Sub-Diffraction Correlation of Quantum Emitters and Local Strain Fields in Strain-Engineered WSe2 Monolayers.

Strain-engineering in atomically thin metal dichalcogenides is a useful method for realizing single-photon emitters (SPEs) for quantum technologies. Correlating SPE position with local strain topography is challenging due to localization inaccuracies from the diffraction limit. Currently, SPEs are assumed to be positioned at the highest strained location and are typically identified by randomly screening narrow-linewidth emitters, of which only a few are spectrally pure. In this work, hyperspectral quantum emitter localization microscopy is used to locate 33 SPEs in nanoparticle-strained WSe2 monolayers with sub-diffraction-limit resolution (≈30 nm) and correlate their positions with the underlying strain field via image registration. In this system, spectrally pure emitters are not concentrated at the highest strain location due to spectral contamination; instead, isolable SPEs are distributed away from points of peak strain with an average displacement of 240 nm. These observations point toward a need for a change in the design rules for strain-engineered SPEs and constitute a key step toward realizing next-generation quantum optical architectures.

Progression of obstructive sleep apnoea after renal denervation is not associated with hypertension exaggeration.

PURPOSE: In a cohort, observational prospective trial, we assessed the long-term dynamics of sleep-disordered breathing in patients with resistant hypertension after renal denervation and their association with blood pressure change at remote follow-up. MATERIALS AND METHODS: Twenty-eight patients with stable hypertension who were recruited for endovascular radiofrequency renal denervation in 2012-2019 and had valid both baseline and follow-up sleep study, were included in the analysis. All patients underwent physical examination, anthropometry, office and ambulatory blood pressure measurements, blood and urine tests, kidney visualization, and full polysomnography before and within 12-36 months after renal denervation. RESULTS: The average follow-up comprised 30.1 ± 8.4 months. At long-term follow-up, no significant changes in creatinine level, estimated glomerular filtration rate, body mass index were registered. There was a significant increase in sleep apnea severity indices: the mean change in apnea-hypopnea index comprised 9.0(-21.1;25.2) episodes/h, in oxygen desaturation index 6.5(-16.8;35.9) episodes/h, in the average SpO2 -1.7(-5.6;1.9)%. Over 12-month follow-up, there were no significant differences in blood pressure response in patients with and without sleep apnea. The baseline apnea-hypopnea and oxygen desaturation indices and the mean SpO2 were associated with the circadian blood pressure profile at follow-up, but did not correlate with the blood pressure response. CONCLUSIONS: Although the severity of sleep apnea worsens at > 12 months follow-up after renal denervation, this is not associated with hypertension exaggeration.

Radiosensitizing Effect of Dextran-Coated Iron Oxide Nanoparticles on Malignant Glioma Cells.

The potential of standard methods of radiation therapy is limited by the dose that can be safely delivered to the tumor, which could be too low for radical treatment. The dose efficiency can be increased by using radiosensitizers. In this study, we evaluated the sensitizing potential of biocompatible iron oxide nanoparticles coated with a dextran shell in A172 and Gl-Tr glioblastoma cells in vitro. The cells preincubated with nanoparticles for 24 h were exposed to ionizing radiation (X-ray, gamma, or proton) at doses of 0.5-6 Gy, and their viability was assessed by the Resazurin assay and by staining of the surviving cells with crystal violet. A statistically significant effect of radiosensitization by nanoparticles was observed in both cell lines when cells were exposed to 35 keV X-rays. A weak radiosensitizing effect was found only in the Gl-Tr line for the 1.2 MeV gamma irradiation and there was no radiosensitizing effect in both lines for the 200 MeV proton irradiation at the Bragg peak. A slight (ca. 10%) increase in the formation of additional reactive oxygen species after X-ray irradiation was found when nanoparticles were present. These results suggest that the nanoparticles absorbed by glioma cells can produce a significant radiosensitizing effect, probably due to the action of secondary electrons generated by the magnetite core, whereas the dextran shell of the nanoparticles used in these experiments appears to be rather stable under radiation exposure.

Combination of personalized computational modeling and machine learning for optimization of left ventricular pacing site in cardiac resynchronization therapy.

