bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intracranial Atherosclerotic Disease in Acute Ischemic Stroke: Clinical Predictors, Imaging Profiles, and Treatment Outcomes: An Analysis from RITE Registry
Authors: Alotaibi Fawaz F. , Mlynash Michael , Muteb M. Aldawsari , AlAbidien Nowar Z. , Alqahtani Mohammed , BinAmir Hussain , AlKawi Ammar , Alreshaid Abdulrahman A. , AlZawahmah Mohamed , Alhazzani Adel , Alabdaly Hani , Alanazi Abdulmajeed , Almansour Nouf , Albers Gregory W. , Shuaib Ashfaq , Al-Ajlan Fahad S. 
Published: November 2024

AbstractBackgroundIntracranial atherosclerotic disease (ICAD) is a leading cause of ischemic stroke worldwide, with a significant prevalence in specific populations. This study aims to compare the clinical characteristics, imaging profiles, and outcomes of stroke patients with large vessel occlusion (LVO) caused by ICAD versus non-ICAD etiologies, particularly in those transferred for endovascular treatment (EVT).MethodsA retrospective analysis was conducted using data from the Riyadh Thrombectomy Registry, including 219 patients with acute ischemic stroke who underwent EVT between January 2019 and March 2024. Clinical, demographic, and imaging data were collected and compared between ICAD and non-ICAD groups. Imaging modalities included computed tomography perfusion (CTP) and angiography, with key metrics such as the hypoperfusion intensity ratio (HIR) and cerebral blood volume (CBV) index evaluated for prognostic utility.ResultsPatients with ICAD were older and demonstrated a higher prevalence of vascular risk factors. ICAD patients presented with better ASPECTS scores, smaller ischemic core volumes, and higher mismatch ratios, reflecting better collateral circulation. However, despite favorable imaging profiles, ICAD patients exhibited higher mortality rates, particularly in cases involving basilar artery occlusion. HIR and CBV indices demonstrated modest diagnostic performance in distinguishing ICAD from non-ICAD, with an area under the curve (AUC) of 0.62 for HIR and 0.57 for CBV.ConclusionsICAD patients undergoing EVT showed distinct clinical and imaging characteristics compared to non-ICAD patients. Despite better collateral circulation, ICAD is associated with higher mortality, especially in posterior circulation strokes. Further research is required to optimize EVT strategies and explore adjunctive therapies tailored to this challenging patient population.
Molecular architecture of thylakoid membranes within intact spinach chloroplasts
Authors: Wietrzynski Wojciech , Lamm Lorenz , Wood William H.J. , Loukeri Matina-Jasemi , Malone Lorna , Peng Tingying , Johnson Matthew P. , Engel Benjamin D. 
Published: November 2024

AbstractThylakoid membranes coordinate the light reactions of photosynthesis across multiple scales, coupling the architecture of an elaborate membrane network to the spatial organization of individual protein complexes embedded within this network. Previously, we usedin situcryo- electron tomography (cryo-ET) to reveal the native thylakoid architecture of the green algaChlamydomonas reinhardtii[1] and then map the molecular organization of these thylakoids with single-molecule precision [2]. However, it remains to be shown how generalizable this green algal blueprint is to the thylakoids of vascular plants, which possess distinct membrane architecture subdivided into grana stacks interconnected by non-stacked stromal lamellae. Here, we continue our cryo-ET investigation to reveal the molecular architecture of thylakoids within intact chloroplasts isolated from spinach (Spinacia oleracea). We visualize the fine ultrastructural details of grana membranes, as well as interactions between thylakoids and plastoglobules. We apply and further develop AI-based computational approaches for automated membrane segmentation and membrane protein picking [3], enabling us to quantify the organization of photosynthetic complexes within the plane of the thylakoid membrane and across adjacent stacked membranes. Our analysis reveals that, despite different 3D architecture, the molecular organization of thylakoid membranes in vascular plants and green algae is strikingly similar. In contrast to isolated plant thylakoids, where semi- crystalline arrays of photosystem II (PSII) appear to hold some membranes together, we find in intact chloroplasts that PSII is non-crystalline and has uniform concentration both within the membrane plane and across stacked grana membranes. Similar toC. reinhardtii, we observe strict lateral heterogeneity of PSII and PSI at the boundary between appressed and non-appressed thylakoid domains, with no evidence for a distinct grana margin region where these complexes have been proposed to intermix. Based on these measurements, we support a simple two-domain model for the molecular organization of thylakoid membranes in both green algae and plants.
Effects of Primed Adipose Mesenchymal Stem Cell-Derived Exosomes on Immunomodulation in Behcet Uveitis
Authors: Gozel Merve , Aydemir Dilara , Kaleli Humeyra Nur , Cosar Feray , Guleser Umit Yasar , Unlu Eda Kusan , Kesim Cem , Sezgin Billur , Sahin Afsun , Ucar Didar , Hatemi Gulen , Hasanreisoglu Murat 
Published: November 2024

