As innovative technologies emerge, extensive research has been undertaken to develop new structural health monitoring procedures. The current methods, involving on-site visual inspections, have proven to be costly, time-consuming, labor-intensive, and highly subjective for assessing the safety and integrity of civil infrastructures. Mobile and stationary LiDAR (Light Detection and Ranging) devices have significant potential for damage detection, as the scans provide detailed geometric information about the structures being evaluated. This paper reviews the recent developments for LiDAR-based structural health monitoring, in particular, for detecting cracks, deformation, defects, or changes to structures over time. In this regard, mobile laser scanning (MLS) and terrestrial laser scanning (TLS), specific to structural health monitoring, were reviewed for a wide range of civil infrastructure systems, including bridges, roads and pavements, tunnels and arch structures, post-disaster reconnaissance, historical and heritage structures, roofs, and retaining walls. Finally, the existing limitations and future research directions of LiDAR technology for structural health monitoring are discussed in detail. Infrastructure, including roads, bridges, and buildings, has significantly deteriorated on a global scale, as many of these structures have a limited duration of exploitation. The prevalence of deteriorating structures, in combination with the increased frequency of natural disaster events within recent decades, has necessitated the development of inspection techniques to ascertain the damage and overall level of safety of structures. Often the nature of these structural damages results in logistic constraints, by which human-based visual inspections cannot be conducted, as they pose a danger to the inspectors’ health or the area under inspection cannot be accessed by normal means. Additionally, the use of contact-based devices is time-consuming as they require an extensive setup to attach the devices to the structure and initiate the data collection process. This ultimately delays the rehabilitation process for damaged structures, often resulting in economic losses. Therefore, the need for rapid inspection methods which implement non-contact sensors within the field of Structural Health Monitoring (SHM) has become more prevalent within the past decades. A non-contact sensor  can be dThe growing popularity of non-contact sensors with SHM has resulted in cameras, smartphones, unmanned aerial vehicles, satellites, ultrasonic devices, and various other sensors being used to conduct structural inspections . OpticalProvide a comprehensive review of LiDAR-based SHM assessment for various aging civil infrastructure systems, including bridges, tunnels, roads, roofs, walls, buildings, and historical structures.Summarize the existing limitations and gap areas for LiDAR-based SHM technology.Articulate the future research direction of the LiDAR-based monitoring and inspection techniques for SHM.Light Detection and Ranging (LiDAR) devices and methods have received significant consideration in the past decade by the SHM research community as a tool for 3D point cloud generation and analysis of structures. Recently, many studies have proposed methodologies to optimize the collection and processing of data to create more time-efficient, and computationally inexpensive, SHM systems. An unmanned aerial vehicle-based LiDAR with an optimized flight path decision-making paradigm was implemented by ,5. Over Applications of LiDAR for SHM typically involve analyzing 3D objects, structural geometries, deformations, crack information, and visualization using a dense 3D dataset with finer resolution and precision ,14,15,16A potential advantage of LiDAR devices over traditional non-contact sensors is that there is no requirement for physical instrumentation and accessibility of the structures, thereby saving a significant amount of time and labor costs and improving the safety of the workplace. Moreover, these devices are independent of natural light sources, serving as excellent field measurement tools. However, LiDAR has several following limitations that prompted SHM researchers to advance this technology over the last several years.Dependency on weather conditions.Expensive, and performance degrades with distance.Non-structural components must often be removed using specific filters.The datasets captured by LiDAR devices are extremely large, meaning that the computational processing time is long.Strategic positioning is required to avoid overlapping or targetless scans. The field of view, or the angle covered by the sensor, impacts what is captured by the sensor.There is often the need for multiple scans at different points; thus, object extraction or interpolation techniques are required.Depending on the mounting mechanism, their application can be categorized into two classes, based on mode of operation: (a) stationary and (b) mobile.Terrestrial laser scanning (TLS) is a stationary instrument (as shown in Mobile Laser Scanning (MLS) refers to a broad category of devices/instruments that are mounted on mobile equipment, such as drones, airplanes, cars, or helicopters, as shown in The difference is that the mobile LiDAR device can travel up to 100 km/h and is free to rotate, which requires the need for a GPS receiver and an inertial measurement unit (IMU). The GPS allows the airborne device/instrument to record the exact location of the system to estimate where the device/instrument reflections are located on the scanned surfaces. The distance recorded by each returned laser pulse is subtracted from the recorded altitude of the system to yield the elevation of the scanned surface. To account for the tilt of the system, when the distance of the returned pulse is calculated, the IMU records the roll, yaw, and pitch of the system at each location. Most pulses are emitted at different angles, so the system also accounts for the pulse angle when calculating the elevation of each point. This information on the speed, angle, and rotation of the mobile system are all important for accurate elevation calculations and, therefore, for the acquirement of an accurate point cloud. Mobility issues also limit the uses by which laser-based scanning can be conducted for pavement damage detection. The sensor must be directly attached to a vehicle to make the data acquisition process time-efficient. Ref.  reviewedRef.  identifiLiDAR-based SHM assessment of bridges has predominately involved characterizing the geometric properties of various components . This information is often used to assess the vertical clearance underneath bridges to ensure that large trucks can safely pass beneath the structure. Various studies using LiDAR data have been conducted to ascertain the correlation between environmental properties, such as loading, temperature, and precipitation, on bridge deformation. A few studies have implemented LiDAR for the quantification of various structural damages, including spalling and crack detection. For example, ref.  proposedA LiDAR-based bridge evaluation for material mass loss quantification was explored by . In a brA novel procedure was presented  to measuTerrestrial photogrammetry was used by  to detecAn automated processing method of laser scanning data for the SHM of piers in masonry arch bridges was proposed by . A full-A deflection and deformation measurement application for bridges was proposed by . The shaA three-dimensional path planning method for LiDAR-equipped UAVs was introduced by  for inspTo date, the use of TLS for quality inspection has been focused on identifying surface defects and the presence of water in structural members through utilizing differential geometry, RGB values, image segmenting, and gradient-based methods, as well as combining different image-based technologies, as summarized by . For assFor underground tunnels, excessive-profile deformations are a significant concern as they often result in the collapse of the structure. Therefore, the majority of LiDAR or TLS-based inspections of these tunnels focus on ongoing data acquisition, which can be used to measure the change in profile deflection with respect to time. An approach for monitoring tunnel profile deformations with the use of multi-epoch LiDAR was established by . The metA method for the automatic extraction of tunnel cross-sections was investigated by  based onA new method was established by  that conSimilar to underground tunnels, excessive-profile deformations in arched structures are a significant concern for the continued integrity of the structure and must be monitored through TLS devices. An experiment was carried out by  on a briA novel algorithm developed by  was implPreservation and rehabilitation of historic structures have become a key component of SHM, as many structures globally have reached, and exceeded, their service lives. Historic structures are often characterized by extreme fragility, and as such often require techniques that reduce physical interaction with the structure. Therefore, the use of non-destructive testing methods, such as laser-based scanning, allows inspectors to assess the structure without direct physical contact with the structure. A comparison of three methods  for characterizing historical building damage, using the intensity data from three different TLSs, found that the fuzzy k-means algorithm resulted in the best accuracy . EvaluatThe vertical deformation of a minaret of a historical mosque was studied by  using TLMobile LiDAR Systems were evaluated by  for the The use of multi-temporal TLS data comparisons was explored in , based oLaser-based scanning of concrete structures provides engineers in the SHM community with information about the severity of the damage. Furthermore, the 3D point clouds generated by these techniques provide quantifiable data about the level of cracking and spalling, which is easily obtainable through other optic-based devices, such as cameras or traditional surveying equipment. Three algorithms proposed and tested by   was applied to the 2.5D map using an estimate of the mortar joint width in . The resA framework to reduce the size of point cloud datasets, while also detecting surface imperfections  and physicochemical issues , in building walls was explored by . The poiApplications for laser-based inspection of roofs have been limited within the SHM field, in comparison to other analyses involving the entire 3D structure or various elements of the structures. As unmanned aerial vehicles with a sufficient payload capable of carrying a laser-based scanning device are required to conduct the survey, the relative accessibility of rooftop inspections becomes restricted. A segmentation method using laser data for damaged roofs was proposed by . The indThe structural damage of roofs was detected in , based oNatural disasters, such as earthquakes, landslides, hurricanes, and floods, often create logistical constraints for structural inspection, thus increasing the difficulty in performing human-based inspections. As such, non-contact devices that can be deployed at a distance from the damaged structure, such as LiDAR devices, are increasingly being implemented for post-disaster reconnaissance of structures and hazard regions. Two processing strategies for post-event ALS data were compared by  to automAn evaluation of multi-temporal and mono-temporal methods for identifying earthquake-induced building damage from optical, LiDAR, and SAR data was reviewed by . The comA framework was introduced by  that estA damage evaluation framework by  integratA novel airborne LiDAR-based approach by  was implA recent study by  consisteThe feasibility of TLS to perform structural change and deformation analysis was outlined in a study by , which pA review of recent methods for change detection was conducted by  using moAlpha-Shapes were applied in  to deterA novel 3D surface descriptor was created by  for the A method for the inspection of piping components was created by , based oThe use of a TLS, compared to Close-Range Photogrammetry (CRP) based on the Structure from Motion (SfM) algorithm, was evaluated by  for measThe performance of different non-contact sensors  and algorithms  was reviewed by  for the Although LiDAR-based structural assessment has received increased attention in the SHM field over recent decades, there are still limitations related to the non-contact sensing process. The