217 results on '"Lin GH"'
Search Results
2. The Effect of Antidepressants on Dental Implant Failure: A Systematic Review and Meta-analysis.
- Author
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Harutyunyan L, Lieuw K, Yang B, Lee E, Yeh YT, Chen HH, and Lin GH
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- Humans, Risk Factors, Selective Serotonin Reuptake Inhibitors adverse effects, Selective Serotonin Reuptake Inhibitors therapeutic use, Antidepressive Agents adverse effects, Antidepressive Agents therapeutic use, Dental Implants statistics & numerical data, Dental Restoration Failure statistics & numerical data
- Abstract
Purpose: To analyze the risk of dental implant failure for patients with a history of antidepressant use through a systematic review and meta-analysis., Materials and Methods: An electronic search was performed up to June 2023 in three databases including PubMed/MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials; data on the comparison of implant failure rate for patients with and without the use of antidepressants were included. Meta-analyses for the risk ratio of implant failure rate at patient level and implant level were performed., Results: Overall, 11 clinical studies were selected for inclusion in this review. The meta-analyses showed a risk ratio of 2.44 (95% CI = 1.75 to 3.39; P < .0001) and 2.44 (95% CI = 1.73 to 3.46; P < .0001) for the implant failure at patient level and implant level, respectively. The comparisons presented a low heterogeneity for the patient-level analysis and a moderate heterogeneity for the implant-level analysis among the pooled studies. Subgroup analyses also revealed that patients who received only selective serotonin reuptake inhibitors (SSRIs) or SSRIs with other types of antidepressants had a higher risk of implant failure than those who were not on any antidepressants., Conclusions: The current review demonstrates that the use of antidepressants such as SSRIs may increase the risk of dental implant failure at both patient level and implant level. Although limited evidence suggests that a certain type of SSRI (sertraline) may have more influence on implant failure than other SSRIs, future studies are needed to confirm this finding.
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- 2024
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3. Survival rate of teeth adjacent and nonadjacent to dental implants: A retrospective cohort study.
- Author
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Chen HH, Lin GH, Kao RT, and Yeh YT
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- Humans, Retrospective Studies, Male, Female, Middle Aged, Adult, Aged, Cohort Studies, Follow-Up Studies, Tooth Fractures etiology, Root Canal Therapy statistics & numerical data, Root Canal Therapy adverse effects, Tooth Root injuries, Risk Factors, Young Adult, Aged, 80 and over, Dental Implants adverse effects, Tooth Loss
- Abstract
Background: The aim of this retrospective study was to investigate the risk of tooth loss for teeth adjacent and nonadjacent to dental implants., Methods: A total of 787 patients with an average follow-up of 57.1 months were examined to define the tooth loss, cumulative survival rate, and odds ratio (OR) for teeth adjacent versus nonadjacent to implants. A multivariate logistic regression was employed to assess the association between dental history and various recorded etiologies of tooth loss among teeth adjacent to implants., Results: The incidence of tooth loss for teeth adjacent to implants was 8.1% at the tooth level and 15.1% at the patient level, while 0.7% and 9.5% at the tooth and patientlevel for teeth nonadjacent to implants. The 10-year cumulative survival rate for teeth adjacent to implants was 89.2%, and the primary etiology of tooth loss was root fracture (45.2%). The risk of tooth loss among teeth adjacent versus nonadjacent to implants was significantly higher (OR 13.15). Among teeth adjacent to implants, root canal-treated teeth had a significantly higher risk of tooth loss due to root fracture (OR 7.72), a history of existing restoration significantly increased the risk of tooth loss due to caries (OR 3.05), and a history of periodontitis significantly increased the risk of tooth loss due to periodontitis (OR 38.24)., Conclusion: The present study demonstrated that after patients received dental implant treatment, teeth adjacent to implants showed a 13.2-fold higher risk of tooth loss compared to teeth nonadjacent to implants, with the primary etiology being root fracture., (© 2024 American Academy of Periodontology.)
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- 2024
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4. eHealth Interventions of Health Literacy for Stroke Survivors: Systematic Review and Meta-Analysis.
- Author
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Vu MTT, Ho HQ, and Lin GH
- Abstract
Background: eHealth literacy interventions have emerged as a new approach in management of stroke survivors. Its effect on knowledge and clinical outcomes presents an inconsistent result in literature., Objectives: We aim to evaluate the impact of eHealth interventions on health literacy, clinical metrics, adherence to healthy behaviors, stroke recurrence, mortality, and health-related quality of life in stroke survivors., Methods: We systematically searched six databases (PubMed, Cochrane Library, CINAHL, EMBASE, Web of Science, ProQuest) up to February 21, 2024, selecting articles that meet these criteria: (i) patients with stroke; (ii) intervention with education content; (iii) eHealth interventions included telehealth, mobile phone, internet or computer; (iv) randomized controlled trials. The mean differences (MD) and standardized mean differences (SMD) between groups were measured. Risk of bias was evaluated using the Cochrane tool., Results: From 16 studies involving 9646 participants, we observed that eHealth interventions significantly improved systolic blood pressure (MD = -2.78 mmHg, 95% confidence interval (CI) [-4.67 to -0.88], p = 0.004), medication adherence (SMD = 0.28, 95% CI [0.04 to 0.52], p = 0.023), and health-related quality of life (SMD = 0.21, 95% CI [0.04 to 0.37], p = 0.013). Meta-regression found that age modified the effect size of systolic blood pressure (p = 0.027). There was insufficient evidence to conclude effects on other outcomes. The quality of evidence was moderate. Outcome variation may be due to the diversity in eHealth intervention approaches. The limited number of studies precluded the subgroup analysis. More interactive interventions with longer follow-ups were more effective., Conclusions: eHealth interventions may benefit stroke survivors in terms of blood pressure, medication adherence, and health-related quality of life., Implications for Nursing Policy: eHealth literacy interventions could be implemented to improve the management of stroke survivors, especially in the context of resource limitations., Trial Registration: PROSPERO registration number: CRD42024502470., (© 2024 Wiley Periodicals LLC.)
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- 2024
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5. Crown-to-implant ratio: A misnomer.
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Misch CM and Lin GH
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- Humans, Dental Implants, Crowns
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- 2024
6. The burden of diagnostic error in dentistry: A study on periodontal disease misclassification.
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Tokede B, Yansane A, Brandon R, Lin GH, Lee CT, White J, Jiang X, Lee E, Alsaffar A, Walji M, and Kalenderian E
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- Humans, Retrospective Studies, Female, Male, Middle Aged, Adult, Diagnostic Errors statistics & numerical data, Periodontal Diseases diagnosis, Periodontal Diseases classification, Periodontal Diseases epidemiology, Electronic Health Records, Algorithms
- Abstract
Background: Periodontal disease constitutes a widely prevalent category of non-communicable diseases and ranks among the top 10 causes of disability worldwide. Little however is known about diagnostic errors in dentistry. In this work, by retrospectively deploying an electronic health record (EHR)-based trigger tool, followed by gold standard manual review, we provide epidemiological estimates on the rate of diagnostic misclassification in dentistry through a periodontal use case., Methods: An EHR-based trigger tool (a retrospective record review instrument that uses a list of triggers (or clues), i.e., data elements within the health record, to alert reviewers to the potential presence of a wrong diagnosis) was developed, tested and run against the EHR at the two participating sites to flag all cases having a potential misdiagnosis. All cases flagged as potentially misdiagnosed underwent extensive manual reviews by two calibrated domain experts. A subset of the non-flagged cases was also manually reviewed., Results: A total of 2,262 patient charts met the study's inclusion criteria. Of these, the algorithm flagged 1,124 cases as potentially misclassified and 1,138 cases as potentially correctly diagnosed. When the algorithm identified a case as potentially misclassified, compared to the diagnosis assigned by the gold standard, the kappa statistic was 0.01. However, for cases the algorithm marked as potentially correctly diagnosed, the review against the gold standard showed a kappa statistic of 0.9, indicating near perfect agreement. The observed proportion of diagnostic misclassification was 32 %. There was no significant difference by clinic or provider characteristics., Conclusion: Our work revealed that about a third of periodontal cases are misclassified. Diagnostic errors have been reported to happen more frequently than other types of errors, and to be more preventable. Benchmarking diagnostic quality is a first step. Subsequent research endeavor will delve into comprehending the factors that contribute to diagnostic errors in dentistry and instituting measures to prevent them., Clinical Significance: This study sheds light on the significance of diagnostic excellence in the delivery of dental care, and highlights the potential role of technology in aiding diagnostic decision-making at the point of care., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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7. The efficacy and safety of antiangiogenesis tyrosine kinase inhibitors in patients with advanced anaplastic thyroid cancer: A meta-analysis of prospective studies.
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Cao RB, Ge Y, Zhang WX, Lin GH, Kuang BH, and Wang BC
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- Humans, Prospective Studies, Sorafenib therapeutic use, Sorafenib adverse effects, Indazoles therapeutic use, Indazoles adverse effects, Phenylurea Compounds therapeutic use, Phenylurea Compounds adverse effects, Progression-Free Survival, Tyrosine Kinase Inhibitors, Pyrimidines, Quinolines, Sulfonamides, Thyroid Carcinoma, Anaplastic drug therapy, Angiogenesis Inhibitors therapeutic use, Angiogenesis Inhibitors adverse effects, Thyroid Neoplasms drug therapy, Protein Kinase Inhibitors therapeutic use, Protein Kinase Inhibitors adverse effects
- Abstract
Background: The poor prognosis of anaplastic thyroid cancer (ATC) patients is associated with limited effective therapeutic strategies. Multiple antiangiogenesis tyrosine kinase inhibitors (TKIs) have been applied in later-line treatment of ATC; however, the results reported in clinical trials were controversial. In this study, we reconstructed the patient-level data to pooled-analyze the survival data, responses, and adverse events., Methods: Online databases (PubMed, Web of Science, Embase, and Cochrane CENTRAL) were searched on September 03, 2023. R software combined with the "metaSurvival" and "meta" packages were used to reconstruct the survival curves and summarize the response rates. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The secondary endpoints were survival rate, objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events., Results: Six prospective clinical trials involving 140 ATC patients were enrolled. Four types of TKIs (imatinib, pazopanib, sorafenib, and lenvatinib) were included. When advanced ATC patients were treated with the TKIs, the median OS was 4.8 months and the median PFS was 2.6 months. The pooled ORR and DCR were 9% and 53%. Hypertension, decreased appetite, rash, and lymphopenia were the most common grade ≥ 3 treatment-related adverse events., Conclusion: Mono-anitangiogenesis TKI therapy showed limited improvements in treating advanced ATC patients. Combining antiangiogenesis TKI therapy with chemotherapy, radiotherapy, or immunotherapy could be the direction of future studies., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)
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- 2024
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8. Emerging chemotherapy-based treatments in anaplastic thyroid cancer: an updated analysis of prospective studies.
- Author
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Wang BC, Lin GH, Kuang BH, and Cao RB
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- Humans, Antineoplastic Agents therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Prospective Studies, Thyroid Carcinoma, Anaplastic drug therapy, Thyroid Carcinoma, Anaplastic pathology, Thyroid Neoplasms drug therapy, Thyroid Neoplasms pathology, Thyroid Neoplasms mortality
- Abstract
Background: For patients with anaplastic thyroid cancer (ATC) without mutational driver genes, chemotherapy is suggested to be the first-line treatment option. However, the benefits of chemotherapy in treating ATC are limited. In this analysis, we collected the prospective data reported since 2010 to analyze the emerging chemotherapy-based treatments in ATC comprehensively., Methods: For this updated analysis, we searched PubMed (MEDLINE), Web of Science, Embase, and Cochrane CENTRAL databases from 1 January 2010 to 7 February 2024 for prospective clinical studies that contained chemotherapy-based treatments. This analysis was done to pool overall survival (OS), progression-free survival (PFS), objective response rates (ORRs), disease control rates (DCRs), and grade 3 or worse treatment-related adverse events (TRAEs)., Results: Six prospective clinical trials with 232 patients were included. Chemotherapy was commonly combined with targeted therapy or radiotherapy. The pooled median OS was 6.0 months (95% CI 4.1-9.7), and the median PFS was 3.2 months (95% CI 1.9-6.0) in patients with ATC who received chemotherapy-based strategies. The integrated ORR and DCR were 21% (95% CI 15%-27%) and 64% (95% CI 55%-72%), respectively. Regarding the grade 3 or worse TRAE, the pooled incidence was 68% (95% CI 47%-86%)., Conclusion: Although the emerging chemotherapy-based treatments showed antitumor activity in patients with ATC, these strategies failed to prolong the survival time substantially. More practical, safe, and novel therapeutic regimens for patients with ATC warrant further investigations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Lin, Kuang and Cao.)
