Ontogenetic change in body shape for white sharks, Carcharodon carcharias, in Australian waters.

The analysis of how biological shape changes across ontogeny can provide us with valuable information on how species adapt behaviorally, physiologically, and ecologically. The white shark Carcharodon carcharias is one of the largest and most widely distributed apex predators globally, yet an understanding of ontogenetic changes in body shape and relative scaling of length and weight measures is limited, especially in relation to foraging ecology. Through analysis of a suite of shape-related metrics, we identified ontogenetic patterns of scaling throughout development.

antimalarial susceptibility profile of isolates in the BEI Resources repository.

BEI Resources, a National Institute of Allergy and Infectious Diseases-funded program managed by the American Type Culture Collection, serves researchers worldwide through the provision of a centralized repository for the acquisition, production, characterization, preservation, storage, and distribution of standardized biological resources targeting National Institutes of Health priority pathogens including bacteria, viruses, pathogenic fungi, and parasitic protozoa. These reference materials are critical for the development of diagnostics, vaccines, and therapeutics and are available to qualified registered investigators and institutions worldwide. Bioresources within BEI include well-characterized malaria isolates as part of the Malaria Research and Reference Reagent Resource Center (MR4).

Establishment of human post-vaccination SARS-CoV-2 standard reference sera.

There is a critical need to understand the effectiveness of serum elicited by different SARS-CoV-2 vaccines against SARS-CoV-2 variants. We describe the generation of reference reagents comprised of post-vaccination sera from recipients of different primary vaccines with or without different vaccine booster regimens in order to allow standardized characterization of SARS-CoV-2 neutralization in vitro. We prepared and pooled serum obtained from donors who received a either primary vaccine series alone, or a vaccination strategy that included primary and boosted immunization using available SARS-CoV-2 mRNA vaccines (BNT162b2, Pfizer and mRNA-1273, Moderna), replication-incompetent adenovirus type 26 vaccine (Ad26.

Deep learning for automatic segmentation of vestibular schwannoma: a retrospective study from multi-center routine MRI.

Automatic segmentation of vestibular schwannoma (VS) from routine clinical MRI has potential to improve clinical workflow, facilitate treatment decisions, and assist patient management. Previous work demonstrated reliable automatic segmentation performance on datasets of standardized MRI images acquired for stereotactic surgery planning. However, diagnostic clinical datasets are generally more diverse and pose a larger challenge to automatic segmentation algorithms, especially when post-operative images are included.

Recommendations for Uniform Variant Calling of SARS-CoV-2 Genome Sequence across Bioinformatic Workflows.

Genomic sequencing of clinical samples to identify emerging variants of SARS-CoV-2 has been a key public health tool for curbing the spread of the virus. As a result, an unprecedented number of SARS-CoV-2 genomes were sequenced during the COVID-19 pandemic, which allowed for rapid identification of genetic variants, enabling the timely design and testing of therapies and deployment of new vaccine formulations to combat the new variants. However, despite the technological advances of deep sequencing, the analysis of the raw sequence data generated globally is neither standardized nor consistent, leading to vastly disparate sequences that may impact identification of variants.

Evaluation of adherence to a daily progestin-only pill in a simulated over-the-counter setting.

Objective: The Adherence with Continuous Dose Oral Contraceptive: Evaluation of Self-Selection and Use (ACCESS) study assessed whether consumers can adhere to the regimen for a progestin-only pill (norgestrel 0.075 mg) in an over-the-counter (OTC) setting.

Study Design: An actual use study in a simulated OTC environment assessed adherence to directions to take norgestrel 0.

Evaluation of consumer self-selection of a proposed over-the-counter, progestin-only daily oral contraceptive.

Objectives: In an effort to switch a norgestrel 0.075 mg progestin-only pill (Opill) from prescription to over-the-counter, we conducted this study to assess whether consumers can use the drug facts label alone to guide appropriate self-selection.

Study Design: Two studies assessed self-selection: (1) an all-comers, actual-use study evaluating self-selection before purchasing and using norgestrel 0.

Cost-effectiveness of axicabtagene ciloleucel versus tisagenlecleucel for the treatment of 3L + relapsed/refractory large B-cell lymphoma in the United States: incorporating longer survival results.