Introduction: The 30-50% non-response rate to cardiac resynchronization therapy (CRT) calls for improved patient selection and optimized pacing lead placement. The study aimed to develop a novel technique using patient-specific cardiac models and machine learning (ML) to predict an optimal left ventricular (LV) pacing site (ML-PS) that maximizes the likelihood of LV ejection fraction (LVEF) improvement in a given CRT candidate. To validate the approach, we evaluated whether the distance DPS between the clinical LV pacing site (ref-PS) and ML-PS is associated with improved response rate and magnitude. Materials and methods: We reviewed retrospective data for 57 CRT recipients. A positive response was defined as a more than 10% LVEF improvement. Personalized models of ventricular activation and ECG were created from MRI and CT images. The characteristics of ventricular activation during intrinsic rhythm and biventricular (BiV) pacing with ref-PS were derived from the models and used in combination with clinical data to train supervised ML classifiers. The best logistic regression model classified CRT responders with a high accuracy of 0.77 (ROC AUC = 0.84). The LR classifier, model simulations and Bayesian optimization with Gaussian process regression were combined to identify an optimal ML-PS that maximizes the ML-score of CRT response over the LV surface in each patient. Results: The optimal ML-PS improved the ML-score by 17 ± 14% over the ref-PS. Twenty percent of the non-responders were reclassified as positive at ML-PS. Selection of positive patients with a max ML-score >0.5 demonstrated an improved clinical response rate. The distance DPS was shorter in the responders. The max ML-score and DPS were found to be strong predictors of CRT response (ROC AUC = 0.85). In the group with max ML-score > 0.5 and DPS< 30 mm, the response rate was 83% compared to 14% in the rest of the cohort. LVEF improvement in this group was higher than in the other patients (16 ± 8% vs. 7 ± 8%). Conclusion: A new technique combining clinical data, personalized heart modelling and supervised ML demonstrates the potential for use in clinical practice to assist in optimizing patient selection and predicting optimal LV pacing lead position in HF candidates for CRT.

Current State and Prospectives for Proton Boron Capture Therapy.

The development of new methods increasing the biological effectiveness of proton therapy (PT) is of high interest in radiation oncology. The use of binary technologies, in which the damaging effect of proton radiation is further enhanced by the selective accumulation of the radiosensitizer in the target tissue, can significantly increase the effectiveness of radiation therapy. To increase the absorbed dose in a tumor target, proton boron capture therapy (PBCT) was proposed based on the reaction of proton capture on the 11B isotope with the formation of three α-particles. This review summarizes data on theoretical and experimental studies on the effectiveness and prospects of proton boron capture therapy.

Chemomechanical modification of quantum emission in monolayer WSe2.

Two-dimensional (2D) materials have attracted attention for quantum information science due to their ability to host single-photon emitters (SPEs). Although the properties of atomically thin materials are highly sensitive to surface modification, chemical functionalization remains unexplored in the design and control of 2D material SPEs. Here, we report a chemomechanical approach to modify SPEs in monolayer WSe2 through the synergistic combination of localized mechanical strain and noncovalent surface functionalization with aryl diazonium chemistry. Following the deposition of an aryl oligomer adlayer, the spectrally complex defect-related emission of strained monolayer WSe2 is simplified into spectrally isolated SPEs with high single-photon purity. Density functional theory calculations reveal energetic alignment between WSe2 defect states and adsorbed aryl oligomer energy levels, thus providing insight into the observed chemomechanically modified quantum emission. By revealing conditions under which chemical functionalization tunes SPEs, this work broadens the parameter space for controlling quantum emission in 2D materials.

Matrix is everywhere: extracellular DNA is a link between biofilm and mineralization in Bacillus cereus planktonic lifestyle.