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- 2024
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9. Developing an Accumulative Assessment System of Upper Extremity Motor Function in Patients With Stroke Using Deep Learning.
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Lin GH, Lee SC, Huang CY, Wang I, Lee YC, Hsueh IP, and Hsieh CL
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- Humans, Male, Female, Middle Aged, Reproducibility of Results, Aged, Stroke physiopathology, Recovery of Function, Upper Extremity physiopathology, Deep Learning, Psychometrics, Disability Evaluation, Stroke Rehabilitation methods
- Abstract
Objective: The Fugl-Meyer assessment for upper extremity (FMA-UE) is a measure for assessing upper extremity motor function in patients with stroke. However, the considerable administration time of the assessment decreases its feasibility. This study aimed to develop an accumulative assessment system of upper extremity motor function (AAS-UE) based on the FMA-UE to improve administrative efficiency while retaining sufficient psychometric properties., Methods: The study used secondary data from 3 previous studies having FMA-UE datasets, including 2 follow-up studies for subacute stroke individuals and 1 test-retest study for individuals with chronic stroke. The AAS-UE adopted deep learning algorithms to use patients' prior information (ie, the FMA-UE scores in previous assessments, time interval of adjacent assessments, and chronicity of stroke) to select a short and personalized item set for the following assessment items and reproduce their FMA-UE scores., Results: Our data included a total of 682 patients after stroke. The AAS-UE administered 10 different items for each patient. The AAS-UE demonstrated good concurrent validity (r = 0.97-0.99 with the FMA-UE), high test-retest reliability (intra-class correlation coefficient = 0.96), low random measurement error (percentage of minimal detectable change = 15.6%), good group-level responsiveness (standardized response mean = 0.65-1.07), and good individual-level responsiveness (30.5%-53.2% of patients showed significant improvement). These psychometric properties were comparable to those of the FMA-UE., Conclusion: The AAS-UE uses an innovative assessment method, which makes good use of patients' prior information to achieve administrative efficiency with good psychometric properties., Impact: This study demonstrates a new assessment method to improve administrative efficiency while retaining psychometric properties, especially individual-level responsiveness and random measurement error, by making good use of patients' basic information and medical records., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2024
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10. Efficacy and safety of combined stent retriever and contact aspiration vs. stent retriever alone on revascularization in patients with acute ischemic stroke: a systematic review and meta-analysis.
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Li W, Lin GH, Li HH, Zhou PB, Chen YY, Sun HT, and Chen HC
- Abstract
Objective: Whether the efficacy of combined stent retriever and contact aspiration (S + A) is superior to stent retriever (S) alone for revascularisation in patients with large vessel occlusive stroke remains uncertain. The aim of this meta-analysis was to assess the safety and efficacy of combined stent retriever and contact aspiration for the treatment of acute ischaemic stroke with large vessel occlusion by comparing it with stent retriever alone., Methods: We systematically searched the PubMed, Embase, Web of Science, and The Cochrane Library databases for randomised controlled trials and observational studies (case-control and cohort studies) published before 1 October 2023 comparing the efficacy of combined stent retriever and contact aspiration versus tent retriever alone in patients with large vessel occlusive stroke. The end point of the primary efficacy observed in this meta-analysis study was the rate of first pass nearly complete or complete recanalisation (mTICI 2c-3). Secondary effectiveness nodes were: rate of first pass successful recanalisation (mTICI 2b-3), rate of near-complete or complete recanalisation of the postoperative vessel, rate of successful recanalisation of the postoperative vessel, and MRS 0-2 within 90 days. Safety endpoints were interoperative embolism, symptomatic intracranial haemorrhage, and mortality within 90 days., Results: A total of 16 studies were included in the literature for this meta-analysis, with a total of 7,320 patients (S + C group: 3,406, S group: 3,914). A comprehensive analysis of the included literature showed that combined stent retriever and contact aspiration had a higher rate of near-complete or complete recanalisation of the postoperative vessel [OR = 1.53, 95% CI (1.24, 1.88), p < 0.0001] and rate of successful recanalisation of the postoperative vessel compared to stent retriever alone [OR = 1.83, 95% CI (1.55, 2.17), p < 0.00001]; there were no statistically significant differences between the two groups in terms of the rate of first pass nearly complete or complete recanalisation [OR = 1.00, 95% CI (0.83, 1.19), p = 0.96], rate of first pass successful recanalisation [OR = 1.02, 95% CI (0.85, 1.24), p = 0.81], interoperative embolism [OR = 0.93, 95% CI (0.72, 1.20), p = 0.56], symptomatic intracranial haemorrhage [OR = 1.14, 95% CI (0.87, 1.48), p = 0.33], MRS 0-2 within 90 days [OR = 0.89, 95% CI (0.76, 1.04), p = 0.14] and mortality within 90 days [OR = 1.11, 95% CI (0.94, 1.31), p = 0.22]., Conclusion: Combined stent retriever and contact aspiration has a higher rate of postprocedural revascularisation (mTICI 2c-3/mTICI 2b-3) compared with stent retriever alone in patients with large vessel occlusion stroke. In addition, it was not superior to stenting alone in terms of the rate of first pass recanalisation (mTICI 2c-3/mTICI 2b-3), interoperative embolisation, symptomatic intracranial haemorrhage, good functional prognosis within 90 days and mortality within 90 days., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Lin, Li, Zhou, Chen, Sun and Chen.)
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- 2024
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11. Leisure Participation for Mental Health Promotion in Later Life: A Six-Year Longitudinal Study.
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Yen HY, Lin GH, and Huang HY
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- Humans, Longitudinal Studies, Male, Aged, Female, Middle Aged, Happiness, Aged, 80 and over, Leisure Activities psychology, Mental Health, Depression psychology, Personal Satisfaction, Health Promotion methods
- Abstract
Engaging in leisure activities is essential for mental health in older adults. This longitudinal study ( n = 1,101, mean age = 69.20 ± 6.23 years at baseline) examined the associations between leisure participation and mental health over 6 years in three waves: 2016, 2018, and 2020. Pearson's correlation analyses and generalized estimating equations were performed for data analyses. The frequency of participation in physical and social activities was significantly positively associated with happiness, life satisfaction, and self-rated health, and significantly negatively associated with depression. Passive activities were significantly positively associated with happiness, life satisfaction, and self-rated health but not with depression. The time effect had no significant association with any mental health outcomes. These findings highlight the importance of leisure activities in promoting mental health among older adults. Policy makers should encourage older adults to engage in physical and social leisure activities., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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- 2024
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12. Immersive virtual reality as a surgical training tool: A cohort study.
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Teo EYL, Choo SZL, Lin GH, Tan AJL, Chen YY, Kirollos RW, and Chen MW
- Abstract
Background: Few studies have studied the efficacy of using immersive virtual reality (iVR) to teach surgical skills, especially by using real-world iVR recordings rather than simulations. This study aimed to investigate whether viewing 360° iVR instructional recordings produces greater improvements in basic suturing skills of students without prior medical training, beyond traditional methods like reading written manuals or watching 2D instructional videos., Materials and Methods: This was a partially blinded randomized cohort study. 44 pre-university students (aged 17) were randomized equally to either the written instruction manual, 2D instructional video, or iVR recordings. All students first watched a silent 2D demonstration video of the suturing task, before attempting to place three simple interrupted sutures on a piece of meat as a baseline. The time taken for the first attempt was recorded. Students were then given an hour to train using their allocated modality. They attempted the suturing task again, and timings were re-recorded. Four blinded surgically-trained judges independently assessed the quality of the stitches placed both pre and post-intervention. One-way analysis of variance tests (ANOVAs) and independent two-sample t-tests were used to determine the effect of training modality on improvements in suturing scores and time taken to complete suturing from pre to post-training., Results: For suturing scores, the iVR group showed significantly larger score improvements than the Written Manual group ( p = 0.031, Cohen's D = 0.92), while this iVR advantage was less pronounced when compared with the 2D Video group ( p = 0.16, Cohen's D = 0.65). Similarly for time taken to complete suturing, the iVR group had significantly larger time improvements than the Written Manual group ( p = 0.045), although this difference was less robust compared to the 2D Instructional Video group ( p = 0.34)., Conclusion: This study demonstrates that iVR training using real-world 360° instructional recordings produced significantly greater training gains in suturing scores and efficiency compared to reading written text. iVR training also led to larger training gains in both outcome measures than viewing 2D instructional videos, although the differences between them did not reach statistical significance., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)
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- 2024
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13. Development and validation of a rule-based algorithm to identify periodontal diagnosis using structured electronic health record data.
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Tokede B, Brandon R, Lee CT, Lin GH, White J, Yansane A, Jiang X, Kalenderian E, and Walji M
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- Humans, Electronic Health Records, Algorithms, Periodontitis, Periodontal Diseases diagnosis, Gingivitis
- Abstract
Aim: To develop and validate an automated electronic health record (EHR)-based algorithm to suggest a periodontal diagnosis based on the 2017 World Workshop on the Classification of Periodontal Diseases and Conditions., Materials and Methods: Using material published from the 2017 World Workshop, a tool was iteratively developed to suggest a periodontal diagnosis based on clinical data within the EHR. Pertinent clinical data included clinical attachment level (CAL), gingival margin to cemento-enamel junction distance, probing depth, furcation involvement (if present) and mobility. Chart reviews were conducted to confirm the algorithm's ability to accurately extract clinical data from the EHR, and then to test its ability to suggest an accurate diagnosis. Subsequently, refinements were made to address limitations of the data and specific clinical situations. Each refinement was evaluated through chart reviews by expert periodontists at the study sites., Results: Three-hundred and twenty-three charts were manually reviewed, and a periodontal diagnosis (healthy, gingivitis or periodontitis including stage and grade) was made by expert periodontists for each case. After developing the initial version of the algorithm using the unmodified 2017 World Workshop criteria, accuracy was 71.8% for stage alone and 64.7% for stage and grade. Subsequently, 16 modifications to the algorithm were proposed and 14 were accepted. This refined version of the algorithm had 79.6% accuracy for stage alone and 68.8% for stage and grade together., Conclusions: Our findings suggest that a rule-based algorithm for suggesting a periodontal diagnosis using EHR data can be implemented with moderate accuracy in support of chairside clinical diagnostic decision making, especially for inexperienced clinicians. Grey-zone cases still exist, where clinical judgement will be required. Future applications of similar algorithms with improved performance will depend upon the quality (completeness/accuracy) of EHR data., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2024
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14. Quantifying Coloring Skills Among Preschoolers.
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Huang CY, Lin GH, Lu SC, and Lee SC
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- Humans, Child, Preschool, Female, Male, Child, Reproducibility of Results, Taiwan, Child Development
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Importance: Coloring is popular with preschool children and reveals their developmental state. However, interpreting coloring performances is challenging because descriptive and subjective evaluations are commonly used with large variations., Objective: To develop a scoring method to objectively quantify children's coloring skills., Design: Colored blank train templates were analyzed using four indicators (entropy, complexity, coloring outside the lines, and unexpected blank areas) to form a summed score., Setting: Kindergarten in a urban city (Tainan, Taiwan)., Participants: Two hundred thirty-nine typically developing children ages 3 to 6 yr., Outcome and Measures: A newly developed method to assess coloring skill on the basis of a colored picture of a train., Results: The summed score exhibited good internal consistency (Cronbach's α = .80), discriminative validity (p = .04), convergent validity (rs = .66 and .59 with age and visual-motor integration), and acceptable factorial validity (comparative fit index = .99, standardized root-mean-square residual = .04, and root-mean-square error of approximation = .13). Moreover, three coloring patterns (mature, transitional, and immature) were identified., Conclusions and Relevance: The new method provides objective, reliable, and valid scores representing coloring skills in typically developing children. In addition, the coloring patterns can be recognized. This method can be used to facilitate comparisons of children's coloring skills with peers and provide valuable insight into children's development. Plain-Language Summary: This study proposes a new method to objectively quantify children's coloring skills with sound reliability and validity in typically developing children. The method can be used to evaluate children's coloring skills and patterns to shed light on their developmental stages., (Copyright © 2024 by the American Occupational Therapy Association, Inc.)
