bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic MRI With Hyperpolarized 13C-Pyruvate for Early Detection of Fibrogenic Kidney Metabolism
Authors: Bøgh Nikolaj , Bertelsen Lotte B. , Rasmussen Camilla W. , Bech Sabrina K. , Keller Anna K. , Madsen Mia G. , Harving Frederik , Thorsen Thomas H. , Mieritz Ida K. , Hansen Esben SS. , Wanders Alkwin , Laustsen Christoffer 
Published: June 2024

Objectives
Fibrosis is the final common pathway for chronic kidney disease and the best predictor for disease progression. Besides invasive biopsies, biomarkers for its detection are lacking. To address this, we used hyperpolarized 13C-pyruvate MRI to detect the metabolic changes associated with fibrogenic activity of myofibroblasts.

Materials and Methods
Hyperpolarized 13C-pyruvate MRI was performed in 2 pig models of kidney fibrosis (unilateral ureteral obstruction and ischemia-reperfusion injury). The imaging data were correlated with histology, biochemical, and genetic measures of metabolism and fibrosis. The porcine experiments were supplemented with cell-line experiments to inform the origins of metabolic changes in fibrogenesis. Lastly, healthy and fibrotic human kidneys were analyzed for the metabolic alterations accessible with hyperpolarized 13C-pyruvate MRI.

Results
In the 2 large animal models of kidney fibrosis, metabolic imaging revealed alterations in amino acid metabolism and glycolysis. Conversion from hyperpolarized 13C-pyruvate to 13C-alanine decreased, whereas conversion to 13C-lactate increased. These changes were shown to reflect profibrotic activity in cultured epithelial cells, macrophages, and fibroblasts, which are important precursors of myofibroblasts. Importantly, metabolic MRI using hyperpolarized 13C-pyruvate was able to detect these changes earlier than fibrosis-sensitive structural imaging. Lastly, we found that the same metabolic profile is present in fibrotic tissue from human kidneys. This affirms the translational potential of metabolic MRI as an early indicator of fibrogenesis associated metabolism.

Conclusions
Our findings demonstrate the promise of hyperpolarized 13C-pyruvate MRI for noninvasive detection of fibrosis development, which could enable earlier diagnosis and intervention for patients at risk of kidney fibrosis.
FDG PET in a Patient on a GLP-1 Agonist/Insulin Secretagogue
Authors: Oldan Jorge D. , Landman Paula G. , Schroeder Jennifer A. , Khandani Amir H. , Solnes Lilja B. , Lee Carrie B. , Rowe Steven P. 
Published: June 2024

Abstract
With the increase in use of GLP-1 receptor agonists such as semaglutide (Ozempic, Wegovy, Rybelsus) in the population, nuclear medicine physicians should be aware of the possibility of nondiagnostic FDG PET scans due to these medications, which work partly by increasing insulin secretion. We demonstrate a case where a patient’s use of such a medication presumptively led to muscular and myocardial uptake, complicating scan interpretation considerably. Clinicians should be aware of the presence of these drugs and their potential effect on biodistribution in FDG PET. Further study is needed to best understand the effects of these medications on FDG biodistribution.
Metastatic Adenoid Cystic Carcinoma of the Bartholin Gland
Authors: Gray Benjamin Cole , Gellatly Matthew James , Oldan Jorge Daniel 
Published: June 2024

Abstract
Adenoid cystic carcinoma (ACC) of the Bartholin gland is an exceedingly rare neoplasm. A 56-year-old woman with remote ACC resection (plus neoadjuvant chemoradiation and adjuvant chemotherapy) presented to an outside institution with shortness of breath. CT showed bilateral pulmonary nodules and mediastinal lymphadenopathy. With high clinical suspicion for metastatic disease, 18F-FDG PET/CT was performed and showed scattered nodules with mild FDG uptake along with FDG-avid mediastinal, bilateral hilar, and bilateral cervical chain lymphadenopathy. Lung biopsy of a hypermetabolic nodule confirmed metastatic ACC.
18F-FDG PET/CT Findings of a Patient With Stercoral Colitis
Authors: Şahin Özlem , Aydın Zeynep , Kerimoğlu Ülkü , Karakaşoğlu Cennet Cansel , Kaya Buğra 
Published: June 2024

