AZD2693, a PNPLA3 antisense oligonucleotide, for the treatment of MASH in 148M homozygous participants: two randomized phase I trials.

Background & Aims: A common genetic variant (rs738409) encoding isoleucine to methionine at position 148 in the PNPLA3 protein is a determinant of hepatic steatosis, inflammation, fibrosis, cirrhosis, and liver-related mortality. AZD2693 is a liver-targeted antisense oligonucleotide against PNPLA3 mRNA. We evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics in single ascending dose (SAD) and multiple ascending dose (MAD) studies.

Evaluating the utility and challenges associated with "unknown" and fictional patients in the electronic medical record.

Electronic medical records (EMRs) allow for the creation of "fictional" and unknown patients within the EMR production environment. Surprisingly, there is sparse literature regarding the use cases for these patients or the challenges associated with their existence in the EMR. Here, we identified three classes of patients in regular use at our institution: true fictional patients with medical record numbers (MRNs) used to test EMR functions in the production environment, "confidential patients" used to store sensitive data, and "unknown" patients that are assigned temporary MRNs in emergency situations until additional information can be acquired.

Affordance norms for 2825 concrete nouns.

Objects are commonly described based on their relations to other objects (e.g., associations, semantic similarity, etc.

Tyrosine Kinase 2 Inhibition With Zasocitinib (TAK-279) in Psoriasis: A Randomized Clinical Trial.

Importance: New, effective, and well-tolerated oral therapies are needed for treating psoriasis. Zasocitinib, a highly selective allosteric tyrosine kinase 2 (TYK2) inhibitor, is a potential new oral treatment for this disease.

Objective: To assess the efficacy, safety, and tolerability of zasocitinib in patients with moderate to severe plaque psoriasis.

Multidisciplinary considerations for implementing Bayesian borrowing in basket trials.

Drug development has historically relied on phase I-III clinical trials including participants sharing the same disease. However, drug development has evolved as the discovery of mechanistic drivers of disease demonstrated that the same therapeutic target may provide benefits across different diseases. A basket trial condenses evaluation of one therapy among multiple related diseases into a single trial and presents an opportunity to borrow information across them rather than viewing each in isolation.

Tango-seq: overlaying transcriptomics on connectomics to identify neurons downstream of clock neurons.

Knowing how neural circuits change with neuronal plasticity and differ between individuals is important to fully understand behavior. Connectomes are typically assembled using electron microscopy, but this is low throughput and impractical for analyzing plasticity or mutations. Here, we modified the -Tango genetic circuit-tracing technique to identify neurons synaptically downstream of s-LNv clock neurons, which show 24hr plasticity rhythms.

Circadian clock neurons use activity-regulated gene expression for structural plasticity.

s-LNv circadian pacemaker neurons show dramatic structural plasticity, with their projections expanded at dawn and then retracted by dusk. This predictable plasticity makes s-LNvs ideal to study molecular mechanisms of plasticity. Although s-LNv plasticity is controlled by their molecular clock, changing s-LNv excitability also regulates plasticity.

The health care experience of adults with metabolic dysfunction-associated steatohepatitis and influence of PNPLA3: A qualitative study.

Background: Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive form of metabolic dysfunction-associated steatotic liver disease, for which there is limited information about patient experience, including the patient journey.

Methods: In this study, we conducted interviews with patients with MASH to qualitatively evaluate the patient journey and help elucidate the experiences of this patient population. We also investigated if the patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M variant (non-Hispanic) or being of Hispanic ethnicity may influence patient experiences because these 2 subgroups develop advanced liver disease more frequently than other patient groups.

Non-invasive assessment of hepatic steatosis by ultrasound-derived fat fraction in individuals at high-risk for metabolic dysfunction-associated steatotic liver disease.

Aims: Given the increasing number of individuals developing metabolic dysfunction-associated steatotic liver disease (MASLD) and the low rate of those with progressive liver disease, there is a pressing need to conceive affordable biomarkers to assess MASLD in general population settings. Herein, we aimed to investigate the performance of the ultrasound-derived fat fraction (UDFF) for hepatic steatosis in high-risk individuals.

Methods: A total of 302 Europeans with obesity, type 2 diabetes, or a clinical history of hepatic steatosis were included in the analyses.

A rapid and dynamic role for FMRP in the plasticity of adult neurons.

Fragile X syndrome (FXS) is a neuro-developmental disorder caused by silencing , which encodes the RNA-binding protein FMRP. Although is expressed in adult neurons, it has been challenging to separate acute from chronic effects of loss of in models of FXS. We have used the precision of genetics to test if acutely affects adult neuronal plasticity , focusing on the s-LNv circadian pacemaker neurons that show 24 hour rhythms in structural plasticity.

The greater impact of PNPLA3 polymorphism on liver-related events in Japanese non-alcoholic fatty liver disease patients: A multicentre cohort study.

Background & Aims: PNPLA3 rs738409 has been associated with an increased risk of liver-related events in patients with non-alcoholic fatty liver disease (NAFLD). In this study, we investigated the epidemiology of NAFLD and the impact of PNPLA3 on prognosis in Japan.

Methods: A longitudinal multicentre cohort study, the JAGUAR study, includes 1550 patients with biopsy-proven NAFLD in Japan.

Universal Urine Drug Screening with Rapid Confirmation upon Admission to Labor and Delivery.

Objective: This study aimed to describe our experience with universal urine drug screening (UDS) with rapid confirmation (RC) via liquid chromatography mass spectrometry (LC-MS) before infant's discharge, in efforts to increase detection of neonates at risk of neonatal opioid withdrawal syndrome (NOWS) while reducing patient burden related to false positive results.

