bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simultaneous Profiling of the Blood and Gut T and B Cell Repertoires in Crohn’s Disease and Symptomatic Controls Illustrates Tissue-specific Alterations in the Immune Repertoire of Crohn’s Disease Patients
Authors: Mahdy Aya K. H. , Schöpfel Valentina , Huppertz-Hauss Gert , Perminow Gøri , Tran Florian , Bang Corinna , Hov Johannes Roksund , Bengtson May-Bente , Ricanek Petr , Opheim Randi , Aabrekk Tone Bergene , Detlie Trond Espen , Kristensen Vendel A. , Poyet Mathilde , Høivik Marte Lie , Franke Andre , ElAbd Hesham 
Published: September 2024

AbstractCrohn’sdisease (CD) is a clinical subset of inflammatory bowel disease that is characterized by patchy transmural inflammation across the gastrointestinal tract. Although the exact etiology remains unknown, recent findings suggest that it is a complex multifactorial disease with contributions from the host genetics and environmental factors such as the microbiome. We have shown that the T cell repertoire of CD patients harbors a group of highly expanded T cells which hints toward an antigen-mediated pathology. To profile the immunological signature of CD at a high-resolution we simultaneously profiled the αβ and γδ T cell repertoire in addition to the B cell repertoire of both the blood and the colonic mucosa for 27 treatment-naïve CD patients and 27 age-matched symptomatic controls. Regardless of disease, we observed multiple physiological differences between the immune repertoire of blood and colonic mucosa. Additionally, by comparing the repertoire of CD patients relative to controls, we observed different alterations that were only detected in the blood or colonic mucosa. These include a depletion of mucosal-associated invariant T (MAIT) cells in the blood repertoire, an expansion ofTRAV29/DV5-TRAJ5+clonotypes and a significant depletion of multipleIGHV3-33-IGHJ4+andIGHV3-33-IGHJ6+clonotypes in the blood and gut IGH repertoire of CD patients. In conclusion, our findings highlight the importance of studying the immune repertoire in a tissue-specific manner and the need to profile the T and B cell immune repertoire of gut tissues.
Optimizing UK Biobank Cloud Based Research Analysis Platform to Fine Map Coronary Artery Disease Loci in Whole Genome Sequencing Data
Authors: Sng Letitia M.F. , Kaphle Anubhav , O’Brien Mitchell J. , Hosking Brendan , Reguant Roc , Verjans Johan , Jain Yatish , Twine Natalie A. , Bauer Denis C. 
Published: September 2024

AbstractWe conducted the first comprehensive association analysis of a coronary artery disease (CAD) cohort within the recently released UK Biobank (UKB) whole genome sequencing dataset. We employed fine mapping tool PolyFun and pinpointrs10757274 as the most likely causal SNV within the 9p21.3 CAD risk locus. Notably, we show that machine-learning (ML) approaches, REGENIE and VariantSpark, exhibited greater sensitivity compared to traditional single-SNV logistic regression, uncoveringrs28451064 a known risk locus in 21q22.11. Our findings underscore the utility of leveraging advanced computational techniques and cloud-based resources for mega-biobank analyses. Aligning with the paradigm shift of bringing compute to data, we demonstrate a 44% cost reduction and 94% speedup through compute architecture optimisation on UK Biobank’s Research Analysis Platform using our RAPpoet approach. We discuss three considerations for researchers implementing novel workflows for datasets hosted on cloud-platforms, to pave the way for harnessing mega-biobank-sized data through scalable, cost-effective cloud computing solutions.
Lipid Fingerprinting by MALDI Biotyper Sirius Instrument Fails to Differentiate the Three Subspecies of theMycobacterium abscessusComplex
Authors: Yoshida Mitsunori , Fukano Hanako , Yahara Koji , Nakano Satoshi , Komine Takeshi , Suzuki Masato , Fujinaga Azumi , Dohke Kohei , Hoshino Yoshihiko 
Published: September 2024

