Verbal Behavior Analysis of Teaching Story Recall to Children with Autism: A Replication and Extension.

Children with autism spectrum disorder (ASD) may struggle with verbal behavior related to recall in various contexts. However, relatively little research has evaluated methods for improving recall among this population, and even fewer from a verbal behavior perspective. One socially important set of skills that relies upon a behavioral repertoire of recall is applied reading skills, such as reading comprehension and story recall. Valentino et al. (2015) designed an intervention package to teach children with ASD to recall short stories and conceptualized the behavior as an intraverbal chain. The present study replicated and extended that study with three school-aged children with ASD using a multiple baseline design across stories. For some participants and some stories, story recall was mastered under less intensive intervention conditions than in the previous study. When it was necessary to implement the full intervention package, the effects largely replicated previous research. Improvements in recall were correlated with increases in correct answers to comprehension questions. These data have important implications for clinicians and educators providing reading and recall interventions to children with ASD. Results also have theoretical implications for verbal behavior accounts of memory and recall, and suggest several possible avenues for future research. Supplementary Information: The online version contains supplementary material available at 10.1007/s40616-023-00183-2.

On the validity of interpreting functional analyses of inappropriate mealtime behavior using structured criteria.

Visual inspection is the traditional method behavior analysts use to interpret functional-analysis results. Limitations of visual inspection include lack of standardized rules, subjectivity, and inconsistent interrater reliability (Fisch, 1998). To address these limitations, researchers have developed, evaluated, and refined structured criteria to aid interpretation of functional analyses of destructive behavior (Hagopian et al., 1997; Roane et al., 2013; Saini et al., 2018). The current study applied the structured criteria Saini et al. (2018) described to functional analyses of inappropriate mealtime behavior. We assessed its predictive validity and evaluated its efficiency relative to 3 post hoc visual inspection procedures. Validity metrics were lower than those in Saini et al. however, ongoing visual inspection increased the efficiency of functional analyses by more than 30%. We discuss these findings relative to the procedural differences between functional analyses of destructive behavior and inappropriate mealtime behavior.

Remdesivir targets a structurally analogous region of the Ebola virus and SARS-CoV-2 polymerases.

Remdesivir is a broad-spectrum antiviral nucleotide prodrug that has been clinically evaluated in Ebola virus patients and recently received emergency use authorization (EUA) for treatment of COVID-19. With approvals from the Federal Select Agent Program and the Centers for Disease Control and Prevention's Institutional Biosecurity Board, we characterized the resistance profile of remdesivir by serially passaging Ebola virus under remdesivir selection; we generated lineages with low-level reduced susceptibility to remdesivir after 35 passages. We found that a single amino acid substitution, F548S, in the Ebola virus polymerase conferred low-level reduced susceptibility to remdesivir. The F548 residue is highly conserved in filoviruses but should be subject to specific surveillance among novel filoviruses, in newly emerging variants in ongoing outbreaks, and also in Ebola virus patients undergoing remdesivir therapy. Homology modeling suggests that the Ebola virus polymerase F548 residue lies in the F-motif of the polymerase active site, a region that was previously identified as susceptible to resistance mutations in coronaviruses. Our data suggest that molecular surveillance of this region of the polymerase in remdesivir-treated COVID-19 patients is also warranted.

Cues used by dentists in the early detection of oral cancer and oral potentially malignant lesions: findings from the National Dental Practice-Based Research Network.

OBJECTIVE: The aim of this study was to assess the influence of clinical cues on risk assessment of cancer-associated mucosal abnormalities. STUDY DESIGN: We differentiated lesions with a low risk from those with a high risk for premalignancy or malignancy by using 4 cues: (1) color, (2) location, (3) induration, and (4) pain on exploration. Combinations of color and location were presented through 8 photographs, with induration and pain status variably presented in the standardized history and physical findings. This created 16 clinical scenarios (vignettes) that were permutations of the 4 cues. Three questions assessed the extent to which each cue was used in obtaining a clinical impression as to whether a lesion was benign, premalignant, or malignant. RESULTS: Completed vignette questionnaires were obtained from 130 of 228 invited dentists, (two-thirds males; 79% white; mean age 52 years; average weekly hours of practice 33 hours). Only 40% of the responding dentists had statistically significant decision policies to assign a clinical diagnosis of a lesion as benign, premalignant, or malignant. Lesion location and color were the 2 dominant cues. As a cue, induration was used as a cue by more of the respondents in determining a clinical diagnosis of malignancy, and pain was infrequently used as a cue. CONCLUSIONS: Many dentists do not to have a decision strategy for the clinical diagnosis and risk stratification of oral potentially malignant lesions.

