I am not sure this editorial comment deserves an abstract. Plesae advise.

Left anterior descending (LAD) coronary arterial injury is an underappreciated and rare consequence of ablation in the right ventricular outflow tract (RVOT). The authors present five cases of acute or subacute LAD injury after RVOT ablation. Most patients had fairly extensive ablation and two had coincident cardiac perforation. The patients reported also had a strikingly similar ECG morphology of their spontaneous ventricular arrhythmias. The authors’ report serves an important cautionary tale regarding ablation of intramural septal VAs.

Predictive Modeling of Lead Durability, An Important Step ForwardGeorge H. Crossley MD, FHRS, FACCVanderbilt Heart and Vascular Institute, Nashville, TN; and Cardiovascular Diseases Section, Vanderbilt University School of MedicineRWI: Dr. Crossley consults for Medtronic, Boston Scientific, and Phillips.Running Title: Lead Durability AnalysisWord Count: 893

Radiofrequency (RF) ablation for the treatment of atrial fibrillation has gained widespread acceptance since the concept was introduced by Haissaguerre et al a quarter of a century ago. High power short duration ablation has been widely adopted in the management of atrial fibrillation. Evidence for combining lesion size index and high power short duration ablation is lacking. In this issue of the journal, Cai et al evaluated the combination of HPSD with LSI with a focus on long-term efficacy.

Transoral robotic surgery (TORS) has evolved into a common surgical modality used to treat primarily oropharyngeal malignant and benign pathologies. The single port Intuitive Surgical da Vinci surgical robotics system facilitates access to the hypopharynx and cervical esophagus. We aim to describe our approach and advantages of the technique.

Viral vectors for gene therapy, such as recombinant Adeno-Associated Viruses (rAAV), are produced in Human Embryonic Kidney (HEK) 293 cells. However, the presence of the SV40 T-antigen-encoding CDS SV40GP6 and SV40GP7 in the HEK293T genome raises safety issues when these cells are used in manufacturing for clinical purposes. We developed a new T-antigen-negative HEK cell line from ExcellGene’s proprietary HEKExpress®, using the CRISPR-Cas9 strategy. We obtained a high number of clonally-derived cell populations and all of them were demonstrated T-antigen negative. Stability study and AAV production evaluation showed that the deletion of the T-antigen-encoding locus did not impact neither cell growth nor viability nor productivity. The resulting CMC-compliant cell line, named HEKzeroT®, is able to produce high AAV titers, from small to large scale.

Objective: To identify postoperative vaginal morphology and position factors associated with prolapse recurrence following vaginal surgery. Design: Secondary analysis of MRIs of the Defining Mechanisms of Anterior Vaginal Wall Descent cross-sectional study. Setting: Eight clinical sites in the US Pelvic Floor Disorders Network. Population: Women who underwent vaginal mesh hysteropexy (hysteropexy) with sacrospinous fixation or vaginal hysterectomy with uterosacral ligament suspension (hysterectomy) for symptomatic uterovaginal prolapse between April 2013 and February 2015. Methods: MRIs (rest, strain) obtained 30-42 months after surgery, or earlier for participants with recurrence who desired reoperation prior to 30 months, were analyzed. Prolapse recurrence was defined as prolapse beyond the hymen at strain on MRI. Vaginal segmentations (at rest) were used to create 3D models placed in a morphometry algorithm to quantify and compare vaginal morphology (angulation, dimensions) and position between groups. Main Outcome Measures: Vaginal angulation (upper, lower, and upper-lower vaginal angles in the sagittal and coronal plane), dimensions (length, maximum transverse width, surface area, volume), and position (apex, mid-vagina) at rest. Results: Of the 82 women analyzed, 12/41 (29%) in the hysteropexy group and 22/41 (54%) in the hysterectomy group had prolapse recurrence. After hysteropexy, recurrences had a more laterally deviated upper vagina (p=0.02) at rest than successes. After hysterectomy, recurrences had a more inferiorly (lower) positioned vaginal apex (p=0.01) and mid-vagina (p=0.01) at rest than successes. Conclusions: Vaginal angulation and position were associated with prolapse recurrence and indicative of vaginal support mechanisms related to surgical technique and unaddressed anatomical defects. Future prospective studies in women before and after prolapse surgery may distinguish these two factors. Funding: Eunice Kennedy Shriver National Institute of Child Health and Human Development-sponsored Pelvic Floor Disorders Network (Grant/Award Number: U10 HD054214, U10 HD041267, U10 HD041261, U10 HD069013, U10 HD069025, U10 HD069010, U10 HD069006, U10 HD054215, U01 HD069031); National Institutes of Health Office of Research on Women’s Health; Boston Scientific Corporation; National Academies of Sciences, Engineering, and Medicine’s Ford Foundation Predoctoral Fellowship Program