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- 2024
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15. Developing a machine learning-based short form of the positive and negative syndrome scale.
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Lin GH, Liu JH, Lee SC, Wu BJ, Li SQ, Chiu HJ, Wang SP, and Hsieh CL
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- Humans, Reproducibility of Results, Psychometrics, Activities of Daily Living
- Abstract
Background and Hypothesis: The Positive and Negative Syndrome Scale (PANSS) consists of 30 items and takes up to 50 minutes to administer and score. Therefore, this study aimed to develop and validate a machine learning-based short form of the PANSS (PANSS-MLSF) that reproduces the PANSS scores. Moreover, the PANSS-MLSF estimated the removed-item scores., Study Design: The PANSS-MLSF was developed using an artificial neural network, and the removed-item scores were estimated using the eXtreme Gradient Boosting classifier algorithm. The reliability of the PANSS-MLSF was examined using Cronbach's alpha. The concurrent validity was examined by the association (Pearson's r) between the PANSS-MLSF and the PANSS. The convergent validity was examined by the association (Pearson's r) between the PANSS-MLSF and the Clinical Global Impression-Severity, Mini-Mental State Examination, and Lawton Instrumental Activities of Daily Living Scale. The agreement of the estimated removed-item scores with their original scores was examined using Cohen's kappa., Study Results: Our analysis included data from 573 patients with moderate severity. The two versions of the PANSS-MLSF comprised 15 items and 9 items were proposed. The PANSS-MLSF scores were similar to the PANSS scores (mean squared error=2.6-24.4 points). The reliability, concurrent validity, and convergent validity of the PANSS-MLSF were good. Moderate to good agreement between the estimated removed-item scores and the original item scores was found in 60% of the removed items., Conclusion: The PANSS-MLSF offers a viable way to reduce PANSS administration time, maintain score comparability, uphold reliability and validity, and even estimate scores for the removed items., Competing Interests: Declaration of Competing Interest The Authors have declared that there are no conflicts of interest in relation to the subject of this study., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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16. Roles of DJ41_1407 and DJ41_1408 in Acinetobacter baumannii ATCC19606 Virulence and Antibiotic Response.
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Toh YH and Lin GH
- Subjects
- Virulence genetics, Anti-Bacterial Agents pharmacology, Biofilms, Biological Assay, Acinetobacter baumannii genetics
- Abstract
Acinetobacter baumannii is a major cause of nosocomial infections, and its highly adaptive nature and broad range of antibiotic resistance enable it to persist in hospital environments. A. baumannii often employs two-component systems (TCSs) to regulate adaptive responses and virulence-related traits. This study describes a previously uncharacterized TCS in the A. baumannii ATCC19606 strain, consisting of a transcriptional sensor, DJ41_1407, and its regulator, DJ41_1408, located adjacent to GacA of the GacSA TCS. Markerless mutagenesis was performed to construct DJ41_1407 and DJ41_1408 single and double mutants. DJ41_1408 was found to upregulate 49 genes and downregulate 43 genes, most of which were associated with carbon metabolism and other metabolic pathways, such as benzoate degradation. MEME analysis revealed a putative binding box for DJ41_1408, 5'TGTAAATRATTAYCAWTWAT3'. Colony size, motility, biofilm-forming ability, virulence, and antibiotic resistance of DJ41_1407 and DJ41_1408 single and double mutant strains were assessed against wild type. DJ41_1407 was found to enhance motility, while DJ41_1408 was found to upregulate biofilm-forming ability, and may also modulate antibiotic response. Both DJ41_1407 and DJ41_1408 suppressed virulence, based on results from a G. mellonella infection assay. These results showcase a novel A. baumannii TCS involved in metabolism, with effects on motility, biofilm-forming ability, virulence, and antibiotic response.
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- 2024
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17. Laser Speckle Contrast Imaging Guides Needling Treatment of Vascular Complications from Dermal Fillers.
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Tsai MF, Yu CM, Chen YF, Chung TY, Lin GH, Lee AL, Yang CY, Yu CM, Huang HY, Liu YC, Huang WC, Tung KY, and Yao WT
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- Humans, Laser Speckle Contrast Imaging, Hyaluronoglucosaminidase, Reproducibility of Results, Percutaneous Collagen Induction, Hyaluronic Acid, Dermal Fillers adverse effects, Cosmetic Techniques adverse effects
- Abstract
Background: Although laser Doppler imaging (LDI) accurately delineates a hypoperfused area to help target hyaluronidase treatment, laser speckle contrast imaging (LSCI) is more appropriate for assessing microvascular hemodynamics and has greater reproducibility than LDI. This study investigated the use of LSCI in the evaluation and treatment of six patients who developed vascular complications after facial dermal filler injections., Methods: The areas of vascular occlusion were accurately defined in real time by LSCI and were more precise than visual inspections or photographic evidence for guiding needling and hyaluronidase treatment., Results: All patients had achieved satisfactory outcomes as early as Day 2 of treatment and no procedure-related complications were reported after a median follow-up of 9.5 (7-37) days., Conclusion: LSCI accurately and noninvasively delineated vascular occlusions in real time among patients experiencing complications of facial dermal filler injections. Moreover, LSCI was more accurate than visual and photographic evaluations. Clinicians can use LSCI to reliably follow-up therapeutic outcomes after salvage interventions for vascular occlusions., Level of Evidence Iv: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)
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- 2024
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18. Lenvatinib Versus Atezolizumab Plus Bevacizumab in the First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Meta-Analysis of Real-World Studies.
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Wang BC, Kuang BH, and Lin GH
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- Humans, Bevacizumab pharmacology, Bevacizumab therapeutic use, Antibodies, Monoclonal, Humanized, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy, Phenylurea Compounds, Quinolines
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Background: Immunotherapy has revolutionized the treatment of hepatocellular carcinoma (HCC). However, whether adding immunotherapy to antiangiogenic therapy benefits patients with unresectable HCC (uHCC) more in the first-line setting remains controversial., Objective: In this analysis, we compared the clinical outcomes of lenvatinib monotherapy with atezolizumab plus bevacizumab combination therapy in advanced uHCC in real-world clinical practice., Methods: The MEDLINE, Embase, and Cochrane CENTRAL databases were systematically searched on 23 April 2023. The "metaSurvival" and "meta" packages of the R software (version 4.2.2) were used to summarize the survival curves and meta-analyze the survival data. Overall survival (OS) and progression-free survival (PFS) were defined as dual primary endpoints. Secondary endpoints included the objective response rate (ORR) and disease control rate (DCR)., Results: Overall, the pooled median OS was 18.4 months in the lenvatinib group versus 18.5 months in the atezolizumab plus bevacizumab group; the pooled median PFS was 6.9 months in the lenvatinib group versus 7.3 months in the atezolizumab plus bevacizumab group. Lenvatinib therapy showed similar OS [hazard ratio (HR): 0.91, 95% confidence interval (CI): 0.55-1.52, p = 0.72] and PFS (HR: 0.79, 95% CI: 0.56-1.12, p = 0.19) compared with atezolizumab plus bevacizumab therapy. In addition, a comparable ORR [odds ratio (OR): 0.89, 95% CI: 0.65-1.20, p = 0.44) was observed between lenvatinib and atezolizumab plus bevacizumab., Conclusions: Comprehensive analysis suggested that lenvatinib monotherapy exhibited survival outcomes comparable to those of atezolizumab plus bevacizumab combination therapy, which may provide useful insights for clinicians in future clinical practice., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
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- 2024
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19. Tyrosine kinase inhibitors in patients with advanced anaplastic thyroid cancer: an effective analysis based on real-world retrospective studies.
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Kuang BH, Zhang WX, Lin GH, Fu C, Cao RB, and Wang BC
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- Humans, Progression-Free Survival, Retrospective Studies, Thyroid Carcinoma, Anaplastic drug therapy, Thyroid Carcinoma, Anaplastic mortality, Thyroid Carcinoma, Anaplastic pathology, Thyroid Neoplasms drug therapy, Thyroid Neoplasms pathology, Thyroid Neoplasms mortality, Tyrosine Kinase Inhibitors therapeutic use
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Background: Tyrosine kinase inhibitors (TKIs) contribute to the treatment of patients with anaplastic thyroid cancer (ATC). Although prospective clinical studies of TKIs exhibit limited efficacy, whether ATC patients benefit from TKI treatment in real-world clinical practice may enlighten future explorations. Therefore, we conducted this effective analysis based on real-world retrospective studies to illustrate the efficacy of TKI treatment in ATC patients., Methods: We systematically searched the online databases on September 03, 2023. Survival curves were collected and reconstructed to summarize the pooled curves. Responses were analyzed by using the "meta" package. The primary endpoints were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR)., Results: 12 studies involving 227 patients were enrolled in the study. Therapeutic strategies included: anlotinib, lenvatinib, dabrafenib plus trametinib, vemurafenib, pembrolizumab plus dabrafenib and trametinib, pembrolizumab plus lenvatinib, pembrolizumab plus trametinib, and sorafenib. The pooled median OS and PFS were 6.37 months (95% CI 4.19-10.33) and 5.50 months (95% CI 2.17-12.03). The integrated ORR and DCR were 32% (95% CI 23%-41%) and 40% (95% CI 12%-74%)., Conclusion: In real-world clinical practice, ATC patients could benefit from TKI therapy. In future studies, more basic experiments and clinical explorations are needed to enhance the effects of TKIs in the treatment of patients with ATC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kuang, Zhang, Lin, Fu, Cao and Wang.)
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- 2024
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20. Gene Expression of Ethanol and Acetate Metabolic Pathways in the Acinetobacter baumannii EmaSR Regulon.
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Huang YW, Shu HY, and Lin GH
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Background: Previous studies have confirmed the involvement of EmaSR (ethanol metabolism a sensor/regulator) in the regulation of Acinetobacter baumannii ATCC 19606 ethanol and acetate metabolism. RNA-seq analysis further revealed that DJ41_568-571 , DJ41_2796 , DJ41_3218 , and DJ41_3568 regulatory gene clusters potentially participate in ethanol and acetate metabolism under the control of EmaSR., Methods: This study fused the EmaSR regulon promoter segments with reporter genes and used fluorescence expression levels to determine whether EmaSR influences regulon expression in ethanol or acetate salt environments. The enzymatic function and kinetics of significantly regulated regulons were also studied., Results: The EmaSR regulons P
2796 and P3218 exhibited > 2-fold increase in fluorescence expression in wild type compared to mutant strains in both ethanol and acetate environments, and PemaR demonstrated a comparable trend. Moreover, increases in DJ41_2796 concentration enhanced the conversion of acetate and succinyl-CoA into acetyl-CoA and succinate, suggesting that DJ41_2796 possesses acetate: succinyl-CoA transferase (ASCT) activity. The kcat /KM values for DJ41_2796 with potassium acetate, sodium acetate, and succinyl-CoA were 0.2131, 0.4547, and 20.4623 mM-1 s-1 , respectively., Conclusions: In A. baumannii , EmaSR controls genes involved in ethanol and acetate metabolism, and the EmaSR regulon DJ41_2796 was found to possess ASCT activity.- Published
- 2024
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21. Proximal Periodontal Support Adjacent to Untreated Peri-implantitis Lesions: A Cross-Sectional Analysis.