Abstract
Stercoral colitis is a colonic inflammation caused by fecal impaction. It is now more commonly discussed in the literature due to its clinical significance, which has gained recognition in recent years. Delayed diagnosis may result in complications such as sepsis and perforation, which have a high mortality rate. Reporting incidentally detected stercoral colitis on FDG PET/CT can help prevent mortality and morbidity by enabling early diagnosis and treatment. In this case, we report on a patient with gastric cancer who was identified with stercoral colitis using FDG PET/CT data.
Unusual Achalasia Presentation Detected on 131I SPECT/CT in a Papillary Thyroid Carcinoma Patient
Authors: Hu Shengqing , Lan Xiaoli , Cao Wei , Gao Zairong , Xia Xiaotian 
Published: June 2024

Abstract
Various factors leading to unexpected false-positive 131I uptake have been extensively studied in patients with differentiated thyroid carcinoma. In this case, we present a patient who underwent achalasia surgery and subsequently exhibited abnormal 131I uptake on SPECT/CT imaging. The patient was a known case of papillary thyroid carcinoma that suggested to 131I therapy. 131I SPECT/CT showed linear increased activity in the distended esophagus.
Brain Nocardiosis Mimicking Intracerebral Invasion on 68Ga-Pentixafor PET/CT in a Patient With Multiple Myeloma
Authors: Zhao Xiujuan , Dai Meng , Li Nuo , Zhang Jingmian , Zhao Xinming 
Published: June 2024

Abstract
Brain nocardiosis is an uncommon but severe disease associated with high mortality. We present a case of brain nocardiosis with elevated tracer uptake on both 68Ga-pentixafor and 18F-FDG PET/CT, mimicking intracerebral invasion of multiple myeloma. This case demonstrates that nocardiosis should be considered in the differential diagnosis of brain lesions found on PET/CT with increased tracer accumulation in immunocompromised patients.
The evolution of passive dispersal versus habitat selection have differing emergent consequences in metacommunities
Authors: McPeek Mark A. , Resetarits William J. , Holt Robert D. 
Published: June 2024

Dispersal among local communities is fundamental to the metacommunity concept but is only important to the metacommunity structure if dispersal causes distortions of species abundances away from what local ecological conditions favour. We know from much previous work that dispersal can cause such abundance distortions. However, almost all previous theoretical studies have only considered one species alone or two interacting species (e.g. competitors or predator and prey). Moreover, a systematic analysis is needed of whether different dispersal strategies (e.g. passive dispersal versus demographic habitat selection) result in different abundance distortion patterns, how these distortion patterns change with local food web structure, and how the dispersal propensities of the interacting species might evolve in response to one another. In this article, we show using computer simulations and analytical models that abundance distortions occur in simple food webs with both passive dispersal and habitat selection, but habitat selection causes larger distortions. Additionally, patterns in the evolution of dispersal propensity in interacting species are very different for these two dispersal strategies. This study identifies that the dispersal strategies employed by interacting species critically shape how dispersal will influence metacommunity structure.
This article is part of the theme issue ‘Diversity-dependence of dispersal: interspecific interactions determine spatial dynamics’.
Landscape configuration can flip species–area relationships in dynamic meta-food-webs
Authors: Ryser Remo , Chase Jonathan M. , Gauzens Benoit , Häussler Johanna , Hirt Myriam R. , Rosenbaum Benjamin , Brose Ulrich 
Published: June 2024

