Mining Public Domain Data to Develop Selective DYRK1A Inhibitors.

Kinases represent one of the most intensively pursued groups of targets in modern-day drug discovery. Often it is desirable to achieve selective inhibition of the kinase of interest over the remaining ∼500 kinases in the human kinome. This is especially true when inhibitors are intended to be used to study the biology of the target of interest.

Biomechanical Stability of Volar Plate Only Versus Addition of Dorsal Ulnar Pin Plate: A Dorsal Ulnar Fragment, C-3-Type, Distal Radius, Cadaver Fracture Model.

Objective: To determine if the addition of a dorsal ulnar pin plate provides improved stability characteristics in the management of intra-articular distal radius fractures with an associated dorsal ulnar fragment.

Methods: OTA/AO type C3 fractures, with a dorsal ulnar fragment of one-third or one-half the width of the distal radius, were simulated in 9 matched pairs of fresh-frozen cadaveric arms randomized between fixed-angle volar plate only versus volar plate with addition of a dorsal ulnar pin plate. Prepared specimens were mounted in a custom load frame and loaded in extension with stepwise cyclic load increase.

Reduced Attentional Control in Older Adults Leads to Deficits in Flexible Prioritization of Visual Working Memory.

Visual working memory (VWM) resources have been shown to be flexibly distributed according to item priority. This flexible allocation of resources may depend on attentional control, an executive function known to decline with age. In this study, we sought to determine how age differences in attentional control affect VWM performance when attention is flexibly allocated amongst targets of varying priority.

Evaluating an Air Quality Health Index (AQHI) amendment for communities impacted by residential woodsmoke in British Columbia, Canada.

Smoke from burning biomass is an important source of fine particulate matter (PM), but the health risks may not be fully captured by the Canadian Air Quality Health Index (AQHI). In May 2018, the province of British Columbia launched an evidence-based amendment (AQHI-Plus) to improve AQHI performance for wildfire smoke, but the AQHI-Plus was not developed or tested on data from the residential woodsmoke season. This study assesses how the AQHI and AQHI-Plus are associated with acute health outcomes during the cooler seasons of 2010-2017 in British Columbia, Canada.

Large granular lymphocytosis in a cynomolgus macaque (Macaca fascicularis) with a subclinical Trypanosoma cruzi infection.

A 5.25-year-old cynomolgus macaque (Macaca fascicularis) was found to have a marked leukocytosis due to a lymphocytosis on routine quarantine laboratory data prior to inclusion in a preclinical research study. The majority of lymphocytes were characterized as intermediate to large with round to convoluted nuclei, coarse to clumped chromatin, rare prominent nucleoli, and moderate amounts of lightly basophilic cytoplasm that frequently contained small magenta granules and/or clear vacuoles.

Our Vision: An Antiracist Journal.

Our renewed vision for the Journal is to be antiracist at every level. To achieve this, we will go beyond our long-standing charge to advance the knowledge of child development, children's mental health, and prevention and treatment of mental illness to solicit and disseminate research that addresses the systemic presence of racism and its influence on the health and well-being of children of color and their families. We acknowledge that our efforts as a journal to address these inequities have been insufficient and that dismantling the threads of White supremacy requires us to take a more active role.

A Wide Spectrum Study of α-Globin Chain Variants: Cases from the UK.

Over many years, cases of suspected α-globin chain variants were collected from different parts of the UK. The suspicion was based on the clinical picture, high performance liquid chromatography (HPLC) variant percentage, retention time (RT) and isoelectric focusing (IEF). DNA sequencing and the restriction enzyme EI were used for definitive diagnosis.

"I'm Kinda Stuck at Home With Unsupportive Parents Right Now": LGBTQ Youths' Experiences With COVID-19 and the Importance of Online Support.

Purpose: LGBTQ youth are a population who experience unique stressors. This study investigated their experiences with the COVID-19 pandemic via Q Chat Space-a national online chat-based support program.

Methods: Transcript data from 31 synchronous, text-based chats collected during the onset of state-based "social distancing" ordinances in Spring 2020 were analyzed.

Sub-Daily Exposure to Fine Particulate Matter and Ambulance Dispatches during Wildfire Seasons: A Case-Crossover Study in British Columbia, Canada.

Background: Exposure to fine particulate matter () during wildfire seasons has been associated with adverse health outcomes. Previous studies have focused on daily exposure, but levels in smoke events can vary considerably within 1 d.

Objectives: We aimed to assess the immediate and lagged relationship between sub-daily exposure to and acute health outcomes during wildfire seasons in British Columbia.

Two weeks of image-guided left dorsolateral prefrontal cortex repetitive transcranial magnetic stimulation improves smoking cessation: A double-blind, sham-controlled, randomized clinical trial.

Background: Previous studies have found that repetitive transcranial magnetic stimulation (rTMS) to the left dorsal lateral prefrontal cortex (LDLPFC) transiently reduces smoking craving, decreases cigarette consumption, and increases abstinence rates.

Objective: We investigated whether 10 daily MRI-guided rTMS sessions over two weeks to the LDLPFC paired with craving cues could reduce cigarette consumption and induce smoking cessation.

Methods: We enrolled 42 treatment-seeking nicotine-dependent smokers (≥10 cigarettes per day) in a randomized, double-blind, sham-controlled trial.

Risk and protective factors of dementia among adults with post-traumatic stress disorder: a systematic review protocol.

Introduction: Post-traumatic stress disorder (PTSD) is associated with an increased risk of dementia. Individual epidemiological studies have controlled for several confounders of the relationship between PTSD and increased dementia risk, yet particular risk factors underlying this relationship have not been determined. This systematic review protocol aims to identify risk and protective factors of dementia among adults with PTSD.

