAM-free causes CRISPR to target itself and edit, which reduces editing efficiency and increases off-target recognition. If PAM-free is combined with Agrobacterium-mediated transient expression or bombardment-mediated RNP delivery, this deficiency may be overcome, and transgene-free plants could be obtained directly. However, compared with classical gene-editing, the editing efficiency of modified gene-editing systems will be reduced, and combinations of modified gene-editing systems may lead to lower editing efficiency. Improving transformation efficiency and screening efficiency could compensate for this issue.Many gene-editing systems have high potential. Therefore, it is expected to see further applications of gene-editing systems in crop research and breeding in the future, which could contribute enormously to solving the problem of human food security.GZ completed literature review and writing of this review. HZ reviewed the review and directed the revisions. Both 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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Literacy skills are essential adult competencies for economic, social, political and cultural participation, which are linked to higher quality of life. Literacy skills are known to be lower for older age groups. However, relatively little is known about cohort and period effects, which provide clues to the sociohistorical impacts on literacy, in addition to the well-known age effects, over the life course. This study analyzed three nationally representative cross-sectional survey data of the U.S. adults at five time points, from the 1994 International Adult Literacy Survey (IALS), 2003 Adult Literacy and Life Skills Survey (ALL), and the 2012/2014/2017 Program for International Assessment of Adult Competencies (PIAAC). The total analytic sample was 17,450 adults age between 18 and 65 years old. The literacy measures were re-scaled (0-500 points) to be comparable across the surveys. An age-period-cohort hierarchical linear model  was constructed using the Bayes estimator. Individuals were cross-classified based on 14 five-year birth cohort and 5 periods (survey years) information. Results showed that literacy skills improved . Additionally, the notable variability across the cohorts and periods  were identified. Possible explanations for the identified age, period and cohort effects on literacy and implications for adult competencies in later life are evaluated.


In this roadmap article, we have focused on the most recent advances in terahertz (THz) imaging with particular attention paid to the optimization and miniaturization of the THz imaging systems. Such systems entail enhanced functionality, reduced power consumption, and increased convenience, thus being geared toward the implementation of THz imaging systems in real operational conditions. The article will touch upon the advanced solid-state-based THz imaging systems, including room temperature THz sensors and arrays, as well as their on-chip integration with diffractive THz optical components. We will cover the current-state of compact room temperature THz emission sources, both optolectronic and electrically driven; particular emphasis is attributed to the beam-forming role in THz imaging, THz holography and spatial filtering, THz nano-imaging, and computational imaging. A number of advanced THz techniques, such as light-field THz imaging, homodyne spectroscopy, and phase sensitive spectrometry, THz modulated continuous wave imaging, room temperature THz frequency combs, and passive THz imaging, as well as the use of artificial intelligence in THz data processing and optics development, will be reviewed. This roadmap presents a structured snapshot of current advances in THz imaging as of 2021 and provides an opinion on contemporary scientific and technological challenges in this field, as well as extrapolations of possible further evolution in THz imaging. The first terahertz  systems  were theRecent advances: Optoelectronic THz time-domain system successfully served in pioneering THz imaging experiment [p-InAs as THz emitter [p-type, it was not suited for 1.55 µm wavelength excitation. To overcome this, molecular beam epitaxy (MBE) synthesis of intrinsic of n-type InGaAs alloyed with Bi content was proposed and successfully demonstrated  doped InGaAs which exhibits a combination of ultrashort trapping time, high electron mobility, and high resistivity . BecauseCurrent challenges and possible future trends: One can identify two key areas that need to be addressed for further optimization of fiber laser-based THz TDS systems.The first one is related to materials engineering and the need to reach higher emission power levels, since the aforementioned values in the µW range cannot be found well-suitable for wide range of THz imaging implementations. Recent novel approaches employing additional mechanisms, such as nanoplasma, enabling switches to amplify optoelectronically generated THz emission , can gaiThe second area concerns the need for effective antenna design aiming to extend the emission bandwidth of the THz TDS system for versatile spectroscopic measurements and its implementation in multispectral THz imaging systems.Finally, deserving of mention is the optical light-to-THz radiation conversion efficiency aspect; longer wavelengths typically lead to more effective conversion. Development of Tm:YAG-based femtosecond lasers and engineering of THz source material, for instance, quaternary GaInAsBi alloy layers with with 6% Bi epitaxially strained to InP substrates, can be a route to a new optoelectronic THz systems using optical excitation pulses with wavelengths longer than 2 µm .Recent advances: Quantum cascade lasers (QCLs) are compact THz emission sources relying on optical transitions between electronic states created by engineering of electronic wavefunctions in MBE grown semiconductor nanostructures [ructures . The QCLructures ,42.Terahertz QCLs, invented in 2002 , have liThermoelectric cooling is important in these applications to achieve a needed device working temperature. An important milestone in this direction is the demonstration of THz QCL emitting radiation around 3.9 THz at 210 K temperature with the use of a small footprint, 4-stage Peltier cooler . It was An alternative approach to THz generation in QCLs at room temperature is the replacement of the conventional THz QCL design with an intra-cavity THz difference-frequency generation scheme under pumping of dual-wavelength mid-IR QCLs ,50. The Current challenges and possible future trends: One of the main current challenges in the development of the conventional THz QCLs is room-temperature operation at reasonable power levels. The emitted power at 240 K amounts to 20 mW [to 20 mW , while t be used . Single  be used . In vert be used . The breFinally, it is worth noting the spectral tunability of these devices. As it was already mentioned, room temperature THz difference-frequency generation scheme QCLs operates slightly below 2 THz , while cAs mentioned above, routes in development of compact room temperature THz radiation sources in subTHz frequencies can be electrically-pumped oscillators or multipliers. Pioneering works ,70 dedicRecent advances: During the last decade, technologies for fabrication of High Electron Mobility Transistors (HEMTs) or Heterojunction FETs (HFETs), have been developed to the level which allows for using them as the key element in Monolithic Microwave Integrated Circuits (MMIC) which are currently breaching the 1 THz limit [Hz limit . These t lengths . Since tHz limit , similarHz limit  and the As HEMTs . AlthougAs HEMTs  or 670 GAs HEMTs , mixers As HEMTs , low noiAs HEMTs ,83,84, aAs HEMTs  with theAs HEMTs .Current challenges and possible future trends: The performance of TMICs as receivers