bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plaque characteristics derived from intravascular optical coherence tomography that predict major adverse cardiovascular events
Authors: Lee Juhwan , Gharaibeh Yazan , Zimin Vladislav N. , Kim Justin N. , Motairek Issam , Hassani Neda S. , Dallan Luis A. P. , Pereira Gabriel T. R. , Makhlouf Mohamed H. E. , Hoori Ammar , Al-Kindi Sadeer , Wilson David L. 
Published: June 2023

AbstractBackgroundWith its near histological resolution and its optical contrast, intravascular optical coherence tomography (IVOCT) is the only imaging modality that allows a unique assessment of microscopic plaque characteristics. This study aimed to investigate whether plaque characteristics derived from IVOCT could predict a long-term major adverse cardiovascular event (MACE).MethodsThis study was a single-center, retrospective study on 104 patients who had undergone IVOCT-guided percutaneous coronary intervention. Plaque characterization was performed using OCTOPUS software developed by our group. A total of 31 plaque features, including lesion length, lumen, calcium, fibrous cap (FC), and vulnerable plaque features (e.g., microchannel and cholesterol crystal), were computed from the baseline IVOCT images (obtained before stenting). For IVOCT plaque features, the discriminatory power for predicting MACE was determined using univariate/multivariate logistic regression as assessed by area under the receiver operating characteristic curve (AUC).ResultsOf 104 patients, MACE was identified in 24 patients (23.1%). Univariate logistic regression revealed that lesion length, maximum calcium angle, maximum calcium thickness, maximum FC angle, maximum FC area, and FC surface area were significantly associated with MACE (p<0.05). Additionally, cholesterol crystal and layered plaque showed a strong association with MACE (p<0.05). In the multivariate logistic analysis, only the FC surface area (OR 2.38, CI 0.98-5.83, p<0.05) was identified as a significant determinant for MACE, highlighting the importance of the 3D lesion analysis. The AUC of FC surface area for predicting MACE was 0.851 (95% CI 0.800-0.927, p<0.05). Luminal stenosis was not a strong predictor of the risk of MACE.ConclusionsPatients with MACE had distinct plaque characteristics in IVOCT. In particular, large FC surface areas were a risk factor. Interestingly, cap thickness, a commonly highlighted feature for lesion vulnerability, was less predictive than cap area. Studies such as this one might someday lead to recommendations for pharmaceutical and interventional approaches.
Red flags for potential serious pathologies masquerading as musculoskeletal neck pain: a protocol for a systematic review of clinical practice guidelines
Authors: Feller Daniel , Chiarotto Alessandro , Koes Bart , Maselli Filippo , Mourad Firas 
Published: June 2023

ABSTRACTBackgroundAlthough benign most of the time, neck pain (NP) has been observed as the early manifestation of various serious cervical pathologies (e.g., malignancies, fractures). Red flags (RF) are signs and symptoms that raise suspicion of serious spinal pathology. Considering that it has been estimated that the incidence of delayed diagnosis of serious cervical pathologies ranges from 5% to 20%, investigating RFs for NP remains a priority for an informed practice and the patient’s safety. Therefore, the following systematic review will aim to identify red flags recommendations to triage serious pathologies in current clinical practice guidelines (CPGs) for patients with NP, to evaluate the consistency between different CPGs regarding RF recommendations, and to investigate on what study type the recommendation of CPGs are based.Material and methodsWe will search for CPGs for patients with specific or non – specific NP by searching MEDLINE (via PubMed), EMBASE, and PEDro electronic databases. Guidelines will also be searched through forward and backward citation tracking strategies (Web of Science), by consulting experts in the field, and by checking guideline organization databases. Also, we will screen the references of two recently published systematic reviews on CPGs for NP. For all the CPGs included, we will extract bibliographic information, the serious pathologies considered, the RF considered for all serious pathologies, the reference used to support all the RF cited in the guideline, and, if available, the diagnostic accuracy data for all the RF. Two authors will independently perform the study selection and data extraction processes.Data synthesisResults will be presented descriptively and using graphs and tables. We will evaluate the consistency among the guidelines in their endorsement of red flags using Fleiss’ kappa. Fleiss’ kappa will be presented separately for all serious pathologies the CPGs consider.
Predicting the impact of rare variants on RNA splicing in CAGI6
Authors: Lord Jenny , Oquendo Carolina Jaramillo , Wai Htoo A. , Douglas Andrew G.L , Bunyan David J. , Wang Yaqiong , Hu Zhiqiang , Zeng Zishuo , Danis Daniel , Katsonis Panagiotis , Williams Amanda , Lichtarge Olivier , Chang Yuchen , Bagnall Richard D. , Mount Stephen M. , Matthiasardottir Brynja , Lin Chiaofeng , van Overeem Hansen Thomas , Leman Raphael , Martins Alexandra , Houdayer Claude , Krieger Sophie , Bakolitsa Constantina , Peng Yisu , Kamandula Akash , Radivojac Predrag , Baralle Diana 
Published: June 2023

