SARS-CoV-2 EndoU-ribonuclease regulates RNA recombination and impacts viral fitness.

Coronaviruses (CoVs) maintain large RNA genomes that frequently undergoes mutations and recombination, contributing to their evolution and emergence. In this study, we find that SARS-CoV-2 has greater RNA recombination frequency than other human CoVs. In addition, coronavirus RNA recombination primarily occurs at uridine (U)-enriched RNA sequences.

Small-molecule disruption of androgen receptor-dependent chromatin clusters.

Sustained androgen receptor (AR) signaling during relapse is a central driver of metastatic castration-resistant prostate cancer (mCRPC). Current AR antagonists, such as enzalutamide, fail to provide long-term benefit for the mCRPC patients who have dramatic increases in AR expression. Here, we report AR antagonists with efficacy in AR-overexpressing models.

Transcriptional regulation of the alternative sex hormone-binding globulin promoter by KLF4.

In most mammals the major site of sex hormone-binding globulin (SHBG) synthesis is the liver wherefrom it is secreted into the bloodstream and is the primary determinant of sex steroid access to target tissues. The minor site of SHBG synthesis is the testis and in lower mammals testicular SHBG has long been known to be synthesized and secreted by Sertoli cells. However, human testicular SHBG is expressed in developing germ cells from an upstream alternative promoter (altP-SHBG).

Heterotopic Ossification and Platelet-Rich Plasma in Core Muscle Injuries: A Single-Institution Experience Over 6 Years.

Background: A 2015 study of platelet-rich plasma (PRP) for groin injuries in National Football League (NFL) players alerted the authors to the possibility that PRP is associated with heterotopic ossification (HO). The current study of athletes seen between 2014 and 2019 provides a more comprehensive analysis of that observation.

Purpose/hypothesis: This report describes the early results of groin surgery for athletes who had experienced failed PRP therapy performed by different practitioners and with an assortment of PRP techniques.

A cell-based assay for rapid assessment of ACE2 catalytic function.

Angiotensin-converting enzyme II (ACE2) is a monocarboxypeptidase expressed throughout multiple tissues and its catalysis of bioactive peptides regulates the renin-angiotensin system mediating blood pressure homeostasis. ACE2 is implicated in a variety of diseases, including obesity, diabetes, and cardiovascular diseases, and is the obligate entry receptor for SARS-CoV-2 infection. Disease-associated genetic variants of ACE2 are increasingly being identified but are poorly characterized.

Postoperative MR Imaging of the Pubic Symphysis and Athletic Pubalgia.

MR imaging evaluation can be valuable in patients with prior surgery for athletic pubalgia presenting with new, recurrent, or persistent groin pain. The clinical and interventional history as well as comparison with preoperative imaging is essential for imaging interpretation. Imagers should be aware of expected and unexpected postoperative findings.

Effects of heterogeneous SPS measures on agricultural growth: Evidence from China.

In order to explore the sustainable growth of Chinese agriculture, this paper assesses how the heterogeneous SPS measures affect China's growth margins and quality upgrading in the agricultural sector. We estimate improved gravity-model that exploit the cross-country differences in SPS measures over the period from 2000 to 2014. Our findings show that the heterogeneous SPS measures restrict the intensive margin and extensive margin, but significantly promote the product quality-even with no significant effect on price index.

Modelling the concentration of anti-SARS-CoV-2 immunoglobulin G in intravenous immunoglobulin product batches.

Background: Plasma-derived intravenous immunoglobulin (IVIg) products contain a dynamic spectrum of immunoglobulin (Ig) G reactivities reflective of the donor population from which they are derived. We sought to model the concentration of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG which could be expected in future plasma pool and final-product batches of CSL Behring's immunoglobulin product Privigen.

Study Design And Methods: Data was extracted from accessible databases, including the incidence of coronavirus disease 2019 and SARS-CoV-2 vaccination status, antibody titre in convalescent and vaccinated groups and antibody half-life.

Ultrasound-guided Procedures Allow Delay of Definitive Treatment for Core Muscle Injuries.

Introduction: Core muscle injuries (CMI) are common in every sport. To minimize lost playing time, providers apply various nonsurgical treatments, including platelet-rich plasma, corticosteroids, ultrasound (US)-guided percutaneous tenotomy, and prolotherapy. Limited data exist with regard to their effectiveness.

Multi-parametric analysis of 57 SYNGAP1 variants reveal impacts on GTPase signaling, localization, and protein stability.