AbstractPurposeThis study sought to investigate the potential role of exosomes of interferon-gamma (IFN-γ) primed (IFN+Exo) and non-primed (IFN-Exo) adipose-derived mesenchymal stem cells (AdMSCs) for the treatment of Behçet Disease (BD) uveitis (BU).MethodsAdMSCs were isolated from adipose tissue. Characterization and multipotency analyses were performed. Exosomes were isolated from the media of AdMSCs and then characterized. Peripheral blood mononuclear cells (PBMC) were isolated from patients with BU and healthy individuals. AdMSCs were preincubated with or without IFN-γ for 48 h. PBMC of patients with BU and healthy controls separately cultured with exosomes for 72 h. After the culture period, lymphocyte proliferation, viability, and apoptosis were carried out via flow cytometry. The expression of interleukin (IL)-10, IL-17, transforming growth factor (TGF)-β, and interferon (IFN)-γ levels were measured by real-time polymerase chain reaction (RT-PCR).ResultsIFN+Exo promoted lymphocyte apoptosis in patients with BU. IFN+Exo suppressed cell viability of T lymphocytes of BU. Exosomes alone did not affect on T lymphocyte proliferation. Additionally, exosomes increased anti-inflammatory cytokine levels and reduced pro-inflammatory cytokine levels of T lymphocytes in patients with BU.ConclusionThis study’s findings can open a new pathway in MSCs/exosome therapy in BU.
Can AI modelling of protein structures distinguish between sensor and helper NLR immune receptors?
Authors: Toghani AmirAli , Frijters Raoul , Bozkurt Tolga O. , Terauchi Ryohei , Kamoun Sophien , Sugihara Yu 
Published: November 2024

ABSTRACTNLR immune receptors can be functionally organized in genetically linked sensor-helper pairs. However, methods to categorize paired NLRs remain limited, primarily relying on the presence of non-canonical domains in some sensor NLRs. Here, we propose that the AI system AlphaFold 3 can classify paired NLR proteins into sensor or helper categories based on predicted structural characteristics. Helper NLRs showed higher AlphaFold 3 confidence scores than sensors when modelled in oligomeric configurations. Furthermore, funnel-shaped structures—essential for activating immune responses—were reliably predicted in helpers but not in sensors. Applying this method to uncharacterized NLR pairs from rice, we found that AlphaFold 3 can differentiate between putative sensors and helpers even when both proteins lack non-canonical domain annotations. These findings suggest that AlphaFold 3 offers a new approach to categorize NLRs and enhances our understanding of the functional configurations in plant immune systems, even in the absence of non-canonical domain annotations.
Assembly and lipid-gating of LRRC8A:D volume-regulated anion channels
Authors: Lurie Antony , Kern David M. , Henn Katharine , Brohawn Stephen G. 
Published: November 2024

