bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma proteins identify increased number of carotid plaques and predict occurring atherosclerotic events
Authors: Baragetti A , Grigore L , Olmastroni E , Mattavelli E , Catapano AL 
Published: September 2023

AbstractBackgroundThe number of carotid plaques independently predicts incident atherosclerotic cardiovascular disease (ACVD).However, performing vascular imaging in apparently healthy subjects is challenging, owing organizational/economical barriers. Plasma proteomics can offer an alternative approach to identify individuals with carotid plaques, at high risk of eventually developing ACVD.MethodsIn this observational study, we studied by Normalized Protein eXpression (NPX; OlinkTM), the plasma levels of 368 proteins in 664 subjects from the PLIC study, who were screened by ultrasound for the presence of carotid plaques. We clustered, by artificial intelligence, the proteins that more accurately identified subjects, stratifying them according to the number of plaques they presented with. We also study prediction of occurring events over 22 years.Results299/664 subjects had at least 1 carotid plaque. Among those, 77 subjects presented with only one plaque, 101 with 2 plaques and 121 with ≥3 plaques (3+). The remaining 365 subjects with no plaques acted as controls. The proteins differently expressed versus controls increased as a function of the number of plaques. 32 proteins were shared among the groups of subjects with plaques, but 87, significantly associated with the presence of 3+ plaques, improved the AUC of the ROC, together with the ACVD risk factors, to discriminate subjects with 3+ plaques versus the AUC of the ROC considering the ACVD risk factors only (AUC= 0.918 (0.887-0.943) vs AUC= 0.760 (0.716-0.801) respectively, p<0.001). The ACVD risk factors barely predicted the 198 occurring events (AUC= 0.559 (0.521-0.598)), but proteomics associated with plaques improved the prediction (AUC= 0.739 (0.704-0.773), p<0.001).By analyzing the biological processes, we identified that chemotaxis/migration of leukocytes and the signaling of interleukins/cytokines were the top pathways involved.ConclusionsPlasma proteomics helps to identify apparently healthy subjects with higher number of carotid plaques more accurately and to predict occurring ACVDs in those individuals.
Voice as a Biomarker to Detect Acute Decompensated Heart Failure: Pilot Study for the Analysis of Voice Using Deep Learning Models
Authors: Lee Jieun , Kim Gwantae , Ham Insung , Ko Kyungdeuk , Park Soohyung , Choi You-Jung , Kang Dong Oh , Choi Jah Yeon , Park Eun Jin , Lee Sunki , Roh Seung Young , Lee Dae-In , Na Jin Oh , Choi Cheol Ung , Kim Jin Won , Rha Seung-Woon , Park Chang Gyu , Kim Eung Ju , Ko Hanseok 
Published: September 2023

AbstractBackgroundAcute decompensated heart failure (ADHF) is a systemic congestion state requiring timely management. Admission for ADHF is closely related to the readmission and post-discharge mortality in patients, which makes it imperative to detect ADHF in its early stage.MethodsPatients with ADHF needed admission were eligible for enrollment, and those with respiratory infection, sepsis, lung/vocal cord disease, acute coronary syndrome, or serum creatinine>3mg/dL were excluded. A total of 112 patients were enrolled between July, 2020 and December, 2022. Voice was recorded two times: at admission for ADHF, and at discharge. Patients were asked to phonate five Korean vowels (‘a/e/i/o/u’) for 3 seconds each, and then to repeat the sentence ‘daehan minkook manse’ five times. Low-level audio features were extracted for classification. Then, Mel-Spectrogram was extracted from waveform and used as input features of the deep learning-based classification models. Two kinds of the deep learning-based classification models, convolutional neural networks and Transformer, were adapted for the further analysis.ResultsFor 100 patients in the final analysis, we randomized patients into two mutually exclusive groups: a training group (n=88) and a test group (n=12). In the analysis with low-level audio features, harmonics-to-noise ratio and Shimmer showed classification potential. Then, deep learning models were trained to classify whether certain voice belongs to ADHF state or recovered state. We treated it as a binary classification task, and the best performing model achieved a classification accuracy of 85.11% with DenseNet201. The classification accuracy was improved as 92.76% with ViT-16-large after inputting additional classic features of heart failure. With adding the low-level audio features in a training process, classification task accuracy was improved in DenseNet201 for about 2%.ConclusionsOur results proposed the clinical possibility of voice as a useful and noninvasive biomarker to detect ADHF in its early stage.
In Vivo Structural Connectivity of the Reward System Along the Hippocampal Long-Axis
Authors: Elliott Blake L. , Mohyee Raana , Ballard Ian C. , Olson Ingrid R. , Ellman Lauren M. , Murty Vishnu P. 
Published: September 2023