AbstractBackgroundVariants which disrupt splicing are a frequent cause of rare disease that have been under-ascertained clinically. Accurate and efficient methods to predict a variant’s impact on splicing are needed to interpret the growing number of variants of unknown significance (VUS) identified by exome and genome sequencing. Here we present the results of the CAGI6 Splicing VUS challenge, which invited predictions of the splicing impact of 56 variants ascertained clinically and functionally validated to determine splicing impact.ResultsThe performance of 12 prediction methods, along with SpliceAI and CADD, was compared on the 56 functionally validated variants. The maximum overall accuracy achieved was 82% from two different approaches, one weighting SpliceAI scores by minor allele frequency, and one applying the recently published Splicing Prediction Pipeline (SPiP). SPiP performed optimally in terms of sensitivity, while an ensemble method combining multiple prediction tools and information from databases exceeded all others for specificity.ConclusionsSeveral challenge methods equalled or exceeded the performance of SpliceAI, with ultimate choice of prediction method likely to depend on experimental or clinical aims. One quarter of the variants were incorrectly predicted by at least 50% of the methods, highlighting the need for further improvements to splicing prediction methods for successful clinical application.
Evidence for glutamate excitotoxicity that occurs before the onset of striatal cell loss and motor symptoms in an ovine Huntington’s Disease model
Authors: Jiang Andrew , You Linya , Handley Renee R. , Hawkins Victoria , Reid Suzanne J. , Jacobsen Jessie C. , Patassini Stefano , Rudiger Skye R. , Mclaughlan Clive J. , Kelly Jennifer M. , Verma Paul J. , Bawden C. Simon , Gusella James F. , MacDonald Marcy E. , Waldvogel Henry J. , Faull Richard L.M. , Lehnert Klaus , Snell Russell G. 
Published: June 2023

AbstractBackgroundHuntington’s disease (HD) is a neurodegenerative genetic disorder caused by an expansion in the CAG repeat tract of the huntingtin (HTT) gene resulting in a triad of behavioural, cognitive, and motor defects. Current knowledge of disease pathogenesis remains incomplete, and no disease course-modifying interventions are in clinical use. We have previously reported the development and characterisation of theOVT73transgenic sheep model of HD.OVT73captures an early prodromal phase of the disease with an absence of motor symptomatology even at 5-years of age and no detectable striatal cell loss.MethodsTo better understand the disease-initiating events we have undertaken a single nuclei transcriptome study of the striatum of an extensively studied cohort of 5-year-oldOVT73HD sheep and age matched wild-type controls.ResultsWe have identified transcriptional upregulation of genes encoding N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate receptors inOVT73medium spiny neurons, the cell type preferentially lost early in HD. This observation supports the glutamate excitotoxicity hypothesis as an early neurodegeneration cascade-initiating process. Moreover, we also observed the downstream consequences of excitotoxic stress, including a downregulation of transcription of components for the oxidative phosphorylation complexes. We also found that pathways whose activity has been proposed to reduce excitotoxicity, including the CREB family of transcription factors (CREB1,ATF2, ATF4andATF7) were transcriptionally downregulated.ConclusionsTo our knowledge, theOVT73model is the first large mammalian HD model that exhibits transcriptomic signatures of an excitotoxic process in the absence of neuronal loss. Our results suggest that glutamate excitotoxicity is a disease-initiating process. Addressing this biochemical defect early may prevent neuronal loss and avoid the more complex secondary consequences precipitated by cell death.
Comprehensive analysis of network reconstruction approaches based on correlation in metagenomic data
Authors: Fuschi Alessandro , Merlotti Alessandra , Tran Thi Dong Binh , Nguyen Hoan , Weinstock George M. , Remondini Daniel 
Published: June 2023

