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This article discusses a study that explores the potential of combining a CDK7 inhibitor with FLT3 inhibitors for the treatment of FLT3-ITD-mutated acute myeloid leukemia (AML). The researchers found that this combination treatment demonstrated synergistic inhibition of cell proliferation in AML cell lines and induced apoptotic cell death in AML cells. The study suggests that targeting both CDK7 and FLT3 could be a promising therapeutic strategy for patients with FLT3-ITD-mutated AML. The study was supported by grants and the authors have no competing interests. [Extracted from the article]

Background and Objectives: This study aimed to explore biomarker change after NAC (neoadjuvant chemotherapy) and to investigate biomarker expression as a prognostic factor in patients with residual disease (RD) after NAC. Materials and Methods: We retrospectively evaluated 104 patients with invasive breast cancer, who underwent NAC and surgery at Pusan National University Hospital from 2015 to July 2022. The expression of the biomarker was assessed, and the overall survival (OS) and disease-free survival (DFS) were investigated. Results: After NAC, 24 patients (23.1%) out of 104 total patients had a pathological complete response (pCR). We found that changes in at least one biomarker were observed in 41 patients (51.2%), among 80 patients with RD. In patients with RD after NAC (n = 80), a subtype change was identified in 20 patients (25.0%). Any kind of change in the HER2 status was present 19 (23.7%) patients. The hormone receptor (HR)+/HER2+ subtype was significantly associated with better disease-free survival (DFS) (HR, 0.13; 95% CI, 0.02–0.99; p = 0.049). No change in p53 was associated with better DFS, and negative-to-positive change in p53 expression after NAC was correlated with worse DFS (p < 0.001). Negative-to-positive change in p53 was an independent, worse DFS factor in the multivariate analysis (HR,18.44; 95% CI, 1.86–182.97; p = 0.013). Conclusions: Biomarker change and subtype change after NAC were not infrequent, which can affect the further treatment strategy after surgery. The expression change of p53 might have a prognostic role. Overall, we suggest that the re-evaluation of biomarkers after NAC can provide a prognostic role and is needed for the best decision to be made on further treatment. [ABSTRACT FROM AUTHOR]

The degradation of road pavements due to environmental factors is a pressing issue in infrastructure maintenance, necessitating precise identification of pavement distresses. The pavement condition index (PCI) serves as a critical metric for evaluating pavement conditions, essential for effective budget allocation and performance tracking. Traditional manual PCI assessment methods are limited by labor intensity, subjectivity, and susceptibility to human error. Addressing these challenges, this paper presents a novel, end-to-end automated method for PCI calculation, integrating deep learning and image processing technologies. The first stage employs a deep learning algorithm for accurate detection of pavement cracks, followed by the application of a segmentation-based skeleton algorithm in image processing to estimate crack width precisely. This integrated approach enhances the assessment process, providing a more comprehensive evaluation of pavement integrity. The validation results demonstrate a 95% accuracy in crack detection and 90% accuracy in crack width estimation. Leveraging these results, the automated PCI rating is achieved, aligned with standards, showcasing significant improvements in the efficiency and reliability of PCI evaluations. This method offers advancements in pavement maintenance strategies and potential applications in broader road infrastructure management. [ABSTRACT FROM AUTHOR]

Background: The impact of tumor-infiltrating neutrophils (TINs) on clinical outcomes has been reported in various cancer types, but their role in hepatocellular carcinoma (HCC) has not been fully evaluated. The aim of this study was to investigate the prognostic values for TINs in HCC patients undergoing curative resection. Methods: We assessed immune markers (CD3, CD4, CD8, CD66b) using immunohistochemistry in 115 patients who underwent curative resection for HCC. We analyzed the prognostic values for tumor-infiltrating immune cells, including neutrophils, and other clinicopathological factors. Results: In the Multivariate Cox analysis of overall survival (OS), alpha-fetoprotein (AFP) ≥ 100 ng/mL (hazard ratio (HR), 2.74, 95% confidence interval (CI), 1.17–6.44; P = 0.021) and Barcelona Clinic Liver Cancer (BCLC) B/C stage (HR, 3.98, 95% CI, 1.68–9.43; P = 0.020) were found to be independent poor prognostic factors in HCC patients undergoing resection. The presence of CD66b+TINs was observed in 66 (57.4%) patients. However, CD66b+TINs were not associated with recurrence-free survival and OS. Conclusions: Our study identified low CD66b+TINs in resectable HCC, and CD66b+ TINs did not have a significant role for the clinical outcomes of patients undergoing curative resection. The results suggest that TINs may play a role in more advanced stages of HCC. [ABSTRACT FROM AUTHOR]