SYNGAP1 is a neuronal Ras and Rap GTPase-activating protein with important roles in regulating excitatory synaptic plasticity. While many SYNGAP1 missense and nonsense mutations have been associated with intellectual disability, epilepsy, schizophrenia, and autism spectrum disorder (ASD), whether and how they contribute to individual disease phenotypes is often unknown. Here, we characterize 57 variants in seven assays that examine multiple aspects of SYNGAP1 function.

A Premalignant Cell-Based Model for Functionalization and Classification of Variants.

As sequencing becomes more economical, we are identifying sequence variations in the population faster than ever. For disease-associated genes, it is imperative that we differentiate a sequence variant as either benign or pathogenic, such that the appropriate therapeutic interventions or surveillance can be implemented. is a frequently mutated tumor suppressor that has been linked to the PTEN hamartoma tumor syndrome.

Multi-model functionalization of disease-associated PTEN missense mutations identifies multiple molecular mechanisms underlying protein dysfunction.

Functional variomics provides the foundation for personalized medicine by linking genetic variation to disease expression, outcome and treatment, yet its utility is dependent on appropriate assays to evaluate mutation impact on protein function. To fully assess the effects of 106 missense and nonsense variants of PTEN associated with autism spectrum disorder, somatic cancer and PTEN hamartoma syndrome (PHTS), we take a deep phenotypic profiling approach using 18 assays in 5 model systems spanning diverse cellular environments ranging from molecular function to neuronal morphogenesis and behavior. Variants inducing instability occur across the protein, resulting in partial-to-complete loss-of-function (LoF), which is well correlated across models.

The AFIP history of ocular leprosy.

Purpose: To investigate the Armed Forces Institute of Pathology (AFIP) experience with Ocular Leprosy.

Methods: The AFIP data banks were screened for cases with diagnosis of ocular leprosy. Files and slides stained with Hematoxylin-eosin and acid-fast staining were reviewed by the Division of Ocular Pathology and by the Infectious Diseases Pathology Branch.

Smartphone-based delivery of oropharyngeal exercises for treatment of snoring: a randomized controlled trial.

Purpose: Upper airway exercises for snoring treatment can be effective but difficult to administer and monitor. We hypothesized that a brief, relatively simple daily upper airway exercise regimen, administered by a smartphone application, would reduce snoring and encourage compliance.

Methods: Targeted vowel sounds causing tongue base movements were incorporated into a voice-controlled smartphone game application.

Subcutaneous Granulomatous Inflammation due to Basidiobolomycosis: Case Reports of 3 Patients in Buruli Ulcer Endemic Areas in Benin.

Background: Basidiobolomycosis is a rare subcutaneous mycosis, which can be mistaken for several other diseases, such as soft tissue tumors, lymphoma, or Buruli ulcer in the preulcerative stage. Microbiological confirmation by PCR for and culture yield the most specific diagnosis, yet they are not widely available in endemic areas and with varying sensitivity. A combination of histopathological findings, namely, granulomatous inflammation with giant cells, septate hyphal fragments, and the Splendore-Hoeppli phenomenon, can confirm basidiobolomycosis in patients presenting with painless, hard induration of soft tissue.

Core Muscle Injuries in Athletes.

Lower abdominal and groin injuries are among the most common causes of pain and lost playing time in sports. Perhaps the most important obstacle in understanding these injuries is the lack of consensus on nomenclature. There have been numerous advances in recent years in the understanding, prevention, diagnosis, and treatment of these injuries.

Acquired uterine arteriovenous fistula following dilatation and curettage: an uncommon cause of vaginal bleeding.

Dysfunctional uterine bleeding is a common presentation of women in the emergency department. We describe the case of a 33-year-old female who presented with intermittent spotting due to an acquired uterine AVF. The patient underwent a transvaginal pelvic ultrasound as well as a CT angiogram.

WHipple-ABACUS, a simple, validated risk score for 30-day mortality after pancreaticoduodenectomy developed using the ACS-NSQIP database.

Background: Pancreaticoduodenectomy needs simple, validated risk models to better identify 30-day mortality. The goal of this study is to develop a simple risk score to predict 30-day mortality after pancreaticoduodenectomy.

Methods: We reviewed cases of pancreaticoduodenectomy from 2005-2012 in the American College of Surgeons-National Surgical Quality Improvement Program databases.

Wearable telescopic contact lens.

We describe the design, fabrication, and testing of a 1.6 mm thick scleral contact lens providing both 1× and 2.8× magnified vision paths, intended for use as a switchable eye-borne telescopic low-vision aid.