Isolation and phylogenomic analysis of buffalopox virus from human and buffaloes in India.

Three genome sequences of Buffalopox virus (BPVX) were retrieved from a human and two buffaloes scab samples. Phylogenomic analysis of the BPXV indicates that it shares a most recent common ancestor with Lister and closely related vaccine strains when compared to potential wild-type VACV strains (like Horsepox virus).

Rousette Bat Dendritic Cells Overcome Marburg Virus-Mediated Antiviral Responses by Upregulation of Interferon-Related Genes While Downregulating Proinflammatory Disease Mediators.

Dysregulated and maladaptive immune responses are at the forefront of human diseases caused by infection with zoonotic viral hemorrhagic fever viruses. Elucidating mechanisms of how the natural animal reservoirs of these viruses coexist with these agents without overt disease, while permitting sufficient replication to allow for transmission and maintenance in a population, is important for understanding the viral ecology and spillover to humans. The Egyptian rousette bat (ERB) has been identified as a reservoir for Marburg virus (MARV), a filovirus and the etiological agent of the highly lethal Marburg virus disease. Little is known regarding how these bats immunologically respond to MARV infection. In humans, macrophages and dendritic cells (DCs) are primary targets of infection, and their dysregulation is thought to play a central role in filovirus diseases, by disturbing their normal functions as innate sensors and adaptive immune response facilitators while serving as amplification and dissemination agents for the virus. The infection status and responses to MARV in bat myeloid-lineage cells are uncharacterized and likely represent an important modulator of the bat's immune response to MARV infection. Here, we generate DCs from the bone marrow of rousette bats. Infection with a bat isolate of MARV resulted in a low level of transcription in these cells and significantly downregulated DC maturation and adaptive immune-stimulatory pathways while simultaneously upregulating interferon-related pathogen-sensing pathways. This study provides a first insight into how the bat immune response is directed toward preventing aberrant inflammatory responses while mounting an antiviral response to defend against MARV infection.IMPORTANCE Marburg viruses (MARVs) cause severe human disease resulting from aberrant immune responses. Dendritic cells (DCs) are primary targets of infection and are dysregulated by MARV. Dysregulation of DCs facilitates MARV replication and virus dissemination and influences downstream immune responses that result in immunopathology. Egyptian rousette bats (ERBs) are natural reservoirs of MARV, and infection results in virus replication and shedding, with asymptomatic control of the virus within weeks. The mechanisms that bats employ to appropriately respond to infection while avoiding disease are unknown. Because DC infection and modulation are important early events in human disease, we measured the transcriptional responses of ERB DCs to MARV. The significance of this work is in identifying cell type-specific coevolved responses between ERBs and MARV, which gives insight into how bat reservoirs are able to harbor MARV and permit viral replication, allowing transmission and maintenance in the population while simultaneously preventing immunopathogenesis.

Characterisation of infectious Ebola virus from the ongoing outbreak to guide response activities in the Democratic Republic of the Congo: a phylogenetic and in vitro analysis.