Alternative cleavage and polyadenylation within introns (intronic APA) generate shorter mRNA isoforms; however, their physiological significance remains elusive. In this study, we developed a comprehensive workflow to analyze intronic APA profiles using the mammalian target of rapamycin (mTOR)-regulated transcriptome as a model system. Our investigation revealed two contrasting effects within the transcriptome in response to fluctuations in cellular mTOR activity: an increase in intronic APA for a subset of genes and a decrease for another subset of genes. The application of this workflow to RNA-seq data from The Cancer Genome Atlas demonstrated that this dichotomous intronic APA pattern is a consistent feature in transcriptomes across both normal tissues and various cancer types. Notably, our analyses of protein length changes resulting from intronic APA events revealed two distinct phenomena in proteome programming: a loss of functional domains due to significant changes in protein length or minimal alterations in C-terminal protein sequences within unstructured regions. Focusing on conserved intronic APA events across 10 different cancer types highlighted the prevalence of the latter cases in cancer transcriptomes, whereas the former cases were relatively enriched in normal tissue transcriptomes. These observations suggest potential, yet distinct, roles for intronic APA events during pathogenic processes and emphasize the abundance of protein isoforms with similar lengths in the cancer proteome. Furthermore, our investigation into the isoform-specific functions of JMJD6 intronic APA events supported the hypothesis that alterations in unstructured C-terminal protein regions lead to functional differences. Collectively, our findings underscore intronic APA events as a discrete molecular signature present in both normal tissues and cancer transcriptomes, highlighting the contribution of APA to the multifaceted functionality of the cancer proteome., (© 2024. The Author(s).)

Study Design: A retrospective study., Objectives: To analyze factors associated with rod fracture (RF) in adult spinal deformity (ASD), and to assess whether the accessory rod (AR) technique can reduce RF occurrence in deformity correction in the setting of minimally invasive lateral lumbar interbody fusion (LLIF)., Summary of Background Data: Instrumentation failure is the most common reason for revision surgery in ASD. Several RF reduction methods have been introduced. However, there are insufficient studies on postoperative RF after deformity correction using minimally invasive LLIF., Materials and Methods: This study included 239 patients (average age 71.4 y and a minimum 2-year follow-up) with ASD who underwent long-segment fusion from T10 to sacrum with sacropelvic fixation. Patients were classified into the non-RF group and the RF group. After logistic regression analysis of the risk factors for RF, subgroup analyses were performed: pedicle subtraction osteotomy (PSO) with two-rod (P2 group) versus PSO with two-rod and AR (P4 group), and LLIF with two-rod (L2 group) versus LLIF with two-rod and AR (L4 group)., Results: RF occurred in 50 patients (21%) at an average of 25 months. RF occurred more frequently in patients who underwent PSO than in those who underwent LLIF ( P =0.002), and the use of the AR technique was significantly higher in the non-RF group ( P <0.05).Following logistic regression analysis, preoperative PI-LL mismatch, PSO, and the AR technique were associated with RF. In subgroup analyses, RF incidence was 65% (24/37 cases) of the P2 group, 8% (4/51 cases) of the P4 group, and 21% (22/105 cases) of the L2 group. In the L4 group, there was no RF., Conclusion: Minimally invasive multilevel LLIF with the AR technique is capable of as much LL correction as conventional PSO and appears to be an effective method for reducing RF., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Current guidelines recommend the perioperative continuation of aspirin in patients with coronary drug-eluting stents (DES) undergoing noncardiac surgery. However, supporting evidence is limited., Objectives: This study aimed to compare continuing aspirin monotherapy vs temporarily holding all antiplatelet therapy before noncardiac surgery in patients with previous DES implantation., Methods: We randomly assigned patients who had received a DES >1 year previously and were undergoing elective noncardiac surgery either to continue aspirin or to discontinue all