Aims: To provide an update on the cost-effectiveness of the chimeric antigen receptor (CAR) T-cell therapies axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) for the treatment of relapsed/refractory (r/r) large B-cell lymphoma (LBCL) among patients who have previously received ≥2 lines of systemic therapy using more mature clinical trial data cuts (60 months for axi-cel overall survival [OS] and 45 months for tisa-cel OS and progression-free survival [PFS]).

Methods: A partitioned survival model consisting of three health states (pre-progression, post-progression and death) was used to estimate quality-adjusted life years (QALYs) and costs associated with axi-cel and tisa-cel over a lifetime horizon. PFS and OS inputs for axi-cel and tisa-cel were based on a previously published matching-adjusted indirect treatment comparison (MAIC).

Evaluation of an Online Dementia Training Program to Reduce Antipsychotic Medication Use in a Nursing Home.

Using the Kirkpatrick Model as a framework, the current program evaluation was performed to examine the effect of an online dementia training program on the rate of antipsychotic medication use in a nursing home. Antipsychotic medication use before program implementation was compared to use post-implementation. Run charts and a Wilcoxon analysis were used to look for trends or variances in antipsychotic medication use before and after implementation of the program.

Diffusion MRI of the facial-vestibulocochlear nerve complex: a prospective clinical validation study.

Objectives: Surgical planning of vestibular schwannoma surgery would benefit greatly from a robust method of delineating the facial-vestibulocochlear nerve complex with respect to the tumour. This study aimed to optimise a multi-shell readout-segmented diffusion-weighted imaging (rs-DWI) protocol and develop a novel post-processing pipeline to delineate the facial-vestibulocochlear complex within the skull base region, evaluating its accuracy intraoperatively using neuronavigation and tracked electrophysiological recordings.

Methods: In a prospective study of five healthy volunteers and five patients who underwent vestibular schwannoma surgery, rs-DWI was performed and colour tissue maps (CTM) and probabilistic tractography of the cranial nerves were generated.

Development and validation of a rapid and easy-to-perform point-of-care lateral flow immunoassay (LFIA) for the detection of SARS-CoV-2 spike protein.

Development and validation of rapid and easy-to-perform diagnostics continue to be a high priority during the current COVID-19 pandemic. Although vaccines are now widely available, early detection and consistent transmission control provide ideal means to mitigate the spread of SARS-CoV-2. Nucleic acid-based real-time PCR tests are widely acknowledged as the gold standard for reliable diagnosis of COVID-19 infection.

Dynamics of parasite growth in genetically diverse Plasmodium falciparum isolates.

Multiple parasite lineages with different proliferation rates or fitness may coexist within a clinical malaria isolate, resulting in complex growth interactions and variations in phenotype. To elucidate the dynamics of parasite growth in multiclonal isolates, we measured growth rates (GRs) of three Plasmodium falciparum Cambodian isolates, including IPC_3445 (MRA-1236), IPC_5202 (MRA-1240), IPC_6403 (MRA-1285), and parasite lineages previously cloned from each of these isolates by limiting dilution. Following synchronization, in vitro cultures of each parasite line were maintained over four consecutive asexual cycles (192 h), with thin smears prepared at each 48-h cycle to estimate GR and fold change in parasitemia (FCP).

Towards increased accuracy and reproducibility in SARS-CoV-2 next generation sequence analysis for public health surveillance.

During the COVID-19 pandemic, SARS-CoV-2 surveillance efforts integrated genome sequencing of clinical samples to identify emergent viral variants and to support rapid experimental examination of genome-informed vaccine and therapeutic designs. Given the broad range of methods applied to generate new viral genomes, it is critical that consensus and variant calling tools yield consistent results across disparate pipelines. Here we examine the impact of sequencing technologies (Illumina and Oxford Nanopore) and 7 different downstream bioinformatic protocols on SARS-CoV-2 variant calling as part of the NIH Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) Tracking Resistance and Coronavirus Evolution (TRACE) initiative, a public-private partnership established to address the COVID-19 outbreak.

Pilot label comprehension study for an over-the-counter combined oral contraceptive pill in the United States.