or active multipliers is just starting to approach those achievable with Schottky diodes [y diodes . Neverthy diodes . HoweverRecent advances: The performance limits of analog high-frequency electronics-based on the industrial mainstream semiconductor fabrication technologies, i.e., a complimentary metal oxide semiconductor (CMOS) and bipolar CMOS (BiCMOS), are now almost comparable to benchmark setting III/V devices. Field-effect transistors (FETs) and, in particular, silicon–germanium (SiGe) heterojunction bipolar transistors (HBTs), now report cut-off frequencies cy range ,89.Profiting from the technological maturity which ensures a high yield and the ability to construct circuits involving a large number of devices, a variety of different approaches for CMOS-based sources have been proposed. One of the first proposed methods to overcome cut-off frequency limitations used the summation technique of several phase-shifted oscillators, or so-called linear superposition technique, which resulted in −46 dBm gain at 324 GHz . One of requency . Yet anorequency .A standard development strategy of high-frequency circuits, which starts from the on-wafer characterization, can be continued to either waveguide-integrated devices or towards monolithic integration of antennas. One of the first reports on efficient realization of antenna-integrated sub-THz oscillator demonstrated up to −4.1 dBm at 288 GHz  emitted The strategy that the oscillator drives integrated antenna is almost naturally fits within so-called Colpitts oscillator implementations. The first implementations using a 90 nm CMOS technology reported up to −8.8 dBm at 217 GHz frequency ; howeverRecent developments in bipolar CMOS technologies, such as 130-nm SiGe with the maximum oscillation frequency reaching 500 GHz, allowed utilization of oscillator concepts and reporting 1 dBm from a single antenna at 245 GHz  or −6.3 Besides the possibility to form clusters of oscillators to increase power, the array of synchronized sources also allows for beam steering. Steering angles of 45 and 50 degrees along two axes were reported in a circuit operating at 338 GHz ; it permThe classical concepts of nonlinear conversion include approaches utilizing varactor-based solutions as either active circuits ,105, or Current challenges and possible future trends: The ongoing improvement in the performance of FETs is driven almost hand-in-hand with requirements to increase the efficiency in digital systems. This implies the reduction in the minimum feature size, as well as involves innovations, such as introduction of high-k dielectrics, implementing silicon-on-insulator (SOI) structures, exploiting strained active regions, etc. From the progress in the field of analog CMOS integrated circuits, there are indications that CMOS FETs already have approached their speed limits at about 45 nm and 65 nm nodes. However, a theoretical analysis of SiGe HBTs indicates that operating frequencies of 1 THz and beyond are plausible in the future [e future .It must be noted that the progress in the development of active circuits, to a large extent, relies on the availability of high-frequency models for devices. Such models are typically validated for the GHz frequency range, yet their application to the THz range becomes disputable due to the importance to account for a high-frequency transport-related phenomena, such as skin currents or plasma waves excitation, which gain importance at higher frequencies and directly affect the efficiency of mixing . HoweverThe main advantage of silicon technologies, regarding their application in THz frequency range, comes from possibilities to form large collaborative acting clusters, allowing the implementation of different than currently established technological approaches or even to enable a new functionality for applications. As an example, one can serve combination of electronic and photonic concepts to extend facilities that other technologies cannot provide currently.Resonant tunneling diodes (RTDs) consist of two or three ultrathin and closely spaced layers of a large-bandgap semiconductor embedded within a lower-bandgap semiconductor (double- or triple-barrier RTDs). They burst onto the scene as room-temperature sources of THz radiation, when a team at the Massachusetts Institute of Technology (MIT) Lincoln Laboratory reported THz emission up to 420 GHz in 1989  and, latRecent advances: The status of the research of RTD devices is described in two informative recent review articles [articles ,122. Whiarticles , it is carticles . This isarticles . Anotherarticles . The powCurrent challenges and possible future trends: The quest for higher power certainly will remain to be a dominant motivation for research in the years to come. Additionally, the continued exploitation of the inherently nonlinear response of the devices may lead to a further increase of the fundamental operation frequency and to the development of novel multipliers, mixers and other nonlinear devices [ devices . With re devices . This wa devices . But, be devices . This all system . Althougl system ) value hRegarding future trends, the question arises as to the potential of van-der-Waals materials as a new basis for RTDs (or other diode-type emitters to be fabricated with them). Theoretical studies suggest that oscillators based on a stack of graphene/hexagonal boron nitride/graphene could operate at a fundamental oscillation frequency of hundreds of GHz at similar output power as existing RTDs . Other sAs imaging applications usually benefit from high radiation power, vacuum electronic devices, which can provide exceptionally high output power, principally are of high interest as radiation sources . HoweverCompact room temperature THz imaging systems and their usage in real working conditions define a large variety of specific requirements for sensing devices. On the one hand, they should be sensitive, exhibit broadband operation and high dynamic range; on the other one, devices should be reliable, electrically and mechanically stable, and, which is of a particular importance, have a possibility to be combined into detector arrays. This criterion imposes a strong preference for planar-technology-based solutions. There are sensors cameras already commercially available for THz imaging ; howeverRecent advances: First concept-breaking reports that the field-effect transistors can be utilized as THz detectors , seem to be promising to tackle the problem of slow response time . GaAs wa3300 V/W . These p3300 V/W .Current challenges and possible future trends: Diode-based sensor further development is mainly aimed at finding planar solutions for sensing arrays and an increase in sensitivity via internal electric field engineering, as, for example, in the case of bow-tie diodes composed of InGaAs or GaN/AlGaN materials.Concerning microbolometers, microelectromechanical systems (MEMS) technology shows a promising development trend. They were realized in silicon wafers, where the readout integrated circuits had been prefabricated to employ VOx film as a bolometer active layer, whose changes in the resistance can be detected and converted to the output voltage or current signals . Other re layers , siliconlometers . An intelometers . As a THlometers .Special attention is required for metamaterials. Since their first demonstration in THz frequencies , metamatSince metamaterials can exhibit perfect absorption properties ,203, theConvenience of room temperature THz imaging systems in regard to their dimensions and on-chip solutions remain a priority to achieve their wider technological adoption. As a rule, the development of solid-state-based solutions for miniaturization of the imaging system active components—emitters and detectors—attracts more attention than passive optical components, like