To date, the mechanisms of biomineralization induced by bacterial cells in the context of biofilm formation remain the subject of intensive studies. In this study, we analyzed the influence of the medium components on the induction of CaCO3 precipitation by the Bacillus cereus cells and composition of the extracellular matrix (ECM) formed in the submerged culture. While the accumulation of extracellular polysaccharides and amyloids appeared to be independent of the presence of calcium and urea during the growth, the accumulation of extracellular DNA (eDNA), as well as precipitation of calcium carbonate, required the presence of both ingredients in the medium. Removal of eDNA, which was sensitive to treatment by DNase, did not affect other matrix components but resulted in disruption of cell network formation and a sixfold decrease in the precipitate yield. An experiment with a cell-free system confirmed the acceleration of mineral formation after the addition of exogenous salmon sperm DNA. The observed pathway for the formation of CaCO3 minerals in B. cereus planktonic culture included a production of exopolysaccharides and negatively charged eDNA lattice promoting local Ca2+ supersaturation, which, together with an increase in the concentration of carbonate ions due to pH rise, resulted in the formation of an insoluble precipitate of calcium carbonate. Precipitation of amorphous CaCO3 on eDNA matrix was followed by crystal formation via the ACC-vaterite-calcite/aragonite pathway and further formation of larger mineral aggregates in complex with extracellular polymeric substances. Taken together, our data showed that DNA in extracellular matrix is an essential factor for triggering the biomineralization in B. cereus planktonic culture.

Quantitative Characterization of the Anisotropic Thermal Properties of Encapsulated Two-Dimensional MoS2 Nanofilms.

Two-dimensional (2D) semiconductors exhibit unique physical properties at the limit of a few atomic layers that are desirable for optoelectronic, spintronic, and electronic applications. Some of these materials require ambient encapsulation to preserve their properties from environmental degradation. While encapsulating 2D semiconductors is essential to device functionality, they also impact heat management due to the reduced thermal conductivity of the 2D material. There are limited experimental reports on in-plane thermal conductivity measurements in encapsulated 2D semiconductors. These measurements are particularly challenging in ultrathin films with a lower thermal conductivity than graphene since it may be difficult to separate the thermal effects of the sample from the encapsulating layers. To address this challenge, we integrated the frequency domain thermoreflectance (FDTR) and optothermal Raman spectroscopy (OTRS) techniques in the same experimental platform. First, we use the FDTR technique to characterize the cross-plane thermal conductivity and thermal boundary conductance. Next, we measure the in-plane thermal conductivity by model-based analysis of the OTRS measurements, using the cross-plane properties obtained from the FDTR measurements as input parameters. We provide experimental data for the first time on the thickness-dependent in-plane thermal conductivity of ultrathin MoS2 nanofilms encapsulated by alumina (Al2O3) and silica (SiO2) thin films. The measured thermal conductivity increased from 26.0 ± 10.0 W m-1 K-1 for monolayer MoS2 to 39.8 ± 10.8 W m-1 K-1 for the six-layer films. We also show that the thickness-dependent cross-plane thermal boundary conductance of the Al2O3/MoS2/SiO2 interface is limited by the low thermal conductance (18.5 MW m-2 K-1) of the MoS2/SiO2 interface, which has important implications on heat management in SiO2-supported and encased MoS2 devices. The measurement methods can be generalized to other 2D materials to study their anisotropic thermal properties.

Worldwide survey on implantation of and outcomes for conduction system pacing with His bundle and left bundle branch area pacing leads.

BACKGROUND: Adoption and outcomes for conduction system pacing (CSP), which includes His bundle pacing (HBP) or left bundle branch area pacing (LBBAP), in real-world settings are incompletely understood. We sought to describe real-world adoption of CSP lead implantation and subsequent outcomes. METHODS: We performed an online cross-sectional survey on the implantation and outcomes associated with CSP, between November 15, 2020, and February 15, 2021. We described survey responses and reported HBP and LBBAP outcomes for bradycardia pacing and cardiac resynchronization CRT indications, separately. RESULTS: The analysis cohort included 140 institutions, located on 5 continents, who contributed data to the worldwide survey on CSP. Of these, 127 institutions (90.7%) reported experience implanting CSP leads. CSP and overall device implantation volumes were reported by 84 institutions. In 2019, the median proportion of device implants with CSP, HBP, and/or LBBAP leads attempted were 4.4% (interquartile range [IQR], 1.9-12.5%; range, 0.4-100%), 3.3% (IQR, 1.3-7.1%; range, 0.2-87.0%), and 2.5% (IQR, 0.5-24.0%; range, 0.1-55.6%), respectively. For bradycardia pacing indications, HBP leads, as compared to LBBAP leads, had higher reported implant threshold (median [IQR]: 1.5 V [1.3-2.0 V] vs 0.8 V [0.6-1.0 V], p = 0.0008) and lower ventricular sensing (median [IQR]: 4.0 mV [3.0-5.0 mV] vs. 10.0 mV [7.0-12.0 mV], p < 0.0001). CONCLUSION: In conclusion, CSP lead implantation has been broadly adopted but has yet to become the default approach at most surveyed institutions. As the indications and data for CSP continue to evolve, strategies to educate and promote CSP lead implantation at institutions without CSP lead implantation experience would be necessary.