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Monje A, Pons R, Amerio E, Lin GH, Ortiz-González L, Kan JY, and Nart J
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- Humans, Cross-Sectional Studies, Peri-Implantitis diagnostic imaging, Peri-Implantitis etiology, Peri-Implantitis pathology, Dental Implants adverse effects, Periodontitis, Tooth pathology, Tooth Loss, Alveolar Bone Loss diagnostic imaging, Alveolar Bone Loss etiology
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Purpose: To assess site-related features of peri-implantitis occurring adjacent to teeth and its association with the proximal periodontal bone level., Materials and Methods: Periapical radiographs were collected from partially edentulous patients exhibiting peri-implantitis adjacent to teeth. The following variables were quantified: intrabony defect width (DW), implant marginal bone loss (MBLi), tooth marginal bone loss (MBLt), implant-tooth distance (ITd), intrabony defect angulation (DA), adjacent periodontal bone peak height (ABPh), and implant-tooth angulation (ITa). A correlation matrix using the Spearman correlation coefficient was created to explore the dependence of these variables. Univariate linear regression analysis was carried out by means of generalized estimating equations (GEE), using MBLt as dependent variable., Results: Overall, 61 patients and 84 implants were included in this study, consisting of a total of 105 implant sites facing adjacent teeth. This resulted in 515 linear and 194 angular measurements. A total of 11 different statistically significant associations were demonstrated between the different variables analyzed. Moreover, the univariate regression analysis revealed significant positive associations between MBLt and MBLi (P = .013) and between MBLt and periodontitis (PD) (P = .014). These associations were confirmed in the multivariate model., Conclusions: Teeth adjacent to untreated peri-implantitis lesions are associated with proximal loss of periodontal support. This finding is more remarkable in scenarios that display short implant-tooth distance.
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- 2023
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22. [Clinical efficacy of fire needling combined with cupping therapy on herpes zoster of acute stage and the effect on Th17/Treg cellular immune balance].
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Zeng JC, Liao YZ, Li JJ, Lu LH, Li HZ, Lu LM, Li QJ, Li LX, Wang SX, and Lin GH
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- Humans, Interleukin-10, Interleukin-17, T-Lymphocytes, Regulatory, Th17 Cells, Treatment Outcome, Tablets, Neuralgia, Postherpetic, Acupuncture Therapy methods, Cupping Therapy, Herpes Zoster therapy
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Objective: To compare the clinical efficacy between the combined therapy of fire needling and cupping, and western medication on herpes zoster of acute stage, as well as the effects on Th17 and Treg cells and inflammatory factors, i.e. IL-10 and IL-17 in the peripheral blood., Methods: Eighty patients with herpes zoster of acute stage were randomly divided into a combined therapy (fire needling plus cupping) group and a western medication group, 40 cases in each one. In the combined therapy group, the pricking and scattering techniques with fire needle were used at ashi points and Jiaji (EX-B 2) corresponding to the affected spinal segments; afterwards, cupping therapy was delivered. The combined treatment was given once daily. In the western medication group, valaciclovir hydrochloride tablet and vitamin B
1 tablet were administered orally. The duration of treatment in each group was 10 days. Before each treatment from day 1 to day 10 and on day 11 , the score of symptoms and physical signs was observed in the two groups separately. Before each treatment from day 1 to day 10 and on day 11, 30, 60, the score of visual analogue scale (VAS) and skin lesion indexes were observed in the two groups. On day 60, the incidence of postherpetic neuralgia was recorded in the two groups. The levels of Th17 and Treg cells, Th17/Treg ratio in the peripheral blood, as well as serum levels of IL-10 and IL-17 were detected before and after treatment in the two groups. The clinical efficacy was compared between the two groups., Results: From day 6 to day 10 during treatment and on day 11, the scores of symptoms and physical signs in the combined therapy group were lower than those of the western medication group ( P <0.05, P <0.01). On day 3, day 6 to day 10 during treatment and day 11, day 30, VAS scores in the combined therapy group were lower than those of the western medication group ( P <0.05, P <0.01). On day 60, the incidence of postherpetic neuralgia in the combined therapy group was lower compared with that in the western medication group ( P <0.05). The blister arresting time and scabbing time in the combined therapy group were shorter than those of the western medication group ( P< 0.05). After treatment, the level of Th17, and Th17/Treg ratio in the peripheral blood, as well as the serum levels of IL-10 and IL-17 were all lower in comparison with those in the western medication group ( P <0.05). The curative and remarkably effective rate was 82.5% (33/40) in the combined therapy group, higher than 62.5% (25/40) in the western medication group ( P <0.05)., Conclusion: The early application of fire needling combined with cupping therapy can effectively treat herpes zoster of acute stage, relieve pain, and reduce the incidence of postherpetic neuralgia, which may be related to reducing the levels of Th17 and Treg cells, and Th17/Treg ratio in the peripheral blood, as well as the serum levels of IL-10 and IL-17 so that the cellular immune balance is modulated.- Published
- 2023
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23. Frequency of screw-retained angulated screw channel single crown following immediate implant placement and provisionalization in the esthetic zone: A cone beam computed tomography study.
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Kan JYK, Rungcharassaeng K, Kamolroongwarakul P, Lin GH, Matsuda H, Yin S, Wang HL, Tarnow D, and Lozada JL
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- Humans, Male, Female, Young Adult, Adult, Middle Aged, Aged, Aged, 80 and over, Esthetics, Dental, Crowns, Cone-Beam Computed Tomography methods, Bone Screws, Alveolar Process, Maxilla diagnostic imaging, Maxilla surgery, Dental Implants, Dental Implants, Single-Tooth
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Objective: The purpose of this cone beam computed tomography (CBCT) study was to determine the frequency percentage of screw-retained crown using angulated screw channel (ASC) abutment for single immediate implant placement and provisionalization (IIPP) in the esthetic zone., Methods: The CBCT images of 200 patients without disease and without metal restorations in maxillary anterior teeth were evaluated. The mid-sagittal-sectional CBCT images of maxillary anterior teeth (#6-#11) were created in an implant planning software, screen-captured, and transferred to a presentation program. Template of tapered implants with diameter of 3.5 mm (for central and lateral incisors) and 4.3 mm (for central incisors and canines) and lengths of 13, 15, and 18 mm were applied to the sagittal images to identify the IIPP cases. To qualify for IIPP, the implant must engage >35% bone with at least 1 mm of surrounding bone and no perforations. The IIPP cases were further divided into straight screw channel (IIPPSSC) abutment or 25-degree angulated screw channel abutment (IIPPASC), based upon its restorability. The frequency percentages of possible IIPP, IIPPSSC, and IIPPASC were reported and compared among all maxillary anterior teeth., Results: A total of 1200 maxillary anterior teeth sagittal images from 200 patients (88 male and 112 female) with a mean age of 51.3 years (range 20-83 years) were evaluated in this study. The overall frequency percentages of IIPP, IIPPSSC, and IIPPASC possibility were 84% (74%-92%), 14% (10%-24%), and 75% (66%-87%), respectively., Conclusion: Within the limitations of this CBCT study, 90% of single IIPP in the esthetic zone can be restored with screw-retained crown when utilizing ASC. In addition, the possibility of using a screw-retained restoration following IIPP increases about five times with ASC abutment compared to the SSC abutment., (© 2023 The Authors. Clinical Implant Dentistry and Related Research published by Wiley Periodicals LLC.)
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- 2023
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24. Using Artificial Intelligence to Identify the Associations of Children's Performance of Coloring, Origami, and Copying Activities With Visual-Motor Integration.
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Huang CY, Yu YT, Chen KL, Lin GH, and Hsieh CL
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- Male, Female, Child, Preschool, Humans, Cross-Sectional Studies, Psychomotor Performance, Neuropsychological Tests, Child Development, Artificial Intelligence
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Importance: Performance of coloring, origami, and copying activities reflects children's visual-motor integration (VMI), but the levels of association remain unclear., Objective: To use artificial intelligence (AI) to investigate associations of performance of coloring, origami, and copying activities with VMI., Design: Cross-sectional study., Setting: Kindergartens., Participants: A sample of 370 children (182 boys and 188 girls) in the second and third years of kindergarten., Outcomes and Measures: Beery-Buktenica Developmental Test of Visual-Motor Integration, 6th Edition (VMI-6)., Results: Data for preschool children from an ongoing project were retrieved. AI models were trained to use photographs of activity products to predict total score on the VMI-6. R2 values were used to identify the variance in VMI-6 standardized scores explained by predicted scores from the activities. That is, R2 values reflected associations between activity performance and VMI. The R2 values for the combination of origami and copying were the largest (.390-.577). These R2 values were larger than those for each individual activity (.340-.473) and similar to those for the combination of all three activities (.400-.550)., Conclusions and Relevance: Because moderate R2 values were found between performance of the three activity products and VMI, the three activities have high potential for use in identifying children's level of VMI or as teaching materials to facilitate the development of children's VMI. Furthermore, combining origami and copying activities is recommended for teachers and clinicians who need to address VMI. What This Article Adds: A combination of origami and copying activities had the strongest associations with children's VMI. Teachers and clinicians can use these two activities when addressing VMI development among preschool children., (Copyright © 2023 by the American Occupational Therapy Association, Inc.)
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- 2023
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25. Novel-fosfamide monotherapy or in combination with doxorubicin versus doxorubicin alone in patients with advanced soft tissue sarcoma: A pooled analysis of randomized clinical trials.
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Liu XX, Han YH, Kuang BH, Lin GH, and Wang BC
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- Humans, Randomized Controlled Trials as Topic, Doxorubicin adverse effects, Soft Tissue Neoplasms, Sarcoma drug therapy, Thrombocytopenia
- Abstract
Background: Novel-fosfamides (NFOs) belong to active metabolites of ifosfamide that bypass the generation of toxic byproducts. In this analysis, we aimed to comprehensively assess the benefits and risks of NFO monotherapy or in combination with doxorubicin (DOX) versus single-drug DOX in previously untreated patients with advanced soft-tissue sarcoma (ASTS)., Methods: Online PubMed, Web of Science, Embase, and Cochrane CENTRAL databases were systematically searched on April 26, 2022. Objective response rate and disease control rate were primary outcomes. Overall survival (OS), progression-free survival (PFS), and grade ≥ 3 treatment-related adverse events were secondary outcomes., Results: In all, 3 randomized clinical trials with a total of 1207 ASTS patients were eligible. DOX plus NFO combination therapy showed higher risk ratios of objective response rate (1.50, 95% CI 1.20-1.68, P = .0003) and disease control rate (1.15, 95% CI 1.05-1.27, P = .0030) compared with DOX monotherapy. Nevertheless, NFO-based monotherapy and combination therapy were found no improvements on OS (hazard ratio 0.93, 95% CI 0.52-1.65, P = .8050) and PFS (hazard ratio 0.88, 95% CI 0.54-1.43, P = .6088) against DOX. More incidences of grade 3 or worse anemia, thrombocytopenia, stomatitis, diarrhea, constipation, and febrile neutropenia were observed in NFO-based treatments., Conclusion: Adding NFO to DOX as first-line therapy improved the responses in ASTS patients but did not prolong OS and PFS. Grade 3 or worse treatment-related adverse events should be treated with caution during the NFO-based therapies., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)
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- 2023
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26. Immunogenetic Metabolomics Reveals Key Enzymes That Modulate CAR T-cell Metabolism and Function.
