Publications by authors named "Funk A"

The striatum is divided into two interdigitated tissue compartments, the striosome and matrix. These compartments exhibit distinct anatomical, neurochemical, and pharmacological characteristics and have separable roles in motor and mood functions. Little is known about the functions of these compartments in humans.

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Objective: Progression of prediabetes to type 2 diabetes has been associated with β-cell dysfunction, whereas its remission to normoglycemia has been related to improvement of insulin sensitivity. To understand the mechanisms and identify potential biomarkers related to prediabetes trajectories, we compared the proteomics and metabolomics profile of people with prediabetes progressing to diabetes or reversing to normoglycemia within 1 year.

Research Design And Methods: The fasting plasma concentrations of 1,389 proteins and the fasting, 30-min, and 120-min post-oral glucose tolerance test (OGTT) plasma concentrations of 152 metabolites were measured in up to 134 individuals with new-onset diabetes, prediabetes, or normal glucose tolerance.

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Background: Ependymomas of the spinal cord are rare among children and adolescents, and the individual risk of disease progression is difficult to predict. This study aims to evaluate the prognostic impact of molecular typing on pediatric spinal cord ependymomas.

Methods: Eighty-three patients with spinal ependymomas ≤22 years registered in the HIT-MED database (German brain tumor registry for children, adolescents, and adults with medulloblastoma, ependymoma, pineoblastoma, and CNS-primitive neuroectodermal tumors) between 1992 and 2022 were included.

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Objectives: Guidelines recommend addressing health behaviors, mental health, and social needs in primary care. However, it is unclear how often patients want support to address these risks. As part of a randomized trial comparing enhanced care planning versus usual care, we evaluated what risks patients wanted to address.

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The worldwide frequency of head and neck squamous cell carcinoma (HNSCC) is approximately 800,000 new cases, with 430,000 deaths annually. We determined that LZK (encoded by ) is a therapeutic target in HNSCC and showed that inhibition with small molecule inhibitors decreases the viability of HNSCC cells with amplified . A drug-resistant mutant of LZK blocks decreases in cell viability due to LZK inhibition, indicating on-target activity by two separate small molecules.

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Background: Pilot data suggest that off-label, unmonitored antiepileptic drug prescribing for behavioral and psychological symptoms of dementia is increasing, replacing other psychotropic medications targeted by purposeful reduction efforts. This trend accelerated during the COVID-19 pandemic. Although adverse outcomes related to this trend remain unknown, preliminary results hint that harms may be increasing and concentrated in vulnerable populations.

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The insula is an integral component of sensory, motor, limbic, and executive functions, and insular dysfunction is associated with numerous human neuropsychiatric disorders. Insular efferents project widely, but insulo-striate projections are especially numerous. The targets of these insulo-striate projections are organized into tissue compartments, the striosome and matrix.

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Background: Carriers of germline pathogenic variants (PVs) in succinate dehydrogenase genes () are at risk of developing tumors, including paragangliomas, gastrointestinal stromal tumors, and renal cell carcinomas. Early tumor detection is paramount for improved clinical outcome. Blood-based biomarkers could aid in identifying individuals with PVs early and provide functional evidence in patients with variants of unknown significance.

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Article Synopsis
  • Unhealthy alcohol use (UAU) is a major health issue, being the fourth leading preventable cause of death in the US, with recommendations for routine screening in primary care that are not widely implemented.
  • A study tested the effectiveness of practice facilitation—providing tailored education and support—in improving UAU screening and interventions compared to usual care in primary care settings in Virginia.
  • Results showed significant improvements in screening rates and brief interventions in practices that received the facilitation, demonstrating that such support can enhance the delivery of care for alcohol misuse.
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Background: Results of population-level studies examining the effect of the COVID-19 pandemic on the risks of perinatal death have varied considerably.

Objectives: To explore trends in the risk of perinatal death among pregnancies beginning prior to and during the pandemic using a pregnancy cohort approach.

Methods: This secondary analysis included data from singleton pregnancies ≥20 weeks' gestation in Alberta, Canada, beginning between 5 March 2017 and 4 March 2021.

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Introduction: Unhealthy alcohol use increases the risk for and exacerbation of chronic health conditions. As such, screening, prevention, and management of unhealthy alcohol use is especially critical to improving health outcomes for patients with multiple chronic health conditions. It is unclear to what extent multiple chronic condition status is a barrier to screening for unhealthy alcohol use in the primary care setting.

