bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep learning-assisted multiple organ segmentation from whole-body CT images
Authors: Salimi Yazdan , Shiri Isaac , Mansouri Zahra , Zaidi Habib 
Published: October 2023

AbstractBackgroundAutomated organ segmentation from computed tomography (CT) images facilitates a number of clinical applications, including clinical diagnosis, monitoring of treatment response, quantification, radiation therapy treatment planning, and radiation dosimetry.PurposeTo develop a novel deep learning framework to generate multi-organ masks from CT images for 23 different body organs.MethodsA dataset consisting of 3106 CT images (649,398 axial 2D CT slices, 13,640 images/segment pairs) and ground-truth manual segmentation from various online available databases were collected. After cropping them to body contour, they were resized, normalized and used to train separate models for 23 organs. Data were split to train (80%) and test (20%) covering all the databases. A Res-UNET model was trained to generate segmentation masks from the input normalized CT images. The model output was converted back to the original dimensions and compared with ground-truth segmentation masks in terms of Dice and Jaccard coefficients. The information about organ positions was implemented during post-processing by providing six anchor organ segmentations as input. Our model was compared with the online available “TotalSegmentator” model through testing our model on their test datasets and their model on our test datasets.ResultsThe average Dice coefficient before and after post-processing was 84.28% and 83.26% respectively. The average Jaccard index was 76.17 and 70.60 before and after post-processing respectively. Dice coefficients over 90% were achieved for the liver, heart, bones, kidneys, spleen, femur heads, lungs, aorta, eyes, and brain segmentation masks. Post-processing improved the performance in only nine organs. Our model on the TotalSegmentator dataset was better than their models on our dataset in five organs out of 15 common organs and achieved almost similar performance for two organs.ConclusionsThe availability of a fast and reliable multi-organ segmentation tool leverages implementation in clinical setting. In this study, we developed deep learning models to segment multiple body organs and compared the performance of our models with different algorithms. Our model was trained on images presenting with large variability emanating from different databases producing acceptable results even in cases with unusual anatomies and pathologies, such as splenomegaly. We recommend using these algorithms for organs providing good performance. One of the main merits of our proposed models is their lightweight nature with an average inference time of 1.67 seconds per case per organ for a total-body CT image, which facilitates their implementation on standard computers.
Effects of System-Level Factors on Race/Ethnic Differences in In-Hospital Mortality after Acute Ischemic Stroke
Authors: Sun Philip , Markovic Daniela , Ibish Abdullah , Faigle Roland , Gottesman Rebecca , Towfighi Amytis 
Published: October 2023

AbstractIntroductionStroke mortality has declined, with differential changes by race; stroke is now the 5th leading cause of death overall, but 2nd leading cause of death in Black individuals. Little is known about recent race/ethnic and sex trends in in-hospital mortality after acute ischemic stroke (AIS) and whether system-level factors contribute to possible differences.MethodsUsing the National Inpatient Sample, adults (≥18 years) with a primary diagnosis of AIS from 2006 to 2017 (n=643,912) were identified. We assessed in-hospital mortality by race/ethnicity (White, Black, Hispanic, Asian/Pacific Islander [API], other), sex, and age. Hospitals were categorized by proportion of non-White patients served: <25% (“predominantly White patients”), 25-50% (“mixed race/ethnicity profile”), and ≥50% (“predominantly non-White patients”). Using survey adjusted logistic regression, the association between race/ethnicity and odds of mortality was assessed, adjusting for key sociodemographic, clinical, and hospital characteristics (e.g., age, comorbidities, stroke severity, do not resuscitate orders, and palliative care).ResultsOverall, mortality decreased from 5.0% in 2006 to 2.9% in 2017 (p<0.001). Comparing 2012-2017 to 2006-2011, there was a 68% reduction in mortality odds overall after adjusting for covariates, most prominent in White individuals (69%) and smallest in Black individuals (57%). Compared to White patients, Black and Hispanic patients had lower odds of mortality (adjusted odds ratio (aOR) 0.82, 95% CI 0.78-0.87 and aOR 0.93, 95% CI 0.87-1.00), primarily driven by those >65 years (age x ethnicity interaction p < 0.0001). Compared to White men, Black, Hispanic, and API men, and Black women had lower aOR of mortality. The differences in mortality between White and non-White patients were most pronounced in hospitals predominantly serving White patients (aOR 0.80, 0.74-0.87) compared to mixed hospitals (aOR 0.85, 0.79-0.91) and predominantly non-White hospitals (aOR 0.88, 0.81-0.95; interaction effect: p=0.005).DiscussionAIS mortality decreased dramatically in recent years in all race/ethnic subgroups. Overall, non-White AIS patients had lower mortality than their White counterparts, a difference that was most striking in hospitals predominantly serving White patients. Further study is needed to understand these differences and to what extent biological, sociocultural, and system-level factors play a role.CategoryHealth Services, Quality Improvement, and Patient-Centered Outcomes
Mini-heterochromatin domains constrain thecis-regulatory impact of SVA transposons in human brain development and disease
Authors: Horváth Vivien , Garza Raquel , Jönsson Marie E. , Johansson Pia A. , Adami Anita , Christoforidou Georgia , Karlsson Ofelia , Vallmanya Laura Castilla , Gerdes Patricia , Pandiloski Ninoslav , Douse Christopher H. , Jakobsson Johan 
Published: October 2023

