Girl-Boy Twins with Developmental Delay from 16p11.2 Triplication due to Biparental Inheritance from Two Parents with 16p11.2 Duplication.

The 16p11.2 duplication is a well-known cause of developmental delay and autism, but there are only 2 previously reported cases of 16p11.2 triplication.

A single residue in influenza virus H2 hemagglutinin enhances the breadth of the B cell response elicited by H2 vaccination.

Conserved epitopes on the influenza hemagglutinin (HA) stem are an attractive target for universal vaccine strategies as they elicit broadly neutralizing antibodies. Such antibody responses to stem-specific epitopes have been extensively characterized for HA subtypes H1 and H5 in humans. H2N2 influenza virus circulated 50 years ago and represents a pandemic threat due to the lack of widespread immunity, but, unlike H1 and H5, the H2 HA stem contains Phe45 predicted to sterically clash with HA stem-binding antibodies characterized to date.

Safety and immunogenicity of a ferritin nanoparticle H2 influenza vaccine in healthy adults: a phase 1 trial.

Currently, licensed seasonal influenza vaccines display variable vaccine effectiveness, and there remains a need for novel vaccine platforms capable of inducing broader responses against viral protein domains conserved among influenza subtypes. We conducted a first-in-human, randomized, open-label, phase 1 clinical trial ( NCT03186781 ) to evaluate a novel ferritin (H2HA-Ferritin) nanoparticle influenza vaccine platform. The H2 subtype has not circulated in humans since 1968.

Biomarker selection and a prospective metabolite-based machine learning diagnostic for lyme disease.

We provide a pipeline for data preprocessing, biomarker selection, and classification of liquid chromatography-mass spectrometry (LCMS) serum samples to generate a prospective diagnostic test for Lyme disease. We utilize tools of machine learning (ML), e.g.

The relationship between repetitive negative thinking, sleep disturbance, and subjective fatigue in women with Generalized Anxiety Disorder.

Objectives: Fatigue is a prominent symptom of Generalized Anxiety Disorder (GAD). However, the pathways contributing to elevated fatigue in GAD are poorly understood. Sleep disturbance, also prominent in GAD, only partially explains elevated fatigue in GAD.

Expert-Moderated Peer-to-Peer Online Support Group for People With Knee Osteoarthritis: Mixed Methods Randomized Controlled Pilot and Feasibility Study.

Background: Osteoarthritis (OA) is a major problem globally. First-line management comprises education and self-management strategies. Online support groups may be a low-cost method of facilitating self-management.

Evaluation of live-attenuated Histomonas meleagridis isolates as vaccine candidates against wild-type challenge.

Repeated serial in vitro passage of Histomonas meleagridis, the etiological agent of histomoniasis (blackhead) of turkeys, was demonstrated to markedly achieve attenuation and reduction of virulence as compared to the original wild-type isolate. Four experiments were performed to evaluate the route (oral vs. intracloacal) and age (day-of-hatch vs.

Localising individual atoms of tryptophan side chains in the metallo--lactamase IMP-1 by pseudocontact shifts from paramagnetic lanthanoid tags at multiple sites.

The metallo--lactamase IMP-1 features a flexible loop near the active site that assumes different conformations in single crystal structures, which may assist in substrate binding and enzymatic activity. To probe the position of this loop, we labelled the tryptophan residues of IMP-1 with 7-C-indole and the protein with lanthanoid tags at three different sites. The magnetic susceptibility anisotropy () tensors were determined by measuring pseudocontact shifts (PCSs) of backbone amide protons.

Maternal Experience Does Not Predict Fear Extinction and Anxiety-Like Behaviour in Primiparous Rats Post-weaning.

Reproductive experience leads to long-lasting changes in anxiety-like behaviour and fear extinction, the laboratory model of exposure therapy for anxiety disorders. For example, fear extinction is influenced by estrous cycle in nulliparous (no reproductive experience) female rats, but this effect is abolished in primiparous (one reproductive experience) females. It is unclear whether such changes are driven by pregnancy, maternal experience of caring for offspring during the postpartum period, or a combination of both experiences.

Development and Validation of a Universal Science Writing Rubric That is Applicable to Diverse Genres of Science Writing.

It is critical for science, technology, engineering, and mathematics (STEM) students to develop competencies in science communication, including science writing. However, it can be difficult for instructors and departments to assess the quality of their students' science writing. Many published science writing rubrics are specific to certain genres like lab reports.

Chimeric Fusion (F) and Attachment (G) Glycoprotein Antigen Delivery by mRNA as a Candidate Nipah Vaccine.

Nipah virus (NiV) represents a significant pandemic threat with zoonotic transmission from bats-to-humans with almost annual regional outbreaks characterized by documented human-to-human transmission and high fatality rates. Currently, no vaccine against NiV has been approved. Structure-based design and protein engineering principles were applied to stabilize the fusion (F) protein in its prefusion trimeric conformation (pre-F) to improve expression and increase immunogenicity.

