Publications by authors named "Hamlin D"

Background: Catatonia is a complex syndrome with prominent psychomotor, cognitive, and affective manifestations. Among the commonly described manifestations of catatonia are mannerisms and stereotypies. Kahlbaum, who coined the term catatonia, described several presentations of mannerisms and stereotypies as complex behaviors in his monograph.

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The α-emitter At deposits a high amount of energy within a few cell diameters, resulting in irreparable DNA double-strand breaks while minimizing off-target toxicity. We investigated the use of the At-labeled anti-CD45 monoclonal antibody (mAb) At-CD45-B10 as a nonmyeloablative conditioning regimen for dog-leukocyte-antigen-haploidentical hematopoietic cell transplantation. Seventeen healthy dogs were injected with either a 0.

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Purpose: Glypican-3 (GPC3)-targeted radioisotope immuno-positron emission tomography (immunoPET) may lead to earlier and more accurate diagnosis of hepatocellular carcinoma (HCC), thus facilitating curative treatment, decreasing early recurrence, and enhancing patient survival. We previously demonstrated reliable HCC detection using a zirconium-89-labeled murine anti-GPC3 antibody (89Zr-αGPC3M) for immunoPET. This study evaluated the efficacy of the humanized antibody successor (αGPC3H) to further clinical translation of a GPC3-based theranostic for HCC.

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Introduction: Tau aggregation into neurofibrillary tangles in Alzheimer's disease (AD) is a dynamic process involving changes in tau phosphorylation, isoform composition, and morphology. To facilitate studies of tangle maturity, we developed an image analysis pipeline to study antibody labeling signatures that can distinguish tangle maturity levels in AD brain tissue.

Methods: Using fluorescent immunohistochemistry, we co-labeled AD brain tissue with four antibodies that bind different tau epitopes.

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Background: Catatonia has been increasingly associated with mood disorders and is recognized as a specifier in the DSM-5 and DSM-5-TR. The DSM-5-TR recognizes melancholia as a specifier for depressive episodes in major depressive disorder and bipolar disorder. It is characterized by severe anhedonia, lack of reactivity, excessive or delusional guilt, and significant vegetative symptoms.

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Large animal models of mild traumatic brain injury (mTBI) are needed to elucidate the pathophysiology of mechanical insult to a gyrencephalic brain. Sheep (ovis aries) are an attractive model for mTBI because of their neuroanatomical similarity to humans; however, few histological studies of sheep mTBI models have been conducted. We previously developed a sheep mTBI model to pilot methods for investigating the mechanical properties of brain tissue after injury.

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Snacks and beverages are often sold in addition to meals in U.S. schools ("competitive foods"), but their current nutritional quality and compliance with national Smart Snacks standards are unknown.

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Purpose: Hematopoietic cell transplantation (HCT) has curative potential for myeloid malignancies, though many patients cannot tolerate myeloablative conditioning with high-dose chemotherapy alone or with total-body irradiation (TBI). Here we report long-term outcomes from a phase I/II study using iodine-131 (131I)-anti-CD45 antibody BC8 combined with nonmyeloablative conditioning prior to HLA-haploidentical HCT in adults with high-risk relapsed/ refractory acute myeloid or lymphoid leukemia (AML or ALL), or myelodysplastic syndrome (MDS; ClinicalTrials.gov, NCT00589316).

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Background: Catatonia is a complex syndrome notable for a highly variable presentation. Standardized exam and criteria can enumerate possible presentations, but recognition of novel catatonic phenomenon may facilitate better understanding of catatonia's core features.

Case Presentation: A 61 year-old divorced pensioner with history of schizoaffective disorder was hospitalized for psychosis in the setting of medication noncompliance.

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Article Synopsis
  • Early recurrence of hepatocellular carcinoma (HCC) after surgery is common and worsened by ineffective imaging, which can miss treatment chances.
  • This study tested a zirconium-89 radiolabeled antibody targeting glypican-3 (GPC3) in mice to improve detection of small HCC tumors using PET imaging.
  • The results showed that the Zr-αGPC3 had 100% sensitivity in identifying tumors as small as 330 μm, but had a specificity of only 60%, indicating that while it effectively detects tumors, it may also misidentify some non-tumor tissues.
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Targeted radiopharmaceutical therapy with alpha-particle emitters (αRPT) is advantageous in cancer treatment because the short range and high local energy deposition of alpha particles enable precise radiation delivery and efficient tumor cell killing. However, these properties create sub-organ dose deposition effects that are not easily characterized by direct gamma-ray imaging (PET or SPECT). We present a computational procedure to determine the spatial distribution of absorbed dose from alpha-emitting radionuclides in tissues using digital autoradiography activity images from an ionizing-radiation quantum imaging detector (iQID).