AbstractSVA retrotransposons remain active in humans and contribute to individual genetic variation. Polymorphic SVA alleles harbor gene-regulatory potential and can cause genetic disease. However, how SVA insertions are controlled and functionally impact human disease is unknown. Here, we dissect the epigenetic regulation and influence of SVAs in cellular models of X-linked dystonia-parkinsonism (XDP), a neurodegenerative disorder caused by an SVA insertion at theTAF1locus. We demonstrate that the KRAB zinc finger protein ZNF91 establishes H3K9me3 and DNA methylation over SVAs, including polymorphic alleles, in human neural progenitor cells. The resulting mini-heterochromatin domains attenuate thecis-regulatory impact of SVAs. This is critical for XDP pathology; removal of local heterochromatin severely aggravates the XDP molecular phenotype, resulting in increasedTAF1intron retention and reduced expression. Our results provide unique mechanistic insights into how human polymorphic transposon insertions are recognized, and their regulatory impact constrained by an innate epigenetic defense system.
RNA Polymerase II-mediated transcription is required for repair of ribosomal DNA breaks in nucleolar caps, guarding against genomic instability
Authors: Checa-Rodríguez Cintia , Suárez-Quintero Beatriz , Contreras Laura , Korsholm Lea , Payne-Larsen Dorthe Helena , de la Cruz Jesús , Bartek Jiri , Gómez-Cabello Daniel 
Published: October 2023

AbstractOversized nucleoli and enhanced ribosome biogenesis are hallmarks of cancer, reflecting tumor cells’ aberrantly high demand for protein synthesis during tumorigenesis. The high-copy ribosomal DNA (rDNA) genes are highly transcribed by RNA Polimerase I (RNAPI) and inherently unstable, often subject to DNA double-strand breaks (DSBs) caused by transcription-replication conflicts. When DSBs happen, RNAPI becomes silenced by ATM signaling and rDNA DSBs are translocated to nucleolar periphery for repair mainly by homologous recombination in newly formed nucleolar caps. The molecular mechanisms underlying these processes are incompletely understood. Herein, we report that rDNA DSB translocation and nucleolar cap formation require the presence and activity of RNAPII. Nascent RNA deficiency upon RNAPII inhibition in rDNA damaged cells provoke rDNA instability and cell death. Finally, the enhanced cytotoxic effect of combined RNA transcription inhibition and rDNA damage, reported here, is consistent with addiction of cancer to nucleolar function, indicating an emerging targetable vulnerability of cancer cells that may inspire innovative treatment strategies in oncology.TeaserNascent RNA synthesis by RNA PolymeraseII safeguards ribosomal DNA integrity to avoid genomic instability in human cells.Graphical Abstract
The nitrogenase cofactor biogenesis enzyme NifB is essential for the viability of methanogens
Authors: Saini Jasleen , Dhamad Ahmed , Muniyasamy Abaranjitha , Alverson Andrew J. , Lessner Daniel J. 
Published: October 2023

