Using computed tomogram atrial myocardial thickness maps in high-power short-duration radiofrequency pulmonary vein isolation: UTMOST AF.

Background: High-power short-duration (HPSD) ablation creates wide, shallow lesions using radiofrequency (RF) heating. It is uncertain if adjusting RF energy based on atrial wall thickness provides extra benefits. We studied the safety and effectiveness of tailored HPSD energy based on left atrial (LA) wall thickness (LAWT) for circumferential pulmonary vein isolation (CPVI) in patients with paroxysmal atrial fibrillation (PAF). Methods: We enrolled 212 patients (68.4% male, mean age: 59.5 ± 11.0 years) and randomly assigned them to two groups: LAWT-guided CPVI (WT, n = 108) and conventional CPVI (control, n = 104). Both groups used an open irrigated-tip deflectable catheter to apply 50 W for 10 s to the posterior LA, while controls used 60 W for 15 s on other LA regions. RF delivery time in WT was titrated (15 s at LAWT > 2.1 mm, 13 s at 1.4-2.1 mm, and 11 s at <1.4 mm) according to the computed tomogram-myocardial thickness color map. Results: After a mean follow-up of 13.4 ± 7.0 months, the WT and control groups showed no significant difference regarding clinical recurrence rate (13.9% vs. 5.8%, respectively; p = .061) and major complication rate (4.6% vs. 3.8%, respectively; p > .999). The total procedure time, cardioversion rate, and post-procedural AAD prescription rates did not significantly differ between the groups. Conclusions: The LAWT-guided energy titration strategy did not result in improved procedural safety and efficacy compared to the conventional 50-60 W-HPSD CPVI in patients with PAF.

Anti- and pro-fibrillatory effects of pulmonary vein isolation gaps in human atrial fibrillation digital twins.

Although pulmonary vein isolation (PVI) gaps and extrapulmonary vein triggers contribute to recurrence after atrial fibrillation (AF) ablation, their precise mechanisms remain unproven. Our study assessed the impact of PVI gaps on rhythm outcomes using a human AF digital twin. We included 50 patients (76.0% with persistent AF) who underwent catheter ablation with a realistic AF digital twin by integrating computed tomography and electroanatomical mapping. We evaluated the final rhythm status, including AF and atrial tachycardia (AT), across 600 AF episodes, considering factors including PVI level, PVI gap number, and pacing locations. Our findings revealed that antral PVI had a significantly lower ratio of AF at the final rhythm (28% vs. 56%, p = 0.002) than ostial PVI. Increasing PVI gap numbers correlated with an increased ratio of AF at the final rhythm (p < 0.001). Extra-PV induction yielded a higher ratio of AF at the final rhythm than internal PV induction (77.5% vs. 59.0%, p < 0.001). In conclusion, our human AF digital twin model helped assess AF maintenance mechanisms. Clinical trial registration: https://www.clinicaltrials.gov ; Unique identifier: NCT02138695.

Extra-Pulmonary Vein Triggers at de novo and the Repeat Atrial Fibrillation Catheter Ablation.

Background: Extra-pulmonary vein triggers can play a significant role in atrial fibrillation recurrence after catheter ablation. We explored the characteristics of the extra-pulmonary vein (PV) triggers in de novo and repeat atrial fibrillation (AF) catheter ablation (AFCA). Methods: We included 2,118 patients who underwent a de novo AFCA (women 27.6%, 59.2 ± 10.9 years old, paroxysmal AF 65.9%) and 227 of them conducted repeat procedures. All included patients underwent isoproterenol provocation tests at the end of the procedure, and then we analyzed extra-PV triggers-related factors. Results: Extra-PV triggers were documented in 11.7% of patients undergoing de novo AFCA (1.22 ± 0.46 foci per patient) and 28.6% undergoing repeat AFCA (1.49 ± 0.73 foci per patient). Older age and higher LA volume index in de novo procedures and women, diabetes, and higher parasympathetic nerve activity (heart rate variability) in repeat-AFCA were independently associated with the existence of extra-PV triggers. The septum (19.9%), coronary sinus (14.7%), and superior vena cava (11.2%) were common extra-PV foci. Among 46 patients who were newly found to have mappable extra-PV triggers upon repeat procedures, 15 (32.6%) matched with the previous focal or empirical extra-PV ablation sites. The rate of AF recurrence was significantly higher in patients with extra-PV triggers than in those without after de novo (HR 1.91, 95% CI 1.54-2.38, p < 0.001) and repeat procedures (HR 2.68, 95% CI 1.63-4.42, p < 0.001). Conclusions: Extra-PV triggers were commonly found in AF patients with significant remodeling and previous empirical extra-PV ablation. The existence of extra-PV triggers was independently associated with poorer rhythm outcomes after the de novo and repeat AFCA.

