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Three-dimensional (3D) printing can be beneficial to tissue engineers and the regenerative medicine community because of its potential to rapidly build elaborate 3D structures from cellular and material inks. However, predicting changes to the structure and pattern of printed tissues arising from the mechanical activity of constituent cells is technically and conceptually challenging. This perspective is targeted to scientists and engineers interested in 3D bioprinting, but from the point of view of cells and tissues as mechanically active living materials. The dynamic forces generated by cells present unique challenges compared to conventional manufacturing modalities but also offer profound opportunities through their capacity to self-organize. Consideration of self-organization following 3D printing takes the design and execution of bioprinting into the fourth dimension of cellular activity. We therefore propose a framework for dynamic bioprinting that spatiotemporally guides the underlying biology through reconfigurable material interfaces controlled by 3D printers., (Copyright © 2024 Cold Spring Harbor Laboratory Press; all rights reserved.)

Background: The reported risk of malignancies (ROM) remains controversial for fine needle aspiration (FNA) of thyroid nodules in the African American (AA) population. Herein, the ROM along with frequency was assessed for each of the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) diagnostic categories., Materials and Methods: The electronic pathology archive of a large academic hospital was retrospectively searched for cytopathology reports of thyroid nodules in AA patients (2010-2019) and Non-African American (NAA) control cases. The patients' demographic, thyroid nodule characteristics, FNA results using TBSRTC and surgical diagnoses were recorded, whenever available., Results: Three hundred ninety-one cases were identified, 317 females (81.1%) and 74 males (18.9%) with median age 50.0 (SD = 14.4). The mean size of the nodules was 2.1 cm (SD = 1.4). The Bethesda categories were: 5.4% (I), 35.0% (II), 35.3% (III), 7.7% (IV), 3.3% (V) and 13.3% (VI). The overall ROM of thyroid nodules was 43.8% (89/203) on surgical follow-up (203/391). The ROM in each Bethesda categories were: 33.3% (I), 11.6% (II), 35.2% (III), 15.8% (IV), 83.3% (V) and 100% (VI) on surgical follow-up. The frequency of thyroid nodules was higher in AA females; however, the ROM was higher in AA males (48.3%) compared with AA females (41.2%)., Conclusion: The ROM in Categories I, II and III was higher than those reported in the TBSRTC while being similar in Categories IV, V and VI. The overall risk of thyroid malignancy in our AA patient population was higher than those in the literature. The overall ROM of thyroid nodules in AA males was higher than of AA females., (© 2024 John Wiley & Sons Ltd.)

Introduction: The risk of malignancy (ROM) remains an area of interest for further evaluation in reporting systems including in International System for reporting serous fluid cytopathology (TIS), which is a standardized system for reporting effusion cytology. Herein, we report our findings in further investigation of ROM in TIS by studying on paired pleural effusion specimens and corresponding pleural biopsies with emphasis on negative for malignancy, and atypia of undetermined significance categories., Materials and Methods: The  Johns Hopkins Hospital pathology database was retrospectively searched for patients with a pleural biopsy (PBX) and a paired pleural effusion (PF) cytology specimens over a 4-year period. We employed the TIS categories. The following statistical parameters were evaluated: sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and ROM., Results: A total of 223 patient cases were included. Effusions TIS reclassification and ROM were as follows: 1.8% non-diagnostic (ROM 75%), 75.8% negative for malignancy (ROM 23%), 4.9% atypical cells of undetermined significance (ROM 45%), 2.2% suspicious for malignancy (ROM 80%), and 15.2% malignant (ROM 100%). Overall accuracy, sensitivity, specificity, PPV and NPV were calculated and were 79.4%, 45%, 97.7%, 91.2% and 77%, respectively. Among, discordant cases diagnosed negative for malignancy on PF and positive for malignancy on PBX, there were significant number of lymphomas, mesotheliomas, and sarcomas. Lung cancer was the most common carcinoma; however, rare types of carcinomas were noted. Cells blocks and immunohistochemistry (IHC) studies were utilized to confirm either malignant conditions or rule out malignancy in both cell blocks and histology biopsies., Conclusion: This study demonstrates the high specificity and ROM for 'malignant' and 'suspicious for malignancy' categories in the TIS reporting system and highlights the modest negative predictive value for the 'negative for malignancy' category. Although Tissue biopsies are usually considered as 'gold standard', any definitive diagnosis of malignancy of body fluid should be considered positive for malignancy in further clinical decision-making., (© 2024 John Wiley & Sons Ltd.)

Organoids are powerful models of tissue physiology, yet their applications remain limited due to their relatively simple morphology and high organoid-to-organoid structural variability. To address these limitations we developed a soft, composite yield-stress extracellular matrix that supports optimal organoid morphogenesis following freeform 3D bioprinting of cell slurries at tissue-like densities. The material is designed with two temperature regimes: at 4 °C it exhibits reversible yield-stress behavior to support long printing times without compromising cell viability. When transferred to cell culture at 37 °C, the material cross-links and exhibits similar viscoelasticity and plasticity to basement membrane extracts such as Matrigel. We first characterize the rheological properties of MAGIC matrices that optimize organoid morphogenesis, including low stiffness and high stress relaxation. Next, we combine this material with a custom piezoelectric printhead that allows more reproducible and robust self-organization from uniform and spatially organized tissue "seeds." We apply MAGIC matrix bioprinting for high-throughput generation of intestinal, mammary, vascular, salivary gland, and brain organoid arrays that are structurally similar to those grown in pure Matrigel, but exhibit dramatically improved homogeneity in organoid size, shape, maturation time, and efficiency of morphogenesis. The flexibility of this method and material enabled fabrication of fully 3D microphysiological systems, including perfusable organoid tubes that experience cyclic 3D strain in response to pressurization. Furthermore, the reproducibility of organoid structure increased the statistical power of a drug response assay by up to 8 orders-of-magnitude for a given number of comparisons. Combined, these advances lay the foundation for the efficient fabrication of complex tissue morphologies by canalizing their self-organization in both space and time., Competing Interests: Declaration of Interest A.J.G., R.G.S., and Z.J.G. are co-inventors on a patent regarding the design and application of the embedded bioprinting material and piezoelectric printhead (U.S. Provisional Patent Application No. 63/605,710). Z.J.G. is an equity holder in Scribe biosciences, Provenance Bio, and Serotiny.

