Association of Race and Ethnicity With Medication Use for Pediatric Lupus in the Childhood Arthritis and Rheumatology Research Alliance Registry.

Objective: Black and Hispanic children with pediatric lupus (pSLE) have higher morbidity and mortality than non-Hispanic White children. The extent to which differences in outcomes are due to treatment disparities, including medication use, is unknown. We aimed to determine whether medication use in pSLE is associated with race and ethnicity in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry.

Mosaicism in Tumor Suppressor Gene Syndromes: Prevalence, Diagnostic Strategies, and Transmission Risk.

A mosaic state arises when pathogenic variants are acquired in certain cell lineages during postzygotic development, and mosaic individuals may present with a generalized or localized phenotype. Here, we review the current state of knowledge regarding mosaicism for eight common tumor suppressor genes-, , , , , , , and -and their related genetic syndromes/entities. We compare and discuss approaches for comprehensive diagnostic genetic testing, the spectrum of variant allele frequency, and disease severity.

Association of Time to Clinical Remission With Sustained Resolution in Children With New-Onset Infantile Spasms.

Background And Objectives: Standard therapies (adrenocorticotropic hormone [ACTH], oral steroids, or vigabatrin) fail to control infantile spasms in almost half of children. Early identification of nonresponders could enable rapid initiation of sequential therapy. We aimed to determine the time to clinical remission after appropriate infantile spasms treatment initiation and identify predictors of the time to infantile spasms treatment response.

Self-assembling short immunostimulatory duplex RNAs with broad-spectrum antiviral activity.

The current coronavirus disease 2019 (COVID-19) pandemic highlights the need for broad-spectrum antiviral therapeutics. Here we describe a new class of self-assembling immunostimulatory short duplex RNAs that potently induce production of type I and type III interferon (IFN-I and IFN-III). These RNAs require a minimum of 20 base pairs, lack any sequence or structural characteristics of known immunostimulatory RNAs, and instead require a unique sequence motif (sense strand, 5'-C; antisense strand, 3'-GGG) that mediates end-to-end dimer self-assembly.

Development of a PET radioligand for α2δ-1 subunit of calcium channels for imaging neuropathic pain.

Neuropathic pain affects 7-10% of the adult population. Being able to accurately monitor biological changes underlying neuropathic pain will improve our understanding of neuropathic pain mechanisms and facilitate the development of novel therapeutics. Positron emission tomography (PET) is a noninvasive molecular imaging technique that can provide quantitative information of biochemical changes at the whole-body level by using radiolabeled ligands.

Managing Female Athlete Health: Auditing the Representation of Female versus Male Participants among Research in Supplements to Manage Diagnosed Micronutrient Issues.

Micronutrient deficiencies and sub-optimal intakes among female athletes are a concern and are commonly prevented or treated with medical supplements. However, it is unclear how well women have been considered in the research underpinning current supplementation practices. We conducted an audit of the literature supporting the use of calcium, iron, and vitamin D.

Immune dysregulation caused by homozygous mutations in CBLB.

CBL-B is an E3 ubiquitin ligase that ubiquitinates proteins downstream of immune receptors to downregulate positive signaling cascades. Distinct homozygous mutations in CBLB were identified in 3 unrelated children with early-onset autoimmunity, one of whom also had chronic urticaria. Patient T cells exhibited hyperproliferation in response to anti-CD3 cross-linking.

The ClinGen Brain Malformation Variant Curation Expert Panel: Rules for somatic variants in AKT3, MTOR, PIK3CA, and PIK3R2.

Purpose: Postzygotic (somatic) variants in the mTOR pathway genes cause a spectrum of distinct developmental abnormalities. Accurate classification of somatic variants in this group of disorders is crucial for affected individuals and their families.

Methods: The ClinGen Brain Malformation Variant Curation Expert Panel was formed to curate somatic variants associated with developmental brain malformations.

Videofluoroscopy Versus Nasopharyngoscopy of Lateral Pharyngeal Wall Movement for Assessment of Velopharyngeal Insufficiency.