Experimental validation of proton boron capture therapy for glioma cells.

Proton boron capture therapy (PBCT) has emerged from particle acceleration research for enhancing the biological effectiveness of proton therapy. The mechanism responsible for the dose increase was supposed to be related to proton-boron fusion reactions (11B + p → 3α + 8.7 MeV). There has been some experimental evidence that the biological efficiency of protons is significantly higher for boron-11-containing prostate or breast cancer cells. The aim of this study was to evaluate the sensitizing potential of sodium borocaptate (BSH) under proton irradiation at the Bragg peak of cultured glioma cells. To address this problem, cells of two glioma lines were preincubated with 80 or 160 ppm boron-11, irradiated both at the middle of 200 MeV beam Spread-Out Bragg Peak (SOBP) and at the distal end of the 89.7 MeV beam SOBP and assessed for the viability, as well as their ability to form colonies. Our results clearly show that BSH provides for only a slight, if any, enhancement of the effect of proton radiation on the glioma cells in vitro. In addition, we repeated the experiments using the Du145 prostate cancer cell line, for which an increase in the biological efficiency of proton irradiation in the presence of sodium borocaptate was demonstrated previously. The data presented add new argument against the efficiency of proton boron capture therapy when based solely on direct dose-enhancement effect by the proton capture nuclear reaction, underlining the need to investigate the indirect effects of the secondary alpha irradiation depending on the state and treatment conditions of the irradiated tissue.

Conversion of Classical Light Emission from a Nanoparticle-Strained WSe2 Monolayer into Quantum Light Emission via Electron Beam Irradiation.

Solid-state single photon emitters (SPEs) within atomically thin transition metal dichalcogenides (TMDs) have recently attracted interest as scalable quantum light sources for quantum photonic technologies. Among TMDs, WSe2 monolayers (MLs) are promising for the deterministic fabrication and engineering of SPEs using local strain fields. The ability to reliably produce isolatable SPEs in WSe2 is currently impeded by the presence of numerous spectrally overlapping states that occur at strained locations. Here nanoparticle (NP) arrays with precisely defined positions and sizes are employed to deterministically create strain fields in WSe2 MLs, thus enabling the systematic investigation and control of SPE formation. Using this platform, electron beam irradiation at NP-strained locations transforms spectrally overlapped sub-bandgap emission states into isolatable, anti-bunched quantum emitters. The dependence of the emission spectra of WSe2 MLs as a function of strain magnitude and exposure time to electron beam irradiation is quantified and provides insight into the mechanism for SPE production. Excitons selectively funnel through strongly coupled sub-bandgap states introduced by electron beam irradiation, which suppresses spectrally overlapping emission pathways and leads to measurable anti-bunched behavior. The findings provide a strategy to generate isolatable SPEs in 2D materials with a well-defined energy range.

Laser renal denervation: A comprehensive evaluation of microstructural renal artery lesions.

Renal artery denervation (RDN) has been proposed for resistant arterial hypertension. Beyond conventional radiofrequency (RF) ablation, there are emerging RDN technologies, including laser catheter ablation. We aimed at evaluamting the local effects of laser ablation on the renal artery and perivascular nerve injury in comparison with radiofrequency ablation. Thirteen pigs (mean weight 36.7 ± 4.7 kg, age 3 months) were divided into three groups: (1) laser ablation in normotensive pigs (LA; n = 3), (2) bipolar RF ablation in normotensive pigs (RF; n = 7), and (3) a sham group (SHAM; n = 3). Transcatheter laser and RF ablations were performed under general anesthesia. After euthanasia, pathology and immunohistochemical studies were performed. Artery wall and perivascular nerve lesions were found in the LA and RF groups. A lower rate of intimal microdissections was evaluated after laser ablation when compared with RF ablation (0 vs. 1.5 [1;2.75] per artery; p < .05). There was a numerical prevalence of nerves with tyrosine hydroxylase expression loss after laser RDN when compared with RF ablation (16.7 [4; 18] vs. 9.1 [0;18] per specimen). Laser ablation is noninferior to RF ablation regarding perivascular nerve injury and is associated with less intimal layer damage.

