Mechanical Characterization of Multifunctional Metal-Coated Polymer Lattice Structures.

Metal-coated lattice structures hold significant promise for customizing mechanical properties in diverse industrial applications, including the mechanical arms of unmanned aerial vehicles. However, their intricate geometries pose computational challenges, resulting in time-intensive and costly numerical evaluations. This study introduces a parameterization-based multiscale method to analyze body-centered cubic lattice structures with metal coatings. We establish the validity and precision of our proposed method with a comparative analysis of numerical results at the Representative Volume Element (RVE) scale and experimental findings, specifically addressing both elastic tensile and bending stiffness. Furthermore, we showcase the method's accuracy in interpreting the bending stiffness of coated lattice structures using a homogenized material-based solid model, underscoring its effectiveness in predicting the elastic properties of such structures. In exploring the mechanical characterization of coated lattice structures, we unveil positive correlations between elastic tensile stiffness and both coating thickness and strut diameter. Additionally, the metal coating significantly enhances the structural elastic bending stiffness multiple times over. The diverse failure patterns observed in coated lattices under tensile and bending loads primarily stem from varied loading-induced stress states rather than external factors. This work not only mitigates computational challenges but also successfully bridges the gap between mesoscale RVE mechanical properties and those at the global structural scale.

Wavelength division multiplexing based on the coupling effect of helical edge states in two-dimensional dielectric photonic crystals.

Photonic topological insulators with topologically protected edge states featuring one-way, robustness and backscattering-immunity possess extraordinary abilities to steer and manipulate light. In this work, we construct a topological heterostructure (TH) consisting of a domain of nontrivial pseudospin-type topological photonic crystals (PCs) sandwiched between two domains of trivial PCs based on two-dimensional all-dielectric core-shell PCs in triangle lattice. We consider three THs with different number of layers in the middle nontrivial domain (i.e., one-layer, two-layer, three-layer) and demonstrate that the projected band diagrams of the three THs host interesting topological waveguide states (TWSs) with properties of one-way, large-area, broad-bandwidth and robustness due to coupling effect of the helical edge states associated with the two domain-wall interfaces. Moreover, taking advantage of the tunable bandgap between the TWSs by the layer number of the middle domain due to the coupling effect, a topological Y-splitter with functionality of wavelength division multiplexing is explicitly demonstrated exploiting the unique feature of the dispersion curves of TWSs in the three THs. Our work not only offers a new method to realize pseudospin-polarized large-area TWSs with tunable mode-width, but also could provide new opportunities for practical applications in on-chip multifunctional (i.e., wavelength division multiplexing) photonic devices with topological protection and information processing with pseudospin-dependent transport.

[The Polymorphism Analysis of HLA Class II Alleles Based on Next-Generation Sequencing and Prevention Strategy for Allele Dropout].

OBJECTIVE: To investigate the accuracy of next-generation sequencing technology (NGS) in detecting the polymorphisms of HLA-DRB1, DQB1, DQA1, DRB3, DRB4, DRB5, DPA1 and DPB1 alleles in randomly-selected unrelated healthy individuals from Shenzhen Han population, investigate the potential reason for HLA-DRB1 allele dropout in routine NGS, and establish an internal quality control system. METHODS: NGS-based HLA class II genotyping was performed on 1 012 samples using the MiSeqDxTM platform. The suspected missed alleles indicated by the quality control software and HLA-DRB1 homozygotes were confirmed by PCR-SSOP or PCR-SBT methods. RESULTS: A total of 139 alleles were detected, including HLA-DRB1(45), DRB3(7), DRB4(5), DRB5(7), DQA1(17), DQB1(21), DPA1(10) and DPB1(27). HLA-DRB1*09:01(17.09%),15:01(10.72%); DRB3*02:02(25.99%),03:01(10.18%); DRB4*01:03(36.46%); DRB5*01:01(15.42%); DQA1*01:02(20.01%),03:02(17.19%); DQB1*03:01(19.47%),03:03(17.98%), 05:02(11.66%), 06:01(10.67%); DPA1*02:02(54.45%), 01:03(31.18%) and DPB1*05:01(39.13%), 02:01(16.90%) alleles were the most common alleles in Shenzhen Han population (frequencies >10%). There was no statistical difference between the gene frequencies of HLA-DRB1 and DQB1 loci in our study. The HLA Common and Well-Documented Alleles in China (CWD2.4) (χ2=12.68, P >0.05). 94 cases of HLA-DRB1 homozygous samples detected by NGS were retested by PCR-SSOP or SBT method, and one case of allele dropout at HLA-DRB1 locus was found. SBT method confirmed that the allele of DRB1*04:03 was missed. The laboratory internal quality control system was established. Two cases of new alleles were detected and named by WHO Nomenclature Committee for Factors of the HLA System. CONCLUSION: The HLA genotyping results based on NGS showed a significantly lower ambiguity rate. The HLA class II alleles exhibit genetic polymorphism in the Han population of unrelated healthy individuals in Shenzhen. The independent method based on NGS in clinical histocompatibility testing has limitations and requires internal quality control strategies to avoid allele-dropout events.

