bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cerebral Thrombus Analysis in Infective Endocarditis: Unveiling Composition for Diagnostic Insight
Authors: Semerano Aurora , Dell’Acqua Beatrice , Montano Manuel , Sanvito Francesca , Genchi Angela , Schwarz Ghil , Bergamaschi Andrea , Sampaolo Michela , Gullotta Giorgia Serena , Falini Andrea , Panni Pietro , Agostoni Elio Clemente , Saliou Guillaume , Hajdu Steven David , Roveri Luisa , Michel Patrik , Martino Gianvito , Filippi Massimo , Strambo Davide , Bacigaluppi Marco 
Published: October 2023

ABSTRACTBackground and AimsInfective endocarditis (IE) is a life-threatening condition known to cause stroke. Swift diagnosis and antibiotic treatment are crucial for preventing cerebral and systemic embolism, therefore reducing mortality and morbidity. However, diagnosing IE can be challenging. In this study, we aimed to assess whether analyzing cerebral thrombi retrieved by endovascular thrombectomy from stroke patients with IE could aid in the diagnosis and shed light on the composition signature of endocarditic thrombi.MethodsWe compared cerebral thrombi from three groups of ischemic stroke patients: those with definite infective endocarditis (IE) (n=10), those with cardioembolic stroke and concomitant infections other than IE (n=10 CE-I+), and those with cardioembolic stroke without infections (n=30 CE-I-). Our multiparameter analysis encompassed histological examinations, molecular biology and microbiological tests to detect microorganisms within the thrombi and to comprehensively assess their structural composition and immune signatures.ResultsWe directly detected invading pathogens through histology or PCR in all cerebral thrombi from IE patients, while none of the control thrombi exhibited such pathogens. Thrombi from IE patients displayed a distinct composition, characterized by a significant lower content of red blood cells, reduced CD14+ monocytes, increased von Willebrand Factor density, and a cell-dominant pattern of Neutrophil Extracellular Traps (NETs) deposition.ConclusionsComprehensive analysis of cerebral thrombi from stroke patients with suspected IE sustains early, definitive endocarditis diagnosis by detecting pathogens and immunothrombotic changes.
Relational One Health: a more-than-biomedical framework for more-than-human health, and lessons learned from Brazil, Ethiopia, and Israel
Authors: Meisner Julianne , McLeland-Wieser Hilary , Traylor Elizabeth E. , Hermesh Barak , Berg Tabata , Roess Amira , Van Patter Lauren , Rosenthal Anat , Davidovitch Nadav , Rabinowitz Peter M. 
Published: October 2023

ABSTRACTThe One Health conceptual framework envisions human, animal, and environmental health as interconnected. This framework has achieved remarkable progress in the control of zoonotic diseases, but it commonly neglects the environmental domain, implicitly prioritizes human life over the life of other beings, and fails to consider the political, cultural, social, historical, and economic contexts that shape the health of multispecies collectives. We have developed a novel theoretical framework, Relational One Health, which expands the boundaries of One Health, clearly defines the environmental domain, and provides an avenue for engagement with critical theory. We present a systematic literature review of One Health frameworks to demonstrate the novelty of Relational One Health, and to orient it with respect to other critically-engaged frameworks for One Health. Our results indicate that while Relational One Health complements several earlier frameworks, these other frameworks are either not intended for research, or for narrow sets of research questions. We then demonstrate the utility of Relational One Health for One Health research through case studies in Brazil, Israel, and Ethiopia. Empirical research which is grounded in theory can speak collectively, increasing the impact of individual studies and the field as a whole. One Health is uniquely poised to address several wicked challenges facing the 21stcentury—climate change, pandemics, neglected zoonoses, and biodiversity collapse—and a unifying theoretical tradition is key to generating the evidence needed to meet these challenges.HIGHLIGHTSOne Health views human, animal, and environmental health as interconnectedBiomedical reductionism in One Health has resulted in a focus on human health threats from animalsThe environmental domain and more-than-biomedical contexts are commonly ignored in One HealthRelational One Health is a new theoretical framework which addresses these limitationsThis theoretical framework is relevant to all One Health research, increasing the field’s impact
Formative Assessment and Cluster Membership of the Homeless Person’s ER Visits
Authors: Cavanaugh Gesulla , Hardigan Patrick , Ownby Raymond , Stanis Stachyse , Karur Prasanna 
Published: October 2023