Engineered living materials combine the advantages of biological and synthetic systems by leveraging genetic and metabolic programming to control material-wide properties. Here, we demonstrate that extracellular electron transfer (EET), a microbial respiration process, can serve as a tunable bridge between live cell metabolism and synthetic material properties. In this system, EET flux from Shewanella oneidensis to a copper catalyst controls hydrogel cross-linking via two distinct chemistries to form living synthetic polymer networks. We first demonstrate that synthetic biology-inspired design rules derived from fluorescence parameterization can be applied toward EET-based regulation of polymer network mechanics. We then program transcriptional Boolean logic gates to govern EET gene expression, which enables design of computational polymer networks that mechanically respond to combinations of molecular inputs. Finally, we control fibroblast morphology using EET as a bridge for programmed material properties. Our results demonstrate how rational genetic circuit design can emulate physiological behavior in engineered living materials., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Previous studies have failed to show an effect of episodic future thinking (EFT) on children's delay of gratification (DoG), contrasting strikingly with adult findings. Recent findings from a sample of 8-11-year-old children by Canning et al. (J. Exp. Child Psychol., 228, 2023, 105618) indicate that EFT cueing is not effective compared to a no-cue control even when it is reward related. Canning et al. suggest children's DoG performance, unlike that of adults, may be negatively affected by the cognitive load of cueing, but this leaves unexplained why EFT reward-related cueing produced significantly better performance than cueing that did not involve EFT in their study. The current study attempted to further delineate the importance of linking future thinking cues to rewards. A reward-related EFT condition was compared to a reward-unrelated EFT condition and a no-cue control on a delay choice task. No significant differences were observed between the three conditions. This suggests that even reward-related future thinking is ineffective at improving children's delayed gratification. Further research is needed to determine why children struggle to benefit from EFT cues., (© 2024 The Authors. British Journal of Developmental Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.)

Mind wandering occurs when attention becomes disengaged from the here-and-now and directed toward internally generated thoughts; this is often associated with poorer performance on educationally significant tasks. In this study, 8- to 9-year-old children (N = 60) listened to audio stories embedded with intermittent thought probes that were used to determine if participants' thoughts were on or off task. The key objective was to explore the impact of probe-caught mind wandering on both immediate and delayed memory retention. Children reported being off task approximately 24% of the time. Most inattention episodes were classified as task-unrelated thoughts (i.e., 'pure' instances of mind wandering, 9%) or attentional failures due to distractions (9%). Higher frequency of mind wandering was strongly associated with poorer memory recall, and task-unrelated thoughts strongly predicted how well children could recall components of the audio story both immediately after the task and after a 1-week delay. This study is the first to demonstrate the impact of mind wandering on delayed memory retention in children. Results suggest that exploring mind wandering in the foundational years of schooling could provide the necessary empirical foundation for the development of practical interventions geared toward detecting and refocusing lapses of attention in educational contexts., (© 2023. The Author(s).)

Stacking monolayer semiconductors creates moiré patterns, leading to correlated and topological electronic phenomena, but measurements of the electronic structure underpinning these phenomena are scarce. Here, we investigate the properties of the conduction band in moiré heterobilayers of WS 2 /WSe 2 using submicrometer angle-resolved photoemission spectroscopy with electrostatic gating. We find that at all twist angles the conduction band edge is the K -point valley of the WS 2 , with a band gap of 1.58 ± 0.03 eV. From the resolved conduction band dispersion, we deduce an effective mass of 0.15 ± 0.02 m e . Additionally, we observe replicas of the conduction band displaced by reciprocal lattice vectors of the moiré superlattice. We argue that the replicas result from the moiré potential modifying the conduction band states rather than final-state diffraction. Interestingly, the replicas display an intensity pattern with reduced 3-fold symmetry, which we show implicates the pseudo vector potential associated with in-plane strain in moiré band formation.

Organic electrochemical transistors (OECTs) are ideal devices for translating biological signals into electrical readouts and have applications in bioelectronics, biosensing, and neuromorphic computing. Despite their potential, developing programmable and modular methods for living systems to interface with OECTs has proven challenging. Here we describe hybrid OECTs containing the model electroactive bacterium Shewanella oneidensis that enable the transduction of biological computations to electrical responses. Specifically, we fabricated planar p-type OECTs and demonstrated that channel de-doping is driven by extracellular electron transfer (EET) from S. oneidensis. Leveraging this mechanistic understanding and our ability to control EET flux via transcriptional regulation, we used plasmid-based Boolean logic gates to translate biological computation into current changes within the OECT. Finally, we demonstrated EET-driven changes to OECT synaptic plasticity. This work enables fundamental EET studies and OECT-based biosensing and biocomputing systems with genetically controllable and modular design elements., (© 2024. The Author(s).)

Encoding and recalling spoken instructions is subject to working memory capacity limits. Previous research suggests action-based encoding facilitates instruction recall, but has not directly compared benefits across different types of action-based techniques. The current study addressed this in two experiments with young adults. In Experiment 1, participants listened to instructional sequences containing four action-object pairs, and encoded these instructions using either a motor imagery or verbal rehearsal technique, followed by recall via oral repetition or enactment. Memory for instructions was better when participants used a motor imagery technique during encoding, and when recalling the instructions by enactment. The advantage of using a motor imagery technique was present in both verbal and enacted recall. In Experiment 2, participants encoded spoken instructions whilst implementing one of four techniques (verbal rehearsal, motor imagery, observation of others' actions or self-enactment), and then recalled the instructions by oral repetition or enactment. For both verbal and enacted recall, memory for instructions was least accurate in the rehearsal condition, while the other encoding conditions did not differ from each other. These novel findings indicate similar benefits of imagining, observation and execution of actions in encoding spoken instructions, and enrich current understanding of action-based benefits in working memory.

Background: Sufficient tumor collection has become of utmost importance in therapeutic experimental protocols. Rapid on-site evaluation (ROSE) ensures adequate sampling for quantification of biomarkers, molecular analyses, and other ancillary studies. The objectives of this study were to evaluate the role of ROSE in trial-associated fine-needle aspiration (FNA) and to analyze predictors of adequacy and cumulative survival from in-house FNA cases used in clinical trials., Methods: Clinical trial FNA biopsies performed at a large academic institution were analyzed over 10 months using a comprehensive chart review of the electronic medical records. SPSS version 28 was used for statistical analysis., Results: Three hundred twenty-five FNAs were collected for 57 clinical trials. In total, 225 individual patients had an average of 1.4 FNA procedures each as a result of a multidepartmental collaborative effort. ROSE was performed for all patients, and adequacy was evaluated by cytotechnologists. Seventy-eight percent of samples were considered adequate, 14% were considered less than optimal, and 8% were considered inadequate, with the latter two categories designated together as less than adequate. The imaging modalities were mainly ultrasound-guided (n = 267; 82%) and computed tomography-guided (n = 58; 18%). There was a statistically significant association between adequate sampling and ultrasound-guided biopsies (83%) compared with computed tomography-guided biopsies (59%; p < .01). The effect of body mass index (BMI) on mortality was also a significant finding. The authors observed a survival benefit in patients who had elevated BMIs (range, 25.0-34.9 kg/m 2 ) compared with those who were underweight (BMI, <18.5 kg/m 2 ) or class III obese (BMI, >35.0 kg/m 2 ; p < .01). Therefore, the best predictors of adequacy and mortality were imaging modality and BMI, respectively., Conclusions: Ultrasound-guided modalities are recommended for obtaining adequate FNA sampling for clinical trials. In addition, patients with cancer who had slightly elevated BMIs (25.0-34.0 kg/m 2 ) had increased overall survival in this cohort., (© 2023 American Cancer Society.)