Efficiency and Durability of EIVOM on Acute Reconnection After Mitral Isthmus Bidirectional Block.

BACKGROUND: Reconnection after mitral isthmus (MI) block with radiofrequency ablation is common. OBJECTIVES: The aim of this study was to investigate the effects of ethanol infusion in the vein of Marshall (EIVOM) on acute reconnection after MI bidirectional block. METHODS: Patients with persistent atrial fibrillation who were scheduled to receive radiofrequency ablation for the first time were randomly assigned to the radiofrequency catheter ablation (RFCA) group (n = 44) or the EIVOM group (n = 45). The RFCA group's strategy was bilateral pulmonary vein ablation and linear ablation; in the EIVOM group, EIVOM was performed first. The primary endpoint was acute reconnection 30 minutes after MI bidirectional block. RESULTS: A total of 89 patients (average age 62.9 years; 57.3% male) were enrolled. The average duration for persistent atrial fibrillation was 2.3 years. Before observation, all patients in the EIVOM group achieved MI bidirectional block (45 of 45 [100%]), compared with 84.1% (37 of 44) in the RFCA group. After the observation, 3 cases of MI reconnection occurred in the EIVOM group and 13 cases in the RFCA group (6.7% vs 35.1%; P < 0.05). After additional ablation, the final MI block rates in the EIVOM and RFCA groups were 97.8% (44 of 45) and 72.7% (32 of 44), respectively. During a 1-year follow-up, 8 of 45 patients who underwent EIVOM had recurrent atrial fibrillation, compared with 14 of 44 in the RFCA group (17.8% vs 31.8%; P < 0.01). CONCLUSIONS: EIVOM can reduce acute reconnection after MI bidirectional block and significantly increase first-pass MI block.

A Molecular Coordination Strategy for Regulating the Interface of MoS2 Field Effect Transistors.

Chemically modifying monolayer two-dimensional transition metal dichalcogenides (TMDs) with organic molecules provides a wide range of possibilities to regulate the electronic and optoelectronic performance of both materials and devices. However, it remains challenging to chemically attach organic molecules to monolayer TMDs without damaging their crystal structures. Herein, we show that the Mo atoms of monolayer MoS2 (1L-MoS2) in defect states can coordinate with both catechol and 1,10-phenanthroline (Phen) groups, affording a facile route to chemically modifying 1L-MoS2. Through the design of two isomeric molecules (LA2 and LA5) comprising catechol and Phen groups, we show that attaching organic molecules to Mo atoms via coordinative bonds has no negative effect on the crystal structure of 1L-MoS2. Both theoretical calculation and experiment results indicate that the coordinative strategy is beneficial for (i) repairing sulfur vacancies and passivating defects; (ii) achieving a long-term and stable n-doping effect; and (iii) facilitating the electron transfer. Field effect transistors (FETs) based on the coordinatively modified 1L-MoS2 show high electron mobilities up to 120.3 cm2 V-1 s-1 with impressive current on/off ratios over 109. Our results indicate that coordinatively attaching catechol- or Phen-bearing molecules may be a general method for the nondestructive modification of TMDs.