Spatial and trophic processes profoundly influence biodiversity, yet ecological theories often treat them independently. The theory of island biogeography and related theories on metacommunities predict higher species richness with increasing area across islands or habitat patches. In contrast, food-web theory explores the effects of traits and network structure on coexistence within local communities. Exploring the mechanisms by which landscape configurations interact with food-web dynamics in shaping metacommunities is important for our understanding of biodiversity. Here, we use a meta-food-web model to explore the role of landscape configuration in determining species richness and show that when habitat patches are interconnected by dispersal, more species can persist on smaller islands than predicted by classical theory. When patch sizes are spatially aggregated, this effect flattens the slope of the species–area relationship. Surprisingly, when landscapes have random patch-size distributions, the slope of the species–area relationships can even flip and become negative. This could be explained by higher biomass densities of lower trophic levels that then support species occupying higher trophic levels, which only persist on small and well-connected patches. This highlights the importance of simultaneously considering landscape configuration and local food-web dynamics to understand drivers of species–area relationships in metacommunities.
This article is part of the theme issue ‘Diversity-dependence of dispersal: interspecific interactions determine spatial dynamics’.
Functionality of BRCA1 supports the survival of prostate cancer cells during the development of castration resistance
Authors: Sriraman Saiganesh , Virtanen Verneri , Kukkula Antti , Toriseva Mervi , Rokka Anne , Lumiainen Anni , Ahlskog Johanna K. , West Gun , Poutanen Matti , Taimen Pekka , Sundvall Maria 
Published: June 2024

AbstractAndrogen deprivation therapy (ADT; castration) is the main treatment option for metastatic prostate cancer (PCa), but eventually, castration-resistant prostate cancer (CRPC) develops with no curative treatments. In CRPC, more than 20% of men carry mutations in DNA damage response (DDR) genes, including BRCA1/2. In this study, we elucidated the prostate tissue-specific functional role of BRCA1 protein. Our results indicate that DDR is dynamically regulated by androgen receptor (AR) signaling, and AR activation by the natural ligand dihydrotestosterone strongly downregulates the expression of BRCA1 in multiple cell lines. Consistent with these findings, our analyses of patient samples and mouse xenografts showed that DNA damage and BRCA1 expression were sustained after ADT. With unbiased mass spectrometry and bioinformatics approaches as well as experimentally, we found that BRCA1 interacts with Raptor, an mTORC1 component, and regulates the mTOR signaling pathway and PCa growthin vitro. Furthermore, we found that mTOR inhibition reduced the recruitment of DDR proteins, BRCA1 and Rad51, to DNA damage sites, creating a vulnerability towards DNA damage-inducing androgen deprivation. Moreover, we observed that BRCA1 supported ADT-induced activation of the oxidative stress sensor NRF2. Our findings shed further light on the complex DDR–AR interplay in PCa and suggest that, during PCa progression, BRCA1 expression may be retained due to the beneficial modulation of mTORC1 signaling in the AR environment by BRCA1.SignificanceAndrogen receptor activation acts as a strong suppressor of BRCA1. Consequently, androgen deprivation activates BRCA1, which in turn promotes survival in castration resistance by supporting mTOR signaling and NRF2-mediated antioxidant processes.
Characterizing and evaluating cell specialization through Gini index of gene expression: TCGA normal vs tumor case study
Authors: Cumbo Fabio , Santoni Daniele 
Published: June 2024

ABSTRACTIn this work we introduce the Gini Index, commonly used as a measure of statistical dispersion to evaluate the income inequality within a nation, as an effective and reliable measure of cell specialization. In particular we use it to evaluate and compare the specialization level of normal and tumor cells according to their gene expressions. Obtained results reveal how Gini Index is able to capture information associated with cell specialization, and show that tumor cells, on average, tend to lose their specialization or in other words their capacity to be the cells they were committed to be, due to cancer.
Cocaine-Induced Gene Regulation in D1 and D2 Neuronal Ensembles of the Nucleus Accumbens Revealed by Single-Cell RNA Sequencing
Authors: Mews Philipp , Mason Autumn VA , Kirchner Emily G , Estill Molly , Nestler Eric J 
Published: June 2024

