Background: Patients who report to be difficult to anesthetize for dental procedures are commonly encountered.Determining their frequency and shared characteristics could improve understanding of pain management failures. Methods: Categorical and continuous variables of 24 demographic, medical history, and dental history variables were compared in a deidentified cross-sectional study using electronic health records (EHR) of patients at the University of Iowa College of Dentistry. Individuals who self-reported to be difficult to anesthetize in their dental health history form were compared to those who reported no complications with local anesthesia. Descriptive, univariate regression, and multivariable regression statistical analyses were completed on the demographic, medical history, and dental history EHR variables. Results: A total of 12,400 deidentified patient records met the inclusion criteria with a 11.4% (n = 1,411) prevalence of difficult to anesthetize self-reports. Eight categorical variables were found to have statistically significant (95% confidence interval [CI]) adjusted odds ratios (AOR) in the multivariable regression of difficult to anesthetize reporting patients: female gender (AOR = 1.61, 95% CI: 1.32-1.96, P < 0.001), dental fear (AOR = 3.60, 95% CI: 3.01-4.31, P < 0.001), mental health disorders (AOR = 1.21, 95% CI: 1.00-1.46, P < 0.045), problems with general anesthesia (AOR = 1.46, 95% CI: 1.11-1.89, P = 0.005), neurologicalerve disorders (AOR = 1.30, 95% CI: 1.05-1.60, P = 0.015), temporomandibular joint clicking/popping (AOR = 1.31, 95% CI: 1.08-1.60, P = 0.006), needle anxiety (AOR = 29.03, 95% CI: 23.80-35.52, P < 0.001), and history of root canal treatment (AOR 0.82, 95% CI: 0.68-0.99, P = 0.035). Conclusion A clinically relevant percentage of patients self-reported being difficult to anesthetize for dental procedures. The relationship between local anesthesia inadequacies and variables such as female gender, dental fear, mental health, and neurological disorders requires further investigation. The use of evidence-based local anesthesia approaches and communication practices is suggested to minimize pain experienced and subsequent fear of dental care.

Clinical guidelines typically endorse conventional therapies such as 5-aminosalicylic acid (5-ASA) as the mainstay of ulcerative colitis management. However, the degree of adoption and application of guideline recommendations by physicians within Asia remains unclear. This study aims to understand the prescribing patterns of 5-ASA and implementation of current guideline recommendations across Asian clinical practice. A physician survey was conducted among inflammatory bowel disease specialists in 8 Asian territories to understand practices and preferences in ulcerative colitis management, focusing on the use of 5-ASA and concordance with guideline recommendations. Survey findings were validated by country experts in diverse healthcare settings. Subgroup analyses stratified data by income levels and treatment reimbursement status. Ninety-eight valid responses were received from inflammatory bowel disease specialists or gastroenterologists among 8 economic entities. Significant differences were found in clinical practices and treatment preferences for ulcerative colitis management among different income-level and government-subsidy groups. Survey results are summarized in 8 findings that illustrate trends in 5-ASA use and guideline implementation across Asian territories. This study emphasizes socioeconomic factors that impact the adoption of guideline recommendations in real-world practice. Our findings indicate an eclectic approach to guideline implementation across Asia, based on resource availability and feasibility of treatment goals.

Clinical guidelines typically endorse conventional therapies such as 5-aminosalicylic acid (5-ASA) as the mainstay of ulcerative colitis management. However, the degree of adoption and application of guideline recommendations by physicians within Asia remains unclear. This study aims to understand the prescribing patterns of 5-ASA and implementation of current guideline recommendations across Asian clinical practice. A physician survey was conducted among inflammatory bowel disease specialists in 8 Asian territories to understand practices and preferences in ulcerative colitis management, focusing on the use of 5-ASA and concordance with guideline recommendations. Survey findings were validated by country experts in diverse healthcare settings. Subgroup analyses stratified data by income levels and treatment reimbursement status. Ninety-eight valid responses were received from inflammatory bowel disease specialists or gastroenterologists among 8 economic entities. Significant differences were found in clinical practices and treatment preferences for ulcerative colitis management among different income-level and government-subsidy groups. Survey results are summarized in 8 findings that illustrate trends in 5-ASA use and guideline implementation across Asian territories. This study emphasizes socioeconomic factors that impact the adoption of guideline recommendations in real-world practice. Our findings indicate an eclectic approach to guideline implementation across Asia, based on resource availability and feasibility of treatment goals.

