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2. Math Agents: Computational Infrastructure, Mathematical Embedding, and Genomics

Author

Swan, Melanie, Kido, Takashi, Roland, Eric, and Santos, Renato P. dos

Subjects
Quantitative Biology - Other Quantitative Biology, Computer Science - Artificial Intelligence, Computer Science - Computation and Language, 68R12, I.2, J.3
Abstract

The advancement in generative AI could be boosted with more accessible mathematics. Beyond human-AI chat, large language models (LLMs) are emerging in programming, algorithm discovery, and theorem proving, yet their genomics application is limited. This project introduces Math Agents and mathematical embedding as fresh entries to the "Moore's Law of Mathematics", using a GPT-based workflow to convert equations from literature into LaTeX and Python formats. While many digital equation representations exist, there's a lack of automated large-scale evaluation tools. LLMs are pivotal as linguistic user interfaces, providing natural language access for human-AI chat and formal languages for large-scale AI-assisted computational infrastructure. Given the infinite formal possibility spaces, Math Agents, which interact with math, could potentially shift us from "big data" to "big math". Math, unlike the more flexible natural language, has properties subject to proof, enabling its use beyond traditional applications like high-validation math-certified icons for AI alignment aims. This project aims to use Math Agents and mathematical embeddings to address the ageing issue in information systems biology by applying multiscalar physics mathematics to disease models and genomic data. Generative AI with episodic memory could help analyse causal relations in longitudinal health records, using SIR Precision Health models. Genomic data is suggested for addressing the unsolved Alzheimer's disease problem.

Published
2023

11. Are minor alleles more likely to be risk alleles?

Author

Kido, Takashi, Sikora-Wohlfeld, Weronika, Kawashima, Minae, Kikuchi, Shinichi, Kamatani, Naoyuki, Patwardhan, Anil, Chen, Richard, Sirota, Marina, Kodama, Keiichi, Hadley, Dexter, and Butte, Atul J

Subjects
Biological Sciences, Genetics, Human Genome, Prevention, 2.1 Biological and endogenous factors, Aetiology, Alleles, Computational Biology, Databases, Genetic, Evolution, Molecular, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Linkage Disequilibrium, GWASs, Complex diseases, Minor alleles, Risk alleles, Negative natural selection, Medical Biochemistry and Metabolomics, Oncology and Carcinogenesis, Genetics & Heredity, Medical biochemistry and metabolomics
Abstract

BackgroundGenome-wide association studies (GWASs) have revealed relationships between over 57,000 genetic variants and diseases. However, unlike Mendelian diseases, complex diseases arise from the interplay of multiple genetic and environmental factors. Natural selection has led to a high tendency of risk alleles to be enriched in minor alleles in Mendelian diseases. Therefore, an allele that was previously advantageous or neutral may later become harmful, making it a risk allele.MethodsUsing data in the NHGRI-EBI Catalog and the VARIMED database, we investigated whether (1) GWASs more easily detect risk alleles and (2) facilitate evolutionary insights by comparing risk allele frequencies of different diseases. We conducted computer simulations of P-values for association tests when major and minor alleles were risk alleles. We compared the expected proportion of SNVs whose risk alleles were minor alleles with the observed proportion.ResultsOur statistical results revealed that risk alleles were enriched in minor alleles, especially for variants with low minor allele frequencies (MAFs  50% risk alleles were minor alleles because of the larger difference in the power of GWASs to differentiate between minor and major alleles, especially with low MAFs or when the number of controls exceeds the number of cases. However, the observed ratios between minor and major alleles in low MAFs (

Published
2018

20. HLA-B54 is an independent risk factor for pneumonia in Japanese patients with interstitial lung disease: A multicenter retrospective cohort study

Author

Sakamoto, Noriho, Ishimoto, Hiroshi, Tahara, Masahiro, Kido, Takashi, Hara, Atsuko, Miyamura, Takuto, Okuno, Daisuke, Tokito, Takatomo, Yoshioka, Sumako, Morimoto, Shimpei, Takazono, Takahiro, Yamamoto, Kazuko, Yamaguchi, Hiroyuki, Obase, Yasushi, Ishimatsu, Yuji, Yatera, Kazuhiro, and Mukae, Hiroshi