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Renauer P, Park JJ, Bai M, Acosta A, Lee WH, Lin GH, Zhang Y, Dai X, Wang G, Errami Y, Wu T, Clark P, Ye L, Yang Q, and Chen S
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- Humans, Immunogenetics, Immunotherapy, Adoptive, Metabolomics, Tumor Microenvironment, T-Lymphocytes, Neoplasms
- Abstract
Immune evasion is a critical step of cancer progression that remains a major obstacle for current T cell-based immunotherapies. Hence, we investigated whether it is possible to genetically reprogram T cells to exploit a common tumor-intrinsic evasion mechanism whereby cancer cells suppress T-cell function by generating a metabolically unfavorable tumor microenvironment (TME). In an in silico screen, we identified ADA and PDK1 as metabolic regulators. We then showed that overexpression (OE) of these genes enhanced the cytolysis of CD19-specific chimeric antigen receptor (CAR) T cells against cognate leukemia cells, and conversely, ADA or PDK1 deficiency dampened this effect. ADA-OE in CAR T cells improved cancer cytolysis under high concentrations of adenosine, the ADA substrate, and an immunosuppressive metabolite in the TME. High-throughput transcriptomics and metabolomics analysis of these CAR T cells revealed alterations of global gene expression and metabolic signatures in both ADA- and PDK1-engineered CAR T cells. Functional and immunologic analyses demonstrated that ADA-OE increased proliferation and decreased exhaustion in CD19-specific and HER2-specific CAR T cells. ADA-OE improved tumor infiltration and clearance by HER2-specific CAR T cells in an in vivo colorectal cancer model. Collectively, these data unveil systematic knowledge of metabolic reprogramming directly in CAR T cells and reveal potential targets for improving CAR T-cell therapy., (©2023 American Association for Cancer Research.)
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- 2023
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27. Development of a 13-item Short Form for Fugl-Meyer Assessment of Upper Extremity Scale Using a Machine Learning Approach.
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Lin GH, Wang I, Lee SC, Huang CY, Wang YC, and Hsieh CL
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- Humans, Disability Evaluation, Recovery of Function physiology, Upper Extremity, Stroke Rehabilitation, Stroke complications
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Objective: To develop and validate a short form of the Fugl-Meyer Assessment of Upper Extremity Scale (FMA-UE) using a machine learning approach (FMA-UE-ML). In addition, scores of items not included in the FMA-UE-ML were predicted., Design: Secondary data from a previous study, which assessed individuals post-stroke using the FMA-UE at 4 time points: 5-30 days post-stroke screen, 2-month post-stroke baseline assessment, 6-month post-stroke assessment, and 12-month post-stroke assessment., Setting: Rehabilitation units in hospitals., Participants: A total of 408 individuals post-stroke (N=408)., Interventions: Not applicable., Main Outcome Measures: The 30-item FMA-UE., Results: We established 29 candidate versions of the FMA-UE-ML with different numbers of items, from 1 to 29, and examined their concurrent validity and responsiveness. We found that the responsiveness of the candidate versions obviously declined when the number of items was less than 13. Thus, the 13-item version was selected as the FMA-UE-ML. The concurrent validity was good (intra-class correlation coefficients ≥0.99). The standardized response means of the FMA-UE-ML and FMA-UE were 0.54-0.88 and 0.52-0.91, respectively. The Pearson's rs between the change scores of the FMA-UE-ML and those of the FMA-UE were 0.96-0.98. The predicted item scores had acceptable to good accuracy (Kappa=0.50-0.92)., Conclusions: The FMA-UE-ML seems a promising short form to improve administrative efficiency while retaining good concurrent validity and responsiveness. In addition, the FAM-UE-ML can provide all item scores of the FMA-UE for users., (Copyright © 2023 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)
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- 2023
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28. An integrated analysis of Sacituzumab govitecan in relapsed or refractory metastatic triple-negative breast cancer.
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Cheng SX, Chen QC, Lin GH, Han YH, Wang BC, Dai Y, and Zhao YX
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- Humans, Antigens, Neoplasm, Camptothecin adverse effects, Diarrhea chemically induced, Prospective Studies, Immunoconjugates adverse effects, Triple Negative Breast Neoplasms drug therapy, Triple Negative Breast Neoplasms pathology
- Abstract
Background: Sacituzumab govitecan (SG) is an antibody-drug conjugate that targets the human trophoblast cell-surface antigen 2 to deliver SN-38 to cancer cells. In this study, we assessed the efficacy and safety of SG in patients with relapsed or refractory metastatic triple-negative breast cancer (RM-TNBC)., Methods: For this integrated analysis, from inception to January 2, 2023, we searched PubMed, Web of Science, Embase, and Cochrane library databases for prospective studies that evaluated SC in RM-TNBC patients. Primary endpoints were survival outcomes and responses. Secondary endpoints were all grade and grade ≥ 3 toxicities., Results: Six hundred potentially relevant records were screened. Our analysis included 3 trials (412 patients). Median overall survival was 12.9 months (95% confidence interval [CI], 11.5-14.4), progression-free survival was 5.7 months (5% CI, 5.1-6.3), and duration of objective response was 7.4 months (5% CI, 5.8-9.0). The objective response rate was 34%, and the disease control rate was 71%. Key grade ≥ 3 toxicities (in over 10% of the patients) included neutropenia (46%), leukopenia (12%), febrile neutropenia (11%), diarrhea (11%), and anemia (10%). Four treatment-related deaths were reported., Conclusion: SG was associated with effectiveness in patients with RM-TNBC. Myelosuppression and diarrhea were the primary treatment-related adverse events., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)
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- 2023
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29. The Effect of Bone Morphogenetic Protein-2 (BMP-2) on Volumetric and Histometric Outcomes for Peri-Implant Defects in the Animal Model: A Systematic Review and Meta-Analysis.
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Lee E, Moy A, Nguyen T, Kao R, and Lin GH
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- Animals, Bone and Bones, Models, Animal, Bone Morphogenetic Proteins, Bone Morphogenetic Protein 2 therapeutic use, Dental Implants
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Purpose: To study the effect of BMP-2 on the volumetric and histometric changes in peri-implant defect treatments in animal models. Materials and Methods: An electronic search of four databases and a manual search of peer-reviewed journals for relevant articles were performed. Animal studies with data that compared the volumetric and/or histometric outcomes of peri-implant defect treatment with and without the use of BMP-2 were included. Meta-analyses were performed to analyze the weighted mean difference (WMD) and confidence interval (CI) for the recorded variables. Results: After completing the search process, 21 randomized controlled trials were included. The results of the meta-analyses showed that the WMD of bone-to-implant contact (%BIC) with 4 to 8 weeks and 12 to 24 weeks of follow-up was 15.50% (95% CI = 3.28% to 27.72%, P = .01) and 16.17% (95% CI = 11.17% to 21.16%, P < .00001), respectively, favoring the BMP-2 group. The WMD for the percentage of defect fill with 4 to 8 weeks and 12 to 24 weeks of follow-up was 15.88% (95% CI = 3.90% to 27.86%, P = .009) and 10.48% (95% CI = 0.95% to 20.02%, P = .03), respectively, favoring the BMP-2 group. The WMD for the vertical bone gain with 8 to 16 weeks of follow-up was 1.63 mm (95% CI = 0.58 to 2.67 mm, P = .002), also favoring the BMP-2 group. Conclusion: This review demonstrated that the use of BMP-2 in treating peri-implant defects showed better clinical and histometric outcomes than defects not treated with BMP-2 in animal models.
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- 2023
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30. Periodontal and endodontic considerations in florid cemento-osseous dysplasia: A case report with 15-year follow-up.
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Dung TS and Lin GH
- Abstract
Competing Interests: The authors have no conflicts of interest relevant to this article.
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- 2023
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31. The association between Aggregatibacter actinomycetemcomitans JP2 clone and periodontitis: A systematic review and meta-analysis.
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Mehta J, Eaton C, AlAmri M, Lin GH, and Nibali L
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- Humans, Child, Adolescent, Young Adult, Adult, Middle Aged, Aggregatibacter actinomycetemcomitans genetics, Exotoxins, Clone Cells, Aggressive Periodontitis, Dental Plaque microbiology
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To appraise the literature on the prevalence of the JP2 clone of Aggregatibacter actinomycetemcomitans (A.a.) and on its association with presence and progression of periodontitis in different populations. A systematic search of the literature was conducted in Medline, Embase and Cochrane Library for studies reporting data on detection of the JP2 clone of A.a. A total of 56 papers were included in the review, from an initial search of 685 titles. Studies were carried out in populations with a mean age of 26.34 years (range 6.24-53.85 years). Just over 16% of the overall population assessed (n = 13 751) had the JP2 clone detected. Meta-analyses included 16 studies and 1775 patients, and revealed an association between detection of the JP2 clone and diagnosis of periodontitis (RR = 1.86, 95% 1.43-2.42) from saliva and plaque, with high heterogeneity (I
2 = 85%, p < .00001). Meta-analyses included 5 studies and 616 patients, and revealed an association between baseline detection of the JP2 clone and onset of periodontitis over 2 to 5 years (RR = 4.12, 95% 2.42-7.00), with high heterogeneity (I2 = 81%, p < .0003). From the overall risk of bias score, 29 papers were judged as low risk of bias, whilst the remaining papers were judged to have an overall medium or high risk of bias. Detection of the JP2 clone of A.a. in subgingival plaque and saliva samples is associated with increased odds of diagnosis of periodontitis and may be able to predict onset of periodontitis. This systematic review provides clear evidence that in certain populations, the JP2 clone of A.a. is associated with early-onset periodontitis. Furthermore, detection of this bacterium seems to be predictive of disease onset., (© 2023 The Authors. Journal of Periodontal Research published by John Wiley & Sons Ltd.)- Published
- 2023
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32. Relationship between intralobar pulmonary sequestration and type A aortic dissection: A case report.
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Wang YJ, Chen YY, and Lin GH
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Background: Pulmonary sequestrations often lead to serious complications such as infections, tuberculosis, fatal hemoptysis, cardiovascular problems, and even malignant degeneration, but it is rarely documented with medium and large vessel vasculitis, which is likely to result in acute aortic syndromes., Case Summary: A 44-year-old man with a history of acute Stanford type A aortic dissection status post-reconstructive surgery five years ago. The contrast-enhanced computed tomography of the chest at that time had also revealed an intralobar pulmonary sequestration in the left lower lung region, and the angiography also presented perivascular changes with mild mural thickening and wall enhancement, which indicated mild vasculitis. The intralobar pulmonary sequestration in the left lower lung region was long-term unprocessed, which was probably associated with his intermittent chest tightness since no specific medical findings were detected but only positive sputum culture with mycobacterium avium-intracellular complex and Aspergillus. We performed uniportal video-assisted thoracoscopic surgery with wedge resection of the left lower lung. Hypervascularity over the parietal pleura, engorgement of the bronchus due to a moderate amount of mucus, and firm adhesion of the lesion to the thoracic aorta were histopathologically noticed., Conclusion: We hypothesized that a long-term pulmonary sequestration-related bacterial or fungal infection can result in focal infectious aortitis gradually, which may threateningly aggravate the formation of aortic dissection., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)
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- 2023
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33. The efficacy of adebrelimab compared with durvalumab and atezolizumab in untreated extensive-stage small-cell lung cancer: a survival analysis of reconstructed patient-level data.
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Wang BC, Fu C, and Lin GH
- Subjects
- Humans, Survival Analysis, Progression-Free Survival, Clinical Trials as Topic, Small Cell Lung Carcinoma drug therapy, Lung Neoplasms drug therapy, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized therapeutic use, Immune Checkpoint Inhibitors therapeutic use, Antineoplastic Agents therapeutic use
- Abstract
Background: Adebrelimab showed excellent efficacy in the first-line treatment for extensive-stage small-cell lung cancer (ES-SCLC). However, whether adebrelimab is superior to durvalumab and atezolizumab remains unclear. Therefore, we, in this study, aimed to compare the survival data of adebrelimab (CAPSTONE-1 trial) with durvalumab (CASPIAN trial) and atezolizumab (IMpower133 trial) in the first-line setting of ES-SCLC patients., Methods: Online databases, including PubMed, Embase, Web of Science, and Cochrane CENTRAL, were systematically searched on December 2, 2022. The metaSurvival and IPDfromKM methods were used to analyze the summary survival curves and the reconstructed patient-level data. The main endpoints were median overall survival (OS) and progression-free survival (PFS)., Results: In this analysis, survival data in the CASPIAN, IMpower133, and CAPSTONE-1 trials were collected from five published studies. The pooled median OS and PFS were 14.0 months (95% CI 11.2-16.6) and 5.6 months (95% CI 4.7-6.7) when ES-SCLC patients received chemotherapy (etoposide and cisplatin/carboplatin) and anti-PD-L1 therapy. Based on the reconstructed patient-level data, adebrelimab significantly prolonged survival outcomes against atezolizumab (OS: Hazard ratio [HR]0.76, 95% CI 0.60-0.95; PFS: HR 0.67, 95% CI 0.54-0.83) and durvalumab (OS: HR 0.75, 95% CI 0.60-0.92)., Conclusion: For previously untreated ES-SCLC patients, longer survival time might be benefited from adding adebrelimab to etoposide-platinum chemotherapy. In future studies, further real-world evidence or head-to-head clinical trials are warranted to confirm the differences between the PD-L1 inhibitors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Fu and Lin.)