AbstractRecent work has identified a critical role for the hippocampus in reward-sensitive behaviors, including motivated memory, reinforcement learning, and decision-making. Animal histology and human functional neuroimaging have shown that brain regions involved in reward processing and motivation are more interconnected with the ventral/anterior hippocampus. However, direct evidence examining gradients of structural connectivity between reward regions and the hippocampus in humans is lacking. The present study used diffusion MRI and probabilistic tractography to quantify the structural connectivity of the hippocampus with key reward processing regions in vivo. Using a large sample of subjects (N=628) from the human connectome dMRI data release, we found that connectivity profiles with the hippocampus varied widely between different regions of the reward circuit. While the dopaminergic midbrain (VTA) showed stronger connectivity with the anterior versus posterior hippocampus, the vmPFC showed stronger connectivity with the posterior hippocampus. The nucleus accumbens (NAc) showed a more homogeneous connectivity profile along the hippocampal long-axis. This is the first study to generate a probabilistic atlas of the hippocampal structural connectivity with reward-related networks, which is essential to investigating how these circuits contribute to normative adaptive behavior and maladaptive behaviors in psychiatric illness. These findings describe nuanced structural connectivity that sets the foundation to better understand how the hippocampus influences reward-guided behavior in humans.
The high infectivity of the SARS-CoV-2 Omicron variant is associated with an exclusive S477N spike receptor-binding domain mutation
Authors: Santos Jadson C. , Tamarozzi Elvira R. , Dametto Mariangela , Bonacin Rodrigo , Donadi Eduardo A. , Passos Geraldo Aleixo 
Published: September 2023

AbstractThe spike glycoprotein receptor-binding domain (RBD) of SARS-CoV-2 facilitates viral binding to the ACE2 receptor and mediates viral infectivity. The Delta and Omicron variants of concern are the most infectious strains, presenting mutated amino acid residues in their spike RBD. The Omicron variant quickly dominated the COVID-19 pandemic, indicating its greater spreadability. Omicron’s spreading might be associated with mutational substitutions at spike RBD residues. We employedin silicomolecular dynamics (MD) simulation of the spike RBD-ACE2 interaction to compare the impact of specific mutations of the Delta and Omicron variants. The MD of the spike-ACE2 interaction showed the following: i) the amino acid profile involved in the spike-ACE2 interaction differs between Delta and Omicron; ii) the Omicron variant establishes several additional interactions, highlighting the spike RBD (S477), which is a flexible mutational residue. Since the S477N mutation is exclusive to Omicron, which may initiate binding with ACE2, the increased infectivity of Omicron might be associated not only with a mutated RBD but also with unmutated (e.g., G476 and L492) residues, initiating binding due to the influence of the N477 mutation. Compared to previous variants, Omicron’s N477 residue represents a novelty within the spike-ACE2 interaction dynamics interface.
APlasmodium falciparumMORC protein complex modulates epigenetic control of gene expression through interaction with heterochromatin
Authors: Singh Maneesh Kumar , Bonnell Victoria A. , Da Silva Israel Tojal , Santiago Verônica Feijoli , Moraes Miriam S. , Adderley Jack , Doerig Christian , Palmisano Giuseppe , Llinás Manuel , Garcia Célia R. S. 
Published: September 2023