AbstractThe number of patients suffering fromMycobacterium abscessuscomplex (MABC) pulmonary diseases is steadily increasing. MABC consists of three subspecies, and it is recommended that the three subspecies be distinguished because of their differing macrolide susceptibilities. Unfortunately, current methods are inefficient due to their high cost, complexity, and time requirements. The third-generation Bruker MALDI Biotyper (MBT) Sirius has the capability to detect phospholipids and glycolipids using negative-ion mode. Mycobacterial cell walls are rich in lipids, and if lipid structure diversity can serve as species-specific fingerprints, this method may provide an alternative for microbial identification. This study aimed to examine the accuracy of discriminating between the three MABC subspecies by lipid profiling. Our best model failed to differentiate the three subspecies. Even in the two-dimensional space of the most significant peaks,M. abscessusandM. massiliensecould not be separated. The agreement rate between lipid fingerprint-based and WGS-based identification was, at most, 47.2% for negative-ion mode. Even after applying recent machine learning algorithms to detect variables and create predictive models, accuracy remained at 50%. Our results suggest that using lipid fingerprinting alone to differentiate the three MABC subspecies is currently inadequate. Further advancements and standardization of MALDI-TOF MS-based methods are necessary for the routine differentiation of MABC subspecies in clinical settings.
Cortico-thalamic tremor circuits and their associations with deep brain stimulation effects in essential tremor
Authors: He Shenghong , West Timothy O , Plazas Fernando R , Wehmeyer Laura , Pogosyan Alek , Deli Alceste , Wiest Christoph , Herz Damian M , Simpson Thomas , Andrade Pablo , Baig Fahd , Hart Michael G , Morgante Francesca , FitzGerald James J. , Barbe Michael T , Visser-Vandewalle Veerle , Green Alexander L , Pereira Erlick A , Cagnan Hayriye , Tan Huiling 
Published: September 2024

AbstractEssential tremor (ET) is one of the most common movement disorders in adults. Deep brain stimulation (DBS) of the ventralis intermediate nucleus (VIM) of the thalamus and/or the posterior subthalamic area (PSA) has been shown to provide significant tremor suppression in patients with ET, but with significant inter-patient variability and habituation to the stimulation. Several non-invasive neuromodulation techniques targeting other parts of the central nervous system, including cerebellar, motor cortex, or peripheral nerves, have also been developed for treating ET, but the clinical outcomes remain inconsistent. Existing studies suggest that pathology in ET may emerge from multiple cortical and subcortical areas, but its exact mechanisms remain unclear. By simultaneously capturing neural activities from motor cortices and thalami, and hand tremor signals recorded via accelerometers in fifteen human subjects who have undergone lead implantations for DBS, we systematically characterized the efferent and afferent cortico-thalamic tremor networks. Through the comparisons of these network characteristics and tremor amplitude between DBS OFF and ON conditions, we further investigated the associations between different tremor network characteristics and the magnitude of DBS effect. Our findings implicate the thalamus, specifically the contralateral hemisphere, as the primary generator of tremor in ET, with a significant contribution of the ipsilateral hemisphere as well. Although there is no direct correlation between the cortico-tremor connectivity and tremor power or reduced tremor by DBS, the strength of connectivity from the motor cortex to the thalamus and vice versa at tremor frequency predicts baseline tremor power and effect of DBS. Interestingly, there is no correlation between these two connectivity pathways themselves, suggesting that, independent of the subcortical pathway, the motor cortex appears to play a relatively distinct role, possibly mediated through an afferent/feedback loop in the propagation of tremor. DBS has a greater clinical effect in those with stronger cortico-thalamo-tremor connectivity involving the contralateral thalamus, which is also associated with bigger and more stable tremor measured with an accelerometer. Interestingly, stronger cross-hemisphere coupling between left and right thalami is associated with more unstable tremor. Together this study provides important insights into a better understanding of the cortico-thalamic tremor generating network and its implication for the development of patient-specific therapeutic approaches for ET.
Fusion of middle ear optical coherence tomography and computed tomography in three ears
Authors: Wang Junzhe , Couvreur Floor , Farrell Joshua D. , Ghedia Reshma , Shoman Nael , Morris David P , Adamson Robert B.A. 
Published: September 2024