AbstractThe evidence is limited as to whether homeless individuals who visit Emergency Departments share similar characteristics with individuals from private households who, upon examination, are confirmed to need emergency health services beyond preventative healthcare. While the literature heavily addresses the homeless person in the ED, similarity and differences in characteristics with other social groups are lacking to guide the development of targeted health care and emergency health services for the homeless person. This explorative study investigates hospital ER data to draw inferences on ER patient characteristics and attempts to categorize patients according to residence. Nominal regression analyses reveal that cluster membership generated from ER data can predict patient residence and suggest that substance abuse and depression can predict 72-hour ER visit recurrence. Despite reporting low comorbidities, homeless patients were more likely to experience frequent ER visits within 72 hours and had higher rates of depression and substance abuse. Based on behavioral, health, and social characteristics of the homeless person, hospitals could consider targeted provisions and a follow-up mechanism to meet the health care needs of homeless patients.
Applying Machine Learning on UK Biobank biomarker data empowers case-control discovery yield
Authors: Garg Manik , Karpinski Marcin , Matelska Dorota , Middleton Lawrence , Mitchell Jonathan , O’Neill Amanda , Wang Quanli , Harper Andrew , Dhindsa Ryan S. , Petrovski Slavé , Vitsios Dimitrios 
Published: October 2023

AbstractMissing or inaccurate diagnoses in biobank datasets can reduce the power of human genetic association studies. We present a machine-learning framework (MILTON) that utilizes the wealth of phenotypic information available in a biobank dataset to identify undiagnosed individuals within the cohort who have biomarker profiles similar to those of positively diagnosed cases. We applied MILTON to perform an augmented phenome-wide association study (PheWAS) based on 405,703 whole exome sequencing samples from UK Biobank, resulting in improved signals for known (p<1×10−8) gene-disease relationships alongside 206 novel gene-disease relationships that only achieved genome-wide significance upon using MILTON. To further validate these putatively novel discoveries, we adopt two orthogonal machine learning methods that prioritise gene-disease relationships using comprehensive publicly available datasets alongside a biological insights knowledge graph. For additional clinical translation utility, MILTON outputs a disease-specific biomarker set per disease as well as comorbidity clusters across ICD10 disease codes based on shared biomarker profiles of positively labelled cases. All the extracted associations and biomarker importance results for the 3,308 studied binary traits will be made available via an interactive web-portal.
When random variation results in functional significance
Authors: Barfield Jacob , Kells Patrick A. , Gautam Shree Hari , Li Jingwen , Shew Woodrow L. 
Published: October 2023

AbstractMany functional properties vary dramatically across neurons in cerebral cortex. Two fundamental goals of systems neuroscience are to determine which neurons execute which functions and how the different functional properties of a neuron are related. Often, it is assumed that if two properties are uncorrelated, then there is no important relationship to report. Here we show that this assumption can lead to wrong conclusions; functional segregation can emerge, by chance, due to random variation when that variation is distributed according to skewed, heavy-tailed distributions. We reinterpret the results we previously reported in Kells et al 2019 [1], showing that they are a prime example of functional segregation due to random variation.
27-hydroxylation of oncosterone by CYP27A1 switchs its activity from pro-tumor to anti-tumor
Authors: Ayadi Silia , Friedrichs Silvia , Soulès Regis , Pucheu Laly , Lütjohann Dieter , Silvente-Poirot Sandrine , Poirot Marc , Medina Philippe de 
Published: October 2023

ABSTRACTOncosterone (6-oxo-cholestane-3β,5α-diol; OCDO) is an oncometabolite and a tumor promoter on estrogen receptor alpha positive breast cancer (ER(+) BC) and triple negative breast cancers (TN BC). OCDO is an oxysterol formed in three steps from cholesterol: 1) oxygen addition at the double bond to give α- or β-isomers of 5,6-epoxycholestanols (5,6-EC), 2) hydrolyses of the epoxide ring of 5,6-ECs to give cholestane-3β,5α,6β-triol (CT), and 3) oxidation of the C6 hydroxyl of CT to give OCDO. On the other hand, cholesterol can be hydroxylated by CYP27A1 at the ultimate methyl carbon of its side chain to give 27-hydroxycholesterol (27HC), which is a tumor promoter for ER(+) BC. It is currently unknown whether OCDO and its precursors can be hydroxylated at position C27 by CYP27A1, as is the impact of such modification on the proliferation of ER(+) and TN BC cells. We investigated, herein, whether 27-hydroxylated-5,6-ECs, -CT and -OCDO exist as metabolites and can be produced by cells expressing CYP27A1. We report, for the first time, that these compounds exist as metabolites in human. We give pharmacological and genetic evidences that CYP27A1 is responsible for their production. Importantly, we found that 27-hydroxy-OCDO (27H-OCDO) inhibits BC cells proliferation and blocks OCDO and 27-HC induced proliferation in BC cells, showing that this metabolic conversion commutes the proliferative properties of OCDO into antiproliferative ones. These data suggest an unprecedented role of CYP27A1 in the control of breast carcinogenesis by inhibiting the tumor promoter activities of oncosterone and 27-HC.
Bacteriophage-host interactions in microgravity onboard the International Space Station
Authors: Huss Phil , Chitboonthavisuk Chutikarn , Meger Anthony , Nishikawa Kyle , Oates R.P. , Mills Heath , Holzhaus Olivia , Raman Srivatsan 
Published: October 2023

