Recent advances in computing technology and the development of data utilization environments have rapidly accelerated the application of artificial intelligence in clinical research and healthcare. This review provides a comprehensive overview of current machine learning techniques for analyzing clinical data, with illustrative examples from the field of allergic diseases. In addition to conventional methods for clinical data analysis, we discuss emerging approaches including medical image analysis and time-series modeling of electronic health record data. Recent developments such as large language models and foundation models trained on massive datasets are also discussed. Looking ahead, we explore future directions in analytical methodology, including mathematical modeling, interpretable artificial intelligence, and multimodal learning that integrates various data types. We also introduce the concept of the digital twin—a virtual representation of an individual patient that simulates disease progression and treatment response—as a promising concept for advancing precision medicine. Finally, we discuss the essential role of physicians in the development and implementation of machine learning tools and discuss emerging ethical issues such as fairness, privacy, and patient autonomy. By synthesizing recent technical advances with clinical relevance, this review aims to provide clinicians and researchers with a practical and forward-looking guide to machine learning in clinical medicine, including its growing application in the field of allergy.
{"title":"Artificial intelligence in clinical data analysis: A review of large language models, foundation models, digital twins, and allergy applications","authors":"Yutaro Fuse , Shawn N. Murphy , Hisahiro Ikari , Akiko Takahashi , Kenshiro Fuse , Eiryo Kawakami","doi":"10.1016/j.alit.2025.06.005","DOIUrl":"10.1016/j.alit.2025.06.005","url":null,"abstract":"<div><div>Recent advances in computing technology and the development of data utilization environments have rapidly accelerated the application of artificial intelligence in clinical research and healthcare. This review provides a comprehensive overview of current machine learning techniques for analyzing clinical data, with illustrative examples from the field of allergic diseases. In addition to conventional methods for clinical data analysis, we discuss emerging approaches including medical image analysis and time-series modeling of electronic health record data. Recent developments such as large language models and foundation models trained on massive datasets are also discussed. Looking ahead, we explore future directions in analytical methodology, including mathematical modeling, interpretable artificial intelligence, and multimodal learning that integrates various data types. We also introduce the concept of the digital twin—a virtual representation of an individual patient that simulates disease progression and treatment response—as a promising concept for advancing precision medicine. Finally, we discuss the essential role of physicians in the development and implementation of machine learning tools and discuss emerging ethical issues such as fairness, privacy, and patient autonomy. By synthesizing recent technical advances with clinical relevance, this review aims to provide clinicians and researchers with a practical and forward-looking guide to machine learning in clinical medicine, including its growing application in the field of allergy.</div></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"74 4","pages":"Pages 499-513"},"PeriodicalIF":6.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144975373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Basophils are the rarest granulocytes and play diverse roles, e.g., in protective immunity and allergic inflammatory reactions. However, the underlying molecules and mechanisms involved in basophil differentiation and functions, particularly in humans, remain largely unknown. This may be due to the lack of high-quality research tools.
Methods
We established a novel, immortalized, human basophil cell line by introducing human papillomavirus 16-E6/E7, c-MYC, and BCL-xL gene expression systems into cultured basophils, and evaluated whether this cell line is useful as a research tool, compared with KU812, which is the most commonly-used human basophil cell line.
Results
This cell line expressed various basophil markers, including CD123, CD203c, and the high-affinity immunoglobulin (Ig)E receptor α-chain and can mature into more differentiated cells under specific culture conditions. The differentiated cells stimulated with anti-IgE antibodies showed increased CD203c expression in a dose-dependent manner, whereas the differentiated KU812 cells showed little activation after the stimulation.
The established cell line also demonstrated increased sensitivity to allergic activation when stimulated with an allergen (NP-BSA) and allergen-specific IgE (anti-NP-IgE). Furthermore, histamine- and interleukin-4-releasing abilities were also confirmed. These allergic activation profiles were similar to those of basophils from healthy individuals, although the activation levels of the established cells were lower than those of basophils from highly-sensitive individuals.