Published
2021
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22. Lung Involvement in Adult T-Cell Lymphoma Diagnosed Using Bronchoscopic Cryobiopsy: A Case Report and Review of the Literature

Author

Tanaka, Yasuhiro, primary, Kido, Takashi, additional, Sakamoto, Noriho, additional, Hara, Atsuko, additional, Kato, Takeharu, additional, Miyashita, Ritsuko, additional, Ozasa, Mutsumi, additional, Tokito, Takatomo, additional, Okuno, Daisuke, additional, Takeda, Kazuaki, additional, Yura, Hirokazu, additional, Takemoto, Shinnosuke, additional, Takazono, Takahiro, additional, Ishimoto, Hiroshi, additional, Obase, Yasushi, additional, Ishimatsu, Yuji, additional, Miyazaki, Yasushi, additional, and Mukae, Hiroshi, additional

Published
2023
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24. Combined detection of lymphocyte clonality and MALT1 translocations in bronchoalveolar lavage fluid for diagnosing pulmonary lymphomas

Author

Kido, Takashi, Ishimoto, Hiroshi, Ishii, Hiroshi, Hara, Kanako, Ozasa, Mutsumi, Kawabata, Hiroki, Kawanami, Toshinori, Suzuki, Yu, Yoshikawa, Hiroki, Hara, Atsuko, Sakamoto, Noriho, Matsumoto, Nobuhiro, Yoshii, Chiharu, Fukuoka, Junya, Fujita, Masaki, Nakazato, Masamitsu, Kadota, Junichi, Mukae, Hiroshi, and Yatera, Kazuhiro

Published
2021
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26. Pulmonary Langerhans cell histiocytosis diagnosed using transbronchial lung cryobiopsy: A case report

Author

Mine, Keisuke, primary, Sakamoto, Noriho, additional, Ozasa, Mutsumi, additional, Tsutsui, Shin, additional, Miyashita, Ritsuko, additional, Tokito, Takatomo, additional, Okuno, Daisuke, additional, Yura, Hirokazu, additional, Kido, Takashi, additional, Ishimoto, Hiroshi, additional, Takemoto, Shinnosuke, additional, Takazono, Takahiro, additional, Obase, Yasushi, additional, Ishimatsu, Yuji, additional, Fukuoka, Junya, additional, and Mukae, Hiroshi, additional

Published
2023
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27. HSP47: A Therapeutic Target in Pulmonary Fibrosis

Author

Sakamoto, Noriho, primary, Okuno, Daisuke, additional, Tokito, Takatomo, additional, Yura, Hirokazu, additional, Kido, Takashi, additional, Ishimoto, Hiroshi, additional, Tanaka, Yoshimasa, additional, and Mukae, Hiroshi, additional

Published
2023
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28. Disseminated Mycobacterium genavense Infection Mimicking Sarcoidosis: A Case Report and Review of Literature on Japanese Patients

Author

Ogata, Ryo, primary, Kido, Takashi, additional, Takeda, Kazuaki, additional, Nemoto, Kazuki, additional, Heima, Riko, additional, Takao, Mami, additional, Miyashita, Ritsuko, additional, Ozasa, Mutsumi, additional, Tokito, Takatomo, additional, Okuno, Daisuke, additional, Ito, Yuya, additional, Yura, Hirokazu, additional, Koga, Tomohiro, additional, Hashimoto, Kunio, additional, Takemoto, Shinnosuke, additional, Takazono, Takahiro, additional, Ishimoto, Hiroshi, additional, Sakamoto, Noriho, additional, Fukuda, Kazumasa, additional, Sasaki, Yuka, additional, Obase, Yasushi, additional, Ishimatsu, Yuji, additional, Yatera, Kazuhiro, additional, Izumikawa, Koichi, additional, and Mukae, Hiroshi, additional

Published
2023
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29. Pulmonary Langerhans Cell Histiocytosis That Progressed from a Single-system to a Multisystem Form despite Smoking Cessation