Despite being implicated in a wide range of psychological and behavioral phenomena, relief remains poorly understood from the perspective of psychological science. What complicates the study of relief is that people seem to use the term to describe an emotion that occurs in two distinct situations: when an unpleasant episode is over, or upon realizing that an outcome could have been worse. This study constitutes a detailed empirical investigation of people's reports of everyday episodes of relief. A set of four studies collected a large corpus ( N = 1,835) of first-person reports of real-life episodes of relief and examined people's judgments about the antecedents of relief, its relation to counterfactual thoughts, and its subsequent effects on decision making. Some participants described relief experiences that had either purely temporal or purely counterfactual precursors. Nevertheless, the findings indicated that the prototypical instance of relief appears to be one in which both these elements are present. The results also suggest that, although relief is frequently experienced in situations in which people are not responsible for the relief-inducing event, nevertheless they typically report that the experience had a positive impact on subsequent decision making. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Organic electrochemical transistors (OECTs) are ideal devices for translating biological signals into electrical readouts and have applications in bioelectronics, biosensing, and neuromorphic computing. Despite their potential, developing programmable and modular methods for living systems to interface with OECTs has proven challenging. Here we describe hybrid OECTs containing the model electroactive bacterium Shewanella oneidensis that enable the transduction of biological computations to electrical responses. Specifically, we fabricated planar p-type OECTs and demonstrated that channel de-doping is driven by extracellular electron transfer (EET) from S. oneidensis . Leveraging this mechanistic understanding and our ability to control EET flux via transcriptional regulation, we used plasmid-based Boolean logic gates to translate biological computation into current changes within the OECT. Finally, we demonstrated EET-driven changes to OECT synaptic plasticity. This work enables fundamental EET studies and OECT-based biosensing and biocomputing systems with genetically controllable and modular design elements., Competing Interests: Competing Interests The authors declare no competing interests.

Cuing adults to imagine their personal futures enhances prudent choice in delay discounting tasks. However, it has not been established that such cueing also reduces discounting in children. We assessed the effect of episodic future thinking (EFT) on delay of gratification in children using EFT cues specifically related to the rewards on offer. One hundred and thirty-nine 8-12-year-olds were assigned to one of three conditions: (i) EFT (imagine spending money in the future), (ii) Imagine Place (imagine being in a certain place), or (iii) No Cue. They were cued on each trial of two tasks: a delay discounting task with hypothetical monetary rewards and a real delay choice task involving choices between real rewards over real delays (coins that could be swapped for treats). In the delay discounting task, the Imagine Place group showed significantly higher discounting than the other two groups. In the real delay choice task, the Imagine Place group made significantly fewer delayed choices than the EFT group. However, the EFT group did not differ from the No Cue group in either task. The lack of a difference between the EFT and No Cue conditions supports previous findings suggesting children struggle to benefit from EFT cues. Poorer performance of the Imagine Place group suggests that cued imagination is cognitively taxing for children, using up cognitive resources required to delay gratification., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Large scale studies in populations of European and Han Chinese ancestry found a series of rare gain-of-function microduplications in VIPR2, encoding VPAC2, a receptor that binds vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide with high affinity, that were associated with an up to 13-fold increased risk for schizophrenia. To address how VPAC2 receptor overactivity might affect brain development, we used a well-characterized Nestin-Cre mouse strain and a knock-in approach to overexpress human VPAC2 in the central nervous system. Mice that overexpressed VPAC2 were found to exhibit a significant reduction in brain weight. Magnetic resonance imaging analysis confirmed a decrease in brain size, a specific reduction in the hippocampus grey matter volume and a paradoxical increase in whole-brain white matter volume. Sex-specific changes in behavior such as impaired prepulse inhibition and contextual fear memory were observed in VPAC2 overexpressing mice. The data indicate that the VPAC2 receptor may play a critical role in brain morphogenesis and suggest that overactive VPAC2 signaling during development plays a mechanistic role in some forms of schizophrenia., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The construction of three-dimensional (3D) microvascular networks with defined structures remains challenging. Emerging bioprinting strategies provide a means of patterning endothelial cells (ECs) into the geometry of 3D microvascular networks, but the microenvironmental cues necessary to promote their self-organization into cohesive and perfusable microvessels are not well known. To this end, we reconstituted microvessel formation in vitro by patterning thin lines of closely packed ECs fully embedded within a 3D extracellular matrix (ECM) and observed how different microenvironmental parameters influenced EC behaviors and their self-organization into microvessels. We found that the inclusion of fibrillar matrices, such as collagen I, into the ECM positively influenced cell condensation into extended geometries such as cords. We also identified the presence of a high-molecular-weight protein(s) in fetal bovine serum that negatively influenced EC condensation. This component destabilized cord structure by promoting cell protrusions and destabilizing cell-cell adhesions. Endothelial cords cultured in the presence of fibrillar collagen and in the absence of this protein activity were able to polarize, lumenize, incorporate mural cells, and support fluid flow. These optimized conditions allowed for the construction of branched and perfusable microvascular networks directly from patterned cells in as little as 3 days. These findings reveal important design principles for future microvascular engineering efforts based on bioprinting and micropatterning techniques. Impact statement Bioprinting is a potential strategy to achieve microvascularization in engineered tissues. However, the controlled self-organization of patterned endothelial cells into perfusable microvasculature remains challenging. We used DNA Programmed Assembly of Cells to create cell-dense, capillary-sized cords of endothelial cells with complete control over their structure. We optimized the matrix and media conditions to promote self-organization and maturation of these endothelial cords into stable and perfusable microvascular networks.