Liquid-Phase Exfoliation of Magnetically and Optoelectronically Active Ruthenium Trichloride Nanosheets.

α-RuCl3 is a layered transition metal halide that possesses a range of exotic magnetic, optical, and electronic properties including fractional excitations indicative of a proximate Kitaev quantum spin liquid (QSL). While previous reports have explored these properties on idealized single crystals or mechanically exfoliated samples, the scalable production of α-RuCl3 nanosheets has not yet been demonstrated. Here, we perform liquid-phase exfoliation (LPE) of α-RuCl3 through an electrochemically assisted approach, which yields ultrathin, electron-doped α-RuCl3 nanosheets that are then assembled into electrically conductive large-area thin films. The crystalline integrity of the α-RuCl3 nanosheets following LPE is confirmed through a wide range of structural and chemical analyses. Moreover, the physical properties of the LPE α-RuCl3 nanosheets are investigated through electrical, optical, and magnetic characterization methods, which reveal a structural phase transition at 230 K that is consistent with the onset of Kitaev paramagnetism in addition to an antiferromagnetic transition at 2.6 K. Intercalated ions from the electrochemical LPE protocol favorably alter the optical response of the α-RuCl3 nanosheets, enabling large-area Mott insulator photodetectors that operate at telecommunications-relevant infrared wavelengths near 1.55 µm. These photodetectors show a linear photocurrent response as a function of incident power, which suggests negligible trap-mediated recombination or photothermal effects, ultimately resulting in a photoresponsivity of ≈2 mA/W.

Morphotaxy of Layered van der Waals Materials.

Layered van der Waals (vdW) materials have attracted significant attention due to their materials properties that can enhance diverse applications including next-generation computing, biomedical devices, and energy conversion and storage technologies. This class of materials is typically studied in the two-dimensional (2D) limit by growing them directly on bulk substrates or exfoliating them from parent layered crystals to obtain single or few layers that preserve the original bonding. However, these vdW materials can also function as a platform for obtaining additional phases of matter at the nanoscale. Here, we introduce and review a synthesis paradigm, morphotaxy, where low-dimensional materials are realized by using the shape of an initial nanoscale precursor to template growth or chemical conversion. Using morphotaxy, diverse non-vdW materials such as HfO2 or InF3 can be synthesized in ultrathin form by changing the composition but preserving the shape of the original 2D layered material. Morphotaxy can also enable diverse atomically precise heterojunctions and other exotic structures such as Janus materials. Using this morphotaxial approach, the family of low-dimensional materials can be substantially expanded, thus creating vast possibilities for future fundamental studies and applied technologies.

Performance of the ablation index during pulmonary vein isolation: periprocedural data from a multicenter registry.

PURPOSE: Our study aimed to assess the achievement of target ablation index (AI) values and their impact on first-pass pulmonary vein isolation (FPI) as well as to identify FPI predictors. METHODS: Atrial fibrillation (AF) ablation was performed according to the local practice, and target AIs were evaluated. The actual AI was calculated as the median value of all ablation points for the anterior and posterior left atrial (LA) walls. RESULTS: A total of 450 patients from nine centers were enrolled. Patients with first-time ablation (n = 408) were divided into the FPI and non-FPI groups. In the FPI group, a higher median target AI was reported for both the anterior and posterior LA walls than those in the non-FPI group. A higher actual AI was observed for the anterior LA wall in the FPI group. The actual AI was equal to or higher than the target AI for the posterior, anterior, and both LA walls in 54%, 47%, and 35% (n = 158) cases, respectively. Parameters such as hypertension, stroke, ablation power, actual AI value on the anterior wall, target AI values on both LA walls, AI achievement on the posterior wall, carina ablation, and operator experience were all associated with FPI in a univariate logistic regression model; only carina ablation was an independent predictor of FPI. CONCLUSIONS: According to our multicenter study, FPI and a target AI were not achieved in a significant proportion of AF ablation procedures. Higher actual and target AI values were associated with FPI, but only carina ablation can independently predict FPI.