Detection and Replication of Moku Virus in Honey Bees and Social Wasps.

Transmission of honey bee viruses to other insects, and vice versa, has previously been reported and the true ecological importance of this phenomenon is still being realized. Members of the family Vespidae interact with honey bees via predation or through the robbing of brood or honey from colonies, and these activities could result in virus transfer. In this study we screened and collected from Europe and China and also honey bees and from the UK for Moku virus (MV), an first discovered in the predatory social wasp in Hawaii.

New Measurement of ^{12}C+^{12}C Fusion Reaction at Astrophysical Energies.

Carbon and oxygen burning reactions, in particular, ^{12}C+^{12}C fusion, are important for the understanding and interpretation of the late phases of stellar evolution as well as the ignition and nucleosynthesis in cataclysmic binary systems such as type Ia supernovae and x-ray superbursts. A new measurement of this reaction has been performed at the University of Notre Dame using particle-γ coincidence techniques with SAND (a silicon detector array) at the high-intensity 5U Pelletron accelerator. New results for ^{12}C+^{12}C fusion at low energies relevant to nuclear astrophysics are reported.

JAACAP's Role in Advancing the Science of Pediatric Mental Health and Promoting the Care of Youth and Families During the COVID-19 Pandemic.

As we pen these words, the COVID-19 pandemic is having profound impacts on human society. Based on decades of research, we know that the accompanying illness, death, social isolation, and malnutrition will have deep and lasting impacts on our children and adolescents, their families, and the communities in which they develop. The pandemic is exposing, with terrible clarity, the disparities in human society-racism, poverty, domestic violence, and child maltreatment and neglect-and tragically will likely amplify the negative impacts that each has on child development and mental health.

A Case of Clinical Scholarship.

A 32-year-old child and adolescent psychiatry resident with a history of presenting an abstract at a local psychiatric conference during residency and fourth authorship on an immunotherapy paper from a summer internship during medical school presents with a new-onset desire to write a case report. She has just come off her consultation liaison rotation, during which she consulted on a 12-year-old boy with attention-deficit/hyperactivity disorder, oppositional defiant disorder, disruptive mood dysregulation disorder, and low depressive state hospitalized for pseudoseizures, a new-onset inability to walk, and aggressive outbursts. He had a negative magnetic resonance imaging scan, negative computed tomography scan, negative laboratory test results, and an unremarkable lumbar puncture.

Using Quality Improvement Methodology to Reduce Costs while Improving Efficiency and Provider Satisfaction in a Busy, Academic Musculoskeletal Radiology Division.

Within an everchanging healthcare system, continuous evaluation of standard operating procedures must be performed to ensure optimization of system level organization, communication, and efficiency. Using the Lean management approach, our institution introduced modifications to our musculoskeletal (MSK) radiology workflow in order to facilitate beneficial change that improved clinical workflow efficiency, reduced moonlighting costs, and improved radiologist satisfaction without sacrificing quality of care. The scope of our study included the MSK division of adult inpatient and outpatient populations at three hospitals in a single academic medical center.

A Placebo-Controlled, Parallel-Group, Randomized Clinical Trial of AC-1204 in Mild-to-Moderate Alzheimer's Disease.

Background: Alzheimer's disease (AD) is characterized by amyloid-β plaques, neurofibrillary tangles, and regional cerebral glucose hypometabolism. Providing an alternative metabolic substrate, such as ketone bodies, may be a viable therapeutic option.

Objective: The objective was to determine the efficacy and safety of the AC-1204 formulation of caprylic triglyceride administered daily for 26 weeks in APOE4 non-carrier participants with mild-to-moderate AD.

Health impact analysis of PM from wildfire smoke in Canada (2013-2015, 2017-2018).

Smoke from wildfires contains many air pollutants of concern and epidemiological studies have identified associations between exposure to wildfire smoke PM and mortality and respiratory morbidity, and a possible association with cardiovascular morbidity. For this study, a retrospective analysis of air quality modelling was performed to quantify the exposure to wildfire-PM across the Canadian population. The model included wildfire emissions from across North America for a 5-month period from May to September (i.

Human oocytes harboring damaged DNA can complete meiosis I.

Objective: To determine whether human oocytes possess a checkpoint to prevent completion of meiosis I when DNA is damaged.

Design: DNA damage is considered a major threat to the establishment of healthy eggs and embryos. Recent studies found that mouse oocytes with damaged DNA can resume meiosis and undergo germinal vesicle breakdown (GVBD), but then arrest in metaphase of meiosis I in a process involving spindle assembly checkpoint (SAC) signaling.

Social connection as a public health adaptation to extreme heat events.

Climate change is an increasingly important public health issue, reflected in morbidity and mortality outcomes during extreme heat events. At the same time, the harms of social isolation with respect to a wide range of health outcomes are becoming better understood. Given that older adults are at higher risk during hot weather and at higher risk of social isolation, they are among those at highest risk for adverse impacts of extreme heat events.

Intervention for children with developmental coordination disorder: How robust is our recent evidence?

Background: The evaluation of methods of intervention for children with developmental coordination disorder (DCD) is an ongoing process. Systematic and meta-analytical reviews play an important role in this process. Before 2015, only four reviews of this type were published on this topic.

Snowfall, Temperature, and the Risk of Death From Myocardial Infarction: A Case-Crossover Study.

Previous research has associated snowfall with risk of myocardial infarction (MI). Most studies have been conducted in regions with harsh winters; it remains unclear whether snowfall is associated with risk of MI in regions with milder or more varied climates. A case-crossover design was used to investigate the association between snowfall and death from MI in British Columbia, Canada.