This work aims to investigate the development and management of cosmetics webcast marketing platforms, offering novel approaches for building and sustaining commercial brands. Firstly, an analysis of the current utilization of cosmetics webcast marketing platforms is conducted, identifying operational challenges associated with these platforms. Secondly, optimization strategies are proposed to address the identified issues by leveraging advancements in 6th Generation (6G) communication technology. Subsequently, a conceptual framework is established, employing big data interaction to examine the influence of webcast marketing platform experiences on brand fit. Multiple hypotheses are formulated to explore the relationship between platform experiences and brand fit. Finally, empirical analysis is performed within the context of the 5th Generation (5G) Mobile Communication Technology and extended to incorporate the 6G Mobile Communication Technology landscape. The results of the validation indicate the following: (1) the content generated by the webcast marketing platform has a positive impact on brand fit ; (2) in the 6G network environment, a webcast marketing platform with high traffic transmission rates may enhance brand fit ; (3) the content generated by the webcast marketing platform exhibits significant positive regulatory effects on information-based and co-generated content . The findings of this work offer valuable insights for other scholars and researchers seeking to optimize webcast marketing platforms. In the digital era, the field of marketing is undergoing an unprecedented transformation. With the continuous advancement of technology and the rapid development of the Internet, webcast marketing has emerged as a crucial tool for brand promotion and consumer interaction , 2. HoweIn today’s fiercely competitive market environment, the efficacy and innovation of brand communication are integral determinants of business success . WebcastThis work aims to comprehensively analyze the favorable outcomes of optimizing webcast marketing platforms through 6G technology advancement, particularly in relation to brand content creation. This investigation takes into account various dimensions encompassing technical performance, user experience, and the effectiveness of brand communication. By delving into the innovative applications of live streaming platforms within the purview of 6G technology, our intention is to furnish tailored strategies for businesses and marketers, thereby facilitating the attainment of their brand communication and marketing objectives more effectively. In essence, this work seeks to contribute valuable research insights and pragmatic implications to both academic and practical domains. By exploring the optimization of webcast marketing platforms within the framework of 6G technology and its consequential impact on brand content creation, our endeavor aspires to provide a significant resource for the progress of webcast marketing in the context of emerging technologies.In recent years, the rise of the online webcast economy has introduced a new marketing model into people’s lives, with companies recognizing online webcast platforms as valuable frontiers for marketing activities. Within the field of webcast marketing, extensive research has been conducted. Zhao et al. (2022) emphasized the growing significance of hosts in webcast marketing models compared to traditional marketing approaches, highlighting them as a research focus. Their study investigated the effects of different product types and host styles on consumer psychology and behavior. The findings revealed that (1) for functional products, the entertainment host style significantly increased consumers’ emotional identification but reduced their perception of authority and knowledge, and (2) for functional products, the knowledge anchor style heightened consumers’ perception of authority and knowledge while diminishing emotional identification . Liao anIn conclusion, notable progress has been achieved in webcast marketing research; however, several limitations persist. The following key issues within the field of webcast marketing research have been identified:Incomplete theoretical framework: The existing theoretical research on webcast marketing is relatively limited, and the available frameworks lack comprehensiveness. There is a dearth of in-depth exploration regarding the characteristics, influencing factors, and effectiveness evaluation of webcast marketing, resulting in a relatively weak theoretical foundation in this domain.Insufficient methodology: The research methods utilized in webcast marketing are still relatively constrained. Many studies heavily rely on questionnaire surveys and case analyses, which lack more systematic and comprehensive research methods and robust data analysis techniques. Conducting additional empirical research and employing quantitative analysis are necessary to enhance the reliability and practicality of future investigations.Inadequate user behavior research: The success of webcast marketing hinges on audience behavior; however, the research on audience behavior remains insufficient. Further inquiry is necessary to understand the motives behind audience participation, their decision-making processes, purchasing intentions, and other relevant aspects. Such insights are critical for optimizing marketing strategies and enhancing the overall user experience.This work on corporate brand image has its roots in marketing and brand management since the 1960s. During this period, companies began recognizing the significance of brand image in consumer purchase decisions and market competition. With the expansion of the global market and intensifying competition, the focus shifted to establishing and managing strong brand images. Over the past few decades, research on corporate brand image has gained prominence as an important academic field. Scholars have explored consumer perceptions and attitudes toward brand image, as well as how companies convey their core values and personality through branding. They have examined the impact of brand identity, brand storytelling, brand experience, and brand communication on brand image. However, certain limitations exist in their research, which can be summarized as follows:Subjectivity and lack of objectivity: Research on corporate brand image often relies on qualitative and quantitative research methods. Qualitative research primarily involves subjective evaluations and opinions of respondents, while quantitative research collects data through methods such as questionnaire surveys. These approaches are susceptible to individual subjectivity, limitations of research samples, and subjective interpretations by researchers, potentially leading to subjective and less objective research findings.Lack of long-term perspective: Research on corporate brand image tends to focus on the current perception and influence of brand image while neglecting long-term development trends. Brand image is a dynamic concept that is continuously influenced by factors such as the market environment, consumer behavior, and competitors. Therefore, research on corporate brand image should incorporate observations and analysis of the evolution and changing trends of brand image. This approach can support companies in formulating long-term brand strategies and plans.Neglect of non-traditional channels and new media: The rise of the Internet and social media has significantly changed brand communication methods and channels. However, some research on corporate brand image still predominantly concentrates on traditional media and channels, overlooking the impact of new media and non-traditional channels on brand image. Therefore, it is crucial to recognize and emphasize the role of emerging media and non-traditional channels in brand image research. This comprehensive understanding enables companies to shape their brand image effectively.Lack of consideration for cultural and regional differences: A company’s brand image may vary across different cultures and regions. However, some research on corporate brand image neglects cultural and regional differences when designing research methods and analyzing results. This oversight may limit the applicability of research findings in diverse cultural and regional contexts. It is essential to consider cultural and regional nuances to ensure the broader relevance of research findings.Future research on corporate brand image can enhance its validity, objectivity, and relevance by addressing these limitations.Webcast marketing has emerged as a new avenue for businesses to engage in marketing and promote their brands, capitalizing on the rapid growth of the live broadcast economy , 11. DurCompanies can effectively meet customer needs by understanding their perceptions, and researcher Alexander Zauner has summarized customer perceived value into three stages in an exploratory study. The first stage involves customers evaluating the quality-price relationship to make overall assessments after considering the costs and benefits of practical products. The second stage introduces the theory of “value” in consumer behavior and defines five dimensions of customer perceived value. These dimensions are conceptually independent, meaning that any of these values can influence customers’ decisions depending on different conditions and the specific product or service under consideration. This definition provides clarity to the configuration of customer-perceived value, enhancing its practicality and scientific basis.In the third stage, customer perceived value is analyzed from dimensions, abstract levels, and model classifications, explaining the applicability of high-level conceptualized customer perceived value to multidimensional conceptualized marketing objectives. From a causal relationship perspective, the different dimensions of customer perceived value are interconnected and can be manifested through certain goods and services. Essentially, they are interchangeable. Considering only the aspect of benefits, customers’ perceived value of a product primarily lies in the ‘trade-off’ between the net benefits gained and the cost differentials incurred.Customer perceived value is primarily measured through three aspects: functional value, emotional value, and social value, all of which can be effectively demonstrated in webcast marketing. Functional value is observed in how a product’s basic attributes or functions can meet customers’ practical needs in specific areas such as communication and home appliances. In the ‘brand + product launch + webcast’ model of webcast marketing, the webcast content focuses on introducing new products and demonstrating their functionality. Through the webcast, consumers can intuitively observe and learn about the specific features and usage of the products, comprehensively reflecting the functional value in customer perceived value within this model.Emotional value is mainly derived from how a brand or product meets customers’ emotional needs. Customers are attracted to consumption based on themes, atmospheres, moods, and more. In the ‘brand + influencer + webcast’ model of webcast marketing, everyday people are chosen as live streamers to create a sense of empathy. Consumers easily resonate with the experiences and emotions associated with certain brands and