Context: A growing body of evidence supports over-the-counter access to oral contraceptives in the United States. An important consideration for over-the-counter approval is consumers' ability to understand key package label messages related to safety and effectiveness without clinician involvement. We developed a prototype over-the-counter Drug Facts Label for a combined oral contraceptive pill and conducted a pilot label comprehension study to evaluate consumer understanding of key messages for use.

Intermolecular charge transfer enhances the performance of molecular rectifiers.

Molecular-scale diodes made from self-assembled monolayers (SAMs) could complement silicon-based technologies with smaller, cheaper, and more versatile devices. However, advancement of this emerging technology is limited by insufficient electronic performance exhibited by the molecular current rectifiers. We overcome this barrier by exploiting the charge-transfer state that results from co-assembling SAMs of molecules with strong electron donor and acceptor termini.

A Trial of Intranasal Corticosteroids to Treat Childhood OSA Syndrome.

Background: Intranasal corticosteroids (INCS) are frequently used to treat OSA syndrome (OSAS) in children. However, their efficacy has not been rigorously tested.

Research Question: Do INCS result in improved OSAS symptoms, polysomnography findings, behavior, and quality of life compared with placebo?

Study Design And Methods: In this randomized, double-blind, placebo-controlled trial, children with OSAS aged 5 to 12 years (N = 134) were randomized 2:1 to receive 3 months of INCS or placebo.

Adherence among a cohort taking progestin-only pills prescribed by a healthcare provider: Results of the BENCHMARK study.

Objectives: To measure adherence over six months of progestin-only pill (POP) use.

Study Design: Prospective observational cohort study measuring adherence to daily dosing and timing of dose in patients prescribed a POP, with up to six months of follow-up, conducted from January to October 2020. A pharmacy benefit manager identified potential participants with a newly prescribed POP and extended an invitation to participate.

Optical properties of human brain and tumour tissue: An ex vivo study spanning the visible range to beyond the second near-infrared window.

Neuro-oncology surgery would benefit from detailed intraoperative tissue characterization provided by noncontact, contrast-agent-free, noninvasive optical imaging methods. In-depth knowledge of target tissue optical properties across a wide-wavelength spectrum could inform the design of optical imaging and computational methods to enable robust tissue analysis during surgery. We adapted a dual-beam integrating sphere to analyse small tissue samples and investigated ex vivo optical properties of five types of human brain tumour (meningioma, pituitary adenoma, schwannoma, low- and high-grade glioma) and nine different types of healthy brain tissue across a wavelength spectrum of 400 to 1800 nm.

Propagation of SARS-CoV-2 in Calu-3 Cells to Eliminate Mutations in the Furin Cleavage Site of Spike.

SARS-CoV-2 pathogenesis, vaccine, and therapeutic studies rely on the use of animals challenged with highly pathogenic virus stocks produced in cell cultures. Ideally, these virus stocks should be genetically and functionally similar to the original clinical isolate, retaining wild-type properties to be reliably used in animal model studies. It is well-established that SARS-CoV-2 isolates serially passaged on Vero cell lines accumulate mutations and deletions in the furin cleavage site; however, these can be eliminated when passaged on Calu-3 lung epithelial cell lines, as presented in this study.

Segmentation of vestibular schwannoma from MRI, an open annotated dataset and baseline algorithm.

Automatic segmentation of vestibular schwannomas (VS) from magnetic resonance imaging (MRI) could significantly improve clinical workflow and assist patient management. We have previously developed a novel artificial intelligence framework based on a 2.5D convolutional neural network achieving excellent results equivalent to those achieved by an independent human annotator.

Culturing Mycobacteria.

Building upon the foundational research of Robert Koch, who demonstrated the ability to grow Mycobacterium tuberculosis for the first time in 1882 using media made of coagulated bovine serum, microbiologists have continued to develop new and more efficient ways to grow mycobacteria. Presently, all known mycobacterial species can be grown in the laboratory using either axenic culture techniques or in vivo passage in laboratory animals. This chapter provides conventional protocols to grow mycobacteria for diagnostic purposes directly from clinical specimens, as well as in research laboratories for scientific purposes.