AbstractBacteriophage-host interactions play a fundamental role in shaping microbial ecosystems. Although researchers have extensively studied phage-host interactions in terrestrial ecosystems, the impact of microgravity on phage-host interactions is yet to be investigated. Here, we report the dynamics of interactions between T7 bacteriophage andE. coliin microgravity onboard the International Space Station (ISS). We found phage activity was delayed but ultimately successful in microgravity. We identified severalde novomutations in phage and bacteria that improved fitness in microgravity. Deep mutational scanning of the receptor binding domain revealed substantial differences in the number, position, and mutational preferences between gravity and microgravity, reflecting underlying differences in the bacterial adaptations. Combinatorial libraries informed by microgravity selections gave T7 mutants with 100-10,000-fold higher activity on uropathogenicE. coliunder terrestrial conditions than wildtype T7. Our findings lay the foundation for future research on the impact of microgravity on phage-host interactions and microbial communities.
Threat-dependent scaling of prelimbic dynamics to enhance fear representation
Authors: Casanova José Patricio , Pouget Clément , Treiber Nadja , Agarwal Ishaant , Brimble Mark Allen , Vetere Gisella 
Published: October 2023

SUMMARYPromptly identifying threatening stimuli is crucial for survival. Freezing is a natural behavior displayed by rodents towards potential or actual threats. While it is known that the prelimbic cortex (PL) is involved in both risk evaluation and in fear and anxiety-like behavior expression, here we explored whether PL neuronal activity can dynamically represent different internal states of the same behavioral output. We found that freezing can always be decoded from PL activity at a population level. However, the sudden presentation of a fearful stimulus quickly reshaped PL to a new neuronal activity state, an effect not observed in other cortical or subcortical regions. This shift changed PL freezing representation and is necessary for fear memory expression. Our data reveal the unique role of PL in detecting threats and internally adjusting to distinguish between different freezing-related states.IN BRIEFThrough a comparative analysis across brain regions and risk situations, we demonstrate the distinctive role of the Prelimbic Cortex (PL) in fear-related behavior representation: the PL promptly detects threat stimuli and adjusts its neuronal configuration accordingly, resulting in a change in freezing representation, which is necessary for memory-associated fear expression.HIGHLIGHTS- PL population activity represents fear-related behavior (i.e., freezing)- Same behavioral outcome (freezing) can be represented as different PL neuronal states- Other brain regions do not show changes in dynamics to represent freezing- PL dynamics following threats are necessary for proper fear memory expression
Convergent Epigenetic Evolution Drives Relapse in Acute Myeloid Leukemia
Authors: Nuno Kevin A. , Azizi Armon , Köhnke Thomas , Lareau Caleb A. , Ediwirickrema Asiri , Ryan Corces M. , Satpathy Ansuman T. , Majeti Ravindra 
Published: October 2023

AbstractRelapse of acute myeloid leukemia (AML) is highly aggressive and often treatment refractory. We analyzed previously published AML relapse cohorts and found that 40% of relapses occur without changes in driver mutations, suggesting that non-genetic mechanisms drive relapse in a large proportion of cases. We therefore characterized epigenetic patterns of AML relapse using 26 matched diagnosis-relapse samples with ATAC-seq. This analysis identified a relapse-specific chromatin accessibility signature for mutationally stable AML, suggesting that AML undergoes epigenetic evolution at relapse independent of mutational changes. Analysis of leukemia stem cell (LSC) chromatin changes at relapse indicated that this leukemic compartment underwent significantly less epigenetic evolution than non-LSCs, while epigenetic changes in non-LSCs reflected overall evolution of the bulk leukemia. Finally, we used single-cell ATAC-seq paired with mitochondrial sequencing (mtscATAC) to map clones from diagnosis into relapse along with their epigenetic features. We found that distinct mitochondrially-defined clones exhibit more similar chromatin accessibility at relapse relative to diagnosis, demonstrating convergent epigenetic evolution in relapsed AML. These results demonstrate that epigenetic evolution is a feature of relapsed AML and that convergent epigenetic evolution can occur following treatment with induction chemotherapy.
How to define, use, and interpret Pagel’s λ (lambda) in ecology and evolution
Authors: Pearse William D. , Davies T. Jonathan , Wolkovich E. M. 
Published: October 2023