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- 2023
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34. Comprehensive Analyses of Prognostic Values and Immune Infiltration of KDM3 Gene Family in Hepatocellular Carcinoma.
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Lin GH, Wu SH, Ko YC, Lin CH, Liao GS, Chen TW, Chen YJ, and Hsu KF
- Subjects
- Humans, Prognosis, CD8-Positive T-Lymphocytes, Jumonji Domain-Containing Histone Demethylases, Carcinoma, Hepatocellular, Liver Neoplasms, MicroRNAs
- Abstract
Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed malignancy globally with a pessimistic prognosis. Previous studies have demonstrated that abnormal expression of genes in the lysine-specific histone demethylase 3 (KDM3) family with epigenetic changes and dysregulation of enzymes promotes cancer progression. In this study, multiomics analyses were utilized to analyze differential expression, prognostic value, genetic alteration, protein-protein interaction, associated biological pathways and immune cell infiltration of KDM3s in patients with HCC. KDM3A-C were significantly upregulated to different extents based on pathologic and tumor grades in patients with HCC compared to normal tissue. Of note, higher KDM3A expression was associated with poor survival in HCC patients, whereas KDM3B and KDM3C were not associated with survival. Furthermore, KDM3A-B genetic alterations had significant effects on survival in patients with HCC. Analyses of the KEGG pathway and miRNAs targets of KDM3A and KDM3B in HCC may provide potential value in tumor behaviors and treatment. The differential expression of the KDM3 family has a strongly significant correlation with the infiltration of the abundance of immune cells, including B cells, CD8
+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells in HCC. This study indicates that KDM3A may have the potential to be a promising molecular target in terms of prognostic biomarkers or therapeutic targets for HCC treatment., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)- Published
- 2023
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35. [CT perfusion combined with energy spectrum imaging to evaluate the short-term efficacy of bronchial arterial chemoembolization for lung cancer].
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Lai LQ, Lin GH, Chen WY, Tu JF, and Ji JS
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- Male, Humans, Female, Retrospective Studies, Tomography, X-Ray Computed methods, Perfusion, Lung Neoplasms, Iodine
- Abstract
Objective: To evaluate the clinical value of dynamic volumetric CT perfusion combined with energy spectrum imaging in bronchial arterial chemoembolization (BACE) in patients with lung cancer. Methods: The data of 31 patients with lung cancer confirmed by pathology and treated with BACE in Lishui Central Hospital from January 2018 to February 2022 were retrospectively collected, including 23 men and 8 women, aged 31-84 (67) years. All patients received perfusion scans of lesion sites within 1 week before surgery and 1 month after surgery. We collected and compared the changes in preoperative and postoperative perfusion parameters such as blood flow (BF), blood volume (BV), mean through time (MTT), permeability surface (PS) and energy spectrum parameters including arterial phase CT value (CTA), venous phase CT value (CTV), arterial phase iodine concentration (ICA), venous phase of iodine concentration (ICV), arterial standardization iodine concentration (NICA), and intravenous standardized iodine concentration (NICV) to confirm the significance of these parameters in evaluating the short-term efficacy of BACE in the treatment of advanced lung cancer. Data normality was tested using the Kolmogorov-Smirnov test and normally distributed measurement data are expressed here as mean ± standard deviation; the independent-samples t -test was used for comparisons between two groups. The measurement data that were not normally distributed are expressed as median (interquartile interval) [ M ( Q
1 , Q3 )], and the comparison between the two groups used the Kruskal-Wallis test. Count data are expressed as cases (%), and comparisons between groups used the χ2 test. Results: The objective response rate (ORR) and disease control rate (DCR) at 1 month after BACE were 54.8% (17/31) and 96.8% (30/31), respectively. CT perfusion parameters and energy spectrum parameters of patients before and after BACE treatment were compared. The results showed that BF, BV, MTT, ICA, ICV and NICV were significantly decreased after BACE treatment compared with before treatment, and the differences were statistically significant[58.06 (40.47,87.22) vs.23.57(10.92, 36.24) ml·min-1 ·100g-1 ,3.33(2.86,6.09) vs.2.12(1.96,3.61)ml/100g,2.70(2.19,3.88) vs.1.53 (1.12,2.25)s, 3.51 (3.11,4.14)vs.1.74 (1.26,2.50)mg/ml,2.00 (1.30,2.45) vs.1.32(0.92,1.76)mg/ml,0.51(0.42,0.57) vs.0.33(0.23,0.39)](all P< 0.05). At the same time, compared with the non-remission group, the study results showed that the difference of parameters in remission group before and after BACE was more obvious, including ΔBF, ΔBV, ΔMTT, ΔPS, ΔCTA, ΔCTV, ΔICA, ΔICV, ΔNICA, ΔNICV were significantly increased, and the difference was statistically significant [36.82(32.38, 45.34) vs.9.50(-1.43, 12.34) ml·min-1 ·100g-1 ,4.46(2.52, 5.79) vs.0.22(-0.76, 4.09) ml/100g,4.22(2.25, 6.77) vs.0.43(-2.53, 1.88) s,10.07 (2.89, 13.13) vs.-2.01(-6.77, 4.28) ml·min-1 ·100g-1 ,14.22(11.88, 20.57) vs.4.18(-5.25, 6.37) HU, 34.6(14.88, 43.15) vs.11.60(0.26, 25.05) HU,0.95(0.54, 1.47) vs.0.11(0.20, 0.59) mg/ml,1.57(1.10, 2.38) vs. 0.26(-0.21, 0.63) mg/ml,0.05(0.03, 0.08) vs.-0.02(-0.04, 0.01),0.18(0.13, 0.21)vs. 0.11(-0.06, 0.16)](all P< 0.05). Conclusions: CT perfusion combined with spectral imaging could effectively evaluate the changes in tumor vascular perfusion in patients with advanced lung cancer before and after BACE treatment, which has important value in judging the short-term efficacy after treatment.- Published
- 2023
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36. The significance of vertical platform discrepancies and splinting on marginal bone levels for adjacent dental implants.
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Lin GH, Tran C, Brzyska K, Kan JY, Wang HL, Curtis DA, and Kao RT
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- Humans, Retrospective Studies, Dental Prosthesis Design, Dental Prosthesis, Implant-Supported, Crowns, Dental Restoration Failure, Dental Implants
- Abstract
Objective: The aim of this retrospective study was to investigate the influence of vertical platform discrepancies for splinted and non-splinted adjacent implants on radiographic marginal bone loss (RMBL)., Methods: Data from January 2000 to February 2021 were collected from the electronic charts of 156 patients with 337 implants at the UCSF School of Dentistry. Five different implant restoration categories were evaluated for radiographic evidence of proximal RMBL. Patients with (1) two adjacent single crowns, (2) two adjacent splinted crowns, (3) three-unit bridges supported by two implants, (4) three adjacent single crowns, and (5) three adjacent splinted crowns. Inclusion required baseline radiograph taken at the time of prosthesis delivery or final impression, and follow-up radiographs at least 12 months after restorations have been in function. Measurements assessed included vertical distance between adjacent implant platforms and proximal RMBL around implants. Odds ratios (ORs) and 95% confidence interval (95% CI) of implants with ≥1 mm RMBL between different type of restorations were calculated., Results: In general, prostheses supported by splinted adjacent implants demonstrated a significant association with the presence of ≥1 mm RMBL (OR = 2.55, 95% CI = 1.17-5.17, p = 0.018) when compared to prostheses supported by non-splinted adjacent implants. In addition, prostheses with a vertical platform discrepancy ≥0.5 mm demonstrated a significant association with the presence of ≥1 mm RMBL (OR = 4.30, 95% CI = 1.85 to 10.01, p = 0.007) when compared to prostheses with a vertical platform discrepancy <0.5 mm. When adjacent implants had ≥0.5 mm vertical platform discrepancy, the majority (66.67%) of three splinted adjacent crowns had at least one implant with ≥1 mm RMBL. This was followed by two splinted adjacent crowns (58.97%), three-unit bridge (25.93%), two single adjacent crowns (24.24%), and three single adjacent crowns (18.18%). When adjacent implants had ≥1 mm vertical platform discrepancy, there was an increased percentage of implants with ≥1 mm RMBL. The restorative design associated with the highest percent of implants with bone loss was three splinted adjacent crowns (70%), two splinted adjacent crowns (61.11%), three single adjacent crowns (40%), and three-unit bridge and two single adjacent implants (21.05%). Three splinted adjacent crowns were significantly associated with ≥1 mm RMBL when compared to three-unit bridge (OR 6.56, 95% CI 1.59-27.07). Similarly, two splinted crowns were significantly associated with ≥1 mm RMBL when compared to two single crowns (OR = 2.50, 95% CI = 1.08-5.79)., Conclusion: Two or three adjacent implants placed with a vertical platform discrepancy, when splinted together, are associated with higherincidence of ≥1 mm RMBL than non-splinted restorations., (© 2023 Wiley Periodicals LLC.)
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- 2023
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37. Immunogenetic metabolomics revealed key enzymes that modulate CAR-T metabolism and function.
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Renauer P, Park JJ, Bai M, Acosta A, Lee WH, Lin GH, Zhang Y, Dai X, Wang G, Errami Y, Wu T, Clark P, Ye L, Yang Q, and Chen S
- Abstract
Immune evasion is a critical step of cancer progression that remains a major obstacle for current T cell-based immunotherapies. Hence, we seek to genetically reprogram T cells to exploit a common tumor-intrinsic evasion mechanism, whereby cancer cells suppress T cell function by generating a metabolically unfavorable tumor microenvironment (TME). Specifically, we use an in silico screen to identify ADA and PDK1 as metabolic regulators, in which gene overexpression (OE) enhances the cytolysis of CD19-specific CD8 CAR-T cells against cognate leukemia cells, and conversely, ADA or PDK1 deficiency dampens such effect. ADA -OE in CAR-T cells improves cancer cytolysis under high concentrations of adenosine, the ADA substrate and an immunosuppressive metabolite in the TME. High-throughput transcriptomics and metabolomics in these CAR-Ts reveal alterations of global gene expression and metabolic signatures in both ADA- and PDK1- engineered CAR-T cells. Functional and immunological analyses demonstrate that ADA -OE increases proliferation and decreases exhaustion in α-CD19 and α-HER2 CAR-T cells. ADA-OE improves tumor infiltration and clearance by α-HER2 CAR-T cells in an in vivo colorectal cancer model. Collectively, these data unveil systematic knowledge of metabolic reprogramming directly in CAR-T cells, and reveal potential targets for improving CAR-T based cell therapy., Synopsis: The authors identify the adenosine deaminase gene (ADA) as a regulatory gene that reprograms T cell metabolism. ADA-overexpression (OE) in α-CD19 and α-HER2 CAR-T cells increases proliferation, cytotoxicity, memory, and decreases exhaustion, and ADA-OE α-HER2 CAR-T cells have enhanced clearance of HT29 human colorectal cancer tumors in vivo .
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- 2023
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38. Machine learning-based brief version of the Caregiver-Teacher Report Form for preschoolers.