A 22-year-old male was admitted to our hospital after taking 2450 mg of pilsicainide. On admission, the patient was in cardiac arrest, and percutaneous cardiopulmonary support was introduced to maintain his circulation. After three days of intensive care, he was no impaired consciousness and transferred another hospital for psychological problem.

The current study focuses on the thermal distribution in the boundary layer of a wedge with a variable surface temperature. The governing equations of MHD flow for variable wall temperature conditions can be converted to ODE by using similarity solutions, and the Hartmann number (Ha) from 1 to 3 can be solved via the colocation method. This method’s results are compared to those of the numerical method, and it is then evaluated and validated. As the angle or Ha increases, the width of the hydrodynamic boundary layer decreases, and the slope of the boundary layer increases, increasing the coefficient of friction on the surface. The results are obtained for variable wall temperature (n), Prandtl number (Pr) and Eckert number (Ec), where they are 0.5≤n≤1.5, 0.5≤Pr≤5, and 0.001≤Ec≤0.002, and at a certain angle. It is observed that when Ha, Pr, and n increase, the thermal boundary layer grows faster than before; thus, thickness decreases and the Nusselt number (Nu) rises; however, as the Ec adds, the Nu decreases on the wall.

Traditional agrosystems, where humans, crops and microbes have coevolved over long periods, can serve as models to understand the eco-evolutionary determinants of disease dynamics and help the engineering of durably resistant agrosystems. Here, we investigated the genetic and phenotypic relationship between rice (Oryza sativa) landraces and their rice blast pathogen (Pyricularia oryzae) in the traditional Yuanyang terraces of flooded rice paddies in China, where rice landraces have been grown and bred over centuries without significant disease outbreaks. Analyses of genetic subdivision revealed that indica rice plants clustered according to landrace names. Three new diverse lineages of rice blast specific to the Yuanyang terraces coexisted with lineages previously detected at the worldwide scale. Population subdivision in the pathogen population did not mirror pattern of population subdivision in the host. Measuring the pathogenicity of rice blast isolates on landraces revealed generalist life histories. Our results suggest that the implementation of disease control strategies based on the emergence or maintenance of a generalist lifestyle in pathogens may sustainably reduce the burden of disease in crops.

Maintaining and restoring ecological connectivity is considered a global imperative to help reverse the decline of biodiversity. To be successful, practitioners need to be guided by connectivity modeling research that is rigorous and reliable for the task at hand. However, the methods and workflows within this rapidly growing field are diverse and few have been rigorously scrutinized. We propose three procedural steps that should be consistently undertaken and reported on in connectivity modeling studies in order to improve rigour and utility: (1) describe the type of connectivity being modeled, (2) assess the uncertainty and sensitivity of model parameters, and (3) validate the model outputs, ideally with independent data. We reviewed the literature to determine the extent to which studies included these three steps. We focused on studies that generated novel landscape connectivity outputs using circuit theory. Among 181 studies meeting our search criteria, 39% communicated the type of connectivity being modeled and 18% conducted some form of sensitivity or uncertainty analysis (or both). Only 19% of studies attempted to validate their connectivity model outputs and only 7% used fully independent data. Our findings highlight a clear need and opportunity to improve the rigour, reliability, and utility of connectivity modeling research. At a minimum, researchers should be transparent about which, if any, of these three steps were undertaken. This will help practitioners make more informed decisions and ensure limited resources for connectivity conservation and restoration are allocated appropriately.

The present study presents an alternative analytical workflow that combines mid-infrared (MIR) microscopic imaging and deep learning to diagnose human lymphoma and differentiate between small and large cell lymphoma. We could show that using a deep learning approach to analyze MIR hyperspectral data obtained from benign and malignant lymph node pathology results in high accuracy for correct classification, learning the distinct region of 3900 cm-1 to 850 cm-1. The accuracy is above 95% for every pair of malignant lymphoid tissue and still above 90% for the distinction between benign and malignant lymphoid tissue for binary classification. These results demonstrate that a preliminary diagnosis and subtyping of human lymphoma could be streamlined by applying a deep learning approach to analyze MIR spectroscopic data.