ABSTRACTDinitrogen (N2) is only bioavailable to select bacteria and archaea that possess the metalloenzyme nitrogenase, which reduces N2to NH3in a process called nitrogen fixation or diazotrophy. A long-term goal is to engineer diazotrophy into plants to decrease the use of nitrogen fertilizers, saving billions of dollars annually and greatly reducing nutrient pollution. This goal has not been realized, in part due to the inability to produce the nitrogenase metallocofactor within plants. Biogenesis of the cofactor requires NifB, a radical S-adenosy-L-methionine (SAM) enzyme that generates a precursor [8Fe-9S-C] cluster that matures into the final metallocofactor. Although maturation of nitrogenase is the only known function of NifB in bacteria, bioinformatic analyses reveal that NifB is conserved across methanogens, including those lacking nitrogenase, which suggests NifB functions outside of nitrogenase maturation. Indeed, several lines of evidence show that NifB is essential for viability of the model diazotroph,Methanosarcina acetivorans. First, CRISPRi repression was unable to abolish NifB production, whereas CRISPRi repression abolishes non-essential nitrogenase production. Second, unlike nitrogenase production, NifB production is not controlled by fixed nitrogen availability. Finally,nifBcould not be deleted fromM. acetivoransunless complementedin transwithnifBfrom other methanogens, includingMethanothrix thermoacetophila, a species that lacks nitrogenase. Notably,M. thermoacetophilaNifB supported diazotrophy inM. acetivorans, demonstrating that NifB from a non-diazotrophic methanogen produces the [8Fe-9S-C] cluster. Overall, these results link the metallocofactor biogenesis function of NifB to nitrogen fixation and methanogenesis, two processes of global importance.SIGNIFICANCEMethanogens directly impact life on Earth since they produce methane, a potent greenhouse gas, and are the principal archaea capable of nitrogen fixation, a process that requires nitrogenase. In this study, we demonstrate that NifB, an enzyme required to produce the metallocofactor in non-essential nitrogenase, is essential to the viability of methanogens. This identifies NifB as a new potential target in the goal of inhibiting methanogens to reduce methane emissions. The discovery that NifB functions outside of nitrogenase maturation will also aid efforts to engineer nitrogen fixation in plants, since NifB is a key factor to achieve this goal. Realization of these goals would have immense economic, environmental, and societal benefits.
ISWI chromatin remodeling complexes recruit NSD2 and H3K36me2 in pericentromeric heterochromatin
Authors: Goto Naoki , Suke Kazuma , Yonezawa Nao , Nishihara Hidenori , Sato Yuko , Kujirai Tomoya , Kurumizaka Hitoshi , Yamagata Kazuo , Kimura Hiroshi 
Published: October 2023

AbstractHistone H3 lysine36 dimethylation (H3K36me2) is generally distributed in the gene body and euchromatic intergenic regions. However, we found that H3K36me2 is enriched in pericentromeric heterochromatin in some mouse cell lines. We here revealed the mechanism of heterochromatin targeting of H3K36me2. Among several H3K36 methyltransferases, NSD2 was responsible for inducing heterochromatic H3K36me2. Depletion and overexpression analyses of NSD2-associating proteins revealed that NSD2 recruitment to heterochromatin was mediated through the imitation switch (ISWI) chromatin remodeling complexes, such as BAZ1B-SMARCA5 (WICH), which directly binds to AT-rich DNA via a BAZ1B domain containing AT-hook-like motifs. The abundance and stoichiometry of NSD2, SMARCA5, and BAZ1B or BAZ2A could determine the localization of H3K36me2 in different cell types. To explore the physiological role of heterochromatic H3K36me2, we analyzed mouse tissues and embryos. As a result, H3K36me2 was found in heterochromatin at the 2- to 4-cell stages of mouse preimplantation embryos, suggesting its involvement in developmental regulation.SummaryThe authors discovered histone H3K36me2, which is believed to be enriched in potentially active genomic regions, is also located in transcriptionally inactive regions called heterochromatin in some cell types. The detailed molecular mechanism of its heterochromatin targeting is now revealed.
Discontinuation of palliative brain radiotherapy in patients with brain metastases
Authors: Windisch Paul , Lütscher Jamie , Förster Robert , Zwahlen Daniel R. , Schröder Christina 
Published: October 2023