Conclusions
These findings suggest that the established basophil cell line has substantially different characteristics from a conventional cell line and could serve as a new tool for investigating basophil differentiation and functions, as well as for testing allergic reactions.
{"title":"Establishment of a novel human basophil cell line for functional analysis and in vitro allergy testing","authors":"Ryo Kurita, Takaaki Abe, Kanako Maebara, Daisuke Takahashi, Shigeki Miyata, Masahiro Satake, Yoshihiko Tani","doi":"10.1016/j.alit.2025.03.003","DOIUrl":"10.1016/j.alit.2025.03.003","url":null,"abstract":"<div><h3>Background</h3><div>Basophils are the rarest granulocytes and play diverse roles, e.g., in protective immunity and allergic inflammatory reactions. However, the underlying molecules and mechanisms involved in basophil differentiation and functions, particularly in humans, remain largely unknown. This may be due to the lack of high-quality research tools.</div></div><div><h3>Methods</h3><div>We established a novel, immortalized, human basophil cell line by introducing human papillomavirus 16-E6<em>/</em>E7, <em>c-MYC</em>, and <em>BCL-xL</em> gene expression systems into cultured basophils, and evaluated whether this cell line is useful as a research tool, compared with KU812, which is the most commonly-used human basophil cell line.</div></div><div><h3>Results</h3><div>This cell line expressed various basophil markers, including CD123, CD203c, and the high-affinity immunoglobulin (Ig)E receptor α-chain and can mature into more differentiated cells under specific culture conditions. The differentiated cells stimulated with anti-IgE antibodies showed increased CD203c expression in a dose-dependent manner, whereas the differentiated KU812 cells showed little activation after the stimulation.</div><div>The established cell line also demonstrated increased sensitivity to allergic activation when stimulated with an allergen (NP-BSA) and allergen-specific IgE (anti-NP-IgE). Furthermore, histamine- and interleukin-4-releasing abilities were also confirmed. These allergic activation profiles were similar to those of basophils from healthy individuals, although the activation levels of the established cells were lower than those of basophils from highly-sensitive individuals.</div></div><div><h3>Conclusions</h3><div>These findings suggest that the established basophil cell line has substantially different characteristics from a conventional cell line and could serve as a new tool for investigating basophil differentiation and functions, as well as for testing allergic reactions.</div></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"74 4","pages":"Pages 579-590"},"PeriodicalIF":6.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143789107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01DOI: 10.1016/j.alit.2025.01.001
Ge Peng , Wanchen Zhao , Alafate Abudouwanli , Quan Sun , Mengyao Yang , Shan Wang , Yi Tan , Arisa Ikeda , Shigaku Ikeda , Hideoki Ogawa , Ko Okumura , François Niyonsaba
Background
Atopic dermatitis (AD), a prevalent chronic inflammatory skin disorder, is characterized by compromised skin barrier and heightened immune responses. The study investigates the therapeutic efficacy of catestatin (CST), a chromogranin A-derived antimicrobial peptide, in mitigating AD-like symptoms.
Methods
Utilizing both keratinocyte cultures and a C57BL/6 mouse model, we examined CST's impact on skin barrier proteins, tight junction (TJ) integrity, inflammatory cytokines, and AD-like symptoms.
Results
CST administration led to a significant upregulation of skin barrier proteins and improved TJ function, counteracting the negative effects of Th2 cytokines on these parameters. In a 2,4-dinitrochlorobenzene-induced AD mouse model, CST treatment markedly reduced AD-like symptoms, including ear thickness, transepidermal water loss, and scratching behavior, and normalized barrier protein expression and TJ barrier function. Furthermore, CST was found to interact with the Notch1 receptor, activating the Notch1/PKC pathway, which may underlie its skin barrier-enhancing properties.