Digital computerised cognitive training for preventing cognitive decline among hypertensive patients: a study protocol for a multicentre randomised controlled trial (DELIGHT trial).

INTRODUCTION: Mild cognitive impairment (MCI) is an important intervenable stage for the prevention of dementia. Hypertension is associated with impaired cognition, and when combined with MCI, it may lead to a poor prognosis. Digital computerised cognitive training (CCT) has recently become a potential instrument for improving cognition, but evidence for its efficacy remains limited. This study aims to evaluate the efficacy of a digital adaptive CCT intervention in older patients with hypertension and MCI. METHODS AND ANALYSIS: The multicentre, double-blinded, randomised, actively -controlled clinical trial will recruit 200 older (≥60 years) patients with hypertension and MCI from 11 hospitals across China. Participants will be randomly assigned in a 1:1 ratio to the intervention group (multidomain adaptative CCT) and active control group (non-adaptive cognitive training) for 12-week cognitive training for 30 min/day and 5 days/week. Those who have completed their 12-week training in the intervention group will be rerandomised into the continuation and discontinuation training groups. All participants will be followed up to 24 weeks. Neuropsychological assessments and structural and functional 7.0 T MRI will be obtained at baseline and at 12-week and 24-week follow-up. The primary outcome is the possible improvement of global cognitive function at 12 weeks, as measured by the Basic Cognitive Aptitude Tests. Secondary and exploratory endpoints include the major cognitive domain function improvement, self-efficacy, mental health, quality of life and MRI measurements of the brain. ETHICS AND DISSEMINATION: The trial has been approved by the institutional review board of Beijing Anzhen Hospital and thereafter by all other participating centres. Trial findings will be disseminated in peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: NCT05704270.

How the social media impact women's psychological well-being in the patriarchal structure? The moderating effect of social capital.

BACKGROUND: Despite technological, political and economic progress, Pakistan is still a traditionally patriarchal society, and cultural norms curb women's freedom of socialization, which contributes to poor mental health. The digital technology spaces are rampant with male dominance, and offline cultural behaviours are replicated. Therefore, the current research in Pakistan intends to focus solely on women, their social media uses and the consequent impact on their psychological well-being. Furthermore, the mediation role of social capital is explored, which is linked to women's socialization. In virtual communication, women can expand their connection or remain limited to known people. METHODS: An online survey collected 240 responses from women social media users. The questionnaire was divided into demographics, social media use patterns like access, online time, frequency of use, social media uses, online social capital and psychological well-being. The obtained responses were statistically analyzed using Smart PLS. RESULTS: Pakistani women use social media extensively; however, their uses are culturally influenced. The women use social media and socialize online but do not openly disclose their personalities and emotions to extend the connection. They seek information only from acquaintances and do not trust newly developed online contacts. Therefore, the mediation role of bonding social capital is significant, referring to the importance of close ties and trust in psychological well-being. Though virtual spaces provide an opportunity for bridging social capital, women use social media for socialization; however, it doesn't contribute to women's psychological well-being. CONCLUSION: Despite the higher penetration of digital technologies, cultural power still rules in developing countries like Pakistan. Social media uses are gender- and culturally specific, contributing to psychological well-being and developing social capital. The results from Pakistani society recommend ensuring a secure digital experience for women to get maximum benefits from social media and enhance their psychological well-being.

The role of magnetoencephalography in preoperative localization and postoperative outcome prediction in patients with posterior cortical epilepsy.