Background: Competent speech requires closure of the velopharyngeal sphincter by dynamic apposition of the velum and posterior and lateral pharyngeal walls. An accurate estimation of lateral pharyngeal wall motion is an important determinant in the planning and the outcome of any operation to correct velopharyngeal insufficiency (VPI). The purpose was to compare the assessment of lateral pharyngeal wall movement by videofluoroscopy (VP) versus nasopharyngoscopy (NP).

Light links neonatal neurons for learning.

The newborn mouse's retina senses light even before the eye opens, informing the developing brain of the visual world. Without this information, the brain forms fewer connections and the adult mouse learns sluggishly.

Heterozygous variants in MYH10 associated with neurodevelopmental disorders and congenital anomalies with evidence for primary cilia-dependent defects in Hedgehog signaling.

Purpose: Nonmuscle myosin II complexes are master regulators of actin dynamics that play essential roles during embryogenesis with vertebrates possessing 3 nonmuscle myosin II heavy chain genes, MYH9, MYH10, and MYH14. As opposed to MYH9 and MYH14, no recognizable disorder has been associated with MYH10. We sought to define the clinical characteristics and molecular mechanism of a novel autosomal dominant disorder related to MYH10.

The Impact of Acute Calcium Intake on Bone Turnover Markers during a Training Day in Elite Male Rowers.

Introduction: Although an acute exercise session typically increases bone turnover markers (BTM), the impact of subsequent sessions and the interaction with preexercise calcium intake remain unclear despite the application to the "real-life" training of many competitive athletes.

Methods: Using a randomized crossover design, elite male rowers ( n = 16) completed two trials, a week apart, consisting of two 90-min rowing ergometer sessions (EX1, EX2) separated by 150 min. Before each trial, participants consumed a high (CAL; ~1000 mg) or isocaloric low (CON; <10 mg) calcium meal.

Training the eye, virtually: adapting an art in medicine curriculum for on-line learning.

Unlabelled: Training the Eye: Improving the Art of Physical Diagnosis is an elective fine art-based medical humanities course at Harvard Medical School held at the Museum of Fine Arts, Boston that aims to improve skills of observation. Due to COVID-19, this curriculum was converted from in-person to a virtual format for the first time in 2020. Students enrolled in the course prior to the pandemic and completed one session in person before transitioning unexpectedly to nine remote sessions through Zoom.

The Endangered State of Medicare Reimbursement for Cardiothoracic Surgery: A Call to Action.

Reimbursement for cardiothoracic surgery continues to be threatened with enormous financial cuts ranging from 5% to 10% in recent years. In this policy perspective, we describe the history of reimbursement for cardiothoracic surgery, highlight areas in need of urgent reform, propose possible solutions that Congress and the Executive Branch may enact, and call cardiothoracic surgeons to action on this critical issue. Meaningful engagement of members of The Society of Thoracic Surgeons with their elected representatives is the only way to prevent these cuts.

Human CIDEC transgene improves lipid metabolism and protects against high-fat diet-induced glucose intolerance in mice.

Cell death-inducing DNA fragmentation factor-like effector C (CIDEC) expression in adipose tissue positively correlates with insulin sensitivity in obese humans. Further, E186X, a single-nucleotide CIDEC variant is associated with lipodystrophy, hypertriglyceridemia, and insulin resistance. To establish the unknown mechanistic link between CIDEC and maintenance of systemic glucose homeostasis, we generated transgenic mouse models expressing CIDEC (Ad-CIDECtg) and CIDEC E186X variant (Ad-CIDECmut) transgene specifically in the adipose tissue.

PIKfyve-specific inhibitors restrict replication of multiple coronaviruses in vitro but not in a murine model of COVID-19.

