bluuebunny/crossref_metadata_2025_split huggingface dataset:
Seizure onset patterns predict outcome after stereotactic electroencephalography-guided laser amygdalohippocampotomy
Authors: Michalak Andrew J. , Greenblatt Adam , Wu Shasha , Tobochnik Steven , Dave Hina , Raghupathi Ramya , Esengul Yasar T. , Guerra Antonio , Tao James X. , Issa Naoum P. , Cosgrove Garth R. , Lega Bradley , Warnke Peter , Chen H. Isaac , Lucas Timothy , Sheth Sameer A. , Banks Garrett P. , Kwon Churl-Su , Feldstein Neil , Youngerman Brett , McKhann Guy , Davis Kathryn A. , Schevon Catherine 
Published: November 2022

AbstractObjectiveStereotactic laser amygdalohippocampotomy (SLAH) is an appealing option for patients with temporal lobe epilepsy, who often require intracranial monitoring to confirm mesial temporal seizure onset. However, given limited spatial sampling, it is possible that stereotactic electroencephalography (sEEG) may miss seizure onset elsewhere. We hypothesized that sEEG seizure onset patterns (SOPs) may differentiate between primary onset and secondary spread and predict postoperative seizure control. In this study, we characterized the two-year outcomes of patients who underwent single-probe SLAH after sEEG and evaluated whether sEEG SOPs predict postoperative seizure freedom.MethodsThis retrospective five-center study included patients with or without mesial temporal sclerosis (MTS) who underwent sEEG followed by single probe SLAH between August 2014 and January 2022. Patients with causative hippocampal lesions apart from MTS or for whom the SLAH was considered palliative were excluded. A SOP catalogue was developed based on literature review. The dominant pattern for each patient was used for survival analysis. The primary outcome was two-year Engel I classification or recurrent seizures before then, stratified by SOP category.Results58 patients were included with a mean follow-up duration of 39 ± 12 months after SLAH. Overall one-, two, and three-year Engel I seizure freedom probability was 54%, 36%, and 33% respectively. Patients with SOPs including low voltage fast activity or low frequency repetitive spiking had a 46% two-year seizure freedom probability, compared to 0% for patients with alpha or theta frequency repetitive spiking or theta or delta frequency rhythmic slowing (log rank test, p = 0.00015).SignificancePatients who underwent SLAH after sEEG had a low probability of seizure freedom at two years, but SOPs successfully predicted seizure recurrence in a subset of patients. This study provides proof of concept that SOPs distinguish between seizure onset and spread and supports using SOPs to improve selection of SLAH candidates.Key PointsWe described extended seizure outcomes in a five-center retrospective review of 58 patients.Seizure onset patterns (SOP) were categorized as putative positive vs. negative predictors of postoperative seizure freedom.Low voltage fast activity or low frequency repetitive spiking are associated with higher seizure freedom probabilityA 0% Engel I probability was found for patients whose dominant SOP was rhythmic slowing or repetitive spiking in the theta or alpha frequency bands.
CRISPRi-Driven Osteogenesis in Adipose-Derived Stem Cells for Bone Healing and Tissue Engineering
Authors: Weston Jacob D. , Austin Brooke , Levis Hunter , Zitnay Jared , Weiss Jeffrey A. , Lawrence Brandon , Bowles Robby D. 
Published: November 2022