AbstractImportanceMiddle ear OCT imaging in patients has not previously been directly compared to a standard of care clinical 3D imaging technology such as CT. This represents the first such comparison and provides new insight into OCT’s capabilities, strengths and limitations.ObjectiveTo qualitatively compare the capabilities of middle ear OCT to CT in normal and pathological ears on representative slices in co-registered OCT and CT datasets.Design, Setting, and ParticipantsOne normal middle ear, one ear affected by traumatic injury and one ear with cholesteatoma were imaged with both OCT and high-resolution clinical temporal bone CT. Participants were drawn from the patient population of a tertiary otology clinic. CT and OCT images were aligned using rigid co-registration with manual landmark selection.Main Outcomes and MeasuresImages were analyzed qualitatively for field of view, resolution, shadowing, artefacts, soft tissue and bony tissue contrast and presentation of diagnostically important features.ResultsIn the three imaged ears, OCT was capable of visualizing many of the important features indicative of middle ear pathology. When compared to CT, OCT was found to exhibit a limited field of view (FOV) largely confined to the mesotympanum and subject to shadowing from bony structures. However, OCT could resolve soft tissue features that were not readily apparent in the CT images, to have a higher resolution than CT and to provide excellent anatomical fidelity with CT which allowed OCT images to be accurately co-registered with CT images.Conclusions and RelevanceThe results support a role for middle ear OCT in otological diagnostics. While OCT is not capable of replacing CT due to its limited FOV and inability to image through thick bony tissues, it can visualize many signs of pathology including some soft tissue features that are difficult to visualize with CT. Given OCT’s ability to image in real-time, its compatibility with in-office imaging and its lack of ionizing radiation, it may, despite its limitations compared to CT, be an appealing imaging modality for many applications in middle ear diagnostics.Key PointsQuestion (1 sentence)What are the strengths and limitations of middle ear optical coherence tomography (OCT) imaging compared to computed tomography (CT) in real-world clinical imaging scenarios?Finding (1-2 sentence)OCT and CT imaging produce complementary diagnostic information with CT offering unobstructed images of bony anatomy and OCT providing the ability to visualize soft tissue.Meaning (1 sentence)OCT, CT and fused OCT/CT imaging can each provide useful, complementary diagnostic information in clinical otology.
Associations Between Lipid Traits and Breast Cancer Risk: A Mendelian Randomization Study in African Women
Authors: Ansah Emmanuel Owusu , Kyei Foster , Opoku Caleb Frimpong , Danquah Andrews , Fosu Kwadwo , Agyenim Emmanuel Boateng , Agyirifo Daniel Sakyi 
Published: September 2024

ABSTRACTBlood lipids are associated with breast cancer. An increasing number of reports have attempted to explore the genetic connection between blood lipids and the risk of developing breast cancer. However, observational studies can be affected by confounding factors and reverse causation, which can compromise the reliability of the findings. We used univariate and multivariable two-sample mendelian randomization to explore the causal association between blood lipids and breast cancer. Summary-level data for lipid traits were obtained from the Africa Wits-INDEPTH partnership for Genomic Research (AWI-Gen) (N= 10,603, 58.5% of women). For breast cancer, we leveraged summary statistics from the most comprehensive Genome-wide Association Studies (GWAS) on breast cancer consisting of 18,034 cases and 22,104 controls of women of African ancestry. Our analysis suggests that genetically predicted triglycerides had a potential protective effect on breast carcinoma (OR = 0.73, 95% CI = 0.56, 0.95, FDR = 0.001). We found no evidence that genetically elevated levels of TC, HDL, and LDL may be associated with the risk of breast cancer TC (OR = 1.04; 95% CI, 0.93, 1.18;FDR= 0.029); HDL (OR = 1.29, 95% CI = 0.93, 1.79, FDR = 0.008); LDL (OR = 1.04, 95% CI = 0.90, 1.20, FDR = 0.036). Multivariate mendelian randomization analysis, which adjusted for the effects of TG, TC, LDL, and HDL, attenuated the observation of TG and breast cancer and also found no relationship between TC, HDL, LDL, and breast cancers. Furthermore, there was no evidence for a causal association between lipid traits and breast cancer subtypes. Our findings were robust in several sensitivity analyses. This study provides strong evidence that circulating TG may be associated with a decreased risk of breast cancer, while TC, LDL and HDL may not be related to the risk of breast cancer among African women.
Awareness about the risk of hearing loss after ototoxic treatments in Swiss childhood cancer survivors
Authors: Jörger Philippa , Nigg Carina , Žarković Maša , Sommer Grit , Kompis Martin , Michel Gisela , Ansari Marc , Waespe Nicolas , Kuehni Claudia E. 
Published: September 2024

