Administrative Aspects of Molecular Diagnostics-Oversight, Regulatory Approval Process, Clinical and Operational Workflows, and Payment Models.

This paper discusses the administrative aspects of molecular diagnostics in oncology, including US Food and Drug Administration (FDA) oversight, the regulatory approval process, clinical, and operational workflows, and payment models. Comprehensive molecular testing is important to deliver optimal oncology care and improve patient outcomes. Despite the potential benefits of testing, utilization remains low.

Evidence for an adult summer diapause in mountain pine beetle (Coleoptera: Curculionidae) that varies geographically and among haplogroups.

Identifying dormancy traits is important for predicting insect population success, particularly in a changing climate that could disrupt evolved traits. The mountain pine beetle (Dendroctonus ponderosae Hopkins) is native to North America, is responsible for millions of acres of tree mortality, and is expanding northward in Canada. Research has identified thermal traits important to epidemic-phase ecology that vary among populations.

Parental age effects and Rett syndrome.

Rett syndrome (RTT) is a progressive neurodevelopmental disorder, and pathogenic Methyl-CpG-binding Protein 2 (MECP2) variants are identified in >95% of individuals with typical RTT. Most of RTT-causing variants in MECP2 are de novo and usually on the paternally inherited X chromosome. While paternal age has been reported to be associated with increased risk of genetic disorders, it is unknown whether parental age contributes to the risk of the development of RTT.

Identification of western North Atlantic odontocete echolocation click types using machine learning and spatiotemporal correlates.

A combination of machine learning and expert analyst review was used to detect odontocete echolocation clicks, identify dominant click types, and classify clicks in 32 years of acoustic data collected at 11 autonomous monitoring sites in the western North Atlantic between 2016 and 2019. Previously-described click types for eight known odontocete species or genera were identified in this data set: Blainville's beaked whales (Mesoplodon densirostris), Cuvier's beaked whales (Ziphius cavirostris), Gervais' beaked whales (Mesoplodon europaeus), Sowerby's beaked whales (Mesoplodon bidens), and True's beaked whales (Mesoplodon mirus), Kogia spp., Risso's dolphin (Grampus griseus), and sperm whales (Physeter macrocephalus).

Neotropical cloud forests and páramo to contract and dry from declines in cloud immersion and frost.

Clouds persistently engulf many tropical mountains at elevations cool enough for clouds to form, creating isolated areas with frequent fog and mist. Under these isolated conditions, thousands of unique species have evolved in what are known as tropical montane cloud forests (TMCF) and páramo. Páramo comprises a set of alpine ecosystems that occur above TMCF from about 11° N to 9° S along the Americas continental divide.

The epilepsy phenotypic spectrum associated with a recurrent CUX2 variant.

Objective: Cut homeodomain transcription factor CUX2 plays an important role in dendrite branching, spine development, and synapse formation in layer II to III neurons of the cerebral cortex. We identify a recurrent de novo CUX2 p.Glu590Lys as a novel genetic cause for developmental and epileptic encephalopathy (DEE).

Fine-scale spatial climate variation and drought mediate the likelihood of reburning.

In many forested ecosystems, it is increasingly recognized that the probability of burning is substantially reduced within the footprint of previously burned areas. This self-limiting effect of wildland fire is considered a fundamental emergent property of ecosystems and is partly responsible for structuring landscape heterogeneity (i.e.

3-Methylcyclohex-2-en-1-one for area and individual tree protection against spruce beetle (Coleoptera: Curculionidae: Scolytinae) attack in the southern Rocky Mountains.

We tested 3-methylcyclohex-2-en-1-one (MCH) and an Acer kairomone blend (AKB) as repellent semiochemicals for area and single tree protection to prevent spruce beetle (Dendroctonus rufipennis Kirby) attacks at locations in Utah and New Mexico. In the area protection study, we compared host infestation rates of MCH applications at three densities (20, 40, and 80 g MCH ha-1) against a control treatment over 0.64 ha plots centered within ~1.

Sex-Positive Assessment and Treatment Among Female Trauma Survivors.

Sexuality and intimacy difficulties are often a part of the aftermath of sexual trauma. We argue that combining techniques from evidence-based, trauma-focused treatment with sex-positive techniques used in sex therapy can best help survivors reduce trauma-related symptoms and develop or regain comfort with their sexuality. In this article, we illustrate this approach by describing the case of a survivor of sexual assault, who completed 20 sessions of treatment that combined modules of trauma-focused therapies, Cognitive Processing Therapy (CPT), and Prolonged Exposure (PE) with sensate focus therapy, a technique often used in sex therapy.

Non-structural carbohydrates in woody plants compared among laboratories.

Non-structural carbohydrates (NSC) in plant tissue are frequently quantified to make inferences about plant responses to environmental conditions. Laboratories publishing estimates of NSC of woody plants use many different methods to evaluate NSC. We asked whether NSC estimates in the recent literature could be quantitatively compared among studies.

Age of diagnosis in Rett syndrome: patterns of recognition among diagnosticians and risk factors for late diagnosis.

Purpose: Diagnosis of Rett syndrome (RTT) is often delayed. We sought to determine the type of physician who typically makes the RTT diagnosis and to identify risk factors for delayed diagnosis.

Methods: A total of 1085 participants from the multicenter longitudinal RTT natural history study with classic and atypical RTT were recruited between 2006 and 2014.

Developmental delay in Rett syndrome: data from the natural history study.

Background: Early development appears normal in Rett syndrome (OMIM #312750) and may be more apparent than real. A major purpose of the Rett Syndrome (RTT) Natural History Study (NHS) was to examine achievement of developmental skills or abilities in classic and atypical RTT and assess phenotype-genotype relations in classic RTT.

Methods: Developmental skills in four realms, gross and fine motor, and receptive and expressive communication from initial enrollment and longitudinal assessments for up to 7 years, were assessed from 542 females meeting criteria for classic RTT and 96 females with atypical RTT divided into two groups: 50 with better and 46 with poorer functional scores.

A new gyrodactylid (Monogenea) parasitizing bay pipefish (Syngnathus leptorhynchus) from the Pacific Coast of North America.

Gyrodactylus leptorhynchi n. sp. (Monogenea) is described from bay pipefish ( Syngnathus leptorhynchus ) (Syngnathidae) in coastal waters of southern California and British Columbia, and from an outbreak of gyrodactylosis at the Cabrillo Marine Aquarium in California.

Hyaluronan turnover and hypoxic brown adipocytic differentiation are co-localized with ossification in calcified human aortic valves.

The calcification process in aortic stenosis has garnered considerable interest but only limited investigation into selected signaling pathways. This study investigated mechanisms related to hypoxia, hyaluronan homeostasis, brown adipocytic differentiation, and ossification within calcified valves. Surgically explanted calcified aortic valves (n=14) were immunostained for markers relevant to these mechanisms and evaluated in the center (NodCtr) and edge (NodEdge) of the calcified nodule (NodCtr), tissue directly surrounding nodule (NodSurr); center and tissue surrounding small "prenodules" (PreNod, PreNodSurr); and normal fibrosa layer (CollFibr).

Peg Restrained Intrinsic Muscle Evaluator (PRIME): development, reliability, and normative values of a device to quantify intrinsic hand muscle strength in children.

Purpose: There is a need for objective measures of pediatric intrinsic hand muscle strength as the current standard, the manual muscle test, lacks sensitivity to clinically important changes in muscle strength. We report the development, reliability, and normative values of the Peg Restrained Intrinsic Muscle Evaluator (PRIME), a device that quantifies intrinsic hand muscle strength.

Methods: Typically developing children, ages 4 to 16 years (n = 119), established normative values of intrinsic strength for thumb palmar abduction, thumb opposition, and index and small finger abduction.

Differential proteoglycan and hyaluronan distribution in calcified aortic valves.

Background: While the prevalence of calcified aortic valve disease continues to rise and no pharmacological treatments exist, little is known regarding the pathogenesis of the disease. Proteoglycans and the glycosaminoglycan hyaluronan are involved in calcification in arteriosclerosis and their characterization in calcified aortic valves may lend insight into the pathogenesis of the disease.

Methods: Fourteen calcified aortic valves removed during valve replacement surgery were immunohistochemically stained for the proteoglycans decorin, biglycan, and versican, as well as the glycosaminoglycan hyaluronan.

Delivery of plasmid DNA encoding bone morphogenetic protein-2 with a biodegradable branched polycationic polymer in a critical-size rat cranial defect model.

This study investigated the delivery of plasmid DNA (pDNA) encoding bone morphogenetic protein-2 in the form of polyplexes with a biodegradable branched triacrylate/amine polycationic polymer (TAPP) that were complexed with gelatin microparticles (GMPs) loaded within a porous tissue engineering scaffold. More specifically, the study investigated the interplay between TAPP degradation, gelatin degradation, pDNA release, and bone formation in a critical-size rat cranial defect model. The pDNA release kinetics in vitro were not affected by the crosslinking density of the GMPs but depended, rather, on the degradation rates of the TAPPs.

Regulated non-viral gene delivery from coaxial electrospun fiber mesh scaffolds.