ABSTRACTEngineered bone tissue synthesized from mesenchymal stem cell progenitors has numerous applications throughout the fields of regenerative medicine and tissue engineering. However, these multipotent cells offer little tissue-building assistance without differentiation direction from environmental cues such as bone morphogenetic proteins (BMPs). Unfortunately, BMP dosing and environmental cues can be difficult to control bothin vitroand afterin vivodelivery. Several BMP antagonists are expressed by cells in response to BMP dosing that bind extracellular BMPs and reduce their effective concentration. Here, we use CRISPR-guided gene-modulation technology to downregulate the expression of three BMP antagonists, noggin, gremlin-1, and gremlin-2, in adipose-derived stem cells (ASCs). We show that regulating noggin using this method results in ASC osteogenesis without the need for exogenous growth factors. To demonstrate the versatility and the precision capabilities of these engineered cells, we employ them with CRISPRa multiplex-engineered chondrogenic cells as a proof-of-concept tissue engineering application by creating a tissue gradient similar to the fibrocartilage-to-mineralized-fibrocartilage gradient in the tendon/ligament enthesis or intervertebral disc attachment. In doing so, we show that multiple CRISPR multiplex engineered cell types can be utilized in concert to provide a high degree of tissue developmental control without the use of exogenous growth factors.
Uptake of tumor-derived microparticles induces metabolic reprogramming of macrophages in the early metastatic lung
Authors: Kersten Kelly , You Ran , Liang Sophia , Tharp Kevin M. , Pollack Joshua , Weaver Valerie M. , Krummel Matthew F. , Headley Mark B. 
Published: November 2022

SummaryThe formation of a pre-metastatic niche is a critical step during the metastatic spread of cancer. One way by which primary tumors prime host cells at future metastatic sites is through local shedding of tumor-derived microparticles as a consequence of vascular sheer flow. However, it remains unclear how the uptake of such particles by resident immune cells affects their phenotype and function. Here we show that ingestion of tumor-derived microparticles by macrophages induces a rapid metabolic and phenotypic switch that is characterized by enhanced mitochondrial mass and function, increased oxidative phosphorylation and upregulation of cellular adhesion molecules resulting in reduced motility in the early metastatic lung. We show that this reprogramming event is dependent on signaling through the mTORC1, but not mTORC2 pathway, and is unique to uptake of tumor-derived microparticles. Together, these data support a mechanism by which uptake of tumor-derived microparticles induces reprogramming of macrophages to shape their fate and function in the early metastatic lung.
68Ga-Bisphosphonates for the Imaging of Extraosseous Calcification by Positron Emission Tomography
Authors: Keeling George. P. , Baark Friedrich , Katsamenis Orestis L. , Xue Jing , Blower Philip J. , Bertazzo Sergio , de Rosales Rafael T. M. 
Published: November 2022

AbstractRadiolabelled bisphosphonates (BPs) and [18F]NaF (18F-fluoride) are the two types of radiotracers available to image calcium mineralin vivo(e.g. bone), yet only [18F]NaF has been widely explored for the non-invasive molecular imaging of extraosseous calcification (EC) using the highly sensitive nuclear imaging technique positron emission tomography (PET). These two radiotracers bind calcium mineral deposits via different mechanisms, with BPs chelating to calcium ions and thus being non-selective, and [18F]NaF being selective for hydroxyapatite (HAp) which is the main component of bone mineral. Taking into account that the composition of EC has been reported to include a diverse range of non-HAp calcium minerals, we hypothesised that BPs may be more sensitive for imaging EC due to their ability to bind to both HAp and non-HAp deposits.To test this hypothesis, we report a comparison between the68Ga-labelled BP tracer [68Ga]Ga-THP-Pam and [18F]NaF for PET imaging in a rat model of EC that develops macro- and microcalcifications in several organs. The presence of macrocalcifications was identified using preclinical computed tomography (CT) and microcalcifications were identified using μCT-based 3D X-ray histology (XRH) on isolated organsex vivo. The morphological and mineral analysis of individual calcified deposits was performed using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). The PET imaging andex vivoanalysis results demonstrated that while both radiotracers behave similarly for bone imaging, the BP-based radiotracer [68Ga]Ga-THP-Pam was able to detect EC more sensitively in several organs in which the mineral composition departs from that of HAp. We conclude that BP-based PET radiotracers such as [68Ga]Ga-THP-Pam have a particular advantage for the sensitive imaging and early detection of EC by being able to detect a wider array of relevant calcium mineralsin vivothan [18F]NaF, and should be evaluated clinically for this purpose.
Cross-protein transfer learning substantially improves disease variant prediction
Authors: Jagota Milind , Ye Chengzhong , Albors Carlos , Rastogi Ruchir , Koehl Antoine , Ioannidis Nilah , Song Yun S. 
Published: November 2022