lenses, mirrors, beam splitters, etc., despite the fact that these can also be bulky and, in a majority of cases, require precise optical alignment.Next, we will discuss some routes in the development of diffractive optics elements. It aims to demonstrate that such elements can provide a platform to fabricate optical components for the needed wavelength range and to manage THz beam profile via interference effects.Recent advances: Extending previous very recent comprehensive overviews on THz diffraction elements [elements ,206 dedielements . Beam maelements , printedelements ,210. To elements  or zone elements . It was elements ,214. Theelements , and it elements .The THz beam engineering, as mentioned above, can also be realized using metamaterials ,218. THzCurrent challenges and possible future trends: Reduction of dimensions in THz imaging systems is one of the main persistent aims and where metamaterials and metasurfaces can contribute as important solutions. In particular, the combination of sub-wavelength optics and plasmonics is expected to grow in the upcoming years [ng years . Deserving years , as wellng years . One canng years  as it wang years .Spatial filtering represents well-known techniques in infrared and visible light microscopy which are used to investigate low absorbing objects, as commonly found in biology. Conventional or bright field imaging is usually employed if samples experience strong absorption; dark-field imaging provides good contrast for weakly absorbing object, since it only captures high-angle scattered light. Phase contrast is used for unstained and transparent biological samples, allowing visualization of their shape and density variations . PioneerRecent advances: Very recently, the spatial filtering concept was extended to THz by application of two spatial filtering methods—phase contrast and dark-field—to resolve weakly absorbing objects in THz imaging at monochromatic light of 0.3 THz frequency [requency . It was requency .Current challenges and possible future trends: These developments will impact THz uses in medicine and biological applications, where weak absorbance of THz radiation, in many cases, is an inherent feature of investigated objects, and where it is a particular interest to differentiate water-induced absorption from the tissue effects. The latter issue requires polarization-sensitive filtering; therefore, one can expect further development in this field. It is worth noting initiatives to apply spatial filtering in pulse shaping to monitor and control emission of compact THz sources. One can mention, for instance, THz QCLs by design of two back-to-back mounted elliptical silicon lenses and an opening aperture defined on a thin gold layer between the lenses [e lenses  which ene lenses , hence eAs already mentioned above, imaging systems operating in real operational conditions must be compact, reliable, and convenient to use. Technically, it means presence of minimal optical alignment issues, enhanced functionalities, and essentially reduced power consumption. CMOS technology can serve as a suitable platform to integrate on-chip emitting and sensing components of THz systems . HoweverRecent advances: Silicon lenses can be useful tool to collect the incident THz light, for instance, into antenna-coupled AlGaN/GaN based HEMT detectors: Silicon hyperspherical lens helps to concentrate even incoherent THz light on a detector chip assembled on the planar surface [ surface . In case surface . MoreoveZone plates can be attractive ingredient in the miniaturization of the THz image recording setups as their rely on planar technology solutions. As an illustrative example, they can serve their on-chip integration with InGaAs-based bow-tie THz detectors . The topAs an another example of planar solution that deserves notice is the standard 180 nm CMOS technology-based diode microbolometer sensor which is monolithically integrated with a broadband THz metamaterial absorber . The givPlanar solutions of integration can be realized using special kind of waveguides. One can note, e.g., comb-shaped waveguide based on the excitation of coupled spoof surface plasmon mode can be found to have a pronounced effect for the enhancement of fingerprint detection sensitivity in the THz range, and it can be an essential tool in biomedical imaging .Current challenges and possible future trends: It is rational to suppose that the trend of on-chip components integration will be kept. Integrated circuits based on CMOS technology are expected to be dominated in the development of subTHz and THz range imaging systems because of their advantage in design and fabrication of compact, low-cost, and low-power consuming microelectronic circuits. Graphene–CMOS integration can evolve as one possible technological trend [al trend ; a signial trend .Computational imaging (CI) presents a highly integrated platform, enabling a tight link between modern sensing devices, advanced optics and post-recorded signal processing . CI alloRecent advances: THz compressed sensing: Solutions in THz range display some specifics due to lack of room temperature high power sources required in their employment together with recording focal plane arrays. To overcome the problem, the compressed imaging using single pixel camera can be used instead [ instead . Compres instead . The com instead ,252,253. instead , spinnin instead ,256, and instead . By usinTHz holography: Holograms, in addition to the light intensity, records phase changed by illuminated objects, hence allowing precise mapping across the imaged object if it is low absorbing or event transparent in THz range. Moreover, it provides a possibility to reveal pattern of object thicknesses, density distribution and relief features. The employment of highly coherent THz sources allows for achieving high-fidelity amplitude and phase reconstructions, as well as indicates ways of how to reconstruct images of complex dielectric targets [ targets . Recent  targets . To real targets . To over targets .THz Fourier imaging: Very recently, Fourier imaging recording the data in the Fourier domain folding the 3D information into 2D in the focal plane of the imaging system and reconstructing the 3D scenario by expanding the 2D data numerically was developed by Yuan etc. [uan etc. . As deliuan etc. . In thisTHz 3D vision: Three-dimensional THz imaging becomes more and more promising as the generation and detection technologies have been developed rapidly. Apart from well-established THz tomography technique, intelligent ideas were taken from the optical range to cope with obstacles in different imaging scenarios. Recent achievements for multi-thin layers 3D scheme reconstruction witness this by the works of ‘Shape-from-focus for real-time terahertz 3D imaging’ [imaging’ , ‘Multi-imaging’ , and ‘Coimaging’ . All of THz super-resolution: Super-resolution is a topic of great concern in the realm of optical imaging, and it also occupies an important position in THz band. Apart from the method to obtain near-field information maintenance in the far-field region, such as the nano-imaging demonstrated in the latter content, a new artifice super-resolution orthogonal deterministic imaging (SODI) is a accomplished by introducing the spacial distributed mask as the “artificial blinking fluorophores” [ophores” . The intNew design: As a breakthrough in evolution of compact computational THz imaging one can assume development of THz source system-on-a-chip specifically designed for computational imaging with a single-pixel camera. The source consisting of an 8 × 8 array of independent, frequency-unlocked THz sources radiate maximum 10.3-dBm power at 0.42 THz and, together with spatial modulation of 10-MHz rate, can capture transmission mode images at 25 frames/s with 40-dB voltage dynamic range [ic range .Current challenges and possible future trends: As a rule, in real implementation conditions, for instance, in security or medicine, THz imaging needs to be done through scattering materials. It implies a search of new imaging techniques to tackle these problems [problems . An imagproblems .The drawback of THz holography is that the resolution is constraint or the imaging speed efficiency is low. In a far-field imaging area, the resolution is inverse proportional to the object distance. However, the object distance of off-axis holography setup is not allowed to be shortened to a small number since the reference beam must not interact with the object. Coming to the in-line holography, the imperfect reference beam will induce ghosting as noise, which will lead to a resolution deterioration. The most widely used ways to alleviate the ghost problem are averaging multi-frame of data or recovering the phase by iteration. Both methods are time consuming. The lacking energy at THz frequencies constrained the imaging field of view and target object distance of holography. This makes harsh obstacles for environment practical applications, such as fire scene, rescue after earthquake, battlefield, etc. Alternatively, it can be done without usage of reference beam employing so-called ptychography, a non-holographic solution of the phase estimation problem. In this technique, one can calculate phase relationships between different parts of the scattered illumination with a incident coherent beam . DespiteWhen phase information can be found not essential, 3D images can be obtained by already well-known 3D tomography approach  based onThe other important issue related to the finding of optimal ways to minimize a coherent source and a camera (without lenses) in the set-up as it was considered in THz imaging  and exteObviously, the Abbe diffraction limit of focusing is a major limitation of THz imaging with free-space radiation. Early attempts to overcome this restriction were based on ideas derived from SNOM , developed in 1981, for the visible and IR spectral regimes, which utilizes metal-coated tapered waveguides, usually glass fibers, whose ends are brought close to the object-under-test for near-field imaging. For the THz and microwave regime, tapered coaxial cables were developed which allowed for sub-wavelength spatial resolution but had low throughput . AnotherWhile the techniques mentioned above reach a spatial resolution on the micrometer scale, three imaging modalities have broken through to the nanometer regime. These are THz imaging through nanoslits, s-SNOM (scattering-type SNOM), and THz-STM (THz scanning tunneling microscopy), the latter having reached atomic spatial resolution.Recent advances: THz sensing and imaging through sub-micron slits: Considering the first approach, near-field sensing and imaging with any type of nano-scale aperture is in principle capable for improved spatial resolution. However, the challenge is to achieve a high enough throughput for a good SNR. This is possible if one accepts electric field confinement in only one direction using micro- and nano-slits in thin metal films, single ones or arrays thereof, with a length which corresponds to a half-wavelength resonance at the targeted THz frequency [requency ,282. Witrequency ,284,285.requency . Imagingrequency .THz s-SNOM: More readily suited to raster-scan imaging is the s-SNOM technique. It builds on atomic force microscopy (AFM) and adds to it optical spectroscopic capabilities. This is achieved by illumination of the AFM probe tip by a tightly focused light beam and detection of the light scattered from the apex of the tip. Both cantilever-type [ver-type  and tuniver-type  probes aver-type ,291 aftever-type , such asver-type ).It is worth mentioning that s-SNOM is not purely surface-sensitive, but probes a volume down to about 50 nm in dielectric media , which gIn the last two decades, developments have focused on the IR spectral regime. The THz regime has seen some early work ,300,301,R = 6 nm, operated at a laser wavelength of 2.52 THz [R = 3 nm) may be possible [R for this resolution. As impressive as this is, it seems that atomic resolution, which AFM itself is capable of, is not attainable with s-SNOM.Important THz-specific technological advances have already taken place. With regard to the probe tips, longer and more resonant tips, which exhibit a stronger field-focusing and scattering efficiency, have been introduced ,305,306.possible . The tapR.Under routine operation conditions, THz s-SNOM reaches the same resolution of typically 50 nm as s-SNOM at shorter wavelengths . A surprWith regard to radiation sources and detection, researchers employ free-space broadband TDS measurement systems ,309,310,Typical applications of THz s-SNOM are the discrimination of materials via their spectral characteristics , which iTHz STM: The best spatial resolution is achieved in experiments, where the specimen is excited by THz radiation and the ensuing nonlinear response is measured via the changes of the tunneling current through an STM. In order to achieve appreciable effects, such experiments are performed with intense THz pulses. In contrast to STM combined with optical excitation at shorter wavelengths, where thermal effects play a significant role [ant role , it was ant role . This tuant role , and to ant role . The tecant role ,331,332.ructures . One canCurrent challenges and possible future trends: The action range of the THz near-field techniques discussed above is solid-state physics, materials science and electronics; in the life sciences, they play no role, or, at best, a marginal role, to date. While first attempts are being made to explore the application of s-SNOM on alive matter in biological contexts [contexts ,335, thiAnother limitation of the techniques discussed above is that they are essentially surface-sensitive techniques . What is missing is THz imaging technique which can probe tiny volumes in the depth of a specimen, especially of biological origin. If one considers sub-wavelength volumetric imaging techniques in the VIS spectral regime, with their enormous driving force being applications in cellular biology, one finds the best spatial resolution to be reached with two families of techniques, Stimulated Emission Depletion (STED), on one hand, and the Stochastic Optical Reconstruction (STORM) with its variants, such as Photoactivated Localization Microscopy (PALM), on the other. Both classes of techniques were honored in 2014 with the Nobel Prize, awarded to Stefan Hell for STED and to Eric Betzig and William Moerner for STORM/PALM, with the prize motivation “for the development of super-resolved fluorescence microscopy” ,337,338.It has been a dream of many to also adopt such concepts at THz frequencies. There are two fundamental challenges here. The first one relates to the availability and the operational conditions of power detectors with a useful response to single or only a few THz photons. One would expect that superconducting detectors are capable of such performance, but their single-detection capability, for various reasons, is limited to shorter wavelengths ,341. SinThe second challenge is the availability of fluorophores. We are not aware of any such compound for THz frequencies. One has to note that a fluorophore is an emitter with a delayed and repeated emission of radiation after excitation. A fluorophore has to be distinguished from contrast agents which are under investigation for the THz regime (and very much so for microwaves), with much work devoted to plasmonic metallic nanoparticles, carbon nanotubes, and graphene , with hyRecent advances: The light-field method relies on the idea to record both intensity and direction of the incoming light rays. This highly versatile computational method is well-known in