Reproducibility of neuroimaging research on infant brain development remains limited due to highly variable protocols and processing approaches. Progress towards reproducible pipelines is limited by a lack of benchmarks such as gold standard brain segmentations. Addressing this core limitation, we constructed the Baby Open Brains (BOBs) Repository, an open source resource comprising manually curated and expert-reviewed infant brain segmentations.
View Article and Find Full Text PDFThe efficacy of affinity-based treatments for cancer and other diseases is often limited by poor distribution throughout the targeted tissue. Although lower-affinity antibodies will penetrate more uniformly, these often reach lower concentrations because of their rapid clearance from the tissue. To increase retention and improve distribution, we created low-affinity photocrosslinkable affibodies that can diffuse into dense tumor matrices with limited tumor barrier formation and then be photocrosslinked in place to cell receptors to increase retention.
View Article and Find Full Text PDFTumor spheroids represent valuable models for studying cancer biology and evaluating therapeutic strategies. In this study, we investigated the impact of varying lengths of DNA-modified cell surfaces on spheroid formation, cellular adhesion molecule expression, and hypoxia levels within 4T1 mouse breast cancer spheroids. Through a series of experiments, we demonstrated that modifying cell surfaces with biotinylated DNA strands of different lengths facilitated spheroid formation without significantly altering the expression of fibronectin and e-cadherin, key cellular adhesion molecules.
View Article and Find Full Text PDFX-ray photoelectron spectroscopy (XPS) depth-profiling with an argon gas cluster ion source (GCIS) was used to characterize the spatial distribution of chlorophyll (Chl) within a poly(cysteine methacrylate) (PCysMA) brush grown by surface-initiated atom-transfer radical polymerization (ATRP) from a planar surface. The organization of Chl is controlled by adjusting the brush grafting density and polymerization time. For , the C, N, S elemental composition remains constant throughout the 36 nm brush layer until the underlying gold substrate is approached.
View Article and Find Full Text PDFBackground: Recent consternation over the number of unfilled Pediatric Anesthesiology fellowship positions in the United States compelled us to assess the change in the ratio of Pediatric Anesthesiology fellows to the number of graduating anesthesiology residents over the 14-year period between 2008 and 2022. We also sought to report the total ratio of anesthesiology fellows to graduating residents and trends in the annual number of fellowship applicants relative to the number of Accreditation Council for Graduate Medical Education (ACGME)-accredited anesthesiology fellowship positions by specialty.
Methods: We used publicly available resources, including ACGME Data Resource Books, National Resident Matching Program (NRMP) data, San Francisco (SF) Match data, and American Board of Medical Specialties (ABMS) data, to determine the ratio of anesthesiology fellows to graduating anesthesiology residents and to compare the number of fellowship applicants to fellowship positions for Adult Cardiothoracic Anesthesiology, Critical Care Anesthesiology, Obstetric Anesthesiology, Pain Medicine and Pediatric Anesthesiology.
Purpose: The Medical Imaging and Data Resource Center (MIDRC) open data commons was launched to accelerate the development of artificial intelligence (AI) algorithms to help address the COVID-19 pandemic. The purpose of this study was to quantify longitudinal representativeness of the demographic characteristics of the primary MIDRC dataset compared to the United States general population (US Census) and COVID-19 positive case counts from the Centers for Disease Control and Prevention (CDC).
Approach: The Jensen-Shannon distance (JSD), a measure of similarity of two distributions, was used to longitudinally measure the representativeness of the distribution of (1) all unique patients in the MIDRC data to the 2020 US Census and (2) all unique COVID-19 positive patients in the MIDRC data to the case counts reported by the CDC.
Objectives: Brain segmentation of infant magnetic resonance (MR) images is vitally important for studying typical and atypical brain development. The infant brain undergoes many changes throughout the first years of postnatal life, making tissue segmentation difficult for most existing algorithms. Here we introduce a deep neural network BIBSNet ( aby and nfant rain egmentation Neural work), an open-source, community-driven model for robust and generalizable brain segmentation leveraging data augmentation and a large sample size of manually annotated images.