ABSTRACTCocaine use disorder is characterized by persistent drug-seeking behavior and a high risk of relapse, driven by lasting molecular and circuit adaptations in the nucleus accumbens. To explore the transcriptomic changes underlying these alterations, we employed fluorescence-activated nucleus sorting coupled with single-nucleus RNA sequencing to analyze D1 and D2 medium spiny neurons in this brain region of male mice subjected to acute cocaine exposure or to prolonged withdrawal from repeated cocaine exposure without or with an acute cocaine rechallenge. This approach allowed us to precisely delineate and contrast transcriptionally distinct neuronal subpopulations─or ensembles – across various treatment conditions. We identified significant heterogeneity within both D1 and D2 MSNs, revealing distinct clusters with unique transcriptional profiles. Notably, we identified a discrete D1 MSN population characterized by the upregulation of immediate early genes, as well as another group of D1 MSNs linked to prolonged withdrawal, uncovering novel regulators of withdrawal-related transcriptome dynamics. Our findings provide a high-resolution transcriptomic map of D1 and D2 MSNs, illustrating the dynamic changes induced by cocaine exposure and withdrawal. These insights into the molecular mechanisms underlying cocaine use disorder highlight potential targets for therapeutic intervention aimed at preventing relapse.
Genetic association data are broadly consistent with stabilizing selection shaping human common diseases and traits
Authors: Koch E. , Connally N. J. , Baya N. , Reeve M. P. , Daly M. , Neale B. , Lander E. S. , Bloemendal A. , Sunyaev S. 
Published: June 2024

AbstractResults from genome-wide association studies (GWAS) enable inferences about the balance of evolutionary forces maintaining genetic variation underlying common diseases and other genetically complex traits. Natural selection is a major force shaping variation, and understanding it is necessary to explain the genetic architecture and prevalence of heritable diseases. Here, we analyze data for 27 traits, including anthropometric traits, metabolic traits, and binary diseases—both early-onset and post-reproductive. We develop an inference framework to test existing population genetics models based on the joint distribution of allelic effect sizes and frequencies of trait-associated variants. A majority of traits have GWAS results that are inconsistent with neutral evolution or long-term directional selection (selection against a trait or against disease risk). Instead, we find that most traits show consistency with stabilizing selection, which acts to preserve an intermediate trait value or disease risk. Our observations also suggest that selection may reflect pleiotropy, with each variant influenced by associations with multiple selected traits.
D1-like receptor activation rescues hippocampal synaptic plasticity and cognitive impairments in the MK-801 schizophrenia model
Authors: Hernández-Frausto Melissa , Galván Emilio J , López-Rubalcava Carolina 
Published: June 2024

AbstractSchizophrenia is a disorder with a higher cognitive decline in early adulthood, causing impaired retention of episodic memories. However, the physiological and behavioral functions that underlie cognitive deficits with a potential mechanism to ameliorate and improve cognitive performance are unknown. In this study, we used the MK-801 neurodevelopmental schizophrenia-like model. Rats were divided into two groups: one received MK-801, and the other received saline for five consecutive days (7-11 postnatal days, PND). Using extracellular field recordings in acute hippocampal slices and the Barnes maze task, we evaluated synaptic plasticity late-LTP and spatial memory in freely moving animals in early adolescence and young adulthood. Next, we examined D1-like activation as a mechanism to ameliorate cognitive impairments. Our results suggest that MK-801 neonatal treatment induces impairment in late-LTP expression and deficits in spatial memory retrieval in early adolescence that is maintained until young adulthood. Furthermore, we found that activation of D1-like dopamine receptors ameliorates the impairments and promotes a robust expression of late-LTP and an improved performance in the Barnes maze task, suggesting a novel and potential therapeutic role in treating cognitive impairments in schizophrenia.Highlights-MK-801 Schizophrenia model induces impairment in Late-LTP at early adolescence and young developmental stage.-Barnes maze recall phase is impaired in the MK-801 Schizophrenia model.-The activation of D1-like receptors promotes recovery and induction of the-Late-LTP in the MK-801 schizophrenia model in adolescent and young adult rats.-Activation of D1-like dopamine receptors improves behavioral performance in the MK-801 schizophrenia model in adolescent and young adult rats.Graphical AbstractDisturbances in episodic memories are observed in patients with schizophrenia and rodent models. Still, the hippocampal physiological substrates with a potential rescue mechanism related to consolidation of memories have not been elucidated. Here, in vitro electrophysiology and in vivo Barnes maze task are used at two ages in the MK-801 neurodevelopmental schizophrenia-like model. We observed a loss of hippocampal late-LTP and impaired recall phase, and the activation of dopamine D1-like receptors attenuated the impairments with a rescue of both late-LTP and recall phase, suggesting an important role of D1-like receptors activity for episodic memory in schizophrenia.
Perturbing human V1 degrades the fidelity of visual working memory
Authors: Dake Mrugank , Curtis Clayton E. 
Published: June 2024