AbstractDiscontinuation of radiotherapy is rarely discussed in the literature. In this retrospective study of 468 consecutive patients receiving palliative radiotherapy for brain metastases, we identified 35 discontinued treatments, mainly due to clinical deterioration. Poor performance status, more advanced disease and, in turn, poor prognosis was associated with higher discontinuation rates.
Secretome of Human Umbilical cord mesenchymal stem cells exerts protective impacts on the blood-brain barrier against alpha-synuclein aggregates using anin vitromodel
Authors: Marzookian Kimia , Aliakbari Farhang , Hourfar Hamdam , sabouni farzaneh , Otzen Daniel E. , Morshedi Dina 
Published: October 2023

AbstractThe blood-brain barrier (BBB) is a highly developed endothelial microvessel network extended to almost all parts of the central nervous system (CNS) that tightly seals cell-to-cell contacts and plays a critical role in maintaining CNS homeostasis. It also protects neurons from factors present in systemic circulation and prevents pathogens from entering the brain. Conversely, BBB disruption can initiate multiple pathways of nerve damage. BBB injury contributes significantly to various neurodegenerative diseases, including Parkinson’s disease (PD). PD is also characterized by aggregation of the protein alpha-synuclein (αSN) to form intracellular inclusions. Recent studies have shown that due to their active secretions, mesenchymal stem cells (MSCs) can effectively relieve the severity of many neurological diseases. However, the impact of MSCs on BBB remains largely unclear. Here, we investigated the effect of Secretome extracted from MSCs on BBB when treated with toxic αSN-aggregates (αSN-AGs). For this purpose, MSCs were first isolated from Umbilical cord tissue (UC-MSC), and their secretome was collected. Then, the impact of the secretome on the cytotoxicity and inflammatory effects of αSN-AGs was examined on hCMEC/D3 cells using in vitro BBB models produced by mono- and co-culture systems. We explored the effects of αSN-AGs in the presence of UC-MSC secretome on permeability, TEER value, and cytokine/chemokine release. We found that the Secretome of UC-MSCs exerts protective effects by inhibiting the toxic effects of αSN-AGs on the BBB. These results strongly support the potential of UC-MSCs secretome for cell-free PD therapy. We also present an improved method for isolation of MSCs from umbilical cord tissue, which we hope will facilitate further studies on the use of these cells.Graphical Abstract
Recombinase Polymerase Amplification Assay for the Field Detection of Mal Secco Disease byPlenodomus tracheiphilus
Authors: Rovetto Ermes Ivan , Garbelotto Matteo , Moricca Salvatore , Amato Marcos , Spada Federico La , Cacciola Santa Olga 
Published: October 2023

SummaryIn this study, we developed a new diagnostic assay based on the recombinase polymerase amplification (RPA) technology to detectPlenodomus tracheiphilus, the anamorphic fungus responsible for the destructive vascular disease of lemon named mal secco, in infected tissues of host plants. A 142 bp RPA-compatible barcode was sought within the 544 bp Internal Transcriber Spacer (ITS) fragment identified in a previous study and itsP. tracheiphilus-specificity was confirmed by BLAST in the NCBI database. This was the premise to design an RPA probe (RPA_Ptrach_Probe). The specificity and inclusivity of the RPA assay were tested on gDNA isolated from tissues ofC. limon, isolates ofP. tracheiphilusof various origins and axenic cultures of non-target organisms, including fungal and oomycete pathogens typically associated to citrus trees, such asAlternariaspp.,Colletotrichumspp.,Phyllostictaspp., Penicilliumspp.,Phytophthoraspp. With a detection threshold of 1.0 pg of gDNA the RPA assay proved to be as sensitive as the SYBR® Green I Real Time-PCR test included in the diagnostic protocol forP. tracheiphilusof the European and Mediterranean Plant Protection Organization. RPA assay was even more sensitive than Real Time-PCR in tests on DNA samples obtained through a rapid extraction method. In tests, on naturally infected lemon twigs, molecular approaches were comparable to each other and performed better than conventional isolation method. Overall, results of this study demonstrate the potential of RPA for rapid, easy to handle and cost effective in-field diagnosis of mal secco.
Addressing the dNTP bottleneck restricting prime editing activity
Authors: Ponnienselvan Karthikeyan , Liu Pengpeng , Nyalile Thomas , Oikemus Sarah , Joynt Anya T. , Kelly Karen , Guo Dongsheng , Chen Zexiang , Lee Jeong Min , Schiffer Celia A. , Emerson Charles P. , Lawson Nathan D. , Watts Jonathan K. , Sontheimer Erik J. , Luban Jeremy , Wolfe Scot A. 
Published: October 2023