most challenging step in LiDAR-based monitoring is acquiring a point cloud that is high quality, dense, and uniform. Errors in the point cloud can yield redundant data or gaps in the point cloud, thus also affecting the application and accuracy of algorithms for detecting structural damage. The quality of data that the MLS or TLS device acquires is highly dependent on several parameters, including the following: (1) the presence of occlusions or redundant objects, (2) surface properties, (3) scanner positioning, (4) scanner specifications, and (5) the environmental conditions. The first major challenge to acquiring a point cloud that is ready for structural analysis is the large amount of redundant data that must be filtered. Dependent on the application, this may include vegetation, people, and non-structural components of the structure or surface being studied. The presence of this redundant data is problematic, due to the direct correlation between computational times with the larger datasets. Also, redundant data can act as obstacles in the scans that prevent the acquisition of data of the objects of interest. One of the main disadvantages of their scanner-based bridge evaluation was the presence of occlusions that prevented the entire scan of the target structure in . LimitedSurface properties also have a significant impact on the quality of the LiDAR scans. The surface smoothness and general features of the surface may enhance noise within the point cloud, making it difficult to differentiate between surface deviations that may or may not impact the structural integrity of the element. A method for identifying cracks in concrete bridges was developed by  but founThe quality and completeness of point cloud data are also heavily correlated to the relative positioning of the scanning device. TLS point clouds can be particularly difficult to obtain due to overlapping or targetless scans if the field of view or incident angle of the sensor is not positioned strategically. The proposed method was not suitable for curvature-based analysis if the noise exceeded a certain threshold in . SimilarScanner specifications, such as the device’s range, the mobility of the device, and the general settings, are important limitations to be considered for LiDAR-based SHM. For surface damage detection, it is a common issue that the scanning precision of the LiDAR device does not allow the identification of smaller defects in the range of several millimeters ,81. WhenFinally, the environment in which the LiDAR scans are taken can create obstacles to performing structural analysis on a high-quality point cloud. The primary environmental factors include surface illumination  and weather conditions . Shadows projected by buildings or vegetation and sunlight contamination all contribute to increased noise within a point cloud. LiDAR devices work by bouncing laser beams off surrounding objects, therefore, rain, snow, fog, or dust do not permit scans with high resolution. ALS is often subject to poorer scanning angles, non-uniform point clouds, and high exposure to the environment; therefore, airborne LiDAR data can have reduced quality. While using mobile LiDAR, poor surface illumination or windy environments both highly affected the quality of the point cloud data and the ability of the proposed algorithms to detect cracks in . From the literature review, research being conducted using MLS, TLS, and other LiDAR-based devices over the past two decades has been extensive, resulting in many advancements to point cloud data capturing and assessment. However, there are still limitations for point cloud acquisition, data processing, and feature extraction that current methodologies have not yet addressed. During the data acquisition phase, noise from environmental factors and low point cloud resolution, due to obscured visual angles, are still prevalent within this research domain. As a result, data acquisition is often inaccurate or constrained by the physical parameters of the site under investigation. Future research should focus on developing optimization methods for parameter selection to automatically reduce noise and occlusion during data acquisition, depending on the type of structure. Additionally, best practices for choosing scanning locations and distances should be developed to ensure the completeness of the scanned data and improve the efficiency of the scanning process.Though extracting 3D point cloud from structures is relatively accessible using LiDAR devices, the complexity and size of the extracted data make the post-collection processing a complicated and time-extensive endeavor. Most datasets can be reduced based on the localization of the analysis that is to be conducted; however, current processes require the manual manipulation of the point cloud to extract relevant information to construct a 3D model. Methods for the automatic conversion of raw point cloud data into a 3D model should be explored to maximize the efficiency of post-collection data processing. Furthermore, the robustness of these data processing techniques must be explored to ensure accurate 3D models are extracted from the existing point cloud data. Domain-specific knowledge extracted from objects scanned by LiDAR can be incorporated in the data post-processing stage to enhance the accuracy of the 3D point cloud conversion. Therefore, future methods should focus on robust methods that include geometric and physical parameters of structures for point cloud processing.Following the processing of point cloud data, the 3D models are used to extract quantitative and descriptive data about the damaged structure through the use of statistical models and Artificial Intelligence (AI) techniques. The quality of information extracted from the model is directly correlated to (1) the quality of the data implemented and (2) the robustness of the analytical technique used for the investigation. Though many AI techniques and statistical models have been applied for the evaluation of point cloud-based models, domain adaptability remain a prevalent issue. Domain adaptation is the ability of an algorithm that is trained on a source domain  to perform on a related target domain (cracked concrete columns). Therefore, future research should improve the domain adaptation of existing classification techniques to improve robustness for damage detection for complex structures with a variety of damage types. Furthermore, the accuracy of the quantification of physical parameters of damages, such as cracks, should be improved for cases where the damage features are small (<1 cm).The increased prevalence of natural disasters in conjunction with global infrastructure reaching the end of its service life has spurred the SHM community to develop efficient monitoring and inspection techniques for structures. The diverse and unique challenges presented by various structural components, such as roads, bridges, retaining walls, buildings, and various other structural elements, have instigated an expanded research effort into sensor technologies for SHM. Non-contact sensing techniques, particularly LiDAR-based analysis, have received growing attention with the SHM community recently for their damage detection abilities through the generation of 3D point clouds. This paper provides a comprehensive review of LiDAR-based SHM techniques and the analysis of structural damages using laser-based point cloud data. The development of algorithms for bridges, tunnels and arch structures, post-disaster reconnaissance, historical and heritage structures, masonry surfaces, roofs, pavement and roads, structural elements, and walls have been summarized, and the existing limitations have been discussed. For LiDAR-based SHM, future research should focus on the development of more computationally efficient, autonomous models that are connected to the physical domain they are derived from.


Cancer is a disease with high morbidity and mortality in the world. In the past, the main treatment methods for cancer patients were surgery, radiotherapy and chemotherapy. However, with early treatment, the recurrence rate of cancer is higher, and the drug resistance of cancer cells is faster. In recent years, with the discovery of immune escape mechanism of cancer cells, Immunotherapy, especially Immune Checkpoint Inhibitors (ICIs), has made a breakthrough in the treatment of solid tumors, significantly prolonging the overall survival time and disease-free progression in some solid tumors, and its clinical benefits are more prominent than those of traditional anti-tumor drugs, which has become the hope of cancer patients after the failure of multi-line therapy. More and more studies have shown that there is a correlation between cancer driving genes and the clinical benefits of ICIs treatment, and the therapeutic effects and adverse reactions of ICIs can be predicted by the status of driving genes. Therefore, screening potential biomarkers of people who may benefit from immunotherapy in order to maximize the therapeutic benefits is a top priority. This review systematically summarizes the cancer driving genes that may affect the clinical benefits of immune checkpoint inhibitors, and provides accurate scientific basis for clinical practice. Tumor immunotherapy is a breakthrough research direction in the field of cancer therapy. It mainly inhibits and kills tumor cells by affecting the body’s immune system and enhancing anti-tumor immunity. This therapy has greatly changed the traditional tumor treatment strategy and brought more survival opportunities for patients , 2. ImmuPD-L1 is an important immune checkpoint, which is called programmed cell death ligand 1 (PD-L1). PD-L1 antigen binding site is located in the variable region of Fab segment in the light chain of antibody structure, which determines the target of antibody and the target cells it acts on, while the constant region Fc segment of antibody structure determines the type of antibody, which binds to Fc receptor expressed by immune cells, resulting in antigen clearance . In currRAS/Mitogen-activated protein kinase (MAPK) pathway plays a central role in the development of human cancer. It is highly activated in a variety of tumors, and many of its components have been identified as oncogene . The mosTP53 gene was first discovered in 1979 and is the first tumor suppressor gene to be discovered . Solid tSTK11 is a key upstream activator of AMP activated protein kinase and a central metabolic sensor, which participates in the response to intracellular energy changes through different cellular processes, including regulating glucose and lipid metabolism, cell growth and homeostasis . This geEpidermal Growth Factor Receptor (EGFR) is a transmembrane glycoprotein and one of the four members of ErbB family of tyrosine kinase receptors. Activation of EGFR leads to autophosphorylation of receptor tyrosine kinase, which initiates a series of downstream signaling pathways involved in regulating cell proliferation, differentiation and survival. EGFR is abnormally activated through various mechanisms , which is related to the occurrence of various human cancers . In cancThe main function of MMR is to correct the errors in DNA replication and ensure the fidelity of replication process. However, the hypermethylation and frameshift mutation of promoter lead to the loss of mismatch repair protein expression, which leads to MSI-H/dMMR. Patients with MSI-H/dMMR may benefit from PD-1/PD-L1 inhibitors, and about 15% of colorectal cancer patients have MSI-H gene test results . ASAOKA Human leukocyte antigen (HLA) is the expression product of human major histocompatibility complex gene. HLA plays an important role in immune presentation and recognition. CD8+T cell-dependent killing requires human leukocyte antigen class I (HLA-I) molecules to present tumor antigens effectively. The loss of HLA diversity will lead to the decrease of immunotherapy response rate . StudiesThis review explored the influence of driving genes on the therapeutic effect of ICIs, but the diversity and complexity of driving genes also have certain influence on tumor microenvironment. At present, it has been found that many immunotherapy markers are related to tumor microenvironment. For example, lymphocytes, macrophages and interstitial cells in tumor immune microenvironment also express PD-L1, and the expression level of PD-L1 also has certain influence on tumor microenvironment. For