A Joining Process between Beryllium and Reduced-Activation Ferritic-Martensitic Steel by Plasma Sintering.

To investigate the growth kinetics of the reaction layer and mechanical strength of joined materials, we joined beryllium and reduced-activation ferritic-martensitic steel (F82H) by plasma sintering under various conditions and characterized the joined region. Scanning electron microscopy revealed that the thickness of the reaction layer increased with an increase in the joining time and temperature. Line analyses and elemental mapping using an electron microprobe analyser showed that the reaction layer consists of Be-Fe intermetallic compounds, including Be12Fe, Be5Fe, and Be2Fe, with small amounts of chromium and tungsten. Owing to the time and temperature dependence of the reaction-layer thickness, the layer growth of Be-Fe intermetallic compounds obeys the parabolic law, and the activation energy for the reaction-layer growth was 116.2 kJ/mol. The bonding strengths of the joined materials varied inversely with the thickness of the reaction layer.

Network-based drug sensitivity prediction.

BACKGROUND: Drug sensitivity prediction and drug responsive biomarker selection on high-throughput genomic data is a critical step in drug discovery. Many computational methods have been developed to serve this purpose including several deep neural network models. However, the modular relations among genomic features have been largely ignored in these methods. To overcome this limitation, the role of the gene co-expression network on drug sensitivity prediction is investigated in this study. METHODS: In this paper, we first introduce a network-based method to identify representative features for drug response prediction by using the gene co-expression network. Then, two graph-based neural network models are proposed and both models integrate gene network information directly into neural network for outcome prediction. Next, we present a large-scale comparative study among the proposed network-based methods, canonical prediction algorithms (i.e., Elastic Net, Random Forest, Partial Least Squares Regression, and Support Vector Regression), and deep neural network models for drug sensitivity prediction. All the source code and processed datasets in this study are available at https://github.com/compbiolabucf/drug-sensitivity-prediction . RESULTS: In the comparison of different feature selection methods and prediction methods on a non-small cell lung cancer (NSCLC) cell line RNA-seq gene expression dataset with 50 different drug treatments, we found that (1) the network-based feature selection method improves the prediction performance compared to Pearson correlation coefficients; (2) Random Forest outperforms all the other canonical prediction algorithms and deep neural network models; (3) the proposed graph-based neural network models show better prediction performance compared to deep neural network model; (4) the prediction performance is drug dependent and it may relate to the drug's mechanism of action. CONCLUSIONS: Network-based feature selection method and prediction models improve the performance of the drug response prediction. The relations between the genomic features are more robust and stable compared to the correlation between each individual genomic feature and the drug response in high dimension and low sample size genomic datasets.

Microstructural Evolution of Hybrid Perovskites Promoted by Chlorine and its Impact on the Performance of Solar Cell.

