Decreased sirtuin 4 levels promote cellular proliferation and invasion in papillary thyroid carcinoma.

Objective: This study examined the effect of sirtuin 4 (SIRT4), a NAD+-dependent deacetylase, on the proliferation and progression of papillary thyroid carcinoma (PTC). Methods: Data from The Cancer Genome Atlas (TCGA) were analyzed to identify SIRT4 expression in thyroid cancer. Subsequently, the correlation between SIRT4 expression and clinical characteristics was examined in 205 PTC tissue samples. In vitro assays using three human thyroid cancer cell lines (B-CPAP, TPC-1, and SNU-790) were conducted to assess the effects of regulated SIRT4 expression on cell growth, apoptosis, invasion, and migration. Furthermore, in vivo experiments were performed in a xenograft mouse model. Results: Gene Expression Omnibus (GEO) and TCGA data indicated that SIRT4 expression is lower in thyroid cancer and SIRT4 downregulation is associated with poor overall survival. In PTC tissues, positive SIRT4 expression was associated with decreased extracapsular extension. In in vitro experiments using three human thyroid cancer cell lines, overexpression of SIRT4 decreased cell survival, clonogenic potential, and invasion and migratory capabilities, as well as inducing apoptosis and increasing reactive oxygen species levels. SIRT4 overexpression upregulated E-cadherin and downregulated N-cadherin, suggesting its potential involvement in the regulation of epithelial-mesenchymal transition. These findings were confirmed in vivo using a xenograft mouse model. Conclusion: This study provides novel insight into the potential contribution of SIRT4 to the regulation of the pathological progression of PTC. The data suggest that SIRT4 plays a tumor-suppressive role in PTC by inhibiting growth, survival, and invasive potential. Future research should investigate the molecular mechanisms underlying these effects of SIRT4.

Determining the debris flow yield strength of weathered soils: a case study of the Miryang debris flow in the Republic of Korea.

Debris flow hazards are often interpreted through back-calculated simulation analysis or empirical methods. The mobility of a debris flow is greatly influenced by mechanical and hydrological parameters. The strength parameters play important roles in the debris flow initiation and flow stages. In particular, the rheological parameters of yield strength and plastic viscosity directly affect the debris flow runout distance and velocity. One of the most important parameters to consider when evaluating debris flow hazards is the shear strength. This strength is called the residual shear strength in the failure stage and the yield strength in the post-failure stage. The residual shear strength obtained from ring shear tests can be related to the initiation of mass movements; the yield strength obtained from rheological tests can be related to the mobilization of debris flows. The residual shear stresses obtained from ring shear tests of weathered soils typically range between 10 and 100 kPa and strongly depend on the normal stress and shear velocity. When progressive slope failure (i.e., strain-softening behavior) occurs at a relatively shallow slope depth (e.g., < 1 m), the soil strength ranges from approximately 5-10 kPa. If the liquid limit state (i.e., solid‒liquid transition) is reached, the shear strength of the soil is approximately 2 kPa. Once the soil fails and mixes with ambient water along the slip surface, the yield strength decreases dramatically, resulting in high mobilization. A suggestion on how strength parameters can be applied to estimate debris flow mobility is presented by considering the 2011 Miryang debris flow, which occurred in weathered soil deposits in Miryang city, Republic of Korea. The best approach for debris flow yield strength estimation would be to consider the residual shear strength in the initiation stage, the yield strength in the flow stage, and the reduction in yield strength with the entrainment effect of the flow in the rapid fluidization stage.

Optical coherence tomography-guided versus angiography-guided percutaneous coronary intervention for patients with complex lesions (OCCUPI): an investigator-initiated, multicentre, randomised, open-label, superiority trial in South Korea.