OBJECTIVE: We aimed to explore the value of magnetoencephalography in the presurgical evaluation of patients with posterior cortex epilepsy. METHODS: A total of 39 patients with posterior cortex epilepsy (PCE) and intact magnetoencephalography (MEG) images were reviewed from August 2019 to July 2022. MEG dipole clusters were classified into single clusters, multiple clusters, and scatter dipoles based on tightness criteria. The association of the surgical outcome with MEG dipole classifications was evaluated using Fisher's exact tests. RESULTS: Among the 39 cases, there were 24 cases of single clusters (61.5%), nine cases of multiple clusters (23.1%), and six cases of scattered dipoles (15.4%). Patients with single dipole clusters were more likely to become seizure-free. Among single dipole cluster cases (n = 24), complete MEG dipole resection yielded a more favorable surgical outcome than incomplete resection (83.3% vs. 16.7%, p = 0.007). Patients with concordant MRI and MEG findings achieved a significantly more favorable surgical outcome than discordant patients (66.7% vs. 33.3%, p = 0.044), especially in single dipole cluster patients (87.5% vs. 25.0%, p = 0.005). SIGNIFICANCE: MEG can provide additional valuable information regarding surgical candidate selection, epileptogenic zone localization, electrode implantation schedule, and final surgical planning in patients with posterior cortex epilepsy.

Association between performance measures and clinical outcomes in patients with heart failure in China: Results from the HERO study.

BACKGROUND: There is great heterogeneity in the quality of care among hospitals in China, but studies on the performance measures and prognosis of patients with heart failure (HF) are still deficient. HYPOTHESIS: Performance measures have been used as a guideline to clinicans, however, the association between them and outcomes among HF patients in China remains unclear. METHODS: We analyzed 4497 patients with HF from the Heart Failure Registry of Patient Outcomes study. Performance measures were determined according to the guidelines, and the patients were divided into four groups based on a composite performance score. Multiple imputation and Cox proportional-hazard regression models were used to assess the association between the performance measures and clinical outcomes. RESULTS: Overall, only 12.5% of patients met the top 25% of the performance measures, whereas 33.5% of patients met the bottom 25% of the measures. A total of 992 (22.2%) patients died within 1 year, involving a larger proportion of patients who had met only the bottom 25% of the performance measures than had met the top 25% (27.0% vs. 16.3%, respectively). The patients who met the top 25% of the measures had a lower 1-year mortality rate (adjusted hazard ratio: 0.78, 95% confidence interval: 0.61-0.98). CONCLUSIONS: The association between performance measures and mortality appeared to follow a dose-response pattern with a larger degree of compliance with performance measures being associated with a lower mortality rate in patients with HF. Accordingly, the quality of care for patients with HF in China needs to be further improved.

Catheter ablation of atrial fibrillation in patients with left bundle branch block.

BACKGROUND: Left bundle branch block (LBBB) and atrial fibrillation (AF) are commonly coexisting conditions. The impact of LBBB on catheter ablation of AF has not been well determined. This study aims to explore the long-term outcomes of patients with AF and LBBB after catheter ablation. METHODS: Forty-two patients with LBBB of 11,752 patients who underwent catheter ablation of AF from 2011 to 2020 were enrolled as LBBB group. After propensity score matching in a 1:4 ratio, 168 AF patients without LBBB were enrolled as non-LBBB group. Late recurrence and a composite endpoint of stroke, all-cause mortality, and cardiovascular hospitalization were compared between the two groups. RESULTS: Late recurrence rate was significantly higher in the LBBB group than that in the non-LBBB group (54.8% vs. 31.5%, p = .034). Multivariate analysis showed that LBBB was an independent risk factor for late recurrence after catheter ablation of AF (hazard ratio [HR] 2.19, 95% confidence interval [CI] 1.09-4.40, p = .031). LBBB group was also associated with a significantly higher incidence of the composite endpoint (21.4% vs. 6.5%, HR 3.98, 95% CI 1.64-9.64, p = .002). CONCLUSIONS: LBBB was associated with a higher risk for late recurrence and a higher incidence of composite endpoint in the patients underwent catheter ablation.

Data-driven classification of left atrial morphology and its predictive impact on atrial fibrillation catheter ablation.