example, lymphocytes, macrophages and interstitial cells in tumor immune microenvironment also express PD-L1, and the expression level of PD-L1 also has certain influence on tumor microenvironment. In lung cancer, the level of PD-L1 was significantly correlated with the site of biopsy, with the highest expression in adrenal and liver metastases and the lowest expression in bone and brain metastases. At the same time, the level of PD-L1 in lung and distant metastatic tissues is positively correlated with clinical benefit, but the level of PD-L1 in lymph node metastasis may not be correlated with clinical benefit. Similar conditions exist in other driving genes, which suggest that driving genes have different roles in different tumor microenvironments.Based on the above research and discussion, it is not difficult to find that the state of tumor driving genes affects the therapeutic effect of ICIs. However, it is more noteworthy that the influence of driving genes on the immune microenvironment of different tumors determines the predicted value of ICIs. As shown in Meichen Gu et al. , KRAS/LKTumor formation is the result of immune escape, and ICIs can reverse immune escape and restore the body’s ability to recognize and eliminate tumor cells. Immunotherapy opens up a new model of cancer treatment. The biomarkers that predict the cancer efficacy, adverse reactions and drug resistance of ICIs play an important role in screening ICIs beneficiaries. Among them, efficacy markers PD-L1, TMB and MSI/MMR have entered the guidelines or consensus, while there are few studies on other driving gene markers of immunotherapy, such as EGFR, HLA, TP53, etc., and the exploration of more accurate biomarkers is still the focus of research. In addition, more related biomarkers and other factors affecting survival and prognosis of immunotherapy  need to be further explored and studied. At present, there are still few large sample trial data based on Chinese population, but with the continuous development of cancer ICIs clinical trials and the increasing number of treatment cases, it is believed that tumor markers will play an increasingly important role in predicting the efficacy, survival prediction and adverse reactions of ICIs. At the same time as the specification of biological detection technology, progress of gene diagnosis technology and medical data, the rapid development of new technologies and means such as artificial intelligence, immunotherapy of cancer will shift from illness condition as they intend and, since the future is expected to be through the detection of biomarkers to predict treatment in patients with different stages of treatment benefits and risks, In this way, precise and individualized treatment plans can be developed to enable patients to have a longer survival time and a higher quality of life. This will be our next research direction.At the same time, it has become the focus of clinical research to explore new and different combination therapy modes and improve the immunotherapy response rate. Combination therapy can overcome the limitations of monotherapy. ICIs has elicited a lasting clinical response in some patients, which is largely dependent on effective T cell infiltration and effector T cell function in TME, while combination therapy is recommended to target multiple abnormalities in the differentiation of cancer cells and normal cells. It mainly includes decreasing TMB and enhancing tumor immunogenicity , enhancing T cell transport and enhancing T cell response. The status of driver genes in cancer cells and normal cells will also provide better strategies for drug combination. In the future, with the progress of genomics, transcriptomics and immunodetection technology, the combination therapy with multiple ICIs will be a new development trend. The establishment of comprehensive biomarker evaluation system through bioinformatics and other methods can predict the efficacy of ICIs more comprehensively, thus promoting the development of tumor precision medicine.As shown in SJ and SG collected data and wrote the paper. XL, CZ, YY, MC and SZ collect literature and information. NS and MD reviewed the paper. All authors read and approved the final manuscript.This work was supported by Beijing Hongdingxiang Public Welfare Development Center (BJ-HDX-20220437) and Project of Beijing Medical Award Foundation (YXJL-2022-0187-0013).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.


This Special Issue focusses on monoamine neurotransmitters responsible for mediating neuronal transmission. They represent a heterogeneous class of compounds, including catecholamines , indoleamines (serotonin and tryptamine), amino acids (γ-aminobutyric acid (GABA), glycine, aspartate, and glutamate), and acetylcholine. They are involved in disorders such as Parkinson’s and Alzheimer’s disease, depression, and other neuropsychiatric diseases in adults. In children, the great majority of developmental disorders such as epilepsy, autism, ADHD, learning and intellectual disabilities, and movement disorders are linked to alterations in the level of monoamine neurotransmitters. Mutations in the genes coding for enzymes/proteins related to neurotransmitter synthesis, metabolism, and transport lead to a variety of inherited deficiencies, globally referred to as neurometabolic disorders. Although some markers for the pathological states due to monoamine neurotransmitter lack or alteration are known, widespread efforts are needed to improve our understanding of pathophysiological mechanisms to design more appropriate systemic approaches. Some of these disorders can be treated pharmacologically; in other cases, the current therapies are only palliative, and thus the identification of specific monoamine pathway defects would enable the selection and development of disease-specific new drugs.ddc coding for aromatic amino acid decarboxylase (AADC) [In this issue, the cross-sectional approach from molecules to mouse models has allowed us to look at neurotransmitter diseases from different points of view. Starting from an initial review of the impairment in the synthesis of dopamine and serotonin due to mutations in the e (AADC)  that leae (AADC) ,3 and See (AADC)  studied 2+ release in neuroendocrine cells through a biochemical experimental approach through dynamic FRET in PC12 cells and amperometric analyses of catecholamines release in the phospho-mimetic and phosphor-null of appropriate protein targets. This level of investigation conjugates biochemical analyses with other biological approaches that are evident in the article of Amakhin [2+-permeable AMPA receptors, leading to the conclusion that the expression of these receptors in principal neurons could be considered a protective factor.Barak-Broker et al.  showed h Amakhin . In thisOverall, the complex world of neurotransmitter impairments could be tackled by differing expertise and point of view to build a more complete picture.Three important lines of intervention can be individuated in future research on monoamine neurotransmitter disorders. A specific ambit of study concerns the relationship between the genotype and clinical phenotype. The knowledge of the correlation between missense mutations and altered protein function in different patients would provide insight into the pathology onset and progression, enabling the design of personalized medicine. A generation of new neuronal models could lead to increased knowledge at the molecular level of these brain disorders and provide platforms for high-throughput drug screening. The identification and development of new biomarkers for early diagnosis could improve the correct identification of the disease, often misdiagnosed, and therefore help develop specific and personalized therapy.


With the increasing uncertainty in the external environment, exploratory innovation has gradually become the key path for enterprises to obtain core competitiveness and achieve sustainable growth. According to the behavioral theory of the firm, performance feedback is an essential driving factor affecting corporate innovation decisions. However, previous studies have ignored the consistency or inconsistency between historical and industry performance feedback, and its impact on exploratory innovation. Based on the data of Chinese companies listed from 2008 to 2019, this paper explores the impact of consistency and inconsistency between historical and industry performance feedback on enterprises’ exploratory innovation. In the cases of consistency, this study finds that the scenario of historical performance shortfall-industry performance shortfall is more likely to promote enterprises’ exploratory innovation than the industry performance surplus-historical performance surplus; in the cases of inconsistency, compared with historical performance surplus-industry performance shortfall, the scenario of historical performance shortfall-industry performance surplus is more likely to promote enterprises’ exploratory innovation. Further research shows that regional institutional development enhances these relationships. This study enriches the driving factors of enterprises’ exploratory innovation from the perspective of multiple performance feedback, which can provide decision-making references for enterprises’ exploratory innovation strategies. In the context of increasing uncertainty, volatility, complexity, and ambiguity in the external environment, technological innovation has become the core driving force for enterprises to enhance competitiveness and achieve sustainable development . ExploraAccording to the behavioral theory of the firm, an enterprise is an organizational system oriented by a goal decision that will establish a reference point (aspiration level) that satisfies the decision-maker when evaluating the operating status of the enterprise  and adjuOther scholars hold the opposite view that when the actual performance exceeds the aspiration level, abundant redundant resources provide sufficient funds for innovation activities, trigger the redundancy-driven search mechanism of enterprises, and improve the enthusiasm of enterprises for innovation . HoweverIn the actual decision-making process of enterprises, decision-makers judge the operating status of enterprises based on both historical and industry aspiration levels rather than a single aspiration level . There aComplex performance feedback situations are the norm in corporate decision-making, which run through the entire process. According to the multiple performance expectations of historical and industry contexts, there are two possibilities regarding consistency and inconsistency, historical performance shortfall-industry performance shortfall and historical performance surplus-industry performance surplus; historical performance shortfall-industry performance surplus and historical performance surplus-industry performance shortfall. Especially in the cases of inconsistency, the business status of the enterprise cannot be defined as loss or gain, and decision-makers need to analyze the above information . InconsiWe systematically explore the impact of the consistency and inconsistency between historical and industry performance feedback on EI based on the behavior theory of the firm. We believe that, in the cases of consistency, the historical performance shortfall-industry performance shortfall is more likely to promote enterprises’ EI than industry performance surplus-historical performance surplus. When both the historical and the industry performance feedback are in shortfall, decision-makers recognize that there are some problems within the enterprise. This creates an impetus within enterprises to change the status quo and enhance competitive advantage, and necessitates enterprises to implement high-profit EI . HoweverIn the cases of inconsistency, historical performance shortfall-industry performance surplus is more likely to promote EI than historical performance surplus-industry performance shortfall. Compared with industry performance feedback, historical performance feedback reflects the management ability of enterprise decision-makers more directly. In the cases of historical performance shortfall-industry performance surplus, decision-makers consider that historical performance shortfall may damage their reputation. To prove their leadership ability, enterprise managers actively use the advantages brought by the industry performance surplus to solve existing