Author

Ishimoto, Hiroshi, Sakamoto, Noriho, Ozasa, Mutsumi, Katoh, Takeharu, Itonaga, Hidehiro, Wataya, Makoto, Takao, Daisuke, Hara, Atsuko, Kido, Takashi, Yamaguchi, Hiroyuki, Yamamoto, Kazuko, Obase, Yasushi, Ishimatsu, Yuji, Miyazaki, Yasushi, and Mukae, Hiroshi

Subjects
Internal Medicine, case report, cavitary lesion, nodular change, General Medicine, pulmonary Langerhans cell histiocytosis, smoking cessation
Abstract

A 36-year-old Japanese man presented with cavities and nodular shadows in the lower lobes of his lungs and osteolytic lesions in the thoracic spine. He was diagnosed with multisystem Langerhans cell histiocytosis (LCH). Three years earlier, he had been noted to have small cavities and granular lesions noted in the upper lobes of his lungs, which later improved with smoking cessation. It was likely that his single-system pulmonary LCH (PLCH) progressed to multisystem LCH despite smoking cessation. Relapse or progression may occur in cases where PLCH lesions improve after smoking cessation. Thus, close follow-up is vital., Internal Medicine, 62(6), pp.877-880; 2023

Published
2023

30. Japanese guideline for the treatment of idiopathic pulmonary fibrosis

Author

Homma, Sakae, Bando, Masashi, Azuma, Arata, Sakamoto, Susumu, Sugino, Keishi, Ishii, Yoshiki, Izumi, Shinyu, Inase, Naohiko, Inoue, Yoshikazu, Ebina, Masahito, Ogura, Takashi, Kishi, Kazuma, Kishaba, Tomoo, Kido, Takashi, Gemma, Akihiko, Goto, Yoshihito, Sasaki, Shinichi, Johkoh, Takeshi, Suda, Takafumi, Takahashi, Kazuhisa, Takahashi, Hiroki, Taguchi, Yoshio, Date, Hiroshi, Taniguchi, Hiroyuki, Nakayama, Takeo, Nishioka, Yasuhiko, Hasegawa, Yoshinori, Hattori, Noboru, Fukuoka, Junya, Miyamoto, Atsushi, Mukae, Hiroshi, Yokoyama, Akihito, Yoshino, Ichiro, and Watanabe, Kentaro

Published
2018
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31. Lymphocytic focus score is positively related to airway and interstitial lung diseases in primary Sjögren's syndrome

Author

Kakugawa, Tomoyuki, Sakamoto, Noriho, Ishimoto, Hiroshi, Shimizu, Toshimasa, Nakamura, Hideki, Nawata, Aya, Ito, Chiyo, Sato, Shuntaro, Hanaka, Tetsuya, Oda, Keishi, Kido, Takashi, Miyamura, Takuto, Nakashima, Shota, Aoki, Takatoshi, Nakamichi, Seiko, Obase, Yasushi, Saito, Kazuyoshi, Yatera, Kazuhiro, Ishimatsu, Yuji, Nakayama, Toshiyuki, Korogi, Yukunori, Kawakami, Atsushi, Tanaka, Yoshiya, and Mukae, Hiroshi

Published
2018
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35. Evaluation of the Effectiveness and Use of Anti-Methicillin-Resistant Staphylococcus aureus Agents for Aspiration Pneumonia in Older Patients Using a Nationwide Japanese Administrative Database

Author

Koga, Satoru, primary, Takazono, Takahiro, additional, Kido, Takashi, additional, Muramatsu, Keiji, additional, Tokutsu, Kei, additional, Tokito, Takatomo, additional, Okuno, Daisuke, additional, Ito, Yuya, additional, Yura, Hirokazu, additional, Takeda, Kazuaki, additional, Iwanaga, Naoki, additional, Ishimoto, Hiroshi, additional, Sakamoto, Noriho, additional, Yatera, Kazuhiro, additional, Izumikawa, Koichi, additional, Yanagihara, Katsunori, additional, Fujino, Yoshihisa, additional, Fushimi, Kiyohide, additional, Matsuda, Shinya, additional, and Mukae, Hiroshi, additional