AbstractVolume-regulated anion channels (VRACs) are ubiquitously expressed vertebrate ion channels that open in response to hypotonic swelling. VRACs assemble as heteromers of LRRC8A and LRRC8B-E subunits, with different subunit combinations resulting in channels with different properties. Recent studies have described the structures of LRRC8A:C VRACs, but how other VRACs assemble, and which structural features are conserved or variant across channel assemblies remains unknown. Herein, we used cryo-EM to determine structures of a LRRC8A:D VRAC with a 4:2 subunit stoichiometry, which we captured in two conformations. The presence of LRRC8D subunits increases hydrophobicity and widens the selectivity filter, which may explain the unique substrate selectivity of LRRC8D-containing VRACs. The structures reveal lipids bound inside the channel pore, similar to those observed in LRRC8A:C VRACs. Using electrophysiological experiments, we confirmed that pore lipids block conduction in the closed state, demonstrating that lipid-gating is a general property of VRACs. Finally, we observe that LRRC8D subunit incorporation disrupts packing of the cytoplasmic LRR domains, increasing channel dynamics and opening lateral fenestrations, which we speculate are necessary for pore lipid evacuation and channel activation.
Intraoperative Augmented Reality for Vitreoretinal Surgery using Edge Computing
Authors: Ye Run Zhou , Iezzi Raymond 
Published: November 2024

ABSTRACTPurposeAugmented reality (AR) may allow vitreoretinal surgeons to leverage microscope-integrated digital imaging systems to analyze and highlight key retinal anatomic features in real-time, possibly improving safety and precision during surgery. By employing convolutional neural networks (CNNs) for retina vessel segmentation, a retinal coordinate system can be created that allows pre-operative images of capillary non-perfusion or retinal breaks to be digitally aligned and overlayed upon the surgical field in real-time. Such technology may be useful in assuring thorough laser treatment of capillary non-perfusion or in using pre-operative optical coherence tomography (OCT) to guide macular surgery when microscope-integrated OCT (MIOCT) is not available.MethodsThis study is a retrospective analysis involving the development and testing of a novel image registration algorithm for vitreoretinal surgery. Fifteen anonymized cases of pars plana vitrectomy with epiretinal membrane peeling, along with corresponding preoperative fundus photographs and optical coherence tomography (OCT) images, were retrospectively collected from the Mayo Clinic database. We developed a TPU (Tensor-Processing Unit)-accelerated CNN for semantic segmentation of retinal vessels from fundus photographs and subsequent real-time image registration in surgical video streams. An iterative patch-wise cross-correlation (IPCC) algorithm was developed for image registration, with a focus on optimizing processing speeds and maintaining high spatial accuracy. The primary outcomes measured were processing speed in frames per second (FPS) and the spatial accuracy of image registration, quantified by the Dice coefficient between registered and manually aligned images.ResultsWhen deployed on an Edge TPU, the CNN model combined with our image registration algorithm processed video streams at a rate of 14 FPS, which is superior to processing rates achieved on other standard hardware configurations. The IPCC algorithm efficiently aligned pre-operative and intraoperative images, showing high accuracy in comparison to manual registration.ConclusionThis study demonstrates the feasibility of using TPU-accelerated CNNs for enhanced AR in vitreoretinal surgery.
Repeated administration of pharmaceutical-grade medium chain triglycerides, a common pharmacologic excipient, confers dose-dependent toxicity by the intraperitoneal but not oral route in mice*
Authors: Adler-Wachter Mitzi , Tsai Julia Y. , Schweitzer Brendan N. , McDonough Ashley , Snyder Jessica M. , Barker-Haliski Melissa , Weinstein Jonathan R. 
Published: November 2024

