Experimental Biology and Medicine最新文献

{"title":"Research of restricted migration evaluation of MDA-MB-231 cells in 2D and 3D co-culture models.","authors":"Zhichang Du, Shaohui Yang, Qingzhong Gong, Zhonghua Lin, Guohong Xiao, Shengli Mi","doi":"10.1177/15353702231214269","DOIUrl":"10.1177/15353702231214269","url":null,"abstract":"<p><p>The restricted migration evaluation is conducive to more complex tumor migration research because of the conformity with <i>in vivo</i> tumors. However, the differences between restricted and unrestricted cell migration and the distinction between different evaluation methods have not been systematically studied, hindering related research. In this study, by constructing the restricted environments on chips, the influence of co-culture conditions on the cancer cell migration capacity was studied. The results showed that the restricted channels can discriminate the influence of weak tumor environmental factors on complex tumor migration behaviors by limiting the free growth instinct of tumor cells. Through the comparison of 2D and 3D restricted migration methods, the extracellular matrix (ECM) restriction was also helpful in distinguishing the influence of the weak tumor environmental factor. However, the 3D ECM can better reflect the tortuosity of the cell migration process and the cooperative behavior among cancer cells. In the anticancer drug evaluation, 3D ECM can more accurately reflect the cytotoxicity of drugs and is more consistent with the drug resistance in the human body. In conclusion, the research will help to distinguish different evaluation methods of cancer cell migration, help researchers select appropriate evaluation models, and promote the research of tumor metastasis.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10903235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139490890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms maintaining cerebral perfusion during systemic hypotension are impaired in elderly adults.","authors":"Kulsum Abdali, Xiaoan Chen, Sarah Ross, Sandra Davis, Zhengyang Zhou, Robert T Mallet, Xiangrong Shi","doi":"10.1177/15353702231209416","DOIUrl":"10.1177/15353702231209416","url":null,"abstract":"<p><p>Postural hypotension abruptly lowers cerebral perfusion, producing unsteadiness which worsens with aging. This study addressed the hypothesis that maintenance of cerebral perfusion weakens in the elderly due to less effective cerebrovascular autoregulation and systemic cardiovascular responses to hypotension. In healthy elderly (<i>n</i> = 13, 68 ± 1 years) and young (<i>n</i> = 13, 26 ± 1 years) adults, systemic hypotension was induced by rapid deflation of bilateral thigh cuffs after 3-min suprasystolic occlusion, while heart rate (HR), mean arterial pressure (MAP), and blood flow velocity of the middle cerebral artery (V_MCA) were recorded. V_MCA/MAP indexed cerebrovascular conductance (CVC). Durations and rates of recovery of MAP and V_MCA from their respective postdeflation nadirs were compared between the groups. Thigh-cuff deflation elicited similar hypotension and cerebral hypoperfusion in the elderly and young adults. However, the time elapsed (T_Δ) from cuff deflation to the nadirs of MAP and V_MCA, and the time for full recovery (T_R) from nadirs to baselines were significantly prolonged in the elderly subjects. The response rates of HR (ΔHR, i.e. cardiac factor), MAP (ΔMAP, i.e. vasomotor factor), and CVC following cuff deflation were significantly slower in the elderly. Collectively, the response rates of the cardiac, vasomotor, and CVC factors largely explained T_RVMCA. However, the T_RVMCA/ΔMAP slope (-3.0 ± 0.9) was steeper (<i>P</i> = 0.046) than the T_RVMCA/ΔHR slope (-1.1 ± 0.4). The T_RVMCA/ΔCVC slope (-2.4 ± 0.6) was greater (<i>P</i> = 0.072) than the T_RVMCA/ΔHR slope, but did not differ from the T_RVMCA/ΔMAP slope (<i>P</i> = 0.52). Both cerebrovascular autoregulatory and systemic mechanisms contributed to cerebral perfusion recovery during systemic hypotension, and the vasomotor factor was predominant over the cardiac factor. Recovery from cerebral hypoperfusion was slower in the elderly adults because of the age-diminished rates of the CVC response and cardiovascular reflex regulation. Systemic vasoconstriction predominated over increased HR for restoring cerebral perfusion after abrupt onset of systemic hypotension.