problems. Consequently, decision-makers actively seek organizational innovation, enhance enterprises’ EI, and obtain more benefits, thereby reducing the historical performance shortfall and maintaining their reputation and image. In the cases of historical performance surplus-industry performance shortfall, decision-makers attribute the industry performance shortfall to the uncertainty factors in the external environment, avoiding personal image and evaluation damage, which stimulates self-enhancement motivation . DecisioFurthermore, the impact of consistency and inconsistency of performance feedback on EI may be restricted by the external environment, primarily regional institutional development. Regional institutional environment development change decision-makers’ understanding and response to feedback signals and affect the relationship between performance feedback and enterprises’ EI . As an iChina is the world’s second-largest economy, and innovation is the core of China’s modernization drive. To build an innovation-oriented country, it is necessary to realize high-quality development of the national economy so that enterprises conduct EI and improve their core competitiveness actively. In addition, China is in a critical period of transformation and upgrading, and the development of the market mechanism is still incomplete. As the main component of the modern market economy, enterprises are the key force for the country to improve its innovation capability and implement the innovation-driven development strategy. Thus, China provides a suitable environment for examining the EI of enterprises.Based on the sample data of Chinese companies listed from 2008 to 2019, we examine the impact of multiple performance feedback on enterprises’ EI. This study finds that after controlling for variables at the level of corporate characteristics and corporate governance, the empirical evidence for the abovementioned theoretical viewpoints holds. In the cases of consistency of performance feedback, historical performance shortfall-industry performance shortfall is more likely to promote enterprises’ EI. In the cases of inconsistency, historical performance shortfall-industry performance surplus is more likely to promote enterprises’ EI. RI strengthens the abovementioned positive relationship. In addition, we replace the measurement indicator of the independent variable, change the measurement method of the independent variable, and used the systematic GMM model to perform an endogeneity test, and the results remain robust.In summary, this paper has three theoretical contributions: First, we enrich relevant research on the driving factors of enterprises’ EI from the perspective of multiple performance feedback. Considering the impact of performance feedback on enterprise innovation prior studies mainly focused on a single reference point, namely, historical performance feedback or industry performance feedback ; few stuSecond, our research expands the existing theoretical model of performance feedback and enterprises’ EI decision-making. Previous studies focused on the influence of internal factors on the relationship between performance feedback and enterprise innovation while ignoring the vital role of the external environment for enterprises’ survival and development . We explThird, this study provides concrete empirical evidence of enterprises’ EI decision-making. From the multiple reference points of historical and industry performance expectation, we explore the differential influences of combination situations with multiple performance feedback on EI of enterprises, providing a practical reference for enterprises to improve EI strategy and achieve sustainable development.The rest of this paper is organized as follows. In the section “Theoretical Analysis and Hypotheses,” we discuss the hypothesis development. In the section “Research Design,” we introduce the data and methods. In the section “Results,” we discuss the empirical results, and in the last section “Conclusion and Discussion,” we conclude the study.Bounded rational decision-makers usually judge the current operating state of an organization based on experience to simplify decision-making. In evaluating the actual performance, a satisfactory reference point, namely the aspiration level, is determined and enterprise decisions are adjusted according to the reference point . ReferenWhen an enterprise has a multiple reference point for historical performance expectation and industry performance expectation, there are two possibilities (consistency and inconsistency) in the performance evaluation results, presenting four different combinations of scenarios, as shown in In the cases of consistency between historical and industry performance feedback, multiple performance reference points provide enterprises with more accurate feedback signals. When both the historical and the industry performance feedback are in surplus, the enterprise is defined as being in an absolute benefit state. This situation leads to behavioral inertia in enterprises, which is not conducive to EI. First, the performance feedback surplus proves to some extent that the current strategic decision is suitable for the development of enterprises and bring higher profits for enterprises. At the same time, considering stakeholders’ demands for organizational stability, enterprises tend to give up EI activities with high risks and high returns to maintain existing benefits . EI needWhen both the historical and the industry performance feedback are in shortfall, it indicates that the actual operating performance of the enterprise is lower than the aspiration level and that the organization’s current business strategy, resource allocation, or market competition mechanism is not perfect; further, the enterprise is defined as being in an absolute loss state. Multiple performance feedback shortfall makes decision-makers realize that there are problems in organizational operation. Thus, enterprises improve their core competitiveness and obtain higher returns only by disrupting organizational inertia and choosing EI with high risks and high returns .On the one hand, a performance lower than the aspiration level will trigger the enterprise problematic search mechanism, according to the existing problems targeted innovation strategy adjustment. Decision-makers optimize the internal resource allocation of enterprises, acquire external novel knowledge, and stimulate a forward-looking thinking mode, thereby enhancing enterprises’ EI to adapt to customer and product market competition and improving enterprise benefit ability . EnterprOn the other hand, when the performance feedback shortfall threatens the organization’s reputation and external legitimacy, decision-makers of enterprises need to make reasonable explanations. When the performance of an organization continues to decline and decision-makers fail to propose corresponding solutions, stakeholders will question the organizational development strategy . The simH1: In the cases of consistency of performance feedback, compared with the historical performance surplus-industry performance surplus, historical performance shortfall-industry performance shortfall is more likely to promote enterprises’ EI.Inconsistent performance feedback includes two scenarios: historical performance surplus-industry performance shortfall and historical performance shortfall-industry performance surplus. The inconsistent feedback information can help them identify the operating state and industry situation under the multiple performance evaluation criteria to conduct targeted innovation strategy adjustments . CompareIn addition, the scenario of the historical performance feedback being in a surplus indicates that the current enterprise innovation strategy will lead to higher profits in the future. Enterprises will continue to keep the original technology, skills, and management style, and discontinue developing new products and technology, and expand product lines to meet more customer needs, thereby lowering the EI of enterprises.When the historical performance shortfall and industry performance surplus occur simultaneously, it indicates that the actual performance is higher than the industry average but does not achieve the self-expected goals, and the enterprise is said to be in a relative loss state. Decision-makers may actively perform EI to obtain excess returns in order to reduce the current situation of historical performance shortfall and maintain their reputation and image proving their leadership and management ability . On the On the other hand, the historical performance shortfall-industry performance surplus may also indicate that with the increasing uncertainty of the external environment, the development of the whole industry is depressed. Although the industry performance is in a surplus, the enterprise cannot be said to be in an excellent state. The decline or recession of the overall industry can cause enterprise decision-makers to be aware of crises, improve enterprises’ risk tolerance, enhance the confidence and ability of enterprises to seize the market, and stimulate enterprises to perform EI . TherefoH2: In the cases of inconsistency of performance feedback, the scenario of historical performance shortfall-industry performance surplus is more likely to promote EI than the scenario of historical performance surplus-industry performance shortfall.New institutional economics indicates that one of the critical factors affecting technological progress and innovation behavior is the development of the regional institutional environment. The development of a regional system includes a series of external environmental factors that include policy, market, and factor environment that enterprises face in the production and management domains. In particular, China is in the process of economic transformation and upgrading, and the interaction between changes in the regional institutional environment and organizational strategic decision-making is more closely related. RI is an essential factor affecting corporate innovation decision-marking .RI can not only ease the impact of uncertain factors on enterprises and give full play to the external governance effect, stimulating enterprises to perform EI activities, but can also reduce their operating cost by optimizing the allocation of innovation resources, thus increasing innovation and helping the sustainable growth of the enterprise . SpecifiRI affects decision-makers’ cognition and judgment of performance feedback information. It determines whether an enterprise will perform the EI behavior of active search and disruptive change. In regions with developed institutions, enterprises attach more importance to the guiding role of the performance feedback mechanism in operation decision-making, and can timely adjust strategic decisions based on feedback signals. Especially in the scenario of historical performance shortfall-industry performance shortfall, RI provides more convenience for enterprises’ EI, strengthens the motivation of enterprises’ EI, and enhances the positive relationship between historical performance shortfall-industry performance shortfall and enterprises’ EI .On the one hand, when the enterprise is in shortfall, enterprise managers actively disrupt the initial organizational inertia and prevalent management thinking and search for existing problems in the enterprise. RI can effectively reduce the cost of problem-driven search to help enterprises improve the current situation. RI can not only provide enterprises with more external resources and information and reduce the difficulty of obtaining external information, but can also optimize the allocation of resources and improve the efficiency of enterprises in creating new knowledge and technology . On the H3: In the cases of consistency of performance feedback, RI positively moderates the relationship between the scenario of historical performance shortfall-industry performance shortfall and enterprises’ EI.When faced with inconsistent performance feedback, especially in the scenario of historical performance shortfall-industry performance surplus, RI can improve the effectiveness of the performance feedback mechanism, strengthen the reputation incentive effect of decision-makers, and enhance the EI of enterprises. In regions where regional institutions are well developed, enterprises face fewer difficulties or obstacles and operate more smoothly, which is