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Using 'Duncan' grapefruit epicotyls as explants, 19 genome-edited grapefruit plants were generated with one biallelic mutant line (#DunYao7). Xcc caused canker symptoms on wild-type and non-biallelic mutant plants but not on #DunYao7. XccPthA4 mutant containing the designer TAL effector dLOB1.5, which recognizes a conserved sequence in both wild-type and #DunYao7, caused canker symptoms on both wild-type and #DunYao7. No off-target mutations were detected in #DunYao7. This study represents the first time that CRISPR-mediated genome editing has been successfully used to generate disease-resistant plants for 'Duncan' grapefruit, paving the way for utilizing disease-resistant varieties to control canker.Background. Chronic foot ulcers are a major cause of morbidity in people with diabetes with a lifetime risk of 25%. selleck chemicals Treatment is challenging and the recurrence rates of foot ulcers are >50% after 3 years. Vitamin D deficiency is more common in people with diabetes with chronic foot ulcers, compared to both people without diabetes as well as people with diabetes but without foot ulcers. Purpose/aim of study. To assess the efficacy of high-dose compared to low-dose Cholecalciferol vitamin D3 on healing of chronic diabetic foot ulcers. Materials and methods. We included people with diabetes with one or more foot ulcers lasting for more than 6 weeks. Patients were randomly allocated to either a daily oral intake of high-dose (170 μg) or low-dose (20 μg) vitamin D3 (Cholecalciferol). We saw patients in the outpatient clinic after 4, 12, 24, 36, and 48 weeks. At each visit, we measured the ulcer with a specialized camera, and associated software and the area (cm2) was calculated. Patients and assessors were blinded.Treating actinic keratosis (AK) and photodamaged skin is critical to reduce the risk of progression to skin cancer. Laser resurfacing for AK treatment is available as either lesion-directed or field therapy. Laser resurfacing removes the superficial epidermis and dermis containing actinic damage, promoting re-epithelialization of healthy skin. Although laser resurfacing has been explored as a modality for AK treatment in the literature, studies summarizing its efficacy in the treatment of AK are lacking. This review summarizes existing research on laser resurfacing as a monotherapy for AK treatment, highlighting the various laser resurfacing modalities available for AK treatment as well as their complications and efficacy in comparison to other therapies. Despite longer healing time, fully ablative laser resurfacing, including carbon dioxide and erbium-doped yttrium aluminum garnet were found to be more effective for AK treatment than fractional ablative techniques. Although some studies suggest laser resurfacing monotherapy as less efficacious than photodynamic therapy, and equally effective to 5-fluorouracil and 30% trichloroacetic acid, clinical trials of larger sample size are required to establish stronger evidence-based conclusions. Moreover, laser resurfacing used as lesion-directed therapy, as opposed to the usual field-therapy, requires further investigation.Burnout in health care employees and leaders is at an all-time high. Strategies to address burnout can fall short of addressing the broad range of underlying causes, including both organizational culture and personal factors. The National Academies of Medicine has set forth recommendations to address health care burnout from a leadership-based systems level that focuses on the whole employee, body, mind, and spirit. Across generations and societies, there is a growing trend toward spirituality and meaning as a critical component of both personal life and work. Among the working-age millennials, values of purpose and greater societal good take precedent and impact work choices and behaviors. Spiritually based values such as a sense of purpose, the transcendence of the self and ego, and the acknowledgment of something greater than our collective selves, are present in both popular culture and research on transcendental models of leadership. This article presents a model of holistic transcendental leadership that can be leveraged in the health care workplace to enhance innovation and creativity, while placing a novel emphasis on the physical, emotional, and spiritual well-being at the individual, group, and organizational level.T cell activation is a critical event in the adaptive immune response, indispensable for cell-mediated and humoral immunity as well as for immune regulation. Recent years have witnessed an emerging trend emphasizing the essential role that physical force and mechanical properties play at the T cell interface. In this review, we integrate current knowledge of T cell antigen recognition and the different models of T cell activation from the perspective of mechanobiology, focusing on the interaction between the T cell receptor (TCR) and the peptide-major histocompatibility complex (pMHC) antigen. We address the shortcomings of TCR affinity alone in explaining T cell functional outcomes and the rising status of force-regulated TCR bond lifetimes, most notably the TCR catch bond. Ultimately, T cell activation and the ensuing physiological responses result from mechanical interaction between TCRs and the pMHC. Expected final online publication date for the Annual Review of Cell and Developmental Biology, Volume 37 is October 2021. Please see http//www.annualreviews.org/page/journal/pubdates for revised estimates.The cell nucleus is best known as the container of the genome. Its envelope provides a barrier for passive macromolecule diffusion, which enhances the control of gene expression. As its largest and stiffest organelle, the nucleus also defines the minimal space requirements of a cell. Internal or external pressures that deform a cell to its physical limits cause a corresponding nuclear deformation. Evidence is consolidating that the nucleus, in addition to its genetic functions, serves as a physical sensing device for critical cell body deformation. Nuclear mechanotransduction allows cells to adapt their acute behaviors, mechanical stability, paracrine signaling, and fate to their physical surroundings. This review summarizes the basic chemical and mechanical properties of nuclear components, and how these properties are thought to be utilized for mechanosensing. Expected final online publication date for the Annual Review of Cell and Developmental Biology, Volume 37 is October 2021. Please see http//www.annualreviews.org/page/journal/pubdates for revised estimates.