ABSTRACTPharmaceutical-grade medium chain triglycerides (MCTs) are common excipients for in vivo pharmacological studies in laboratory animals, and as an experimental therapeutic in certain metabolic and neurological disorders. In this study, we examined the tolerability of repeated administration of a pharmaceutical-grade formulation of three MCTs—caprylic, capric, and lauric acid - in mice via the oral (PO) and intraperitoneal (IP) routes. We administered either 8 or 4 µL of 100% MCTs or saline/gram of body weight twice daily for seven days. During administration and for seven days after, we monitored weight change and clinical presentation. On day 14, or upon meeting euthanasia criteria, animals were sacrificed for gross necropsy, histology, and complete blood count. We observed significant weight loss, clinical decline and 100% mortality in animals receiving 8 µL/g of MCTs via the IP route of administration. Gross necropsy revealed serosanguinous fluid in the thoracic cavity, dark red mottled lungs, and adhesions in the abdominal cavity. Histology confirmed inflammation of the lungs, mediastinum, and peritoneum. Mild gross lesions and initial weight loss (through day 3) were also present in mice receiving 4 µL/g of MCTs IP. However, these animals regained weight by day seven and exhibited no clinical decline or mortality. None of these adverse effects were seen in animals receiving either 8 µL/g of MCTs PO or 8 µL/g of saline IP. These findings suggest repeated IP administration of MCTs may cause dose-dependent toxicity, and mortality at high doses, but confers no adverse effects when administered via the PO route.SIGNIFICANCE STATEMENTMedium chain triglycerides (MCTs) are commonly used as an excipient in pharmacological studies involving laboratory animals. Our work provides much needed safety information regarding adverse effects of repeated MCTs administration via the intraperitoneal, but not the oral, route in mice.
Intraspecific and intraindividual trait variability decrease with tree species richness in a subtropical tree biodiversity experiment
Authors: Sánchez-Bermejo Pablo Castro , Carmona Carlos Pérez , Schuman Meredith Christine , Benavides Raquel , Sachsenmaier Lena , Li Shan , Liu Xiaojuan , Haider Sylvia 
Published: November 2024

ABSTRACTPhenotypic variability within tree species responds to local tree species richness. However, we lack evidence on how different sources of trait variation shape tree-tree interactions. Along a diversity gradient from one to eight tree species, we sampled 4,568 leaves from 381 trees to study changes in intraspecific and intraindividual leaf trait variability and assessed their contribution to community functional diversity. Intraspecific variability decreased with tree species richness, while intraindividual variability barely responded. Functional overlap between conspecific trees increased with tree species richness and through intraindividual variation, but was reduced through intraspecific variability, meaning that intraspecific variability may reduce intraspecific competitive interactions while intraindividual variability could arise due to varying microenvironmental conditions within the canopy. Last, intraspecific and intraindividual variability explained high community functional richness and divergence, respectively, especially in mixtures. Our findings emphasize that fine-scale variability influences tree-tree interactions and can be a driver of local functional diversity.TeaserTrait variability within tree species decreases with diversity and explains high forest functional diversity.
De novoprotein-coding gene variants in developmental stuttering
Authors: Eising Else , Dzinovic Ivana , Vino Arianna , Stipdonk Lottie , Pavlov Martin , Winkelmann Juliane , Sommer Martin , Franken Marie-Christine J.P. , Oexle Konrad , Fisher Simon E. 
Published: November 2024

AbstractStuttering is a common neurodevelopmental condition characterized by disfluencies in speech, such as blocks, prolongations, and repetitions. While most children who stutter do so only transiently, there are some for whom stuttering persists into adulthood. Rare-variant screens in families including multiple relatives with persistent stuttering have so far identified six genes carrying putative pathogenic variants hypothesized to act in a monogenic fashion. Here, we applied a complementary study design, searching instead forde novovariants in exomes of 85 independent parent-child trios, each with a child with transient or persistent stuttering. Exome sequencing analysis yielded a pathogenic variant inSPTBN1as well as likely pathogenic variants inPRPF8,TRIO, andZBTB7A- four genes previously implicated in neurodevelopmental disorders with or without speech problems. Our results also highlighted two further genes of interest for stuttering:FLT3andIREB2. We used extensive bioinformatic approaches to investigate overlaps in brain-related processes among the twelve genes associated with monogenic forms of stuttering. Analyses of gene-expression datasets of the developing and adult human brain, and data from a genome-wide association study of human brain structural connectivity, did not find links of monogenic stuttering to specific brain processes. Overall, our results provide the first direct genetic link between stuttering and other neurodevelopmental disorders, including speech delay and aphasia. In addition, we systematically demonstrate a dissimilarity in biological pathways associated with the genes thus far implicated in monogenic forms of stuttering, indicating heterogeneity in the etiological basis of this condition.
Genomic predictors of response to antidepressants in Major depressive disorder (MDD): A GWAS-Based Study on Indian cohort
Authors: Goel Isha , Hans Gagan , Kumar Nand , Karmakar Subhradip 
Published: November 2024