AbstractMicrobiome analysis is transforming our understanding of biological processes related to human health, epidemiology (antimicrobial resistance, horizontal gene transfer) environmental and agricultural studies. At the core of microbiome analysis is the description of microbial communities based on quantification of microbial taxa and dynamics. In the study of bacterial abundances, it is becoming more relevant to consider their relationship, to embed these data in the framework of network theory, allowing characterization of features like node relevance, pathway and community structure. In this work we characterize the principal biases in reconstructing networks from correlation measures, associated with the compositional character of relative abundance data, the diversity of abundances and the presence of unobserved species within a single sample, that might lead to wrong correlation estimates. We show how most of these problems can be overcome by applying typical transformations for compositional data, that allow the application of simple measures such as Pearson’s correlation to correctly identify the positive and negative relationships between relative abundances, when data dimensionality is sufficiently high. Some issues remain, like the role of data sparsity, that if not properly addressed can lead to imbalances in correlation coefficient distribution.
A Systems Level Explanation for Gompertzian Mortality Patterns is provided by the “Multiple and Inter-dependent Component Cause Model”
Authors: Nielsen Pernille Yde , Jensen Majken K , Mitarai Namiko , Bhatt Samir 
Published: June 2023

AbstractUnderstanding and facilitating healthy aging has become a major goal in medical research and it is becoming increasingly acknowledged that there is a need for understanding the aging phenotype as a whole rather than focusing on individual factors. Here, we provide a universal explanation for the emergence of Gompertzian mortality patterns using a systems approach to describe aging in complex organisms that consist of many inter-dependent subsystems. Our model relates to the Sufficient-Component Cause Model, widely used within the field of epidemiology, and we show that including inter-dependencies between subsystems and modeling the temporal evolution of subsystem failure results in Gompertizan mortality on the population level. Our model also provides temporal trajectories of mortality-risk for the individual. These results may give insight into understanding how biological age evolves stochastically within the individual, and how this in turn leads to a natural heterogeneity of biological age in a population.
High prevalence of haemosporidian parasites in Eurasian Jays
Authors: Schumm Yvonne R. , Lederer-Ponzer Naemi , Masello Juan F. , Quillfeldt Petra 
Published: June 2023

AbstractAvian haemosporidians are vector-borne blood parasites, which infect a great variety of avian host species. The order Passeriformes has the highest average infection probability; nevertheless, some common species of this order have been rather poorly studied in terms of haemosporidian prevalence and diversity. In this study, we investigated the prevalence of haemosporidians in one of such species, the Eurasian JayGarrulus glandarius(Corvidae), from a forest population in Hesse, Central Germany. All individuals were infected with at least one haemosporidian genus, i.e. an overall prevalence of 100%. The most common infection pattern was a mixed infection withHaemoproteusandLeucocytozoon, whereas noPlasmodiuminfection was detected. Our results regarding lineage diversity combined with data from other studies indicate a rather pronounced host-specificity ofHaemoproteusandLeucocytozoonlineages infecting birds of the family Corvidae.
Metabolic transitions regulate global protein fatty acylation
Authors: Talwadekar Manasi , Khatri Subhash , Balaji Chinthapalli , Chakraborty Arnab , Basak Nandini-Pal , Kamat Siddhesh , Kolthur-Seetharam Ullas 
Published: June 2023

