Publications by authors named "Kohler R"

Background: Cervical cancer disparities persist among minoritized women due to infrequent screening and poor follow-up. Structural and psychosocial barriers to following up with colposcopy are problematic for minoritized women. Evidence-based interventions using patient navigation and tailored telephone counseling, including the Tailored Communication for Cervical Cancer Risk (TC3), have modestly improved colposcopy attendance.

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The R47H variant of the triggering receptor expressed on myeloid cells 2 (TREM2) is a risk factor for Alzheimer's disease in humans and leads to lower bone mass accrual in female but not male 12-mo-old mice. To determine whether, as with aging, gonadectomy results in sex-specific musculoskeletal effects, gonad removal or SHAM surgery was performed in 4-mo-old TREM2 mice and WT male and female littermates ( = 10-12/group), with sexes analyzed separately. Body weight was lower in males, but higher in females after gonadectomy, independently of their genotype.

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Cancer-associated fibroblasts (CAFs) expressing fibroblast activation protein alpha (FAP) are abundant in tumor microenvironments and represent an emerging target for PET cancer imaging. While different quinolone-based small molecule agents have been developed for whole-body imaging, there is a scarcity of well-validated fluorescent small molecule imaging agents to better study these cells in vivo. Here, we report the synthesis and characterization of a series of fluorescent FAP imaging agents based on the common quinolone azide inhibitor.

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Purpose: Breast cancer (BC) is the most common female cancer worldwide, and the burden is increasing across sub-Saharan Africa. For women with hormone receptor-positive (HR+) cancers, endocrine therapy (ET) taken for 5-10 years can reduce the risk of recurrence by half. We explored experiences with ET and barriers to utilization among survivors in Botswana.

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Secreted phosphosprotein 1 (SPP1) tumor-associated macrophages (TAM) are abundant tumor myeloid cells that are immunosuppressive, pro-tumorigenic, and have a highly negative prognostic factor. Despite this, there is a lack of efficient TAM-specific therapeutics capable of reducing SPP1 expression. Here, on a phenotypic screen is reported to identify small molecule SPP1 modulators in macrophages.

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Brain rhythms can facilitate neural communication for the maintenance of brain function. Beta rhythms (13-35 Hz) have been proposed to serve multiple domains of human ability, including motor control, cognition, memory, and emotion, but the overarching organisational principles remain unknown. To uncover the circuit architecture of beta oscillations, we leverage normative brain data, analysing over 30 hr of invasive brain signals from 1772 channels from cortical areas in epilepsy patients, to demonstrate that beta is the most distributed cortical brain rhythm.

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Intravital deep bone marrow imaging is crucial to studying cellular dynamics and functions but remains challenging, and minimally invasive methods are needed. We employed a high pulse-energy 1650 nm laser to perform three-photon microscopy , reaching ≈400 μm depth in intact mouse tibia. Repetition rates of 3 and 4 MHz allowed us to analyze motility patterns of fast and rare cells within unperturbed marrow and to identify a bi-modal migratory behavior for plasma cells.

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HPV-associated cancer disparities disproportionately affect Black/African American and Hispanic individuals in the U.S. HPV vaccination, which can prevent many HPV-associated cancers, should be clearly recommended by pediatricians to parents of adolescents aged 9-12, yet uptake and completion remain lower than other adolescent vaccinations.

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The ability to initiate volitional action is fundamental to human behaviour. Loss of dopaminergic neurons in Parkinson's disease is associated with impaired action initiation, also termed akinesia. Both dopamine and subthalamic deep brain stimulation (DBS) can alleviate akinesia, but the underlying mechanisms are unknown.

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Methodology is described for the synthesis of C derivatives of raloxifene, a prescribed drug for the treatment and prevention of osteoporosis. Studies have explored the incorporation of electron-withdrawing substituents at C of the benzothiophene core. Efficient processes are also examined to introduce hydrogen bond donor and acceptor functionality.

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Purpose: The purpose of this study was to analyze the prevalence of and complications resulting from temporal bone fractures in adult and pediatric patients evaluated for cranio-facial trauma in an emergency setting.

Methods: A retrospective blinded analysis of CT scans of a series of 294 consecutive adult and pediatric patients with cranio-facial trauma investigated in the emergency setting was conducted. Findings were compared between the two populations.

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As international incidence of diabetes and diabetes-driven comorbidities such as chronic kidney disease (CKD) continue to climb, interventions are needed that address the high-risk skeletal fragility of what is a complex disease state. Romosozumab (Romo) is an FDA-approved sclerostin inhibitor that has been shown to increase bone mineral density and decrease fracture rates in osteoporotic patients with mild to severe CKD, but its effect on diabetes-weakened bone is unknown. We aimed to test Romo's performance in a model of combined diabetes and CKD.