BACKGROUND: The ongoing Ebola virus outbreak in the Ituri and North Kivu Provinces of the Democratic Republic of the Congo, which began in July, 2018, is the second largest ever recorded. Despite civil unrest, outbreak control measures and the administration of experimental therapies and a vaccine have been initiated. The aim of this study was to test the efficacy of candidate therapies and diagnostic tests with the outbreak strain Ituri Ebola virus. Lacking a virus isolate from this outbreak, a recombinant Ituri Ebola virus was compared with a similarly engineered Makona virus from the 2013-16 outbreak. METHODS: Using Ebola virus sequences provided by organisations in DR Congo and a reverse genetics system, we generated an authentic Ebola virus from the ongoing outbreak in Ituri and North Kivu provinces. To relate this virus to other Ebola viruses in DR Congo, we did a phylogenetic analysis of representative complete Ebola virus genome sequences from previous outbreaks. We evaluated experimental therapies being tested in clinical trials in DR Congo, including remdesivir and ZMapp monoclonal antibodies, for their ability to inhibit the growth of infectious Ituri Ebola virus in cell culture. We also tested diagnostic assays for detection of the Ituri Ebola virus sequence. FINDINGS: The phylogenetic analysis of whole-genome sequences from each Ebola virus outbreak suggests there are at least two Ebola virus strains in DR Congo, which have independently crossed into the human population. The Ituri Ebola strain initially grew slower than the Makona strain, yet reached similar mean yields of 3 × 107 50% tissue culture infectious dose by 72 h infection in Huh-7 cells. Ituri Ebola virus was similar to Makona in its susceptibility to inhibition by remdesivir and to neutralisation by monoclonal antibodies from ZMapp and other monoclonal antibodies. Remdesivir inhibited Ituri Ebola virus at a 50% effective concentration (EC50) of 12nM (with a selectivity index of 303) and Makona Ebola virus at 13nM (with a selectivity index of 279). The Zmapp monoclonal antibodies 2G4 and 4G7 neutralised Ituri Ebola virus with a mean EC50 of 0·24 µg/mL and 0·48 µg/mL, and Makona Ebola virus with a mean EC50 of 0·45 µg/mL and 0·2 µg/mL. The Xpert Ebola and US Centers for Disease Control and Prevention real-time RT-qPCR diagnostic assays detected Ituri and Makona Ebola virus sequences with similar sensitivities and efficiencies, despite primer site binding mismatches in the Ituri Ebola virus. INTERPRETATION: Our findings provide a rationale for the continued testing of investigational therapies, confirm the effectiveness of the diagnostic assays used in the region, and establish a paradigm for the use of reverse genetics to inform response activities in an outbreak. FUNDING: US Centers for Disease Control and Prevention.

Hoarding: A meta-analysis of age of onset.

Hoarding disorder is present in 2-6% of the population and can have an immense impact on the lives of patients and their families. Before its inclusion the Diagnostic and Statistical Manual of Mental Disorders, 5th edition, pathological hoarding was often characterized as a symptom of obsessive-compulsive disorder, and several different diagnostic assessment methods were used to identify and characterize it. Although the age of onset of pathological hoarding is an important epidemiological measure, as clarifying the age of onset of hoarding symptoms may allow for early identification and implementation of evidence-based treatments before symptoms become clinically significant, the typical age of onset of hoarding is still uncertain. To that end, this study is a systematic review and meta-analysis of research published in English between the years 1900 and 2016 containing information on age of onset of hoarding symptoms. Twenty-five studies met inclusion criteria. The mean age of onset of hoarding symptoms across studies was 16.7 years old, with evidence of a bimodal distribution of onset. The authors conclude by discussing practice implications for early identification and treatment.

Antibody-Mediated Virus Neutralization Is Not a Universal Mechanism of Marburg, Ebola, or Sosuga Virus Clearance in Egyptian Rousette Bats.

Although bats are increasingly being recognized as natural reservoir hosts of emerging zoonotic viruses, little is known about how they control and clear virus infection in the absence of clinical disease. Here, we test >50 convalescent sera from Egyptian rousette bats (ERBs) experimentally primed or prime-boosted with Marburg virus, Ebola virus, or Sosuga virus for the presence of virus-specific neutralizing antibodies, using infectious reporter viruses. After serum neutralization testing, we conclude that antibody-mediated virus neutralization does not contribute significantly to the control and clearance of Marburg virus, Ebola virus, or Sosuga virus infection in ERBs.