Background: Patients who report to be difficult to anesthetize for dental procedures are commonly encountered.Determining their frequency and shared characteristics could improve understanding of pain management failures. Methods: Categorical and continuous variables of 24 demographic, medical history, and dental history variables were compared in a deidentified cross-sectional study using electronic health records (EHR) of patients at the University of Iowa College of Dentistry. Individuals who self-reported to be difficult to anesthetize in their dental health history form were compared to those who reported no complications with local anesthesia. Descriptive, univariate regression, and multivariable regression statistical analyses were completed on the demographic, medical history, and dental history EHR variables. Results: A total of 12,400 deidentified patient records met the inclusion criteria with a 11.4% (n = 1,411) prevalence of difficult to anesthetize self-reports. Eight categorical variables were found to have statistically significant (95% confidence interval [CI]) adjusted odds ratios (AOR) in the multivariable regression of difficult to anesthetize reporting patients: female gender (AOR = 1.61, 95% CI: 1.32-1.96, P < 0.001), dental fear (AOR = 3.60, 95% CI: 3.01-4.31, P < 0.001), mental health disorders (AOR = 1.21, 95% CI: 1.00-1.46, P < 0.045), problems with general anesthesia (AOR = 1.46, 95% CI: 1.11-1.89, P = 0.005), neurologicalerve disorders (AOR = 1.30, 95% CI: 1.05-1.60, P = 0.015), temporomandibular joint clicking/popping (AOR = 1.31, 95% CI: 1.08-1.60, P = 0.006), needle anxiety (AOR = 29.03, 95% CI: 23.80-35.52, P < 0.001), and history of root canal treatment (AOR 0.82, 95% CI: 0.68-0.99, P = 0.035). Conclusion A clinically relevant percentage of patients self-reported being difficult to anesthetize for dental procedures. The relationship between local anesthesia inadequacies and variables such as female gender, dental fear, mental health, and neurological disorders requires further investigation. The use of evidence-based local anesthesia approaches and communication practices is suggested to minimize pain experienced and subsequent fear of dental care.

Clinical guidelines typically endorse conventional therapies such as 5-aminosalicylic acid (5-ASA) as the mainstay of ulcerative colitis management. However, the degree of adoption and application of guideline recommendations by physicians within Asia remains unclear. This study aims to understand the prescribing patterns of 5-ASA and implementation of current guideline recommendations across Asian clinical practice. A physician survey was conducted among inflammatory bowel disease specialists in 8 Asian territories to understand practices and preferences in ulcerative colitis management, focusing on the use of 5-ASA and concordance with guideline recommendations. Survey findings were validated by country experts in diverse healthcare settings. Subgroup analyses stratified data by income levels and treatment reimbursement status. Ninety-eight valid responses were received from inflammatory bowel disease specialists or gastroenterologists among 8 economic entities. Significant differences were found in clinical practices and treatment preferences for ulcerative colitis management among different income-level and government-subsidy groups. Survey results are summarized in 8 findings that illustrate trends in 5-ASA use and guideline implementation across Asian territories. This study emphasizes socioeconomic factors that impact the adoption of guideline recommendations in real-world practice. Our findings indicate an eclectic approach to guideline implementation across Asia, based on resource availability and feasibility of treatment goals.