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: Nucleic acid constructs are commonly used for vaccination, immune stimulation, and gene therapy, but their use in cancer still remains limited. One of the reasons is that systemic delivery to tumor-associated antigen-presenting cells (dendritic cells and macrophages) is often inefficient, while off-target nucleic acid-sensing immune pathways can stimulate systemic immune responses. Conversely, certain carbohydrate nanoparticles with small molecule payloads have been shown to target these cells efficiently in the tumor microenvironment.

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A-MYB (MYBL1) is a transcription factor with a role in meiosis in spermatocytes. The related B-MYB protein is a key oncogene and a master regulator activating late cell cycle genes. To activate genes, B-MYB forms a complex with MuvB and is recruited indirectly to cell cycle genes homology region (CHR) promoter sites of target genes.

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The ParABS system is crucial for the faithful segregation and inheritance of many bacterial chromosomes and low-copy-number plasmids. However, despite extensive research, the spatiotemporal dynamics of the ATPase ParA and its connection to the dynamics and positioning of the ParB-coated cargo have remained unclear. In this study, we utilize high-throughput imaging, quantitative data analysis, and computational modeling to explore the in vivo dynamics of ParA and its interaction with ParB-coated plasmids and the nucleoid.

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Article Synopsis
  • Type 2 diabetes (T2D) is linked to higher rates of fractures and related mortality, with effective mouse models for studying its impact on bone health being limited.
  • The KK/A mouse model, with a mutation in the agouti gene, reliably induces T2D with persistent hyperglycemia in both male and female subjects, making it suitable for bone studies.
  • Findings indicate that KK/A mice represent the early stages of T2D characterized by high blood glucose and insulin levels, though the presence of diabetic male control mice presents some limitations for comparison.
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Osteogenesis imperfecta (OI) increases fracture risk due to changes in bone quantity and quality caused by mutations in collagen and its processing proteins. Current therapeutics improve bone quantity, but do not treat the underlying quality deficiencies. Male and female G610C+/- mice, a murine model of OI, were treated with a combination of raloxifene and in vivo axial tibial compressive loading starting at 10 weeks of age and continuing for 6 weeks to improve bone quantity and quality.

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Purpose: Evaluate the impact of high vs low intraoperative intraocular pressure (IOP) during phacoemulsification on anterior and posterior physiology.

Setting: Private practice in Des Moines, Iowa.

Design: Prospective, randomized, paired-eye clinical trial of patients anticipating bilateral cataract surgery.

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Individual differences in gray-matter morphometry in the limbic system and frontal cortex have been linked to clinical features of cocaine use disorder (CUD). Self-administration paradigms can provide more direct measurements of the relationship between the regulation of cocaine use and gray-matter morphometry when compared to self-report assessments. Our goal was to investigate associations with self-administration behavior in subcortical and cortical brain regions.

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Analyzing immune cell interactions in the bone marrow is vital for understanding hematopoiesis and bone homeostasis. Three-dimensional analysis of the complete, intact bone marrow within the cortex of whole long bones remains a challenge, especially at subcellular resolution. We present a method that stabilizes the marrow and provides subcellular resolution of fluorescent signals throughout the murine femur, enabling identification and spatial characterization of hematopoietic and stromal cell subsets.

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Article Synopsis
  • Researchers are developing a new method for detecting trace gases in the air using ionization energies, which can be miniaturized and fine-tuned.
  • Traditional methods for identification rely on large equipment, like mass spectrometers, but this new approach uses electron impact ionization, generated via the photoelectric effect, for better sensitivity at a lower scale.
  • The method achieves sensitivity levels of 1 ppm, comparable to classic photoionization detection (PID), and can identify substances with an accuracy of 30 meV, supported by quantum mechanical models.
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Tumor-associated macrophages (TAM) are a diverse population of myeloid cells that are often abundant and immunosuppressive in human cancers. CXCL9 TAM has recently been described to have an antitumor phenotype and is linked to immune checkpoint response. Despite the emerging understanding of the unique antitumor TAM phenotype, there is a lack of TAM-specific therapeutics to exploit this new biological understanding.

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A 7-year-old female spayed Australian shepherd dog was presented for an acute onset of inability to stand. On physical examination, the dog was unable to support weight on the thoracic limbs. On neurological examination, the thoracic limbs had absent hopping and paw placement and reduced withdrawal reflexes bilaterally.

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Background: Deep brain stimulation (DBS) is an invasive treatment option for patients with Parkinson's disease. Recently, adaptive DBS (aDBS) systems have been developed, which adjust stimulation timing and amplitude in real-time. However, it is unknown how changes in parameters, movement states and the controllability of subthalamic beta activity affect aDBS performance.

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