AbstractThe main function of working memory is to extend the duration with which information remains available for use by a host of high-level cognitive systems1. Decades of electrophysiological studies provide compelling evidence that persistent neural activity in prefrontal cortex is a key mechanism for working memory2. Surprisingly, sophisticated human neuroimaging studies have convincingly demonstrated that the contents of working memory can be decoded from primary visual cortex (V1)3,4. The necessity of this mnemonic information remains unknown and contentious. Here, we provide causal evidence that transcranial magnetic stimulation to human V1 disrupted the fidelity of visual working memory. Magnetic stimulation during the retention interval of a visuospatial working memory task caused a systematic increase in memory errors. Errors increased only for targets that were remembered in the portion of the visual field disrupted by stimulation, and were invariant to when in the delay stimulation was applied. Moreover, concurrently measured electroencephalography confirmed that stimulation disrupted not only memory behavior, but a standard neurophysiological signature of working memory. These results change the question from whether V1 is necessary for working memory into what mechanisms does V1 use to support memory. Moreover, they point to models in which the mechanisms supporting working memory are distributed across brain regions, including sensory areas that here we show are critical for memory storage.
Glia-enriched stem-cell 3D model of the human brain mimics the glial-immune neurodegenerative phenotypes of multiple sclerosis
Authors: Fagiani Francesca , Pedrini Edoardo , Taverna Stefano , Brambilla Elena , Murtaj Valentina , Podini Paola , Ruffini Francesca , Butti Erica , Braccia Clarissa , Andolfo Annapaola , Magliozzi Roberta , Smirnova Lena , Kuhlmann Tanja , Quattrini Angelo , Calabresi Peter A. , Reich Daniel S. , Martino Gianvito , Panina-Bordignon Paola , Absinta Martina 
Published: June 2024

SUMMARYThe role of central nervous system (CNS) glia in sustaining self-autonomous inflammation and driving clinical progression in multiple sclerosis (MS) is gaining scientific interest. We applied a single transcription factor (SOX10)-based protocol to accelerate oligodendrocyte differentiation from hiPSC-derived neural precursor cells, generating self-organizing forebrain organoids. These organoids include neurons, astrocytes, oligodendroglia, and hiPSC-derived microglia to achieve immunocompetence. Over 8 weeks, organoids reproducibly generated mature CNS cell types, exhibiting single-cell transcriptional profiles similar to the adult human brain. Exposed to inflamed cerebrospinal fluid (CSF) from MS patients, organoids properly mimic macroglia-microglia neuro-degenerative phenotypes and intercellular communication seen in chronic active MS. Oligodendrocyte vulnerability emerged by day 6 post-MS-CSF exposure, with nearly 50% reduction. Temporally-resolved organoid data support and expand on the role of soluble CSF mediators in sustaining downstream events leading to oligodendrocyte death and inflammatory neurodegeneration. Such findings support implementing this organoid model for drug screening to halt inflammatory neurodegeneration.
Targeted Photoactivatable Green-Emitting BODIPY Based on Directed Photooxidation Induced Activation and its Application to Live Dynamic Super-Resolution Microscopy
Authors: Saladin Lazare , Le Berruyer Valentine , Bonnevial Maxence , Didier Pascal , Collot Mayeul 
Published: June 2024

AbstractPhotoactivatable fluorescent probes are valuable tools in bioimaging for tracking cells down to single molecules and for single molecule localization microscopy. For the latter application, green emitting dyes are in demand. We herein developed an efficient green-emitting photoactivatable furanyl-BODIPY (PFB) and we established a new mechanism of photoactivation called Directed Photooxidation Induced Activation (DPIA) where the furan is photo-oxidized in a directed manner by the singlet oxygen produced by the probe. The efficient photoconverter (93-fold fluorescence enhancement at 510 nm, 49% yield conversion) is functionalizable and allowed targeting of several subcellular structures and organelles, which were photoactivated in live cells. Finally, we demonstrated the potential of PFB in super-resolution imaging by performing PhotoActivated Localization Microscopy (PALM) in live cells.