visible light in enriched new facilities of synthesizing novel imaging views [ng views . The ligng views . It was Current challenges and possible future trends: The realization of light field imaging in THz range using compact electronic transistor-based arrays can allow for reconstruction of 3D image using computer algorithms. In addition, using shape-from-focus method, one can collect additional information about the object along the depth dimension, which can be attractive for medical and other applications. However, the image recording in reflection mode, when the surface is rough, causes tremendous difficulties [iculties , hence niculties .Recent advances: Phase-sensitive detection provides the possibility to enhance a detected signal by orders of magnitudes by a proper selection of its phase difference in respect to a strong local oscillator either in heterodyne or homodyne operation mode. Homodyne scheme does not require two emission sources synchronized via phase-locking loop and, thus, can be more attractive in comparison to heterodyne. Recently, the theory of homodyne phase-sensitive THz spectrometer based on nanometric FETs was developed, revealing that the FET can be used as a sensitive spectrometer and/or interferometer when exposed to a strong tunable local oscillator signal with the varying frequencies and phases [d phases . The gairesented . It was Phase-sensitive detection can be realized in graphene FET connected to specially designed antennas : Here, tCurrent challenges and possible future trends: Aforementioned techniques were developed for spectroscopy aims, and their extension and adoption in compact phase- and polarization sensitive THz imaging systems would be an important step in their broadening facilities, particularly in development of systems equipped with all-electric detectors for determination of THz radiation polarization state.Realization of optical frequency comb using QCLs paved a novel route for the development of highly sensitive compact spectroscopic systems ,350. An Recent advances: The demonstration of dual-comb spectroscopy in the mid-infrared QCLs frequency combs unveiled a potential of the approach as the basis for a compact and all solid-state-based broadband chemical sensing [ sensing . Relying sensing , on-chip sensing . Here, t sensing , proving sensing . As a si sensing . In this sensing . This ap sensing . The bloCurrent challenges and possible future trends: Despite a rapid evolution both in quantum and photonic THz-comb generation technologies, challenges remain in achieving broad spectral spans and the flat spectral intensity distributions. Compact solutions using QCLs in gas and condensed-phase spectroscopy revealed the potential of frequency comb and dual-comb spectroscopy approaches. The implementation of these principles in compact THz imaging can stimulate technological developments in on-chip-scale multispectral imagers for materials discrimination, biomedicine, and security application, as well as their implementation in environmental monitoring.modulated continuous wave and denotes a family of techniques known from radar to determine distances [MCW stands for istances . This isIn the THz regime, above 300 GHz, the exploration of FMCW saw a high tide ten to fifteen years ago, driven by the goal to develop active imaging systems for stand-off security applications ,366,367.The FMCW technique had more and continued success in its use for non-destructive testing, where it allows tomographic imaging of THz-transparent media. This application was pioneered by Synview GmbH, founded in 2007, which developed scanners at several frequency bands from 0.1 THz up to 0.8 THz ,367. TheRecent advances: In order to improve the security scanners, Synview GmbH adopted multistatic/MIMO radar concepts in the THz frequency regime. A near-real-time FMCW-SAR imager with up to eight transmitters and 16 receivers working in the 220–320 GHz frequency range are reported [reported ,374. It reported .In addition, with a view towards multi-channel systems, the Jet Propulsion Laboratory in the USA and others embarked on a large development effort devoted to Si micromachining . Unlike With regard to the inspection of materials and objects, FMCW techniques at the interface between the microwave and THz frequency regimes have established themselves by now ,379,380,Current challenges and possible future trends: Concerning security scanners, which seem to be little explored until now, are distributed MIMO systems, with emitters and sensors spread out over a large range of angles around the region of interest.Concerning all kinds of applications, sensor fusion is still in its infancy. Furthermore, as the hardware aspects mature, smart image acquisition and processing techniques, e.g., employing sparse imaging techniques, become more significant ,387,388.Imaging with  radiation emitted from the object-under-study or its surroundings avoids the use of additional active illumination. The concept is best known from radioastronomy, where usually superconducting receivers are employed for heterodyne detection with ultimate sensitivity. Passive detection was then also found to be very interesting for security scanners with microwaves and THz radiation. First, one avoids the costs of the active illumination, and, second, the thermal radiation penetrates the region of interest omnidirectionally, which immediately solves the problem of incomplete object images which one obtains with active systems because of the specular reflection characteristics of skin . HoweverPassive imaging for security purposes made a major step forward at about the turn of the millenium, when HEMT-based low-noise amplifiers in GaAs, and especially InP technology, became available for frequencies up to 100 GHz. They made it possible to amplify the weak thermal signals over a large bandwidth with a gain of 50 dB . A numbeThese technical developments (combined with rising fears of terrorist acts) triggered intensive research into stand-off security scanning (active and passive) in the decade around the year 2010. With the advance of microelectronic amplifier technology, it was shown that direct detection of thermal radiation is possible even at the remarkably high frequency of 670 GHz. This was demonstrated with an InP HEMT amplifier and a zero-bias Schottky diode as the detector. Measurements on a heated test object showed that a noise-equivalent temperature difference (NETD) of 2 K was reached (1/30 s integration time) . For fasTrue real-time operation of security scanners was reached with passive imagers based on superconducting microbolometers. A system based on Nb transition-edge sensors , are sensitive enough to be useful for operation with QCLs emitting at 2.52 THz . Camerasread-out . The optout [1/2 , good enout [1/2 . Similarout [1/2 ,411. NECout [1/2 ,411. Thiout [1/2 .A successful alternative to such photoelectric detectors are bolometers, devices exploiting the change of resistance of a conductor upon radiative heating . SeveralRecent advances: Recent years have seen continued development of imagers, and progress here is closely associated with improvements of the detectors [Superconducting systems have seen the development of arrays based on kinetic-inductance detectors. Two of their advantages are that they allow relatively easy up-scaling of the number of detector elements to form large arrays, and that operation of the NbN sensor elements is possible at somewhat elevated temperature—5–10 K—compared to transition edge bolometers. Ref.  reports A prototype of a security scanner, also based on kinetic inductance detectors, was recently introduced in Reference . It has Photoelectric rectifiers: The design of a 12-pixel array of Schottky diodes with differential read-out was introduced in Reference . It is tDirect power detection