Conclusions
Collectively, these findings suggest CST as a promising therapeutic agent for AD, capable of enhancing skin barrier function, modulating immune responses, and targeting the Notch1/PKC pathway, offering a novel approach to AD treatment focusing on barrier restoration and immune modulation.
{"title":"Improvement of atopic dermatitis-like symptoms in a murine model via the chromogranin A-derived peptide catestatin","authors":"Ge Peng , Wanchen Zhao , Alafate Abudouwanli , Quan Sun , Mengyao Yang , Shan Wang , Yi Tan , Arisa Ikeda , Shigaku Ikeda , Hideoki Ogawa , Ko Okumura , François Niyonsaba","doi":"10.1016/j.alit.2025.01.001","DOIUrl":"10.1016/j.alit.2025.01.001","url":null,"abstract":"<div><h3>Background</h3><div>Atopic dermatitis (AD), a prevalent chronic inflammatory skin disorder, is characterized by compromised skin barrier and heightened immune responses. The study investigates the therapeutic efficacy of catestatin (CST), a chromogranin A-derived antimicrobial peptide, in mitigating AD-like symptoms.</div></div><div><h3>Methods</h3><div>Utilizing both keratinocyte cultures and a C57BL/6 mouse model, we examined CST's impact on skin barrier proteins, tight junction (TJ) integrity, inflammatory cytokines, and AD-like symptoms.</div></div><div><h3>Results</h3><div>CST administration led to a significant upregulation of skin barrier proteins and improved TJ function, counteracting the negative effects of Th2 cytokines on these parameters. In a 2,4-dinitrochlorobenzene-induced AD mouse model, CST treatment markedly reduced AD-like symptoms, including ear thickness, transepidermal water loss, and scratching behavior, and normalized barrier protein expression and TJ barrier function. Furthermore, CST was found to interact with the Notch1 receptor, activating the Notch1/PKC pathway, which may underlie its skin barrier-enhancing properties.</div></div><div><h3>Conclusions</h3><div>Collectively, these findings suggest CST as a promising therapeutic agent for AD, capable of enhancing skin barrier function, modulating immune responses, and targeting the Notch1/PKC pathway, offering a novel approach to AD treatment focusing on barrier restoration and immune modulation.</div></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"74 4","pages":"Pages 563-571"},"PeriodicalIF":6.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Allergic diseases are characterized by heterogeneity driven by complex interactions between genetic, environmental, and immunological factors. Conventional classifications based solely on clinical phenotypes often fails to capture the underlying molecular diversity, thereby limiting therapeutic precision and patient outcomes. Integrative omics—encompassing genomics, transcriptomics, proteomics, metabolomics, and microbiomics—has emerged as a powerful approach to redefine disease mechanisms and advance precision medicine. By integrating high-dimensional molecular data with clinical phenotyping, omics approaches enable the identification of disease endotypes, biomarker discovery, and patient stratification.
This review highlights recent developments in clinical-omics integration, with a focus on atopic dermatitis (AD) as a prototypical allergic disease. Drawing from our studies, we illustrate how tissue-level transcriptomic profiling, combined with unbiased computational analysis, can uncover immunological heterogeneity and treatment-response patterns in AD. Additional examples in asthma and food allergy demonstrate how integrated multi-omics can uncover gene-environment interactions and elucidate mechanisms behind disease severity and health disparities.
We also address practical and ethical challenges in data harmonization, privacy, and interoperability, and underscore the critical role of computational methods and infrastructure development in enabling clinically meaningful interpretation. Importantly, successful translation of multi-omics data into clinical practice requires iterative, interdisciplinary collaboration between clinicians, data scientists, and basic researchers.
By bridging molecular complexity and clinical heterogeneity, integrative omics is reshaping the landscape of allergy research. As technologies evolve, this framework will be crucial for developing predictive models and personalized therapeutic strategies, ultimately bringing us closer to individualized, data-driven care in allergic diseases.