INTRODUCTION: Various left atrial (LA) anatomical structures are correlated with postablative recurrence for atrial fibrillation (AF) patients. Comprehensively integrating anatomical structures, digitizing them, and implementing in-depth analysis, which may supply new insights, are needed. Thus, we aim to establish an interpretable model to identify AF patients' phenotypes according to LA anatomical morphology, using machine learning techniques. METHODS AND RESULTS: Five hundred and nine AF patients underwent first ablation treatment in three centers were included and were followed-up for postablative recurrent atrial arrhythmias. Data from 369 patients were regarded as training set, while data from another 140 patients, collected from different centers, were used as validation set. We manually measured 57 morphological parameters on enhanced computed tomography with three-dimensional reconstruction technique and implemented unsupervised learning accordingly. Three morphological groups were identified, with distinct prognosis according to Kaplan-Meier estimator (p < .001). Multivariable Cox model revealed that morphological grouping were independent predictors of 1-year recurrence (Group 1: HR = 3.00, 95% CI: 1.51-5.95, p = .002; Group 2: HR = 4.68, 95% CI: 2.40-9.11, p < .001; Group 3 as reference). Furthermore, external validation consistently demonstrated our findings. CONCLUSIONS: Our study illustrated the feasibility of employing unsupervised learning for the classification of LA morphology. By utilizing morphological grouping, we can effectively identify individuals at different risks of postablative recurrence and thereby assist in clinical decision-making.

Effect and Safety of Herbal Medicine Foot Baths in Patients with Diabetic Peripheral Neuropathy: A Multicenter Double-Blind Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect and safety of foot baths with Tangbi Waixi Decoction (TW) in treating patients with diabetic peripheral neuropathy (DPN). METHODS: It is a multicenter double-blinded randomized controlled trial. Participants with DPN were recruited between November 18, 2016 and May 30, 2018 from 8 hospitals in China. All patients received basic treatments for glycemic management. Patients received foot baths with TW herbal granules either 66.9 g (intervention group) or 6.69 g (control group) for 30 min once a day for 2 weeks and followed by a 2-week rest, as a therapeutic course. If the Toronto Clinical Scoring System total score (TCSS-TS) ⩾6 points, the patients received a total of 3 therapeutic courses (for 12 weeks) and were followed up for 12 weeks. The primary outcome was change in TCSS-TS score at 12 and 24 weeks. Secondary outcomes included changes in bilateral motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) of the median and common peroneal nerve. Safety was also assessed. RESULTS: Totally 632 patients were enrolled, and 317 and 315 were randomized to the intervention and control groups, respectively. After the 12-week intervention, patients in both groups showed significant declines in TCSSTS scores, and significant increases in MNCV and SNCV of the median and common peroneal nerves compared with pre-treatment (P<0.05). The reduction of TCSS-TS score at 12 weeks and the increase of SNCV of median nerve at 24 weeks in the control group were greater than those in the intervention group (P<0.05). The number of adverse events did not differ significantly between groups (P>0.05), and no serious adverse event was related with treatment. CONCLUSION: Treatment of TW foot baths was safe and significantly benefitted patients with DPN. A low dose of TW appeared to be more effective than a high dose. (Registry No. ChiCTR-IOR-16009331).

Strategies on biosynthesis and production of bioactive compounds in medicinal plants.

Medicinal plants are a valuable source of essential medicines and herbal products for healthcare and disease therapy. Compared with chemical synthesis and extraction, the biosynthesis of natural products is a very promising alternative for the successful conservation of medicinal plants, and its rapid development will greatly facilitate the conservation and sustainable utilization of medicinal plants. Here, we summarize the advances in strategies and methods concerning the biosynthesis and production of natural products of medicinal plants. The strategies and methods mainly include genetic engineering, plant cell culture engineering, metabolic engineering, and synthetic biology based on multiple "OMICS" technologies, with paradigms for the biosynthesis of terpenoids and alkaloids. We also highlight the biosynthetic approaches and discuss progress in the production of some valuable natural products, exemplifying compounds such as vindoline (alkaloid), artemisinin and paclitaxel (terpenoids), to illustrate the power of biotechnology in medicinal plants.