Bromhexine Hydrochloride Prophylaxis of COVID-19 for Medical Personnel: A Randomized Open-Label Study.

BACKGROUND: Bromhexine hydrochloride has been suggested as a TMPRSS2 protease blocker that precludes the penetration of SARS-CoV-2 into cells. We aimed to assess the preventive potential of regular bromhexine hydrochloride intake for COVID-19 risk reduction in medical staff actively involved in the evaluation and treatment of patients with confirmed or suspected SARS-CoV-2 infection. METHODS: In a single-centre randomized open-label study, medical staff managing patients with suspected and confirmed COVID-19 were enrolled and followed up for 8 weeks. The study began at the initiation of COVID-19 management in the clinic. The study was prematurely terminated after the enrollment of 50 participants without a history of SARS-CoV-2 infection: 25 were assigned to bromhexine hydrochloride treatment (8 mg 3 times per day), and 25 were controls. The composite primary endpoint was a positive nasopharyngeal swab polymerase chain reaction (PCR) test for SARS-CoV-2 or signs of clinical infection within 28 days and at week 8. Secondary endpoints included time from the first contact with a person with COVID-19 to the appearance of respiratory infection symptoms; the number of days before a first positive SARS-CoV-2 test; the number of asymptomatic participants with a positive nasopharyngeal swab test; the number of symptomatic COVID-19 cases; and adverse events. RESULTS: The rate of the combined primary endpoint did not differ significantly between the active treatment group (2/25 [8%]) and control group (7/25 [28%]); P=0.07. A fewer number of participants developed symptomatic COVID-19 in the treatment group compared to controls (0/25 vs. 5/25; P=0.02). CONCLUSION: Although the study was underpowered, it showed that Bromhexine hydrochloride prophylaxis was associated with a reduced rate of symptomatic COVID-19. The prophylactic treatment was not associated with a lower combined primary endpoint rate, a positive swab PCR test, or COVID-19 (ClinicalTrials.gov number, NCT04405999).

Transcatheter radiofrequency pulmonary artery denervation in swine: the evaluation of lesion degree, hemodynamics and pulmonary hypertension inducibility.

BACKGROUND: Mechanisms of positive effects of pulmonary artery (PA) denervation (PADN) remain poorly understood. The study aimed to evaluate pulmonary hemodynamic changes after PADN and their association with the extent of PA wall damage in an acute thromboxane A2 (TXA2)-induced pulmonary hypertension (PH) model in swine. METHODS: In this experimental sham-controlled study, 17 normotensive male white Landrace pigs (the mean weight 36.2 ± 4.5 kg) were included and randomly assigned to group I (n = 9)-PH modeling before and after PADN, group II (n = 4)-PADN only, or group III (n = 4)-PH modeling before and after a sham procedure. Radiofrequency (RF) PADN was performed in the PA trunk and at the proximal parts of the right and left PAs. PA wall lesions were characterized at the autopsy study using histological and the immunohistochemical examination. RESULTS: In groups I and II, no statistically significant changes in the mean pulmonary arterial pressure nor systemic blood pressure were found after PADN (-0.8 ± 3.4 vs 4.3 ± 8.6 mmHg, P = 0.47; and 6.0 ± 15.9 vs -8.3 ± 7.5 mmHg, P = 0.1; correspondingly). There was a trend towards a lower diastolic pulmonary arterial pressure after PADN in group I when compared with group III during repeat PH induction (34.4 ± 2.9 vs 38.0 ± 0.8; P = 0.06). Despite the presence of severe PA wall damage at the RF application sites, S100 expression was preserved in the majority of PA specimens. The presence of high-grade PA lesions was associated with HR acceleration after PADN (ρ = 0.68, p = 0.03). No significant correlation was found between the grade of PA lesion severity and PA pressure after PADN with or without PH induction. CONCLUSIONS: Extended PADN does not affect PH induction using TXA2. Significant PA adventitia damage is associated with HR acceleration after PADN. Possible delayed effects of PADN on perivascular nerves and pulmonary hemodynamics require further research in chronic experiments.