How working memory supports dual-task performance is the focus of a long-standing debate. Most previous research on this topic has focused on participant performance data. In three experiments, we investigated whether changes in participant-reported strategies across single- and dual-task conditions might help resolve this debate by offering new insights that lead to fruitful integration of theories rather than perpetuating debate by attempting to identify which theory best fits the data. Results indicated that articulatory suppression was associated with reduced reports of the use of rehearsal and clustering strategies but to an increase of the reported use of a visual strategy. Elaboration and clustering strategies were reported less for memory under dual task compared with single task. Under both dual task and articulatory suppression, more participants reported attempting to remember fewer memory items than were presented (memory reduction strategy). For arithmetic verification, articulatory suppression and dual task resulted in a reduction in reports of a counting strategy and an increase in reports of a retrieval strategy for arithmetic knowledge. It is argued that experimenters should not assume that participants perform the same task in the same way under different experimental conditions and that carefulty investigation of how participants change their strategies in response to changes in experimental conditions has considerable potential for resolving theoretical challenges. It is argued further that this approach points toward the value of attempting to integrate rather than proliferate theories of working memory. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Developmentalists have investigated relief as a counterfactually mediated emotion, but not relief experienced when negative events end-so-called temporal relief. This study represents the first body of work to investigate the development of children's understanding of temporal relief and compare it with their understanding of counterfactual relief. Across four experiments (407 children aged 4-11 years and 60 adults; 52% female), we examined children's ability to attribute counterfactual and temporal relief to others. In Experiment 1, 7- to 10-year-olds typically judged that two characters would feel equally happy despite avoiding or enduring an event that was unpleasant for one character. Using forced-choice procedures, Experiments 2 to 4 showed that a fledgling ability to attribute relief to others emerges at 5 to 6 years of age and that the tendency to make these attributions increases with age. The experiments in this study provide the first positive evidence in the literature as to when children can begin to attribute both counterfactual and temporal instances of relief to others. Overall, there was little evidence for separate developmental trajectories for understanding counterfactual and temporal relief, although in Experiment 4 there was an indication that, under scaffolded contexts, some children find it easier to attribute counterfactual relief rather than temporal relief to others., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Mind wandering is a common everyday experience during which attention shifts from the here and now; in adults and adolescents, it is associated with poorer performance in educationally significant tasks. This study is the first to directly assess the impact of mind wandering on memory retention in children before the adolescent period. A sample of 97 children aged 6-11 years engaged in a listening activity, and the frequency of mind wandering was measured using intermittent thought probes. Participants then completed a memory retention test. Children reported mind wandering on ∼25% of the thought probes, and frequency did not increase with age. When controlling for the impact of age and vocabulary skills, mind wandering frequency accounted for a large and significant portion of variance in memory scores. Mind wandering frequency also mediated the relation between children's ratings of topic interest and memory scores. The results indicate that mind wandering can be reliably measured in children and is of educational significance., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to assess the association between electrocardiographic imaging (ECGI) parameters and voltage from simultaneous electroanatomic mapping (EAM)., Background: ECGI offers noninvasive assessment of electrophysiologic features relevant for mapping ventricular arrhythmia and its substrate, but the accuracy of ECGI in the delineation of scar is unclear., Methods: Sixteen patients with structural heart disease underwent simultaneous ECGI (CardioInsight, Medtronic) and contact EAM (CARTO, Biosense-Webster) during ventricular tachycardia catheter ablation, with 7 mapped epicardially. ECGI and EAM geometries were coregistered using anatomic landmarks. ECGI points were paired to the closest site on the EAM within 10 mm. The association between EAM voltage and ECGI features from reconstructed epicardial unipolar electrograms was assessed by mixed-effects regression models. The classification of low-voltage regions was performed using receiver-operating characteristic analysis., Results: A total of 9,541 ECGI points (median: 596; interquartile range: 377-737 across patients) were paired to an EAM site. Epicardial EAM voltage was associated with ECGI features of signal fractionation and local repolarization dispersion (N = 7; P < 0.05), but they poorly classified sites with bipolar voltage of <1.5 mV or <0.5 mV thresholds (median area under the curve across patients: 0.50-0.62). No association was found between bipolar EAM voltage and low-amplitude reconstructed epicardial unipolar electrograms or ECGI-derived bipolar electrograms. Similar results were found in the combined cohort (n = 16), including endocardial EAM voltage compared to epicardial ECGI features (n = 9)., Conclusions: Despite a statistically significant association between ECGI features and EAM voltage, the accuracy of the delineation of low-voltage zones was modest. This may limit ECGI use for pr-procedural substrate analysis in ventricular tachycardia ablation, but it could provide value in risk assessment for ventricular arrhythmias., Competing Interests: Funding Support and Author Disclosures Dr Graham was supported by a Barts Charity grant. Dr Lambiase was supported by University College London Hospital Biomedicine National Institute for Health Research and Barts Biomedical Research Centre; has received research grants from Boston Scientific, Medtronic, and Abbott; and has received speaker fees from Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Extracellular electron transfer (EET) is an anaerobic respiration process that couples carbon oxidation to the reduction of metal species. In the presence of a suitable metal catalyst, EET allows for cellular metabolism to control a variety of synthetic transformations. Here, we report the use of EET from the electroactive bacterium Shewanella oneidensis for metabolic and genetic control over Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC). CuAAC conversion under anaerobic and aerobic conditions was dependent on live, actively respiring S. oneidensis cells. The reaction progress and kinetics were manipulated by tailoring the central carbon metabolism. Similarly, EET-CuAAC activity was dependent on specific EET pathways that could be regulated via inducible expression of EET-relevant proteins: MtrC, MtrA, and CymA. EET-driven CuAAC exhibited modularity and robustness in the ligand and substrate scope. Furthermore, the living nature of this system could be exploited to perform multiple reaction cycles without regeneration, something inaccessible to traditional chemical reductants. Finally, S. oneidensis enabled bioorthogonal CuAAC membrane labeling on live mammalian cells without affecting cell viability, suggesting that S. oneidensis can act as a dynamically tunable biocatalyst in complex environments. In summary, our results demonstrate how EET can expand the reaction scope available to living systems by enabling cellular control of CuAAC., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

In electronic and optoelectronic devices made from van der Waals heterostructures, electric fields can induce substantial band structure changes which are crucial to device operation but cannot usually be directly measured. Here, we use spatially resolved angle-resolved photoemission spectroscopy to monitor changes in band alignment of the component layers, corresponding to band structure changes of the composite heterostructure system, that are produced by electrostatic gating. Our devices comprise graphene on a monolayer semiconductor, WSe 2 or MoSe 2 , atop a boron nitride dielectric and a graphite gate. Applying a gate voltage creates an electric field that shifts the semiconductor bands relative to those in the graphene by up to 0.2 eV. The results can be understood in simple terms by assuming that the materials do not hybridize.

Non-invasive electrocardiographic imaging (ECGI) is a novel clinical tool for mapping ventricular arrhythmia. Using multiple body surface electrodes to collect unipolar electrograms and conventional medical imaging of the heart, an epicardial shell can be created to display calculated electrograms. This calculation is achieved by solving the inverse problem and allows activation times to be calculated from a single beat. The technology was initially pioneered in the US using an experimental torso-shaped tank. Accuracy from studies in humans has varied. Early data was promising, with more recent work suggesting only moderate accuracy when reproducing cardiac activation. Despite these limitations, the system has been successfully used in pioneering work with non-invasive cardiac radioablation to treat ventricular arrhythmia. This suggests that the resolution may be sufficient for treatment of large target areas. Although untested in a well conducted clinical study it is likely that it would not be accurate enough to guide more discreet radiofrequency ablation., Competing Interests: Disclosure: RJS receives research grants and advisory fees from Biosense, Abbott, Medtronic and Boston Scientific and is on the Arrhythmia & Electrophysiology Review editorial board; this did not influence peer review. AJG is the holder of an educational grant from Abbot., (Copyright © 2021, Radcliffe Cardiology.)