The role of Cl in halide hybrid perovskites CH3NH3PbI3(Cl) (MAPbI3(Cl)) on the augmentation of grain size is still unclear although many reports have referred to these phenomena. Herein, we synthesized MAPbI3(Cl) perovskite films by using excess MACl-containing precursors, which exhibited approximately an order of magnitude larger grain size with higher <110>-preferred orientation compared with that from stoichiometric precursors. Comprehensive mechanisms for the large grain evolution by Cl incorporation were elucidated in detail by correlating the changes in grain orientation, distribution of grain size, and the remaining Cl in the perovskite during thermal annealing. In the presence of Cl, <110>- and <001>-oriented grains grew faster than other grains at the initial stage of annealing. Further annealing led to the dissipation of Cl, resulting in the shrinkage of <001> grains while <110> grains continuously grew, as analyzed by x-ray rocking curve and diffraction. As a result of reduced grain boundaries and enhanced <110> texture, the trap density of perovskite solar cells diminished by ~10% by incorporating MACl in the precursor, resulting in a fill factor more than 80%.

Electronic Traps and Their Correlations to Perovskite Solar Cell Performance via Compositional and Thermal Annealing Controls.

Herein, underlying factors for enabling efficient and stable performance of perovskite solar cells are studied through nanostructural controls of organic-inorganic halide perovskites. Namely, MAPbI3, (FA0.83MA0.17)Pb(I0.83Br0.17)3, and (Cs0.10FA0.75MA0.15)Pb(I0.85Br0.15)3 perovskites (abbreviated as MA, FAMA, and CsFAMA, respectively) are examined with a grain growth control through thermal annealing. FAMA- and CsFAMA-based cells result in stable photovoltaic performance, while MA cells are sensitively dependent on the perovskite grain size dominated by annealing time. Micro-/nanoscopic features are comprehensively analyzed to unravel the origin that is directly correlated to the cell performance with the applications of electronic-trap characterizations such as photoconductive noise microscopy and capacitance analyses. It is revealed that CsFAMA has a lower trap density compared to MA and FAMA through the analyses of 1/ f noises and trapping/detrapping capacitances. Also, an open-circuit voltage ( Voc) change is correlated to the variation of trap states during the shelf-life test: FAMA and CsFAMA cells with the negligible change of Voc over weeks exhibit trap states shifting toward the band edge, although the power-conversion efficiencies are clearly reduced. The origins that critically affect the solar cell performance through the characterizations of shallow/deep traps with additional mobile defects in the perovskite and interfaces are discussed.

Optimum Morphology of Mixed-Olivine Mesocrystals for a Li-Ion Battery.

In this present work, we report on the synthesis of micron-sized LiMn0.8Fe0.2PO4 (LMFP) mesocrystals via a solvothermal method with varying pH and precursor ratios. The morphologies of resultant LMFP secondary particles are classified into two major classes, flakes and ellipsoids, both of which are featured by the mesocrystalline aggregates where the primary particles constituting LMFP secondary particles are crystallographically aligned. Assessment of the battery performance reveals that the flake-shaped LMFP mesocrystals exhibit a specific capacity and rate capability superior to those of other mesocrystals. The origin of the enhanced electrochemical performance is investigated in terms of primary particle size, pore structure, antisite-defect concentration, and secondary particle shape. It is shown that the shape of the secondary particle has just as much of a significant effect on the battery performance as the crystallite size and antisite defects do. We believe that this work provides a rule of design for electrochemically favorable meso/nanostructures, which is of great potential for improving battery performance by tuning the morphology of particles on multilength scales.

Chemistry-First Approach for Nomination of Personalized Treatment in Lung Cancer.

Diversity in the genetic lesions that cause cancer is extreme. In consequence, a pressing challenge is the development of drugs that target patient-specific disease mechanisms. To address this challenge, we employed a chemistry-first discovery paradigm for de novo identification of druggable targets linked to robust patient selection hypotheses. In particular, a 200,000 compound diversity-oriented chemical library was profiled across a heavily annotated test-bed of >100 cellular models representative of the diverse and characteristic somatic lesions for lung cancer. This approach led to the delineation of 171 chemical-genetic associations, shedding light on the targetability of mechanistic vulnerabilities corresponding to a range of oncogenotypes present in patient populations lacking effective therapy. Chemically addressable addictions to ciliogenesis in TTC21B mutants and GLUT8-dependent serine biosynthesis in KRAS/KEAP1 double mutants are prominent examples. These observations indicate a wealth of actionable opportunities within the complex molecular etiology of cancer.