AbstractDynamic control of gene expression is critical for blood stage development of malaria parasites. Here, we used multi-omic analyses to investigate transcriptional regulation by the chromatin-associated microrchidia protein, MORC, during asexual blood stage development of the human malaria parasitePlasmodium falciparum. We show thatPfMORC (PF3D7_1468100) interacts with a suite of nuclear proteins, including APETALA2 (AP2) transcription factors (PfAP2-G5,PfAP2-O5,PfAP2-I, PF3D7_0420300, PF3D7_0613800, PF3D7_1107800, and PF3D7_1239200), a DNA helicase DS60 (PF3D7_1227100), and other chromatin remodelers (PfCHD1 andPfEELM2). Transcriptomic analysis ofPfMORCHA-glmSknockdown parasites revealed 163 differentially expressed genes belonging to hypervariable multigene families, along with upregulation of genes mostly involved in host cell invasion.In vivogenome-wide chromatin occupancy analysis during both trophozoite and schizont stages of development demonstrates thatPfMORC is recruited to repressed, multigene families, including thevargenes in subtelomeric chromosomal regions. Collectively, we find thatPfMORC is found in chromatin complexes that play a role in the epigenetic control of asexual blood stage transcriptional regulation and chromatin organization.
Design and validation of a PCR protocol to specifically detect the clade ofPhilastersp. associated withDiadema antillarumscuticociliatosis
Authors: Vilanova-Cuevas Brayan Y. , Reyes-Chavez Brandon , Breitbart Mya , Hewson Ian 
Published: September 2023

ABSTRACTDiadema antillarumscuticociliatosis (DaSc), caused by a scuticociliate closely related toPhilaster apodigitiformis, has affected Caribbean long-spined urchins since at least January 2022. Quantitative PCR (qPCR) is currently the standard method for detection of this ciliate in tissue and coelomic fluid samples, yet this method requires specialized equipment and is more expensive than standard PCR methods. The DaSc scuticociliate occurs against a backdrop of endo- and ecto-symbiotic ciliates which complicate detection using universal or pan-phylum PCR primer sets. To overcome these limitations, we designed and validated a sensitive and specific PCR primer (scutico-634F) and nested two-step PCR protocol to detect this taxon, which excludes other ciliates associated withD. antillarumand has poor affinity for other related ciliates. This primer and protocol for the DaSc-associated Philaster clade (DaScPc) allow for widely-accessible investigation of this pathogen in new regions and within environmental reservoirs.
Temperature and transmission: novel estimates of the effects of temperature on the human malaria parasite,Plasmodium falciparum
Authors: Suh Eunho , Stopard Isaac J. , Lambert Ben , Waite Jessica L. , Dennington Nina L. , Churcher Thomas S. , Thomas Matthew B. 
Published: September 2023

AbstractMalaria transmission is strongly influenced by traits such as mosquito life expectancy, vector competence, and the Extrinsic Incubation Period (EIP, which is the development time of the parasite inside the mosquito). Even though these traits are known to be shaped by environmental temperature and there is considerable concern that climate change could increase disease risk in certain areas, surprisingly, these temperature dependencies are poorly characterized. Here, we use a mechanistic model fitted to novel experimental data to describe howPlasmodium falciparuminfection of the African malaria vector,Anopheles gambiae,is modulated by temperature, including its influences on parasite establishment, conversion efficiency through parasite developmental stages, EIP and overall competence. We use these data, together with novel estimates of the survival of infected blood-fed mosquitoes, to explore the potential influence of temperature on transmission in four locations in Kenya, considering recent conditions and future climate change. Results provide insights into factors limiting transmission in cooler environments and indicate that increases in malaria transmission efficiency due to climate warming in areas like the Kenyan Highlands, might be less than previously predicted.
Biological and Genetic Determinants of Glycolysis: Phosphofructokinase Isoforms Boost Energy Status of Stored Red Blood Cells and Transfusion Outcomes
Authors: Nemkov Travis , Stephenson Daniel , Earley Eric J. , Keele Gregory R , Hay Ariel , Key Alicia , Haiman Zachary , Erickson Christopher , Dzieciatkowska Monika , Reisz Julie A. , Moore Amy , Stone Mars , Deng Xutao , Kleinman Steven , Spitalnik Steven L , Hod Eldad A , Hudson Krystalyn E , Hansen Kirk C , Palsson Bernhard O. , Churchill Gary A , Roubinian Nareg , Norris Philip J. , Busch Michael P. , Zimring James C , Page Grier P. , D’Alessandro Angelo 
Published: September 2023