Objectives: The goal of this study was to develop a risk score model for patients with Brugada syndrome (BrS)., Background: Risk stratification in BrS is a significant challenge due to the low event rates and conflicting evidence., Methods: A multicenter international cohort of patients with BrS and no previous cardiac arrest was used to evaluate the role of 16 proposed clinical or electrocardiogram (ECG) markers in predicting ventricular arrhythmias (VAs)/sudden cardiac death (SCD) during follow-up. Predictive markers were incorporated into a risk score model, and this model was validated by using out-of-sample cross-validation., Results: A total of 1,110 patients with BrS from 16 centers in 8 countries were included (mean age 51.8 ± 13.6 years; 71.8% male). Median follow-up was 5.33 years; 114 patients had VA/SCD (10.3%) with an annual event rate of 1.5%. Of the 16 proposed risk factors, probable arrhythmia-related syncope (hazard ratio [HR]: 3.71; p < 0.001), spontaneous type 1 ECG (HR: 3.80; p < 0.001), early repolarization (HR: 3.42; p < 0.001), and a type 1 Brugada ECG pattern in peripheral leads (HR: 2.33; p < 0.001) were associated with a higher risk of VA/SCD. A risk score model incorporating these factors revealed a sensitivity of 71.2% (95% confidence interval: 61.5% to 84.6%) and a specificity of 80.2% (95% confidence interval: 75.7% to 82.3%) in predicting VA/SCD at 5 years. Calibration plots showed a mean prediction error of 1.2%. The model was effectively validated by using out-of-sample cross-validation according to country., Conclusions: This multicenter study identified 4 risk factors for VA/SCD in a primary prevention BrS population. A risk score model was generated to quantify risk of VA/SCD in BrS and inform implantable cardioverter-defibrillator prescription., Competing Interests: Funding Support and Author Disclosures Dr. Lambiase is supported by the Stephen Lyness Memorial Fund, UCLH Biomedicine National Institutes of Health Research, Barts Biomedical Research Centre; and has obtained research grants and speaker fees from Medtronic, Abbott, and Boston Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: Optimum timing of pacemaker implantation following cardiac surgery is a clinical challenge. European and American guidelines recommend observation, to assess recovery of atrioventricular block (AVB) (up to 7 days) and sinus node (5 days to weeks) after cardiac surgery. This study aims to determine rates of cardiac implantable electronic devices (CIEDs) implants post-surgery at a high-volume tertiary centre over 3 years. Implant timing, patient characteristics and outcomes at 6 months including pacemaker utilization were assessed., Methods and Results: All cardiac operations (n = 5950) were screened for CIED implantation following surgery, during the same admission, from 2015 to 2018. Data collection included patient, operative, and device characteristics; pacing utilization and complications at 6 months. A total of 250 (4.2%) implants occurred; 232 (3.9%) for bradycardia. Advanced age, infective endocarditis, left ventricle systolic impairment, and valve surgery were independent predictors for CIED implants (P < 0.0001). Relative risk (RR) of CIED implants and proportion of AVB increased with valve numbers operated (single-triple) vs. non-valve surgery: RR 5.4 (95% CI 3.9-7.6)-21.0 (11.4-38.9) CIEDs. Follow-up pacing utilization data were available in 91%. Significant utilization occurred in 82% and underutilization (<1% A and V paced) in 18%. There were no significant differences comparing utilization rates in early (≤day 5 post-operatively) vs. late implants (P = 0.55)., Conclusion: Multi-valve surgery has a particularly high incidence of CIED implants (14.9% double, 25.6% triple valve). Age, left ventricle systolic impairment, endocarditis, and valve surgery were independent predictors of CIED implants. Device underutilization was infrequent and uninfluenced by implant timing. Early implantation (≤5 days) should be considered in AVB post-multi-valve surgery., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Introduction: Smoking cessation activities incorporated into lung cancer screening programs have been broadly recommended, but studies to date have not exhibited increased quit rates associated with cessation programs in this setting. We aimed to determine the long-term effectiveness of smoking cessation counseling in smokers presenting for lung cancer screening., Methods: This was a randomized control trial of an intensive, telephone-based smoking cessation counseling intervention incorporating lung cancer screening results versus usual care (information pamphlet). This analysis reports on the long-term impact (24-mo) of the intervention on abstinence from smoking., Results: A total of 337 active smokers who participated in the screening study were randomized to active smoking cessation counseling (n = 171) or control arm (n = 174) and completed a 24-month assessment. The 30-day smoking abstinence rates at 24 months postrandomization was 18.3% and 21.4% in the control and intervention arms, respectively-a 3.1% difference (95% confidence interval: -5.4 to 11.6, p  = 0.48). No statistically significant differences in the 7-day abstinence, the use of pharmacologic cessation aids, nicotine replacement therapies, nor intent to quit in the following 30 days were noted ( p > 0.05). The abstinence rates at 24-months were higher overall than at 12-months (19.9% versus 13.3%, p < 0.001), and smoking intensity was lower than at baseline for ongoing smokers., Conclusions: A telephone-based smoking cessation counseling intervention incorporating lung cancer screening results did not result in increased long-term cessation rates versus written information alone in unselected smokers undergoing lung cancer screening. Overall, quit rates were high and continued to improve throughout participation in the screening program. (ClinicalTrials.govNCT02431962)., (© 2020 The Authors.)

Performing radical polymerizations under ambient conditions is a major challenge because molecular oxygen is an effective radical quencher. Here we show that the facultative electrogen Shewanella oneidensis can control metal-catalysed living radical polymerizations under apparent aerobic conditions by first consuming dissolved oxygen via aerobic respiration, and then directing extracellular electron flux to a metal catalyst. In both open and closed containers, S. oneidensis enabled living radical polymerizations without requiring the preremoval of oxygen. Polymerization activity was closely tied to S. oneidensis anaerobic metabolism through specific extracellular electron transfer proteins and was effective for a variety of monomers using low (parts per million) concentrations of metal catalysts. Finally, polymerizations survived repeated challenges of oxygen exposure and could be initiated using lyophilized or spent (recycled) cells. Overall, our results demonstrate how the unique ability of S. oneidensis to use both oxygen and metals as respiratory electron acceptors can be leveraged to address salient challenges in polymer synthesis.

Background: Identifying arrhythmogenic sites to improve ventricular tachycardia (VT) ablation outcomes remains unresolved. The reentry vulnerability index (RVI) combines activation and repolarization timings to identify sites critical for reentrant arrhythmia initiation without inducing VT., Objective: The purpose of this study was to provide the first assessment of RVI's capability to identify VT sites of origin using high-density contact mapping and comparison with other activation-repolarization markers of functional substrate., Methods: Eighteen VT ablation patients (16 male; 72% ischemic) were studied. Unipolar electrograms were recorded during ventricular pacing and analyzed offline. Activation time (AT), activation-recovery interval (ARI), and repolarization time (RT) were measured. Vulnerability to reentry was mapped based on RVI and spatial distribution of AT, ARI, and RT. The distance from sites identified as vulnerable to reentry to the VT site of origin was measured, with distances <10 mm and >20 mm indicating accurate and inaccurate localization, respectively., Results: The origins of 18 VTs (6 entrainment, 12 pace-mapping) were identified. RVI maps included 1012 (408-2098) (median, 1st-3rd quartiles) points per patient. RVI accurately localized 72.2% VT sites of origin, with median distance of 5.1 (3.2-10.1) mm. Inaccurate localization was significantly less frequent for RVI than AT (5.6% vs 33.3%; odds ratio 0.12; P = .035). Compared to RVI, distance to VT sites of origin was significantly larger for sites showing prolonged RT and ARI and were nonsignificantly larger for sites showing highest AT and ARI gradients., Conclusion: RVI identifies vulnerable regions closest to VT sites of origin. Activation-repolarization metrics may improve VT substrate delineation and inform novel ablation strategies., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Enhancing materials with the qualities of living systems, including sensing, computation, and adaptation, is an important challenge in designing next-generation technologies. Living materials address this challenge by incorporating live cells as actuating components that control material function. For abiotic materials, this requires new methods that couple genetic and metabolic processes to material properties. Toward this goal, we demonstrate that extracellular electron transfer (EET) from Shewanella oneidensis can be leveraged to control radical cross-linking of a methacrylate-functionalized hyaluronic acid hydrogel. Cross-linking rates and hydrogel mechanics, specifically storage modulus, were dependent on various chemical and biological factors, including S. oneidensis genotype. Bacteria remained viable and metabolically active in the networks for a least 1 week, while cell tracking revealed that EET genes also encode control over hydrogel microstructure. Moreover, construction of an inducible gene circuit allowed transcriptional control of storage modulus and cross-linking rate via the tailored expression of a key electron transfer protein, MtrC. Finally, we quantitatively modeled hydrogel stiffness as a function of steady-state mtrC expression and generalized this result by demonstrating the strong relationship between relative gene expression and material properties. This general mechanism for radical cross-linking provides a foundation for programming the form and function of synthetic materials through genetic control over extracellular electron transfer.