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The Centers for Medicare & Medicaid Services (CMS) grades nursing home performance in antipsychotic prescribing quarterly, publishing findings as a quality measure. While scores have improved since 2011, marked performance variation between facilities persists. To assess quality gap changes between best- and worst-performing deciles, we compared quarterly prescribing changes between these groups pre-pandemic (April 2011 to March 2020) and during the pandemic (April 2020 to March 2022).

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The insula is an integral component of sensory, motor, limbic, and executive functions, and insular dysfunction is associated with numerous human neuropsychiatric disorders. Insular afferents project widely, but insulo-striate projections are especially numerous. The targets of these insulo-striate projections are organized into tissue compartments, the striosome and matrix.

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The US Preventive Services Task Force (USPSTF) recommends screening and behavioral counseling for adults over 18 years for unhealthy alcohol use. Recommended screening instruments include the Alcohol Use Disorders Identification Test-Concise and or Single Alcohol Screening Question. Behavioral counseling is feasible in primary care, taking on average 30 minutes.

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Background: Asymptomatic SARS-CoV-2 infection in children is highly prevalent but its acute and chronic implications have been minimally described.

Methods: In this controlled case-ascertained household transmission study, we recruited asymptomatic children <18 years with SARS-CoV-2 nucleic acid testing performed at 12 tertiary care pediatric institutions in Canada and the United States. We attempted to recruit all test-positive children and 1 to 3 test-negative, site-matched controls.

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Shape memory alloy structures for actuator and vibration damper applications may be manufactured using wire arc additive manufacturing (WAAM), which is one of the additive manufacturing technologies. Multilayer deposition causes heat accumulation during WAAM, which rises the preheat temperature of the previously created layer. This leads to process instabilities, which result in deviations from the desired dimensions and mechanical properties changes.

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Information is scarce on how environmental and dispersal processes interact with biological features of the organisms, such as their habitat affinity, to influence patterns in biodiversity. We examined the role of habitat specialist vs. generalist species, and the spatial configuration, connectivity, and different environmental characteristics of river-floodplain habitats to get a more mechanistic understanding of alpha and beta diversity of fish metacommunities.

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MISTRG is an immunodeficient mouse strain that expresses multiple human cytokines that support hematopoietic stem cell maintenance and myelopoiesis. While establishing a breeding colony of MISTRG mice in a dedicated barrier room, 6 cases of death or disease occurred in pregnant or postpartum mice. Clinically, this manifested as hunched posture, dyspnea, and 1 case of emaciation with ataxia.

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Article Synopsis
  • Each striatal compartment has unique connections and influences on neighboring structures like the globus pallidus interna (GPi) and thalamic nuclei, with different pathways exhibiting varied connectivity patterns.
  • Research using diffusion tractography in humans revealed significant differences in how striosome and matrix connectivity interact with thalamic nuclei, confirming findings from animal studies.
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Background: To assist clinicians with identifying children at risk of severe outcomes, we assessed the association between laboratory findings and severe outcomes among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected children and determined if SARS-CoV-2 test result status modified the associations.

Methods: We conducted a cross-sectional analysis of participants tested for SARS-CoV-2 infection in 41 pediatric emergency departments in 10 countries. Participants were hospitalized, had laboratory testing performed, and completed 14-day follow-up.

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The loss of longitudinal connectivity affects river systems globally, being one of the leading causes of the freshwater biodiversity crisis. Barriers alter the dispersal of aquatic organisms and limit the exchange of species between local communities, disrupting metacommunity dynamics. However, the interplay between connectivity losses due to dams and other drivers of metacommunity structure, such as the configuration of the river network, needs to be explored.

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Importance: The US and Canada currently have no formal published nationwide guidelines for specialists in poison information or emergency departments for the management of acetaminophen poisoning, resulting in significant variability in management.

Objective: To develop consensus guidelines for the management of acetaminophen poisoning in the US and Canada.

Evidence Review: Four clinical toxicology societies (America's Poison Centers, American Academy of Clinical Toxicology, American College of Medical Toxicology, and Canadian Association of Poison Control Centers) selected participants (n = 21).

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The expression of biosynthetic genes in bacterial hosts can enable access to high-value compounds, for which appropriate molecular genetic tools are essential. Therefore, we developed a toolbox of modular vectors, which facilitate chromosomal gene integration and expression in KT2440. To this end, we designed an integrative sequence, allowing customisation regarding the modes of integration (random, at Tn7, or into the 16S rRNA gene), promoters, antibiotic resistance markers as well as fluorescent proteins and enzymes as transcription reporters.

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