BACKGROUND: Despite the detailed imaging information provided by optical coherence tomography (OCT) during percutaneous coronary intervention (PCI), clinical benefits of this imaging technique in this setting remain uncertain. The aim of the OCCUPI trial was to compare the clinical benefits of OCT-guided versus angiography-guided PCI for complex lesions, assessed as the rate of major adverse cardiac events at 1 year. METHODS: This investigator-initiated, multicentre, randomised, open-label, superiority trial conducted at 20 hospitals in South Korea enrolled patients aged 19-85 years for whom PCI with drug-eluting stents was clinically indicated. After diagnostic angiography, clinical and angiographic findings were assessed to identify patients who met the criterion of having one or more complex lesions. Patients were randomly assigned 1:1 to receive PCI with OCT guidance (OCT-guidance group) or angiography guidance without OCT (angiography-guidance group). Web-response permuted-block randomisation (mixed blocks of four or six) was used at each participating site to allocate patients. The allocation sequence was computer-generated by an external programmer who was not involved in the rest of the trial. Outcome assessors were masked to group assignment. Patients, follow-up health-care providers, and data analysers were not masked. PCI was done according to conventional standard methods with everolimus-eluting stents. The primary endpoint was major adverse cardiac events (a composite of cardiac death, myocardial infarction, stent thrombosis, or ischaemia-driven target-vessel revascularisation), 1 year after PCI. The primary analysis was done in the intention-to-treat population. The margin used to establish superiority was 1·0 as a hazard ratio. This trial is registered with ClinicalTrials.gov (NCT03625908) and is completed. FINDINGS: Between Jan 9, 2019, and Sept 22, 2022, 1604 patients requiring PCI with drug-eluting stents for complex lesions were randomly assigned to receive either OCT-guided PCI (n=803) or angiography-guided PCI (n=801). 1290 (80%) of 1604 patients were male and 314 (20%) were female. The median age of patients at randomisation was 64 years (IQR 57-70). 1588 (99%) patients completed 1-year follow-up. The primary endpoint occurred in 37 (5%) of 803 patients in the OCT-guided PCI group and 59 (7%) of 801 patients in the angiography-guided PCI group (absolute difference -2·8% [95% CI -5·1 to -0·4]; hazard ratio 0·62 [95% CI 0·41 to 0·93]; p=0·023). Rates of stroke, bleeding events, and contrast-induced nephropathy were not significantly different across the two groups. INTERPRETATION: Among patients who required drug-eluting stent implantation for complex lesions, OCT guidance resulted in a lower incidence of major adverse cardiac events at 1 year compared with angiography guidance. These findings indicate the existence of a therapeutic benefit of OCT as an intravascular imaging technique for PCI guidance in patients with complex coronary lesions. FUNDING: Abbott Vascular and Cardiovascular Research Center. TRANSLATION: For the Korean translation of the abstract see Supplementary Materials section.

Sub-lethal effects of metals and pesticides on the freshwater dinoflagellate Palatinus apiculatus and environmental implications.

Microalgae are unicellular, photosynthetic organisms in aquatic environments and are sensitive to water quality and contaminants. While green algae and diatoms are widely used for toxicity assessments, there is a relatively limited amount of toxicity data available for freshwater dinoflagellates. Here, we evaluated the sub-lethal effects of the metals Cu, Cr, Ni, and Zn and the herbicides atrazine and S-metolachlor on the freshwater dinoflagellate Palatinus apiculatus. Based on the 72-h median effective concentration (EC50), P. apiculatus showed sensitive responses to metals in the order of Cu (0.052 mg L-1), Cr (0.085 mg L-1), Zn (0.098 mg L-1), and Ni (0.13 mg L-1). Among the tested herbicides, P. apiculatus was more sensitive to atrazine (0.0048 mg L-1) than S-metolachlor (0.062 mg L-1). In addition, we observed morphological alterations and significant increases in reactive oxygen species (ROS) production in cells exposed to 0.05 mg L-1 of Cu and 0.005 mg L-1 of atrazine. These indicated that metals and pesticides induced oxidative stress in cellular metabolic processes and consequently caused severe physiological damage to the cells. Our results provide baseline data on the toxic effects of typical environmental contaminants on freshwater dinoflagellate, suggesting that P. apiculatus could be used as a bioindicator in freshwater toxicity assessments. PRACTITIONER POINTS: The sub-lethal effects of metals and pesticides on the freshwater dinoflagellate Palatinus apiculatus were evaluated. Palatinus sensitively responded to metals and pesticides; of test chemicals, atrazine (0.0048 mg L-1 of EC50) was the most sensitive. Metals and pesticides induced oxidative stress and consequently caused severe physiological damage to the Palatinus cells. The freshwater dinoflagellate Palatinus can be used as a bioindicator in freshwater toxicity assessments.

Treatment extent of femoropopliteal disease and clinical outcomes following endovascular therapy.

