Comparative Mutational Profiling of Hematopoietic Progenitor Cells and Circulating Endothelial Cells (CECs) in Patients with Primary Myelofibrosis.

A role of endothelial cells (ECs) in Primary Myelofibrosis (PMF) was supposed since mutation was found in endothelial precursor cells (EPCs) and in ECs captured by laser microdissection. By Cell Search method, the circulating endothelial cells (CECs) from 14 PMF patients and 5 healthy controls have been isolated and compared by NGS with CD34+Hematopoietic stem and progenitors cells (HSPCs) for panel of 54 myeloid-associated mutations. PMF patients had higher levels of CECs.

Electronic Coherences Steer the Strong Isotope Effect in the Ultrafast Jahn-Teller Structural Rearrangement of Methane Cation upon Tunnel Ionization.

We report on fully quantum electronic-nuclear dynamics following sudden ionization from the neutral in the three lowest electronic states of the CH and CD cations. There is a strong Jahn-Teller effect in the Franck-Condon region, and we employ two nuclear degrees of freedom that span the internal coordinates involved in the Jahn-Teller coupling. The initial state results from tunneling ionization by a strong IR field which coherently pumps the three lowest states of the cation, D, D, and D.

Toward More Complete Prognostication for Patients with Clonal Hematopoiesis.

The study of clonal hematopoiesis is rapidly evolving, with the highest prevalence in aging populations and wide-ranging implications for health and disease, including an increased risk of subsequent myeloid malignancies and cardiovascular disease. In their article, Feusier and colleagues report on an expanded driver mutation list for capture of higher-risk clonal hematopoiesis mutations implicated in leukemia transformation. They also describe the prevalence of clonal hematopoiesis in several additional large studies, including, most importantly, in the pediatric context, which has not yet been extensively studied with respect to clonal hematopoiesis and clonal hematopoiesis-related sequelae.

Clonal hematopoiesis is associated with risk of severe Covid-19.

Acquired somatic mutations in hematopoietic stem and progenitor cells (clonal hematopoiesis or CH) are associated with advanced age, increased risk of cardiovascular and malignant diseases, and decreased overall survival. These adverse sequelae may be mediated by altered inflammatory profiles observed in patients with CH. A pro-inflammatory immunologic profile is also associated with worse outcomes of certain infections, including SARS-CoV-2 and its associated disease Covid-19.

Relative Impact of Surgical Mitral Repair and MitraClip on Annular Remodeling-A Potential Mechanism for Therapeutic Response to Mitral Repair for Degenerative Mitral Regurgitation.

Objectives: Three-dimensional transesophageal echocardiography (TEE) is widely used to guide decision-making for mitral repair. The relative impact of surgical mitral valve repair (MVr) and MitraClip on annular remodeling is unknown. The aim was to determine the impact of both mitral repair strategies on annular geometry, including the primary outcome of annular circumference and area.

Corporate immunity to the COVID-19 pandemic.

We evaluate the connection between corporate characteristics and the reaction of stock returns to COVID-19 cases using data on more than 6,700 firms across 61 economies. The pandemic-induced drop in stock returns was milder among firms with stronger pre-2020 finances (more cash and undrawn credit, less total and short-term debt, and larger profits), less exposure to COVID-19 through global supply chains and customer locations, more corporate social responsibility activities, and less entrenched executives. Furthermore, the stock returns of firms controlled by families (especially through direct holdings and with non-family managers), large corporations, and governments performed better, and those with greater ownership by hedge funds and other asset management companies performed worse.

Short-Term Case Reports Demonstrating the Use of Volume-Stable Collagen Matrix.

A proper diagnostic and treatment planning process for dental implant rehabilitations should include a checklist of key factors to help clinicians avoid potential complications. Such a checklist should encompass evaluation of the soft- and hard-tissue volume buccal to each implant, as this has been shown to aid in maintaining marginal bone levels long-term. Thus, as part of surgical planning, a decision to augment the soft tissue should be considered.

Aire regulates chromatin looping by evicting CTCF from domain boundaries and favoring accumulation of cohesin on superenhancers.

Aire controls immunological tolerance by driving promiscuous expression of a large swath of the genome in medullary thymic epithelial cells (mTECs). Its molecular mechanism remains enigmatic. High-resolution chromosome-conformation capture (Hi-C) experiments on ex vivo mTECs revealed Aire to have a widespread impact on higher-order chromatin structure, disfavoring architectural loops while favoring transcriptional loops.

Integration of Functional Imaging, Cytometry, and Unbiased Proteomics Reveals New Features of Endothelial-to-Mesenchymal Transition in Ischemic Mitral Valve Regurgitation in Human Patients.

Following myocardial infarction, mitral regurgitation (MR) is a common complication. Previous animal studies demonstrated the association of endothelial-to-mesenchymal transition (EndMT) with mitral valve (MV) remodeling. Nevertheless, little is known about how MV tissue responds to ischemic heart changes in humans.

A Snapshot of Current US Medical School Off-Ramp Programs-a Way to Leave Medical School with Another Degree.

Although most students finish medical school, those who do not frequently have no obvious programmatic alternatives. In recent years, a growing number of medical schools have been developing "off-ramp" programs to help such learners. We surveyed 12 medical schools with off-ramp programs to understand their characteristics and challenges.

Convergence of a Reconstructed Density Matrix to a Pure State Using the Maximal Entropy Approach.

