Research indicates complex associations between adverse childhood experiences (ACEs) and adolescent peer relationships. ACEs are related to lower peer status, yet the links between ACEs, peer characteristics, and peer relationship quality are inconclusive. The current literature has several further conceptual and methodological limitations, including a lack of attention to ACEs' co-occurring nature, the developmental timing of ACEs during adolescence, and the multifaceted nature of peer relationships.
View Article and Find Full Text PDFOptical imaging of metabolism can provide key information about health and disease progression in cells and tissues; however, current methods have lacked gold-standard information about histological structure. Conversely, histology and virtual histology methods have lacked metabolic contrast. Here, we present metabolic light absorption, scattering, and emission (MetaLASE) microscopy, which rapidly provides a virtual histology and optical metabolic readout simultaneously.
View Article and Find Full Text PDFAims: To determine the associations between COVID-19 school closures and school readiness skills for Chinese kindergarteners.
Design: We utilized the natural experimental condition created by local COVID-19 outbreaks in 2022 (Study 1) to compare school readiness skills of children whose kindergartens were closed for 5 months (Group 1) with children whose kindergartens stayed open (Group 2). We further compared the school readiness skills of one pre-COVID-19 cohort (Cohort 2019) with one COVID-19 cohort (Cohort 2021) from a fifth kindergarten (Study 2).
Inhibiting MerTK on macrophages is a promising therapeutic strategy for augmenting anti-tumor immunity. However, blocking MerTK on retinal pigment epithelial cells (RPEs) results in retinal toxicity. Bispecific antibodies (bsAbs) containing an anti-MerTK therapeutic and anti-PD-L1 targeting arm were developed to reduce drug binding to MerTK on RPEs, since PD-L1 is overexpressed on macrophages but not RPEs.
View Article and Find Full Text PDFConventional type 1 dendritic cells (cDC1s) are superior in antigen cross-presentation and priming CD8 T cell anti-tumor immunity and thus, are a target of high interest for cancer immunotherapy. Type I interferon (IFN) is a potent inducer of antigen cross-presentation, but, unfortunately, shows only modest results in the clinic given the short half-life and high toxicity of current type I IFN therapies, which limit IFN exposure in the tumor. CD8 T cell immunity is dependent on IFN signaling in cDC1s and preclinical studies suggest targeting IFN directly to cDC1s may be sufficient to drive anti-tumor immunity.
View Article and Find Full Text PDFAlzheimer's disease (AD), recognized as the leading cause of dementia, occupies a prominent position on the list of significant neurodegenerative disorders, representing a significant global health concern with far-reaching implications at both individual and societal levels. The primary symptom of Alzheimer's disease is a decrease in synaptic potency along with synaptic connection loss. Synapses, which act as important linkages between neuronal units within the cerebral region, are critical in signal transduction processes essential to orchestrating cognitive tasks.
View Article and Find Full Text PDFWe analyzed changes in total costs for National Institutes of Health (NIH) awarded Research Project Grants (RPGs) issued from fiscal years (FYs) 1998 to 2021 . Costs are measured in 'nominal' terms, meaning exactly as stated, or in 'real' terms, meaning after adjustment for inflation. The NIH uses a data-driven price index - the Biomedical Research and Development Price Index (BRDPI) - to account for inflation, enabling assessment of changes in real (that is, BRDPI-adjusted) costs over time.
View Article and Find Full Text PDFThe advent of clustered regularly interspaced short palindromic repeat (CRISPR) genome editing, coupled with advances in computing and imaging capabilities, has initiated a new era in which genetic diseases and individual disease susceptibilities are both predictable and actionable. Likewise, genes responsible for plant traits can be identified and altered quickly, transforming the pace of agricultural research and plant breeding. In this Review, we discuss the current state of CRISPR-mediated genetic manipulation in human cells, animals, and plants along with relevant successes and challenges and present a roadmap for the future of this technology.
View Article and Find Full Text PDFObjective: We examined the impact of the strict lockdown on 130 preschool-age children's daily routines and how their routine changes from pre-lockdown were related to child-parent relationship quality during the lockdown.
Background: To contain the spread of the COVID-19, the city of Wuhan underwent a strict 76-day lockdown, during which children's routines were drastically altered, yet families did not have a frame of reference to use to determine how changes in children's routines would be related to their family dynamics.
Method: Parents provided survey data on the amount of time their children spent daily on learning, screen devices, play and exercise, and nighttime sleep before, during, and after the lockdown.
Here, we explore whether PEGylation of antibodies can modulate their biodistribution to the eye, an organ once thought to be immune privileged but has recently been shown to be accessible to IV-administered large molecules, such as antibodies. We chose to PEGylate an anti-MerTK antibody, a target with known potential for ocular toxicity, to minimize biodistribution to retinal pigment epithelial cells (RPEs) in the eye by increasing the hydrodynamic volume of the antibody. We used site-specific conjugation to an engineered cysteine on anti-MerTK antibody to chemically attach 40-kDa branched or linear PEG polymers.