Background: Patients who report to be difficult to anesthetize for dental procedures are commonly encountered.Determining their frequency and shared characteristics could improve understanding of pain management failures. Methods: Categorical and continuous variables of 24 demographic, medical history, and dental history variables were compared in a deidentified cross-sectional study using electronic health records (EHR) of patients at the University of Iowa College of Dentistry. Individuals who self-reported to be difficult to anesthetize in their dental health history form were compared to those who reported no complications with local anesthesia. Descriptive, univariate regression, and multivariable regression statistical analyses were completed on the demographic, medical history, and dental history EHR variables. Results: A total of 12,400 deidentified patient records met the inclusion criteria with a 11.4% (n = 1,411) prevalence of difficult to anesthetize self-reports. Eight categorical variables were found to have statistically significant (95% confidence interval [CI]) adjusted odds ratios (AOR) in the multivariable regression of difficult to anesthetize reporting patients: female gender (AOR = 1.61, 95% CI: 1.32-1.96, P < 0.001), dental fear (AOR = 3.60, 95% CI: 3.01-4.31, P < 0.001), mental health disorders (AOR = 1.21, 95% CI: 1.00-1.46, P < 0.045), problems with general anesthesia (AOR = 1.46, 95% CI: 1.11-1.89, P = 0.005), neurologicalerve disorders (AOR = 1.30, 95% CI: 1.05-1.60, P = 0.015), temporomandibular joint clicking/popping (AOR = 1.31, 95% CI: 1.08-1.60, P = 0.006), needle anxiety (AOR = 29.03, 95% CI: 23.80-35.52, P < 0.001), and history of root canal treatment (AOR 0.82, 95% CI: 0.68-0.99, P = 0.035). Conclusion A clinically relevant percentage of patients self-reported being difficult to anesthetize for dental procedures. The relationship between local anesthesia inadequacies and variables such as female gender, dental fear, mental health, and neurological disorders requires further investigation. The use of evidence-based local anesthesia approaches and communication practices is suggested to minimize pain experienced and subsequent fear of dental care.

Objective:To evaluate the efficacy of gadolinium ethoxybenzyl- diethy-lenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced MRI features in the preoperative prediction of tertiary lymphoid structures (TLS) within hepatocellular carcinoma (HCC) lesions.Methods:This retrospective cross-sectional study included clinical and pathological data from 297 HCC patients treated at the Southwest Hospital, Army Medical University between June 2021 and November 2022. Based on postoperative pathology, patients were categorized into TLS-negative ( n=93) and TLS-positive ( n=204) groups. MRI features of HCC lesions using Gd-EOB-DTPA enhancement and relevant clinical data were analyzed. Intergroup comparisons of imaging features and laboratory findings were performed using independent sample t-test, Mann-Whitney U test, χ2 test, or Fisher exact test, as appropriate. The logistic regression analysis was conducted to identify independent predictors of TLS positivity. A predictive model was constructed and visualized using a nomogram. The model′s predictive performance and clinical utility were assessed using the receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). The area under the ROC curve (AUC) was compared using the DeLong test. Results:Significant differences were observed between the TLS-negative and TLS-positive groups in alpha-fetoprotein (AFP) levels, intratumoral hemorrhage, and peritumoral satellite nodules in the hepatobiliary phase ( P<0.05). Multivariate logistic regression identified intratumoral hemorrhage ( OR=0.123, 95% CI 0.070-0.216, P<0.001) and peritumoral satellite nodules in the hepatobiliary phase ( OR=0.236, 95% CI 0.093-0.596, P=0.002) as independent predictive factors for TLS-positivity. The imaging model based on these two features yielded an AUC of 0.764 (95% CI 0.709-0.809) for predicting TLS-positivity. When combined with AFP levels, the resulting clinical-imaging model achieved a superior AUC of 0.784 (95% CI 0.732-0.829), which was significantly higher than that of the imaging model alone ( Z=2.20, P=0.028). A nomogram was constructed based on the clinical-imaging model. The calibration curve demonstrated good predictive performance of the nomogram, and the DCA showed that the curve remained above the default line across a range of reasonable threshold probabilities, indicating that patients could derive clinical benefit. Conclusion:A nomogram model based on Gd-EOB-DTPA enhanced MRI features combined with AFP levels can effectively predict the presence of TLS in HCC.