Background: ECG imaging (ECGI) has been used to guide treatment of ventricular ectopy and arrhythmias. However, the accuracy of ECGI in localizing the origin of arrhythmias during catheter ablation of ventricular tachycardia (VT) in structurally abnormal hearts remains to be fully validated., Methods: During catheter ablation of VT, simultaneous mapping was performed using electroanatomical mapping (CARTO, Biosense-Webster) and ECGI (CardioInsight, Medtronic) in 18 patients. Sites of entrainment, pace-mapping, and termination during ablation were used to define the VT site of origin (SoO). Distance between SoO and the site of earliest activation on ECGI were measured using co-registered geometries from both systems. The accuracy of ECGI versus a 12-lead surface ECG algorithm was compared., Results: A total of 29 VTs were available for comparison. Distance between SoO and sites of earliest activation in ECGI was 22.6, 13.9 to 36.2 mm (median, first to third quartile). ECGI mapped VT sites of origin onto the correct AHA segment with higher accuracy than a validated 12-lead ECG algorithm (83.3% versus 38.9%; P =0.015)., Conclusions: This simultaneous assessment demonstrates that CardioInsight localizes VT circuits with sufficient accuracy to provide a region of interest for targeting mapping for ablation. Resolution is not sufficient to guide discrete radiofrequency lesion delivery via catheter ablation without concomitant use of an electroanatomical mapping system but may be sufficient for segmental ablation with radiotherapy.

Background The relationship between structural pathology and electrophysiological substrate in cardiac amyloidosis is unclear. Differences between light-chain (AL) and transthyretin (ATTR) cardiac amyloidosis may have prognostic implications. Methods and Results ECG imaging and cardiac magnetic resonance studies were conducted in 21 cardiac amyloidosis patients (11 AL and 10 ATTR). Healthy volunteers were included as controls. With respect to ATTR, AL patients had lower amyloid volume (51.0/37.7 versus 73.7/16.4 mL, P=0.04), lower myocardial cell volume (42.6/19.1 versus 58.5/17.2 mL, P=0.021), and higher T1 (1172/64 versus 1109/80 ms, P=0.022) and T2 (53.4/2.9 versus 50.0/3.1 ms, P=0.003). ECG imaging revealed differences between cardiac amyloidosis and control patients in virtually all conduction-repolarization parameters. With respect to ATTR, AL patients had lower epicardial signal amplitude (1.07/0.46 versus 1.83/1.26 mV, P=0.026), greater epicardial signal fractionation (P=0.019), and slightly higher dispersion of repolarization (187.6/65 versus 158.3/40 ms, P=0.062). No significant difference between AL and ATTR patients was found using the standard 12-lead ECG. T1 correlated with epicardial signal amplitude (cc=-0.78), and extracellular volume with epicardial signal fractionation (cc=0.48) and repolarization time (cc=0.43). Univariate models based on single features from both cardiac magnetic resonance and ECG imaging classified AL and ATTR patients with an accuracy of 70% to 80%. Conclusions In this exploratory study cardiac amyloidosis was associated with ventricular conduction and repolarization abnormalities, which were more pronounced in AL than in ATTR. Combined ECG imaging-cardiac magnetic resonance analysis supports the hypothesis that additional mechanisms beyond infiltration may contribute to myocardial damage in AL amyloidosis. Further studies are needed to assess the clinical impact of this approach.

Introduction: Smoking cessation activities incorporated into lung cancer screening programs have been broadly recommended, but studies to date have not shown increased quit rates associated with cessation programs in this setting. We aimed to determine the effectiveness of smoking cessation counseling in smokers presenting for lung cancer screening., Methods: This study is a randomized control trial of an intensive telephone-based smoking cessation counseling intervention incorporating lung cancer screening results versus usual care (information pamphlet). All active smokers enrolled in the Alberta Lung Cancer Screening Study cohort were randomized on a 1:1 ratio with a primary endpoint of self-reported 30-day abstinence at 12 months., Results: A total of 345 active smokers participating in the screening study were randomized to active smoking cessation counseling (n = 171) or control arm (n = 174). Thirty-day smoking abstinence at 12 months post-randomization was noted in 22 of 174 (12.6%) and 24 of 171 (14.0%) of participants in the control and intervention arms, respectively, a 1.4% difference (95% confidence interval: -5.9 to 8.7, p = 0.7). No statistically significant differences in 7-day or point abstinence were noted, nor were differences at 6 months or 24 months., Conclusions: A telephone-based smoking cessation counseling intervention incorporating lung cancer screening results did not result in increased 12-month cessation rates versus written information alone in unselected smokers undergoing lung cancer screening. Routine referral of all current smokers to counseling-based cessation programs may not improve long-term cessation in this patient cohort. Future studies should specifically focus on this subgroup of older long-term smokers to determine the optimal method of integrating smoking cessation with lung cancer screening (clinicaltrials.govNCT02431962)., (Copyright © 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

The ability to directly monitor the states of electrons in modern field-effect devices-for example, imaging local changes in the electrical potential, Fermi level and band structure as a gate voltage is applied-could transform our understanding of the physics and function of a device. Here we show that micrometre-scale, angle-resolved photoemission spectroscopy 1-3 (microARPES) applied to two-dimensional van der Waals heterostructures 4 affords this ability. In two-terminal graphene devices, we observe a shift of the Fermi level across the Dirac point, with no detectable change in the dispersion, as a gate voltage is applied. In two-dimensional semiconductor devices, we see the conduction-band edge appear as electrons accumulate, thereby firmly establishing the energy and momentum of the edge. In the case of monolayer tungsten diselenide, we observe that the bandgap is renormalized downwards by several hundreds of millielectronvolts-approaching the exciton energy-as the electrostatic doping increases. Both optical spectroscopy and microARPES can be carried out on a single device, allowing definitive studies of the relationship between gate-controlled electronic and optical properties. The technique provides a powerful way to study not only fundamental semiconductor physics, but also intriguing phenomena such as topological transitions 5 and many-body spectral reconstructions under electrical control.