1AbstractPagel’s λ (lambda) is a critical tool in ecology and evolution for describing trait evolution, imputing missing species’ data, and generalising ecological relationships beyond their study system. Yet the interpretation of λ depends on context, and there are many misconceptions about metrics that are similar but not identical to λ. As an index of phylogenetic signal applied to continuous traits, λ typically (but not always) ranges between 0 and 1, and is a rate-independent measure of the degree to which closely-related species resemble one-another relative to a Brownian motion expectation. But this measure is biased by non-random species sampling—a common characteristic of ecological data—which also makes phylogenetic imputation of missing traits challenging. The λ estimated in regression models has little to do with the phylogenetic signal of measured traits and is better considered as either a statistical correction or a measure of the impact of unmeasured (latent) traits in the model. In other contexts, such as hierarchical models including intra-specific variation, λ is frequently confused with distinct metrics such ash2. We show how confusion in defining and using λ can mislead our interpretation of ecological and evolutionary processes.Open research statementNo data were used or collected as part of this work.
Antisense RNA C9orf72 Hexanucleotide Repeat Associated With Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Forms A Triplex-Like Structure and Binds Small Synthetic Ligand
Authors: Błaszczyk Leszek , Ryczek Marcin , Das Bimolendu , Mateja-Pluta Martyna , Bejger Magdalena , Nakatani Kazuhiko , Kiliszek Agnieszka 
Published: October 2023

ABSTRACTThe abnormal expansion of GGGGCC/CCCCGG hexanucleotide repeats (HR) in C9orf72 is associated with familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Structural polymorphisms of HR result in the multifactorial pathomechanism of ALS/FTD. Consequently, many ongoing studies are focused at developing therapies targeting pathogenic HR RNA. One of them involves small molecules blocking the sequestration of important proteins, preventing the formation of toxic nuclear foci. However, rational design of potential therapeutics is hindered by limited number of structural studies of RNA-ligand complexes. We determined the crystal structure of antisense HR RNA in complex with ANP77 ligand and in the free form. HR RNA folds into a triplex structure composed of four RNA chains. ANP77 interacted with two neighboring single-stranded cytosines to form pseudo-canonical base pairs by adopting sandwich-like conformation and adjusting the position of its naphthyridine units to the helical twist of the RNA. In the unliganded structure, the cytosines formed a peculiar triplex i-motif, assembled by trans C•C+ pair and a third cytosine located at the Hoogsteen edge of the C•C+ pair. These results extend our knowledge of the structural polymorphisms of HR and can be used for the rational design of small molecules targeting disease-related RNAs.
Cell motility greatly empowers bacterial contact weapons
Authors: Booth Sean C. , Meacock Oliver J. , Foster Kevin R. 
Published: October 2023

AbstractMany bacteria kill competitors using short-range weapons, such as the Type VI Secretion System (T6SS) and Contact Dependent Inhibition (CDI). While these can deliver powerful toxins, they rely on direct contact between attacker and target cells. We hypothesised that movement enables attackers to contact more targets and thus greatly empower their weapons. To explore this, we developed individual-based and continuum models to show that motility greatly improves contact-dependent toxin delivery through two underlying processes. First, genotypic mixing increases the inter-strain contact probability of attacker and sensitive cells. Second, target switching ensures attackers constantly attack new cells, instead of repeatedly hitting the same cell. We test our predictions with the pathogen Pseudomonas aeruginosa, using genetically engineered strains to study the interaction between CDI and twitching motility. As predicted, we find that motility massively improves the effectiveness of CDI, in some cases up to 10,000-fold. Moreover, we demonstrate that both mixing processes occur using timelapse single-cell microscopy and quantify their relative importance by combining experimental data with our models. Our work shows how bacteria combine cell movement with contact-based weapons to launch powerful attacks on their competitors.
Efficacy of the first bioactive peptide from the pearl
Authors: Wu Chaoyi , Yin Zehui , Wang Yayu , Chen Xinjiani , Li Bailei , