Actionable Structural Variant Detection via RNA-NGS and DNA-NGS in Patients With Advanced Non-Small Cell Lung Cancer.

Importance: The National Comprehensive Cancer Network (NCCN) guidelines for non-small cell lung cancer suggest that RNA next-generation sequencing (NGS) may improve the detection of fusions and splicing variants compared with DNA-NGS alone. However, there is limited adoption of RNA-NGS in routine oncology clinical care today.

Objective: To analyze clinical evidence from a diverse cohort of patients with advanced lung adenocarcinoma and compare the detection of NCCN-recommended actionable structural variants (aSVs; fusions and splicing variants) via concurrent DNA and RNA-NGS vs DNA-NGS alone.

Long-Term Temporal Trends of Real-World Healthcare Costs Associated with Nivolumab Plus Ipilimumab and Pembrolizumab Plus Axitinib as First-Line Treatment for Advanced or Metastatic Renal Cell Carcinoma.

Introduction: Nivolumab plus ipilimumab (NIVO + IPI) and pembrolizumab plus axitinib (PEM + AXI) are first-line (1L) treatments for advanced or metastatic renal cell carcinoma (aRCC), although the long-term trends in their associated real-world healthcare costs are not well defined. We compared the real-world healthcare costs of patients with aRCC who received 1L NIVO + IPI or PEM + AXI over 24 months.

Methods: Adults with RCC and secondary malignancy who initiated 1L NIVO + IPI or PEM + AXI were identified in the Merative MarketScan Commercial and Medicare Supplemental Databases (01/01/2004 to 09/30/2021).

Real-world use and clinical impact of an electronic patient-reported outcome tool in patients with solid tumors treated with immuno-oncology therapy.

Background: Utilization of electronic patient-reported outcome (ePRO) tools to monitor symptoms in patients undergoing cancer treatment has shown clinical benefits. Tennessee Oncology (TO) implemented an ePRO platform in 2019, allowing patients to report their health status online. We conducted a real-world, multicenter, observational, non-interventional cohort study to evaluate utilization of this platform in adults with solid tumors who initiated immuno-oncology (IO) therapy as monotherapy or in combination at TO clinics.

Depuration of ingested C-labelled polystyrene nanospheres in the Atlantic scallop (Placopecten magellanicus).

The presence of nano-plastics in marine bivalves is well established and may represent a risk to human consumption. The main objective of our work was to study the detailed tissue distribution of 14C-radiolabelled polystyrene nanospheres (PSNP; 325 nm) following their ingestion by commercial-size Atlantic scallop (Placopecten magellanicus) using whole-body autoradiography to assess their translocation, bioaccumulation and depuration mechanisms over a short-term exposure (6h) and a long-term exposure (2 weeks). Results showed that the nanospheres (PSNP) did not accumulate in scallop tissues despite the fact they were ingested and transported all along the digestive system.

Assessing the utility of molecular diagnostic classification for cancers of unknown primary.

Background: Roughly 5% of metastatic cancers present with uncertain origin, for which molecular classification could influence subsequent management; however, prior studies of molecular diagnostic classifiers have reported mixed results with regard to clinical impact. In this retrospective study, we evaluated the utility of a novel molecular diagnostic classifier by assessing theoretical changes in treatment and additional testing recommendations from oncologists before and after the review of classifier predictions.

Methods: We retrospectively analyzed de-identified records from 289 patients with a consensus diagnosis of cancer of uncertain/unknown primary (CUP).

Brain structural differences in children with fetal alcohol spectrum disorder and its subtypes.

Introduction: The teratogenic effects of prenatal alcohol exposure (PAE) have been examined in animal models and humans. The current study extends the prior literature by quantifying differences in brain structure for individuals with a fetal alcohol spectrum disorder (FASD) compared to typically developing controls, as well as examining FASD subtypes. We hypothesized the FASD group would reveal smaller brain volume, reduced cortical thickness, and reduced surface area compared to controls, with the partial fetal alcohol syndrome (pFAS)/fetal alcohol syndrome (FAS) subtypes showing the largest effects and the PAE/alcohol-related neurodevelopmental disorder (ARND) subtype revealing intermediate effects.

Carcinoma of unknown primary (CUP): an update for histopathologists.

Carcinoma of unknown primary (CUP) is a heterogeneous group of metastatic cancers in which the site of origin is not identifiable. These carcinomas have a poor outcome due to their late presentation with metastatic disease, difficulty in identifying the origin and delay in treatment. The aim of the pathologist is to broadly classify and subtype the cancer and, where possible, to confirm the likely primary site as this information best predicts patient outcome and guides treatment.

Validation of a Transcriptome-Based Assay for Classifying Cancers of Unknown Primary Origin.

Introduction: Cancers assume a variety of distinct histologies, and may originate from a myriad of sites including solid organs, hematopoietic cells, and connective tissue. Clinical decision-making based on consensus guidelines such as the National Comprehensive Cancer Network (NCCN) is often predicated on a specific histologic and anatomic diagnosis, supported by clinical features and pathologist interpretation of morphology and immunohistochemical (IHC) staining patterns. However, in patients with nonspecific morphologic and IHC findings-in addition to ambiguous clinical presentations such as recurrence versus new primary-a definitive diagnosis may not be possible, resulting in the patient being categorized as having a cancer of unknown primary (CUP).

Ultra-Early Cranioplasty versus Conventional Cranioplasty: A Retrospective Cohort Study at an Academic Level 1 Trauma Center.

The goal of this study was to ascertain the efficacy, safety, and comparability of ultra-early cranioplasty (CP; defined here as <30 days from the original craniectomy) to conventional cranioplasty (defined here as >30 days from the original craniectomy). A retrospective review of CPs performed at our institution between January 2016 and July 2020 was performed. Craniectomies initially performed at other institutions were excluded.

Impact of clinical pathways on treatment patterns and outcomes for patients with non-small-cell lung cancer: real-world evidence from a community oncology practice.

The evolving treatment landscape for non-small-cell lung cancer (NSCLC) and complexities of regulations and reimbursement present challenges to community oncologists. Clinical pathways are tools to optimize care, but information on their value in the real world is limited. This retrospective study assessed treatment patterns and clinical outcomes in patients with stage I-III NSCLC pre- and post-pathways implementation at Tennessee Oncology, a large, community-based oncology practice in the USA.

Sport-Related Structural Brain Injury and Return to Play: Systematic Review and Expert Insight.

Background: Sport-related structural brain injury (SRSBI) is intracranial pathology incurred during sport. Management mirrors that of non-sport-related brain injury. An empirical vacuum exists regarding return to play (RTP) following SRSBI.

Self-regulation and emotional reactivity in infants with prenatal exposure to opioids and alcohol.

Background: Infants with prenatal substance exposure are at increased risk for developmental problems, with self-regulatory challenges being some of the most pronounced. The current study aimed to investigate the extent to which prenatal substance exposure (alcohol, opioids) impacts infant self-regulation during a relational stressor and the association between self-regulation and infant affect.

Methods: Participants were 100 mother-child dyads recruited prenatally (Mean = 23.

Soluble terminal complement activation fragment sC5b-9: a new serum biomarker for traumatic brain injury?

Purpose: Terminal complement pathway activation after traumatic brain injury (TBI) leads to formation of the membrane attack complex (MAC/C5b-9) which induces neuronal cell death and host-mediated secondary brain injury. Serum levels of soluble MAC (sC5b-9) have not been previously determined in patients with isolated TBI.

Methods: A prospective observational cohort study was performed during a 5-year time-period on adult patients with isolated TBI admitted to an academic level I trauma center in the United States.

Clinical validity of expanded carrier screening: Evaluating the gene-disease relationship in more than 200 conditions.

Clinical guidelines consider expanded carrier screening (ECS) to be an acceptable method of carrier screening. However, broader guideline support and payer adoption require evidence for associations between the genes on ECS panels and the conditions for which they aim to identify carriers. We applied a standardized framework for evaluation of gene-disease association to assess the clinical validity of conditions screened by ECS panels.

Acute stress impairs children's sustained attention with increased vulnerability for children of mothers reporting higher parenting stress.

Despite evidence that acute stress impairs attention in adults, there has been minimal research in children. Here, the effects of acute stress on Go/No-go performance were examined in young children (M age = 5.41 years).

Androgen Receptor-Mediated Regulation of Intracellular Calcium in Human Airway Smooth Muscle Cells.

Background/aims: With the prevalence of asthma being greater in women, detrimental effects of female sex steroids have been explored, but potential protective effects of androgens are not established. Airway smooth muscle (ASM) is a key cell type in contractility and remodelling of asthma. There are no data on expression and functionality of androgen receptor (AR) in human ASM cells.

Correction: Sequencing as a first-line methodology for cystic fibrosis carrier screening.

The original version of this Article contained an error in Figure 3. Specifically, the result "3 (67%) TOP" should read "2 (67%) TOP." This has now been corrected in both the PDF and HTML versions of the Article.

The dynamic conformational landscape of the protein methyltransferase SETD8.

Elucidating the conformational heterogeneity of proteins is essential for understanding protein function and developing exogenous ligands. With the rapid development of experimental and computational methods, it is of great interest to integrate these approaches to illuminate the conformational landscapes of target proteins. SETD8 is a protein lysine methyltransferase (PKMT), which functions in vivo via the methylation of histone and nonhistone targets.

Sequencing as a first-line methodology for cystic fibrosis carrier screening.

Purpose: Medical society guidelines recommend offering genotyping-based cystic fibrosis (CF) carrier screening to pregnant women or women considering pregnancy. We assessed the performance of sequencing-based CF screening relative to genotyping, in terms of analytical validity, clinical validity, clinical impact, and clinical utility.

Methods: Analytical validity was assessed using orthogonal confirmation and reference samples.

A Preliminary Study Investigating Maternal Neurocognitive Mechanisms Underlying a Child-Supportive Parenting Intervention.

Although interventions that promote child-supportive parenting for children have been shown to positively impact caregiving behaviors as well as child behavioral and neurobiological functioning, less is known about which aspects of maternal brain functioning are affected by such interventions. In the present study, we conducted a preliminary evaluation of the impact of the Filming Interactions to Nurture Development (FIND) video coaching program on mothers with at least one child age four or younger. We employed a waitlist control design with pre-post data.

Clinical impact and cost-effectiveness of a 176-condition expanded carrier screen.

Purpose: Carrier screening identifies couples at high risk for conceiving offspring affected with serious heritable conditions. Minimal guidelines recommend offering testing for cystic fibrosis and spinal muscular atrophy, but expanded carrier screening (ECS) assesses hundreds of conditions simultaneously. Although medical societies consider ECS an acceptable practice, the health economics of ECS remain incompletely characterized.

Quantifying Configuration-Sampling Error in Langevin Simulations of Complex Molecular Systems.

While Langevin integrators are popular in the study of equilibrium properties of complex systems, it is challenging to estimate the timestep-induced discretization error: the degree to which the sampled phase-space or configuration-space probability density departs from the desired target density due to the use of a finite integration timestep. Sivak et al., introduced a convenient approach to approximating a natural measure of error between the sampled density and the target equilibrium density, the Kullback-Leibler (KL) divergence, in , but did not specifically address the issue of , which are much more commonly of interest in molecular simulations.

Escaping Atom Types in Force Fields Using Direct Chemical Perception.

Traditional approaches to specifying a molecular mechanics force field encode all the information needed to assign force field parameters to a given molecule into a discrete set of atom types. This is equivalent to a representation consisting of a molecular graph comprising a set of vertices, which represent atoms labeled by atom type, and unlabeled edges, which represent chemical bonds. Bond stretch, angle bend, and dihedral parameters are then assigned by looking up bonded pairs, triplets, and quartets of atom types in parameter tables to assign valence terms and using the atom types themselves to assign nonbonded parameters.