products during the webcast process, satisfying their emotional needs and establishing emotional value towards the brand and products.Social value is evident when a product represents a customer’s social status, economic strength, and self-realization value, such as high-end watches, luxury handbags, and other luxury goods. In the ‘brand + celebrity + webcast’ model, companies select celebrities that align with the brand’s identity and product positioning as live streamers. Typically, celebrities with higher popularity and social influence are chosen. Consumers watching the live stream are inclined to choose brands and products that match their personal identity and status, driven by their self-value needs and the celebrity effect. The subsequent use of the products allows consumers to display their identity and status, providing additional social recognition and thereby achieving social value.Most customers choose brands and purchase products and services primarily to satisfy one or several of these values. Therefore, in the webcast marketing model, if a company’s brand and products can meet customers’ preferences or needs, customer-perceived value naturally increases, and establishing customer trust in brand perception becomes relatively easy.In conclusion, with the emergence of social media marketing, customers have diversified channels to perceive value. By utilizing these social media marketing tools based on customer-perceived value, companies can significantly enhance the possibilities of brand marketing. Furthermore, with the continuous development of the Internet economy, social marketing models are constantly evolving and improving. The emergence of online webcast platforms has introduced a novel approach to social media marketing, making webcast marketing a distinct and innovative subdivision.This work aims to address the intricate and uncontrollable factors that impact the sales volume of live-streaming e-commerce. To achieve this objective, it introduces artificial neural networks into sales forecasting for online webcasts. Specifically, this work conducts an empirical investigation using cosmetics as a case study. The neural network architecture is designed to encompass the input layer, output layer, and hidden layer neurons. A Back Propagation (BP) neural network model is constructed to forecast sales in online webcasts. Training and optimization tests are carried out with varying numbers of hidden layer neurons. In this empirical study, diverse data related to influencing factors are collected from live-streaming cosmetics and used as input data, while the number of payment orders represents the output data. A BP neural network model is established, and a set of samples is chosen as validation data to empirically evaluate the effectiveness of sales volume forecasting for live-streaming cosmetics.Cosmetics webcasts, which combine ‘live broadcast + cosmetics,’ have demonstrated the ability to enhance brand awareness and generate substantial revenue. Consequently, numerous cosmetics companies have leveraged the growing trend of webcast marketing by collaborating with Internet celebrities or popular personalities to promote their brands and sell their products during live webcasts. While webcast marketing has the potential to generate significant revenue, it also presents several limitations that can be categorized into three main areas.Immature economic form: Despite facilitating significant economic benefits and contributing to the continuous growth of e-commerce, webcast marketing remains an evolving and developing economic structure , 18. CurVisual appeal-focused marketing model: The marketing approach in webcast marketing predominantly relies on visual appeal. Utilizing celebrities and endorsed brands to promote the effectiveness of cosmetic products aims to captivate the modern mindset of young consumers, who are often influenced by attractive individuals or follow their idols to fulfill their consumption needs, thereby driving high sales.Lack of depth and brand concept: In pursuit of profit, many cosmetics brands neglect the importance of establishing meaningful connections with their audience and assisting them in finding the products that suit their needs. Consequently, these brands often fail to sustain the initial sales enthusiasm following a period of immense success, resulting in the brand losing its relevance and struggling to retain customers.By addressing these limitations and embracing a more comprehensive approach to webcast marketing, cosmetics brands can establish a stronger foundation for long-term success and customer loyalty.Drawing on cognitive psychology and information processing theory, Vessey 1991) proposed the cognitive matching theory as a research paradigm to investigate individual decision-making processes 91 propos. The cogThis work examines customer perceptions of psychological distance as a response to emotional states and brand fit behavior as a response to behavioral states. The external environmental stimuli considered in this research comprise seller-generated content characterized by different information features and social media influencer-generated content characterized by different tones –23. Fig The concept of big data originated from a collaborative effort among several Internet companies in the United States. In contrast to traditional data, big data stands out due to its large volume, variety, rapid input and processing speed, and low data value density. To some extent, webcast marketing strategies can address the limitations of traditional marketing approaches, such as inadequate communication and low engagement. By leveraging webcast marketing, customers’ familiarity and satisfaction with promoted products can be enhanced, reducing the psychological distance between customers and the brand. Moreover, interactive content delivered by brand sellers has the potential to strengthen customers’ positive associations with the brand, consequently narrowing the psychological gap between the brand and its products. For example, brand sellers can actively respond to consumer inquiries and provide additional information through online interactions . TherefoH1a: The interactive content generated by the seller has a positive impact on perceived psychological distance.H1b: The interactive content generated by social media influencers has a positive impact on perceived psychological distance.The impersonal nature of online purchasing can create a psychological distance between customers and the brands they purchase, which in turn may impede customer adaptation behavior towards a brand. To address this issue, marketing initiatives that focus on reducing psychological barriers between the brand and the target audience can positively impact customer brand loyalty, repeat purchases, and brand advocacy. Brands hold significant importance for customers, and facilitating brand adaptation can encourage more frequent consumption, ultimately enhancing the brand’s credibility . TherefoH2a: Perceived psychological distance positively impacts brand fit transactional behavior.H2b: Perceived psychological distance has a positive impact on brand fit non-transactional behavior.Customers’ perception of the psychological distance between themselves and a brand influences their evaluations and responses toward the brand. This phenomenon, in turn, aids businesses in enhancing product awareness and strengthening customer relationships through social networks , therebyH3a: Content generated by social media influencers with a positive tone has a positive impact on perceived psychological distance.H3b: Content generated by social media influencers with a negative tone has a negative impact on perceived psychological distance.Customers’ growing skepticism towards webcasts has resulted in increased obstacles in online shopping and posed challenges for brands in building connections with them. Social media influencers play a crucial role in effectively promoting brand products to customers to tackle this problem. Influencers can divert customers’ attention toward the promotional content itself, thereby mitigating the impact of their personal characteristics by employing storytelling techniques and adopting unique tones .Therefore, this work proposes the following hypotheses:H4a: Positive-toned social media influencer-generated content enhances the relationship between seller-informatively-generated content and perceived psychological distance.H4b: Social media influencer-generated content with a positive tone strengthens the relationship between seller-generated interactive content and perceived psychological distance.H4c: Social media influencer-generated content with a negative tone weakens the relationship between seller-generated informative content and perceived psychological distance.This work examines the influence of content marketing on brand fit behavior in the context of webcasting by utilizing cosmetics sold on the Kuaishou live stream e-commerce platform as a case study. Secondly, the cosmetics market represents a vast and competitive industry with continually growing consumer demand. The Kuaishou e-commerce webcast platform provides a direct channel for cosmetics brands and sellers to engage with consumers and promote their products. Investigating cosmetics sales on this platform can provide deeper insights into consumer demand, purchasing behavior, and brand loyalty within the cosmetics industry.Thirdly, the webcast format offers distinct advantages for e-commerce, delivering a more immersive and engaging shopping experience through real-time video demonstrations and interactive communication. Particularly for cosmetics, a webcast allows for the effective showcasing of product usage, the demonstration of effects, and the provision of makeup techniques, thereby capturing consumer interest and influencing purchase intent. Consequently, examining cosmetics sales on the Kuaishou e-commerce webcast platform facilitates an exploration of the role and influencing factors of the webcast format in shaping consumer purchasing decisions.Lastly, the Kuaishou e-commerce webcast platform places significant emphasis on social interaction, enabling consumers to actively engage with hosts and other viewers through bullet comments, comments, and interactive features . This soIn conclusion, selecting cosmetics sold on the Kuaishou e-commerce webcast platform as a research case provides valuable insights into e-commerce webcast trends, consumer purchasing behavior, and brand influence within the cosmetics market.This work opts for the Kuaishou live e-commerce platform as the research backdrop and beauty products as the focal subject of analysis to examine the influence of content marketing on brand congruence behavior within the realm of online live streaming. The dataset encompasses the subsequent primary constituents: Live streaming platform data encapsulates parameters pertinent to live streaming technology, network performance data within the 6G environment, and the temporal extent of live streaming sessions. User interaction data comprises metrics such as user viewing duration, likes, comments, and sharing activities . Brand cThis work investigates the impact of content marketing on brand fit behavior in the context of webcasts, focusing on the raw material of live clips from the Racer live e-commerce platform. A