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The POU domain gene family of transcription factors share a conserved bipartite DNA binding domain, and exhibit distinct temporal and spatial patterns of expression during development, particularly in the forebrain. A cDNA encoding a new member of the POU-III class of the POU domain gene family, referred to as Brn-4, was isolated from a rat hypothalamic cDNA library. Like other mammalian POU-III genes previously characterized (Brn-1, Brn-2, Tst-1), Brn-4 transcripts are initially widely expressed at all levels of the developing neural tube, but in contrast to other previously described POU-III genes, are subsequently restricted to only a few regions of the adult forebrain, including the supraoptic and paraventricular nuclei of the hypothalamus. Brn-4 was shown to bind to DNA sequences containing the octamer motif and to trans-activate promoters containing this DNA binding motif, based on the actions of a unique N-terminal information. This ontogenic pattern of Brn-4 expression in concert with that of Oct-2 and Pit-1, indicates that certain POU domain genes potentially exert their primary functions widely during early neural development, and in a very limited set of neurons in the mature brain.

To investigate the effects of inhibiting the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome on neuronal damage and chronic pro-inflammatory responses during epileptogenesis in a mouse model of pilocarpine-induced status epilepticus (SE). Methods: Mice were randomly allocated into three groups: control, SE, and SE + MCC 950. The expression patterns of M1 and M2 microglial biomarkers in the hippocampus were quantified using Western blotting, quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and immunofluorescence staining. Additionally, seizure susceptibility, video-electroencephalography recording, Morris water maze test, and brain immunofluorescence staining were performed to evaluate the epileptic brain 4 weeks post-SE. Results: Within 72 hours post-SE, hippocampal microglia demonstrated a preferential polarization towards the M1 phenotype, a trend that was mitigated by NLRP3 inflammasome inhibition. During epileptogenesis, SE mice treated with NLRP3 inflammasome inhibition exhibited reduced neuronal damage, improved cognitive function, decreased seizure susceptibility, and attenuated chronic pro-inflammatory responses. Conclusion: Inhibition of NLRP3 inflammasome post-SE effectively ameliorates neuronal loss, seizure susceptibility, and cognitive dysfunction during epileptogenesis. This neuroprotective effect may be mediated through the mitigation of chronic pro-inflammatory responses within the epileptic brain. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) is the most common renal tumor in adults, arising from renal tubular epithelial cells. Approximately 30% of patients with RCC have metastases at the time of diagnosis, while metastases can be seen in 40% of patients during follow-up after nephrectomy. Metastases most commonly occur in the lung, bone, and lymph nodes. In our study, we aimed to retrospectively examine the cases diagnosed with RCC metastasis and evaluate their clinicopathological features. Age, gender, metastasis site, number of metastatic foci, localization of primary kidney tumor, histopathological type of primary kidney tumor, diameter of primary kidney tumor, grade of primary kidney tumor, and survival status of 52 patients diagnosed with RCC metastasis were recorded. Eleven (21.2%) of the cases had primary RCC and simultaneous (synchronous) RCC metastasis in the kidney. In 27 (51.9%) cases, RCC metastasis was detected in the follow-up period (metachronous) after nephrectomy due to the diagnosis of primary. The number of patients who were initially diagnosed with RCC metastasis and then were found to have primary RCC in the kidney was 14 (26.9%). Thirty-nine (75%) cases had a single metastatic focus. Metastasis site distribution of the cases; bone 18 (34.6%), lung 16 (30.8%), lymph nodes 8 (15.4%), liver 6 (11.5%), adrenal gland 6 (11.5%), brain 4 (7.7%) was. RCC metastases can occur as metastatic disease before primary tumor diagnosis, at the time of primary tumor diagnosis, or years after nephrectomy. [ABSTRACT FROM AUTHOR]

