Autism and Access to Care During the COVID-19 Crisis.

Case: Brian is a 6-year-old boy who was diagnosed with autism spectrum disorder (ASD) and global developmental delay at age 2. He has no other health conditions of note. Brian lives with his parents and an older brother, who also has ASD, in a rural area 2 hours from the center where he was diagnosed.

Nanosilk Increases the Strength of Diabetic Skin and Delivers CNP-miR146a to Improve Wound Healing.

Diabetes mellitus is a metabolic disorder associated with properties and an increased risk of chronic wounds due to sustained pro-inflammatory response. We have previously of radical scavenging cerium oxide nanoparticles (CNP) conjugated to the anti-inflammatory microRNA (miR)-146a, termed CNP-miR146a, improves diabetic wound healing by synergistically lowering oxidative stress and inflammation, and we sought to evaluate this treatment in a topical application. Silk fibroin is a biocompatible polymer that can be fabricated into nanostructures, termed nanosilk.

i-CONTENT tool for assessing therapeutic quality of exercise programs employed in randomised clinical trials.

Objective: When appraising the quality of randomised clinical trial (RCTs) on the merits of exercise therapy, we typically limit our assessment to the quality of the methods. However, heterogeneity across studies can also be caused by differences in the quality of the exercise interventions (ie, 'the potential effectiveness of a specific intervention given the potential target group of patients')-a challenging concept to assess. We propose an internationally developed, consensus-based tool that aims to assess the quality of exercise therapy programmes studied in RCTs: the international Consensus on Therapeutic Exercise aNd Training (i-CONTENT) tool.

Secretory Mucin 5AC Promotes Neoplastic Progression by Augmenting KLF4-Mediated Pancreatic Cancer Cell Stemness.

Secreted mucin 5AC (MUC5AC) is the most abundantly overexpressed member of the mucin family during early pancreatic intraepithelial neoplasia stage I (PanIN-I) of pancreatic cancer. To comprehend the contribution of Muc5ac in pancreatic cancer pathology, we genetically ablated it in an autochthonous murine model (KrasG12D; Pdx-1cre, KC), which mirrors the early stages of pancreatic cancer development. Neoplastic onset and the PanIN lesion progression were significantly delayed in Muc5ac knockout (KrasG12D; Pdx-1 cre; Muc5ac-/-, KCM) animals with a 50% reduction in PanIN-2 and 70% reduction in PanIN-3 lesions compared with KC at 50 weeks of age.

Practical Challenges and Considerations for Early Introduction of Potential Food Allergens for Prevention of Food Allergy.

Recent randomized controlled trials aimed at the prevention of food allergy have led to sweeping changes in food allergy prevention guidelines. Emphasis is now on the introduction of potential food allergens, particularly peanut and egg, rather than avoidance. Although guidelines recommend against delaying the introduction of other potential allergens, there remains little or no evidence of the benefit of their early introduction.

Human macrophages engineered to secrete a bispecific T cell engager support antigen-dependent T cell responses to glioblastoma.

Background: Targeted and effective treatment options are needed for solid tumors, including glioblastoma (GBM), where survival rates with standard treatments are typically less than 2 years from diagnosis. Solid tumors pose many barriers to immunotherapies, including therapy half-life and persistence, tumor penetrance, and targeting. Therapeutics delivered systemically may not traffic to the tumor site.

Special Issue: Frontiers in RNA Structure.

The frontiers of our knowledge about RNA structure are rapidly moving [...

Disruption of Zika Virus xrRNA1-Dependent sfRNA1 Production Results in Tissue-Specific Attenuated Viral Replication.

The Zika virus (ZIKV), like other flaviviruses, produces several species of sub-genomic RNAs (sfRNAs) during infection, corresponding to noncoding RNA fragments of different lengths that result from the exonuclease degradation of the viral 3' untranslated region (UTR). Over the course of infection, these sfRNAs accumulate in the cell as a result of an incomplete viral genome degradation of the 3' UTR by the host 5' to 3' exoribonuclease, Xrn1. The halting of Xrn1 in the 3' UTR is due to two RNA pseudoknot structures in the 3' UTR, termed exoribonuclease-resistant RNA1 and 2 (xrRNA1&2).

Maternal Prenatal Depression in Pregnancies With Female and Male Fetuses and Developmental Associations With C-reactive Protein and Cortisol.

Background: Prenatal depression has lasting effects on development in offspring, including later mental illness risk. Maternal responses to depression include inflammation and hypothalamic-pituitary-adrenal axis stimulation. Effects on development of cerebral inhibitory neurocircuits may differ for female and male fetuses.

Multisystem comorbidities in classic Rett syndrome: a scoping review.

Background: Rett syndrome (RTT) is a severe, progressive neurodevelopmental disorder with multisystem comorbidities that evolve across a patient's lifespan requiring attentive coordination of subspecialty care by primary care providers. A comprehensive, up-to-date synthesis of medical comorbidities in RTT would aid care coordination and anticipatory guidance efforts by healthcare providers. Our objective was to review and summarise published evidence regarding prevalence of RTT medical comorbidities across all relevant organ systems.

Structural diversity and phylogenetic distribution of valyl tRNA-like structures in viruses.

Viruses commonly use specifically folded RNA elements that interact with both host and viral proteins to perform functions important for diverse viral processes. Examples are found at the 3' termini of certain positive-sense ssRNA virus genomes where they partially mimic tRNAs, including being aminoacylated by host cell enzymes. Valine-accepting tRNA-like structures (TLS) are an example that share some clear homology with canonical tRNAs but have several important structural differences.

Different tertiary interactions create the same important 3D features in a distinct flavivirus xrRNA.