{"title":"Integrative omics redefining allergy mechanisms and precision medicine","authors":"Ayano Fukushima-Nomura , Hiroshi Kawasaki , Masayuki Amagai","doi":"10.1016/j.alit.2025.08.007","DOIUrl":"10.1016/j.alit.2025.08.007","url":null,"abstract":"<div><div>Allergic diseases are characterized by heterogeneity driven by complex interactions between genetic, environmental, and immunological factors. Conventional classifications based solely on clinical phenotypes often fails to capture the underlying molecular diversity, thereby limiting therapeutic precision and patient outcomes. Integrative omics—encompassing genomics, transcriptomics, proteomics, metabolomics, and microbiomics—has emerged as a powerful approach to redefine disease mechanisms and advance precision medicine. By integrating high-dimensional molecular data with clinical phenotyping, omics approaches enable the identification of disease endotypes, biomarker discovery, and patient stratification.</div><div>This review highlights recent developments in clinical-omics integration, with a focus on atopic dermatitis (AD) as a prototypical allergic disease. Drawing from our studies, we illustrate how tissue-level transcriptomic profiling, combined with unbiased computational analysis, can uncover immunological heterogeneity and treatment-response patterns in AD. Additional examples in asthma and food allergy demonstrate how integrated multi-omics can uncover gene-environment interactions and elucidate mechanisms behind disease severity and health disparities.</div><div>We also address practical and ethical challenges in data harmonization, privacy, and interoperability, and underscore the critical role of computational methods and infrastructure development in enabling clinically meaningful interpretation. Importantly, successful translation of multi-omics data into clinical practice requires iterative, interdisciplinary collaboration between clinicians, data scientists, and basic researchers.</div><div>By bridging molecular complexity and clinical heterogeneity, integrative omics is reshaping the landscape of allergy research. As technologies evolve, this framework will be crucial for developing predictive models and personalized therapeutic strategies, ultimately bringing us closer to individualized, data-driven care in allergic diseases.</div></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"74 4","pages":"Pages 514-524"},"PeriodicalIF":6.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Exacerbated signs of atopic dermatitis with gut dysbiosis predominate in male than in female adult patients","authors":"Susumu Ichiyama , Kozo Ohkusu-Tsukada , Hidehisa Saeki","doi":"10.1016/j.alit.2025.04.002","DOIUrl":"10.1016/j.alit.2025.04.002","url":null,"abstract":"","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"74 4","pages":"Pages 633-636"},"PeriodicalIF":6.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Schnitzler syndrome (SchS) is a late-onset autoinflammatory disease characterized by urticarial rash and monoclonal gammopathy. SchS shares clinical features with cryopyrin-associated periodic syndrome, which is driven by gain-of-function mutations in NLRP3, and while IL-1β-targeted therapies have shown efficacy, the underlying pathogenesis of SchS remains unclear.
Methods
During a multicenter, single-arm, open-label, investigator-initiated trial evaluating the efficacy and safety of canakinumab in five Japanese patients with SchS (named the SCan Study after SchS and Canakinumab), based on a similar study conducted in Germany, we measured 32 cytokines/chemokines and 11 complement-related factors in plasma and analyzed their correlations with changes in clinical symptoms during treatment. Furthermore, in two cases, single-cell RNA sequencing of peripheral blood and spatial transcriptomic analysis of lesional skin were performed to identify IL1B-expressing cells.
Results
The improvement in clinical symptoms and quality of life was maintained for 48 weeks following canakinumab treatment. Notably, these changes in clinical symptoms strongly correlated with WBC count, neutrophil count, CRP, and serum amyloid A levels, which were used as evaluation parameters in this study. In contrast, IL-1β and most other cytokines/chemokines exhibited distinct patterns and were not useful as markers of disease activity. IgM levels remained stable without an upward trend. Additionally, IL1B-expressing cells were predominantly neutrophils in both peripheral blood and lesional skin. Furthermore, neutrophil counts in peripheral blood decreased following canakinumab administration.