The ongoing COVID-19 pandemic has claimed more than 6 million lives and continues to test the world economy and healthcare systems. To combat this pandemic, the biological research community has shifted efforts to the development of medical countermeasures, including vaccines and therapeutics. However, to date, the only small molecules approved for the treatment of COVID-19 in the United States are the nucleoside analogue Remdesivir and the protease inhibitor Paxlovid, though multiple compounds have received Emergency Use Authorization and many more are currently being tested in human efficacy trials.

Exploring Factors Associated with Decisions about Feminizing Genitoplasty in Differences of Sex Development.

Study Objective: Infants with genital development considered atypical for assigned female sex may undergo feminizing genitoplasty (clitoroplasty and/or vaginoplasty) in early life. We sought to identify factors associated with parent/caregiver decisions regarding genitoplasty for their children with genital virilization.

Design: Longitudinal, observational study SETTING: Twelve pediatric centers in the United States with multidisciplinary differences/disorders of sex development clinics, 2015-2020 PARTICIPANTS: Children under 2 years old with genital appearance atypical for female sex of rearing and their parents/caregivers INTERVENTIONS/OUTCOME MEASURES: Data on the child's diagnosis and anatomic characteristics before surgery were extracted from the medical record.

Trends in pelvic pain symptoms over 2 years of follow-up among adolescents and young adults with and without endometriosis.

We described trends in pelvic pain characteristics over 2 years of follow-up among adolescents and adults with and without endometriosis participating in the longitudinal observational cohort of the Women's Health Study: From Adolescence to Adulthood, using data reported at baseline and at years 1 and 2 of follow-up. Participants completed a questionnaire at baseline (between November 2012 and May 2019) and annually thereafter that included validated measures of severity, frequency, and life interference of dysmenorrhea, acyclic pelvic pain, and dyspareunia. Our study population included 620 participants with surgically confirmed endometriosis (rASRM stage I/II = 95%) and 671 community-based and hospital-based controls, with median age = 19 and 24 years, respectively.

Hierarchical Annotation for Building A Suite of Clinical Natural Language Processing Tasks: Progress Note Understanding.

Applying methods in natural language processing on electronic health records (EHR) data is a growing field. Existing corpus and annotation focus on modeling textual features and relation prediction. However, there is a paucity of annotated corpus built to model clinical diagnostic thinking, a process involving text understanding, domain knowledge abstraction and reasoning.

Cytotoxic T Lymphocyte Antigen 4 Haploinsufficiency Presenting As Refractory Celiac-Like Disease: Case Report.

Primary immunodeficiency may present with treatment-refractory enteropathy. We present two patients with celiac/celiac-like disease diagnosed in early childhood and refractory to the gluten-free diet. One patient had features of multi-system autoimmunity, whereas the other had celiac-like disease as an isolated clinical finding.

Differences in clinical presentation, severity, and treatment of COVID-19 among individuals with Down syndrome from India and high-income countries: Data from the Trisomy 21 Research Society survey.

Background: People with Down syndrome (DS) are one of the highest risk groups for mortality associated with COVID-19, but outcomes may differ across countries due to different co-morbidity profiles, exposures, and societal practices, which could have implications for disease management. This study is designed to identify differences in clinical presentation, severity, and treatment of COVID-19 between India and several high-income countries (HICs).

Methods: We used data from an international survey to examine the differences in disease manifestation and management for COVID-19 patients with DS from India vs HIC.

Heterotopic Hepatic Tissue in the Placenta: A Case Report.

Heterotopic hepatic tissue in placenta or umbilical cord is rare. The exact mechanism by which this heterotopia occurs has not been fully understood but is thought to be related to yolk sac primordia. To date, a handful of such cases have been reported.

Learning the Regularization in DCE-MR Image Reconstruction for Functional Imaging of Kidneys.

Kidney DCE-MRI aims at both qualitative assessment of kidney anatomy and quantitative assessment of kidney function by estimating the tracer kinetic (TK) model parameters. Accurate estimation of TK model parameters requires an accurate measurement of the arterial input function (AIF) with high temporal resolution. Accelerated imaging is used to achieve high temporal resolution, which yields under-sampling artifacts in the reconstructed images.