Suggested blood donor deferral strategy regarding hepatitis B infections in China.

BACKGROUND: Hepatitis B virus (HBV) reactivity in individual immunologic and nucleic acid tests (NAT) tests does not represent the true infectious status of the blood donor. This study discusses the use of confirmatory tests to determine when deferral of blood donors is appropriate. METHODS: HBsAg or HBV NAT reactive samples were confirmed via a neutralisation test. All the HBsAg reactive but neutralisation test negative samples were subjected to further anti-HBc testing. The receiver operating characteristic curve was used to obtain the best threshold value using signal-to-cut-off ratios of two HBsAg enzyme-linked immunosorbent assay reagents. RESULTS: Of the 780 HBV reactive samples collected, there were 467 HBsAg reactive but HBV DNA negative samples, of which 65 (13.92%) and 402 (86.08%) were neutralisation test positive and negative, respectively. Of the 402, 91 samples (30% of tested samples) were anti-HBc reactive. HBV DNA positive specimens negative by virus neutralisation were >80% HBcAg positive. A screening strategy was proposed for Chinese blood collection agencies. CONCLUSION: These findings suggest that adopting a screening algorithm for deferring HBV reactive blood donors based on HBsAg and NAT testing followed with HBsAg S/CO consideration and HBcAg testing can be both safe and feasible in China.

Meta-synthesis of qualitative studies on patient perceptions and requirements during the perioperative period of robotic surgery.

This research undertakes a comprehensive evaluation and amalgamation of patient experiences and requirements during the perioperative period of robot-assisted surgery (RS), with the goal of enriching clinical practice with patient-centered insights. A meta-synthesis was performed and reported according to the preferred reporting Items for systematic reviews and meta-analyses and the enhancing transparency in reporting the synthesis of qualitative research statement. A rigorous literature search was conducted across multiple Chinese and English databases, namely PubMed, CINAHL (EBSCO), Embase, Web of Science, Scopus, China Biomedical Literature Database (CBLD), China National Knowledge Infrastructure (CNKI), Wanfang Data, and VIP Information. This study incorporated ten qualitative studies, the outcomes were classified into three overarching themes: personalized patient requirements related to RS; the psychological and physiological experiences of patients; and the divergent perceptions of male and female patients regarding RS. Greater emphasis needs to be placed on patient comprehension of RS, augmenting focus on patient psychological experiences, recognizing unique patient needs at various stages of RS, and providing patients with specialized knowledge and technical support.

SN-38, an active metabolite of irinotecan, inhibits transcription of nuclear factor erythroid 2-related factor 2 and enhances drug sensitivity of colorectal cancer cells.

Nuclear factor erythroid 2-related factor 2 (Nrf2) significantly contributes to drug resistance of cancer cells, and Nrf2 inhibitors have been vigorously pursued. Repurposing of existing drugs, especially anticancer drugs, is a straightforward and promising strategy to find clinically available Nrf2 inhibitors and effective drug combinations. Topoisomerase inhibitors SN-38 (an active metabolite of irinotecan), topotecan, mitoxantrone, and epirubicin were found to significantly suppress Nrf2 transcriptional activity in cancer cells. SN-38, the most potent one among them, significantly inhibited the transcription of Nrf2, as indicated by decreased mRNA level and binding of RNA polymerase II to NFE2L2 gene, while no impact on Nrf2 protein or mRNA degradation was observed. SN-38 synergized with Nrf2-sensitive anticancer drugs such as mitomycin C in killing colorectal cancer cells, and irinotecan and mitomycin C synergistically inhibited the growth of SW480 xenografts in nude mice. Our study identified SN-38 and three other topoisomerase inhibitors as Nrf2 inhibitors, revealed the Nrf2-inhibitory mechanism of SN-38, and indicate that clinically feasible drug combinations could be designed based on their interactions with Nrf2 signaling.

Generation and characterization of nanobodies targeting human pepsinogens.