Conclusions
This study demonstrated that the primary source of IL1B-expressing cells in SchS is neutrophils. Moreover, canakinumab improves clinical symptoms by regulating neutrophil dynamics in peripheral blood.
{"title":"Neutrophils predominate as IL1B-expressing cells in Schnitzler syndrome: Insights from the SCan study to evaluate the efficacy and safety of canakinumab in Japanese patients","authors":"Naotomo Kambe , Norimitsu Inoue , Yoko Ueki , Yuyi Zhou , Satoru Yonekura , Kosuke Katsuo , Satoshi Nakamizo , Hiroshi Tsujimoto , Katsuki Ohtani , Hajime Yoshifuji , Tomoyasu Jo , Kazushi Izawa , Mayuko Yamamoto , Koji Takemura , Shin-ichiro Kagami , Yoshie Kawahara , Yoko Amino , Yumiko Ibi , Satoshi Morita , Nobuo Kanazawa","doi":"10.1016/j.alit.2025.04.003","DOIUrl":"10.1016/j.alit.2025.04.003","url":null,"abstract":"<div><h3>Background</h3><div>Schnitzler syndrome (SchS) is a late-onset autoinflammatory disease characterized by urticarial rash and monoclonal gammopathy. SchS shares clinical features with cryopyrin-associated periodic syndrome, which is driven by gain-of-function mutations in <em>NLRP3</em>, and while IL-1β-targeted therapies have shown efficacy, the underlying pathogenesis of SchS remains unclear.</div></div><div><h3>Methods</h3><div>During a multicenter, single-arm, open-label, investigator-initiated trial evaluating the efficacy and safety of canakinumab in five Japanese patients with SchS (named the SCan Study after SchS and Canakinumab), based on a similar study conducted in Germany, we measured 32 cytokines/chemokines and 11 complement-related factors in plasma and analyzed their correlations with changes in clinical symptoms during treatment. Furthermore, in two cases, single-cell RNA sequencing of peripheral blood and spatial transcriptomic analysis of lesional skin were performed to identify <em>IL1B</em>-expressing cells.</div></div><div><h3>Results</h3><div>The improvement in clinical symptoms and quality of life was maintained for 48 weeks following canakinumab treatment. Notably, these changes in clinical symptoms strongly correlated with WBC count, neutrophil count, CRP, and serum amyloid A levels, which were used as evaluation parameters in this study. In contrast, IL-1β and most other cytokines/chemokines exhibited distinct patterns and were not useful as markers of disease activity. IgM levels remained stable without an upward trend. Additionally, <em>IL1B</em>-expressing cells were predominantly neutrophils in both peripheral blood and lesional skin. Furthermore, neutrophil counts in peripheral blood decreased following canakinumab administration.</div></div><div><h3>Conclusions</h3><div>This study demonstrated that the primary source of <em>IL1B-</em>expressing cells in SchS is neutrophils. Moreover, canakinumab improves clinical symptoms by regulating neutrophil dynamics in peripheral blood.</div></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"74 4","pages":"Pages 605-615"},"PeriodicalIF":6.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01DOI: 10.1016/j.alit.2025.02.002
Stefan Zielen , Hartmut Richter , Petra Zieglmayer , Michael Gerstlauer , Josiane Cognet-Sicé , Silvia Scurati , Philippe Devillier
Background
Patients with allergic rhinitis (AR) and/or mild or moderate asthma derived from birch-family pollen allergy can be treated with liquid sublingual immunotherapy (SLIT-liquid). This study evaluated the impact of two SLIT extracts on AR and asthma progression or onset in these patients.
Methods
This was a sub-analysis of a retrospective, longitudinal comparative cohort study that used a German prescription database. Patients treated with 3-tree (birch/alder/hazel) or birch-only SLIT-liquid and followed up for up to 6 years after treatment were compared with controls dispensed symptomatic medications. Multiple regression analysis compared dispensation data as a proxy for disease status and progression.