Background: The reporting of adverse events (AE) remains an important part of quality improvement in thoracic surgery. The best methodology for AE reporting in surgery is unclear. An AE reporting system using an electronic discharge summary with embedded data collection fields, specifying surgical procedure and complications, was developed. The data are automatically transferred daily to a web-based reporting system., Methods: We determined the accuracy and sustainability of this electronic real time data collection system (ERD) by comparing the completeness of record capture on procedures and complications with coded discharge data (administrative data), and with the standard of chart audit at two intervals. All surgical procedures performed for 2 consecutive months at initiation (Ti) and 1 year later (T1yr) were audited by an objective trained abstractor. A second abstractor audited 10% of the charts., Results: The ERD captured 71/72 (99%) of charts at Ti and 56/65 (86%) at T1yr. Comparing the presence/absence of complications between ERD and chart audit demonstrated at Ti a high sensitivity and specificity, positive predictive value (PPV) of 95.5%, negative predictive value (NPV) of 93.9% with a kappa of 0.872 (95% CI 0.750 to 0.994), and at T1yr a sensitivity, specificity, PPV and NPV of 100% with a kappa of 1.0 (95% CI 1.0). Comparing the presence/absence of complications between administrative data and chart audit at Ti demonstrated a low sensitivity, high specificity and a kappa of 0.471 (95% CI 0.256 to 0.686), and at T1yr a low sensitivity, high specificity of 85% and a kappa of 0.479 (95% CI 0.245 to 0.714)., Conclusions: We found that the ERD can provide accurate real time AE reporting in thoracic surgery, has advantages over previous reporting methodologies and is an alternative system for surgical clinical teams developing AE reporting systems., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The accuracy of ECG imaging (ECGI) in structural heart disease remains uncertain. This study aimed to provide a detailed comparison of ECGI and contact-mapping system (CARTO) electrograms., Methods: Simultaneous epicardial mapping using CARTO (Biosense-Webster, CA) and ECGI (CardioInsight) in 8 patients was performed to compare electrogram morphology, activation time (AT), and repolarization time (RT). Agreement between AT and RT from CARTO and ECGI was assessed using Pearson correlation coefficient, ρ AT and ρ RT , root mean square error, E AT and E RT , and Bland-Altman plots., Results: After geometric coregistration, 711 (439-905; median, first-third quartiles) ECGI and CARTO points were paired per patient. AT maps showed ρ AT =0.66 (0.53-0.73) and E AT =24 (21-32) ms, RT maps showed ρ RT =0.55 (0.41-0.71) and E RT =51 (38-70) ms. The median correlation coefficient measuring the morphological similarity between the unipolar electrograms was equal to 0.71 (0.65-0.74) for the entire signal, 0.67 (0.59-0.76) for QRS complexes, and 0.57 (0.35-0.76) for T waves. Local activation map correlation, ρ AT , was lower when default filters were used (0.60 (0.30-0.71), P=0.053). Small misalignment of the ECGI and CARTO geometries (below ±4 mm and ±4°) could introduce variations in the median ρ AT up to ±25%. Minimum distance between epicardial pacing sites and the region of earliest activation in ECGI was 13.2 (0.0-28.3) mm from 25 pacing sites with stimulation to QRS interval <40 ms., Conclusions: This simultaneous assessment demonstrates that ECGI maps activation and repolarization parameters with moderate accuracy. ECGI and contact electrogram correlation is sensitive to electrode apposition and geometric alignment. Further technological developments may improve spatial resolution.

The relative scarcity of well-defined genetic and metabolic linkages to material properties impedes biological production of inorganic materials. The physiology of electroactive bacteria is intimately tied to inorganic transformations, which makes genetically tractable and well-studied electrogens, such as Shewanella oneidensis, attractive hosts for material synthesis. Notably, this species is capable of reducing a variety of transition-metal ions into functional nanoparticles, but exact mechanisms of nanoparticle biosynthesis remain ill-defined. We report two key factors of extracellular electron transfer by S. oneidensis, the outer membrane cytochrome, MtrC, and soluble redox shuttles (flavins), that affect Pd nanoparticle formation. Changes in the expression and availability of these electron transfer components drastically modulated particle synthesis rate and phenotype, including their structure and cellular localization. These relationships may serve as the basis for biologically tailoring Pd nanoparticle catalysts and could potentially be used to direct the biogenesis of other metal nanomaterials.

Background: The aim of this study was to assess the inter observer and intra observer reliability of acute scaphoid fracture classification methods including a novel 'long axis' measurement, a simple method which we have developed with the aim of improving agreement when describing acute fractures., Methods: We identified sixty patients with acute scaphoid fractures at two centres who had been investigated with both plain radiographs and a CT (Computed Tomography) scan within 4 weeks of injury. The fractures were assessed by three observers at each centre using three commonly used classification systems and the 'long axis' method., Results: Inter observer reliability: based on X-rays the 'long axis' measurement demonstrated substantial agreement (Intraclass Correlation Coefficient (ICC) =0.76) and was significantly more reliable than the Mayo (p < 0.01), the most reliable of the established classification systems with moderate levels of agreement (kappa = 0.56). Intra observer reliability: the long axis measurement demonstrated almost perfect agreement whether based on X-ray (ICC = 0.905) or CT (ICC = 0.900)., Conclusions: This study describes a novel pragmatic 'long axis' method for the assessment of acute scaphoid fractures which demonstrates substantial inter and intra observer reliability. The 'long axis' measurement has clear potential benefits over traditional classification systems which should be explored in future clinical research.

Metabolic engineering has facilitated the production of pharmaceuticals, fuels, and soft materials but is generally limited to optimizing well-defined metabolic pathways. We hypothesized that the reaction space available to metabolic engineering could be expanded by coupling extracellular electron transfer to the performance of an exogenous redox-active metal catalyst. Here we demonstrate that the electroactive bacterium Shewanella oneidensis can control the activity of a copper catalyst in atom-transfer radical polymerization (ATRP) via extracellular electron transfer. Using S. oneidensis , we achieved precise control over the molecular weight and polydispersity of a bioorthogonal polymer while similar organisms, such as Escherichia coli , showed no significant activity. We found that catalyst performance was a strong function of bacterial metabolism and specific electron transport proteins, both of which offer potential biological targets for future applications. Overall, our results suggest that manipulating extracellular electron transport pathways may be a general strategy for incorporating organometallic catalysis into the repertoire of metabolically controlled transformations., Competing Interests: Conflict of interest statement: The authors have filed a patent based on this work.

Introduction: Cardiac resynchronization using a left ventricular (LV) epicardial lead placed in the coronary sinus is now routinely used in the management of heart failure patients. LV endocardial pacing is an alternative when this is not feasible, with outcomes data sparse., Objective: To review the available evidence on the efficacy and safety of endocardial LV pacing via meta-analysis., Methods: EMBASE, MEDLINE, and COCHRANE databases with the search term "endocardial biventricular pacing" or "endocardial cardiac resynchronization" or "left ventricular endocardial" or "endocardial left ventricular." Comparisons of pre-and post-QRS width, LV ejection fraction (LVEF), and New York Heart Association (NYHA) functional classification was performed, and mean differences (and respective 95% confidence interval [CI]) applied as a measurement of treatment effect., Results: Fifteen studies, including 362 patients, were selected. During a mean follow-up of 40 ± 24.5 months, death occurred in 72 patients (11 per 100 patient-years). Significant improvements in LVEF (mean difference 7.9%, 95% CI 5-10%, P < 0.0001; I 2  = 73%), QRS width (mean difference: -41% 95% -75 to -7%; P < 0.0001; I 2  = 94%), and NYHA class (mean difference: -1.06, 95% CI -1.2 to -0.9, P < 0.0001; I 2  = 60%), (all P < 0.0001) occurred. Stroke rate was 3.3-4.2 per 100 patient-years, which is higher than equivalent heart failure trial populations and recent meta-analysis that included small case series., Conclusion: LV endocardial lead implantation is a potentially efficacious alternative to CS lead placement, but preliminary data suggest a potentially higher risk of stroke during follow-up when compared to the expected incidence of stroke in similar cohorts of patients., (© 2018 Wiley Periodicals, Inc.)