BACKGROUND: Endovascular therapy (EVT) has become the preferred treatment modality for femoropopliteal disease. However, there is limited evidence regarding its procedural and clinical outcomes according to the affected area. AIMS: The aim of this study is to investigate clinical outcomes and device effectiveness according to treatment extent in the superficial femoral artery (SFA), popliteal artery (PA), or both. METHODS: In this study, we analysed EVT for SFA (2,404 limbs), PA (155 limbs), SFA/PA (383 limbs) using the population in the K-VIS ELLA (Korean Vascular Intervention Society Endovascular Therapy in Lower Limb Artery Diseases) registry. The primary endpoint was target lesion revascularisation (TLR) at 2 years. RESULTS: The SFA/PA group exhibited a higher prevalence of anatomical complexity, characterised by long lesions, moderate to severe calcification, and total occlusion. The procedures were successful in 97.2% of SFA, 92.9% of PA, and 95.6% of SFA/PA EVTs. The 2-year TLR rates were 21.1%, 18.6%, and 32.7% in the SFA, PA, and SFA/PA groups, respectively. SFA/PA EVT was associated with a significantly increased risk for TLR compared to the SFA group (adjusted hazard ratio [HR] 1.48 [1.09-2.00]; p=0.008) and a trend towards an increased risk compared to the PA group (adjusted HR 1.80 [1.00-3.27]; p=0.052). After overlap weighting, the use of a drug-coated balloon (DCB) was shown to be beneficial, with the lowest TLR rate after SFA and SFA/PA EVT. CONCLUSIONS: In this large real-world registry, SFA/PA EVT was associated with an increased risk for TLR at 2 years compared to the SFA or PA EVT groups, with favourable outcomes when using a DCB or drug-eluting stent in the SFA/PA EVT group.

Automated Idiopathic Normal-Pressure Hydrocephalus Diagnosis via Artificial Intelligence-Based 3D T1 MRI Volumetric Analysis.

BACKGROUND AND PURPOSE: Idiopathic normal pressure hydrocephalus (iNPH) is reversible dementia, that is underdiagnosed. The purpose of this study was to develop an automated diagnostic method for iNPH using artificial intelligence techniques with a T1-weighted MRI scan. MATERIALS AND METHODS: We quantified iNPH, Parkinson's disease, Alzheimer's disease, and healthy control patients on T1-weighted 3D brain MRI scans using 452 scans for training and 110 scans for testing. Automatic component measurement algorithms were developed for Evans' index, Sylvian fissure enlargement, high-convexity tightness, callosal angle, and normalized lateral ventricle volume. XGBoost models were trained for both automated measurements and manual labels for iNPH prediction. RESULTS: A total of 452 patients (200 men; mean age ± standard deviation, 73.2 ± 6.5 years) were included in the training set. Of the 452 patients, 111 (24.6%) had iNPH. We obtained AUC values of 0.956 for automatically measured high-convexity tightness and 0.830 for Sylvian fissure enlargement. Intra-class correlation values of 0.824 for the callosal angle and 0.924 for Evans' index were measured. Using the decision tree of the XGBoost model, the model trained on manual labels obtained an average cross-validation AUC of 0.988 on the training set and 0.938 on the unseen test set, while the fully automated model obtained a cross-validation AUC of 0.983 and an unseen test AUC of 0.936. CONCLUSION: We demonstrated a machine-learning algorithm capable of diagnosing iNPH from a 3D T1-weighted MRI scan that is robust to the failure. We propose a method to scan large numbers of 3D T1-weighted MRI scans with minimal human intervention, making possible large-scale iNPH screening. ABBREVIATIONS: iNPH = idiopathic normal-pressure hydrocephalus; PD = Parkinson's disease; AD = Alzheimer's disease; HC = healthy control; CSF = cerebrospinal fluid; DESH = disproportionately enlarged subarachnoid space hydrocephalus; 3D = three-dimensional.

Drug-coated balloon versus drug-eluting stent for femoropopliteal total occlusions: intraluminal versus subintimal approaches.

Because there is a lack of comparative studies assessing drug-coated balloon (DCB) and drug-eluting stent (DES) outcomes with respect to intraluminal (IL) and subintimal (SI) approaches in femoropopliteal (FP) total occlusive lesions, we compared the outcomes between DCB (including bailout stenting) and DES treatments for this lesion. A total of 487 limbs (434 patients) were divided into the IL (n = 344, DCB: n = 268, DES: n = 76) and SI (n = 143, DCB: n = 83, DES: n = 60) approach groups. The primary outcome was a major adverse limb event (MALE), defined as above-ankle amputation or repeat revascularization of the index limb. Secondary outcomes included clinically driven target lesion revascularization (TLR), loss of clinical patency, and all-cause death. After adjustment, in each IL and SI approach, the 2-year rates of MALE (p = 0.180 and p = 0.236, respectively), TLR, loss of clinical patency, and all-cause death were similar between the DCB and DES groups. In the DCB and DES groups, both primary and secondary outcomes were similar between the IL and SI approaches. DCB and DES strategies for patients presenting with FP total occlusive lesions demonstrated similar outcomes regardless of the IL or SI approach.Clinical Trial Registration: NCT02748226.