conducive to maintaining the reputation of enterprises’ decision-makers and improving their leadership . When anAdditionally, RI reduces decision-makers’ worries about the uncertain industrial environment and improves their risk tolerance, promoting enterprises to actively reform and innovate . Some enH4: In cases of inconsistency of perform feedback, RI positively moderates the relationship between the scenario of historical performance shortfall-industry performance surplus and enterprises’ EI.We selected Chinese A-share listed companies from 2008 to 2019 as the research samples to explore the impact of performance feedback on enterprises’ EI. We chose 2008 as the starting year because China implemented new accounting standards in 2007. To ensure the rationality of sample selection and follow the results of previous studies, we strictly screened research samples according to the following exclusion criteria There are many ways to measure EI. a is an adjustment parameter between  and represents the weight between the performance of the current period and the aspiration level of the previous period in the HA level of the current period. This is based on research of Drawing on the practice of According to Regional institutional development (RI) as a comprehensive external environment may play a moderating role in the impact of performance feedback on enterprises’ EI. To account for alternative explanations, we include a comprehensive set of control variables from the level of corporate characteristics and governance . At the At the level of corporate governance, board size represents the natural logarithm of the number of directors after adding 1, and the board of directors decides the strategies and their scale influences the EI of enterprises. The ownership concentration refers to the shareholding ratio of the largest shareholder of an enterprise, which reflects the internal control problems of the enterprise. Additionally, we controlled for the individual effect (ID) and time effect (YEAR) to eliminate the factors that do not change with time at the enterprise level and the influence of common time trends on the EI of enterprises.We constructed the following regression model to test the impact of multiple performance feedback on enterprises’ EI  and the where a1 = 0.1196, p < 0.01), indicating that in the cases of consistency, the historical performance shortfall-industry performance shortfall is more conducive to the enterprises’ EI, H1 is supported. Model 4 indicates that multiple performance feedback in the cases of inconsistency has a significant positive impact on the EI of enterprises , indicating that in the cases of inconsistency, the historical performance shortfall-industry performance surplus is more conducive to the enterprises’ EI, supporting H2.b13 = 0.0440, p < 0.01), indicating that in the cases of consistency, the RI positively enhances the relationship between the historical performance shortfall-industry performance shortfall and the enterprises’ EI, H3 is supported. Model 4 analyzes the moderating effect of RI on the relationship between the multiple performance feedback in the cases of inconsistency and enterprises’ EI. The empirical analysis results of Model 4 show that it has a significant positive moderating effect , indicating that in the cases of inconsistency, RI positively enhances the relationship between the historical performance shortfall-industry performance surplus and enterprises’ EI, supporting H4.The test results of the moderating effect of RI are shown in a1 = 1.8230, p < 0.01), indicating that a positive relationship exists between the historical performance shortfall-industry performance shortfall and enterprises’ EI. Model 4 indicates that the multiple performance feedback in the cases of inconsistency has a significant positive impact on enterprises’ EI , indicating a positive relationship between the historical performance shortfall-industry performance surplus and enterprises’ EI, which was similar to our assumptions. This indicates that our research conclusions have high robustness.We also conducted the following tests to ensure the robustness of the research conclusions. First, we replaced the measurement indicator of the independent variable. We used ROA to measure the performance of the enterprise. To ensure the robustness of the research conclusions, we change the performance measurement indicator to further test the hypothesis. We replace the enterprise performance measurement indicator with OROA, namely, the operating profit margin on total assets. a1 = 0.1345, p < 0.01), indicating that the historical performance shortfall-industry performance shortfall is more conducive to the enterprises’ EI. Model 4 shows that the multiple performance feedback in the cases of inconsistency has a significant positive impact on enterprises’ EI , indicating that the historical performance shortfall-industry performance surplus is more conducive to the enterprises’ EI.Second, we modified the measurement method of the independent variable. When we measured the performance feedback, the actual performance weight in the calculation formula of the aspiration level was set to 0.6. Considering that different weight settings will affect the results of the aspiration level, we set the actual performance weight in the aspiration level to 0.5. The results were still significant. a1 = 0.2163, p < 0.05), and Model 2 shows that the multiple performance feedback in the cases of inconsistency has a significant positive impact on enterprises’ EI , which is the same as our assumptions, indicating that our research conclusions are still highly robust after controlling endogeneity to a certain extent.Finally, considering the problem of endogeneity, the performance feedback of the enterprise affects the EI of the enterprise. In turn, the EI of the enterprise affects the business performance, and subsequently affects the performance feedback. To reduce the impact caused by endogeneity, we constructed a dynamic panel model with a lag of one period of enterprise EI and used the systematic GMM estimation method, which can control endogeneity . Table 7We used the data of Chinese A-share listed companies from 2008 to 2019 as samples for hypothesis testing and drew the following conclusions: (1) In the cases of consistent performance feedback, compared with the scenario of historical performance surplus-industry performance surplus, historical performance shortfall-industry performance shortfall is more likely to promote EI, which is conducive to sustainable growth. In the scenario of historical performance shortfall-industry performance shortfall, enterprises need to adjust innovation strategy to adapt to the competition of customers and the product market. To actively change the shortfall state of enterprises and obtain excess profits, decision-makers are more willing to try risk-taking or innovative behaviors, thus promoting the EI of enterprises. (2) In the cases of inconsistent performance feedback, compared with the scenario of historical performance surplus-industry performance shortfall, historical performance shortfall-industry performance surplus is more likely to promote EI. In the scenario of historical performance shortfall-industry performance surplus, enterprises may lack sufficient resource input, resulting in an unsustainable competitive advantage. To narrow the historical performance shortfall and secure the position of the industry, enterprises will actively conduct EI to provide the impetus for the healthy development of enterprises. (3) In the cases of consistent performance feedback, especially in the scenario of historical performance shortfall-industry performance shortfall, decision-makers of enterprises make full use of the RI to obtain more policy support and market information, which can effectively reduce the cost of enterprise problematic search and improve the enthusiasm of enterprises’ EI. RI strengthens the positive impact of the historical and industry performance shortfall on enterprises’ EI. (4) In the cases of inconsistent performance feedback, especially in the scenario of historical performance shortfall-industry performance surplus, the optimized RI weakens decision-makers’ perception of external environment uncertainty and improves enterprises’ confidence in EI. RI enhances the positive impact of the historical performance shortfall-industry performance surplus on enterprises’ EI.Our study has the following implications for management: (1) Enterprises usually revise strategic decisions based on the experience of learning as an adaptive rational system. The performance feedback mechanism provides an important reference point for enterprises. In the actual operation of enterprises, decision-makers should adopt a positive attitude when selecting the reference points, and rationally change the strategic decision of enterprises according to the performance feedback. Concerning the reference to the multiple enterprise expectation gap, enterprises should constantly optimize resource allocation and actively obtain external information, knowledge, and other resources to achieve the target aspiration level. (2) Decision-makers must treat the inconsistent performance feedback rationally. When faced with fuzzy performance feedback signals, decision-makers should reduce the self-enhancing effect. Considering self-reputation, managers attach great importance to historical performance feedback. Industry performance feedback can reflect the industry’s competitive position, which plays an essential role in the long-term development of enterprises. Decision-makers should pay attention to the impact of historical performance feedback on enterprises and improve the importance of industry performance feedback. Enterprise should make full use of the feedback results of consistency and inconsistency to promote EI and enhance the ability of enterprises to adapt to the external environment, achieving sustainable growth of enterprises. (3) In the scenario of industry performance surplus-historical performance feedback surplus, the enterprise is in a state of absolute benefit. In this scenario, decision-makers should make full use of the redundant resource search motivation, improve the EI ability of enterprises, and change the tendency of invariability when enterprises are flourishing. In the scenario of industry performance shortfall-historical performance shortfall, the enterprise is in a state of complete loss. In this scenario, decision-makers should take advantage of the problem to search for motivation and actively seek breakthroughs. Enterprises should further optimize the allocation of resources, acquire external knowledge and technology, and enhance their EI ability. (4) When making innovation decisions, enterprises should not only consider the impact of performance feedback on EI, but also pay attention to external regional institutional development, actively use the convenience brought by RI for EI, and reduce the cost of EI and promote the sustainable development of the enterprise.Our study has the following limitations. We divided the cases of inconsistency based on the direction of surplus or shortfall, exploring the impact of different cases of historical performance feedback and industry performance feedback on enterprises’ EI. However, performance feedback is not only inconsistent in terms of direction, but may also inconsistent in intensity. For example, in the case of surplus or shortfall, there are differences in the intensity of historical and industry performance surplus, which should be discussed in future research. When selecting the regulatory variable, we perform an in-depth analysis of the RI of the relationship between performance feedback and EI, from the perspective of transformation in China. However, we did not fully consider the contingency influence of internal factors, such as precipitated redundant resources or non-precipitated redundant resources, this issue can be taken up by future research.The data supporting the conclusions of this article will be made available by the authors, without undue reservation.XS collected literature. WF designed the research and wrote the manuscript. XS and WF performed the empirical analysis. All authors contributed to the article and approved the submitted version.This research was supported by the National Social Science Foundation of China (19BGL150).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.