A document by David Slotwiner. Click on the document to view its contents.

Rapid urbanization and global climate change are likely to exacerbate urban flooding intensity, frequency, and uncertainty. Thus, it is fundamental and crucial to investigate the dominant influencing factors for the mitigation of urban flooding. However, the influence of building patterns on urban flooding remains limited. Taking Beijing, a typical megacity, as a case study area, we quantified the importance of building patterns and their interaction effect at the subwatershed scale using the boosted regression tree (BRT) and geographical detector model (GeoD). The results indicated that (1) the landscape shape index, slope, green space ratio and waterbody ratio were the most important influencing factors determining urban flooding, with a total relative contribution of 67.23%, (2) building metrics had a certain impact on urban flooding, and the sum of the relative contribution can reach 21.03%, (3) with urban flooding density, the landscape shape index, slope, and green space ratio exhibited a combination of negative and positive correlation, and (4) an enhancement effect existed between building metrics, especially the building congestion degree and building density. These findings provide quantitative insights that rational urban morphology planning can improve stormwater management and promote urban sustainability in megacities.

Plants can detect neighbouring plants through a reduction in the ratio between red and far-red light (R:FR). This provides a signal of plant-plant competition and induces rapid plant growth while inhibiting defence against biotic stress, two interlinked responses designated as the shade avoidance syndrome (SAS). Consequently, the SAS can influence plant-herbivore interactions that could cascade to higher trophic levels. However, little is known on how the expression of the SAS can influence tritrophic interactions. We investigated whether changes in R:FR affect the emission of herbivore-induced plant volatiles (HIPVs), and whether these changes influence the attraction of the zoophytophagous predator Macrolophus pygmaeus. We also studied how the expression of the SAS and subsequent inhibition of plant defences affects the reproduction of M. pygmaeus in both the presence and absence of the greenhouse whitefly ( Trialeurodes vaporariorum) as arthropod prey. The results show that changes in R:FR have little effect on HIPV emissions and predator attraction. However, a reduction in R:FR leads to increased reproduction of both the predator and the whiteflies. We conclude that shade avoidance responses can increase the population development of M. pygmaeus directly by reducing plant defences, and indirectly by supporting higher herbivore densities.

This paper aims to understand the binding strategies of a nanobody-protein pair by studying known complexes. Rigid body protein-ligand docking programs produce several complexes, called decoys, which are good candidates with high scores of shape complementarity, electrostatic interactions, desolvation, buried surface area, and Lennard-Jones potentials. It is not known which decoy represents the true structure. We studied thirty-seven nanobody-protein complexes from the Single Domain Antibody Database, sd-Ab DB, [http://www.sdab-db.ca/](http://www.sdab-db.ca/). For each structure, a large number of decoys are generated using the Fast Fourier Transform algorithm of the software ZDOCK. The decoys were ranked according to their target protein-nanobody interaction energies, calculated by using the Dreiding Force Field, with rank 1 having the lowest interaction energy. Out of thirty-six PDB structures, twenty-five true structures were predicted as rank 1. Eleven of the remaining structures required Ångstrom size rigid body translations of the nanobody relative to the protein to match the given PDB structure. After the translation the Dreiding interaction (DI) energies of all complexes decreased and became rank 1. In one case, rigid body rotations as well as translations of the nanobody were required for matching the crystal structure. We used a Monte Carlo algorithm that randomly translates and rotates the nanobody of a decoy and calculates the DI energy. Results show that rigid body translations and the DI energy are sufficient for determining the correct binding location and pose of ZDOCK created decoys. A survey of the sd-Ab DB showed that each nanobody makes at least one salt bridge with its partner protein, indicating that salt bridge formation is an essential strategy in nanobody-protein recognition. Based on the analysis of the thirty-six crystal structures and evidence from existing literature, we propose a set of principles that could be used in the design of nanobodies.

Title: Sweet syndrome masquerading as a disseminated and pulmonary fungal disease in a child with acute myeloid leukemia: case report and review of the literature

Here we present a diagnostically challenging Bing-Neel Syndrome (BNS) case successfully treated with systemic chemoimmunotherapy and ibrutinib, with remarkable clinical response. BNS is an extremely rare direct central nervous system infiltration by malignant lymphoplasmocytic lymphoma cells in patients with Waldenstroms macroglobulinaemia.