From Nanostructural Evolution to Dynamic Interplay of Constituents: Perspectives for Perovskite Solar Cells.

Moving away from the high-performance achievements in organometal halide perovskite (OHP)-based optoelectronic and photovoltaic devices, intriguing features have been reported in that photocarriers and mobile ionic species within OHPs interact with light, electric fields, or a combination of both, which induces both spatial and temporal changes of optoelectronic properties in OHPs. Since it is revealed that the transport of photocarriers and the migration of ionic species are affected not only by each other but also by the inhomogeneous character, which is a consequence of the route selected to deposit OHPs, understanding the nanostructural evolution during OHP deposition, in terms of the resultant structural defects, electronic traps, and nanoscopic charge behaviors, will be valuable. Investigation of the film-growth mechanisms and strategies adopted to realize OHP films with less-defective large grains is of central importance, considering that single-crystalline OHPs have exhibited the most beneficial properties, including carrier lifetimes. Critical factors governing the behavior of photocarriers, mobile ionic species, and nanoscale optoelectronic properties resulting from either or all of them are further summarized, which may potentially limit or broaden the optoelectronic and photovoltaic applications of OHPs. Through inspection of the recent advances, a comprehensive picture and future perspective of OHPs are provided.

Route to Improving Photovoltaics Based on CdSe/CdSexTe1-x Type-II Heterojunction Nanorods: The Effect of Morphology and Cosensitization on Carrier Recombination and Transport.

One-dimensionally elongated nanoparticles with type-II staggered band offset are of potential use as light-harvesting materials for photovoltaics, but only a limited attention has been given to elucidate the factors governing the cell performance obtainable from such materials. Herein, we describe a combined strategy to enhance charge collection from CdSe/CdSexTe1-x type-II heterojunction nanorods (HNRs) utilized as light harvesters for sensitized solar cells. By integrating morphology- and composition-tuned type-II HNRs into solar cells, factors that yield interfaces favorable both for the electron injection into TiO2 and hole transfer to electrolyte are examined. Furthermore, it is shown that a more efficient photovoltaic system results from cosensitization with CdS quantum dots (QDs) predeposited on a TiO2 scaffold, which improves charge collection from HNRs. Electrochemical impedance spectroscopy (EIS) analysis suggests that such a synergistically enhanced system benefits from the decreased recombination within HNRs and facilitated charge transport through the cosensitized TiO2 electrode, even with the activation of a recombination path presumably related to the photogenerated holes in CdS QDs.

Tailoring the Mesoscopic TiO2 Layer: Concomitant Parameters for Enabling High-Performance Perovskite Solar Cells.

Architectural control over the mesoporous TiO2 film, a common electron-transport layer for organic-inorganic hybrid perovskite solar cells, is conducted by employing sub-micron sized polystyrene beads as sacrificial template. Such tailored TiO2 layer is shown to induce asymmetric enhancement of light absorption notably in the long-wavelength region with red-shifted absorption onset of perovskite, leading to ~20% increase of photocurrent and ~10% increase of power conversion efficiency. This enhancement is likely to be originated from the enlarged CH3NH3PbI3(Cl) grains residing in the sub-micron pores rather than from the effect of reduced perovskite-TiO2 interfacial area, which is supported from optical bandgap change, haze transmission of incident light, and one-diode model parameters correlated with the internal surface area of microporous TiO2 layers. With the templating strategy suggested, the necessity of proper hole-blocking method is discussed to prevent any direct contact of the large perovskite grains infiltrated into the intended pores of TiO2 scaffold, further mitigating the interfacial recombination and leading to ~20% improvement in power conversion efficiency compared with the control device using conventional solution-processed hole blocking TiO2. Thereby, the imperatives that originate from the structural engineering of the electron-transport layer are discussed to understand the governing elements for the improved device performance.