by distributive resistive mixing in antenna-coupled FETs was tested in several papers with regard to passive detection and imaging. Ref.  reportedMicrobolometer arrays: The adaption of uncooled microbolometer arrays to THz frequency by the optimization of the cavity structures and antennas, respectively, metamaterial absorbers, as well as the read-out, continued to improve the sensitivity to a level that the cameras can be employed for passive imaging ,423,424,etectors .SupercoCurrent challenges and possible future trends: Today’s imagers with superconducting detectors build on Nb or NbN technology. Although cryo-cooling has advanced enormously and closed-cycle cooling units avoid the costs for the delivery of cryogenic liquids, it seems that THz (security) scanners which require sub-10 K cooling are not accepted commercially. It is an interesting question whether detectors based on high-Tnductors ,426 coulRadio astronomy remains to be a technology driver for heterodyne systems developments especially aiming for higher THz frequencies (mainly for gas spectroscopy) ,428. An However, for the advancement of non-space applications of heterodyne detection—aiming at either fast, multi-pixel passive imaging or at coherent imaging, e.g., for holographic purposes—receiver arrays for operation at room temperature should be developed and be implemented in mainstream semiconductor technologies. Promising research is ongoing in this regard. A challenge is the LO power supply, with many issues, such as total power needed, on-chip power distribution, synchronization, and phase noise. The notion derived from space applications that one would need about 1 mW of LO power for each (Schottky-diode-based) mixer has been shown to be incorrect for THz imaging; much lower LO power levels permit coherent imaging and dynamic-range improvements over direct power detection ,431. RecSuitable quality for THz images of packaged objects or samples placed in optically scattering media, as a rule, becomes worse and a challenge to interpret, thus requiring either essential an increase of recording time, special means to subtract the background, or use an array of sensitive detectors. However, there is another—a “soft” way—to circumvent the aforesaid problems by application of artificial intelligence (AI) methods. In what follows, we shortly discuss AI-related routes dedicated for more effective operation of THz imaging systems.Recent advances: Deep learning (DL) is a class of function interpolation algorithms which can be found to be especially attractive when the measurement is noisy, performed imperfectly in a real operational conditions, or image is recorded through a strongly scattering medium [g medium . Additiog medium . Other Ag medium . In addig medium . The sigg medium .Current challenges and possible future trends: One can expect further intensive implementation of DL and other AI instruments into THz imaging and spectroscopic systems [ systems , both fo systems . The DL  systems  or to re systems .High quality, effective, and reliable operation of room temperature THz imaging systems pose several challenging technological requirements. On the one hand, they should be compact and adhere to low power consumption, but, on the other hand, equipped with still powerful enough (in mW range) and preferably tunable THz emitter sources, compatible with diffractive optical elements and fast response , and high sensitivity  containing both optically-gated emitters-detectors pairs. It is seen that frequency-difference THz quantum cascade lasers-based compact imaging systems can be constructed only using silicon nanometric transistors or microbolometers down to the lowest reported QCL emission frequency of 1.9 THz. The RTDs can also reach this frequency, which can allow, in principle, their employment together with Schottky diodes, silicon nanoFETs, and microbolometers; however, the emitted powers at the highest—1.92 THz—operational frequencies are below 1 µW . It is sA similar tendency can be seen in the evolution of femtosecond fiber lasers-based optoelectronics THz systems: Their emitted power has increased from several microwats  in 2010 The conventional THz QCLs from cryogenically-cooled conditions have reached the operation temperature of 250 K with their length of a few millimeters , thus exOn the other hand, from the side of software, the installation of artificial intelligence in THz image processing and the simultaneous system integration create a wide basis for a new generation of THz imaging systems, making them compact electronically, “smart” computationally, and, hence, turning to the level of high quality standards already available in mobile phones’ cameras.Concerning industrial applications of THz imaging and sensing, their possibilities were well-described recently ,447. Sin


Objectives: Acute type A aortic dissection (aTAAD) is usually lethal without emergency surgery. Although veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is widely used in patients with cardiogenic shock following cardiac surgery, VA-ECMO support following aTAAD surgery has not been well-described. Based on our 6-year experience, we aimed to retrospectively analyze risk factors, application and timing of VA-ECMO, and outcomes in aTAAD patients.Methods: In this retrospective, single-center study, we enrolled adult patients who underwent aTAAD surgery from January 2014 to December 2019 and were supported with VA-ECMO. Patients were divided into two groups according to whether or not they were successfully weaned from VA-ECMO. Preoperative, intraoperative and postoperative variables were assessed and analyzed. Outcomes of the patients were followed up until discharge.Results: Twenty-seven patients who received aTAAD surgery with VA-ECMO support were included in the study. Nine patients (33.3%) were successfully weaned from VA-ECMO. The median VA-ECMO support time and length of hospital stay in the successfully weaned group were significantly longer than in the group could not be successfully weaned . Overall in-hospital mortality was 81.5%. The main causes of death were bleeding (37%), neurological complications (15%), and multiple organ dysfunction syndrome (15%). Preoperative levels of creatine kinase-MB (CK-MB) were lower in patients who were successfully weaned from VA-ECMO than in the failed group . Postoperative peak levels of CK-MB, cardiac troponin T, lactate dehydrogenase, and lactate were significantly lower in the successful group than in the failed group.Conclusion: Postoperative VA-ECMO support was rarely used in aTAAD patients. Our study showed that VA-ECMO can be considered as a salvage treatment in aTAAD patients, despite the high rate of complications and mortality. Acute type A aortic dissection (aTAAD) is a cardiovascular emergency associated with the formation of a false lumen in the media, caused by intimal weakness or tear. Blood surges through the false lumen and enlarges the tear at the proximal, distal, or both ends . BecauseThe heart is one of the organs most commonly affected by aTAAD, which can lead to cardiac tamponade, acute severe aortic regurgitation, and/or coronary artery involvement. Preoperative coronary artery dissection is usually associated with acute myocardial infarction and heart failure. A previous study showed that mortality associated with aTAAD involving the coronary artery was as high as 20% . Poor myVeno-arterial extracorporeal membrane oxygenation (VA-ECMO), which provides temporary circulatory support for critically ill patients with refractory cardiogenic shock and cardiac arrest, can be used as a bridge to myocardial recovery in aTAAD patients , 7. SincIn this retrospective, single-center study, we reviewed the records of adult patients who received VA-ECMO support after aTAAD surgery at Zhongshan Hospital, Fudan