AbstractBackgroundMajor depressive disorder (MDD) affects a significant portion of the population, with approximately 70% of patients not achieving adequate remission using anti-depressant monotherapy, a condition known as inadequate treatment response (ITR). In the Indian population, few studies have explored the genetic associations of this response, and those that exist are underpowered. This study aims to identify single nucleotide variations associated with ITR in the Indian population. The goal is to develop a population-specific gene panel that can identify subjects at risk for ITR, allowing alternative treatment modalities.MethodsSubjects satisfying inclusion-exclusion criteria were enrolled for the study following institutional ethical approval. We recruited 120 subjects with MDD and assessed their response to monotherapy (Escitalopram) using the Hamilton Depression Rating Scale (HAMD) before and 4-6 weeks after medication. Responders (n=45) and non-responders (n=75) were genotyped using the Infinium Global Screening SNP-Array-24 v3.0. A genome-wide association study (GWAS) was performed to identify SNPs associated with ITR.ResultsTwelve lead-significant SNPs with a threshold of < 1E-05 were identified, suggesting an association with ITR. Among these, four SNPs were located in the intronic/regulatory regions of the genesLRSAM1, EFCAB2, TRIM56andZNF17. The remaining eight SNPs were near genesALDH1A2, LIPC, MYOCD, SPRY2, ANKRD18B, CCDC54, TNS3, ANKRD46, andFCRL2. These genes are involved in critical functions related to cell signalling, immune response, neurodevelopment, regulating intracellular levels, and transcription factor binding.ConclusionsOur study identified several novel SNPs that may be associated with ITR in MDD patients, reported for the first time in an Indian cohort. Further investigations are underway to determine their clinical significance and potential to be used for screening individuals responding to drug interventions as user-friendly gene panels.
Relationships between 25-Hydroxyvitamin D and Alpha-synucleinopathies: A Mendelian Randomization Study
Authors: Li Fu-Jia , Geng Ru-Lin , Wen Cheng , Huang Kai-Xun , Lin Dan-Yu , Li Zhong-Gui , Zhang Jie-Li , Xu Chuan-Ying , Zhang Wei , Zu Jie , Dong Li-Guo , Wang Wen-Xin , Ruan Zhi-Jia , Yin Pei-Xiao , Guan Chen-Yang , Cui Gui-Yun , Tao En-Xiang 
Published: November 2024

AbstractBackgroundAlpha-synucleinopathies, including Parkinson’s disease (PD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB), are neurodegenerative diseases characterized by abnormal aggregation of alpha-synuclein. Isolated REM sleep behavior disorder (iRBD) is a prodromal stage of these disorders. While 25-hydroxyvitamin D (25[OH]D) has been linked to PD in previous studies, its causal role remains unclear, and its relationship with iRBD, MSA, and DLB is rarely explored.ObjectivesThis study used Mendelian randomization (MR) to investigate the causal relationship between 25(OH)D and iRBD, PD, MSA, and DLB.MethodsGWAS data for 25(OH)D were sourced from the UK Biobank, and outcome data for PD were obtained from the latest FinnGen R12 database. Data for iRBD, PD onset age, PD clinical progression, MSA, and DLB were derived from a broader European population. The study had two steps: univariable MR (UVMR) using genome-wide IV selection as the primary analysis, with replication analyses using biological function-based IV selection and sunlight exposure and vitamin D supplementation-related factors as exposures. Multivariable MR (MVMR) was then conducted to adjust for 13 covariates, testing the robustness of findings.Results25(OH)D showed a significant protective effect on MSA across all UVMR (both primary and replication) and MVMR analyses. It also exhibited a nominal protective effect on PD in the Finnish population in primary UVMR analysis, but this was not replicated. No associations were found between 25(OH)D and iRBD, PD onset age, PD clinical progression, or DLB. Power analyses indicated insufficient sensitivity to detect weak effects of 25(OH)D on iRBD and DLB.ConclusionsMR analysis supports a protective role of 25(OH)D against MSA. While nominally protective for PD in the Finnish population, the effect was not robust. Weak effects on iRBD and DLB cannot be excluded.