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The alpha particle-emitting radionuclide astatine-211 (At) is of interest for targeted radiotherapy; however, low in vivo stability of many At-labeled cancer-targeting molecules has limited its potential. As an alternative labeling method, we evaluated whether a specific type of astatinated aryl compound that has the At atom in a higher oxidation state might be stable to in vivo deastatination. In the research effort, para-iodobenzoic acid methyl ester and dPEG-amino acid methyl ester derivatives were prepared as HPLC standards.

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Article Synopsis
  • Radioimmunotherapy (RIT) is being explored to enhance treatment for acute leukemia and higher-risk myelodysplastic syndrome (MDS), focusing on alpha-particle emitters like astatine-211 (At) that can kill target cells effectively within a short distance.* -
  • Researchers developed murine monoclonal antibodies (mAbs) that specifically target the CD123 antigen, found on acute leukemia and MDS cells, and confirmed that these mAbs could be linked to a boron compound and labeled with At for targeted treatment.* -
  • In experiments with immunodeficient mice, the At-labeled anti-CD123 mAbs specifically reduced tumor size and improved survival rates in CD123-positive leukemia models, suggesting that
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Symmetric dimethylarginine (SDMA) is an excretory renal function biomarker shown to correlate well with glomerular filtration rate in dogs, cats, humans, and rats. The objectives of this study were to determine utility of serum SDMA as a renal biomarker in a rat model of gentamicin-induced renal injury and to provide validation of a commercially available SDMA immunoassay for rat serum. Rats were randomly assigned to one of three dose levels of gentamicin (20, 50, or 100 mg/kg) or a vehicle control group and dosed once daily by subcutaneous injection for either four or ten days.

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Article Synopsis
  • Hepatocellular carcinoma (HCC) is a serious global health issue with few effective treatments for advanced stages, prompting research into targeted therapies like α-therapy which involves delivering α-particle-emitting radionuclides, such as Th, specifically to cancer cells.
  • The study focuses on developing a Th-labeled antibody (Th-octapa-αGPC3) that targets Glypican-3 (GPC3), a protein often overexpressed in HCC, showing high efficiency in labeling and maintaining stability in vitro.
  • In preclinical tests involving mice with HCC, Th-octapa-αGPC3 effectively accumulated in tumors while sparing normal tissue, leading to a significant tumor reduction at specific
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Community-engaged research (CEnR) has emerged within public health and medicine as an approach to research designed to increase health equity, reduce health disparities, and improve community and population health. We sought to understand how CEnR has been conducted and to identify needs to support CEnR within an emerging academic learning health system (aLHS). We conducted individual semi-structured interviews with investigators experienced in CEnR at an emerging aLHS in the southeastern United States.

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In a canine model of presensitization using donor blood transfusions, 100% of historical control dogs receiving 9.2 Gy total body irradiation (TBI) conditioning before dog leukocyte antigen (DLA)-identical marrow grafts had graft rejection. In this presensitization model, we investigated whether the addition of monoclonal antibody (mAb)-based targeted radioimmunotherapy (RIT) with astatine-211 (At) to TBI could overcome graft rejection.

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Glypican-3 (GPC3) is a tumor associated antigen expressed by hepatocellular carcinoma (HCC) cells. This preclinical study evaluated the efficacy of a theranostic platform using a GPC3-targeting antibody αGPC3 conjugated to zirconium-89 (Zr) and yttrium-90 (Y) to identify, treat, and assess treatment response in a murine model of HCC. A murine orthotopic xenograft model of HCC was generated.

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Academic medical centers (AMCs) face challenges in conducting research among traditionally marginalized communities due to long-standing community mistrust. Evidence suggests that some AMC faculty and staff lack an understanding of the history of distrust and social determinants of health (SDH) affecting their communities. Wake Forest Clinical and Translational Science Institute Program in Community Engagement (PCE) aims to build bridges between communities and Wake Forest Baptist Health by equipping faculty, clinicians, administrators, and staff (FCAS) with a better understanding of SDH.

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Pretargeted radioimmunotherapy (PRIT) has been investigated as a multi-step approach to decrease relapse and toxicity for high-risk acute myeloid leukemia (AML). Relevant factors including endogenous biotin and immunogenicity, however, have limited the use of PRIT with an anti-CD45 antibody streptavidin conjugate and radiolabeled DOTA-biotin. To overcome these limitations we designed anti-murine and anti-human CD45 bispecific antibody constructs using 30F11 and BC8 antibodies, respectively, combined with an anti-yttrium (Y)-DOTA single-chain variable fragment (C825) to capture a radiolabeled ligand.

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Background: Delayed Post Hypoxic Leukoencephalopathy (DPHL) is a syndrome that occurs after hypoxia, and can present with a variety of neuropsychiatric symptoms, including catatonia and paroxysmal sympathetic hyperactivity (PSH). The gold standard for the treatment of catatonia is electroconvulsive therapy (ECT). However, ECT can exacerbate the paroxysms of sympathetic hyperactivity and complicate recovery from DPHL.

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