Human pepsinogens (mainly pepsinogen I and pepsinogen II) are the major inactive precursor forms of the digestive enzyme pepsin which play a crucial role in protein digestion. The levels and ratios of human pepsinogens have demonstrated potential as diagnostic biomarkers for gastrointestinal diseases, particularly gastric cancer. Nanobodies are promising tools for the treatment and diagnosis of diseases, owing to their unique recognition properties. In this study, recombinant human pepsinogens proteins were expressed and purified as immunized antigens. We constructed a VHH phage library and identified several nanobodies via phage display bio-panning. We determined the binding potency and cross-reactivity of these nanobodies. Our study provides technical support for developing immunodiagnostic reagents targeting human pepsinogens.

Live-cell target engagement of allosteric MEKi on MEK-RAF/KSR-14-3-3 complexes.

The RAS-mitogen-activated protein kinase (MAPK) pathway includes KSR, RAF, MEK and the phospho-regulatory sensor 14-3-3. Specific assemblies among these components drive various diseases and likely dictate efficacy for numerous targeted therapies, including allosteric MEK inhibitors (MEKi). However, directly measuring drug interactions on physiological RAS-MAPK complexes in live cells has been inherently challenging to query and therefore remains poorly understood. Here we present a series of NanoBRET-based assays to quantify direct target engagement of MEKi on MEK1 and higher-order MEK1-bound complexes with ARAF, BRAF, CRAF, KSR1 and KSR2 in the presence and absence of 14-3-3 in living cells. We find distinct MEKi preferences among these complexes that can be compiled to generate inhibitor binding profiles. Further, these assays can report on the influence of the pathogenic BRAF-V600E mutant on MEKi binding. Taken together, these approaches can be used as a platform to screen for compounds intended to target specific complexes in the RAS-MAPK cascade.

Impact of diagnosis-to-ablation time on clinical outcomes in patients with early-onset atrial fibrillation.

BACKGROUND: Evidence was lacking for the early choice of radiofrequency ablation (RFA) among patients with early-onset atrial fibrillation (AF). HYPOTHESIS: This study aimed to explore whether earlier RFA was associated with better clinical outcomes among early-onset AF patients. METHODS: Patients, who were diagnosed with AF before 45 years and underwent their first RFA procedures at baseline of the China Atrial Fibrillation registry, were enrolled and divided into four diagnosis-to-ablation time (DAT) groups: DAT ≤ 1 year, 1 year < DAT ≤ 3 years, 3 years < DAT ≤ 6 years, and DAT > 6 years. Another group of nonablation patients, who were newly diagnosed with AF and younger than 45 years, were also included. Adjusted associations of groups with composite cardiovascular events (cardiovascular death, embolism, major hemorrhages, or cardiac rehospitalization) or recurrent AF were analyzed using Cox proportional hazards models. RESULTS: Among 1694 patients who underwent their first RFA at enrollment, incidences of composite cardiovascular outcomes were increasing with extension of DAT (DAT ≤ 1 year: 6.1/100 person-years, 1 year < DAT ≤ 3 years: 7.9/100 person-years, 3 years < DAT ≤ 6 years: 7.6/100 person-years, DAT > 6 years: 10.5/100 person-years; p < .001). In comparison with DAT > 6 years group, the DAT ≤ 1 year group was associated with reduced risk of cardiovascular events (adjusted hazard ratio, HR [95% confidence interval, CI] = 0.64 [0.47-0.87], p = .005) and AF recurrence (adjusted HR [95% CI] = 0.70 [0.57-0.88], p = .002). Associations remained similar after stratified by AF types. Compared to nonablation group (n = 413), DAT ≤ 1year patients tended to show lower cardiovascular risk (adjusted HR [95% CI] = 0.78 [0.58-1.05], p = .099) and lower risk of recurrent AF (adjusted HR [95% CI] = 0.46 [0.38-0.55], p < .001). CONCLUSIONS: A shorter DAT was associated with a lower risk of cardiovascular events and recurrent AF for early-onset AF patients.