Study Design: Two-phase retrospective study of all pregnant women admitted to our labor and delivery (L&D) unit before (phase 1, April 2018-March 2019) and after (phase 2, October 2019-September 2020) RC of UDS was initiated. Urine samples were obtained on admission and screened for drugs using an enzyme immunoassay with positive results reflexed to confirmation via LC-MS.

Blood-based Proteomic Signatures Associated With MEN1-related Duodenopancreatic Neuroendocrine Tumor Progression.

Purpose: Patients with multiple endocrine neoplasia type 1 (MEN1) are predisposed to develop duodenopancreatic neuroendocrine tumors (dpNETs), and metastatic dpNET is the primary cause of disease-related mortality. Presently, there is a paucity of prognostic factors that can reliably identify patients with MEN1-related dpNETS who are at high risk of distant metastasis. In the current study, we aimed to establish novel circulating molecular protein signatures associated with disease progression.

Urinary Tract Infections in Low Birth Weight Neonates.

Objective: Our objective was to evaluate the incidence of urinary tract infections (UTIs) in low birth weight (LBW) neonates and to evaluate the compliance of neonatal intensive care unit (NICU) providers in performing urine cultures as a part of late-onset sepsis (LOS) evaluations following an educational intervention.

Study Design: A retrospective chart review for all LBW infants undergoing LOS evaluations was performed. An educational intervention was conducted to encourage NICU providers to perform urine cultures in LOS evaluations.

Anatomic pathology quality assurance: Developing an LIS based tracking and documentation module for intradepartmental consultations.

Background: An electronic intradepartmental consultation system for anatomic pathology (AP) was conceived and developed in the laboratory information system (LIS) in 2019. Previously, all surgical pathology intradepartmental consultative activities were initiated and documented with paper forms which circulated with the pertinent microscopic slides and were eventually filed. In this study, we discuss the implementation and utilization of an electronic intradepartmental AP consultation system.

Metastatic Grade 3 Neuroendocrine Tumor in Multiple Endocrine Neoplasia Type 1 Expressing Somatostatin Receptors.

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) may occur in 30% to 90% of patients with multiple endocrine neoplasia type 1 (MEN1). However, only 1% of GEP-NETs are grade 3 (G3). Given the rarity of these aggressive tumors, treatment of advanced G3 GEP-NETs in MEN1 is based on the treatment guidelines for sporadic GEP-NETs.

Determination of FGF23 Levels for the Diagnosis of FGF23-Mediated Hypophosphatemia.

Fibroblast growth factor-23 (FGF23) measurement is a critical tool in the evaluation of patients with disordered phosphate homeostasis. Available laboratory reference ranges for blood FGF23 were developed using samples from normophosphatemic individuals. Reliance on such values can lead to misdiagnosis in patients with FGF23-mediated hypophosphatemia, such as X-linked hypophosphatemia (XLH) and tumor-induced osteomalacia (TIO), in whom pathology-driving FGF23 levels can be in the "normal range.

Family Conflict, Physical Symptoms, and Post Traumatic Stress among Sexual Minorities during the COVID Pandemic: A Moderated Mediation Model.

Sexual minorities experience health disparities compared to heterosexuals due to their stigmatized identies. The COVID- 19 pandemic has further exacerbated these disparities. Sexual minorities were surveyed about their experiences during the pandemic and asked about family conflict and minority stress as predictors of Post Traumatic Stress Symptoms (PTSS) and physical health symptoms, as well as psychological symptoms as a mediator of these relationships.

Contextualizing Breast Implant Removal Patterns with Google Trends: Big Data Applications in Surgical Demand.

Unlabelled: The demand for breast implant removal (BIR) has increased substantially in recent years. This study leveraged large datasets available through Google Trends to understand how changes in public perception could be influencing surgical demand, both geographically and temporally.

Methods: Using Google Trends, we extracted relative search volume for BIR-related search terms in the United States from 2006 to 2019.

Parathyroid Hormone Resistance and Autoantibodies to the PTH1 Receptor.

We describe two cases of acquired parathyroid hormone (PTH) resistance consequent to the development of serum PTH type 1 receptor (PTH1R) autoantibodies, which block PTH binding and signaling. Both cases were associated with other autoimmune manifestations, and one case was associated with atypical membranous glomerulonephritis. In vitro binding and signaling assays identified the presence of PTH1R-blocking IgG autoantibodies, which were not present in serum samples from patients with other renal or autoimmune disorders.

Clinical Competency Committees in Plastic Surgery Residency.

Background: Clinical competency committees (CCCs) are now an Accreditation Council on Graduate Medical Education (ACGME) requirement for plastic surgery training programs. They serve to monitor resident progress and make formal recommendations to program directors on promotion, remediation, and dismissal, based on resident progress toward the curricular milestones.

Methods: Here, we present an overview on building, conducting, and improving a CCC, reviewing the literature available regarding best practices regarding this novel assessment system, with attention to the particular requirements for plastic surgery training.

Validity of Secretin Stimulation Testing on Proton Pump Inhibitor Therapy for Diagnosis of Zollinger-Ellison Syndrome.

Introduction: Zollinger-Ellison syndrome (ZES) is characterized by gastrinoma-induced hypergastrinemia causing excessive gastric acid secretion. Secretin stimulation tests (SSTs) are required for diagnosis in the majority of patients. Two case reports suggest that proton pump inhibitors (PPIs) cause false SST results.