University  from January 2014 to December 2019. Exclusion criteria included: an age <18 years old or pregnancy. Zhongshan Hospital performs over 150 aTAAD surgeries per year, including ascending aortic and hemi- or total-arch replacement, with or without concomitant surgical treatment of the aortic root, as well as elephant trunk stent procedures for the descending aorta. The study was approved by the Ethics Committee of Zhongshan Hospital.Patients were divided into two groups according to whether the VA-ECMO was successfully removed or not (patients were defined as successfully weaned from VA-ECMO if they survived for longer than 48 h after VA-ECMO explantation) . BaselinAll aTAAD patients underwent emergency surgery, unless the patient refused surgery or had preoperative neurological complications. Surgical repair was performed under CPB and deep hypothermic circulatory arrest. In some patients, replacement of the ascending and proximal arch was sufficient, but when the intimal tear was in the aortic arch, total arch replacement was performed. We routinely used unilateral selective antegrade cerebral perfusion with deep hypothermic circulatory arrest as a cerebral protection strategy during emergent surgical repair of aTAAD. We used continuous cerebral near-infrared spectroscopy to monitor brain oxygenation during surgery.The decision to use VA-ECMO was made by the cardiac surgeon in the operating room or by the intensivist in the cardiac surgery ICU. Indications for VA-ECMO therapy included difficulty weaning from CPB or postoperative refractory cardiogenic shock despite adequate volumes and high doses of inotropes such as norepinephrine, dobutamine, epinephrine, and milrinone. A femoral venous cannula placed from the femoral vein to the right atrium was used as the VA-ECMO venous cannula. The femoral artery is most commonly used for arterial catheterization in adult patients, but this puts the aTAAD patients at risk of developing Harlequin syndrome. Because of this, we routinely used right axillary artery catheterization in aTAAD patients with refractory hypoxemia.In the initial stage of VA-ECMO, the target mean arterial pressure was maintained at ≥60 mmHg, thus, ensuring tissue perfusion without excessive increase of afterload. Serum lactate level was used as an indicator of tissue hypoperfusion and has been proved to predict outcomes of cardiogenic shock associated with organ failure . Cardiac9/L  was given intravenously. During VA-ECMO support, heparin was used as an anticoagulant. Active clotting time was maintained at 180–200 s or activated partial thromboplastin time was maintained at 50–80 s in patients with low bleeding risk. In patients with high bleeding risk, active clotting time was maintained at 160 s. Platelets were transfused when the patient's platelet count fell below 50 × 109/L .2O, a respiratory rate of 10–12 times/min and fraction of inspired oxygen no more than 50%. All patients received remifentanil and midazolam to achieve target sedation and underwent daily awakening trials. We routinely monitored cerebral oxygen saturation and carried out a physical examination of the nervous system .Continuous data are expressed as mean ± standard deviation (SD), if normally distributed, or median (IQR), if not normally distributed. For continuous variables, the normality of distribution was evaluated using the Kolmogorov–Smirnov test. Categorical variables are summarized as percentages (%). Categorical variables were analyzed using the χp < 0.01). Age and preoperative cardiac troponin T (cTnT), lactate dehydrogenase (LDH), and creatinine (Cr) levels were higher in the failed group than in the successful group , but the differences between the two groups were not statistically significant (p > 0.05).Twenty-seven patients, who were supported with VA-ECMO following aTAAD surgery, were enrolled in the study between January 2014 and December 2019 . The meap > 0.05). Postoperative peak CK-MB, cTnT, and LDH levels were all significantly higher in patients who failed withdrawal of VA-ECMO . Postoperative peak lactate levels were also higher in the successful group than in the failed group .Peri-operative details of the 27 patients who were supported with VA-ECMO are summarized in Seventeen patients received VA-ECMO support in the operating room because of difficulty in weaning from CPB, and ten patients had VA-ECMO initiated in the cardiac surgery ICU because of refractory postoperative cardiogenic shock. No progression of aortic dissection was observed during VA-ECMO support. After a median period of 192 h of support, nine patients (33%) were successfully weaned from VA-ECMO support and five patients (19%) survived to hospital discharge. One patient had residual right lower limb movement disorder. The in-hospital mortality rate was 81% (22 patients). The follow-up survival rate of aTAAD patients who required perioperative VA-ECMO support was relatively low .p < 0.01), a longer ICU stay  and a longer hospital stay , compared with patients who failed weaning from VA-ECMO. No patient was lost to follow-up during this period. Details of VA-ECMO implementation and outcomes are presented in Additionally, patients who were successfully weaned from VA-ECMO had a longer mechanical ventilation time , have led to a gradual decrease in the mortality rate of aTAAD, with mortality rates reported to be 15–30% . VA-ECMOSeveral factors may be associated with VA-ECMO weaning failure. Younger age, lower preoperative CK-MB levels, reduced postoperative blood transfusion, higher antegrade cannulation rates, lower lactate levels, lower rates of continuous renal replacement therapy, and organ ischemia have all been shown to influence survival of aTAAD patients after VA-ECMO support , 17. We In terms of cannulation strategies, peripheral cannulation is minimally invasive and is the routine pathway for most adult patients. Although femoral artery-femoral vein catheterization is easier and faster, we preferred to cannulate in the right axillary artery because of residual aortic dissection in aTAAD patients. Axillary artery cannulation is, however, technically more difficult than the femoral artery and there is also a risk of hyperperfusion of the ipsilateral arm and brain . We compComplications of VA-ECMO support following aTAAD surgery include bleeding, cerebral dysfunction, malperfusion of vital organs, and infection. In our study, death usually occurred soon after surgery and major bleeding was the most common cause of death in patients who could not be successfully weaned from VA-ECMO. Causes of postoperative bleeding may be multifactorial –26. SystOur study has several limitations. Firstly, the study was a single-center, retrospective study. Secondly, because of the rarity of aTAAD with VA-ECMO support, the sample size was too small and the follow-up time was relatively short, which meant that detailed analysis of risk factors was not possible. In the future, multicenter studies, with large patient populations, are needed to optimize management strategies and improve outcomes in this rare but complex cardiac emergency.This study showed that the use of VA-ECMO in aTAAD patients is a viable salvage strategy, despite the relatively high rate of complications and mortality. VA-ECMO could provide a bridge-to-recovery for aTAAD patients with refractory cardiogenic shock.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.J-yH, G-wT, and ZL contributed to study design. Y-xS, J-yH, HW, HL, J-lZ, and Jc-L contributed to enrollment of participants. J-lZ and XL contributed to study management and data collection. J-yH and C-sW contributed to manuscript writing. G-wT and ZL contributed to data analyses and manuscript revision. All authors have read and approved the final manuscript.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.