structural equation model is employed to examine the relationships among various factors and their impacts on each other. This work specifically investigates the relationships between user-generated content and psychological distance, user-generated content and brand fit behavior, and media-generated content and psychological distance. This work examines the differential impact of information-based sellers’ and interactive sellers’ content during live broadcasts, aiming to explore the moderating role of customers’ perceived psychological distance from businesses. The proposed optimized webcast marketing plan is incorporated as an input variable in a conventional forecasting model to predict the sales of three upcoming live broadcasts on the platform. This work gathers data from the Shenzhen Guotaian database and the Juchao Information Website to survey a total of one hundred organizations intending to adopt webcast marketing by 2022. As a control group, one hundred businesses that have not yet employed live marketing were selected, with this work and comparison samples divided into Groups A and B, respectively. The analysis focuses on optimizing the webcast platform, anchor performance, and creating brand content. The Levene test was conducted to examine the variance equation, revealing an F-value of 0.431 and a Sig. value of 0.513 for ROE, as well as an F-value of 1.949 and a Sig. value of 0.165 for EPS. In both cases, the variables showed significance levels greater than 0.05. Consequently, there were no significant differences observed between the study samples in Group A and Group B. Moreover, the Sig. values for both ROE and EPS were 0.162 and 0.602, respectively, indicating that the variance was equal between the two groups. Both significance levels were greater than 0.05, further supporting the lack of difference between Group A and Group B in terms of their mean values for ROE and EPS.The experimental findings indicate that the network webcast marketing platform, leveraging 6G development, significantly influences the optimization of brand content creation and marketing strategies. Firstly, the adoption of high-speed and low-latency communication technology ensures smoother and real-time webcasts, enabling the audience to enjoy higher-quality video content. This enhanced streaming capability empowers brands to effectively showcase their products and services, providing a more immersive and captivating brand experience, thus fostering increased audience engagement and interest. Secondly, the ability for cross-device and cross-platform interaction introduces new possibilities for brand content creation. The audience can interact with brands through various devices and platforms, such as real-time comments, likes, and shares. Brands can promptly respond to audience feedback and demands, making real-time adjustments and personalized content creations that align with audience preferences. This dynamic approach enhances audience engagement and strengthens brand identification. Furthermore, the webcast platform based on 6G technology offers brands diversified communication channels, including augmented reality and virtual reality technologies. By leveraging these innovative communication methods, brands can create more immersive and enriched brand experiences for the audience. Interacting with the virtual world allows the audience to better understand product features, experience services, and establish a closer relationship with the brand. Additionally, data-driven marketing strategies become more effective on the 6G webcast platform. The platform collects abundant real-time data, providing brands with in-depth insights into audience behavior patterns, preferences, and demands. This enables more precise targeting and personalized content creation. By analyzing the data, brands can better anticipate market trends, formulate targeted marketing strategies, and enhance brand awareness and loyalty among the audience. In conclusion, the experimental results of the network webcast marketing platform based on 6G development demonstrate its positive impact on optimizing brand content creation and marketing strategies. This advancement offers brands innovative, interactive, and personalized opportunities, fostering interaction and engagement between brands and the audience. Consequently, it enhances brand influence, recognition, and market competitiveness.Theoretically, this work delves into the potential of optimizing webcast marketing platforms through 6G development and examines the impact of such optimization on-brand content creation. It presents a novel perspective for comprehending and leveraging the future possibilities of 6G technology in the marketing domain. By investigating the application of 6G in webcast marketing, a deeper understanding of the influence of 6G technology on brand marketing strategies and user experiences can be attained, providing a solid theoretical foundation for future research and practical implementation. Practically, this work offers valuable insights for businesses and marketing practitioners. Firstly, businesses can enhance the effectiveness and appeal of brand content creation by optimizing webcast marketing platforms and integrating innovative 6G technology applications. This improvement enables businesses to differentiate themselves in a competitive market, attract a larger target audience, and augment brand visibility and reputation. Secondly, this work underscores the pivotal role of brand content creation in webcast marketing. By comprehending the impact of 6G technology on content creation, businesses can leverage innovative technological means and strategies to design and disseminate brand content, thereby achieving higher levels of brand attention and user engagement. Additionally, this work emphasizes the significance of businesses staying abreast of future development trends and application prospects of 6G technology. With the continuous advancement of 6G technology, webcast marketing will witness further innovation and transformation, necessitating businesses to proactively monitor and adapt to these changes to maintain a competitive edge. In summary, this work contributes to the understanding and utilization of 6G technology in optimizing webcast marketing platforms. It sheds light on the impact of 6G on-brand content creation, offering valuable insights for businesses and marketing practitioners. Furthermore, it underscores the importance of keeping abreast of future developments in 6G technology to remain competitive in the dynamic landscape of webcast marketing.When comparing the findings of this work with the research conducted by Rakshit et al. (2022) , it is eAccording to the findings presented in Webcast marketing has emerged as a prominent advertising method, gaining popularity among businesses due to its accessibility, cost-effectiveness, quick results, and precise targeting capabilities. It represents a new marketing tool that has evolved alongside technological advancements in the modern era. Webcast marketing enables brands to achieve high-efficiency results at a low cost by leveraging pinpoint marketing, big data technologies, interactivity, and measurable performance. The growth of webcasting technology has led to the proliferation of live stream services, prompting the need to analyze and research the best webcast marketing practices to attain desired communication outcomes. This work examines the current landscape of cosmetic webcast marketing platforms and develops a theoretical framework to evaluate the impact of the webcast marketing platform experience on brand fit. Additionally, several hypotheses are proposed to explore the relationship between participation in a live marketing platform and business success. The empirical analysis is conducted in the context of 5G to test these hypotheses. The findings of this work demonstrate the following key results: Firstly, the active content generated through the webcast marketing platform positively influences brand fit . Secondly, in a 6G network environment, there is a significant positive correlation between the transmission rate of the webcast marketing platform and brand fit . Lastly, the content generated by the webcast marketing platform exerts a significant positive regulatory effect on information-based and interactive generated content . In conclusion, webcast marketing presents a promising avenue for businesses to achieve their marketing objectives. This work’s findings highlight the positive impact of active content and transmission rate on brand fit, underscoring the importance of utilizing webcast marketing platforms effectively. By generating engaging and interactive content, businesses can enhance their brand fit and capitalize on the advantages offered by webcast marketing. These insights contribute to the understanding of the role of webcast marketing in driving brand success, particularly in the context of 6G networks.The work presents several limitations that should be acknowledged. Firstly, while the current status and issues of the webcast marketing platform are analyzed, there is a lack of in-depth exploration regarding specific methods and implementation strategies to address these problems. The optimization solutions provided lack detailed explanations on how to apply sixth-generation communication technology to improve the platform’s operations and functionalities. Secondly, although a conceptual framework is constructed for the relationship between the webcast marketing platform experience and brand fit, along with the proposal of relevant hypotheses, there is no clear indication of the specific methods and indicators for measuring and evaluating these concepts and relationships. Furthermore, only empirical analysis in the context of 5G is considered when validating the hypotheses, lacking actual verification in a 6G environment.Future studies should consider the following aspects:Elaborate on the optimization solutions by providing more specific methods and implementation strategies to address the current issues of the webcast marketing platform. Explore how advanced communication technologies can be leveraged to improve platform performance and functionality in conjunction with the development status of sixth-generation communication technology.Develop measurement and evaluation methods to establish reliable metrics and evaluation criteria for the relationship between the webcast marketing platform experience and brand fit. Quantify and validate the correlation between these concepts through accurate indicators and robust data collection methods, thereby enhancing the credibility and practicality of the research.Consider verification in a 6G environment by extending the validation results from the context of 5G to a 6G background, comprehensively evaluating the performance and impact of the webcast marketing platform under different communication environments. Take into account the characteristics and technologies of 6G to further explore the relationship between the webcast marketing platform and brand fit.Through in-depth research in these areas, a better understanding of the success factors of the webcast marketing platform can be achieved, leading to more specific and feasible solutions to improve platform performance and generate new brand content.S1 Data(ZIP)Click here for additional data file.