Published
2023
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37. Impact of Administering Intravenous Azithromycin within 7 Days of Hospitalization for Influenza Virus Pneumonia: A Propensity Score Analysis Using a Nationwide Administrative Database

Author

Tokito, Takatomo, primary, Kido, Takashi, additional, Muramatsu, Keiji, additional, Tokutsu, Kei, additional, Okuno, Daisuke, additional, Yura, Hirokazu, additional, Takemoto, Shinnosuke, additional, Ishimoto, Hiroshi, additional, Takazono, Takahiro, additional, Sakamoto, Noriho, additional, Obase, Yasushi, additional, Ishimatsu, Yuji, additional, Fujino, Yoshihisa, additional, Yatera, Kazuhiro, additional, Fushimi, Kiyohide, additional, Matsuda, Shinya, additional, and Mukae, Hiroshi, additional

Published
2023
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42. Presence of heat shock protein 47-positive fibroblasts in cancer stroma is associated with increased risk of postoperative recurrence in patients with lung cancer

Author

Miyamura, Takuto, Sakamoto, Noriho, Ishida, Kaori, Kakugawa, Tomoyuki, Taniguchi, Hirokazu, Akiyama, Yoshiko, Okuno, Daisuke, Hara, Atsuko, Kido, Takashi, Ishimoto, Hiroshi, Miyazaki, Takuro, Matsumoto, Keitaro, Tsuchiya, Tomoshi, Yamaguchi, Hiroyuki, Miyazaki, Taiga, Obase, Yasushi, Ishimatsu, Yuji, Nagayasu, Takeshi, and Mukae, Hiroshi

Published
2020
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44. Reports of the AAAI 2019 Spring Symposium Series

Author

Baldini, Ioana, Barrett, Clark, Chella, Antonio, Cinelli, Carlos, Gamez, David, Gilpin, Leilani H., Hinkelmann, Knut, Holmes, Dylan, Kido, Takashi, Kocaoglu, Murat, Lawless, William F., Lomuscio, Alessio, Macbeth, Jamie C., Martin, Andreas, Mittu, Ranjeev, Patterson, Evan, Sofge, Donald, Tadepalli, Prasad, Takadama, Keiki, and Wilson, Shomir

Subjects
Privacy -- Conferences, meetings and seminars -- Forecasts and trends, Machine learning -- Conferences, meetings and seminars -- Forecasts and trends, Natural language processing -- Conferences, meetings and seminars -- Forecasts and trends, Social networks -- Conferences, meetings and seminars -- Forecasts and trends, Artificial neural networks -- Conferences, meetings and seminars -- Forecasts and trends, Cognitive biases, Technology, Neural network, Market trend/market analysis, Privacy issue, Business, Stanford University -- Conferences, meetings and seminars
Abstract

* The AAAI 2019 Spring Symposium Series was held Monday through Wednesday, March 25-27, 2019, on the campus of Stanford University, adjacent to Palo Alto, California. The titles of the [...]

Published
2019

45. Reports on the 2018 AAAI Spring Symposium Series

Author

Amato, Christopher, Ammar, Haitham Bou, Churchill, Elizabeth, Karpas, Erez, Kido, Takashi, Kuniavsky, Mike, Lawless, W.F., Oliehoek, Frans A., Rossi, Francesca, Russell, Stephen, Srivastava, Siddharth, Takadama, Keiki, van Allen, Philip, Venable, K. Brent, Tuyls, Karl, Vrancx, Peter, and Zhang, Shiqi

Subjects
Business
Abstract

The Association for the Advancement of Artificial Intelligence, in cooperation with Stanford University's Department of Computer Science, presented the 2018 Spring Symposium Series, held March 26-28, 2018, on the campus [...]