Decreased sirtuin 4 levels promote cellular proliferation and invasion in papillary thyroid carcinoma.

Objective: This study examined the effect of sirtuin 4 (SIRT4), a NAD+-dependent deacetylase, on the proliferation and progression of papillary thyroid carcinoma (PTC). Methods: Data from The Cancer Genome Atlas (TCGA) were analyzed to identify SIRT4 expression in thyroid cancer. Subsequently, the correlation between SIRT4 expression and clinical characteristics was examined in 205 PTC tissue samples. In vitro assays using three human thyroid cancer cell lines (B-CPAP, TPC-1, and SNU-790) were conducted to assess the effects of regulated SIRT4 expression on cell growth, apoptosis, invasion, and migration. Furthermore, in vivo experiments were performed in a xenograft mouse model. Results: Gene Expression Omnibus (GEO) and TCGA data indicated that SIRT4 expression is lower in thyroid cancer and SIRT4 downregulation is associated with poor overall survival. In PTC tissues, positive SIRT4 expression was associated with decreased extracapsular extension. In in vitro experiments using three human thyroid cancer cell lines, overexpression of SIRT4 decreased cell survival, clonogenic potential, and invasion and migratory capabilities, as well as inducing apoptosis and increasing reactive oxygen species levels. SIRT4 overexpression upregulated E-cadherin and downregulated N-cadherin, suggesting its potential involvement in the regulation of epithelial-mesenchymal transition. These findings were confirmed in vivo using a xenograft mouse model. Conclusion: This study provides novel insight into the potential contribution of SIRT4 to the regulation of the pathological progression of PTC. The data suggest that SIRT4 plays a tumor-suppressive role in PTC by inhibiting growth, survival, and invasive potential. Future research should investigate the molecular mechanisms underlying these effects of SIRT4.

Ticagrelor monotherapy in ST-elevation myocardial infarction: An individual patient-level meta-analysis from TICO and T-PASS trials.

BACKGROUND: Patients with ST-elevation myocardial infarction (STEMI) tend to be excluded or under-represented in randomized clinical trials evaluating the effects of potent P2Y12 inhibitor monotherapy after short-term dual antiplatelet therapy (DAPT). METHODS: Individual patient data were pooled from randomized clinical trials that included STEMI patients undergoing drug-eluting stent (DES) implantation and compared ticagrelor monotherapy after short-term (≤3 months) DAPT versus ticagrelor-based 12-month DAPT in terms of centrally adjudicated clinical outcomes. The co-primary outcomes were efficacy outcome (composite of all-cause death, myocardial infarction, or stroke) and safety outcome (Bleeding Academic Research Consortium type 3 or 5 bleeding) at 1 year. FINDINGS: The pooled cohort contained 2,253 patients with STEMI. The incidence of the primary efficacy outcome did not differ between the ticagrelor monotherapy group and the ticagrelor-based DAPT group (1.8% versus 2.0%; hazard ratio [HR] = 0.88; 95% confidence interval [CI] = 0.49-1.61; p = 0.684). There was no difference in cardiac death between the groups (0.6% versus 0.7%; HR = 0.89; 95% CI = 0.32-2.46; p = 0.822). The incidence of the primary safety outcome was significantly lower in the ticagrelor monotherapy group (2.3% versus 4.0%; HR = 0.56; 95% CI = 0.35-0.92; p = 0.020). No heterogeneity of treatment effects was observed for the primary outcomes across subgroups. CONCLUSIONS: In patients with STEMI treated with DES implantation, ticagrelor monotherapy after short-term DAPT was associated with lower major bleeding without an increase in the risk of ischemic events compared with ticagrelor-based 12-month DAPT. Further research is necessary to extend these findings to non-Asian patients. FUNDING: This study was funded by Biotronik (Bülach, Switzerland).

Effect of rosuvastatin versus atorvastatin on new-onset diabetes mellitus in patients treated with high-intensity statin therapy for coronary artery disease: a post-hoc analysis from the LODESTAR randomized clinical trial.