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Lin GH, Lee SC, Yu YT, and Huang CY
- Subjects
- Child, Humans, Emotions, Caregivers, Problem Behavior
- Abstract
Background: The Caregiver-Teacher Report Form of the Child Behavior Checklist for Ages 1½-5 (C-TRF) is a widely used checklist to identify emotional and behavioral problems in preschoolers. However, the 100-item C-TRF restricts its utility., Aims: This study aimed to develop a machine learning-based short-form of the C-TRF (C-TRF-ML)., Methods and Procedures: Three steps were executed. First, we split the data into three datasets in a ratio of 3:1:1 for training, validation, and cross-validation, respectively. Second, we selected a shortened item set and trained a scoring algorithm using joint learning for classification and regression using the training dataset. Then, we evaluated the similarity of scores between the C-TRF-ML and the C-TRF by r-squared and weighted kappa values using the validation dataset. Third, we cross-validated the C-TRF-ML by calculating the r-squared and weighted kappa values using the cross-validation dataset., Outcomes and Results: Data of 363 children were analyzed. Thirty-six items of the C-TRF were retained. The r-squared values of C-TRF-ML scores were 0.86-0.96 in the cross-validation dataset. Weighted kappa values of the syndrome/problem grading were 0.72-0.94 in the cross-validation dataset., Conclusions and Implications: The C-TRF-ML had about 60 % fewer items than the C-TRF but yielded comparable scores with the C-TRF., Competing Interests: Financial interests All authors declare they have no financial interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
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- 2023
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39. Whole-Exome Sequencing Identifies Genetic Variants for Severe Adolescent Idiopathic Scoliosis in a Taiwanese Population.
- Author
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Lin MR, Chou PH, Huang KJ, Ting J, Liu CY, Chou WH, Lin GH, Chang JG, Ikegawa S, Wang ST, and Chang WC
- Abstract
Adolescent idiopathic scoliosis (AIS) is a three-dimensional spinal curvature deformity that appears in the adolescent period. In this study, we performed whole-exome sequencing on 11 unrelated Taiwanese patients with a Cobb's angle greater than 40 degrees. Our results identified more than 200 potential pathogenic rare variants, however, most of which were carried only by one individual. By in silico pathogenicity annotation studies, we found that TTN , CLCN1 , and SOX8 were the most important genes, as multiple pathogenic variants were within these genes. Furthermore, biological functional annotation indicated critical roles of these AIS candidate genes in the skeletal muscle. Importantly, a pathogenic variant on SOX8 was shared by over 35% of the patients. These results highlighted TTN , CLCN1 , and SOX8 as the most likely susceptibility genes for severe AIS.
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- 2022
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40. The Pattern of Tooth Loss for Periodontally Favorable Teeth: A Retrospective Study.
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Yanni P, Curtis DA, Kao RT, and Lin GH
- Abstract
To retrospectively analyze local and systemic factors that resulted in the short-term tooth loss of teeth that were previously assigned a favorable prognosis in patients who were seen and treated over an observational five-year period. This retrospective study included the records of patients who had a minimum of two dental exams at least twelve months apart over a 5-year period. This study investigated extracted teeth with an initially favorable periodontal prognosis that were then divided into one of four categories based on the reason for extraction: caries, periodontal disease, endodontic reasons, or fracture. Patient- and tooth-related factors associated with the extracted teeth were recorded: crown-to-root ratio, initial pocket depth, initial periodontal diagnosis, maintenance interval, presence of existing restoration, furcation involvement, and systemic conditions. Data analysis was performed using a linear mixed model. A total of 50 patients with 111 teeth met the inclusion criteria for this study. A higher odds ratio (OR) for tooth loss due to caries, endodontic reasons, and fracture were found in teeth with a history of root canal treatment with an OR of 3.61, 3.86, and 2.52, respectively. For tooth loss due to periodontal disease, higher ORs were found in patients who were on anti-depressants (OR = 4.28) and patients who had an initial diagnosis of Stage III/IV periodontitis (OR = 2.66). In addition, teeth with initial probing depths ≥5 mm (OR = 4.32) and with furcation involvement (OR = 1.93) showed a higher OR for tooth loss due to periodontal disease. Within the limitations of this study, previously root-canal-treated teeth present a higher OR for early loss due to caries, recurrent endodontic lesions, or fracture. In addition, patients with anti-depressant medication use, sporadic maintenance, initial probing depths ≥5 mm, and furcation involvement represent a significantly higher OR of tooth loss due to periodontal disease even for initially favorable teeth.
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- 2022
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41. [Professor LIN Guo - hua 's experience in the clinical application of "Dayingxiang"].
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Xiao QE, Wei YZ, Lin SY, and Lin GH
- Subjects
- Vascular Surgical Procedures, Moxibustion, Acupuncture Therapy methods, Acupuncture
- Abstract
The paper introduces professor LIN Guo - hua 's experience in treatment with acupuncture-moxibustion at "Dayingxiang". Based on the application of Neiyingxiang (internal LI 20), professor LIN defines the entire nasal cavity and its adjacent nasopharynx as "Dayingxiang", of which, "Neiyingxiang" and "Biyandian" (nasopharynx point) are commonly stimulated with acupuncture-moxibustion. "Dayingxiang" may regulate lung qi and promote the circulation of the marrow sea in treatment of the disorders of lung system and the marrow. Fire needling with twirling or burning-scallion technique is predominated in manipulation. "Neiyingxiang" is stimulated for the shallow-located disorders, while, "Biyandian" is for the deep-located ones. These two points are optioned alternatively or in combination to enhance the therapeutic effect.
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- 2022
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42. A Bayesian network analysis of immunotherapy and taxane chemotherapy as second- or later-line treatments in non-small cell lung cancer.
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Liu XX, Lin GH, and Wang BC
- Subjects
- Humans, Docetaxel therapeutic use, Bayes Theorem, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Immunotherapy, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung etiology, Lung Neoplasms drug therapy, Lung Neoplasms etiology
- Abstract
Background: Taxane chemotherapy represents the standard of care in the second-line setting for non-small cell lung cancer (NSCLC) patients, but immunotherapy agents pose great challenges. Whether immunotherapy/chemotherapy alone or combination therapy has more benefits remains controversial. In this study, we provided comparisons to integrate the efficacy of immunotherapy and taxane chemotherapy as second- or later-line treatments in advanced NSCLC., Methods: PubMed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials were systematically searched from inception to September 1, 2020. Randomized controlled trials comparing immunotherapy and taxane chemotherapy were enrolled in the Bayesian network analysis. Overall survival (OS) and progression-free survival (PFS) with hazard ratios (HRs) were investigated., Results: Eight trials in 13 studies with 4398 patients comparing seven treatments were identified. Pembrolizumab 10 mg/kg was associated with the best improved OS, with significant differences versus docetaxel (HR 0.81, 95% credible interval [CrI] 0.74-0.88), avelumab (HR 0.84, 95% CrI 0.75-0.95), and pembrolizumab 200 mg plus docetaxel (HR 0.75, 95% CrI 0.56-1.00). Although pembrolizumab 200 mg plus docetaxel ranked the last in terms of OS, the combination therapy showed the most favorable PFS. Additionally, the anti-programmed death-ligand 1 (PD-L1) agent, avelumab, was associated with the least improvement in PFS., Conclusion: As second- or later-line therapeutic strategies, pembrolizumab 10 mg/kg provided the largest OS benefits and pembrolizumab 200 mg plus docetaxel improved PFS to the greatest extent. Considering that immunotherapy has been recommended to the first-line setting of NSCLC, advanced patients who have not received immunotherapy previously might be the suitable population for our findings., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)
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- 2022
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43. Poziotinib in non-small-cell lung cancer patients with HER2 exon 20 mutations: A pooled analysis of randomized clinical trials.
- Author
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Wang BC, Kuang BH, Liu XX, and Lin GH
- Subjects
- Humans, Exons, Mutation, Prospective Studies, Protein Kinase Inhibitors therapeutic use, Randomized Controlled Trials as Topic, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung chemically induced, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Lung Neoplasms chemically induced
- Abstract
Background: Non-small-cell lung cancer (NSCLC) harboring human epidermal growth factor receptor 2 (HER2) exon 20 mutant occurs in 3% of NSCLCs. Targeted agents for this population remain an unmet need. In this analysis, we pooled-analyzed the efficacy and safety of poziotinib, a novel tyrosine kinase inhibitor, in HER2 exon 20 mutant NSCLC., Methods: PubMed, Embase, Web of Science, and Cochrane CENTRAL databases were systematically searched on March 9, 2022. The primary endpoints were objective response rate (ORR) and disease control rate. The secondary endpoint was treatment-related adverse events., Results: Three prospective clinical trials, involving 126 patients, were identified. The pooled ORR and disease control rate of poziotinib in HER2 exon 20 mutant NSCLC were 27% (95% CI, 19-35) and 72% (95% CI, 64-80), respectively. Patients with G778_P780dupGSP had the highest ORR (88%; 95% CI, 33-100; n = 12), followed by Y772_A775dupYVMA (20%; 95% CI, 12-30; n = 88) and G776delinsVC (19%; 95% CI, 0-50; n = 13). The most common grade 3 to 4 treatment-related adverse events were skin rash (36%), diarrhea (23%), and oral mucositis (13%)., Conclusion: Poziotinib demonstrates moderate antitumor activity in previously treated HER2 exon 20 mutant NSCLC patients with a manageable safety profile. In addition, different subgroup mutations show various benefits of poziotinib treatment. Large-scale and multiarm clinical trials are warranted to confirm a suitable population and therapeutic strategies., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)
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- 2022
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44. Development of a Short-Form Stroke Impact Scale Using a Machine Learning Algorithm for Patients at the Subacute Stage.
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Lee SC, Wang I, Lin GH, Li PC, Lee YC, Chou CY, Huang CY, and Hsieh CL
- Subjects
- Humans, Reproducibility of Results, Machine Learning, Algorithms, Stroke, Stroke Rehabilitation
- Abstract
Importance: Several short forms of the Stroke Impact Scale Version 3.0 (SIS 3.0) have been proposed in order to decrease its administration time of about 20 min. However, none of the short-form scores are comparable to those of the original measure., Objective: To develop a short-form SIS 3.0 using a machine learning algorithm (ML-SIS)., Design: We developed the ML-SIS in three stages. First, we calculated the frequencies of items having the highest contribution to predicting the original domain scores across 50 deep neural networks. Second, we iteratively selected the items showing the highest frequency until the coefficient of determination (R2) of each domain was ≥.90. Third, we examined the comparability and concurrent and convergent validity of the ML-SIS., Setting: Hospitals., Participants: We extracted complete data for 1,010 patients from an existing data set., Results: Twenty-eight items were selected for the ML-SIS. High average R2s (.90-.96) and small average residuals (mean absolute errors and root-mean-square errors = 0.49-2.84) indicate good comparability. High correlations (rs = .95-.98) between the eight domain scores of the ML-SIS and the SIS 3.0 indicate sufficient concurrent validity. Similar interdomain correlations between the two measures indicate satisfactory convergent validity., Conclusions and Relevance: The ML-SIS uses about half of the items in the SIS 3.0, has an estimated administration time of 10 min, and provides valid scores comparable to those of the original measure. Thus, the ML-SIS may be an efficient alternative to the SIS 3.0. What This Article Adds: The ML-SIS, a short form of the SIS 3.0 developed using a machine learning algorithm, shows good potential to be an efficient and informative measure for clinical settings, providing scores that are valid and comparable to those of the original measure., (Copyright © 2022 by the American Occupational Therapy Association, Inc.)
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- 2022
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45. Role of EmaSR in Ethanol Metabolism by Acinetobacter baumannii .
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Shu HY, Huang YW, Tsai PY, Hsieh KS, and Lin GH
- Subjects
- Sodium Acetate, Virulence genetics, Ethanol metabolism, Carbon metabolism, Biofilms, Bacterial Proteins genetics, Bacterial Proteins metabolism, Acinetobacter baumannii metabolism
- Abstract
Acinetobacter baumannii is a well-known nosocomial pathogen that can survive in different environments through the use of intricate networks to regulate gene expression. Two-component systems (TCS) form an important part of such regulatory networks, and in this study, we describe the identification and characterization of a novel EmaSR TCS in A. baumannii . We constructed a Tn 5 -tagged mutagenesis library, from which an emaS sensor kinase gene and emaR response regulator gene were identified. We found that emaS / emaR single-mutants and double-mutants were unable to replicate in M9 medium with 1% ethanol as the single carbon source. Motility and biofilm formation were negatively affected in double-mutants, and transcriptomic analysis showed that mutation of emaSR dysregulated genes required for carbon metabolism. In addition, emaS / emaR single-mutants and double-mutants were unable to survive in acetic acid- and sodium acetate-containing medium, indicating that the EmaSR TCS is also important for acetate metabolism. Furthermore, virulence against Galleria mellonella was diminished in emaS / emaR single- and double-mutants. Taken together, these results show that this novel EmaSR TCS is involved in the regulation of A. baumannii ethanol metabolism and acetate metabolism, with important implications on motility, biofilm formation, and virulence if mutated. Further research on the underlying mechanisms is warranted.