Machine Learning Prediction of Cardiac Resynchronisation Therapy Response From Combination of Clinical and Model-Driven Data.

Background: Up to 30-50% of chronic heart failure patients who underwent cardiac resynchronization therapy (CRT) do not respond to the treatment. Therefore, patient stratification for CRT and optimization of CRT device settings remain a challenge. Objective: The main goal of our study is to develop a predictive model of CRT outcome using a combination of clinical data recorded in patients before CRT and simulations of the response to biventricular (BiV) pacing in personalized computational models of the cardiac electrophysiology. Materials and Methods: Retrospective data from 57 patients who underwent CRT device implantation was utilized. Positive response to CRT was defined by a 10% increase in the left ventricular ejection fraction in a year after implantation. For each patient, an anatomical model of the heart and torso was reconstructed from MRI and CT images and tailored to ECG recorded in the participant. The models were used to compute ventricular activation time, ECG duration and electrical dyssynchrony indices during intrinsic rhythm and BiV pacing from the sites of implanted leads. For building a predictive model of CRT response, we used clinical data recorded before CRT device implantation together with model-derived biomarkers of ventricular excitation in the left bundle branch block mode of activation and under BiV stimulation. Several Machine Learning (ML) classifiers and feature selection algorithms were tested on the hybrid dataset, and the quality of predictors was assessed using the area under receiver operating curve (ROC AUC). The classifiers on the hybrid data were compared with ML models built on clinical data only. Results: The best ML classifier utilizing a hybrid set of clinical and model-driven data demonstrated ROC AUC of 0.82, an accuracy of 0.82, sensitivity of 0.85, and specificity of 0.78, improving quality over that of ML predictors built on clinical data from much larger datasets by more than 0.1. Distance from the LV pacing site to the post-infarction zone and ventricular activation characteristics under BiV pacing were shown as the most relevant model-driven features for CRT response classification. Conclusion: Our results suggest that combination of clinical and model-driven data increases the accuracy of classification models for CRT outcomes.

Pulmonary and Systemic Hemodynamics following Multielectrode Radiofrequency Catheter Renal Denervation in Acutely Induced Pulmonary Arterial Hypertension in Swine.

OBJECTIVE: We aimed to assess the effects of renal denervation (RDN) on systemic and pulmonary hemodynamics in a swine model of thromboxane A2- (TXA2-) induced pulmonary arterial hypertension (PAH). METHODS: The study protocol comprised two PAH inductions with a target mean pulmonary artery pressure (PAP) of 40 mmHg at baseline and following either the RDN or sham procedure. Ten Landrace pigs underwent the first PAH induction; then, nine animals were randomly allocated in 1 : 1 ratio to RDN or sham procedure; the second PAH induction was performed in eight animals (one animal died of pulmonary embolism during the first PAH induction, and one animal died after RDN). In the RDN group, ablation was performed in all available renal arteries, and balloon inflation within artery branches was performed in controls. An autopsy study of the renal arteries was performed. RESULTS: At baseline, the target mean PAP was achieved in all animals with 25.0 [20.1; 25.2] mcg of TXA2. The second PAH induction required the same mean TXA2 dose and infusion time. There was no statistically significant difference in the mean PAP at second PAH induction between the groups (39.0 ± 5.3 vs. 39.75 ± 0.5 mmHg, P > 0.05). In the RDN group, the second PAH induction resulted in a numerical but insignificant trend toward a decrease in the mean systemic blood pressure and systemic vascular resistance, when compared with the baseline induction (74 ± 18.7 vs. 90.25 ± 28.1 mmHg and 1995.3 ± 494.3 vs. 2433.7 ± 1176.7 dyn∗sec∗cm -5, P > 0.05, respectively). No difference in hemodynamic parameters was noted in the sham group between the first and second PAH induction. Autopsy demonstrated artery damage in both groups, but RDN resulted in more severe lesions. CONCLUSIONS: According to our results, RDN does not result in significant acute pulmonary or systemic hemodynamic changes in the TXA2-induced PAH model. The potential chronic effects of RDN on PAH require further research.