Purpose: A possible pathway behind gadolinium retention in brain is leakage of contrast agents from blood to cerebrospinal fluid and entry into brain along perivascular (glymphatic) pathways. The object of this study was to assess for signs of gadolinium retention in brain 4 weeks after intrathecal contrast enhanced MRI. Methods: We prospectively applied standardized T1 mapping of the brain before and 4 weeks after intrathecal administration of 0.5 mmol gadobutrol in patients under work-up of cerebrospinal fluid circulation disorders. Due to methodological limitations, a safety margin for percentage change in T1 time was set to 3%. Region-wise differences were assessed by pairwise comparison using t-tests and forest plots, and statistical significance was accepted at.05 level (two-tailed). Results: In a cohort of 76 participants (mean age 47.2 years ± 17.9 [standard deviation], 47 women), T1 relaxation times remained unchanged in cerebral cortex and basal ganglia 4 weeks after intrathecal gadobutrol. T1 was reduced from 1082 ± 46.7 ms to 1070.6 ± 36.5 ms (0.98 ±2.9%) (mean [standard deviation]) (p=0.001) in white matter, thus within the pre-defined 3% safety margin. The brain stem and cerebellum could not be assessed due to poor alignment of posterior fossa structures at scans from different time points. Conclusion: Gadolinium retention was not detected in the cerebral hemispheres 4 weeks after an intrathecal dose of 0.5 mmol gadobutrol, implying that presence of contrast agents in cerebrospinal fluid is of minor importance for gadolinium retention in brain. [ABSTRACT FROM AUTHOR]

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Analysis of the organization becomes necessary when the organization shows certain phenomena such as performance decreasing or increasing sharply, organizations structural changes, organizational climate is not conducive, the number of employee changes, and so on. This study explores the implementation of Morgan's Organizational Metaphor Theory in the management practice within a private higher education institution in Jakarta. This study helps to interpret the advancements and barriers in the current management practice. This study uses a qualitative research method with a case study approach. Some analyses were made based on the eight metaphors about organizations according to Morgan, namely the metaphor of the organization 1) as a machine, 2) as an organism, 3) as the brain, 4) as culture, 5) as a political system, 6) as a physical prison, 7) as a dynamic and transforming reality, and 8) as an instrument of domination. The results show that the institutions should strive to make some important changes in their management practice, especially by applying the recent management practices, including treating lecturers and staff as partners. This study implies that the implementation of modern management must be accompanied by the leadership. [ABSTRACT FROM AUTHOR]

Large language models (LLMs) are a new asset class in the machine-learning landscape. Here we offer a primer on defining properties of these modeling techniques. We then reflect on new modes of investigation in which LLMs can be used to reframe classic neuroscience questions to deliver fresh answers. We reason that LLMs have the potential to (1) enrich neuroscience datasets by adding valuable meta-information, such as advanced text sentiment, (2) summarize vast information sources to overcome divides between siloed neuroscience communities, (3) enable previously unthinkable fusion of disparate information sources relevant to the brain, (4) help deconvolve which cognitive concepts most usefully grasp phenomena in the brain, and much more. Bzdok et al. discuss large language models (LLMs) as a recently emerged toolkit in an age when neurobiology too has become "computable." [ABSTRACT FROM AUTHOR]

Here we characterize 6 cases (4 autopsies and 2 biopsies) of histiocytic sarcoma in the CNS of cats. All affected cats had chronic, progressive clinical signs. Three autopsied cats were euthanized because of a poor prognosis, and one died. The clinical outcome for the biopsy cases remains unknown. Tumors occurred in the brain (4 cases), spinal cord (1 case), and brain and spinal cord (1 case). Neoplasms were restricted to the CNS in 3 cases. Reported gross changes in the 4 autopsy cases consisted of neuroparenchymal swelling with or without tissue pallor or gray discoloration (2 cases) and a yellow or dark-gray mass (2 cases). Histologically, pleomorphic, round-to-elongate neoplastic cells with typical histiocytic morphology effaced the neuroparenchyma and leptomeninges. Multinucleate neoplastic cells were observed in all cases. The mitotic count was 1–24 in 2.37 mm2 (10 FN22 40× fields). Neoplastic cells in all cases had positive immunolabeling for Iba1; immunolabeling was negative for E-cadherin, CD3, CD79, and MUM1, confirming their histiocytic origin. [ABSTRACT FROM AUTHOR]