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10903242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138498199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quercetin suppresses ovariectomy-induced osteoporosis in rat mandibles by regulating autophagy and the NLRP3 pathway.","authors":"Yue Xiong, Cheng-Wei Huang, Chao Shi, Liang Peng, Yu-Ting Cheng, Wei Hong, Jian Liao","doi":"10.1177/15353702231211977","DOIUrl":"10.1177/15353702231211977","url":null,"abstract":"<p><p>With the aging population and the popularity of implant prostheses, an increasing number of postmenopausal osteoporosis (PMOP) patients require implant restorations; however, poor bone condition affects the long-term stability of implant prostheses. This study aimed to investigate the therapeutic effect of quercetin (QR) compared with alendronate (ALN), the primary treatment for PMOP, on mandibular osteoporosis (OP) induced by ovariectomy (OVX) in female rats. Adult female rats were treated with QR (50 mg/kg/day), ALN (6.25 mg/kg/week) by gavage for 8 weeks, chloroquine (CQ, 10 mg/kg/twice a week), and cytokine release inhibitory drug 3 (MCC950, 10 mg/kg/three times a week) by intraperitoneal injection for 8 weeks after bilateral OVX. Blood samples were collected prior to euthanasia; the mandibles were harvested and subjected to micro-computed tomography (micro-CT) and pathological analysis. QR administration controlled weight gain and significantly improved the bone microstructure in OVX rats, increasing bone mass, and bone mineral density (BMD), reducing bone trabecular spacing, and decreasing osteoclast numbers. Western blotting, real-time quantitative PCR (RT-qPCR), and serum markers confirmed that QR inhibited interleukin- 1β (IL-1β) and interleukin-18 (IL-18) on the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) protein 3 (NLRP3) pathway thereby inhibiting osteoclast differentiation, immunofluorescence and western blotting also confirmed that QR inhibited autophagy in OVX rats and suppressed the number of tartrate-resistant acid phosphatase (TRAP)-stained positive osteoclasts. The findings suggest that QR may protect the bone structure and prevent bone loss in osteoporotic rats by inhibiting the NLRP3 pathway and autophagy in osteoclasts with comparable effects to ALN, thus QR may have the potential to be a promising alternative supplement for the preventive and therapeutic treatment of PMOP.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10903250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139490885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic profile of the mechanosensitive ion channelome in human cardiac fibroblasts.","authors":"Vadim Mitrokhin, Andrei Bilichenko, Viktor Kazanski, Roman Schobik, Stanislav Shileiko, Veronika Revkova, Vladimir Kalsin, Olga Kamkina, Andre Kamkin, Mitko Mladenov","doi":"10.1177/15353702231218488","DOIUrl":"10.1177/15353702231218488","url":null,"abstract":"<p><p>Human cardiac fibroblasts (HCFs) have mRNA transcripts that encode different mechanosensitive ion channels and channel regulatory proteins whose functions are not known yet. The primary goal of this work was to define the mechanosensitive ion channelome of HCFs. The most common type of cationic channel is the transient receptor potential (TRP) family, which is followed by the TWIK-related K⁺ channel (TREK), transmembrane protein 63 (TMEM63), and PIEZO channel (PIEZO) families. In the sodium-dependent NON-voltage-gated channel (SCNN) subfamily, only SCNN1D was shown to be highly expressed. Particular members of the acid-sensing ion channel (ASIC) (ASIC1 and ASIC3) subfamilies were also significantly expressed. The transcripts per kilobase million (TPMs) for Piezo 2 were almost 100 times less abundant than those for Piezo 1. The tandem of P domains in a weak inward rectifying K⁺ channel (TWIK)-2 channel, TWIK-related acid-sensitive K⁺ channel (TASK)-5, TASK-1, and the TWIK-related K1 (TREK-1) channel were the four most prevalent types in the K2P subfamily. The highest expression in the TRPP subfamily was found for PKD2 and PKD1, while in the TRPM subfamily, it was found for TRPM4, TRPM7, and TRPM3. TRPV2, TRPV4, TRPV3, and TRPV6 (all members of the TRPV subfamily) were also substantially expressed. A strong expression of the TRPC1, TRPC4, TRPC6, and TRPC2 channels and all members of the TRPML subfamily (MCOLN1, MCOLN2, and MCOLN3) was also shown. In terms of the transmembrane protein 16 (TMEM16) family, the HCFs demonstrated significant expression of the TMEM16H, TMEM16F, TMEM16J, TMEM16A, and