Results
A total of 493 patients treated with 3-tree SLIT-liquid and 311 treated with birch SLIT-liquid were analysed vs. 44,835 patients included as controls. Overall, 70.5 % of patients presented solely AR, 24.2 % solely asthma, and 5.3 % both diseases. Compared with controls, patients treated with 3-tree SLIT-liquid had reduced risk of AR [odds ratio (OR) = 3.21, 95 % CI 2.54–4.06, p < 0.001], asthma progression (OR = 2.03, 95 % CI 1.43–2.89, p < 0.0001), or asthma onset (OR = 0.592, 95 % CI, 0.408–0.860, p = 0.006). Birch-only SLIT-liquid showed similar effectiveness in reducing AR and asthma medication dispensation but no significant effect in reducing new-onset asthma.
Conclusions
This real-world study demonstrated the effectiveness of treatment with 3-tree SLIT-liquid or birch SLIT-liquid in slowing the progression of birch-family pollen allergy. 3-tree SLIT-liquid covering a broader repertoire of epitopes mimicking natural exposure throughout the year may be valuable for patients sensitised to birch and/or alder and/or hazel pollen suffering from overlapping tree-pollen seasons.
{"title":"Long-term impact of a birch/alder/hazel or birch-only liquid sublingual immunotherapy on birch-family pollen respiratory allergy: A real-world study","authors":"Stefan Zielen , Hartmut Richter , Petra Zieglmayer , Michael Gerstlauer , Josiane Cognet-Sicé , Silvia Scurati , Philippe Devillier","doi":"10.1016/j.alit.2025.02.002","DOIUrl":"10.1016/j.alit.2025.02.002","url":null,"abstract":"<div><h3>Background</h3><div>Patients with allergic rhinitis (AR) and/or mild or moderate asthma derived from birch-family pollen allergy can be treated with liquid sublingual immunotherapy (SLIT-liquid). This study evaluated the impact of two SLIT extracts on AR and asthma progression or onset in these patients.</div></div><div><h3>Methods</h3><div>This was a sub-analysis of a retrospective, longitudinal comparative cohort study that used a German prescription database. Patients treated with 3-tree (birch/alder/hazel) or birch-only SLIT-liquid and followed up for up to 6 years after treatment were compared with controls dispensed symptomatic medications. Multiple regression analysis compared dispensation data as a proxy for disease status and progression.</div></div><div><h3>Results</h3><div>A total of 493 patients treated with 3-tree SLIT-liquid and 311 treated with birch SLIT-liquid were analysed vs. 44,835 patients included as controls. Overall, 70.5 % of patients presented solely AR, 24.2 % solely asthma, and 5.3 % both diseases. Compared with controls, patients treated with 3-tree SLIT-liquid had reduced risk of AR [odds ratio (OR) = 3.21, 95 % CI 2.54–4.06, p < 0.001], asthma progression (OR = 2.03, 95 % CI 1.43–2.89, p < 0.0001), or asthma onset (OR = 0.592, 95 % CI, 0.408–0.860, p = 0.006). Birch-only SLIT-liquid showed similar effectiveness in reducing AR and asthma medication dispensation but no significant effect in reducing new-onset asthma.</div></div><div><h3>Conclusions</h3><div>This real-world study demonstrated the effectiveness of treatment with 3-tree SLIT-liquid or birch SLIT-liquid in slowing the progression of birch-family pollen allergy. 3-tree SLIT-liquid covering a broader repertoire of epitopes mimicking natural exposure throughout the year may be valuable for patients sensitised to birch and/or alder and/or hazel pollen suffering from overlapping tree-pollen seasons.</div></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"74 4","pages":"Pages 572-578"},"PeriodicalIF":6.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01DOI: 10.1016/j.alit.2025.08.004
Kairi Furui, Koh Sakano, Masahito Ohue
Protein language models (pLMs) are rapidly emerging as revolutionary artificial intelligence technologies that bring transformative changes to drug discovery and therapeutic research. pLMs acquire rich representational capabilities from large-scale sequence datasets, enabling the solution of various biological problems that were difficult with conventional methods. In this review, we provide a comprehensive overview of various pLMs and their implementations, exploring their potential utility in drug discovery and therapeutic research. First, we systematically classify pLMs based on their architectures and information sources while discussing their development to the present. We also explain recent trends in multimodal approaches that integrate co-evolutionary information, structural information, and functional information, as well as domain-specific models specialized for particular domains such as antibodies and T-cell receptors. We then provide a comprehensive overview of various therapeutic applications of pLMs, including mutation effect prediction, function prediction, and structure prediction. Finally, we discuss future prospects of pLMs toward therapeutic applications and challenges for transforming them into technologies that contribute to actual diseases.