Foodborne bacteria interconnect food and human health. Despite significant progress in food safety regulation, bacterial contamination is still a serious public health concern and the reason for significant commercial losses. The screening of the microbiome in meals is one of the main aspects of food production safety influencing the health of the end-consumers. Our research provides an overview of proteomics findings in the field of food safety made over the last decade. It was believed that proteomics offered an accurate snapshot of the complex networks of the major biological machines called proteins. The proteomic methods for the detection of pathogens were armed with bioinformatics algorithms, allowing us to map the data onto the genome and transcriptome. The mechanisms of the interaction between bacteria and their environment were elucidated with unprecedented sensitivity, specificity, and depth. Using our web-based tool ScanBious for automated publication analysis, we analyzed over 48,000 scientific articles on antibiotic and disinfectant resistance and highlighted the benefits of proteomics for the food safety field. The most promising approach to studying safety in food production is the combination of classical genomic and metagenomic approaches and the advantages provided by proteomic methods with the use of panoramic and targeted mass spectrometry. The safety of meat products is one of the most important current and future challenges requiring the attention of the food industry, scientists, and public health authorities.Despite the significant advancement of sequencing technologies and the giant pools of NGS data accumulated, robust, cost-effective, and reliable techniques, allowing the annotation of the microbial status of food, remain a challenge for the scientific community. Today, MS-based technologies to detect foodborne pathogens complement the classical methods and NGS. We would like to highlight two directions in the trends in pathogen proteomics. The first direction, which has obvious practical value, is supported by the efforts of the entire proteomic community to ensure in-process control and reduce batch-to-batch variations, especially in label-free techniques.Taking into account the short duration of the “life” of certain meat products, there is a need for robust and cost-effective methods for pathogen detection, applicable both in the laboratory and in marketable products . We expeThe second hot topic in the field of foodborne pathogens is of high fundamental importance in the context of host–pathogen interactions covering all stages of infection from invasion to dissemination. It would not be an exaggeration to say that the interactions between molecules enable life. To understand the molecular mechanisms behind the life cycle of common foodborne infections, a complete map of the interactions between the proteins and metabolites of pathogens, food products, and, in fact, the end consumer must be formed. We are seeing similar interactive initiatives in the fight against seed-borne diseases in wheat, which lead to the reduced quality and quantity of the crop, and expect similar initiatives from the research community focused on meat products ,3.To date, genomic and transcriptomic methods have a clear advantage over proteomic methods in the field of food production state monitoring due to several reasons. Genomic and transcriptomic methods are more mature and have a longer history of use, the instruments are cheaper and, accordingly, more common. If we compare the genomic and proteomic research intensities for food production safety monitoring, there are 6-times more publications that correspond to genomic research  than to proteomic research . In addition, some mechanisms of bacterial resistance are based on genome changes. Furthermore, for each technology, we can observe a gap between the fundamental research and the applied application in food production safety monitoring for both genomics and proteomics. The turning point is, among other things, the emergence of regulatory documents that allow the use of technology to assess the safety of production. WGS (whole-genome sequencing) gained acceptance as a prospective surveillance tool for foodborne illness in 2016 ,5,6, andAt the same time, proteomic methods give an opportunity to detect rapid changes in the molecular responses of bacterial cells to aggressive stimuli such as antibiotic damage. Therefore, the usefulness of these methods will provide more information about the mechanisms of bacterial resistance and the strains’ life cycles in food production.Traditionally, meat spoilage pathogens are identified with culture-based methods focused on the biochemical, physiological, and morphological properties of the microorganisms under study. These classical methods typically require several days to obtain the results. Moreover, these methods do not provide valuable information on the dead pathogen cells or toxins. Despite the tremendous democratization of NGS methods, high-throughput mass spectrometry-based proteomics has been recognized as an essential tool to reliably identify and quantify thousands of proteins in complex biological matrices.Foodomics renders mass spectrometry as a major “working horse” for its “direct” nature of qualitative and quantitative data on the molecules of interest with great performance and adaptability.Technical progress and scientific curiosity are bringing to the market new MS devices with increased robustness, sensitivity, and selectivity, and decreased sample demand. The variety of mass spectrometric methods is expansive; however, in a broad sense, all MS approaches can be divided into panoramic (or “shotgun”) and targeted groups ,10. In tObviously, all fundamental and practical questions cannot be incorporated into one analytical device, providing panoramic or targeted snapshots of the sample under study. The range of problems that proteomics solves is wider than just the panoramic or targeted search. Often, a researcher analyzes proteins with specific biochemical properties , conformational changes, post-translational modifications, or certain interacting partners ,13. To aSalmonella enterica, Listeria monocytogenes, and Pseudomonas aeruginosa) and the poisoning products that cause infectious diseases. The final part includes data on the markers of disinfectant and antibiotic resistance.The first part of the article is devoted to the methods used for microbial strain analysis, focused on food pathogens. Further review is focused on three key strains  or, for example, diseases (“Diseases”).An essential task in determining the composition of microbial communities is assessing resistance to various types of disinfectants, for example, antibiotics; the effectiveness of measures aimed at the safety of food production directly depends on this. The scientific works in this area characterize the MeSH terms associated with drugs  and methods for studying antibiotic resistance in animals and cell lines . Proteobacteria  and Actinobacteria (79.72%). As biofilms mature, the species composition changes somewhat, but Pseudomonas, Enterobacteriaceae, and Firmicutes are also widely encountered [In a study  on the mountered .Pseudomonas are ubiquitous bacteria due to their versatile set of proteins involved in metabolism [Pseudomonas from raw materials or treated surfaces, cooling air, or water can proliferate in a food product, especially under aerobic conditions [Pseudomonas dominates and spoils the meat through proteolytic, lipolytic, saccharolytic, and biosurfactant processes [Pseudomonas aeruginosa remains one of the most important species in terms of antibiotic resistance due to its high tendency to acquire polyresistance [tabolism . Studiesnditions . At the rocesses . Pseudomsistance ,29,30.Salmonella enterica (family Enterobacteriaceae) is an intracellular parasite that invades small intestinal mucosal cells. Entering the human body with food, this bacterium causes the dangerous disease salmonellosis, which accounts for 25% of all human diarrheal diseases, ranging from mild infections to death [Salmonella strains with resistance to multiple antimicrobials have long spread in developed and developing countries [Gram-negative to death . Salmoneountries . It is gListeria monocytogenes is a member of Firmicutes, a rod-shaped, Gram-positive pathogenic bacterium that is a facultative intracellular parasite. Once in the human body, Listeria monocytogenes causes the dangerous invasive disease listeriosis, an infection that accounts for about 28% of deaths due to foodborne diseases [Listeria monocytogenes can grow at refrigeration temperatures [diseases . This paeratures , therebyBacterial resistance research is complicated due to the bacteria’s ability to form biofilms. A biofilm is a structured community of bacterial cells enclosed in a self-produced matrix that adheres to inert or living surfaces, including tissues, industrial surfaces, and artificial devices, such as intrauterine contraceptive devices, implants and prosthetic medical devices, catheters, dental materials, cardiac valves, and contact lenses. Biofilms form when bacterial colonizers adhere to surfaces in aqueous environments and excrete a slimy, glue-like substance composed of exopolysaccharides (EPS) . It giveThe essence of this problem is that bacteria, organized on any surface as complex communities (biofilms), acquire qualitatively new properties. The biofilm bacteria can increase resistance to immune system effectors, antibiotics, and disinfectants. Food preservatives, disinfectants, and resistance to antiseptics are under-explored , and bioOne of the leading positions in Salmonella enterica, Listeria monocytogenes, and Pseudomonas aeruginosa, acquire resistance to antimicrobial agents through the following mechanisms: (1) structure change of the antibiotic target (mutation), (2) enzymatic degradation or restructuring of the antibiotic, (3) active cell release of antibiotics or efflux, (4) reduced permeability to antibiotics, (5) use of alternative metabolic pathways, (6) and formation of biofilms [Bacteria, including the considered biofilms ,44.Resistance mechanisms may be driven by acquiring three types of mobile genetic elements: self-transferring plasmids, mobilizable plasmids, and conjugative transposons . RegardiDetermining the resistance genes and assessing their expression at the transcriptomic level do not recreate the complete picture of the systemic rearrangements of cellular processes under the stress caused by antibiotics. Currently, studies are underway to establish the position of small non-coding RNAs in rearranging metabolic networks under external stress, including that caused by antibiotics ,47. RNA-Combining several omics technologies makes it possible to recreate the complete network of molecular interactions. Proteomics is evolving rapidly, and its flexibility and potential have yet to be fully exploited. Sidoli et al. even supposed that, in the next ten years, every biological institute will have at least one mass spectrometer . Mass spThe results of the literature analysis devoted mainly to the genotypic methods for studying the resistance in selected strains are presented in According to (a)Panoramic mass spectrometryPanoramic mass spectrometry, or shotgun proteomics, determines the complete set of proteins in a complex multi-component cell extract. Shotgun proteomics uses a liquid chromatograph with a tandem mass spectrometer. This method is considered panoramic because the mass spectrometer registers all peptide ions of the isolated proteins. Shotgun proteomics for studying the mechanisms of the development of resistance in