BACKGROUND: The impact of rosuvastatin versus atorvastatin on new-onset diabetes mellitus (NODM) among patients treated with high-intensity statin therapy for coronary artery disease (CAD) remains to be clarified. This study aimed to evaluate the risk of NODM in patients with CAD treated with rosuvastatin compared to atorvastatin in the randomized LODESTAR trial. METHODS: In the LODESTAR trial, patients with CAD were randomly assigned to receive either rosuvastatin or atorvastatin using a 2-by-2 factorial randomization. In this post-hoc analysis, the 3-year incidence of NODM was compared between rosuvastatin and atorvastatin treatment in the as-treated population with high-intensity statin therapy as the principal population of interest. RESULTS: Among 2932 patients without diabetes mellitus at baseline, 2377 were included in the as-treated population analysis. In the as-treated population with high-intensity statin therapy, the incidence of NODM was not significantly different between the rosuvastatin and atorvastatin groups (11.4% [106/948] versus 8.8% [73/856], hazard ratio [HR] = 1.32, 95% confidence interval [CI] = 0.98 to 1.77, P = 0.071). When the risk of NODM with rosuvastatin versus atorvastatin was assessed according to the achieved low-density lipoprotein cholesterol (LDL-C) level, the risk of NODM began to increase at a LDL-C level below 70 mg/dL. The incidence of NODM was significantly greater in the rosuvastatin group than it was in the atorvastatin group when the achieved LDL-C level was < 70 mg/dL (13.9% versus 8.0%; HR = 1.79, 95% CI 1.18 to 2.73, P = 0.007). CONCLUSIONS: Among CAD patients receiving high-intensity statin therapy, the incidence of NODM was not significantly different between rosuvastatin and atorvastatin. However, a drug effect of the statin type on NODM was observed when the achieved LDL-C level was < 70 mg/dL. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT02579499.

Development of Clinically Validated Artificial Intelligence Model for Detecting ST-segment Elevation Myocardial Infarction.

STUDY OBJECTIVE: Although the importance of primary percutaneous coronary intervention has been emphasized for ST-segment elevation myocardial infarction (STEMI), the appropriateness of the cardiac catheterization laboratory activation remains suboptimal. This study aimed to develop a precise artificial intelligence (AI) model for the diagnosis of STEMI and accurate cardiac catheterization laboratory activation. METHODS: We used electrocardiography (ECG) waveform data from a prospective percutaneous coronary intervention registry in Korea in this study. Two independent board-certified cardiologists established a criterion standard (STEMI or Not STEMI) for each ECG based on corresponding coronary angiography data. We developed a deep ensemble model by combining 5 convolutional neural networks. In addition, we performed clinical validation based on a symptom-based ECG data set, comparisons with clinical physicians, and external validation. RESULTS: We used 18,697 ECGs for the model development data set, and 1,745 (9.3%) were STEMI. The AI model achieved an accuracy of 92.1%, sensitivity of 95.4%, and specificity of 91.8 %. The performances of the AI model were well balanced and outstanding in the clinical validation, comparison with clinical physicians, and the external validation. CONCLUSION: The deep ensemble AI model showed a well-balanced and outstanding performance. As visualized with gradient-weighted class activation mapping, the AI model has a reasonable explainability. Further studies with prospective validation regarding clinical benefit in a real-world setting should be warranted.

Intravascular ultrasound-guided drug-coated balloon angioplasty for femoropopliteal artery disease: a clinical trial.

BACKGROUND AND AIMS: Drug-coated balloons (DCBs) have demonstrated favourable outcomes following endovascular therapy for femoropopliteal artery (FPA) disease. However, uncertainty remains whether the use of intravascular ultrasound (IVUS) can improve the outcomes of DCBs. METHODS: This prospective, multicentre, randomized trial, conducted at seven centres in South Korea, compared the outcomes of IVUS-guided vs. angiography-guided angioplasty for treating FPA disease with DCBs. Patients were assigned to receive IVUS-guided (n = 119) or angiography-guided (n = 118) angioplasty using DCBs. The primary endpoint was 12-month primary patency. RESULTS: Between May 2016 and August 2022, 237 patients were enrolled and 204 (86.0%) completed the trial (median follow-up; 363 days). The IVUS guidance group showed significantly higher primary patency [83.8% vs. 70.1%; cumulative difference 19.6% (95% confidence interval 6.8 to 32.3); P = .01] and increased freedom from clinically driven target lesion revascularization [92.4% vs. 83.0%; difference 11.6% (95% confidence interval 3.1 to 20.1); P = .02], sustained clinical improvement (89.1% vs. 76.3%, P = .01), and haemodynamic improvement (82.4% vs. 66.9%, P = .01) at 12 months compared with the angiography guidance group. The IVUS group utilized larger balloon diameters and pressures for pre-dilation, more frequent post-dilation, and higher pressures for post-dilation, resulting in a greater post-procedural minimum lumen diameter (3.90 ± 0.59 vs. 3.71 ± 0.73 mm, P = .03). CONCLUSIONS: Intravascular ultrasound guidance significantly improved the outcomes of DCBs for FPA disease in terms of primary patency, freedom from clinically driven target lesion revascularization, and sustained clinical and haemodynamic improvement at 12 months. These benefits may be attributed to IVUS-guided optimization of the lesion before and after DCB treatment.