Published
2018

47. A case of drug-induced organizing pneumonia caused by amikacin liposome inhalation suspension

Author

Takao, Daisuke, primary, Takeda, Kazuaki, additional, Takazono, Takahiro, additional, Ozasa, Mutsumi, additional, Ito, Yuya, additional, Ashizawa, Nobuyuki, additional, Hirayama, Tatsuro, additional, Iwanaga, Naoki, additional, Takemoto, Shinnosuke, additional, Ide, Shotaro, additional, Tashiro, Masato, additional, Hosogaya, Naoki, additional, Kido, Takashi, additional, Sakamoto, Noriho, additional, Obase, Yasushi, additional, Okano, Shinji, additional, Izumikawa, Koichi, additional, Yanagihara, Katsunori, additional, and Mukae, Hiroshi, additional

Published
2023
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48. Urinary titin N-fragment as a predictor of decreased skeletal muscle mass in patients with interstitial lung diseases

Author

Hanada, Masatoshi, Ishimatsu, Yuji, Sakamoto, Noriho, Akiyama, Yoshiko, Kido, Takashi, Ishimoto, Hiroshi, Oikawa, Masato, Nagura, Hiroki, Takeuchi, Rina, Sato, Shuntaro, Takahata, Hideaki, Mukae, Hiroshi, Kozu, Ryo, Hanada, Masatoshi, Ishimatsu, Yuji, Sakamoto, Noriho, Akiyama, Yoshiko, Kido, Takashi, Ishimoto, Hiroshi, Oikawa, Masato, Nagura, Hiroki, Takeuchi, Rina, Sato, Shuntaro, Takahata, Hideaki, Mukae, Hiroshi, and Kozu, Ryo

Abstract

This study aimed to examine the validity of urinary N-terminal titin fragment/creatinine (urinary N-titin/Cr) reflecting muscle damage biomarker in patients with interstitial lung disease. This retrospective study enrolled patients with interstitial lung disease. We measured urinary N-titin/Cr. Furthermore, we measured the cross-sectional areas of the pectoralis muscles above the aortic arch (PMCSA) and erector spinae muscles of the 12th thoracic vertebra muscles (ESMCSA) to assess muscle mass until 1 year. We examined the correlation between urinary N-titin/Cr and the change in muscle mass. We plotted receiver operating characteristic curves to estimate the cut-off points for urinary N-titin/Cr for distinguishing the greater-than-median and smaller-than-median reduction of muscle mass after 1 year. We enrolled 68 patients with interstitial lung disease. The median urinary N-titin/Cr value was 7.0 pmol/mg/dL. We observed significant negative correlations between urinary N-titin/Cr and changes in the PMCSA after 1 year (p < 0.001) and changes in the ESMCSA after 6 months (p < 0.001) and 1 year (p < 0.001). The cut-off points for urinary N-titin/Cr were 5.2 pmol/mg/dL and 10.4 pmol/mg/dL in the PMCSA and ESMCSA, respectively. In summary, urinary N-titin/Cr may predict muscle loss in the long-term and act as a clinically useful biomarker reflecting muscle damage., Scientific Reports, 13(1), art. no. 9723; 2023

Published
2023

49. Disseminated Mycobacterium genavense Infection Mimicking Sarcoidosis: A Case Report and Review of Literature on Japanese Patients

Author

Ogata, Ryo, Kido, Takashi, Takeda, Kazuaki, Nemoto, Kazuki, Heima, Riko, Takao, Mami, Miyashita, Ritsuko, Ozasa, Mutsumi, Tokito, Takatomo, Okuno, Daisuke, Ito, Yuya, Yura, Hirokazu, Koga, Tomohiro, Hashimoto, Kunio, Takemoto, Shinnosuke, Takazono, Takahiro, Ishimoto, Hiroshi, Sakamoto, Noriho, Fukuda, Kazumasa, Sasaki, Yuka, Obase, Yasushi, Ishimatsu, Yuji, Yatera, Kazuhiro, Izumikawa, Koichi, Mukae, Hiroshi, Ogata, Ryo, Kido, Takashi, Takeda, Kazuaki, Nemoto, Kazuki, Heima, Riko, Takao, Mami, Miyashita, Ritsuko, Ozasa, Mutsumi, Tokito, Takatomo, Okuno, Daisuke, Ito, Yuya, Yura, Hirokazu, Koga, Tomohiro, Hashimoto, Kunio, Takemoto, Shinnosuke, Takazono, Takahiro, Ishimoto, Hiroshi, Sakamoto, Noriho, Fukuda, Kazumasa, Sasaki, Yuka, Obase, Yasushi, Ishimatsu, Yuji, Yatera, Kazuhiro, Izumikawa, Koichi, and Mukae, Hiroshi