Giant inclusions and Auer bodies in promyeloblasts were investigated in a study which included transmission electron microscopy (TEM) for morphology and ultrastructural cytochemistry for myeloperoxidase in 10 patients with acute promyelocytic leukemia (APL). Ultrastructural cytochemistry demonstrated positive myeloperoxidase reactivity in giant inclusions, expanded rER cisternae, Auer bodies and primary granules. TEM revealed that giant inclusions were adorned by degenerated rER membrane, some of them sharing features with Auer bodies. We hypothesize a novel origin for Auer body development in promyeloblasts of APL, namely that they originate from peroxidase-positive and expanded rER cisternae, and that primary granules were directly released from these expanded rER elements, bypassing the Golgi apparatus. They are negative for lipase, glycogen and deoxyribonucleic acid.giant inclusions, and which coexist with typical Auer bodies in the leukemic blasts in APL. The morphologic characteristics and distinctive substructure of these giant inclusions suggest an alternative origin for Auer bodies in the cells of APL.Here, we demonstrate the presence of large cytoplasmic bodies, which we refer to as 11 For comparison, mononuclear cells from bone-marrow aspirates of anemic patients were observed as control cells for the leukemic cells of APL.Ten previously untreated APL patients were referred to the Blood Diseases Hospital, Tianjin, between 2012 and 2022. They included 8 males and 2 females, aged between 10 and 50 years old. All patients were subjected to light microscope morphology, flow cytometry, cytogenetic analysis and molecular biological characterization, as well as TEM and ultrastructural cytochemistry. All patients were characterized by hypercellularity of myeloid blasts, the cytogenetic abnormality t   and positivity of PML/RAR. Diagnoses were made on the basis of the World Health Organization classification of myeloid neoplasms and acute leukemia.Bone-marrow aspirate smears were stained with Wright-Giemsa and cytochemical stains, which included Sudan black, myeloperoxidase, PAS staining, alpha-naphthyl butyrate esterase (α-NBE), and naphthol AS-D acetate esterase (AS-D NAE).13A portion of the mononuclear cells from the bone-marrow aspirates was conventionally fixed and embedded in resin. Briefly, the samples were fixed in 2.5% glutaraldehyde, postfixed in 1% osmium tetroxide, washed in phosphate-buffered saline, dehydrated in graded alcohols and embedded in Epon 812. Ultrathin sections at 60 nm were cut and stained with uranyl acetate and lead citrate. For detection of myeloperoxidase activity, mononuclear cells were incubated for 1 hour in Graham and Karnovsky medium, and then processed for electron microscopy as described above, and unstained sections observed by TEM.The Wright-Giemsa stain exhibited hyper-proliferation of promyelocytes in bone-marrow smears in all cases. All promyelocytes contained numerous round azurophilic granules, but a small proportion of cells included rod-like Auer bodies and irregularly shaped inclusions Fig. A and B. Normally, neutrophils included slender profiles of rough endoplasmic reticulum (rER), primary granules in promyelocytes, and specific granules in myelocytes to segmented granulocytes; few of the above organelles are found in myeloblasts. There were no Auer bodies, irregularly shaped inclusions or expanded rER cisternae by morphological TEM or ultrastructural myeloperoxidase staining Fig. .In contrast, in most of the promyeloblasts in APL, rER cisternae were noticeably expanded and filled with a homogeneous matrix, so that some of them looked like irregular lakes in the cytoplasm. Primary granules varied in size and electron density, whereas specific granules were seldom found in promyeloblasts. Sometimes, structures resembling a simple vesicle, with a clear unstructured content, were observed and it was difficult to know whether these structures were elements of rER or a variant of primary granules Fig. A–D.The ultrastructural myeloperoxidase stain exhibited distinct reactivity of the amorphous matrix within expanded rER cisternae, the numerous primary granules, as well as lake-like rER elements and giant inclusions in APL promyeloblasts Fig. E–H.In the promyeloblasts of APL on TEM Fig. A and B, Some giant inclusions had features in common with Auer bodies in having a rod-like main body like Auer bodies, but retaining the lace-like dense membrane profiles like those around the dense giant inclusions Fig. A–D. We rThere were prominent primary granules with myeloperoxidase reactivity in the cytoplasm of promyeloblasts; some of them were budding out from pro-Auer bodies and giant inclusions Fig. D, and soAuer bodies were often needle or rod-shaped, and had a smooth surface. Some of them contained homogeneous content, while others showed a fine lamellar or crystal-like inclusion Fig. B–D. Crys1 of the bodies named after him as Auer bodies or Auer rods, having a splinter-like appearance and tubular substructure on Wright’s stain by light microscopy, various pink-staining inclusions and granules occurring in leukemic blasts and nonleukemic cells have been reported.14 Some inclusions had a tubular substructure similar to Auer rods,15 but some inclusions were more voluminous and irregularly shaped, and were called “giant inclusions” or “megagranules.”16Following the description in acute leukemia by Auer17 Ultrastructural investigation demonstrated that Auer bodies were large membrane-bound organelles with a crystalline core, although some of them exhibited a more lamellar texture.18 The above descriptions of Auer bodies were consistent with findings in the present study based on cytochemistry and ultrastructure.Auer bodies were predominantly found in APL and were characterized by activity for Sudan black B and the PAS reaction cytochemically. It was thought that Auer bodies resulted from the fusion of primary granules in promyeloblasts based on their shared cytochemical reactions.20Giant inclusions were often demonstrated in neutrophils from patients with the Chediak-Higashi syndrome (CHS), occasionally found in acute myelomonocytic leukemia. These giant granules contained heterogeneous deposits and filamentous materials, and were thought to result from the fusion of primary and secondary granules based on their activity of myeloperoxidase under pathologic conditions.21In this study, the homogeneous dense matrix, the positivity for myeloperoxidase, and the surrounding lace-like dense membrane mark them as different from the giant granules in CHS. The dense lace-like membrane associated with giant inclusions in our study was continuous with rER profiles nearby, some of which looked like the double-membrane-limited lysosomes found in CHS monocytes by combined electron microscopy and ultrastructural cytochemistry.22 In this study, all the giant inclusions, Auer bodies, rER, and primary granule were characterized by high electron density and activity of myeloperoxidase of APL. This suggested that the giant inclusions might originate from expanded rER cisternae with abundant synthesized matrix within the cisternae. The presumption was substantiated by common myeloperoxidase activity of the giant inclusions and rER in promyeloblasts.23An ultrastructural study demonstrated that prominent dilated rER, multi-laminar rER and complex stellate arrangements of rER appeared to be morpho-genetically related in APL.10 and the novel hypothesis requires further identified using advanced devices.Additionally, some giant inclusions showed an intermediate state between giant inclusions and Auer bodies, including a rod-like main body, furcate terminals and fewer, small membrane loops. We interpret the membrane loops as membrane being removed as the content of the body condenses and the body, as a whole, evolves from a more rounded or oval giant inclusion (asterisked in Fig. 24 Performing above diverse functions requires such distinct domains of ER with different architectures as tubules, sheets, and nuclear envelope.26 These structures are consisted with variant morphologies of Auer bodies and giant inclusions in this study, although transformation processes of giant inclusions associated with ER and rER to Auer bodies need to be demonstrated by dynamic techniques such as super-resolution microscopy and 3D correlative fluorescence and electron microscopy that developed in recent years.27ER is a dynamic membrane and serves many roles, including calcium storage, protein synthesis, transport and folding, lipid and steroid synthesis, and carbohydrate metabolism.It is also possible that there is a morphological heterogeneity to Auer bodies, reflecting abnormalities that are almost a hallmark of the neoplastic process. One aspect of their development relates to how the crystalline component arises. This remains to be addressed in future work, although our preliminary findings include crystalline inclusions found within some rER cisternae; in a process as not yet defined, these rER cisternae may enter into the developmental process of Auer rod formation as illustrated in our Figure This study suggests the novel idea that expanded rER cisternae transform into giant inclusions and then Auer bodies partly as a result of the intracisternal accumulation of compounds rich in peroxides, and the progressive condensation of internal material by the release of loop-like membranous elements; further, that primary granules were directly released from pro-Auer bodies in a process which bypasses the Golgi apparatus in promyeloblasts of APL.