Treat-to-target or high-intensity statin treatment in older adults with coronary artery disease: a post hoc analysis of the LODESTAR trial.

BACKGROUND: The optimal statin treatment strategy that is balanced for both efficacy and safety has not been clearly determined in older adults with coronary artery disease (CAD). METHODS: In the post hoc analysis of the LODESTAR (low-density lipoprotein cholesterol-targeting statin therapy versus intensity-based statin therapy in patients with coronary artery disease) trial, the impact between a treat-to-target strategy versus a high-intensity statin therapy strategy was compared in older adults (aged 75 years or older). The goal of treat-to-target low-density lipoprotein cholesterol (LDL-C) level was 50-70 mg/dl. The primary endpoint comprised the three-year composite of all-cause death, myocardial infarction, stroke or coronary revascularisation. RESULTS: Among 4,400 patients with CAD enrolled in the LODESTAR trial, 822 (18.7%) were aged 75 years or older. Poor clinical outcomes and risk factors for atherosclerosis were more frequently observed in older adults than in younger population (<75 years old). Among these older adults with CAD, the prescription rate of high-intensity statin was significantly lower in the treat-to-target strategy group throughout the study period (P < 0.001). The mean LDL-C level for three years was 65 ± 16 mg/dl in the treat-to-target strategy group and 64 ± 18 mg/dl in the high-intensity statin group (P = 0.34). The incidence of primary endpoint occurrence was 10.9% in the treat-to-target strategy group and 12.0% in the high-intensity statin group (hazard ratio 0.92, 95% confidence interval 0.61-1.38, P = 0.69). CONCLUSIONS: High-intensity statin therapy is theoretically more necessary in older adults because of worse clinical outcomes and greater number of risk factors for atherosclerosis. However, the primary endpoint occurrence with a treat-to-target strategy with an LDL-C goal of 50-70 mg/dl was comparable to that of high-intensity statin therapy and reduced utilisation of a high-intensity statin. Taking efficacy as well as safety into account, adopting a tailored approach may be considered for this high-risk population. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02579499.

Unusual Dzyaloshinskii-Moriya Interaction in Graphene/Fe3GeTe2 Van der Waals Heterostructure.

Dzyaloshinskii-Moriya interaction (DMI) is shown to induce a topologically protected chiral spin texture in magnetic/nonmagnetic heterostructures. In the context of van der Waals spintronic devices, graphene emerges as an excellent candidate material. However, due to its negligible spin-orbit interaction, inducing DMI to stabilize topological spins when coupled to 3d-ferromagnets remains challenging. Here, it is demonstrated that, despite these challenges, a sizeable Rashba-type spin splitting followed by significant DMI is induced in graphene/Fe3GeTe2. This is made possible due to an interfacial electric field driven by charge asymmetry together with the broken inversion symmetry of the heterostructure. These findings reveal that the enhanced DMI energy parameter, resulting from a large effective electron mass in Fe3GeTe2, remarkably contributes to stabilizing non-collinear spins below the Curie temperature, overcoming the magnetic anisotropy energy. These results are supported by the topological Hall effect, which coexists with the non-trivial breakdown of Fermi liquid behavior, confirming the interplay between spins and non-trivial topology. This work paves the way toward the design and control of interface-driven skyrmion-based devices.

MAST4 regulates stem cell maintenance with DLX3 for epithelial development and amelogenesis.

The asymmetric division of stem cells permits the maintenance of the cell population and differentiation for harmonious progress. Developing mouse incisors allows inspection of the role of the stem cell niche to provide specific insights into essential developmental phases. Microtubule-associated serine/threonine kinase family member 4 (Mast4) knockout (KO) mice showed abnormal incisor development with low hardness, as the size of the apical bud was decreased and preameloblasts were shifted to the apical side, resulting in amelogenesis imperfecta. In addition, Mast4 KO incisors showed abnormal enamel maturation, and stem cell maintenance was inhibited as amelogenesis was accelerated with Wnt signal downregulation. Distal-Less Homeobox 3 (DLX3), a critical factor in tooth amelogenesis, is considered to be responsible for the development of amelogenesis imperfecta in humans. MAST4 directly binds to DLX3 and induces phosphorylation at three residues within the nuclear localization site (NLS) that promotes the nuclear translocation of DLX3. MAST4-mediated phosphorylation of DLX3 ultimately controls the transcription of DLX3 target genes, which are carbonic anhydrase and ion transporter genes involved in the pH regulation process during ameloblast maturation. Taken together, our data reveal a novel role for MAST4 as a critical regulator of the entire amelogenesis process through its control of Wnt signaling and DLX3 transcriptional activity.

The Direct Tendon Suture and Paratenon Repair Technique for Acute Tendinous Mallet Finger: A Case Series.

(1) Introduction: Tendinous mallet finger is a frequent deformity that occurs after an extensor tendon injury during sports or daily life activities. Despite the existence of numerous non-operative and operative techniques to address this deformity, there is a controversy on its optimal management. In this study, we aimed to present a direct tendon suture technique using the distal interphalangeal (DIP) joint open approach for treating tendinous mallet finger injury. (2) Methods: Between 2019 and 2021, 19 patients with closed non-fracture tendinous mallet fingers underwent the direct tendon and paratenon repair technique. After skin incision, we opened the paratenon with lazy S shape incision and found the ruptured proximal and distal tendon ends. We reapproximated the tendons using a simple interrupted suture with Prolene #6/0. After that, we meticulously performed paratenon repair using PDS #6/0 for preventing readherence. Temporary trans-articular Kirschner wire fixation was used for 4 weeks. (3) Results: All patients were followed-up for 3-8 months (mean: 4.8 months). The mean final extension lag was 6.5 degrees, and the overall rate of cases with excellent and good outcomes using Crawford's criteria was 85%. (4) Conclusions: In conclusion, this surgical approach could be a reliable alternative for the treatment of tendinous mallet finger injuries.

Modulation of macrophage transcript and secretion profiles by Sargassum Serratifolium extract is associated with the suppression of muscle atrophy.

Recent research has emphasized the role of macrophage-secreted factors on skeletal muscle metabolism. We studied Sargassum Serratifolium ethanol extract (ESS) in countering lipopolysaccharide (LPS)-induced changes in the macrophage transcriptome and their impact on skeletal muscle. Macrophage-conditioned medium (MCM) from LPS-treated macrophages (LPS-MCM) and ESS-treated macrophages (ESS-MCM) affected C2C12 myotube cells. LPS-MCM upregulated muscle atrophy genes and reduced glucose uptake, while ESS-MCM reversed these effects. RNA sequencing revealed changes in the immune system and cytokine transport pathways in ESS-treated macrophages. Protein analysis in ESS-MCM showed reduced levels of key muscle atrophy-related proteins, TNF-α, IL-6, IL-1, and GDF-15. These proteins play crucial roles in muscle function. These findings highlight the intricate relationship between the macrophage transcriptome and their secreted factors in either impairing or enhancing skeletal muscle function. ESS treatment has the potential to reduce macrophage-derived cytokines, preserving skeletal muscle function.

Korean Multicenter Registry of ELUVIA Stent for Femoropopliteal Artery Disease: K-ELUVIA Registry.