SMARCA4-inactivating mutations increase sensitivity to Aurora kinase A inhibitor VX-680 in non-small cell lung cancers.

Mutations in the SMARCA4/BRG1 gene resulting in complete loss of its protein (BRG1) occur frequently in non-small cell lung cancer (NSCLC) cells. Currently, no single therapeutic agent has been identified as synthetically lethal with SMARCA4/BRG1 loss. We identify AURKA activity as essential in NSCLC cells lacking SMARCA4/BRG1. In these cells, RNAi-mediated depletion or chemical inhibition of AURKA induces apoptosis and cell death in vitro and in xenograft mouse models. Disc large homologue-associated protein 5 (HURP/DLGAP5), required for AURKA-dependent, centrosome-independent mitotic spindle assembly is essential for the survival and proliferation of SMARCA4/BRG1 mutant but not of SMARCA4/BRG1 wild-type cells. AURKA inhibitors may provide a therapeutic strategy for biomarker-driven clinical studies to treat the NSCLCs harbouring SMARCA4/BRG1-inactivating mutations.

Evaluating the Optoelectronic Quality of Hybrid Perovskites by Conductive Atomic Force Microscopy with Noise Spectroscopy.

Organic-inorganic hybrid perovskite solar cells have emerged as promising candidates for next-generation solar cells. To attain high photovoltaic efficiency, reducing the defects in perovskites is crucial along with a uniform coating of the films. Also, evaluating the quality of synthesized perovskites via facile and adequate methods is important as well. Herein, CH3NH3PbI3 perovskites were synthesized by applying second solvent dripping to nonstoichiometric precursors containing excess CH3NH3I. The resulting perovskite films exhibited a larger average grain size with a better crystallinity compared to that from stoichiometric precursors. As a result, the performance of planar perovskite solar cells was significantly improved, achieving an efficiency of 14.3%. Furthermore, perovskite films were effectively analyzed using a conductive AFM and noise spectroscopy, which have been uncommon in the field of perovskite solar cells. Comparing the topography and photocurrent maps, the variation of photocurrents in nanoscale was systematically investigated, and a linear relationship between the grain size and photocurrent was revealed. Also, noise analyses with a conductive probe enabled examination of the defect density of perovskites at specific grain interiors by excluding the grain-boundary effect, and reduced defects were clearly observed for the perovskites using CH3NH3I-rich precursors.

Chemical Amination via Cycloaddition of Graphene for Use in a Glucose Sensor.

Graphene was chemically aminated via cycloaddition. Aziridine-ring linkages were formed by covalently modifying the C-C double bonds in graphene. The aminated graphene presents an enhanced hydrophilicity, the contact angle with water decreases from 80.5 degrees to 58.5 degrees. And the conductivity of aminated graphene exhibits exponential decay as the reaction time increase. If the reaction time is 90 min, the resistance of aminated graphene was increased from -32 Ω to -2744 Ω. Because the amino group has good biocompatibility, the aminated graphene is designed for use as an enzyme sensor platform, such as glucose sensor based on glucose oxidase. The aminated graphene exhibited a good detection response for glucose. The increase in device current is about 12% in 1.2 mg/mL glucose solution.

Solvent and Intermediate Phase as Boosters for the Perovskite Transformation and Solar Cell Performance.

High power conversion efficiency and device stabilization are two major challenges for CH3NH3PbI3 (MAPbI3) perovskite solar cells to be commercialized. Herein, we demonstrate a diffusion-engineered perovskite synthesis method using MAI/ethanol dipping, and compared it to the conventional synthesis method from MAI/iso-propanol. Diffusion of MAI/C2H5OH into the PbCl2 film was observed to be more favorable than that of MAI/C3H7OH. Facile perovskite conversion from ethanol and highly-crystalline MAPbI3 with minimized impurities boosted the efficiency from 5.86% to 9.51%. Additionally, we further identified the intermediates and thereby the reaction mechanisms of PbCl2 converting into MAPbI3. Through straightforward engineering to enhance the surface morphology as well as the crystallinity of the perovskite with even faster conversion, an initial power conversion efficiency of 11.23% was obtained, in addition to superior stability after 30 days under an ambient condition.