antiplatelet agents 5 days before noncardiac surgery. Antiplatelet therapy was recommended to be resumed no later than 48 hours after surgery, unless contraindicated. The primary outcome was a composite of death from any cause, myocardial infarction, stent thrombosis, or stroke between 5 days before and 30 days after noncardiac surgery., Results: A total of 1,010 patients underwent randomization. Among 926 patients in the modified intention-to-treat population (462 patients in aspirin monotherapy group and 464 patients in the no-antiplatelet therapy group), the primary composite outcome occurred in 3 patients (0.6%) in the aspirin monotherapy group and 4 patients (0.9%) in the no antiplatelet group (difference, -0.2 percentage points; 95% CI: -1.3 to 0.9; P > 0.99). There was no stent thrombosis in either group. The incidence of major bleeding did not differ significantly between groups (6.5% vs 5.2%; P = 0.39), whereas minor bleeding was significantly more frequent in the aspirin group (14.9% vs 10.1%; P = 0.027)., Conclusions: Among patients undergoing low-to-intermediate risk noncardiac surgery >1 year after stent implantation primarily with a DES, in the setting of lower-than-expected event rates, we failed to identify a significant difference between perioperative aspirin monotherapy and no antiplatelet therapy with respect to ischemic outcomes or major bleeding. (Perioperative Antiplatelet Therapy in Patients With Drug-eluting Stent Undergoing Noncardiac Surgery [ASSURE-DES]; NCT02797548)., Competing Interests: Funding Support and Author Disclosures This research was supported by the CardioVascular Research Foundation (Seoul, Korea) (grant number: AMCCV2016-10), a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (grant number: HC19C0022), and Medtronic. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Thrombus aspiration (TA) is used to decrease large thrombus burden (LTB), but it can cause distal embolization., Objectives: The aim of this study was to investigate the impact of TA failure on defective myocardial perfusion in patients with ST-segment elevation myocardial infarction (STEMI) and LTB., Methods: In total, 812 consecutive patients with STEMI and LTB (thrombus grade ≥3) were enrolled, who underwent manual TA during the primary percutaneous coronary intervention. TA failure was defined as the absence of thrombus retrieval, presence of prestenting thrombus residue, or distal embolization. The final TIMI (Thrombolysis In Myocardial Infarction) flow grades and other myocardial perfusion parameters of the failed TA group were matched with those of the successful TA group., Results: The proportion of final TIMI flow grade 3 was lower (74.6% vs 82.2%; P = 0.011) in the failed TA group (n = 279 [34.4%]) than in the successful TA group (n = 533 [65.6%]). The failed TA group also had lower myocardial blush grade, lower ST-segment resolution, and a higher incidence of microvascular obstruction than the successful TA group. TA failure was independently associated with low final TIMI flow grade (risk ratio: 1.525; 95% CI: 1.048-2.218; P = 0.027). Old age, Killip class ≥III, vessel tortuosity, calcification, and a culprit vessel other than the left anterior descending coronary artery were associated with TA failure., Conclusions: TA failure is associated with reduced myocardial perfusion in patients with STEMI and LTB. Advanced age, hemodynamic instability, hostile coronary anatomy such as tortuosity or calcification, and non-left anterior descending coronary artery status might attenuate TA performance. (Gangwon PCI Prospective Registry [GWPCI]; NCT02038127)., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Study Design: A retrospective study., Objective: To investigate the usefulness of corner osteotomy (CO) in patients with adult spinal deformity (ASD) by comparing with pedicle subtraction osteotomy (PSO) for lordosis correction., Summary of Background Data: PSO remains a valuable procedure for patients with ASD, but it has a limit to obtaining correction angles exceeding 45° in patients with a large pelvic incidence or with previous spinal fusion surgeries. Theoretically, CO can exceed the limitation of PSO and can achieve a wide range of correction angles. However, no study has analyzed the clinical data and usefulness of CO., Methods: This study included 115 patients (mean age 71.1 y, mean follow-up period 78.9 mo) with ASD who underwent deformity correction using PSO or CO. Comparative analysis was performed on spinopelvic parameters including segmental angle (SA) around the osteotomy site, and clinical and surgical assessment between the PSO and corner groups., Results: In the corner group, the postoperative SA (35° vs. -39.3°, P=0.004) and the degree of SA correction (34.8° vs. 39.7°, P=0.004) were greater, and a broader range of SA correction was also possible (18-51° vs. 18-61°). Although the operative time was longer in the corner group (316.8 min vs. 342.3 min, P=0.014), the estimated blood loss (EBL) was lower (2841.3 mL vs. 2465.4 mL, P=0.032). There was no difference in major complication rates, but the frequency of rod fracture (RF) was lower in the corner group (36/27 vs. 1/51, P<0.05)., Conclusion: CO showed a greater SA correction and achieved a broader range of SA correction angles than PSO with no difference in the incidence of major complications. In addition, the EBL and the frequency of RF were lower. Based on these results, we expect that CO can serve as a promising surgical alternative to PSO for spinal deformity correction among patients with ASD., Competing Interests: *Conflict of interest disclosures: the authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Objectives: Angiographic assessment of coronary stenosis severity using quantitative coronary angiography (QCA) is often inconsistent with that based on fractional flow reserve (FFR) or intravascular ultrasound (IVUS). We investigated the incidence of discrepancies between QCA and FFR or IVUS, and the outcomes of FFR- and IVUS-guided strategies in discordant coronary lesions., Methods: This study was a post-hoc analysis of the FLAVOUR study. We used a QCA-derived diameter stenosis (DS) of 60% or greater, the highest tertile, to classify coronary lesions as concordant or discordant with FFR or IVUS criteria for percutaneous coronary intervention (PCI). The patient-oriented composite outcome (POCO) was defined as a composite of death, myocardial infarction, or revascularization at 24 months., Results: The discordance rate between QCA and FFR or IVUS was 30.2% (n=551). The QCA-FFR discordance rate was numerically lower than the QCA-IVUS discordance rate (28.2% vs. 32.4%, p=0.050). In 200 patients with ≥60% DS, PCI was deferred according to negative FFR (n=141) and negative IVUS (n=59) (15.3% vs. 6.5%, p<0.001). The POCO incidence was comparable between the FFR- and IVUS-guided deferral strategies (5.9% vs. 3.4%, p=0.479). Conversely, 351 patients with DS <60% underwent PCI according to positive FFR (n=118) and positive IVUS (n=233) (12.8% vs. 25.9%, p<0.001). FFR- and IVUS-guided PCI did not differ in the incidence of POCO (9.5% vs. 6.5%, p=0.294)., Conclusions: The proportion of QCA-FFR or IVUS discordance was approximately one third for intermediate coronary lesions. FFR- or IVUS-guided strategies for these lesions were comparable with respect to POCO at 24 months., Trial Registration: ClinicalTrials.gov Identifier: NCT02673424., Competing Interests: Dr. Joo Myung Lee has received institutional research grants from Abbott Vascular, Boston Scientific, Philips Volcano, Terumo Corporation, Donga-ST, and Zoll Medical. Dr. Joo-Yong Hahn received an Institutional Research Grant from the National Evidence-based Healthcare Collaborating Agency, Ministry of Health & Welfare, Republic of Korea, Abbott Vascular, Biosensors, Boston Scientific, Daiichi Sankyo, Donga-ST, Hanmi Pharmaceutical, and Medtronic Inc. Dr. Bon-Kwon Koo received an institutional research grant from Abbott Vascular, Boston Scientific, and Phillips. The authors declare no competing interests., (Copyright © 2024. The Korean Society of Cardiology.)

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder characterized by extracellular amyloid plaques composed of amyloid β-peptide (Aβ). Studies have indicated that Ca 2+ dysregulation is involved in AD pathology. It is reported that decreased capacitative Ca 2+ entry (CCE), a refilling mechanism of intracellular Ca 2+ , resulting in increased Aβ production. In contrast, constitutive activation of CCE could decrease Aβ production. Panax ginseng Meyer is known to enhance memory and cognitive functions in healthy human subjects. We have previously reported that some ginsenosides decrease Aβ levels in cultured primary neurons and AD mouse model brains. However, mechanisms involved in the Aβ-lowering effect of ginsenosides remain unclear. In this study, we investigated the relationship between CCE and Aβ production by examining the effects of various ginsenosides on CCE levels. Aβ-lowering ginsenosides such as Rk1, Rg5, and Rg3 potentiated CCE. In contrast, ginsenosides without Aβ-lowering effects (Re and Rb2) failed to potentiate CCE. The potentiating effect of ginsenosides on CCE was inhibited by the presence of 2-aminoethoxydipherryl borate (2APB), an inhibitor of CCE. 2APB alone increased Aβ42 production. Furthermore, the presence of 2APB prevented the effects of ginsenosides on Aβ42 production. Our results indicate that ginsenosides decrease Aβ production via potentiating CCE levels, confirming a close relationship between CCE levels and Aβ production. Since CCE levels are closely related to Aβ production, modulating CCE could be a novel target for AD therapeutics.