SummaryMature red blood cells (RBCs) lack mitochondria, and thus exclusively rely on glycolysis to generate adenosine triphosphate (ATP) during aging in vivo or storage in the blood bank. Here we leveraged 13,029 volunteers from the Recipient Epidemiology and Donor Evaluation Study to identify an association between end-of-storage levels of glycolytic metabolites and donor age, sex, and ancestry-specific genetic polymorphisms in regions encoding phosphofructokinase 1, platelet (detected in mature RBCs), hexokinase 1, ADP-ribosyl cyclase 1 and 2 (CD38/BST1). Gene-metabolite associations were validated in fresh and stored RBCs from 525 Diversity Outbred mice, and via multi-omics characterization of 1,929 samples from 643 human RBC units during storage. ATP and hypoxanthine levels – and the genetic traits linked to them – were associated with hemolysis in vitro and in vivo, both in healthy autologous transfusion recipients and in 5,816 critically ill patients receiving heterologous transfusions, suggesting their potential as markers to improve transfusion outcomes.eTOC and HighlightsHighlightsBlood donor age and sex affect glycolysis in stored RBCs from 13,029 volunteers;Ancestry, genetic polymorphisms in PFKP, HK1, CD38/BST1 influence RBC glycolysis;Modeled PFKP effects relate to preventing loss of the total AXP pool in stored RBCs;ATP and hypoxanthine are biomarkers of hemolysis in vitro and in vivo.
PfMORC protein regulates chromatin accessibility and transcriptional repression in the human malaria parasite,Plasmodium falciparum
Authors: Chahine Z , Gupta M , Lenz T , Hollin T , Abel S , Banks CAS , Saraf A , Prudhomme J , Bhanvadia S , Florens L , Le Roch KG 
Published: September 2023

AbstractThe environmental challenges the human malaria parasite,Plasmodium falciparum, faces during its progression into its various lifecycle stages warrant the use of effective and highly regulated access to chromatin for transcriptional regulation. Microrchidia (MORC) proteins have been implicated in DNA compaction and gene silencing across plant and animal kingdoms. Accumulating evidence has shed light into the role MORC protein plays as a transcriptional switch in apicomplexan parasites. In this study, using CRISPR/Cas9 genome editing tool along with complementary molecular and genomics approaches, we demonstrate thatPfMORC not only modulates chromatin structure and heterochromatin formation throughout the parasite erythrocytic cycle, but is also essential to the parasite survival. Chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) experiments suggest thatPfMORC binds to not only sub-telomeric regions and genes involved in antigenic variation but may also play a role in modulating stage transition. Protein knockdown experiments followed by chromatin conformation capture (Hi-C) studies indicate that downregulation ofPfMORC impairs key histone marks and induces the collapse of the parasite heterochromatin structure leading to its death. All together these findings confirm thatPfMORC plays a crucial role in chromatin structure and gene regulation, validating this factor as a strong candidate for novel antimalarial strategies.
The colocatome as a spatial -omic reveals shared microenvironment features between tumour–stroma assembloids and human lung cancer
Authors: Bouchard Gina , Zhang Weiruo , Li Irene , Ilerten Ilayda , Bhattacharya Asmita , Li Yuanyuan , Trope Winston , Shrager Joseph B , Kuo Calvin , Tian Lu , Giaccia Amato J , Plevritis Sylvia K 
Published: September 2023

AbstractComputational frameworks to quantify and compare microenvironment spatial features of in-vitro patient-derived models and clinical specimens are needed. Here, we acquired and analysed multiplexed immunofluorescence images of human lung adenocarcinoma (LUAD) alongside tumour– stroma assembloids constructed with organoids and fibroblasts harvested from the leading edge (Tumour-Adjacent Fibroblasts;TAFs) or core (Tumour Core Fibroblasts;TCFs) of human LUAD. We introduce the concept of the “colocatome” as a spatial -omic dimension to catalogue all proximate and distant colocalisations between malignant and fibroblast subpopulations in both the assembloids and clinical specimens. The colocatome expands upon the colocalisation quotient (CLQ) through a nomalisation strategy that involves permutation analysis and thereby allows comparisons of CLQs under different conditions. Using colocatome analysis, we report that both TAFs and TCFs protected cancer cells from targeted oncogene treatment by uniquely reorganising the tumour–stroma cytoarchitecture, rather than by promoting cellular heterogeneity or selection. Moreover, we show that the assembloids’ colocatome recapitulates the tumour–stroma cytoarchitecture defining the tumour microenvironment of LUAD clinical samples and thereby can serve as a functional spatial readout to guide translational discoveries.Abstract Figure
Decoding biological age from face photographs using deep learning
Authors: Zalay Osbert , Bontempi Dennis , Bitterman Danielle S , Birkbak Nicolai , Shyr Derek , Haugg Fridolin , Qian Jack M , Roberts Hannah , Perni Subha , Prudente Vasco , Pai Suraj , Dekker Andre , Haibe-Kains Benjamin , Guthier Christian , Balboni Tracy , Warren Laura , Krishan Monica , Kann Benjamin H , Swanton Charles , Ruysscher Dirk De , Mak Raymond H , Aerts Hugo JWL 
Published: September 2023