TMEM16G channels. TMC3 is the most expressed channel in HCFs of all known members of the transmembrane channel-like protein (TMC) family. This analysis of the mechanosensitive ionic channel transcriptome in HCFs: (1) agrees with previously documented findings that all currently identified mechanosensitive channels play a significant and well recognized physiological function in elucidating the mechanosensitive characteristics of HCFs; (2) supports earlier preliminary reports that point to the most common expression of the TRP mechanosensitive family in HCFs; and (3) points to other new mechanosensitive channels (TRPC1, TRPC2, TWIK-2, TMEM16A, ASIC1, and ASIC3).</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10903254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139073799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insulin-like growth factor 2 mRNA-binding protein 2 is a therapeutic target in ovarian cancer.","authors":"Jia Yuan, Xin Li, Fanchen Wang, Huiqiang Liu, Wencai Guan, Guoxiong Xu","doi":"10.1177/15353702231214268","DOIUrl":"10.1177/15353702231214268","url":null,"abstract":"<p><p>Ovarian cancer (OC) is a fatal gynecologic disease. The most common treatment for OC patients is surgery combined with chemotherapy but most patients at advanced stages eventually develop relapse due to chemoresistance. This study examined the role and function of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) in OC. We observed that the expression of IGF2BP2 mRNA and protein was up-regulated in OC cells and tissues using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot, respectively. An increase in IGF2BP2 expression at mRNA and protein levels was verified by the analyses of The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC), respectively. Gene Expression Omnibus (GEO) and Cancer Cell Line Encyclopedia (CCLE) databases were applied to analyze the expression and clinical value of IGF2BP2. Gene set enrichment analysis (GSEA), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology (GO) analyses explored biological functions and the involvement of IGF2BP2 in cell growth. Indeed, the knockdown of IGF2BP2 resulted in the inhibition of OC cell proliferation evaluated by the Cell Counting Kit-8 assay. Genomic amplification of IGF2BP2 partly accounted for its overexpression. High expression of IGF2BP2 was associated with signal transducer and activator of transcription 1 (STAT1) and drug sensitivity and was correlated with an unfavorable survival outcome in OC patients. Furthermore, the responsiveness of chemotherapy and immunotherapy were analyzed using the \"pRRophetic\" R package and The Cancer Immune Atlas (TCIA) database, respectively. The low expression of IGF2BP2 was associated with chemoresistance but with high tumor microenvironment scores and tumor-infiltrating immune cells, suggesting that immunotherapy may apply in chemoresistant patients. The alteration of IGF2BP2 expression may respond to chemotherapy and immunotherapy. Thus, IGF2BP2 shows potential as a therapeutic target and diagnostic biomarker for OC.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10903241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138801371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Visceral fat sympathectomy ameliorates systemic and local stress response related to chronic sleep restriction.","authors":"Lucia E Azuara-Alvarez, Mauricio Díaz-Muñoz, Adrián Báez Ruiz, Nadia Saderi, Oscar Daniel Ramírez-Plascencia, Skarleth Cárdenas-Romero, Omar Flores-Sandoval, Roberto Salgado-Delgado","doi":"10.1177/15353702231214267","DOIUrl":"10.1177/15353702231214267","url":null,"abstract":"<p><p>Disturbance of sleep homeostasis encompasses health issues, including metabolic disorders like obesity, diabetes, and augmented stress vulnerability. Sleep and stress interact bidirectionally to influence the central nervous system and metabolism. Murine models demonstrate that decreased sleep time is associated with an increased systemic stress response, characterized by endocrinal imbalance, including the elevated activity of hypothalamic-pituitary-adrenal axis, augmented insulin, and reduced adiponectin, affecting peripheral organs physiology, mainly the white adipose tissue (WAT). Within peripheral organs, a local stress response can also be activated by promoting the formation of corticosterone. This local amplifying glucocorticoid signaling is favored through the activation of