Immune checkpoint inhibitors (ICIs) have rejuvenated therapeutic approaches in oncology. Although responses tend to be durable, response rates vary in many cancer types. Thus, the identification and validation of predictive biomarkers is a key clinical priority, the answer to which is likely to lie in the tumour microenvironment (TME). A wealth of data demonstrates the huge impact of the TME on ICI response and resistance. However, these data also reveal the complexity of the TME composition including the spatiotemporal interactions between different cell types and their dynamic changes in response to ICIs. Here, we briefly review some of the modalities that sculpt the TME, in particular the metabolic milieu, hypoxia and the role of cancer-associated fibroblasts. We then discuss recent approaches to dissect the TME with a focus on single-cell RNA sequencing, spatial transcriptomics and spatial proteomics. We also discuss some of the clinically relevant findings these multi-modal analyses have yielded. •The TME shapes responses to ICIs.•We discuss how metabolites, hypoxia and cancer-associated fibroblasts sculpt the TME.•We discuss single-cell omics technologies to analyse and quantify the TME.•We survey spatial transcriptomics and proteomics technologies for analysing the TME.•We discuss the clinical impact of TME spatial and single-cell analysis. Apart from the cancer cells, the TME comprises different cellular components including stromal cells, endothelial cells and immune cells, as well as non-cellular components such as growth factors, cytokines and metabolites, which collectively can either promote or suppress tumour growth.In recent years, the TME has become a major therapeutic target as a result of the successful development and approval of immune checkpoint inhibitors (ICIs).This review focuses on approaches for understanding the interface where tumour and immune cells directly interact, i.e. the TME, which is critical for understanding the variability in ICI response rates not only between different types of cancer but also between individual patients.,,,T cells are an important component of the TME. Cytotoxic CD8+ T cells and CD4+ T helper cells are involved in anti-tumourigenic functions, while regulatory T cells (Tregs) contribute to pro-tumourigenic functions.,,The presence of CD8 and CD4 T cells, B cells and NK cells in the TME generally correlates with favourable prognosis and may help predict responses to ICIs.These findings were extended by numerous subsequent surveys of different cancer types. For instance, the analysis of a TCGA dataset comprising >10 000 patients representing 33 different cancer types revealed six immune subtypes showing differences in lymphocyte and macrophage signatures, Th1 : Th2 cell ratios, tumoural heterogeneity, mutational tumour burden and prognosis.The different cell types present in the TME form an intricate network of interactions that involve direct physical interactions and indirect communications via cytokines and metabolites . Below w32Malignant cells are highly metabolically active and rely on metabolic pathways similar to activated immune cells in order to support their metabolic demands. This creates metabolic competition in the TME, which challenges immune cells to operate in an environment where key nutrients required for their optimal function, such as glucose, glutamine, methionine, tryptophan and arginine, are scarce. Immune cell activation is accompanied by a metabolic switch from oxidative phosphorylation to aerobic glycolysis and biosynthetic pathways that provide the building blocks which support rapid cell proliferation.,The resulting nutrient competition between cancer and immune cells in the TME compromises immune cell effector functions and impedes an efficient antitumour immune response. One example of this phenomenon is the competition for glucose in the TME, which is a major energy source for both cancer cells and proliferating T cells. Tumour cells consume more glucose than normal cells to satisfy their increased demand for molecular building blocks that enable unrestricted cell division.,,high TAMs, while promoting arginine metabolism and the immunosuppressive functions of MHC-IIlow TAMs.in vivo.,In addition to restricting the availability of key nutrients such as glucose, tumours can also actively produce metabolic byproducts with immunosuppressive properties. Examples of these include kynurenine, adenosine and lactate. The latter can reach up to 10-30 mM in some tumours,,,in vivo.,,,Another modality that shapes the TME is the intrinsic propensity of tumours cells to acquire a lipogenic phenotype. The TME is a lipid-rich environment, abundant in various species of free fatty acids, triacylglycerols and oxidized lipids,,,,,in vivo.,,,Another key barrier to cancer immunotherapy is the dysregulated vasculature associated with tumourigenesis, which leads to the formation of hypoxic pockets in the TME, particularly in the tumour core. A growing body of evidence indicates that T cells cannot function optimally in the oxygen-low environment, adopting an exhausted and dysfunctional phenotype.Importantly, it is not just infiltrating immune cells but also tumour stromal cells that can shape the TME and outcomes of cancer therapy. Cancer-associate fibroblasts (CAFs) are major drivers of extracellular matrix (ECM) remodelling, angiogenesis and immunosuppressive mediator expression in the TME, including lactate, adenosine, arginase, indoleamine 2,3-dioxygenase (IDO) as well as multiple inhibitory cytokines and chemokines, particularly TGF-β and chemokine (C-X-C motif) ligand 12 (CXCL12). CAF abundance is strongly associated with poor prognosis and the promotion of the T-cell-excluded phenotype, which responds poorly to ICIs.As discussed in the preceding text, we have to decipher the complexity of the TME both on the cellular and molecular levels in order to understand how we can optimize immunotherapy responses and efficacies. Below we present some of the key methods and illustrative applications. A summary is provided in scRNA-seq is a powerful technique for resolving cellular composition, functional states of immune cells, developmental lineages and reconstruction of the cellular communication network in the TME.,The main scRNA platforms were recently comparedThe use of multiple surface antigens to isolate distinct cell populations by FACS for subsequent scRNA-seq showed that combining protein and mRNA expression provided higher resolution of cell identities.Epigenetic changes play a major role in cell fate decisions and immune cell development. Many methods developed for bulk analysis were adapted for single-cell analysis, including methods for mapping DNA methylation (bisulfite sequencing),,,The spatial organization of the TME is a critical regulator of ICI response.,,,,However, to facilitate integration of molecular with histopathological features, the whole tissue context needs to be preserved. There are many methods based on two main principles .103,104 in situ T-cell clones demonstrated differential expression of a gene set associated with poor ICI response depending on their spatial location. A dominant T-cell clonotype displayed high expression near the tumour’s edge, but low expression deeper in the tumour compartment. Thus, T cells of a common ancestry may exhibit mixed