Background: Hijacking the transferrin receptor (TfR) is an effective strategy to transport amyloid-beta (Aβ) immuno-positron emission tomography (immunoPET) ligands across the blood–brain barrier (BBB). Such ligands are more sensitive and specific than small-molecule ligands at detecting Aβ pathology in mouse models of Alzheimer's disease (AD). This study aimed to determine if this strategy would be as sensitive in rats and to assess how TfR affinity affects BBB transport of bispecific immunoPET radioligands. Methods: Two affinity variants of the rat TfR antibody, OX26, were chemically conjugated to a F(ab′)2 fragment of the anti-Aβ antibody, bapineuzumab (Bapi), to generate two bispecific fusion proteins: OX265-F(ab′)2-Bapi and OX2676-F(ab′)2-Bapi. Pharmacokinetic analyses were performed 4 h and 70 h post-injection of radioiodinated fusion proteins in wild-type (WT) rats. [124I]I-OX265-F(ab′)2-Bapi was administered to TgF344-AD and WT rats for in vivo PET imaging. Ex vivo distribution of injected [124I]I-OX265-F(ab′)2-Bapi and Aβ pathology were assessed. Results: More [125I]I-OX265-F(ab′)2-Bapi was taken up into the brain 4 h post-administration than [124I]I-OX2676-F(ab′)2-Bapi. [124I]I-OX265-F(ab′)2-Bapi PET visualized Aβ pathology with significantly higher signals in the TgF344-AD rats than in the WT littermates without Aβ pathology. The PET signals significantly correlated with Aβ levels in AD animals. Conclusion: Affinity to TfR affects how efficiently a TfR-targeting bispecific fusion protein will cross the BBB, such that the higher-affinity bispecific fusion protein crossed the BBB more efficiently. Furthermore, bispecific immunoPET imaging of brain Aβ pathology using TfR-mediated transport provides good imaging contrast between TgF344-AD and WT rats, suggesting that this immunoPET strategy has the potential to be translated to higher species. [ABSTRACT FROM AUTHOR]

Given the clear role of inflammation in the pathogenesis of Parkinson's disease (PD) and its impact on incidence and phenotypical characteristics, this review provides an overview with focus on inflammatory biofluid markers in blood and cerebrospinal fluid (CSF) in PD patient cohorts. In preparation for clinical trials targeting the immune system, we specifically address the following questions: 1) What evidence do we have for pro-inflammatory profiles in blood and in CSF of sporadic and genetic PD patients? 2) Is there a role of anti-inflammatory mediators in blood/CSF? 3) Do inflammatory profiles in blood reflect those in CSF indicative of a cross-talk between periphery and brain? 4) Do blood/CSF inflammatory profiles change over the disease course as assessed in repeatedly taken biosamples? 5) Are blood/CSF inflammatory profiles associated with phenotypical trajectories in PD? 6) Are blood/CSF inflammatory profiles associated with CSF levels of neurodegenerative/PD-specific biomarkers? Knowledge on these questions will inform future strategies for patient stratification and cohort enrichment as well as suitable outcome measures for clinical trials. [ABSTRACT FROM AUTHOR]

Hyperspectral imaging (HSI) is a promising imaging modality that uses visible light to obtain information about blood flow. It has the distinct advantage of being noncontact, nonionizing, and noninvasive without the need for a contrast agent. Among the many applications of HSI in the medical field are the detection of various types of tumors and the evaluation of their blood flow, as well as the healing processes of grafts and wounds. Since tumor perfusion is one of the critical factors in oncology, we assessed the value of HSI in quantifying perfusion changes during interventions in clinical oncology through a systematic review of the literature. The PubMed and Web of Science electronic databases were searched using the terms "hyperspectral imaging perfusion cancer" and "hyperspectral imaging resection cancer". The inclusion criterion was the use of HSI in clinical oncology, meaning that all animal, phantom, ex vivo, experimental, research and development, and purely methodological studies were excluded. Twenty articles met the inclusion criteria. The anatomic locations of the neoplasms in the selected articles were as follows: kidneys (1 article), breasts (2 articles), eye (1 article), brain (4 articles), entire gastrointestinal (GI) tract (1 article), upper GI tract (5 articles), and lower GI tract (6 articles). HSI is a potentially attractive imaging modality for clinical application in oncology, with assessment of mastectomy skin flap perfusion after reconstructive breast surgery and anastomotic perfusion during reconstruction of gastrointenstinal conduit as the most promising at present. [ABSTRACT FROM AUTHOR]