AbstractIntermediary metabolites and flux through various pathways have emerged as key determinants of post-translational modifications. Independently, dynamic fluctuations in their concentrations are known to drive cellular energetics in a bi-directional manner. Notably, intracellular fatty acid pools that drastically change during fed and fasted states act as precursors for both ATP production and fatty acylation of proteins. Protein fatty acylation is well regarded for its role in regulating structure and functions of diverse proteins, however the effect of intracellular concentrations of fatty acids on protein modification is less understood. In this regard, we unequivocally demonstrate that metabolic contexts, viz. fed and fasted states, dictate the extent of global fatty acylation. Moreover, we show that presence or absence of glucose, that influences cellular and mitochondrial uptake/utilization of fatty acids, affects palmitoylation and oleoylation, which is consistent with their intracellular abundance in fed and fasted states. Employing complementary approaches including click-chemistry, lipidomics and imaging, we show the top-down control of cellular metabolic state. Importantly, our results establish the crucial role of mitochondria and retrograde signaling components like SIRT4, AMPK and mTOR in orchestrating protein fatty acylation at a whole cell level. Specifically, pharmacogenetic perturbations that alter either mitochondrial functions and/or retrograde signaling affect protein fatty acylation. Besides illustrating the cross-talk between carbohydrate and lipid metabolism in mediating bulk post-translational modification, our findings also highlight the involvement of mitochondrial energetics.
Epigenomic analysis of Formalin-Fixed Paraffin-Embedded samples by CUT&Tag
Authors: Henikoff Steven , Henikoff Jorja G. , Ahmad Kami , Paranal Ronald M. , Janssens Derek H. , Russell Zachary R. , Szulzewsky Frank , Kugel Sita , Holland Eric C. 
Published: June 2023

AbstractFor more than a century, Formalin Fixed Paraffin Embedded (FFPE) sample preparation has been the preferred method for long-term preservation of biological material. However, the use of FFPE samples for epigenomic studies has been difficult because of chromatin damage from long exposure to high concentrations of formaldehyde. Previously, we introduced Cleavage Under Targeted Accessible Chromatin (CUTAC), an antibody-targeted chromatin accessibility mapping protocol based on CUT&Tag. Here we show that simple modifications of our single-tube CUTAC protocol are sufficient to produce high-resolution maps of paused RNA Polymerase II (RNAPII) at enhancers and promoters using FFPE samples. We find that transcriptional regulatory element differences produced by FFPE-CUTAC distinguish between mouse brain tumor specimens and identify regulatory element markers with high confidence and precision. Our simple work-flow is suitable for automation, making possible affordable epigenomic profiling of archived biological samples for biomarker identification, clinical applications and retrospective studies.
Mechanism of DNA origami folding elucidated by mesoscopic simulations
Authors: DeLuca Marcello , Ye Tao , Poirier Michael , Ke Yonggang , Castro Carlos , Arya Gaurav 
Published: June 2023

AbstractDNA nanotechnology leverages the canonical base-pairing rules and geometry of DNA to create highly precise nanoscale structures with many potential applications. While the design and fabrication of DNA nanostructures is well-established, the self-assembly process that produces these structures is still poorly understood, especially for DNA origami that involve the assembly of hundreds of strands. Many experimental and computational efforts have sought to better understand DNA origami folding, but the small length and time scales of individual binding events and the long timescale over which folding occurs have posed significant challenges. Here, we present a new mesoscopic model that uses a switchable force field to capture the mechanical behavior of single- and double-stranded DNA motifs and transition between them at a coarseness level of up to 8 nucleotides per particle, allowing access to the long assembly timescales of DNA origami up to several kilobases in size. Brownian dynamics simulations of 4-helix bundle (4HB) structures using this model reveal a hierarchical folding process involving the zipping of structural domains into a partially folded precursor structure followed by gradual crystallization into the final structure. We elucidate the role of hybridization strength, scaffold routing, and staple design in the folding order and kinetics. Simulation of larger 32HB structures reveals heterogeneous staple incorporation kinetics and frequent trapping in metastable states, as opposed to smaller, more accessible structures like the 4HB, which exhibit first-order kinetics and virtually defect-free folding. The development of this model opens an avenue to better understand and design DNA nanostructures for improved yield and folding performance.
Transcriptional profiling of aging tissues from female and male African turquoise killifish
Authors: Xu Alan , Teefy Bryan B. , Lu Ryan J. , Nozownik Séverine , Tyers Alexandra M. , Valenzano Dario R. , Benayoun Bérénice A. 
Published: June 2023

