BRCAness is considered a predictive biomarker to platinum and poly(ADP‐ribose) polymerase (PARP) inhibitors. However, recent trials showed that its predictive value was limited in triple‐negative ...breast cancer (TNBC) treated with platinum. Moreover, tumors with mutations of DNA damage response (DDR) genes, such as homologous recombination (HR) genes, could be sensitive to platinum and PARP inhibitors. Thus, we aim to explore the relationship between mutation status of DDR genes and BRCAness in TNBC. We sequenced 56 DDR genes in 120 TNBC and identified BRCAness by array comparative genomic hybridization. The sequencing results showed that 13, 14, and 14 patients had BRCA, non‐BRCA HR, and non‐HR DDR gene mutations, respectively. Array comparative genomic hybridization revealed that BRCA‐mutated and HR gene‐mutated TNBC shared similar BRCAness features, both having higher numbers and longer length of large‐scale structural aberration (LSA, >10 Mb) and similar altered chromosomal regions of LSA. These suggested non‐BRCA HR gene‐mutated TNBC shared similar characteristics with BRCA‐mutated TNBC, indicating non‐BRCA HR gene‐mutated TNBC sensitive to platinum and PARP inhibitors. Among tumors with mutation of non‐HR DDR genes, 3 PTEN and 1 MSH6 mutation also contained significant LSAs (BRCAness); however, they had different regions of genomic alteration to BRCA and HR gene‐mutated tumors, might explain prior findings that PTEN‐ and MSH6‐mutated cancer cells not sensitive to PARP inhibitors. Therefore, we hypothesize that the heterogeneous genomic background of BRCAness indicates different responsiveness to platinum and PARP inhibitors. Direct sequencing DDR genes in TNBC should be applied to predict their sensitivity toward platinum and PARP inhibitors.
High‐grade genomic instability (BRCAness) can be present in triple‐negative breast cancer with BRCA, non‐BRCA HR gene, PTEN and MSH6 mutation. We hypothesize that the heterogeneous genomic background of BRCAness indicates different responsiveness to platinum and PARP inhibitors.
Introduction
Carina breakthrough (CB) at the right pulmonary vein (RPV) can occur after circumferential pulmonary vein isolation (PVI) due to epicardial bridging or transient tissue edema. High‐power ...short‐duration (HPSD) ablation may increase the incidence of RPV CB. Currently, the surrogate of ablation parameters to predict RPV CB is not well established. This study investigated predictors of RPV CB in patients undergoing ablation index (AI)‐guided PVI with HPSD.
Methods
The study included 62 patients with symptomatic atrial fibrillation (AF) who underwent AI‐guided PVI using HPSD. Patients were categorized into two groups based on the presence or absence of RPV CB. Lesions adjacent to the RPV carina were assessed, and CB was confirmed through residual voltage, low voltage along the ablation lesions, and activation wavefront propagation.
Results
Out of the 62 patients, 21 (33.87%) experienced RPV CB (Group 1), while 41 (66.13%) achieved first‐pass RPV isolation (Group 2). Despite similar AI and HPSD, patients with RPV CB had lower contact force (CF) at lesions adjacent to the RPV carina. Receiver operating characteristic (ROC) curve analysis identified CF < 10.5 g as a predictor of RPV CB, with 75.7% sensitivity and 56.2% specificity (area under the curve: 0.714).
Conclusion
In patients undergoing AI‐guided PVI with HPSD, lower CF adjacent to the carina was associated with a higher risk of RPV CB. These findings suggest that maintaining higher CF during ablation in this region may reduce the occurrence of RPV CB.
Introduction
Despite undergoing an index ablation, some patients progress from paroxysmal atrial fibrillation (PAF) to persistent AF (PersAF), and the mechanism behind this is unclear. The aim of ...this study was to investigate the predictors of progression to PersAF after catheter ablation in patients with PAF.
Methods
This study included 400 PAF patients who underwent an index ablation between 2015 and 2019. The patients were classified into three groups based on their outcomes: Group 1 (PAF to sinus rhythm, n = 226), Group 2 (PAF to PAF, n = 146), and Group 3 (PAF to PersAF, n = 28). Baseline and procedural characteristics were collected, and predictors for AF recurrence and progression were evaluated.
Results
The mean age of the patients was 58.4 ± 11.1 years, with 272 males. After 3 years of follow‐up, 7% of the PAF cases recurred and progressed to PersAF despite undergoing an index catheter ablation. In the multivariable analysis, a larger left atrial (LA) diameter and the presence of non‐pulmonary vein (PV) triggers during the index procedure independently predicted recurrence. Moreover, a larger LA diameter, the presence of non‐PV triggers, and a history of thyroid disease independently predicted AF progression.
Conclusion
The progression from PAF to PersAF after catheter ablation is associated with a larger LA diameter, history of thyroid disease, and the presence of non‐PV triggers. Meticulous preprocedural evaluation, patient selection, and comprehensive provocation tests during catheter ablation are recommended.
The study investigated the outcomes of 400 patients with PAF who underwent an index ablation procedure, while also identifying the predictors associated with recurrence and progression to PersAF.
CI, confidence interval; OR, odd ratio; PAF, paroxysmal atrial fibrillation; PersAF, persistent atrial fibrillation; SR, sinus rhythm.
The high entropy nitride coatings (Cr0.35Al0.25Nb0.12Si0.08V0.20)N with high hardness of 35 GPa and a high H3/E2 of 0.52 were fabricated by RF magnetron sputtering system via tuning the processing ...parameters, such as substrate temperature and bias. The chemical composition, crystal structure, grain size, and residual stress were measured and analyzed to determine the mechanisms of hardness improvement. The crystal structure maintained B1 face-center cubic structure throughout all the conditions. The hardness was improved from 28 GPa to 35 GPa by sputtering at 300 °C with −150 V bias. Such hardness was achieved due to increased densification and compressive residual stress. Furthermore, the wear test of high hardness and high value of H3/E2 coatings were performed at both ambient temperature and 600 °C. The correlation among H3/E2, oxidation resistance, and wear rate was addressed and discussed.
•A high entropy nitride coating with high hardness (35 GPa) and high value of H3/E2 (0.52) was deposited.•Such coating outperformed almost all the previously reported high entropy nitride coatings in ambient wear test.•The scarcely reported high temperature wear behavior of high entropy nitride coatings was investigated in this work.•The hardness improvement was mainly attributed to densification and compressive residual stress.
When assessing ischemic stroke risk in patients with atrial fibrillation (AF), the CHA2DS2-VASc score is calculated based on the baseline risk factors, and the outcomes are determined after a ...follow-up period. However, the stroke risk in patients with AF does not remain static, and with time, patients get older and accumulate more comorbidities.
This study hypothesized that the “Delta CHA2DS2-VASc score,” which reflects the change in score between baseline and follow-up, would be more predictive of ischemic stroke compared with the baseline CHA2DS2-VASc score.
A total of 31,039 patients with AF who did not receive antiplatelet agents or oral anticoagulants, and who did not have comorbidities of the CHA2DS2-VASc score except for age and sex, were studied. The Delta CHA2DS2-VASc scores were defined as the differences between the baseline and follow-up CHA2DS2-VASc scores. During 171,956 person-years, 4,103 patients experienced ischemic stroke. The accuracies of baseline, follow-up, and Delta CHA2DS2-VASc scores in predicting ischemic stroke were analyzed and compared.
The mean baseline CHA2DS2-VASc score was 1.29, which increased to 2.31 during the follow-up, with a mean Delta CHA2DS2-VASc score of 1.02. The CHA2DS2-VASc score remained unchanged in only 40.8% of patients. Among 4,103 patients who experienced ischemic stroke, 89.4% had a Delta CHA2DS2-VASc score ≥1 compared with only 54.6% in patients without ischemic stroke, and 2,643 (64.4%) patients had ≥1 new-onset comorbidity, the most common being hypertension. The Delta CHA2DS2-VASc score was a significant predictor of ischemic stroke that performed better than baseline or follow-up CHA2DS2-VASc scores, as assessed by the C-index and the net reclassification index.
In this AF cohort, the authors demonstrated that the CHA2DS2-VASc score was not static, and that most patients with AF developed ≥1 new stroke risk factor before presentation with ischemic stroke. The Delta CHA2DS2-VASc score, reflecting the change in score between baseline and follow-up, was strongly predictive of ischemic stroke, reflecting how stroke risk in AF is a dynamic process due to increasing age and incident comorbidities.
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Soft electronic devices and sensors have shown great potential for wearable and ambulatory electrophysiologic signal monitoring applications due to their light weight, ability to conform to human ...skin, and improved wearing comfort, and they may replace the conventional rigid electrodes and bulky recording devices widely used nowadays in clinical settings. Herein, we report an elastomeric sponge electrode that offers greatly reduced electrode–skin contact impedance, an improved signal-to-noise ratio (SNR), and is ideally suited for long-term and motion-artifact-tolerant recording of high-quality biopotential signals. The sponge electrode utilizes a porous polydimethylsiloxane sponge made from a sacrificial template of sugar cubes, and it is subsequently coated with a poly(3,4-ethylenedioxythiophene) polystyrenesulfonate (PEDOT:PSS) conductive polymer using a simple dip-coating process. The sponge electrode contains numerous micropores that greatly increase the skin–electrode contact area and help lower the contact impedance by a factor of 5.25 or 6.7 compared to planar PEDOT:PSS electrodes or gold-standard Ag/AgCl electrodes, respectively. The lowering of contact impedance resulted in high-quality electrocardiogram (ECG) and electromyogram (EMG) recordings with improved SNR. Furthermore, the porous structure also allows the sponge electrode to hold significantly more conductive gel compared to conventional planar electrodes, thereby allowing them to be used for long recording sessions with minimal signal degradation. The conductive gel absorbed into the micropores also serves as a buffer layer to help mitigate motion artifacts, which is crucial for recording on ambulatory patients. Lastly, to demonstrate its feasibility and potential for clinical usage, we have shown that the sponge electrode can be used to monitor uterine contraction activities from a patient in labor. With its low-cost fabrication, softness, and ability to record high SNR biopotential signals, the sponge electrode is a promising platform for long-term wearable health monitoring applications.
Apical lesions, the general term for chronic infectious diseases, are very common dental diseases in modern life, and are caused by various factors. The current prevailing endodontic treatment makes ...use of X-ray photography taken from patients where the lesion area is marked manually, which is therefore time consuming. Additionally, for some images the significant details might not be recognizable due to the different shooting angles or doses. To make the diagnosis process shorter and efficient, repetitive tasks should be performed automatically to allow the dentists to focus more on the technical and medical diagnosis, such as treatment, tooth cleaning, or medical communication. To realize the automatic diagnosis, this article proposes and establishes a lesion area analysis model based on convolutional neural networks (CNN). For establishing a standardized database for clinical application, the Institutional Review Board (IRB) with application number 202002030B0 has been approved with the database established by dentists who provided the practical clinical data. In this study, the image data is preprocessed by a Gaussian high-pass filter. Then, an iterative thresholding is applied to slice the X-ray image into several individual tooth sample images. The collection of individual tooth images that comprises the image database are used as input into the CNN migration learning model for training. Seventy percent (70%) of the image database is used for training and validating the model while the remaining 30% is used for testing and estimating the accuracy of the model. The practical diagnosis accuracy of the proposed CNN model is 92.5%. The proposed model successfully facilitated the automatic diagnosis of the apical lesion.
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