ABSTRACTBecause humans age at different rates, a person’s physical appearance may yield insights into their biological age and physiological health more reliably than their chronological age. In medicine, however, appearance is incorporated into medical judgments in a subjective and non-standardized fashion. In this study, we developed and validated FaceAge, a deep learning system to estimate biological age from easily obtainable and low-cost face photographs. FaceAge was trained on data from 58,851 healthy individuals, and clinical utility was evaluated on data from 6,196 patients with cancer diagnoses from two institutions in the United States and The Netherlands. To assess the prognostic relevance of FaceAge estimation, we performed Kaplan Meier survival analysis. To test a relevant clinical application of FaceAge, we assessed the performance of FaceAge in end-of-life patients with metastatic cancer who received palliative treatment by incorporating FaceAge into clinical prediction models. We found that, on average, cancer patients look older than their chronological age, and looking older is correlated with worse overall survival. FaceAge demonstrated significant independent prognostic performance in a range of cancer types and stages. We found that FaceAge can improve physicians’ survival predictions in incurable patients receiving palliative treatments, highlighting the clinical utility of the algorithm to support end-of-life decision-making. FaceAge was also significantly associated with molecular mechanisms of senescence through gene analysis, while age was not. These findings may extend to diseases beyond cancer, motivating using deep learning algorithms to translate a patient’s visual appearance into objective, quantitative, and clinically useful measures.
Systematic identification of transcriptional activator domains from non-transcription factor proteins in plants and yeast
Authors: Hummel Niklas F. C. , Markel Kasey , Stefani Jordan , Staller Max V. , Shih Patrick M. 
Published: September 2023

AbstractTranscription factors promote gene expression via trans-regulatory activation domains. Although whole genome scale screens in model organisms (e.g. human, yeast, fly) have helped identify activation domains from transcription factors, such screens have been less extensively used to explore the occurrence of activation domains in non-transcription factor proteins, such as transcriptional coactivators, chromatin regulators and some cytosolic proteins, leaving a blind spot on what role activation domains in these proteins could play in regulating transcription. We utilized the activation domain predictor PADDLE to mine the entire proteomes of two model eukaryotes,Arabidopsis thalianaandSaccharomyces cerevisiae(1). We characterized 18,000 fragments covering predicted activation domains from >800 non-transcription factor genes in both species, and experimentally validated that 89% of proteins contained fragments capable of activating transcription in yeast. Peptides with similar sequence composition show a broad range of activities, which is explained by the arrangement of key amino acids. We also annotated hundreds of nuclear proteins with activation domains as putative coactivators; many of which have never been ascribed any function in plants. Furthermore, our library contains >250 non-nuclear proteins containing peptides with activation domain function across both eukaryotic lineages, suggesting that there are unknown biological roles of these peptides beyond transcription. Finally, we identify and validate short, ‘universal’ eukaryotic activation domains that activate transcription in both yeast and plants with comparable or stronger performance to state-of-the-art activation domains. Overall, our dual host screen provides a blueprint on how to systematically discover novel genetic parts for synthetic biology that function across a wide diversity of eukaryotes.Significance StatementActivation domains promote transcription and play a critical role in regulating gene expression. Although the mapping of activation domains from transcription factors has been carried out in previous genome-wide screens, their occurrence in non-transcription factors has been less explored. We utilize an activation domain predictor to mine the entire proteomes ofArabidopsis thalianaandSaccharomyces cerevisiaefor new activation domains on non-transcription factor proteins. We validate peptides derived from >750 non-transcription factor proteins capable of activating transcription, discovering many potentially new coactivators in plants. Importantly, we identify novel genetic parts that can function across both species, representing unique synthetic biology tools.