bacteria can be applied similarly to the genotypic approach to measure protein concentrations in strains pretreated with antimicrobial agents, identify overexpression, and try to establish a relationship.Salmonella enterica (Typhimurium serovar) to fluoroquinolone antibiotics using proteomic methods. The protein expression was assessed using two-dimensional HPLC-MS. The increased expression of AcrAB/TolC proteins (efflux pump proteins) is associated with the development of antibiotic resistance. Qi et al. also associated the AcrB efflux pump protein with antibiotic resistance, but they also mentioned the BaeSR protein system [Salmonella enterica proteins, which, in turn, leads to the development of drug resistance.Coldham et al.  studied n system . They suStaphylococcus aureus, which has 15 variants of the toxin [Ultra-high-performance liquid chromatography with tandem mass spectrometry is often used to detect bacterial aggression factors. For example, the authors of the following work identified enterotoxins of he toxin .Similarly, using tandem mass spectrometry with electrospray ionization coupled with liquid chromatography (LC–ESI–MS/MS) in a large-scale study , 395 proSalmonella enterica. A high content of acetylated lysine characterizes the proteins of resistant Salmonella enterica.As mentioned earlier, the post-translational modifications of proteins also impact bacterial resistance to antibiotics . For exaPseudomonas aeruginosa to ofloxacin, post-translational modifications of PheA and SpuC proteins (succinylation and acetylation) were revealed. The study showed that the modifications of pheA and spuC modulate resistance to ofloxacin. The presence of post-translational modifications on these two proteins could direct the protein to a different cellular function and promote the survival of P. aeruginosa.Similarly, in work  devoted Pseudomonas quinolone signal transduction (PQS) (PqsBCDH), phenazine biosynthesis , outer membrane proteins , and fatty acid biosynthesis (FabG).The changes in the metabolic pathways that cause the development of antibiotic resistance can also be captured using proteomic methods. Erdmann J. and colleagues established the quantitative ratio of the core proteome for 27 clinical isolate samples using the DIA technology (data independent acquisition) on the nanoLC-ESI-MS/MS platform (TripleTOF 5600+) . GenomicPanoramic proteomics can be successfully incorporated into multi-omics projects to visualize the multi-dimensional nature of foodborne pathogens in the context of genomics, proteomics, metabolomics, and clinical data. The major advantage of panoramic MS over targeted techniques is that it fuels non-hypothesis-driven proteomic research, making it superior for the early stages of biomarker discovery when dealing with complex biological matrices. Another MS benefit is the ability to explore the processes performed by the whole microbial community at the time of sample collection in time- and cost-effective ways.(b)Targeted mass spectrometryIn the targeted proteome analysis, the mass spectrometer is tuned to detect specific peptide ions related to target proteins. Methods for multiple reactions monitoring and selected reactions monitoring  make it possible to select peptide ions with specified mass-to-charge characteristics at the first and second stages of tandem mass spectrometry. Such methods have several undeniable advantages in comparison with panoramic MS analysis. Bao and colleagues applied MRM with isotopically labeled peptide standards to detect and quantify the staphylococcal enterotoxin SEB in raw chicken . Three pThe extraction of proteins for LC-MS/MS-based analysis involves using gels or long-term immunoaffinity purification to obtain a pure sample for analysis. Anjelkovich and colleagues presented a combination of LC-MS/MS and in silico, solid-phase extraction via MRM , eliminaShigella dysenteriae shigatoxin, STX1 and STX2 (Escherichia coli), and CDT (Campylobacter jejuni). The experimental results confirmed the method’s high sensitivity to toxin concentrations corresponding to food poisoning. In the same work, a unique author’s method for detecting enterotoxins was presented: immuno-LC-MS/MS in combination with PRM. Antitoxin monoclonal antibodies were covalently bound to magnetic elements after which, upon contact with isotope-labeled toxins, selective recognition and binding of the latter occurred. Thus, using the quadrupole–Orbitrap instrument, at least seven peptides were detected for each of the three toxins . The advantage of this method is its rapidity; in the experiment, which took 5 h, the limit of quantitation was reached at the level of 1 ng ml-1 or lower.The LC-SRM method is considered the most sensitive . Dupre eMass spectrometers are very sensitive quantitative instruments with an attomole detection limit; however, determining the threshold between signal and noise in MS signals is often challenging. Although mass spectrometry cannot provide the depth of coverage of high-throughput sequencing, this method is actively used to identify the proteomes of bacterial strains. Sequencing techniques are inferior to proteomics based on mass spectrometry since proteins can be altered post-translationally, and their structure and function will be altered accordingly. This information cannot be read from gene sequences or transcripts.The systemic analysis of the literature was performed using an automated text-mining tool and manual approaches. It revealed that proteomic methods have the potential to identify differentially regulated bacterial proteins in food samples or in response to drugs and disinfectants as well as to describe the mechanisms of biofilm formation and the host–parasite relationship. The current technologies offer two major scenarios of food production proteomic profiling. The first one involves the comprehensive, rapid, and robust analysis of key markers of food production status to detect bacterial strains and/or markers of their resistance . The secBased on the above, the proteomics approach serves as a complement to the genomic and transcriptomic approaches. Proteomics is effective in the study of complex mapping of bacterial proteomes, post-translational modifications of proteins, and pathogen–host interactions, as well as in antimicrobial resistance and the discovery of new protein biomarkers. A knowledge base is needed in which bacterial genes are annotated in the context of antibiotic resistance. Such an information resource will allow the creation of more sensitive methods for assessing the state of food production and considering the variety of bacteria and the resistance of specific strains to disinfectants. Proteomic bacterial resistance research is at its early stages but shows great perspectives. However, the most advantageous strategy is the use of a multi-omics approach. It provides cross-validation of the results and gives a complete understanding of the molecular processes characterizing the food production bacterial communities. The multi-omics approach can undercover the mechanisms of biofilm resistance, tracking the most dangerous combinations of bacterial strains and surfaces on which they are attached.The text-mining approach gives us an opportunity to process large amounts of papers and to extract the most valuable information about the proteomic basics of bacterial resistance. The semantic networks are useful instruments for scientific literature surfing.


Ultrasound-guided interfascial plane blocks performed on the anterior and lateral thoracic wall have become an important adjuvant method to general anesthesia and an independent method of local anesthesia and pain management. These procedures diminish the harmful effects of anesthesia on respiratory function and reduce the risk of phrenic nerve paralysis or iatrogenic pneumothorax. In postoperative pain management, interfascial plane blocks decrease the dosage of intravenous drugs, including opioids. They can also eliminate the complications associated with general anesthesia when used as the sole method of anesthesia for surgical procedures. The following procedures are classified as interfascial plane blocks of the anterior and lateral thoracic wall: pectoral nerve plane block (PECS), serratus anterior plane block (SAP), transversus thoracic muscle plane block (TTP), pectoral interfascial plane block (PIF), and intercostal nerve block (ICNB). These blocks are widely used in emergency medicine, oncologic surgery, general surgery, thoracic surgery, cardiac surgery, orthopedics, cardiology, nephrology, oncology, palliative medicine, and pain medicine. Regional blocks are effective for analgesic treatment, both as an anesthesia procedure for surgery on the anterior and lateral thoracic wall and as an analgesic therapy after trauma or other conditions that induce pain in this area. In the era of the COVID-19 pandemic, ultrasound-guided interfascial plane blocks are safe alternatives for anesthesia in patients with symptoms of respiratory distress related to SARS-CoV-2 and appear to reduce the risk of COVID-19 infection among medical personnel. With the development of interventional medicine and surgery, it is possible to carry out more complicated procedures in patients with a high burden of chronic diseases. Due to the growing group of patients taking medications influencing coagulation, including platelet aggregation, it is necessary to search for safe methods of anesthesia that have little effect on the circulatory or respiratory systems. In particular, in patients with cardiovascular disease and patients after COVID-19 infection, general anesthesia or central blockade may pose a risk of postoperative respiratory failure or may not be possible due to the use of anticoagulants. With the development of ultrasonography, it is possible to safely and fully control regional blockades, which can be an alternative to pain management in case of contraindications to taking nonsteroidal analgesics. The use of a regional blockade further reduces the risk of drug interactions.Pain Medicine have published a common statement in their recommendations regarding the possibility of regional blocks as a safe method of patient anesthesia [Ultrasonography procedures in anesthesiology and intensive care have allowed the popularization of regional anesthesia as an effective treatment for acute and chronic pain. Regional anesthesia performed by a fascial plane block has become an important adjuvant method to general anesthesia, and an independent method of local anesthesia and pain management. In 2019–2021, the high risk of exposure associated with airway instrumentation during SARS-CoV-2 infection led to increased focus on regional anesthesia as an alternative to intubation and general anesthesia. The European Society of Regional Anaesthesia (ESRA), the American Society of Regional Anesthesia (ASRA), and The choice of the regional anesthesia method should be guided by its negligible impact on respiratory function, reducing the risk of phrenic nerve palsy or iatrogenic pneumothorax. Furthermore, the doses administered to reduce the possibility of a toxic reaction after administering local anesthetics should minimize the risk of respiratory depression requiring oxygen therapy. As part of postoperative pain management, regional anesthesia also reduces the doses of intravenous analgesics used, particularly opioids.Ultrasound-guided interfascial blocks of the anterior and lateral thoracic wall are safe and relatively easy to perform. Therefore, they are widely used in emergency medicine, oncologic surgery, general surgery, thoracic surgery, cardiac surgery, orthopedics, cardiology, nephrology, oncology, palliative