In an effort to add to the versatility of three-dimensional scaffolds for tissue engineering applications, recent experimental designs are incorporating biological molecules such as plasmids and proteins within the scaffold structure. Such scaffolds act as reservoirs for the biological molecules of interest while regulating their release over various durations of time. Here, we describe the use of coaxial electrospinning as a means for the fabrication of fiber mesh scaffolds and the encapsulation and subsequent release of a non-viral gene delivery vector over a period of up to 60 days.

Significant changes in mitral valve leaflet matrix composition and turnover with tachycardia-induced cardiomyopathy.

Background: Dilated cardiomyopathy (DCM) involves significant remodeling of the left ventricular-mitral valve (MV) complex, but little is known regarding the remodeling of the mitral leaflets. The aim of this study was to assess changes in matrix composition and turnover in MV leaflets with DCM.

Methods And Results: Radiopaque markers were implanted in 24 sheep to delineate the MV; 10 sheep underwent tachycardia-induced cardiomyopathy (TIC), whereas 14 sheep remained as controls.

Repair of osteochondral defects with biodegradable hydrogel composites encapsulating marrow mesenchymal stem cells in a rabbit model.

This work investigated the delivery of marrow mesenchymal stem cells (MSCs), with or without the growth factor transforming growth factor-beta1 (TGF-beta1), from biodegradable hydrogel composites on the repair of osteochondral defects in a rabbit model. Three formulations of oligo(poly(ethylene glycol) fumarate) (OPF) hydrogel composites containing gelatin microparticles (GMPs) and MSCs were implanted in osteochondral defects, including (i) OPF/GMP hydrogel composites; (ii) OPF/GMP hydrogel composites encapsulating MSCs; and (iii) OPF hydrogel composites containing TGF-beta1-loaded GMPs and MSCs. At 12weeks, the quality of new tissue formed in chondral and subchondral regions of defects was evaluated based on subjective and quantitative histological analysis.

Dose effect of dual delivery of vascular endothelial growth factor and bone morphogenetic protein-2 on bone regeneration in a rat critical-size defect model.

The dose effect of dual delivery of vascular endothelial growth factor (VEGF) and bone morphogenetic protein-2 (BMP-2) on bone regeneration was investigated in a rat cranial critical-size defect (CSD). It was hypothesized that decreasing amounts of BMP-2 would result in a dose-dependent decrease in bone formation, and that this reduction in bone formation could be reversed by adding increasing amounts of VEGF. In vitro release kinetics of VEGF or BMP-2 were examined over 28 days.

Fabrication of nonwoven coaxial fiber meshes by electrospinning.

There is a great need for biodegradable polymer scaffolds that can regulate the delivery of bioactive factors such as drugs, plasmids, and proteins. Coaxial electrospinning is a novel technique that is currently being explored to create such polymer scaffolds by embedding within them aqueous-based biological molecules. In this study, we evaluated the influence of various processing parameters such as sheath polymer concentration, core polymer concentration and molecular weight, and salt ions within the core polymer on coaxial fiber morphology.

Donor age and cell passage affects differentiation potential of murine bone marrow-derived stem cells.

Background: Bone marrow-derived mesenchymal stem cells (BMSCs) are a widely researched adult stem cell population capable of differentiation into various lineages. Because many promising applications of tissue engineering require cell expansion following harvest and involve the treatment of diseases and conditions found in an aging population, the effect of donor age and ex vivo handling must be understood in order to develop clinical techniques and therapeutics based on these cells. Furthermore, there currently exists little understanding as to how these two factors may be influenced by one another.

Microcomputed tomography characterization of neovascularization in bone tissue engineering applications.

Vasculogenesis and angiogenesis have been studied for decades using numerous in vitro and in vivo systems, fulfilling the need to elucidate the mechanisms involved in these processes and to test potential therapeutic agents that inhibit or promote neovascularization. Bone tissue engineering in particular has benefited from the application of proangiogenic strategies, considering the need for an adequate vascular supply during healing and the challenges associated with the vascularization of scaffolds implanted in vivo. Conventional methods of assessing the in vivo angiogenic response to tissue-engineered constructs tend to rely on a two-dimensional assessment of microvessel density within representative histological sections without elaboration of the true vascular tree.

Development and characterization of a rabbit alveolar bone nonhealing defect model.

The aim of this study was to develop an easily accessible and reproducible, nonhealing alveolar bone defect in the rabbit mandible. Twenty-four adult male New Zealand white rabbits underwent unilateral mandibular defect surgery. Two types of defect in the premolar/molar region were compared: (1) a 10-mm "full thickness" cylindrical defect removing both cortical plates and the intervening trabecular bone and tooth roots; (2) a 10-mm "partial thickness" cylindrical defect removing only the lateral bony cortex, trabecular bone, and tooth roots.