responses to ICI depending on their spatial localization. Another study leveraged spatial profiling by the Nanostring GeoMx Immune Pathway Assay to provide spatial context to the role of TAMs in the phenomenon of hyper-progression in NSCLC patients following ICI treatment.Spatial transcriptomics is also enriching immunological research. A recently developed method, Slide-TCR-seq, allows the spatial mapping of T-cell receptors and transcriptomes.The relative abundance of mRNA and cognate protein expression varies across tissues,Results from these technologies are starting to impact immuno-oncology research. For instance, single-cell multiplexed immunohistochemistry imaging of HNSCC tumours demonstrated that neoplastic tumour immune cell spatial compartmentalization, rather than mixing, is associated with longer progression-free survival.,Similarly, the IMC analysis of primary brain tumours and brain metastases revealed single-cell interactions and spatial cellular neighbourhoods connected to immune response and survival.While responses to ICIs tend to be durable, the response rates in most cancer types are low. However, selecting patients who will benefit from ICIs has proven challenging and finding reliable biomarkers is key. Assays such as tumour mutational burden, PD-L1 immunohistochemistry, microsatellite instability or mismatch repair status are in clinical use, but their predictive power is limited. These assays reasonably assume that ICIs work, if the expression of the target is increased and if more neoantigens are generated due to increased mutational burden or increased genomic instability. The most advanced classification of the TME and its impact on survival is the Immunoscore.Alone or in combination with complementary methods, scRNA-seq has been applied for dissecting the TME in immunotherapy studies. Analysing 390 000 TILs from 316 patients across 21 cancer types revealed heterogeneous T-cell competencies in different cancer types and two main pathways to T-cell exhaustion.,For both clinical and research purposes, the TME is now segregated into three major tumour immune phenotypes: immune-desert, immune-excluded and immune-inflamed.Recognizing the importance of spatial organization, a powerful approach seems the combination of scRNA-seq and spatial transcriptomics/proteomics. For instance, in colorectal cancer the formation of immune-excluded desmoplastic structure hinders T-cell infiltration and the response to ICIs.Despite its power, the combination of scRNA-seq and spatial transcriptomics/proteomics will be difficult to implement into clinical routine due its cost, complexity and specialized infrastructure requirements. By contrast, bulk RNA-seq is already widely established in the clinic. Therefore, approaches that utilize scRNA-seq data to provide deeper interpretation of standard bulk RNA-seq data are likely to gain clinical importance.Another exciting development is that tumour-specific responses can be observed in the periphery. A personalized screening for tumour neoantigen-specific lymphocytes uncovered a small population of tumour-specific T cells in the peripheral blood of melanoma patients.


While the exact cause of IBD is unknown, there are a number of factors that are thought to contribute to its development, including environmental and genetic factors. While exclusive enteral nutrition (EEN) is a promising therapy for Crohn's disease (CD), it is not yet considered a first-line treatment. Additionally, the efficacy of EEN compared to corticosteroid treatment is still being investigated. EEN is suggested as a first-line therapy by which guidelines and in which age groups, as it may differ in pediatric and adult recommendations. Another finding was that dietary changes involving an increase in anti-inflammatory foods and decreased intake of foods high in inflammatory compounds are linked to a beneficial outcome both metabolically and microbiologically in patients with ulcerative colitis (UC) in remission.For relevant medical literature, we examined PubMed/Medline, the Cochrane Library, and Google Scholar as examples of medical databases. The articles were identified, evaluated, and eligibility applied, and nine publications were found. The finished articles investigated the role of several diet alternatives for patients with IBD. Some others have shown that following a normal low-fat diet may be effective in reducing the occurrence of subclinical colitis. The EEN and partial enteral nutrition (PEN) indicated no significant differences between both regimens, but both had good outcomes during active IBD. Other strict diets, such as the specific carbohydrate diet (SCD) versus the Mediterranean diet (MD), demonstrate excellent outcomes in patients with IBD. Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) dietary counseling improves gastrointestinal symptoms and quality of life in IBD patients. Based on the above, we concluded that more studies determining which component of the diet is not clear  or diet types are required to establish a particular diet employed as a treatment intervention in these individuals. Crohn's disease (CD) and ulcerative colitis (UC) are linked with significant morbidity and higher healthcare costs. The current model of CD pathogenesis implies that environmental variables and the gut microbiota interact in those who are genetically predisposed to the condition . SteroidIn pediatric CD, exclusive enteral nutrition (EEN) is the sole recognized nutritional therapy, notably in Europe. In nearly 80% of patients, EEN causes clinical remission and supports gut repair . The EENMethodologyWe did a systematic evaluation using free full-length papers and the Preferred Reporting Items checklist to describe our approach and results. This review was started on May 15, 2023.Search StrategyPubMed, Google Scholar, and Cochrane were used to collect databases using studies performed in the last two years using the following: Inflammatory bowel disease OR bloody diarrhea OR colitis (("Inflammatory Bowel Diseases/diet therapy"[Majr] OR "Inflammatory Bowel Diseases/prevention and control"[Majr])) OR ("Inflammatory Bowel Diseases/diet therapy"[Mesh:NoExp] OR "Inflammatory Bowel Diseases/prevention and control"[Mesh:NoExp]) AND Crohn's disease ("Crohn Disease/diet therapy"[Majr]) OR "Crohn Disease/diet therapy"[Majr:NoExp] AND Ulcerative colitis, bloody diarrhea  OR "Colitis, Ulcerative/diet therapy" [Majr:NoExp].Eligibility Criteria and Study SelectionTo assess eligibility, two investigators carefully read the full title and content of each paper. We selected the latest literature and articles published in the past five years, including papers written in the English language or if a full free-text English-language translation is available. Articles were excluded if the full free text of the papers could not be retrieved. Articles focusing on the different diets used as optional therapeutics for IBD  were also not included.Quality AssessmentWe used the Assessment of Multiple Systematic Reviews (AMSTAR) form and the Cochrane Risk of Bias assessment tools for clinical trials, systematic reviews, and meta-analyses.ResultsSearch ResultsA total of 5,435 studies were found after searching PubMed, Google Scholar, and Cochrane Library. A total of 4,904 were marked as ineligible by an automation tool. A total of 531 studies underwent title and abstract screening, and 506 papers were discarded. The remaining 25 papers were chosen for full-free text evaluation in the previous two years, and after discarding duplicates, resulting in the elimination of 16 studies, 9 studies were enlisted for the final collection of data  and Mediterranean diet (MD) in treating CD symptoms. While both diets decreased symptoms, we found no indication of an SCD advantage over MD in achieving symptomatic remission at six or twelve weeks, as well as no evidence of treatment effect heterogeneity depending on the presence or absence of verified inflammation during screening .Cox et al. conducted a randomized, placebo-controlled experiment to show that low-FODMAP dietary guidance improves gastrointestinal symptoms and quality of life in patients with quiescent IBD when compared to sham dietary counseling. In an untargeted study, a low FODMAP diet did not affect the intestinal microbiota, but it did affect the immune components of the GI microbiota. Despite this, neither clinical disease activity nor inflammatory markers changed .Milajerdi et al. showed