the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). In WAT, 11β-HSD1 activity is upregulated by the sympathetic nervous system, suggesting a link between sleep loss, augmented stress response, and a potential WAT metabolic disturbance. To gain more understanding about this relationship, metabolic and stress responses of WAT-sympathectomized rats were analyzed to identify the contribution of the autonomic nervous system to stress response-related metabolic disorders during chronic sleep restriction. Male Wistar rats under sleep restriction were allowed just 6 h of daily sleep over eight weeks. Results showed that rats under sleep restriction presented higher serum corticosterone, increased adipose tissue 11β-HSD1 activity, weight loss, decreased visceral fat, augmented adiponectin, lower leptin levels, glucose tolerance impairment, and mildly decreased daily body temperature. In contrast, sympathectomized rats under sleep restriction exhibited decreased stress response (lower serum corticosterone and 11β-HSD1 activity). In addition, they maintained weight loss, explained by a reduced visceral fat pad, leptin, and adiponectin, improved glucose management, and persisting decline in body temperature. These results suggest autonomic nervous system is partially responsible for the WAT-exacerbated stress response and its metabolic and physiological disturbances.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10903249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139032154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A quantum-based oversampling method for classification of highly imbalanced and overlapped data.","authors":"Bei Yang, Guilan Tian, Joseph Luttrell, Ping Gong, Chaoyang Zhang","doi":"10.1177/15353702231220665","DOIUrl":"10.1177/15353702231220665","url":null,"abstract":"<p><p>Data imbalance is a challenging problem in classification tasks, and when combined with class overlapping, it further deteriorates classification performance. However, existing studies have rarely addressed both issues simultaneously. In this article, we propose a novel quantum-based oversampling method (QOSM) to effectively tackle data imbalance and class overlapping, thereby improving classification performance. QOSM utilizes the quantum potential theory to calculate the potential energy of each sample and selects the sample with the lowest potential as the center of each cover generated by a constructive covering algorithm. This approach optimizes cover center selection and better captures the distribution of the original samples, particularly in the overlapping regions. In addition, oversampling is performed on the samples of the minority class covers to mitigate the imbalance ratio (IR). We evaluated QOSM using three traditional classifiers (support vector machines [SVM], k-nearest neighbor [KNN], and naive Bayes [NB] classifier) on 10 publicly available KEEL data sets characterized by high IRs and varying degrees of overlap. Experimental results demonstrate that QOSM significantly improves classification accuracy compared to approaches that do not address class imbalance and overlapping. Moreover, QOSM consistently outperforms existing oversampling methods tested. With its compatibility with different classifiers, QOSM exhibits promising potential to improve the classification performance of highly imbalanced and overlapped data.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10854475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139569636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developing a SARS-CoV-2 main protease binding prediction random forest model for drug repurposing for COVID-19 treatment.","authors":"Jie Liu, Liang Xu, Wenjing Guo, Zoe Li, Md Kamrul Hasan Khan, Weigong Ge, Tucker A Patterson, Huixiao Hong","doi":"10.1177/15353702231209413","DOIUrl":"10.1177/15353702231209413","url":null,"abstract":"<p><p>The coronavirus disease 2019 (COVID-19) global pandemic resulted in millions of people becoming infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and close to seven million deaths worldwide. It is essential to further explore and design effective COVID-19 treatment drugs that target the main protease of SARS-CoV-2, a major target for COVID-19 drugs. In this study, machine learning was applied for predicting the SARS-CoV-2 main protease binding of Food and Drug Administration (FDA)-approved drugs to assist in the identification of potential repurposing candidates for COVID-19 