AbstractGenetic variation in the human genome is a major determinant of individual disease risk, but the vast majority of missense variants have unknown etiological effects. Here, we present a robust learning framework for leveraging saturation mutagenesis experiments to construct accurate computational predictors of proteome-wide missense variant pathogenicity. We train cross-protein transfer (CPT) models using deep mutational scanning data from only five proteins and achieve state-of-the-art performance on clinical variant interpretation for unseen proteins across the human proteome. High sensitivity is crucial for clinical applications and our model CPT-1 particularly excels in this regime. For instance, at 95% sensitivity of detecting human disease variants annotated in ClinVar, CPT-1 improves specificity to 68%, from 27% for ESM-1v and 55% for EVE. Furthermore, for genes not used to train REVEL, a supervised method widely used by clinicians, we show that CPT-1 compares favorably with REVEL. Our framework combines predictive features derived from general protein sequence models, vertebrate sequence alignments, and AlphaFold2 structures, and it is adaptable to the future inclusion of other sources of information. We find that vertebrate alignments, albeit rather shallow with only 100 genomes, provide a strong signal for variant pathogenicity prediction that is complementary to recent deep learning-based models trained on massive amounts of protein sequence data. We release predictions for all possible missense variants in 90% of human genes. Our results demonstrate the utility of mutational scanning data for learning properties of variants that transfer to unseen proteins.
Elevated energy costs of biomass production in mitochondrial-respiration deficientSaccharomyces cerevisiae
Authors: Grigaitis Pranas , van den Bogaard Samira L. , Teusink Bas 
Published: November 2022

AbstractMicrobial growth requires energy for maintaining the existing cells and producing components for the new ones. Microbes therefore invest a considerable amount of their resources into proteins needed for energy harvesting. Growth in different environments is associated with different energy demands for growth of yeastSaccharomyces cerevisiae, although the cross-condition differences remain poorly characterized. Furthermore, a direct comparison of the energy costs for the biosynthesis of the new biomass across conditions is not feasible experimentally; computational models, on the contrary, allow comparing the optimal metabolic strategies and quantify the respective costs of energy and nutrients. Thus in this study, we used a resource allocation model ofS. cerevisiaeto compare the optimal metabolic strategies between different conditions. We found thatS. cerevisiaewith respiratory-impaired mitochondria required additional energetic investments for growth, while growth on amino acid-rich media was not affected. Amino acid supplementation in anaerobic conditions also was predicted to rescue the growth reduction in mitochondrial respiratory shuttle-deficient mutants ofS. cerevisiae. Collectively, these results point to elevated costs of resolving the redox imbalance caused byde novobiosynthesis of amino acids in mitochondria. To sum up, our study provides an example of how resource allocation modeling can be used to address and suggest explanations to open questions in microbial physiology.
The critical role of BTRC in hepatic steatosis as an ATGL E3 ligase
Authors: Qi Weiwei , Fang Zhenzhen , Luo Chuanghua , Hong Honghai , Long Yanlan , Dai Zhiyu , Liu Junxi , Zeng Yongcheng , Zhou Ti , Xia Yong , Yang Xia , Gao Guoquan 
Published: November 2022

AbstractObjectiveNon-alcoholic fatty liver disease (NAFLD), characterized by hepatic steatosis, is one of the most common causes of liver dysfunction. ATGL is closely related to hepatic steatosis as the speed-limited triacylglycerol lipase. Nevertheless, the expression and regulation of ATGL in NAFLD remain unclear.MethodsUsing immunohistochemistry and qRT-PCR to detect the expression of ATGL and BTRC in different models with hepatic steatosis. Co-IP evaluated the binding of ATGL and BTRC. Knockdown of BTRC employed by adenoviruses and then analyzed the ATGL expression, triglyceride levels, and lipid droplets accumulation.ResultsOur results revealed that ATGL protein level was decreased in animal and cellular models of hepatic steatosis and the liver tissues of cholangioma/hepatic carcinoma patients with hepatic steatosis, while the ATGL mRNA level had hardly changed; which means the decreased ATGL mainly degraded through the proteasome pathway. BTRC was identified as the E3 ligase for ATGL, up-regulated, and negatively correlated with ATGL level. Moreover, adenovirus-mediated knockdown of BTRC ameliorated hepatic steatosisviaup-regulating ATGL level.ConclusionsOur study demonstrates a crucial role of elevated BTRC in hepatic steatosis through promoting ATGL proteasomal degradation as a new ATGL E3 ligase and suggests BTRC may serve as a potential therapeutic target for NAFLD.FundingThis study was supported by The National Natural Science Foundation of China (Grants 82070888, 82070882, 82100917, 81872165, 82273116, 82203661, 81901557 and 81902693); Key Project of Nature Science Foundation of Guangdong Province, China (Grant 2019B1515120077); National Key R&D Program of China (Grant 2018YFA0800403); Guangdong Special Support Program for Young Top Scientist (Grant 201629046); Guangdong Natural Science Fund (Grant 2019A1515011810, 2021A1515010434, 2022A1515012423 and 2022A1515012513); Key Sci-Tech Research Project of Guangzhou Municipality (Grants 202201010820) Fundamental Research Funds for the Central Universities (Grant 50000-31620106); China Postdoctoral Science Foundation (Grant 2021M703679, 2020M683110).
Fusion of Video and Inertial Sensing Data via Dynamic Optimization of a Biomechanical Model
Authors: Pearl Owen , Shin Soyong , Godura Ashwin , Bergbreiter Sarah , Halilaj Eni 
Published: November 2022

ABSTRACTInertial sensing and computer vision are promising alternatives to traditional optical motion tracking, but until now these data sources have been explored either in isolation or fused via unconstrained optimization, which may not take full advantage of their complementary strengths. By adding physiological plausibility and dynamical robustness to a proposed solution, biomechanical modeling may enable better fusion than unconstrained optimization. To test this hypothesis, we fused RGB video and inertial sensing data via dynamic optimization with a nine degree-of-freedom model and investigated when this approach outperforms video-only, inertial-sensing-only, and unconstrained-fusion methods. We used both experimental and synthetic data that mimicked different ranges of RGB video and inertial measurement unit (IMU) data noise. Fusion with a dynamically constrained model significantly improved estimation of lower-extremity kinematics over the video-only approach and estimation of joint centers over the IMU-only approach. It consistently outperformed single-modality approaches across different noise profiles. When the quality of video data was high and that of inertial data was low, dynamically constrained fusion improved estimation of joint kinematics and joint centers over unconstrained fusion, while unconstrained fusion was advantageous in the opposite scenario. These findings indicate that complementary modalities and techniques can improve motion tracking by clinically meaningful margins and that data quality and computational complexity must be considered when selecting the most appropriate method for a particular application.
Use of the Vitiligo Extent Score Vitiligo: A Protocol for a Scoping Review
Authors: Rueda-Galvis Paola Andrea , Orozco-Jiménez Sara , Builes-Montaño Carlos E. , Arango-Salgado Andrea 
Published: November 2022