View Article and Find Full Text PDFNat Rev Microbiol
November 2022
CRISPR-Cas systems provide resistance against foreign mobile genetic elements and have a wide range of genome editing and biotechnological applications. In this Review, we examine recent advances in understanding the molecular structures and mechanisms of enzymes comprising bacterial RNA-guided CRISPR-Cas immune systems and deployed for wide-ranging genome editing applications. We explore the adaptive and interference aspects of CRISPR-Cas function as well as open questions about the molecular mechanisms responsible for genome targeting.
View Article and Find Full Text PDFA previous report found an association of topic choice with race-based funding disparities among R01 applications submitted to the National Institutes of Health ('NIH') between 2011 and 2015. Applications submitted by African American or Black ('AAB') Principal Investigators ('PIs') skewed toward a small number of topics that were less likely to be funded (or 'awarded'). It was suggested that lower award rates may be related to topic-related biases of peer reviewers.
View Article and Find Full Text PDFThe paper describes the applicability and acceptability of a selective intervention-Motivation, Assessment, and Planning (MAP)-for high school students that was developed based on the principles of motivational interviewing (MI) and tailored to the unique needs and strengths of students taking accelerated coursework, specifically Advanced Placement (AP) and International Baccalaureate (IB) classes. In addition to detailing the intervention in terms of MI spirit, processes, and relational and technical skills, we report applicability and acceptability data from a second iteration of MAP implementation in eight AP/IB programs in a Southeastern state during spring 2018. We analyzed quantitative and qualitative acceptability data from 121 high school freshmen (97 from AP and 24 from IB courses), as well as the seven MAP coaches who were trained using the Motivational Interview Training and Assessment System (Frey et al.
View Article and Find Full Text PDFImmune evasion and altered metabolism, where glucose utilization is diverted to increased lactic acid production, are two fundamental hallmarks of cancer. Although lactic acid has long been considered a waste product of this alteration, it is now well accepted that increased lactic acid production and the resultant acidification of the tumor microenvironment (TME) promotes multiple critical oncogenic processes including angiogenesis, tissue invasion/metastasis, and drug resistance. We and others have hypothesized that excess lactic acid in the TME is responsible for suppressing anticancer immunity.
View Article and Find Full Text PDFWe examined the predictive relations of social media and smartphone use to body esteem in female adolescents and the mechanism that underlies these relations. As a result of frequent social media and smartphone use, adolescents are continually exposed to appearance-related media content. This likely reinforces a thin ideal and fosters appearance-based comparison and increases fear of external evaluation.
View Article and Find Full Text PDFThis report presents a digital technique for the fabrication of a two-piece hollow bulb maxillary obturator prosthesis. The procedure described resulted in an accurate prosthesis while avoiding the discomfort associated with analog impressions. The manipulation of a routine postoperative CT scan in conjunction with a 3D printer allowed for the fabrication of a 3D-printed anatomical cast, from which the two-piece hollow bulb obturator was fabricated.
View Article and Find Full Text PDFObjective: To determine the rate and risk factors for osteoradionecrosis (ORN) in osseous free flaps after postoperative radiation therapy (PORT). To describe the treatment of free flap ORN.
Methods: Seventy-four patients undergoing osseous free flap reconstruction were analyzed.
Bacterial autotrophs often rely on CO concentrating mechanisms (CCMs) to assimilate carbon. Although many CCM proteins have been identified, a systematic screen of the components of CCMs is lacking. Here, we performed a genome-wide barcoded transposon screen to identify essential and CCM-related genes in the γ-proteobacterium Halothiobacillus neapolitanus.
View Article and Find Full Text PDFThis report describes the combination of analog and digital techniques for the fabrication of a 2-piece hollow bulb maxillary obturator. The procedure described provides an accurate representation of the surgical defect while avoiding the discomfort associated with analog impressions. The manipulation of a routine postoperative computed tomography (CT) scanner in conjunction with a 3D printer allowed for the fabrication of a 3D-printed anatomic cast from which the 2-piece hollow bulb obturator was fabricated.
View Article and Find Full Text PDFCRISPR-Cas immunity requires integration of short, foreign DNA fragments into the host genome at the CRISPR locus, a site consisting of alternating repeat sequences and foreign-derived spacers. In most CRISPR systems, the proteins Cas1 and Cas2 form the integration complex and are both essential for DNA acquisition. Most type V-C and V-D systems lack the cas2 gene and have unusually short CRISPR repeats and spacers.
View Article and Find Full Text PDFIntroduction: A multitiered system of supports (MTSS) represents a widely adopted public health approach to education in the USA. Researchers agree professional learning is critical for educators to implement the critical components of MTSS; however, professional learning approaches vary in their designs and targeted outcomes. While researchers increasingly focus their inquiries on professional learning for MTSS, no systematic research review exists.
View Article and Find Full Text PDFJ Prosthet Dent
October 2018
This report describes the treatment of a 68-year-old man with basosquamous cell carcinoma of the left auricular area. His oncologic treatment resulted in the loss of his left ear and much of the left temporal bone. The loss of a significant portion of the temporal bone precluded the use of extraoral implants.
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