AbstractObjectivesThe International Guideline Harmonization Group recommends childhood cancer survivors (CCS) exposed to ototoxic treatments be aware of the risk of hearing loss. We assessed awareness among adult CCS.MethodsWe identified adults diagnosed with cancer <20 years who received ototoxic treatments through the Swiss Childhood Cancer Registry (ChCR) and invited them to the HEAR-study. Participants completed a questionnaire and underwent pure-tone audiometry. Cancer and treatment data came from the ChCR. We used logistic regression to explore factors influencing awareness.Results105 of 424 invited CCS participated (25%). 57% did not remember receiving information on hearing loss prior to the study. CCS who remembered being informed were more likely diagnosed after 1995 (OR: 4.5, 95% CI: 1.3-15.4), reported hearing problems (10.9, 2.6-45.1) and other late effects (4.1, 1.3-13.2), and treated with platinum chemotherapy only (10.8, 2.2-53.2) versus cranial radiotherapy only. 44% of participants presented clinically relevant hearing loss.ConclusionsOver half of CCS exposed to ototoxic treatments were unaware of their risk of hearing loss.Practice ImplicationsEducating CCS about potential late effects of ototoxic treatments is important to allow early diagnosis and treatment, especially for those who had cancer longer ago and those exposed to cranial radiation.HighlightsHalf of CCS exposed to ototoxic treatment were unaware of the risk of hearing lossCCS treated before 1995 were less aware about the risk of hearing lossInformation provision is key to effective monitoring and early intervention
Integrating Kolmogorov-Arnold Networks with Ordinary Differential Equations for Efficient, Interpretable and Robust Deep Learning: A Case Study in the Epidemiology of Infectious Diseases
Authors: Ma Kexin , Lu Xu , Bragazzi Nicola Luigi , Tang Biao 
Published: September 2024

AbstractIn this study, we extend the universal differential equation (UDE) framework by integrating Kolmogorov-Arnold Network (KAN) with ordinary differential equations (ODEs), herein referred to as KAN-UDE models, to achieve efficient and interpretable deep learning for complex systems. Our case study centers on the epidemiology of emerging infectious diseases. We develop an efficient algorithm to train our proposed KAN-UDE models using time series data generated by traditional SIR models. Compared to the UDE based on multi-layer perceptrons (MLPs), training KAN-UDE models shows significantly improves fitting performance in terms of the accuracy, as evidenced by a rapid and substantial reduction in the loss. Additionally, using KAN, we accurately reconstruct the nonlinear functions represented by neural networks in the KAN-UDE models across four distinct models with varying incidence rates, which is robustness in terms of using a subset of time series data to train the model. This approach enables an interpretable learning process, as KAN-UDE models were reconstructed to fully mechanistic models (RMMs). While KAN-UDE models perform well in short-term prediction when trained on a subset of the data, they exhibit lower robustness and accuracy when real-world data randomness is considered. In contrast, RMMs predict epidemic trends robustly and with high accuracy over much longer time windows (i.e., long-term prediction), as KAN precisely reconstructs the mechanistic functions despite data randomness. This highlights the importance of interpretable learning in reconstructing the mechanistic forms of complex functions. Although our validation focused on the transmission dynamics of emerging infectious diseases, the promising results suggest that KAN-UDEs have broad applicability across various fields.
Longitudinal Monitoring of Glioblastoma Small Extracellular Vesicle Evolution Using a Nanodiagnostic to Detect Emergence of Glioma Stem Cells Driving Recurrent Disease
Authors: Zhang Zhen , Lobb Richard J , Tooney Paul , Wang Jing , Lane Rebecca , Zhou Quan , Niu Xueming , Faulkner Sam , Day Bryan W , Puttick Simon , Rose Stephen , Fay Mike , Trau Matt 
Published: September 2024

AbstractAssessing therapeutic response in glioblastoma (GBM) is a major factor limiting the clinical development of new and effective therapies. The intracranial location limits serial biopsies, and only provides an intermittent view of the tumor molecular profile from the initial resection. Liquid biopsy techniques, specifically small extracellular vesicle (sEV) analysis, have the potential to overcome these limitations by providing a window into the brain using peripheral blood. To address the need for monitoring tumor evolution and therapeutic resistance, we developed a GBM biomarker panel (ATP1B2, EAAT2, CD24, CD44, CD133 and EGFR) for multiplexed profiling of sEVs using an advanced GBM Extracellular vesicle Monitoring Phenotypic Analyzer Chip (GEMPAC). We successfully tracked patient response to treatment by monitoring changes in glioma stem cell markers on circulating sEVs. We propose that these results provide a strong rationale for using GBM sEVs as a serial monitoring tool in the future clinical management of GBM patients.
WITHDRAWN: Comprehensive Analysis of Theoretical Models and Frameworks for Investigating Determinants of Breast Cancer Screening Participation: A Scoping Review
Authors: Zheng Dandan , Sriyuktasuth Aurawamon , Lekdamrongkul Pichitra 
Published: September 2024