BACKGROUND AND OBJECTIVES: The K-ELUVIA study aimed to investigate the clinical effectiveness and safety of Eluvia™, a polymer-coated, paclitaxel-eluting stent, for femoropopliteal artery disease using data from a prospective Korean multicenter registry. METHODS: A total of 105 patients with femoropopliteal artery disease who received endovascular treatment (EVT) with Eluvia™ stents at 7 Korean sites were enrolled in a prospective cohort and followed for 2 years. The primary endpoint was the 2-year clinical patency. The secondary endpoint was 2-year freedom from clinically driven target lesion revascularization (TLR). RESULTS: Mean patient age was 68.2±10.4 years, and most patients (82.7%) were male. Mean lesion length was 168.3±117.6 mm. Chronic total occlusion was found in 57.7% of patients. Trans-Atlantic Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II) type C or D lesions were present in 46.1% of patients. Procedural success was achieved in 99.0% of patients. The clinical patency rate was 84.4% at 1 year after EVT and 76.3% at 2 years post-EVT. The freedom from TLR rate was 89.1% at 1 year after EVT and 79.1% at 2 years post-EVT. Chronic total occlusion (hazard ratio [HR], 3.53; 95% confidence interval [CI], 1.08-11.67; p=0.039) and smaller mean stent diameter (HR, 0.40; 95% CI, 0.16-0.98; p=0.044) were identified as independent predictors of loss of clinical patency at 2 years. CONCLUSIONS: The K-ELUVIA study demonstrated favorable 2-year clinical effectiveness and safety outcomes of Eluvia stent for femoropopliteal artery lesions in real-world practice.

Ticagrelor monotherapy for acute coronary syndrome: an individual patient data meta-analysis of TICO and T-PASS trials.

BACKGROUND AND AIMS: In patients with acute coronary syndrome (ACS), dual antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor is recommended for 12 months after drug-eluting stent (DES) implantation. Monotherapy with a potent P2Y12 inhibitor after short-term DAPT is an attractive option to better balance the risks of ischaemia and bleeding. Therefore, this study evaluated the efficacy and safety of ticagrelor monotherapy after short-term DAPT, especially in patients with ACS. METHODS: Electronic databases were searched from inception to 11 November 2023, and for the primary analysis, individual patient data were pooled from the relevant randomized clinical trials comparing ticagrelor monotherapy after short-term (≤3 months) DAPT with ticagrelor-based 12-month DAPT, exclusively in ACS patients undergoing DES implantation. The co-primary endpoints were ischaemic endpoint (composite of all-cause death, myocardial infarction, or stroke) and bleeding endpoint [Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding] at 1 year. RESULTS: Individual patient data from two randomized clinical trials including 5906 ACS patients were analysed. At 1 year, the primary ischaemic endpoint did not differ between the ticagrelor monotherapy and ticagrelor-based DAPT groups [1.9% vs. 2.5%; adjusted hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.56-1.13; P = .194]. The incidence of the primary bleeding endpoint was lower in the ticagrelor monotherapy group (2.4% vs. 4.5%; adjusted HR 0.54; 95% CI 0.40-0.72; P < .001). The results were consistent in a secondary aggregate data meta-analysis including the ACS subgroup of additional randomized clinical trials which enrolled patients with ACS as well as chronic coronary syndrome. CONCLUSIONS: In ACS patients undergoing DES implantation, ticagrelor monotherapy after short-term DAPT was associated with less major bleeding without a concomitant increase in ischaemic events compared with ticagrelor-based 12-month DAPT. STUDY REGISTRATION: PROSPERO (ID: CRD42023476470).

Clinical Outcomes After Drug-Coated Balloon Treatment in Popliteal Artery Disease: K-POP Registry 12-Month Results.

BACKGROUND AND OBJECTIVES: The popliteal artery is generally regarded as a "no-stent zone." Limited data are available on the outcomes of drug-coated balloons (DCBs) for popliteal artery disease. This study aimed to evaluate the 12-month clinical outcomes among patients who received DCB treatment for atherosclerotic popliteal artery disease. METHODS: This prospective, multicenter registry study enrolled 100 patients from 7 Korean endovascular centers who underwent endovascular therapy using IN.PACT DCB (Medtronic) for symptomatic atherosclerotic popliteal artery disease. The primary endpoint was 12-month clinical primary patency and the secondary endpoint was clinically driven target lesion revascularization (TLR)-free rate. RESULTS: The mean age of the study cohort was 65.7±10.8 years, and 77% of enrolled patients were men. The mean lesion length was 93.7±53.7 mm, and total occlusions were present in 45% of patients. Technical success was achieved in all patients. Combined atherectomy was performed in 17% and provisional stenting was required in 11%. Out of the enrolled patients, 91 patients completed the 12-month follow-up. Clinical primary patency and TLR-free survival rates at 12 months were 76.0% and 87.2%, respectively. A multivariate Cox regression analysis identified female and longer lesion length as the significant independent predictors of loss of patency. CONCLUSIONS: DCB treatment yielded favorable 12-month clinical primary patency and TLR-free survival outcomes in patients with popliteal artery disease. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02698345.