Chemical and Physical Characteristics of Doxorubicin Hydrochloride Drug-Doped Salmon DNA Thin Films.

Double-stranded salmon DNA (SDNA) was doped with doxorubicin hydrochloride drug molecules (DOX) to determine the binding between DOX and SDNA, and DOX optimum doping concentration in SDNA. SDNA thin films were prepared with various concentrations of DOX by drop-casting on oxygen plasma treated glass and quartz substrates. Fourier transform infrared (FTIR) spectroscopy was employed to investigate the binding sites for DOX in SDNA, and electrical and photoluminescence (PL) analyses were used to determine the optimum doping concentration of DOX. The FTIR spectra showed that up to a concentration of 30 µM of DOX, there was a tendency for binding with a periodic orientation via intercalation between nucleosides. The current and PL intensity increased as the DOX concentration increased up to 30 µM, and then as the concentration of DOX further increased, we observed a decrease in current as well as PL quenching. Finally, the optical band gap and second band onset of the transmittance spectra were analyzed to further verify the DOX binding and optimum doping concentration into SDNA thin films as a function of the DOX concentration.

Network-based Phenome-Genome Association Prediction by Bi-Random Walk.

MOTIVATION: The availability of ontologies and systematic documentations of phenotypes and their genetic associations has enabled large-scale network-based global analyses of the association between the complete collection of phenotypes (phenome) and genes. To provide a fundamental understanding of how the network information is relevant to phenotype-gene associations, we analyze the circular bigraphs (CBGs) in OMIM human disease phenotype-gene association network and MGI mouse phentoype-gene association network, and introduce a bi-random walk (BiRW) algorithm to capture the CBG patterns in the networks for unveiling human and mouse phenome-genome association. BiRW performs separate random walk simultaneously on gene interaction network and phenotype similarity network to explore gene paths and phenotype paths in CBGs of different sizes to summarize their associations as predictions. RESULTS: The analysis of both OMIM and MGI associations revealed that majority of the phenotype-gene associations are covered by CBG patterns of small path lengths, and there is a clear correlation between the CBG coverage and the predictability of the phenotype-gene associations. In the experiments on recovering known associations in cross-validations on human disease phenotypes and mouse phenotypes, BiRW effectively improved prediction performance over the compared methods. The constructed global human disease phenome-genome association map also revealed interesting new predictions and phenotype-gene modules by disease classes.

Improving scattering layer through mixture of nanoporous spheres and nanoparticles in ZnO-based dye-sensitized solar cells.

A scattering layer is utilized by mixing nanoporous spheres and nanoparticles in ZnO-based dye-sensitized solar cells. Hundred-nanometer-sized ZnO spheres consisting of approximately 35-nm-sized nanoparticles provide not only effective light scattering but also a large surface area. Furthermore, ZnO nanoparticles are added to the scattering layer to facilitate charge transport and increase the surface area as filling up large voids. The mixed scattering layer of nanoparticles and nanoporous spheres on top of the nanoparticle-based electrode (bilayer geometry) improves solar cell efficiency by enhancing both the short-circuit current (J sc) and fill factor (FF), compared to the layer consisting of only nanoparticles or nanoporous spheres.

A simple template-free 'sputtering deposition and selective etching' process for nanoporous thin films and its application to dye-sensitized solar cells.

A facile and straightforward method is suggested to synthesize nanoporous-TiO2 thin films for dye-sensitized solar cells (DSSCs). Silver/TiO2 co-sputtering led to the formation of nanocomposite films which consisted of silver nanoclusters with surrounding TiO2 matrices, and metal particles were subsequently etched by just immersing in nitric acid. Nanoporous-TiO2 DSSCs fabricated by this simple and effective process showed power-conversion efficiencies of up to 3.4% at a thickness of only 1.8 µm, which is much superior to that of conventional nanoparticulate-TiO2 DSSCs with similar thickness.