Withdrawal Statement“The authors have withdrawn this manuscript because of erroneous data, with potential implications of academic misconduct. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.”
Climate Adaptation and Genetic Differentiation in the Mosquito SpeciesCulex tarsalis
Authors: Liao Yunfei , Islam Touhid , Noorai Rooksana , Streich Jared , Saski Christopher , Cohnstaedt Lee W. , Cooper Elizabeth A. 
Published: September 2024

AbstractThe increasing prevalence of vector-borne diseases around the world highlights the pressing need for an in-depth exploration of the genetic and environmental factors that shape the adaptability and widespread distribution of mosquito populations. This research focuses onCulex tarsalis, a principal vector for various viral diseases including West Nile Virus (WNV). Through the development of a new reference genome and the examination of Restriction-Site Associated DNA sequencing (RAD-seq) data from over 300 individuals and 28 locations, we demonstrate that variables such as temperature, evaporation rates, and the density of vegetation significantly impact the genetic makeup ofCx. tarsalispopulations. Among the alleles most strongly associated with environmental factors is a nonsynonymous mutation in a key gene related to circadian rhythms. These results offer new insights into the mechanisms of spread and adaptation in a key North American vector species, which is poised to become a growing health threat to both humans and animals in the face of ongoing climate change.
Camera Paths, Modeling, and Image Processing Tools for ArtiaX
Authors: Ermel Utz H. , Moser Deborah , Roth Pauline , Arctaedius Gunnar , Wehrheim Maren , Scheffer Margot P. , Frangakis Achilleas S. 
Published: September 2024

AbstractThe enhancement of biomolecular image analysis and data interpretation is significantly improved through the application of advanced visualization techniques. Numerous visualization packages are currently available, spanning a broad spectrum of applications. Recently, we have extended the capabilities of UCSF ChimeraX to address the specific demands of cryo-electron tomography. Here, we introduce the evolution of our existing plugin, ArtiaX, designed to generate models that facilitate particle selection, define camera recording paths, and execute particle selection routines. In particular, diverse models can be generated and populated with putative particle positions and orientations. A specifically tailored coarse grained algorithm was developed to rectify overlaps, as encountered in template matching, employing a rapid and efficient approach. In addition, models can be used to drive the camera position, thereby simplifying the process of movie creation. The plugin incorporates fundamental image filtering options for the on-the-fly analysis of tomographic data and also provides compatibility of particle lists with RELION-5 star files. Collectively, this update of ArtiaX comprehensively encompasses essential tools for the analysis and visualization of electron tomograms. It retains its hallmark attributes of speed, reliability, and user-friendliness, fostering seamless human-machine interaction.
GRAS Family Transcription Factor Binding Behaviors in Sorghum bicolor, Oyrza, and Maize
Authors: Gladman Nicholas , Kumari Sunita , Fahey Audrey , Regulski Michael , Ware Doreen 
Published: September 2024

AbstractIdentifying non-coding regions that control gene expression has become an essential aspect of understanding gene regulatory networks that can play a role in crop improvements such as crop manipulation, stress response, and plant evolution. Transcription Factor (TF)-binding approaches can provide additional valuable insights and targets for reverse genetic approaches such as EMS-induced or natural SNP variant screens or CRISPR editing techniques (e.g. promoter bashing). Here, we present the first ever DAP-seq profiles of three GRAS family TFs (SHR, SCL23, and SCL3) in the cropSorghum bicolor,Oryza sativa japonica, andZea mays. The binding behaviors of the three GRAS TFs display unique and shared gene targets and categories of previously characterized DNA-binding motifs as well as novel sequences that could potentially be GRAS family-specific recognition motifs. Additional transcriptomic and chromatin accessibility data further facilitates the identification of root-specific GRAS regulatory targets corresponding to previous studies. These results provide unique insights into the GRAS family of TFs and novel regulatory targets for further molecular characterization.