However, the studies had generally high heterogeneity (I2 greater than 50%) and overall moderate-to-severe risk for bias. Moving forward, a randomised, controlled trial is necessary to shed light on the subject.Despite numerous technological and medical advances, out-of-hospital cardiac arrests (OHCAs) still suffer from suboptimal survival rates and poor subsequent neurological and functional outcomes amongst survivors. Multiple studies have investigated the implementation of high-quality prehospital resuscitative efforts, and across these studies, different terms describing high-quality resuscitative efforts have been used, such as high-performance CPR (HP CPR), multi-tiered response (MTR) and minimally interrupted cardiac resuscitation (MICR). There is no universal definition for HP CPR, and dissimilar designs have been employed. This systematic review thus aimed to review current evidence on HP CPR implementation and examine the factors that may influence OHCA outcomes. Eight studies were systematically reviewed, and seven were included in the final meta-analysis. Random-effects meta-analysis found a significantly improved likelihood of prehospital return of spontaneous circulation (pooled odds ratio (OR) = 1.46, 95% CI: 1.16 to 1.82,  Of the myriad prehospital challenges confronting emergency medical services (EMS) systems worldwide, out-of-hospital cardiac arrests (OHCAs) remain a global challenge ,2,3,4,5.Interruptions to chest compressions persistently emerge as a major contributor to the high mortality associated with OHCAs . The effThe ongoing coronavirus disease 2019 (COVID-19) pandemic has significantly impeded each link in the chain of survival ,11, provIn recent years, there is growing interest in the advantages and implementation of high-quality prehospital OHCA resuscitative efforts. Multiple approaches as to what defines high quality have been used. This includes high-performance CPR (HP CPR), multi-tiered response (MTR) and minimally interrupted cardiac resuscitation (MICR) ,14,15,16Yet, these studies together have not managed to provide a conclusive answer on the optimal EMS team configuration or ascertain that high-quality resuscitative efforts, henceforth labelled as HP CPR, can provide the holy grail to better outcomes for OHCAs. The implementation of HP CPR in some EMS systems has found nonsignificant differences for prehospital return of spontaneous circulation (ROSC) in some instances . There iClinicaltrials.gov, Web of Science, and Google Scholar databases yielded 208 papers published in English between 1 January 1988 and 31 March 2021. To maximise sensitivity, the search strategies relied on blended subject headings and keyword (free text) approaches. Attempts were made to search the gray literature as well using the Google search and hand searching. Title/abstract screening was performed independently by two researchers (Q.X.N. and M.X.H.) to identify articles of interest. For relevant abstracts, full articles were obtained, reviewed and also checked for references of interest. If necessary, the authors of the articles were contacted to provide additional data.A systematic literature search was performed in accordance with the latest Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines . Using tp-values were calculated. Heterogeneity among the different studies pooled was examined using the I2 statistic and Cochran’s Q test. Publication bias was assessed using a funnel plot and the Egger test [Full articles were obtained for all selected abstracts and reviewed by three researchers  for inclusion. Any disagreement was resolved by discussion and consensus. The inclusion criteria for this review were as follows: (i) original published study, (ii) implementation of HP CPR or similar minimally interrupted CPR or a multi-tiered response system and (iii) reporting of OHCA outcomes. Non-human studies, abstracts and conference proceedings were excluded from review. The primary outcome measures of interest were neurological outcomes, survival-to-discharge and ROSC rates in patients who received an HP CPR intervention or similar interventions as opposed to controls. Data such as study design, sample size and study population were extracted from the studies reviewed and are summarised in ger test . All anaThe quality and risk of bias of the studies were also assessed with the Risk Of Bias In Non-randomized Studies—of Interventions (ROBINS-I) tool , graded As seen in 2 is greater than 50%), the forest plot (p < 0.001), supporting a significantly improved likelihood of survival.Using a random-effects model .When examining the pooled OR for any ROSC , there wp < 0.001) also supports significantly better neurological recovery with such interventions  with HP CPR or similar intervention. The pooled OR of 1.24 ; however, the reliability of the Egger test was limited by the small number of studies, that is, less than 10 studies [Visual examination of the funnel  and Egge studies . No sensAs for the risk of bias of the various studies  HP CPR can lead to improved ROSC rates and survival-to-discharge and (2) the HP CPR team composition matters. This could drive changes in paramedic training and protocol development in order to improve patient outcomes. 2 statistic (>50%). This could be attributed to differences in the various EMS configurations, the population under study, the providers’ training standards and corresponding CPR quality. The research designs across the included studies were also not homogenous as different EMS systems have a different number of team members and composition. Fourthly, only three studies reflected the secondary outcome of neurological status. Finally, as most of the included studies employed an observational design, it was difficult to adjust for potential confounding factors such as event-related factors and patient demographics. The studies had an overall moderate-to-serious risk of bias, and the findings must be interpreted in light of these shortcomings. The potential limitations of this study have to be acknowledged. Firstly, the review protocol was not prospectively registered. Secondly, given the different operating contexts and team configurations of the EMS systems covered in this study, we are still admittedly unclear on what the best configuration is for HP CPR. This would depend on the local context and geography. Thirdly, there was significant heterogeneity observed in the meta-analysis, as seen in the forest plots and reflected by the generally high ICurrent evidence suggests that HP CPR, MTR and similar interventions significantly improve prehospital ROSC, survival-to-discharge and neurological recovery for OHCA patients. However, the operating context matters, and the optimal EMS team configuration remains unknown. The skill level and EMT-to-paramedic ratio plays a part as well. More paramedics rather than more EMTs, with their additional armamentarium of drugs and skills, may make more difference than the actual increased hands-on-chest time afforded by non-EMS-heavy teams. Realistically, HP CPR and the MTR may be more resource-intensive than a single-tiered response system and may be difficult to support as EMS utilisation continues to increase. It is thus important to accurately triage and identify OHCA cases early. Future studies should also measure and control for community, patient and hospital characteristics. A randomised, controlled trial design might help shed more light on the topic as well.