treatment. Ligands bound to the SARS-CoV-2 main protease in the Protein Data Bank and compounds experimentally tested in SARS-CoV-2 main protease binding assays in the literature were curated. These chemicals were divided into training (516 chemicals) and testing (360 chemicals) data sets. To identify SARS-CoV-2 main protease binders as potential candidates for repurposing to treat COVID-19, 1188 FDA-approved drugs from the Liver Toxicity Knowledge Base were obtained. A random forest algorithm was used for constructing predictive models based on molecular descriptors calculated using Mold2 software. Model performance was evaluated using 100 iterations of fivefold cross-validations which resulted in 78.8% balanced accuracy. The random forest model that was constructed from the whole training dataset was used to predict SARS-CoV-2 main protease binding on the testing set and the FDA-approved drugs. Model applicability domain and prediction confidence on drugs predicted as the main protease binders discovered 10 FDA-approved drugs as potential candidates for repurposing to treat COVID-19. Our results demonstrate that machine learning is an efficient method for drug repurposing and, thus, may accelerate drug development targeting SARS-CoV-2.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10798185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138298827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"X-linked hypophosphatemia, fibroblast growth factor 23 signaling, and craniosynostosis.","authors":"Chelsey Grimbly, Daniel Graf, Leanne M Ward, R Todd Alexander","doi":"10.1177/15353702231222023","DOIUrl":"10.1177/15353702231222023","url":null,"abstract":"<p><p>This review summarizes the current knowledge of fibroblast growth factor 23 signaling in bone and its role in the disease pathology of X-linked hypophosphatemia. Craniosynostosis is an under-recognized complication of X-linked hypophosphatemia. The clinical implications and potential cellular mechanisms invoked by increased fibroblast growth factor 23 signaling causing craniosynostosis are reviewed. Knowledge gaps are identified and provide direction for future clinical and basic science studies.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10800125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139477724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bidirectional Encoder Representations from Transformers-like large language models in patient safety and pharmacovigilance: A comprehensive assessment of causal inference implications.","authors":"Xingqiao Wang, Xiaowei Xu, Zhichao Liu, Weida Tong","doi":"10.1177/15353702231215895","DOIUrl":"10.1177/15353702231215895","url":null,"abstract":"<p><p>Causality assessment is vital in patient safety and pharmacovigilance (PSPV) for safety signal detection, adverse reaction management, and regulatory submission. Large language models (LLMs), especially those designed with transformer architecture, are revolutionizing various fields, including PSPV. While attempts to utilize Bidirectional Encoder Representations from Transformers (BERT)-like LLMs for causal inference in PSPV are underway, a detailed evaluation of \"fit-for-purpose\" BERT-like model selection to enhance causal inference performance within PSPV applications remains absent. This study conducts an in-depth exploration of BERT-like LLMs, including generic pre-trained BERT LLMs, domain-specific pre-trained LLMs, and domain-specific pre-trained LLMs with safety knowledge-specific fine-tuning, for causal inference in PSPV. Our investigation centers around (1) the influence of data complexity and model architecture, (2) the correlation between the BERT size and its impact, and (3) the role of domain-specific training and fine-tuning on three publicly accessible PSPV data sets. The findings suggest that (1) BERT-like LLMs deliver consistent predictive power across varied data complexity levels, (2) the predictive performance and causal inference results do not directly correspond to the BERT-like model size, and (3) domain-specific pre-trained LLMs, with or without safety knowledge-specific fine-tuning, surpass generic pre-trained BERT models in causal inference. The findings are valuable to guide the future application of LLMs in a broad range of application.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10798182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138801352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}