Abstract

Sarcoidosis is a systemic inflammatory disease characterized by noncaseating epithelioid cell granulomas. However, certain infections can exhibit similar histological findings. We present a case of a 69-year-old man who was initially diagnosed with sarcoidosis and later was confirmed, through 16S rRNA sequencing, to have disseminated Mycobacterium genavense infection. Acid-fast bacteria were detected in the bone marrow biopsy using Ziehl–Neelsen staining, but routine clinical tests did not provide a definitive diagnosis. The patient tested negative for HIV, anti-interferongamma antibodies, and genetic immunodeficiency disorders. He was treated with multiple drugs, including aminoglycosides and macrolides, but showed no improvement in fever and pancytopenia. However, these clinical signs responded favorably to steroid therapy. We reviewed 17 Japanese cases of M. genavense infection. All cases were in males; 7/17 (41%) were HIV-negative; and 12/17 (71%) had a decreased CD4 count. Genetic analysis confirmed M. genavense isolation, and macrolides were used universally. Mycobacterium genavense infection is challenging to identify and mimics other systemic inflammatory diseases such as sarcoidosis. There are no standard treatment protocols. Our case report and Japanese case review contribute to understanding this rare disease., Microorganisms, 11(9), art. no. 2145; 2023

Published
2023

50. Evaluation of the Effectiveness and Use of Anti-Methicillin-Resistant Staphylococcus aureus Agents for Aspiration Pneumonia in Older Patients Using a Nationwide Japanese Administrative Database

Author

Koga, Satoru, Takazono, Takahiro, Kido, Takashi, Muramatsu, Keiji, Tokutsu, Kei, Tokito, Takatomo, Okuno, Daisuke, Ito, Yuya, Yura, Hirokazu, Takeda, Kazuaki, Iwanaga, Naoki, Ishimoto, Hiroshi, Sakamoto, Noriho, Yatera, Kazuhiro, Izumikawa, Koichi, Yanagihara, Katsunori, Fujino, Yoshihisa, Fushimi, Kiyohide, Matsuda, Shinya, Mukae, Hiroshi, Koga, Satoru, Takazono, Takahiro, Kido, Takashi, Muramatsu, Keiji, Tokutsu, Kei, Tokito, Takatomo, Okuno, Daisuke, Ito, Yuya, Yura, Hirokazu, Takeda, Kazuaki, Iwanaga, Naoki, Ishimoto, Hiroshi, Sakamoto, Noriho, Yatera, Kazuhiro, Izumikawa, Koichi, Yanagihara, Katsunori, Fujino, Yoshihisa, Fushimi, Kiyohide, Matsuda, Shinya, and Mukae, Hiroshi

Abstract

Studies indicated potential harm from empirical broad-spectrum therapy. A recent study of hospitalizations for community-acquired pneumonia suggested that empirical anti-methicillin-resistant Staphylococcus aureus (MRSA) therapy was associated with an increased risk of death and other complications. However, limited evidence supports empirical anti-MRSA therapy for older patients with aspiration pneumonia. In a nationwide Japanese database, patients aged ≥65 years on admission with aspiration pneumonia were analyzed. Patients were divided based on presence of respiratory failure and further sub-categorized based on their condition within 3 days of hospital admission, either receiving a combination of anti-MRSA agents and other antibiotics, or not using MRSA agents. An inverse probability weighting method with estimated propensity scores was used. Out of 81,306 eligible patients, 55,098 had respiratory failure, and 26,208 did not. In the group with and without respiratory failure, 0.93% and 0.42% of the patients, respectively, received anti-MRSA agents. In patients with respiratory failure, in-hospital mortality (31.38% vs. 19.03%, p < 0.001), 30-day mortality, and 90-day mortality were significantly higher, and oxygen administration length was significantly longer in the anti-MRSA agent combination group. Anti-MRSA agent combination use did not improve the outcomes in older patients with aspiration pneumonia and respiratory failure, and should be carefully and comprehensively considered., Microorganisms, 11(8), art. no. 1905; 2023

Published
2023

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