The human antibody repertoire is a unique repository of information regarding infection, inflammation, and autoimmunity of the past, present, and future. However, antibodies can span vast ranges of concentrations with varying affinities and the repertoire is often heavily polarized by a few species. These complexities lead to difficulties detecting and characterizing low abundance antibody species that may be relevant to disease. We therefore developed a method to selectively remove antibodies from a sample in proportion to the titer of the species prior to analysis, referred to as high-titer depletion (HTD). Peptides from a large random peptide display library were enriched towards binding high-titer antibody species and utilized as binding reagents to deplete the corresponding species from the specimen. HTD enabled the discovery of antibody binding specificities using random peptide library screening with reduced cross-reactivity and background signal and improved coverage of low abundance species. With HTD, three monoclonal antibody species were detected at concentrations at least an order of magnitude lower than without HTD. Additionally, 92 serum antibody specificities were readily discovered from an individual specimen using HTD compared to only 25 specificities without HTD. Parameters affecting the extent of depletion such as the concentration of depleted serum were also adjusted to reproducibly improve the coverage of antibody specificities. These results demonstrate that HTD could be employed for the discovery of rare specificities related to disease and enable extensive characterization of the antibody repertoire. Moreover, the strategy of depletion in proportion to titer could be extended to other applications with complex biological samples to improve discovery., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Many zeolitic imidazolate frameworks (ZIFs) are promising candidates for use in separation technologies. Comprising large cavities interconnected by small windows they can be used, at least in principle, as molecular sieves where molecules smaller than the window size are able to diffuse into the material while larger molecules are rejected. However, "swing effect" or "gate opening" phenomena resulting in an enlargement of the windows have proven to be detrimental. Here, we present the first systematic experimental and computational study of the effect of chemical functionalization of the imidazole linker on the framework dynamics. Using high-pressure (HP) single-crystal X-ray diffraction, density functional theory, and grand canonical Monte Carlo simulations, we show that in the isostructural ZIF-8, ZIF-90, and ZIF-65 functional groups of increasing polarity (-CH 3 , -CHO, and -NO 2 ) on the imidazole linkers provide control over the degree of rotation and thus the critical window diameter. On application of pressure, the substituted imidazolate rings rotate, resulting in an increase in both pore volume and content. Our results show that the interplay between the guest molecules and the chemical function of the imidazole linker is essential for directing the swing effect in ZIF frameworks and therefore the adsorption performance.

Background: Trans-septal puncture (TSP) is routinely performed during treatment of atrial fibrillation (AF) and other electrophysiology procedures. The purpose of this retrospective observational study was the analysis of a novel needle free technique employed to gain access to the left atrium (LA)., Methods: The SafeSept Needle Free guidewire was delivered, using no needle, to the interatrial septum via a standard cryoablation sheath and dilator under transoesophageal guidance. The wire was then advanced into the LA with position confirmed by fluoroscopy. All cases were performed under general anaeasthetic (GA)., Results: The novel procedure was performed in 43 patients (38 paroxysmal AF (88.4%) and 5 persistent AF (11.4%)) with 100% success rate in accessing the LA. The procedure times (51.70 ±18.18) and fluoroscopy times (2.75 ± 3.35) were recorded. There were no complications seen in the cohort., Conclusion: Using SafeSept Needle Free wire for TSP had a high success rate and resulted in no complications, with the potential to reduce procedure and fluoroscopy times.

Recurrent episodes of ventricular tachycardia in patients with structural heart disease are associated with increased mortality and morbidity, despite the life-saving benefits of implantable cardiac defibrillators. Reducing implantable cardiac defibrillator therapies is important, as recurrent shocks can cause increased myocardial damage and stunning, despite the conversion of ventricular tachycardia/ventricular fibrillation. Catheter ablation has emerged as a potential therapeutic option either for primary or secondary prevention of these arrhythmias, particularly in post-myocardial infarction cases where the substrate is well defined. However, the outcomes of catheter ablation of ventricular tachycardia in structural heart disease remain unsatisfactory in comparison with other electrophysiological procedures. The disappointing efficacy of ventricular tachycardia ablation in structural heart disease is multifactorial. In this review, we discuss the issues surrounding this and examine the limitations of current mapping approaches, as well as newer technologies that might help address them., Competing Interests: Disclosure: Pier D Lambiase receives speaker fees, educational grants and research grants from Medtronic and Boston Scientific.

Background: Relapses of multiple sclerosis decrease during pregnancy, when the hormone estriol is increased. Estriol treatment is anti-inflammatory and neuroprotective in preclinical studies. In a small single-arm study of people with multiple sclerosis estriol reduced gadolinium-enhancing lesions and was favourably immunomodulatory. We assessed whether estriol treatment reduces multiple sclerosis relapses in women., Methods: We did a randomised, double-blind, placebo-controlled phase 2 trial at 16 academic neurology centres in the USA, between June 28, 2007, and Jan 9, 2014. Women aged 18-50 years with relapsing-remitting multiple sclerosis were randomly assigned (1:1) with a random permuted block design to either daily oral estriol (8 mg) or placebo, each in combination with injectable glatiramer acetate 20 mg daily. Patients and all study personnel, except for pharmacists and statisticians, were masked to treatment assignment. The primary endpoint was annualised relapse rate after 24 months, with a significance level of p=0.10. Relapses were confirmed by an increase in Expanded Disability Status Scale score assessed by an independent physician. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00451204., Findings: We enrolled 164 patients: 83 were allocated to the estriol group and 81 were allocated to the placebo group. The annualised confirmed relapse rate was 0.25 relapses per year (95% CI 0.17-0.37) in the estriol group versus 0.37 relapses per year (0.25-0.53) in the placebo group (adjusted rate ratio 0.63, 95% CI 0.37-1.05; p=0.077). The proportion of patients with serious adverse events did not differ substantially between the estriol group and the placebo group (eight [10%] of 82 patients vs ten [13%] of 76 patients). Irregular menses were more common in the estriol group than in the placebo group (19 [23%] vs three [4%], p=0.0005), but vaginal infections were less common (one [1%] vs eight [11%], p=0.0117). There were no differences in breast fibrocystic disease, uterine fibroids, or endometrial lining thickness as assessed by clinical examination, mammogram, uterine ultrasound, or endometrial lining biopsy., Interpretation: Estriol plus glatiramer acetate met our criteria for reducing relapse rates, and treatment was well tolerated over 24 months. These results warrant further investigation in a phase 3 trial., Funding: National Institutes of Health, National Multiple Sclerosis Society, Conrad N Hilton Foundation, Jack H Skirball Foundation, Sherak Family Foundation, and the California Community Foundation., (Copyright © 2016 Elsevier Ltd. All rights reserved.)