Objective To target at the NKG2A-HLA-E inhibitory axis,a pluripotent stem cell(iPSC)-derived geneti-cally engineered natural killer cells(NK cells)with NKG2A knockout(NKG2A KO-iNK)were prepared and then their tumor-killing efficacy was evaluated in vitro.Methods NKG2A was knocked out in iPSCs using gene-editing technology.These cells were then differentiated into NKG2A KO-iNK cells.Surface markers at each differentiation stage were analyzed by flow cytometry.Western blot confirmed NKG2A knockout,and flow cytometry assessed expres-sion of activating receptors(NKG2D)and natural cytotoxicity receptors(NKp30,NKp44,NKp46)in NKG2A KO-iNK cells.Cytotoxic activity against tumor cell lines with varying human leukocyte antigen E(HLA-E)expression level was evaluated via lactate dehydrogenase(LDH)release assay.Results Co-transfection of iPSCs with Cas9 pro-tein and three small-guide RNAs(sgRNAs)targeting at exons 1 and 2 of the KLRC1 gene(encoding NKG2A)suc-cessfully generated monoclonal NKG2A-knockout iPSCs(NKG2A KO-iPSCs)with a single T-base insertion in exon 1.During iPSC differentiation into NK cells,CD34 expression reached 30％-50％at the embryoid body(EB)stage(day 8),while CD56 and CD 16 expression exceeded 80％by day 28.Western blot confirmed complete NKG2A knockout in NKG2A KO-iNK cells.Flow cytometry revealed comparable expression level of activating receptor NKG2D and cytotox-icity receptors(NKp30,NKp44,NKp46)between NKG2A KO-iNK and wild-type iNK(WT-iNK)cells.The LDH assay results indicated that the cytotoxic activity of NKG2A KO-iNK cells against the HLA-E highly-expressed B-cell precursor leukemia cell line Nalm6 cells was significantly higher than that of WT-iNK cells,while there was no signif-icant difference between them and human myeloma cell line H929 cells with low HLA-E expression and human hepa-tocellular carcinoma cell line HepG2 cells with almost no HLA-E expression.Interferon-γ(IFN-γ)pretreatment up regulated HLA-E expression in Nalm6 cells,further amplifying NKG2A KO-iNK-mediated cytotoxicity.Conclusions By disrupting the NKG2A-HLA-E inhibitory axis,NKG2A KO-iNK cells exhibit markedly enhanced in vitro cytotoxic-ity against HLA-E-high tumor cells.This result highlights their potential function as a novel adoptive cell therapy strategy for cancers reliant on HLA-E-mediated immune evasion.

Objective:To evaluate the efficacy of gadolinium ethoxybenzyl- diethy-lenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced MRI features in the preoperative prediction of tertiary lymphoid structures (TLS) within hepatocellular carcinoma (HCC) lesions.Methods:This retrospective cross-sectional study included clinical and pathological data from 297 HCC patients treated at the Southwest Hospital, Army Medical University between June 2021 and November 2022. Based on postoperative pathology, patients were categorized into TLS-negative ( n=93) and TLS-positive ( n=204) groups. MRI features of HCC lesions using Gd-EOB-DTPA enhancement and relevant clinical data were analyzed. Intergroup comparisons of imaging features and laboratory findings were performed using independent sample t-test, Mann-Whitney U test, χ2 test, or Fisher exact test, as appropriate. The logistic regression analysis was conducted to identify independent predictors of TLS positivity. A predictive model was constructed and visualized using a nomogram. The model′s predictive performance and clinical utility were assessed using the receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). The area under the ROC curve (AUC) was compared using the DeLong test. Results:Significant differences were observed between the TLS-negative and TLS-positive groups in alpha-fetoprotein (AFP) levels, intratumoral hemorrhage, and peritumoral satellite nodules in the hepatobiliary phase ( P<0.05). Multivariate logistic regression identified intratumoral hemorrhage ( OR=0.123, 95% CI 0.070-0.216, P<0.001) and peritumoral satellite nodules in the hepatobiliary phase ( OR=0.236, 95% CI 0.093-0.596, P=0.002) as independent predictive factors for TLS-positivity. The imaging model based on these two features yielded an AUC of 0.764 (95% CI 0.709-0.809) for predicting TLS-positivity. When combined with AFP levels, the resulting clinical-imaging model achieved a superior AUC of 0.784 (95% CI 0.732-0.829), which was significantly higher than that of the imaging model alone ( Z=2.20, P=0.028). A nomogram was constructed based on the clinical-imaging model. The calibration curve demonstrated good predictive performance of the nomogram, and the DCA showed that the curve remained above the default line across a range of reasonable threshold probabilities, indicating that patients could derive clinical benefit. Conclusion:A nomogram model based on Gd-EOB-DTPA enhanced MRI features combined with AFP levels can effectively predict the presence of TLS in HCC.

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition.The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and anti resorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to anti resorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for in dividuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.