View Article and Find Full Text PDFA small receptor molecule composed of a porphyrin core with tetrakis-ammonium glycine pickets (liptin 3e) appears to target anionic phosphatidylglycerol (PG) lipid head groups through multifunctional binding-pocket complementarity. Although a major component of bacterial cell membranes, PG is not widely found in animal cells, making PG potentially selective for bacterial targeting. Growth of microbial isolates was monitored in liquid cultures treated with liptin 3e by dilution plate counts and turbidity.
View Article and Find Full Text PDFThe COVID-19 pandemic has had a profound impact on the nation's health care system, including on graduate medical education (GME) training programs. Traditionally, residency and fellowship training program applications involve in-person interviews conducted on-site, with only a minority of programs offering interviews remotely via a virtual platform. However, in light of the COVID-19 pandemic, it is anticipated that most interviews will be conducted virtually for the 2021 application cycle and possibly beyond.
View Article and Find Full Text PDFPost-translational modifications (PTMs) greatly expand the structures and functions of proteins in nature. Although synthetic protein functionalization strategies allow mimicry of PTMs, as well as formation of unnatural protein variants with diverse potential functions, including drug carrying, tracking, imaging and partner crosslinking, the range of functional groups that can be introduced remains limited. Here we describe the visible-light-driven installation of side chains at dehydroalanine residues in proteins through the formation of carbon-centred radicals that allow C-C bond formation in water.
View Article and Find Full Text PDFPharmacological treatments can extend mouse lifespan, but lifespan effects often differ between sexes. 17-α estradiol (17aE2), a less feminizing structural isomer of 17-β estradiol, produces lifespan extension only in male mice, suggesting a sexually dimorphic mechanism of lifespan regulation. We tested whether these anti-aging effects extend to anatomical and functional aging-important in late-life health-and whether gonadally derived hormones control aging responses to 17aE2 in either sex.
View Article and Find Full Text PDFFor commercial protein therapeutics, Chinese hamster ovary (CHO) cells have an established history of safety, proven capability to express a wide range of therapeutic proteins and high volumetric productivities. Expanding global markets for therapeutic proteins and increasing concerns for broadened access of these medicines has catalyzed consideration of alternative approaches to this platform. Reaching these objectives likely will require an order of magnitude increase in volumetric productivity and a corresponding reduction in the costs of manufacture.
View Article and Find Full Text PDFInterventions that extend lifespan in mice can show substantial sexual dimorphism. Here, we show that male-specific lifespan extension with two pharmacological treatments, acarbose (ACA) and 17-α estradiol (17aE2), is associated, in males only, with increased insulin sensitivity and improved glucose tolerance. Females, which show either smaller (ACA) or no lifespan extension (17aE2), do not derive these metabolic benefits from drug treatment.
View Article and Find Full Text PDFPosttranslational modification of proteins expands their structural and functional capabilities beyond those directly specified by the genetic code. However, the vast diversity of chemically plausible (including unnatural but functionally relevant) side chains is not readily accessible. We describe C (sp)-C (sp) bond-forming reactions on proteins under biocompatible conditions, which exploit unusual carbon free-radical chemistry, and use them to form Cβ-Cγ bonds with altered side chains.
View Article and Find Full Text PDFBackground: Surgical positioning of the HeartMate II (HMII) left ventricular assist device assuring an unobstructed blood flow path is essential for optimal device function and hemodynamic support. We report a non-invasive radiologic assessment of HMII position after implant and long-term follow-up.
Methods: We reviewed 132 consecutive patients (age 64 ± 14 years; 86% male; 60% destination therapy) implanted with an HMII from January 2009 to December 2012 and followed for them for up to 4 years.