During infection by a flavivirus (FV), cells accumulate noncoding subgenomic flavivirus RNAs (sfRNAs) that interfere with several antiviral pathways. These sfRNAs are formed by structured RNA elements in the 3' untranslated region (UTR) of the viral genomic RNA, which block the progression of host cell exoribonucleases that have targeted the viral RNA. Previous work on these exoribonuclease-resistant RNAs (xrRNAs) from mosquito-borne FVs revealed a specific three-dimensional fold with a unique topology in which a ring-like structure protectively encircles the 5' end of the xrRNA.

A New Subclass of Exoribonuclease-Resistant RNA Found in Multiple Genera of .

Viruses have developed innovative strategies to exploit the cellular machinery and overcome the antiviral defenses of the host, often using specifically structured RNA elements. Examples are found in the genus (in the family ), where during flaviviral infection, pathogenic subgenomic flaviviral RNAs (sfRNAs) accumulate in the cell. These sfRNAs are formed when a host cell 5' to 3' exoribonuclease degrades the viral genomic RNA but is blocked by an exoribonuclease-resistant RNA structure (xrRNA) located in the viral genome's 3' untranslated region (UTR).

CPSF6-Dependent Targeting of Speckle-Associated Domains Distinguishes Primate from Nonprimate Lentiviral Integration.

Lentiviral DNA integration favors transcriptionally active chromatin. We previously showed that the interaction of human immunodeficiency virus type 1 (HIV-1) capsid with cleavage and polyadenylation specificity factor 6 (CPSF6) localizes viral preintegration complexes (PICs) to nuclear speckles for integration into transcriptionally active speckle-associated domains (SPADs). In the absence of the capsid-CPSF6 interaction, PICs uncharacteristically accumulate at the nuclear periphery and target heterochromatic lamina-associated domains (LADs) for integration.

Consensus guidelines on managing Rett syndrome across the lifespan.

Background: Rett syndrome (RTT) is a severe neurodevelopmental disorder with complex medical comorbidities extending beyond the nervous system requiring the attention of health professionals. There is no peer-reviewed, consensus-based therapeutic guidance to care in RTT. The objective was to provide consensus on guidance of best practice for addressing these concerns.

Outcomes of Severe Seronegative Hepatitis-associated Aplastic Anemia: A Pediatric Case Series.

Objectives: Hepatitis-associated aplastic anemia (HAAA) is a potentially life-threatening diagnosis without clear treatment guidelines. The goal of the study was to characterize the presentation, evaluation, histopathology, and outcomes of therapy in children with HAAA to guide future research and to develop standardized care guidelines for this rare disease.

Methods: Retrospective chart review of 4 patients with HAAA who presented to Children's Hospital Colorado between 2016 and 2019 was conducted.

Responsive neurostimulation for refractory epilepsy in the pediatric population: A single-center experience.

Drug-resistant focal epilepsy (DRFE) in children can impair cognition and behavior, and lead to premature death. Increased pediatric epilepsy surgery numbers reflect the improvements in seizure control and long-term developmental outcomes. Yet, many children with DRFE are not candidates for surgical resection due to overlap of the seizure network with eloquent cortex or multiple seizure-onset zones, making surgery dangerous or ineffective.

Transmission of Intergenerational Parenting Attitudes and Natural Mentorship: Associations Within the LONGSCAN population.

Background: Evidence suggests that families transmit child maltreatment and parenting attitudes. Natural mentorship may mediate intergenerational parenting attitudes' risk for maltreatment but has not been studied.

Objective: To compare parenting attitudes between adolescents exposed to or at risk for maltreatment and their caregivers and to determine if natural mentorship mediates differences in parenting attitudes' maltreatment risk.

The crystal structure of a Polerovirus exoribonuclease-resistant RNA shows how diverse sequences are integrated into a conserved fold.

Exoribonuclease-resistant RNAs (xrRNAs) are discrete elements that block the progression of 5' to 3' exoribonucleases using specifically folded RNA structures. A recently discovered class of xrRNA is widespread in several genera of plant-infecting viruses, within both noncoding and protein-coding subgenomic RNAs. The structure of one such xrRNA from a dianthovirus revealed three-dimensional details of the resistant fold but did not answer all questions regarding the conservation and diversity of this xrRNA class.

HITM-SURE: Hepatic immunotherapy for metastases phase Ib anti-CEA CAR-T study utilizing pressure enabled drug delivery.

In recent years, cell therapy technologies have resulted in impressive results in hematologic malignancies. Treatment of solid tumors with chimeric antigen receptor T-cells (CAR-T) has been less successful. Solid tumors present challenges not encountered with hematologic cancers, including high intra-tumoral pressure and ineffective CAR-T trafficking to the site of disease.

Improvements in Quality of Life in Children Following Epicutaneous Immunotherapy (EPIT) for Peanut Allergy in the PEPITES and PEOPLE Studies.

Background: Food allergy quality of life (FAQL) is impaired in children with peanut allergy. Food Allergy Quality of Life Questionnaires (FAQLQs) provide disease-specific insight into the burden of peanut allergy and potential FAQL changes after peanut immunotherapy.

Objective: To examine FAQL changes in children after treatment with epicutaneous immunotherapy for peanut allergy (250 μg, daily epicutaneous peanut protein; DBV712 250 μg).

Clinical Research in Hepatology in the COVID-19 Pandemic and Post-Pandemic Era: Challenges and the Need for Innovation.

The severe acute respiratory syndrome coronavirus 2 pandemic has drastically altered all facets of clinical care and research. Clinical research in hepatology has had a rich tradition in several domains, including the discovery and therapeutic development for diseases such as hepatitis B and C and studying the natural history of many forms of chronic liver disease. National Institutes of Health, foundation, and industry funding have provided important opportunities to advance the academic careers of young investigators while they strived to make contributions to the field.