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- 2022
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46. The efficacy and tolerability of combining pemetrexed-based chemotherapy with gefitinib in the first-line treatment of non-small cell lung cancer with mutated EGFR: A pooled analysis of randomized clinical trials.
- Author
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Wang BC, Zhang WX, Kuang BH, and Lin GH
- Subjects
- Antineoplastic Combined Chemotherapy Protocols therapeutic use, ErbB Receptors, Humans, Mutation, Randomized Controlled Trials as Topic, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Gefitinib therapeutic use, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Pemetrexed therapeutic use, Protein Kinase Inhibitors therapeutic use
- Abstract
Background: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) monotherapy is the standard of care in treating advanced non-small cell lung cancer (NSCLC). Nevertheless, whether adding pemetrexed-based chemotherapy to EGFR-TKI targeted therapy furtherly prolongs survival outcomes and improves responses remains controversial. Therefore, we conducted this pooled analysis to compare the efficacy and tolerability between gefitinib plus pemetrexed-based chemotherapy and gefitinib alone in the first-line treatment of advanced NSCLC patients with mutated EGFR., Methods: We systematically searched PubMed, Web of Science, Embase, and Cochrane CENTRAL on June 23, 2022. Eligible studies were registered randomized clinical trials comparing gefitinib plus pemetrexed-based chemotherapy with gefitinib alone. The primary outcomes were overall survival (OS) and progression-free survival (PFS). Objective response rate (ORR), disease control rate (DCR), and discontinuation rate (DR) were explored as secondary outcomes., Results: Eight studies within five randomized clinical trials were eligible. Gefitinib combined with pemetrexed-based chemotherapy significantly prolonged OS (hazard ratio [HR] 0.57, 95% confidence interval [CI] 0.37-0.89, p = 0.0125) and PFS (HR 0.52, 95% CI 0.39-0.70, p < 0.0001) versus gefitinib alone. In subgroup analysis, patients with EGFR exon 19 deletion and exon 21 L858R could benefit from the addition of pemetrexed-based chemotherapy to gefitinib in terms of PFS (EGFR exon 19 deletion: HR 0.50, 95% CI 0.34-0.75, p = 0.0008; EGFR exon 21 L858R: HR 0.46, 95% CI 0.26-0.82, p = 0.0079) but not OS. In addition, ORR was improved after the administration of gefitinib plus pemetrexed-based chemotherapy against gefitinib (odds ratio [OR] 1.91, 95% CI 1.44-2.55, p < 0.0001). Both strategies showed comparable DCRs (OR 1.46, 95% CI 0.94-2.26, p = 0.0952) and DRs (risk ratio [RR] 2.80, 95% CI 0.69-11.44, p = 0.1509)., Conclusion: Compared with gefitinib alone, combining pemetrexed-based chemotherapy with gefitinib significantly improved OS and PFS in advanced EGFR-mutant NSCLC patients with acceptable tolerability. However, the accurate sub-population who could have OS benefits requires further validation., Competing Interests: The authors have declared that no competing interests exist.
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- 2022
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47. Translating periodontal data to knowledge in a learning health system.
- Author
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Tokede B, Yansane A, White J, Bangar S, Mullins J, Brandon R, Gantela S, Kookal K, Rindal D, Lee CT, Lin GH, Spallek H, Kalenderian E, and Walji M
- Subjects
- Dental Informatics, Humans, Population Health, Learning Health System, Periodontal Diseases complications, Periodontal Diseases epidemiology, Periodontal Diseases prevention & control, Periodontitis, Tooth Loss epidemiology, Tooth Loss prevention & control
- Abstract
Background: A learning health system (LHS) is a health system in which patients and clinicians work together to choose care on the basis of best evidence and to drive discovery as a natural outgrowth of every clinical encounter to ensure the right care at the right time. An LHS for dentistry is now feasible, as an increased number of oral health care encounters are captured in electronic health records (EHRs)., Methods: The authors used EHRs data to track periodontal health outcomes at 3 large dental institutions. The 2 outcomes of interest were a new periodontitis case (for patients who had not received a diagnosis of periodontitis previously) and tooth loss due to progression of periodontal disease., Results: The authors assessed a total of 494,272 examinations (new periodontitis outcome: n = 168,442; new tooth loss outcome: n = 325,830), representing a total of 194,984 patients. Dynamic dashboards displaying performance on both measures over time allow users to compare demographic and risk factors for patients. The incidence of new periodontitis and tooth loss was 4.3% and 1.2%, respectively., Conclusions: Periodontal disease, diagnosis, prevention, and treatment are particularly well suited for an LHS model. The results showed the feasibility of automated extraction and interpretation of critical data elements from the EHRs. The 2 outcome measures are being implemented as part of a dental LHS. The authors are using this knowledge to target the main drivers of poorer periodontal outcomes in a specific patient population, and they continue to use clinical health data for the purpose of learning and improvement., Practical Implications: Dental institutions of any size can conduct contemporaneous self-evaluation and immediately implement targeted strategies to improve oral health outcomes., (Copyright © 2022 American Dental Association. Published by Elsevier Inc. All rights reserved.)
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- 2022
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48. A Comprehensive Evaluation of Prognostic Value and Immune Infiltration of KDM1 Family in Hepatocellular Carcinoma.
- Author
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Ko YC, Wu SH, Lin GH, Lin CH, Liao GS, Chen YJ, and Hsu KF
- Subjects
- Biomarkers, Tumor, Disease-Free Survival, Histone Demethylases, Humans, Prognosis, Carcinoma, Hepatocellular genetics, Carcinoma, Hepatocellular pathology, Liver Neoplasms genetics, Liver Neoplasms pathology
- Abstract
Introduction: Hepatocellular carcinoma (HCC) is one of the most lethal malignancies in the world. Previous studies indicated that the expression of the KDM1 genes (KDM1s), members of the amine oxidase superfamily, has prognostic value for breast and prostate cancer and malignant neuroblastoma. This study aimed to investigate the expression of KDM1s, their prognostic value, and their correlation with immune infiltration in patients with HCC., Methods: Multiomics analyses were utilized to analyze differential expression, prognostic value, genetic alteration, and immune cell infiltration of KDM1s in patients with HCC., Results: The high expression of KDM1A indicated poor overall survival (OS) and disease-free survival, whereas the high expression of KDM1B was significantly associated with poor OS. The genetic alterations and biological interaction network of KDM1s may provide detailed information for the dysregulated function of KDM1s in patients with HCC. KDM1-related signaling pathways and miRNA targets were explored and may provide value as therapeutic targets or tumor progression markers. The increased mRNA expression of KDM1s was significantly correlated with the infiltration of diverse immune cells in HCC., Conclusions: This data-driven study indicates that KDM1s are promising prognostic biomarkers for survival and have the potential to become novel molecular targets in HCC treatments., (© 2022. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)
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- 2022
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49. Immunotherapy Alone or in Combination with Stereotactic Body Radiotherapy in Advanced Lung Cancer: A Pooled Analysis of Randomized Clinical Trials.
- Author
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Wang BC, Kuang BH, and Lin GH
- Abstract
Background: Immunotherapy has revolutionized the treatment of advanced lung cancer. Nevertheless, it remains unclear whether adding stereotactic body radiotherapy (SBRT) to immunotherapy (IT) further improves responses and survival outcomes. Therefore, in this pooled analysis, we comprehensively compared IT plus SBRT with IT alone in patients with advanced lung cancer., Methods: Online databases, including PubMed, Web of Science, Embase, and Cochrane CENTRAL, were systematically searched on April 24, 2022. Eligible studies were randomized clinical trials comparing IT plus SBRT to IT. The primary outcomes were the objective response rate (ORR) and disease control rate (DCR). Progression-free survival (PFS) and overall survival (OS) were explored as secondary outcomes., Results: Overall, three phase 2 randomized clinical trials with a total of 146 previously treated lung cancer patients were enrolled. The median PFS and OS were 3.8 months and 9.5 months for IT plus SBRT versus 2.4 months and 6.1 months for IT. Comparing IT plus SBRT with IT alone, pooled risk ratios for ORR and DCR were 1.95 (95% confidence interval 1.07-3.53, p = 0.03) and 1.28 (0.94-1.73, p = 0.12). While pooled hazard ratios were 0.77 (0.25-2.42, p = 0.66) for PFS and 0.71 (0.16-3.21, p = 0.65) for OS, respectively. No publication bias was found across the trials., Conclusion: Compared to IT alone, the addition of SBRT improved the best response but failed to prolong the survival outcomes in treating advanced lung cancer patients. Future studies are necessary to explore new modalities of the combination of IT and SBRT., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Bi-Cheng Wang et al.)
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- 2022
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50. Relationship between the stroke mechanism of symptomatic middle cerebral artery atherosclerotic diseases and culprit plaques based on high-resolution vessel wall imaging.
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Lin GH, Song JX, Huang TD, Fu NX, and Zhong LL
- Abstract
Purpose: For patients with symptomatic middle cerebral artery (MCA) atherosclerotic stenosis, identifying the potential stroke mechanisms may contribute to secondary prevention. The purpose of the study is to explore the relationship between stroke mechanisms and the characteristics of culprit plaques in patients with atherosclerotic ischemic stroke in the M1 segment of the middle cerebral artery (MCA) based on high-resolution vessel wall imaging (HR-VWI)., Methods: We recruited 61 patients with acute ischemic stroke due to MCA atherosclerotic stenosis from Shenzhen Bao'an District People's Hospital. According to prespecified criteria based on infarct topography and magnetic resonance angiography, possible stroke mechanisms were divided into parent artery atherosclerosis occluding penetrating artery (P), artery-to-artery embolism (A), hypoperfusion (H), and mixed mechanisms (M). The correlation between the characteristics of MCA M1 culprit plaque and different stroke mechanisms was analyzed using HR-VWI. The indicators included plaque surface irregularity, T1 hyperintensity, location, plaque burden (PB), remodeling index (RI), enhancement rate, and stenosis rate., Results: Parental artery atherosclerosis occluding penetrating artery was the most common mechanism (37.7%). The proposed criteria showed substantial to excellent interrater reproducibility (κ, 0.728; 0.593-0.863). Compared with the P group, the surface irregularity, T1 hyperintensity, and obvious enhancement of the culprit plaque in the A group were more common ( p < 0.0125). Compared with the other stroke mechanisms, positive remodeling of culprit plaques was more common ( p < 0.0125), the RI was greater ( p < 0.05), and the PB was the smallest ( p < 0.05) in the P group. The enhancement ratio (ER) was smaller in the P group ( p < 0.05). Compared with the A group, T1 hyperintensity of the culprit plaque was more common in the H group ( p < 0.0125), and the stenosis rate was greater ( p < 0.05). After adjustment for clinical demographic factors in the binary logistic regression analysis, the enhancement level (odds ratio [ OR ] 0.213, 95% CI (0.05-0.91), p = 0.037) and PB of culprit plaque ( OR 0, 95% CI (0-0.477), p = 0.034) were negatively associated with P groups., Conclusion: The culprit plaque characteristics of patients with symptomatic MCA atherosclerotic in different stroke mechanisms may be evaluated using HR-VWI. The plaque characteristics of different stroke mechanisms may have clinical value for the selection of treatment strategies and prevention of stroke recurrence., Clinical Trial Registration: Identifier: ChiCTR1900028533., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lin, Song, Huang, Fu and Zhong.)
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- 2022
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