Protection from SARS-CoV-2 Delta one year after mRNA-1273 vaccination in rhesus macaques coincides with anamnestic antibody response in the lung.

mRNA-1273 vaccine efficacy against SARS-CoV-2 Delta wanes over time; however, there are limited data on the impact of durability of immune responses on protection. Here, we immunized rhesus macaques and assessed immune responses over 1 year in blood and upper and lower airways. Serum neutralizing titers to Delta were 280 and 34 reciprocal ID at weeks 6 (peak) and 48 (challenge), respectively.

Estimating prevalence of human traits among populations from polygenic risk scores.

The genetic basis of phenotypic variation across populations has not been well explained for most traits. Several factors may cause disparities, from variation in environments to divergent population genetic structure. We hypothesized that a population-level polygenic risk score (PRS) can explain phenotypic variation among geographic populations based solely on risk allele frequencies.

Variant SARS-CoV-2 mRNA vaccines confer broad neutralization as primary or booster series in mice.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of a global pandemic. Safe and effective COVID-19 vaccines are now available, including mRNA-1273, which has shown 94% efficacy in prevention of symptomatic COVID-19 disease. However, the emergence of SARS-CoV-2 variants has led to concerns of viral escape from vaccine-induced immunity.

Protection from SARS-CoV-2 Delta one year after mRNA-1273 vaccination in nonhuman primates is coincident with an anamnestic antibody response in the lower airway.

mRNA-1273 vaccine efficacy against SARS-CoV-2 Delta wanes over time; however, there are limited data on the impact of durability of immune responses on protection. We immunized rhesus macaques at weeks 0 and 4 and assessed immune responses over one year in blood, upper and lower airways. Serum neutralizing titers to Delta were 280 and 34 reciprocal ID at weeks 6 (peak) and 48 (challenge), respectively.

A broadly cross-reactive antibody neutralizes and protects against sarbecovirus challenge in mice.

Severe acute respiratory syndrome coronaviruses 1 (SARS-CoV) and 2 (SARS-CoV-2), including SARS-CoV-2 variants of concern, can cause deadly infections. The mortality associated with sarbecovirus infection underscores the importance of developing broadly effective countermeasures against them, which could be key in the prevention and mitigation of current and future zoonotic events. Here, we demonstrate the neutralization of SARS-CoV; bat coronaviruses WIV-1 and RsSHC014; and SARS-CoV-2 variants D614G, B.

Stabilized coronavirus spike stem elicits a broadly protective antibody.

Current coronavirus (CoV) vaccines primarily target immunodominant epitopes in the S1 subunit, which are poorly conserved and susceptible to escape mutations, thus threatening vaccine efficacy. Here, we use structure-guided protein engineering to remove the S1 subunit from the Middle East respiratory syndrome (MERS)-CoV spike (S) glycoprotein and develop stabilized stem (SS) antigens. Vaccination with MERS SS elicits cross-reactive β-CoV antibody responses and protects mice against lethal MERS-CoV challenge.

Protection against SARS-CoV-2 Beta variant in mRNA-1273 vaccine-boosted nonhuman primates.

Neutralizing antibody responses gradually wane against several variants of concern (VOCs) after vaccination with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine messenger RNA-1273 (mRNA-1273). We evaluated the immune responses in nonhuman primates that received a primary vaccination series of mRNA-1273 and were boosted about 6 months later with either homologous mRNA-1273 or heterologous mRNA-1273.β, which encompasses the spike sequence of the B.

Symptom fluctuation over the menstrual cycle in anxiety disorders, PTSD, and OCD: a systematic review.

Anxiety disorders are more prevalent and severe in women than men. Extant research suggests that the menstrual cycle modulates the severity and expression of anxiety symptoms across a range of disorders. The aims of this systematic review were to synthesise the existing literature investigating menstrual phase-related fluctuations in symptoms of anxiety disorders, and related conditions PTSD and OCD, in menstruating women, and to evaluate the methodologies used.

Examining prevalence and correlates of smoking opioids in British Columbia: opioids are more often smoked than injected.

Background: British Columbia (BC) is in the midst of an opioid overdose crisis. Since 2017, smoking illicit drugs has been the leading mode of drug administration causing overdose death. Yet, little is known about people who smoke opioids, and factors underlying choice of mode of administration.

Efficacy of the mRNA-1273 SARS-CoV-2 Vaccine at Completion of Blinded Phase.

Background: At interim analysis in a phase 3, observer-blinded, placebo-controlled clinical trial, the mRNA-1273 vaccine showed 94.1% efficacy in preventing coronavirus disease 2019 (Covid-19). After emergency use of the vaccine was authorized, the protocol was amended to include an open-label phase.

Immobilization of Proteinase K for urine pretreatment to improve diagnostic accuracy of active tuberculosis.

The World Health Organization (WHO) calls for the development of a rapid, biomarker-based, non-sputum test capable of detecting all forms of tuberculosis (TB) at the point-of-care to enable immediate treatment initiation. Lipoarabinomannan (LAM) is the only WHO-endorsed TB biomarker that can be detected in urine, an easily collected sample matrix. For obtaining optimal sensitivity, we and others have shown that some form of sample pretreatment is necessary to remove background from patient urine samples.