AbstractPrime editing efficiency is modest in cells that are quiescent or slowly proliferating where intracellular dNTP levels are tightly regulated. MMLV-reverse transcriptase - the prime editor polymerase subunit - requires high intracellular dNTPs levels for efficient polymerization. We report that prime editing efficiency in primary cells andin vivois increased by mutations that enhance the enzymatic properties of MMLV-reverse transcriptase and can be further complemented by targeting SAMHD1 for degradation.
Epidemiology and outcomes of head trauma in rural and urban populations: A systematic review and meta-analysis
Authors: Chequer de Souza Julia , Dobson Geoffrey P , Lee Celine J , Letson Hayley L 
Published: October 2023

AbstractObjectiveTo identify and describe differences in demographics, injury characteristics, and outcomes between rural and urban head injury patients.Data SourcesCINAHL, Emcare, MEDLINE, and Scopus.Review MethodsA systematic review and meta-analysis of studies comparing epidemiology and outcomes of rural and urban head trauma was conducted in accordance with PRISMA and MOOSE guidelines.Results36 studies with ∼2.5-million patients were included. Incidence of head injury was higher in males, regardless of location. Rates of transport-related head injuries, particularly involving motorized vehicles other than cars, were significantly higher in rural populations (OR:3.63, 95% CI[1.58,8.35], p=0.002), whereas urban residents had more fall-induced head trauma (OR:0.73, 95% CI[0.66,0.81], p<0.00001). Rural patients were 28% more likely to suffer severe injury, indicated by Glasgow Coma Scale (GCS)≤8 (OR:1.28, 95% CI[1.04,1.58], p=0.02). There was no difference in mortality (OR:1.09, 95% CI[0.73,1.61], p=0.067), however, urban patients were twice as likely to be discharged with a good outcome (OR:0.52, 95% CI[0.41,0.67], p<0.00001).ConclusionsRurality is associated with greater severity and poorer outcomes of traumatic head injury. Transport accidents disproportionally affect those travelling on rural roads. Future research recommendations include addition of prehospital data, adequate follow-up, standardized measures, and sub-group analyses of high-risk groups, e.g., Indigenous populations.
Modeling cardiac fibroblast heterogeneity from human pluripotent stem cell-derived epicardial cells
Authors: Fernandes Ian , Funakoshi Shunsuke , Hamidzada Homaira , Epelman Slava , Keller Gordon 
Published: October 2023

Abstract (Summary)Cardiac fibroblasts play an essential role in the development of the heart and have been implicated in disease progression in the context of fibrosis and regeneration. Here, we established a simple organoid culture platform using human pluripotent stem cell-derived epicardial cells and ventricular cardiomyocytes to study cardiac fibroblasts’ development, maturation and heterogeneity under normal conditions and following treatment with pathological stimuli. We demonstrated that this system models the early interactions between epicardial cells and cardiomyocytes to generate a population of fibroblasts that recapitulates many aspects of fibroblast behaviourin vivoincluding changes associated with maturation and in response to pathological stimuli associated with cardiac injury. Using single cell transcriptomics, we show that the hPSC-derived organoid fibroblast population displays a high degree of heterogeneity that approximates the heterogeneity of populations in both the normal and diseased human heart. Additionally, we identified a unique subpopulation of fibroblasts possessing reparative features previously characterized in the hearts of model organisms. Taken together, our system recapitulates many aspects of human cardiac fibroblast specification, development and maturation providing a platform to investigate the role of these cells in human cardiovascular development and disease.