medicine, and pain medicine ,4.This paper presents a systematized review of the regional fascial blocks used for procedures performed within the anterior and lateral thoracic wall. The principles of their selection are presented according to their method, intended effect, and location of the surgery. The techniques for performing particular blocks and their typical clinical applications are described. Finally, the importance of fascial blocks in anesthesiology and analgesic treatment is discussed, along with the current principles of regional blocks during the COVID-19 pandemic.The regional blocks of the anterior and lateral thoracic wall include the pectoral nerve plane block (PECS), serratus anterior plane block (SAP), transversus thoracic muscle plane block (TTP), pectoral interfascial plane block (PIF), parasternal intercostal nerve block (PSI), and intercostal nerve block (ICNB) .The anterior and lateral thoracic wall is innervated by short branches of the brachial plexus, ventral branches of spinal nerves Th2–Th6 , and supraclavicular nerves (C3–C4), which are branches of the cervical plexus. The most important nerves in this group include the thoracic , thoracodorsal, subscapular (upper and lower), axillary, long thoracic, and cutaneous intercostal nerves . The neuroanatomy of the anterior and lateral thoracic wall is shown in Pectoral nerve block type I (PECS I) involves the medial and lateral thoracic nerves. This method was first described in 2011 by Blanco . The anePectoral nerve block type II (PECS II) is an improvement of the PECS I block, described by Blanco . In addiTechnique: The classic approach to performing PECS I and PECS II blocks is to localize the anatomic structures using a linear ultrasound transducer (with a standard frequency range of 5–12 MHz). The patient is supine, with their arms along the body and the head slightly rotated in the direction opposite to the blockade performed. The head is placed parallel to the clavicle and in the midclavicular line. After locating the vessels in the midclavicular line below the clavicle, the ultrasound transducer is inferiorly and laterally moved until the third rib is visualized. The sonoanatomical image identifies the pectoralis major, pectoralis minor, and serratus muscles, with the fascial spaces between them. The characteristic sonoanatomical landmark is the thoracic branch of the thoracoacromial artery running in the space between the pectoral minor and major muscles. The medial distribution of anesthetic for PECS I blocks allows for anesthesia of the anterior cutaneous branches of the intercostal nerves; in turn, lateral distribution may involve the lateral cutaneous branches of the intercostal nerves. In PECS II, the medial distribution increases the extent of the lateral thoracic wall block mainly supplied by the long thoracic nerve and dorsal thoracic nerve, involving the axillary fossa, subclavian region, and deltoid muscle ; mastectomy; minimally invasive aortic valve replacement; thoracoscopy; minithoracotomy; rib fractures; postmastectomy pain syndrome; neoplastic pain; and pacemaker/cardioverter implantation (mainly PECS II) [PECS II) ,8,9,10.Mini-review: In recent years, there has been a significant spread of PECS blockade use. Its ease and universality of use have contributed to the expansion of available applications in thoracic surgery, e.g., in analgesic treatment after cardiac surgery of mitral/tricuspid valve replacement [lacement . In addilacement . The saflacement . An incrlacement . The PEClacement  describelacement .The Serratus anterior plane block (SAP) was developed in 2013 by Blanco et al.  during tTechnique: The anatomical structures are localized using a linear ultrasound transducer (with a standard frequency range of 5–12 MHz). The patient is supine with an arm abducted at least 90° on the block side. After locating the vessels in the midclavicular line just below the clavicle, the ultrasound transducer is laterally moved and rotated by 90°, positioned along the vertical axis of the thorax to reach the lateral sectors of intercostal IV and V in the midaxillary line. When identifying the major and minor pectoralis muscles, ribs, with their neurovascular bundles, are moved over the latissimus dorsi and serratus anterior muscle. Directing the needle “on the rib” facilitates the correct deposition of local analgesics. Depending on the selected variant of the SAP anesthesia, the drug is administered above or below the serratus anterior muscle ; electrophysiological implantations, for example, subcutaneous implantable cardioverter-defibrillators (SICD); pain management after a rib injury; or implantation of tunneled permanent catheters [atheters ,21,22,23Mini-review: The SAP block is often used in combined anesthesia in thorax and cardiac surgery [ surgery ,25. In a surgery ,27. A no surgery ,29.The transversus thoracic muscle plane block (TTP) involves depositing an anesthetic in the space between the transversus thoracis muscle and intercostal muscles. The extent of anesthesia corresponds to the medial part of the sternum, depending on which side of the block is performed, along with the medial part of the thoracic wall. The blockade includes the anterior ends of the intercostal nerve branches. The method was described in 2005 as a parasternal block and is performed without ultrasound guidance. This technique is used to reduce the requirement for analgesics after sternotomy following cardiac surgery . In a TTTechnique: A linear ultrasound transducer (with a standard frequency range of 5–12 MHz) is placed parallel to the sternum in the parasternal line, sonoanatomically identifying the space between the second and fourth ribs. The needle is cranially directed, starting from the lower intercostal region. Due to the rich vascularization, injury to the venous perforators and intercostal veins, which run down the internal thoracic vein, should be avoided. The needle is successively passed through the pectoralis major and the external and internal intercostal muscles, reaching the surface of the transverse muscle, where the local anesthetic is deposited  block is performed in the parasternal space between the pectoralis major and the internal intercostal muscles. The technique is very similar to the TTP block. The anesthesia covers the anterior ends of the intercostal nerve branches, relieving pain in the parasternal region and the sternal area on the block side ,38.Technique: Analogous to the TTP block, the linear ultrasound transducer (with a standard frequency range of 5–12 MHz) is positioned parallel to the sternum in the parasternal line, exposing the space between the pectoralis major and the intercostal muscles; anesthetic should be deposited in the layer between these muscles  is most commonly performed as a pain management method and has little relevance in surgical procedures. This block involves targeted anesthetic delivery to the intercostal nerve region; the extent of anesthesia covers a specific intercostal space.Technique: A linear ultrasound transducer (with a standard frequency range of 5–12 MHz) is placed in the near sagittal axis , starting from the posterior axillary line ; electrophysiological procedures (subcutaneous implantation of cardioverter-defibrillators or pacemaker devices); and pleural puncture or thoracoscopy. Furthermore, new local anesthetics, such as the left-handed enantiomers of bupivacaine or ropivacaine, can reduce the probability of symptoms of local anesthetic systemic toxicity (LAST). This improves the safety of postoperative care in patients after thoracic trauma or rib fractures . The volOngoing studies of the anatomical structures of the chest wall are promising. A better understanding of these structures may help develop new regional anesthesia techniques, with the possibility of their application in minimally invasive surgeries, such as same-day surgery ,49.The COVID-19 pandemic affected the unfavorable perception of the use of general anesthesia concerning safety risks to operating room personnel. The use of general anesthesia in patients with respiratory infections due to SARS-CoV-2 significantly increases the risk of postoperative respiratory complications. The risk of respiratory depression in this group of patients is higher than in the general population. In the era of the COVID-19 pandemic, minimally invasive regional anesthesia techniques combined with an appropriate hygiene regimen appear to increase patient safety and reduce the risk of infection to operating room personnel ,51,52.Most of these techniques can serve as the only method of anesthesia and do not require additional sedation or general anesthesia. Techniques such as PECS, SAP, TTP, and PIF blocks can be used as the only method of anesthesia and postoperative pain management for selected procedures ,56,57,58The COVID-19 pandemic has also restricted access to surgical procedures for uninfected patients and delayed treatment for patients with active infection. Patients with SARS-CoV-2 infection represent a group at increased perioperative risk, which correlates with both the effects of active SARS-CoV2 infection and the increasingly well-known and population-relevant long-term effects of COVID-19—the so-called ‘post-COVID-19 syndrome’ or ‘long COVID-19’—primarily in the respiratory and central nervous systems .Analysis of the global COVID-19 statistics indicates no reasonable prognosis that the pandemic will end in the first half of 2022. Moreover, many European countries have a growing population of people vaccinated against COVID-19, mainly medical personnel, who must be prepared to provide services over the next few months to patients infected or recovering from COVID-19 ,61:Nonurgent procedures should be performed at a later date.Before regional anesthesia is administered, the extent and length of the procedure should be carefully considered.Any intraoperative conversions are highly undesirable; if the risk of conversion is high, it is better to perform general anesthesia from the beginning.Regional anesthesia, by definition, does not produce additional aerosol; however, if possible, it should be performed in an isolation room in COVID-19-positive patients; ultrasound-guided blocks should be performed.Regional anesthesia should be the method of choice in all cases without contraindications.The following are the key recommendations for COVID-19 issued by ESRA/ASRA, dated 31 March 2020 [Considering the enormous development of surgical medicine and the popularization of ultrasonography, using regional blocks both in anesthesiology and for analgesia brings enormous benefits. Owing to the use of ultrasound, the risk of complications is minimal and the drugs act locally. They are often the only alternative to general anesthesia in patients using drugs that affect coagulation. Furthermore, they are an alternative to oral or intravenous analgesics in patients hospitalized in intensive care units. A reduced need for nonsteroidal anti-inflammatory drugs or opioids can be obtained owing to regional blockages.Regional blocks are an effective method of analgesic treatment, both for anesthesia in surgical procedures on the anterior and lateral thoracic wall and for analgesic therapy after trauma or conditions inducing pain in this area. Ultrasound-guided techniques and modern, minimally toxic local anesthetics significantly increase patient safety and comfort. In the era of the COVID-19 pandemic, fascial block techniques provide a safe alternative to anesthesia for patients with symptoms of respiratory distress related to SARS-CoV-2. Moreover, these approaches appear to reduce the risk of infection of medical personnel.