that a low-FODMAP diet may decrease inflammation by modifying bacterial growth and will most likely limit IBD incidence and progression; however, this theory has yet to be validated in clinical studies. As a result, the lack of a clear therapy for IBD, as well as many drug-related problems, has raised attention to the use of alternative therapies .Clostridium difficile infection who were given preset diets, namely a microparticle diet, a semi-vegetarian diet, and an immunoglobulin exclusion diet [Ruminococcus gnavus) combined with decreases in protective groups , for which different diets will help in the formation of different bacteria colonies [Comeche et al. conducted an SRL meta-analysis. The fundamental idea of these diets was to reduce some pro-inflammatory foods while increasing others that are thought to maintain a healthy gut microbiota . In lighion diet . It is gcolonies -20.Finally, we demonstrated that following a diet that reduces inflammation may prevent its recurrence in UC patients in clinical remission. Following this conclusion, there were significant systemic changes in the intestinal microbiota of anti-inflammatory diet patients. These results are promising, and they suggest that bigger, more rigorous randomized controlled trials of nutritional therapies for maintaining remission in UC patients are warranted.CD patients with mild-to-severe symptoms tolerated MD and SCD well. Good symptomatic outcomes were prevalent with both diets, and they did not seem to be affected by the presence or lack of verified inflammation before randomization. We advise as well that a four-week FODMAP diet combined with professional counseling and regular follow-up will be helpful in the therapy of persistent gastrointestinal symptoms in quiescent IBD, although care should be used in the long run.


Transcranial magnetic stimulation (TMS) is a widely used noninvasive brain stimulation technique for psychiatric and cognitive disorders. In recent years, deep TMS (dTMS) has shown promise as an enhanced form of TMS able to stimulate deeper brain structures and target broader networks. Various magnetic Hesed-coil (H-coil) designs—a novel feature of dTMS—have been used to stimulate brain regions implicated in the pathophysiology of specific psychiatric and cognitive disorders, thereby producing therapeutic effects. Given the novelty of dTMS in psychiatry, little is known about the clinical efficacy of dTMS across psychiatric and cognitive disorders—that is, whether dTMS performs superiorly to sham or control.In this paper, we outline a protocol for a systematic review investigating the clinical efficacy of dTMS. The primary objective is to conduct a systematic review of the literature on dTMS for psychiatric and cognitive disorders and, if feasible, a meta-analysis to compare the efficacy of active dTMS versus sham/control for psychiatric disorders. Dementia and related cognitive disorders will also be examined. A secondary objective will be to examine subgroup differences  to evaluate whether dTMS differentially influences clinical outcomes based on these factors.A comprehensive search of the APA PsycINFO, Embase, MEDLINE, and PubMed databases will be conducted using keywords such as “H-coil” and “dTMS.” Two authors (AD and MD) will be responsible for screening relevant articles, assessing article eligibility (according to predetermined inclusion and exclusion criteria), and data extraction. All included articles will undergo a quality and risk of bias assessment. Data from included articles will be summarized qualitatively in a systematic review. If a sufficient number of equivalent studies are available, a meta-analysis will be performed to (1) determine the effect of active versus sham dTMS (or another control arm) across psychiatric and cognitive disorders, and (2) examine subgroup effects of clinical outcomes.The preliminary search rendered a total of 1134 articles from the APA PsycINFO, Embase, and MEDLINE databases. After full-text screening, 21 eligible articles remained. One additional article was identified from the references section of an existing systematic review. In total, 22 eligible articles were included. Data extraction and quality of assessment procedures are ongoing.We will outline the evidence relating to the clinical efficacy of dTMS in various psychiatric and cognitive disorders. The results of the prospective systematic review will provide clinicians with valuable insight into the clinical  and methodological factors  which may contribute to dTMS efficacy, and thereby may assist clinicians in their decision to prescribe dTMS for specific psychiatric and cognitive disorders.PROSPERO CRD42022360066; https://tinyurl.com/5ev6byrnDERR1-10.2196/45213 Psychiatric ,2 and coGiven the prevalence of treatment resistance in response to first-line pharmacological interventions in psychiatric disorders, as well as the lack of available treatment options to effectively treat and manage cognitive disorders, new effective treatments are urgently needed. One such technique is brain stimulation.Brain stimulation methods have shown increasing promise and widespread acceptance as nonpharmacological interventions to treat various psychiatric ,25 and cAnother promising method—known as deep TMS (dTMS)—is a noninvasive technique allowing for stimulation of deeper cortical areas and presumably deeper neural networks ,39. SincThe aim of dTMS is to modulate brain activity by applying an electrical current over the scalp. Brief magnetic pulses cause widespread neural depolarization in deep regions of the brain, resulting in reduced focal distribution of the electric field . Trains 3 [3 of breadth in the medial prefrontal cortex and anterior cingulate cortex [3 [3 [H-coils have complex winding designs and broad dimensions to encompass a larger surface area for stimulation of the electric field . The dif3 . Furthere cortex , while tortex [3 . In compex [3 [3 . The mosex [3 [3 .Given the increasing interest in the application of dTMS in psychiatry , it is cA single systematic review and meta-analysis have examined the clinical efficacy of dTMS for treatment-resistant depression . The autTo date, no systematic review has investigated the clinical efficacy of dTMS across multiple psychiatric and cognitive disorders, as determined by the examination of sham-controlled or controlled (without sham coil) trials. There is a growing need for a new systematic review to synthesize the findings of recent dTMS clinical trials in patients with various psychiatric and cognitive disorders, including Alzheimer disease , attentiSpecifically, the proposed systematic review that follows this paper’s protocol will aim to:Systematically review and summarize existing research to examine the clinical efficacy of dTMS versus sham/controls for psychiatric disorders and (if available) cognitive disorders.Integrate statistical results of included clinical trials in a meta-analysis, if feasible , to determine the effect of dTMS active stimulation versus sham (or control arm) across psychiatric and pertinent cognitive disorders.Conduct subgroup analyses  to determine if dTMS differentially influences clinical outcomes within these subgroups.A systematic search of the PubMed, APA PsycINFO, Embase, and MEDLINE databases will be conducted to identify relevant articles. The Cochrane database will also be explored for pertinent articles. Two authors (AD and MD) will be responsible for independently conducting the searches. The core keywords used in the searches will include “dTMS,” “deep rTMS,” “deep TMS,” “deep transcranial magnetic stimulation,” and “H-coil.” All articles will be independently screened and assessed for eligibility by 2 authors (AD and MD) according to the predetermined inclusion criteria. We will include clinical trials reporting the clinical effect of dTMS interventions for psychiatric and cognitive disorders compared to a sham-controlled or control arm. The full inclusion and exclusion criteria are presented in Inclusion criteria:Article typeClinical trials and randomized controlled trialsStudies including a sham or control conditionStudies comparing active deep transcranial magnetic stimulation to a sham or control conditionArticles of any publication yearStudy participantsParticipants with a valid diagnosis of a psychiatric or cognitive disorder according to a recognized diagnostic manual , or a clinicianLanguageArticles written in EnglishExclusion criteria:Article