AbstractThe African turquoise killifish is an emerging vertebrate model organism with great potential for aging research due to its naturally short lifespan. Thus far, turquoise killifish aging ‘omic’ studies using RNA-seq have examined a single organ, single sex and/or evaluated samples from non-reference strains. Here, we describe a resource dataset of ribosomal RNA depleted RNA-seq libraries generated from the brain, heart, muscle, and spleen from both sexes, as well as young and old animals, in the reference GRZ turquoise killifish strain. We provide basic quality control steps and demonstrate the utility of our dataset by performing differential gene expression and gene ontology analyses by age and sex. Importantly, we show that age has a greater impact than sex on transcriptional landscapes across probed tissues. Finally, we confirm transcription of transposable elements (TEs), which are highly abundant and increase in expression with age in brain tissue. This dataset will be a useful resource for exploring gene and TE expression as a function of both age and sex in a powerful naturally short-lived vertebrate model.
Co-occurrence of ST412Klebsiella pneumoniaeisolates with hypermucoviscous and no-mucoviscous phenotypes in a short-term hospitalized patient
Authors: Liang Qinghua , Zhang Biying , Wang Wei , Chen Nan , Luo Jingjing , Zhong Ying , Zhang Feiyang , Zhang Zhikun , Martín–Rodríguez Alberto J. , Wang Ying , Xiang Li , Zhuang Jiaru , Hu Renjing , Zhou Yingshun 
Published: June 2023

AbstractHypermucoviscosity(HMV) is a phenotype that is commonly associated with hypervirulence inKlebsiella pneumoniae. The factors that contribute to the emergence of HMV subpopulations remain unclear. In this study, eightK. pneumoniaestrains were recovered from an inpatient who were hospitalized for 20 days. Three of the isolates exhibited a non-HMV phenotype, which was concomitant with increased biofilm formation and higher siderophore secretion than the other five HMV isolates. All eight isolates were highly susceptible to serum killing, albeit HMV strains were remarkably more infective than non-HMV counterparts in a mouse model of infection. Whole genome sequencing(WGS) showed that the eight isolates belonged to the K57-ST412 lineage. Average nucleotide identity(ANI) analysis indicated that eight isolates share 99.96% to 99.99% similarity and were confirmed to be the same clone. Through comparative genomics analysis, 12 non-synonymous mutations were found among these isolates, seven of which in the non-HMV variants, includingrmpA(R96G) andwbap(S435R), which are assumed to be associated with the non-HMV phenotype. The mutationsmanB(G440L),dmsB(R193W) andtkt(A643N) occurred in HMV isolates only. RNA-Seq and RT-qPCR revealed transcripts of genes involved in transporter activity, carbohydrate metabolism and energy metabolism, includingcysK,paaF,vasD,celCandfruA, to be significantly dysregulated in the non-HMV strain K201060 compared to the HMV strain K201059, suggesting a participation in HMV phenotype development. This study suggests that co-occurrence of HMV and non-HMV phenotypes in the same clonal population may be mediated by mutational mechanisms as well as by certain genes involved in transport and central metabolism.ImportanceK. pneumoniaewith a hypermucoviscosity(HMV) phenotype is a community-acquired pathogen that associated with increased invasiveness and pathogenicity, and underlying diseases are the most common comorbid risk factors inducing metastatic complications. HMV was earlier attributed to the overproduction of capsular polysaccharide, and more data point to the possibility of several causes contribute to this bacterial phenotype. Here, we describe a unique event in which the same clonal population showed both HMV and non-HMV characteristics. Studies have demonstrated that this process is influenced by mutational processes and genes related to transport and central metabolism. These finding provide fresh insight into the mechanisms between behind co-occurrence of HMV and non-HMV phenotypes in monoclonal populations as well as potentially being critical in developing strategies to control the further spread of HMVK. pneumoniae.