{"title":"Predictive and therapeutic applications of protein language models","authors":"Kairi Furui, Koh Sakano, Masahito Ohue","doi":"10.1016/j.alit.2025.08.004","DOIUrl":"10.1016/j.alit.2025.08.004","url":null,"abstract":"<div><div>Protein language models (pLMs) are rapidly emerging as revolutionary artificial intelligence technologies that bring transformative changes to drug discovery and therapeutic research. pLMs acquire rich representational capabilities from large-scale sequence datasets, enabling the solution of various biological problems that were difficult with conventional methods. In this review, we provide a comprehensive overview of various pLMs and their implementations, exploring their potential utility in drug discovery and therapeutic research. First, we systematically classify pLMs based on their architectures and information sources while discussing their development to the present. We also explain recent trends in multimodal approaches that integrate co-evolutionary information, structural information, and functional information, as well as domain-specific models specialized for particular domains such as antibodies and T-cell receptors. We then provide a comprehensive overview of various therapeutic applications of pLMs, including mutation effect prediction, function prediction, and structure prediction. Finally, we discuss future prospects of pLMs toward therapeutic applications and challenges for transforming them into technologies that contribute to actual diseases.</div></div>","PeriodicalId":48861,"journal":{"name":"Allergology International","volume":"74 4","pages":"Pages 534-548"},"PeriodicalIF":6.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01DOI: 10.1016/j.alit.2025.08.005
Teppei Shimamura
Single-cell RNA sequencing (scRNA-seq) has revolutionized biology through high-throughput quantification of gene expression at individual cell resolution. However, standard scRNA-seq provides only static cellular snapshots, obscuring dynamic processes that unfold temporally, such as differentiation, reprogramming, and disease progression. RNA Velocity, introduced in 2018, offers a groundbreaking solution. By leveraging unspliced pre-mRNA and spliced mRNA information, RNA Velocity models infer instantaneous gene expression change rates and effectively predict future transcriptional states over hour-long timescales. This review charts the evolution of this powerful concept, beginning with foundational principles and mathematical models of transcriptional dynamics. We explore Velocyto’s pioneering implementation, discuss successes and limitations, and then examine second-generation advanced computational tools that generalize the framework, including scVelo, dynamo, and CellRank. A dedicated section highlights growing applications in allergy and immunology research, where these methods reveal novel disease mechanisms in asthma, atopic dermatitis, and chronic inflammation by analyzing immune cell differentiation and state transitions. We explored modern frontiers, including RNA Velocity integration with spatial and multimodal data, and the latest deep learning-based methods. Finally, we addressed the current challenges and remaining limitations of RNA Velocity analysis, offering insights into best practices and future directions. Throughout, we emphasize applications to allergic and immune-mediated diseases—including asthma, atopic dermatitis, and prurigo nodularis—to guide researchers and clinicians in allergy and immunology. RNA Velocity is becoming indispensable for navigating the complex, dynamic cellular world and transforming our understanding of temporal biological processes from static observations to predictive, dynamic insights that illuminate cellular fate decisions and disease mechanisms.
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