Impressive progress has been made in the past decade in the study of technological applications of varied types of quantum systems. With industry giants like IBM laying down their roadmap for scalable quantum devices with more than 1000-qubits by the end of 2023, efficient validation techniques are also being developed for testing quantum processing on these devices. The characterization of a quantum state is done by experimental measurements through the process called quantum state tomography (QST) which scales exponentially with the size of the system.

Somatosensory Pulsatile Tinnitus Syndrome (SSPT) Revisited.

Introduction: Our initial study reported consecutive patients with constant cardiac synchronous subjective tinnitus (pulsatile tinnitus without an identifiable acoustic source (P)) all of whom could suppress their pulsations with head and neck intense muscle contractions ("somatic testing" (ST)). The term somatosensory pulsatile tinnitus syndrome (SSPT) was coined to refer to this type of P. With now more than a decade of clinical experience with P, herein are reported (a) other ways P can present, beside SSPT, (b) how P is related to the somatosensory system and recumbency, and (c) what treatments have been effective.

Plasma kallikrein predicts primary graft dysfunction after heart transplant.

Background: Primary graft dysfunction (PGD) is the leading cause of early mortality after heart transplant. Pre-transplant predictors of PGD remain elusive and its etiology remains unclear.

Methods: Microvesicles were isolated from 88 pre-transplant serum samples and underwent proteomic evaluation using TMT mass spectrometry.

Mitral Annular Dynamics in AF Versus Sinus Rhythm: Novel Insights Into the Mechanism of AFMR.

Objectives: This study aimed to investigate mitral annular dynamics in atrial fibrillation (AF) and after sinus rhythm restoration, and to assess the relationship between annular dynamics and mitral regurgitation (MR).

Background: AF can be associated with MR that improves after sinus rhythm restoration. Mechanisms underlying this atrial functional MR (AFMR) are ill-understood and generally attributed to left atrial remodeling.

The density matrix via few dominant observables: The quantum interference in the isotope effect for atto-pumped N.

Atto- and sub-femto-photochemistry enables preparation of molecules in a coherent superposition of several electronic states. Recently [Ajay et al., Proc.

UVB mutagenesis differs in - and -mutant mouse models of melanoma.

-mutant melanomas are more likely than -mutant melanomas to arise in anatomical locations protected from chronic sun damage. We hypothesized that this discrepancy in tumor location is a consequence of the differential sensitivity of and -mutant melanocytes to ultraviolet light (UV)-mediated carcinogenesis. We tested this hypothesis by comparing the mutagenic consequences of a single neonatal, ultraviolet-AI (UVA; 340-400 nm) or ultraviolet-B (UVB; 280-390 nm) exposure in mouse models heterozygous for mutant or homozygous for mutant Tumor onset was accelerated by UVB, but not UVA, and the resulting melanomas contained recurrent mutations affecting the RING domain of MAP3K1 and Actin-binding domain of Filamin A.

DNA-based constitutional dynamic networks as functional modules for logic gates and computing circuit operations.

A nucleic acid-based constitutional dynamic network (CDN) is introduced as a single computational module that, in the presence of different sets of inputs, operates a variety of logic gates including a half adder, 2 : 1 multiplexer and 1 : 2 demultiplexer, a ternary multiplication matrix and a cascaded logic circuit. The CDN-based computational module leads to four logically equivalent outputs for each of the logic operations. Beyond the significance of the four logically equivalent outputs in establishing reliable and robust readout signals of the computational module, each of the outputs may be fanned out, in the presence of different inputs, to a set of different logic circuits.

A precision medicine classification for treatment of acute myeloid leukemia in older patients.

Background: Older patients (≥ 60 years) with acute myeloid leukemia (AML) often have multiple, sequentially acquired, somatic mutations that drive leukemogenesis and are associated with poor outcome. Beat AML is a Leukemia and Lymphoma Society-sponsored, multicenter umbrella study that algorithmically segregates AML patients based upon cytogenetic and dominant molecular abnormalities (variant allele frequencies (VAF) ≥ 0.2) into different cohorts to select for targeted therapies.

Xpert HPV as a Screening Tool for Anal Histologic High-Grade Squamous Intraepithelial Lesions in Women Living With HIV.

Background: Women living with HIV (WLWH) experience high rates of anal cancer. Screening using anal cytology, high-resolution anoscopy (HRA) with biopsies, can histologically diagnose anal cancer precursors called high-grade squamous intraepithelial lesions (HSIL). The low specificity of screening using anal cytology results in HRA referral for many WLWH without HSIL.

Virtual reality simulation for critical pediatric airway management training.

Background: Pediatric airway emergencies are relatively rare, but have potentially devastating consequences. Simulation based education is important in providing zero-risk management experience for these critical events.

Aims: The aim of the study was to assess usability and feasibility of combined interactive instructional videos and a novel Virtual Reality (VR) trainer for healthcare professionals and to evaluate the impact of this combination on learners' knowledge of critical airway events in children.

Recurrent Mutations in Cyclin D3 Confer Clinical Resistance to FLT3 Inhibitors in Acute Myeloid Leukemia.

Purpose: Biomarkers of response and resistance to FLT3 tyrosine kinase inhibitors (TKI) are still emerging, and optimal clinical combinations remain unclear. The purpose of this study is to identify co-occurring mutations that influence clinical response to the novel FLT3 inhibitor pexidartinib (PLX3397).

Experimental Design: We performed targeted sequencing of pretreatment blasts from 29 patients with internal tandem duplication (ITD) mutations treated on the phase I/II trial of pexidartinib in relapsed/refractory -ITD+ acute myeloid leukemia (AML).