Myocarditis is one of the most common causes leading to heart failure in children and a possible genetic background has been postulated. We sought to characterize the clinical and genetic characteristics in patients with myocarditis ≤18 years of age to predict outcome.

A cohort of 42 patients (Genetics in Pediatric Myocarditis) with biopsy-proven myocarditis underwent genetic testing with targeted panel sequencing of cardiomyopathy-associated genes. Genetics in Pediatric Myocarditis patients were divided into subgroups according to the phenotype of dilated cardiomyopathy (DCM) at presentation, resulting in 22 patients without DCM (myocarditis without phenotype of DCM) and 20 patients with DCM (myocarditis with phenotype of DCM).

Myocarditis with phenotype of DCM patients (median age 1.4 years) were younger than myocarditis without phenotype of DCM patients (median age 16.1 years;

<0.001) and were corresponding to heart failure-like and coronary syndrome-like phenotypes, respectively. At least one lewly diagnosed with myocarditis and DCM phenotype is warranted.

We report heterozygous likely pathogenic/pathogenic variants in biopsy-proven pediatric myocarditis. Myocarditis patients with DCM phenotype were characterized by early-onset heart failure, significant enrichment of likely pathogenic/pathogenic variants, and poor outcome. These phenotype-specific and age group-specific findings will be useful for personalized management of these patients. Genetic evaluation in children newly diagnosed with myocarditis and DCM phenotype is warranted.Purpose The aim of this study was to extract key learning from intervention studies in which qualitative aspects of dosage, dose form, have been examined for children with developmental language disorder (DLD)-in vocabulary, morphosyntax, and phonology domains. This research paper emerged from a pair of systematic reviews, aiming to synthesize available evidence regarding qualitative and quantitative aspects of dosage. While quantitative aspects had been experimentally manipulated, the available evidence for dose form (tasks or activities within which teaching episodes are delivered) was less definitive. Despite this, the review uncovered insights of value to DLD research. Method A preregistered systematic review (PROSPERO ID CRD42017076663) adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was completed. Included papers were quasi-experimental, randomized controlled trial, or cohort analytic studies, published in any language between January 2006 and May 2019; pathology research would benefit from an agreed taxonomy of dose form components and standardized reporting of intervention studies, to enable cross-study comparisons and a systematic accrual of knowledge to identify optimal dose form for clinical application.This corrects the article DOI 10.1103/PhysRevLett.125.051101.In equilibrium liquid crystals, chirality leads to a variety of spectacular three-dimensional structures, but chiral and achiral phases with the same broken continuous symmetries have identical long-time, large-scale dynamics. In this Letter, starting from active model H^*, the general hydrodynamics of a pseudoscalar in a momentum-conserving fluid, we demonstrate that chirality qualitatively modifies the dynamics of layered liquid crystals in active systems in both two and three dimensions due to an active "odder" elasticity. In three dimensions, we demonstrate that the hydrodynamics of active cholesterics differs fundamentally from smectic-A liquid crystals, unlike their equilibrium counterpart. This distinction can be used to engineer a columnar array of vortices, with an antiferromagnetic vorticity alignment, that can be switched on and off by external strain. A two-dimensional chiral layered state-an array of lines on an incompressible, freestanding film of chiral active fluid with a preferred normal direction-is generically unstable. However, this instability can be tuned in easily realizable experimental settings when the film is either on a substrate or in an ambient fluid.Time-periodic driving facilitates a wealth of novel quantum states and quantum engineering. The interplay of Floquet states and strong interactions is particularly intriguing, which we study using time-periodic fields in a one-dimensional quantum gas, modeled by a Luttinger liquid with periodically changing interactions. By developing a time-periodic operator algebra, we are able to solve and analyze the complete set of nonequilibrium steady states in terms of a Floquet-Bogoliubov ansatz and known analytic functions. Complex valued Floquet eigenenergies occur when integer multiples of the driving frequency approximately match twice the dispersion energy, which correspond to resonant states. In experimental systems of Lieb-Liniger bosons we predict a change from power-law correlations to dominant collective density wave excitations at the corresponding wave numbers as the frequency is lowered below a characteristic cutoff.