typeConference abstractsLetters to the editorBooksLiterature reviews, systematic reviews, or meta-analysesCase reports or case studies.Study participantsParticipants are healthy individualsLanguageArticles not written in EnglishTwo authors (AD and MD) will conduct the abstract and full-text screening of relevant articles. Articles will be screened in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)  guidelinAll articles will be assessed according to the grading of recommendations, assessment, development, and evaluations (GRADE) checklist ,62 to evThe following data variables will be extracted from each included article: country of publication, study type, comparison type , participant sample size, participant sex, and mean age. The psychiatric or cognitive disorder diagnosis and diagnostic criteria  of patients will be recorded. Regarding treatment procedures, this study will report treatment duration, number of treatment sessions, H-coil type, and the brain regions of interest . Additionally, this study will report the dTMS parameters, including frequency (Hz), intensity, pulses per session, time per session, trains per session, and intertrain interval duration. Posttreatment comparisons between dTMS efficacy in active versus sham/control groups will be reported, including data on remission rates, response rates, or posttreatment score changes on psychiatric and cognitive rating scales. Remission criteria and response criteria will also be reported. Additionally, we will include data related to side effects and adverse events. The proposed systematic review will evaluate the clinical efficacy of dTMS for psychiatric and cognitive disorders by comparing active versus sham dTMS treatment groups , as well as active versus control groups . To do this, we will compare response rates, remission rates, and the overall efficacy of the dTMS treatment in active versus sham/control conditions. Additionally, if at least 4 substantively equivalent investigations are present in a given area, we will perform a meta-analysis to ascertain aggregate clinical effects across studies in sham/control trials. Further subgroup analyses will be conducted on age, sex, H-coil type, and dTMS parameters to the extent possible. Risk of bias and article quality assessments will be used when considering evidence and analyzing data from included studies. Moreover, the study will summarize the proposed review’s findings on the clinical efficacy of dTMS for psychiatric and (if available) cognitive disorders, identify evidence that may assist clinicians in their practice, and highlight future directions for research.Q test, I2, and τ2. A random effects model will be used, if appropriate, to account for potential between-studies variance in treatment effect.For the prospective meta-analysis, analyses will be conducted using Stata (StataCorp). Heterogeneity will be assessed using the The proposed systematic review aims to evaluate the clinical efficacy of active dTMS versus sham/control in various psychiatric (and if available) cognitive disorders. Additionally, a meta-analysis will be performed (if a sufficient number of studies are available) exploring the effects of dTMS parameters, age, sex, and H-coil type on clinical outcomes.Thus far, 22 eligible studies have been included from the following databases: APA PsycINFO, Embase, and MEDLINE refer to . A searcA search of the Cochrane database still needs to be performed to identify other potential articles. The data extraction process is ongoing. Once the data extraction is complete, we will determine if there are enough suitable articles to conduct a meta-analysis. We aim to have this project complete by the end of 2023.The preliminary screening stages of the ongoing systematic review have rendered a total of 22 eligible articles comparing the efficacy of dTMS to a sham/control condition. While dTMS treatment has been shown to effectively alleviate clinical symptoms for psychiatric and cognitive disorders, the current state of literature lacks insight into the clinical efficacy of dTMS interventions across such disorders. Data from all 22 articles identified in the preliminary search may help to bridge this gap in the literature by conducting a comprehensive systematic review, and prospective meta-analysis, to determine the efficacy of dTMS across diverse psychiatric and cognitive disorders.The proposed review will be the first, to our knowledge, to evaluate the clinical efficacy of dTMS across psychiatric and pertinent cognitive disorders. The knowledge gathered from this systematic review holds great clinical value. First, it can inform clinicians about the potential clinical benefits of dTMS in specific psychiatric populations. Second, by further conducting subgroup analyses , this study aims to identify subgroup variables that may affect clinical outcomes following dTMS treatment. This subgroup data has valuable clinical implications, as the identification of such clinical and methodological factors may influence clinicians’ decisions to support dTMS over another treatment regimen. Thus, future dTMS treatments can be tailored to fulfill the patient’s needs and customize treatments to optimize therapeutic effects.The systematic review that follows this protocol may have limitations. First, sham-controlled studies exploring the clinical efficacy of dTMS are limited. Second, there may not be sufficient studies to examine the clinical efficacy of dTMS for each psychiatric and cognitive disorder. Thus, a meta-analysis may not be possible for all conditions, which may hinder assessments of subgroup variables potentially influencing dTMS efficacy.In this protocol, the authors openly review the methodological procedures of a systematic review  designed to effectively determine the clinical efficacy of dTMS for psychiatric and cognitive disorders. This protocol was published to ensure the originality of this research and to contribute to data availability.


In recent decades, people in the industrialized world have increased the demand for meat-free foods motivated by health, environmental, and animal welfare reasons. Thus, plant products and their derivatives have gained great popularity in nutrition . MeanwhiThe high consumption of plant products has generated an increase in the study of the beneficial properties of their components beyond their basic macro- and micro-nutrients ,4. In thCastana sativa (chestnut) that was shown to have antimicrobial activity against Streptococcus and Staphylococcus, among others [Chenopodium quinoa (quinoa), Amaranthus retroflexus (amaranth), and Fagopyrum esculentum (buckwheat), obtained by simulated gastrointestinal digestion, showed protective effects against IL-1-induced inflammation in vitro [Protium heptaphyllum gum resin has been shown to reduce cholesterol production in human liver cells and regulate the gene expression of several proteins involved in cholesterol metabolism [In this Special Issue, several studies in which different vegetable extracts were tested have been compiled. The enzyme-assisted extraction of plant compounds is a widely used method and can be a strategy for sustainable and functional applications . This meg others . These min vitro . Additiotabolism .Methyl p-coumarate, an esterified derivative of p-coumaric acid and a naturally occurring compound in plants, has been shown to be an effective agent for reducing inflammation in an experimental in vivo model of allergic asthma, reducing the influx of immune cells and mucus secretion in the lung, among other activities .Lupins angustifolius (lupin) was able to reduce anxiety in mice evaluated by the elevated plus maze and Morris water maze behavior tests [Another natural compound was also tested in a mouse model of anxiety. In that study, a protein hydrolysate from or tests .Rosmarinus officinalis (rosemary) was studied in four patients with osteogenesis imperfecta, a genetic connective tissue disease [The clinical application of a vegetable extract of  disease . In thisLycium barbarum berries [Annonaceae species [Finally, the biological effects of  berries , the ess species , antioxi species , as well species , and dif species  were revThis Special Issue provides an overview of the current research being carried out with vegetable-derived bioactive compounds. All of these findings confirm and point out that these compounds may be possible new nutraceuticals capable of preventing or treating several diseases.