AbstractIntroductionVitiligo is a chronic skin condition with no cure. Clinical assessment and treatment evaluation relays heavily on clinometry tools and expert knowledge. The Vitiligo Extent Score has been proposed as one of the most reliable and easy-to-use clinometry tools for vitiligo.Methods and analysisWe proposed a scoping review to identify all the available evidence on the clinical research availability around the Vitiligo Extent Score. This review will follow the approach proposed in the Joanna Briggs Institute Reviewer’s Manual Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews.Ethics and disseminationWe intend to publish the results in a specialized peer-reviewed journal and local, national, and international conference presentations. It will also be incorporated as educational material in our institution’s postgraduate program in dermatology.Article summaryStrengths and limitations of this studyThis scoping review will be the first to review the available literature on VES extensively.The search strategy includes an extensive search of grey literature besides the primary medical databases and no language restriction, ensuring the inclusion of all the available literature.The research questions will allow us to assess the main aspects of a measurement instrument.This scoping review will only evaluate one of the several available measurement instruments for vitiligo.
Endoparasitoid lifestyle promotes endogenization and domestication of dsDNA viruses
Authors: Guinet Benjamin , Lepetit David , Charlat Sylvain , Buhl Peter N , Notton David G , Cruaud Astrid , Rasplus Jean-Yves , Stigenberg Julia , de Vienne Damien M. , Bastien Boussau , Varaldi Julien 
Published: November 2022

AbstractThe accidental endogenization of viral elements within eukaryotic genomes can occasionally provide significant evolutionary benefits, giving rise to their long-term retention, that is, to viral domestication. For instance, in some endoparasitoid wasps (whose immature stages develop inside their hosts), the membrane-fusion property of double-stranded DNA viruses has been repeatedly domesticated following ancestral endogenizations. The endogenized genes provide female wasps with a delivery tool to inject virulence factors that are essential to the developmental success of their offspring. Because all known cases of viral domestication involve endoparasitic wasps, we hypothesized that this lifestyle, relying on a close interaction between individuals, may have promoted the endogenization and domestication of viruses. By analyzing the composition of 124 Hymenoptera genomes, spread over the diversity of this clade and including free-living, ecto- and endoparasitoid species, we tested this hypothesis. Our analysis first revealed that double-stranded DNA viruses, in comparisons with other viral genomic structures (ssDNA, dsRNA, ssRNA), are more often endogenized and domesticated (that is, retained by selection) than expected from their estimated abundance in insect viral communities. Secondly, our analysis indicates that the rate at which dsDNA viruses are endogenized is higher in endoparasitoids than in ectoparasitoids or free-living hymenopterans, which also translates into more frequent events of domestication. Hence, these results are consistent with the hypothesis that the endoparasitoid lifestyle has facilitated the endogenization of dsDNA viruses, in turn increasing the opportunities of domestications that now play a central role in the biology of many endoparasitoid lineages.
Identifying genes and pathways linking astrocyte regional specificity to Alzheimer’s disease susceptibility
Authors: Zhang Ran , Knudsen Margarete , Vasques Pedro Del Cioppo , Tadych Alicja , Rodriguez-Rodriguez Patricia , Greengard Paul , Roussarie Jean-Pierre , Milosevic Ana , Troyanskaya Olga 
Published: November 2022

AbstractAstrocytes have been shown to play a central role in Alzheimer’s Disease (AD). However, the genes and biological pathways underlying disease manifestation are unknown, and it is unclear whether regional molecular differences among astrocytes contribute to regional specificity of disease. Here, we began to address these challenges with integrated experimental and computational approaches. We constructed a human astrocyte-specific functional gene network using Bayesian integration of a large compendium of human functional genomics data, as well as regional astrocyte gene expression profiles we generated in the mouse. This network identifies likely region-specific astrocyte pathways that operate in healthy brains. We leveraged our findings to compile genome-wide astrocyte-associated disease-gene predictions, employing a novel network-guided differential expression analysis (NetDIFF). We also used this data to predict a list of astrocyte-expressed genes mediating region-specific human disease, using a network-guided shortest path method (NetPATH). Both the network and our results are publicly available using an interactive web interface athttp://astrocyte.princeton.edu. Our experimental and computational studies propose a strategy for disease gene and pathway prediction that may be applied to a host of human neurological disorders.