A growing body of literature suggests that the homologous recombination/repair (HR) pathway cooperates with components of the shelterin complex to promote both telomere maintenance and nontelomeric HR. This may be due to the ability of both HR and shelterin proteins to promote strand invasion, wherein a single-stranded DNA (ssDNA) substrate base pairs with a homologous double-stranded DNA (dsDNA) template displacing a loop of ssDNA (D-loop). Rad51 recombinase catalyzes D-loop formation during HR, and telomere repeat binding factor 2 (TRF2) catalyzes the formation of a telomeric D-loop that stabilizes a looped structure in telomeric DNA (t-loop) that may facilitate telomere protection.
View Article and Find Full Text PDFRNA chaperones are ubiquitous, heterogeneous proteins essential for RNA structural biogenesis and function. We investigated the mechanism of chaperone-mediated RNA folding by following the time-resolved dimerization of the packaging domain of a retroviral RNA at nucleotide resolution. In the absence of the nucleocapsid (NC) chaperone, dimerization proceeded through multiple, slow-folding intermediates.
View Article and Find Full Text PDFWe describe biophysical and ultrastructural differences in genome release from adeno-associated virus (AAV) capsids packaging wild-type DNA, recombinant single-stranded DNA (ssDNA), or dimeric, self-complementary DNA (scDNA) genomes. Atomic force microscopy and electron microscopy (EM) revealed that AAV particles release packaged genomes and undergo marked changes in capsid morphology upon heating in physiological buffer (pH 7.2).
View Article and Find Full Text PDFPurpose: Fertility is a concern for many cancer patients diagnosed during their reproductive years. Although African American women are more likely to be diagnosed with early breast cancer (i.e.
View Article and Find Full Text PDFSpectral domain phase microscopy (SDPM) is an extension of spectral domain optical coherence tomography (SDOCT) that exploits the extraordinary phase stability of spectrometer-based systems with common-path geometry to resolve sub-wavelength displacements within a sample volume. This technique has been implemented for high resolution axial displacement and velocity measurements in biological samples, but since axial displacement information is acquired serially along the lateral dimension, it has been unable to measure fast temporal dynamics in extended samples. Depth-Encoded SDPM (DESDPM) uses multiple sample arms with unevenly spaced common path reference reflectors to multiplex independent SDPM signals from separate lateral positions on a sample simultaneously using a single interferometer, thereby reducing the time required to detect unique optical events to the integration period of the detector.
View Article and Find Full Text PDFThe GH/IGF-I axis has both pre- and postpubertal metabolic effects. However, the differential effects of GH and/or IGF-I on animal physiology or the plasma proteome are still being unraveled. In this report, we analyzed several physiological effects along with the plasma proteome after treatment of mice with recombinant bovine GH or recombinant human IGF-I.
View Article and Find Full Text PDFBackground: This study sought to determine the prevalence of distribution of fertility preservation (FP) materials, source of the materials, and providers' perceived relevance of the materials among a sample of US oncologists.
Methods: A 53-item survey was administered via mail and the Web to a stratified sample of oncologists from the American Medical Association Masterfile. This study represents a subset of results, reporting on three survey items.
Posthumous reproduction is an issue fraught with legal, ethical, religious, and moral debate. The involvement of the hospice and palliative care community in this debate may be peripheral due to the fact that other health care professionals would be actually delivering the services. However, the hospice and palliative care community are more likely to treat patients considering posthumous reproduction as they near the end of their lives.
View Article and Find Full Text PDFBackground: In this study, we report on the changes in psychosocial functioning over 1 year following breast cancer surgery in 3 groups of women, including those with mastectomy alone, those with mastectomy and immediate reconstruction, and those with delayed reconstruction.
Methods: Women with breast cancer at 2 teaching hospitals in Ontario who were undergoing mastectomy alone, mastectomy with immediate reconstruction, or delayed reconstruction were asked to complete a battery of psychosocial questionnaires at their preoperative appointment and 1 year following surgery.
Results: A total of 190 women consented to participate in the study and completed the presurgical questionnaires.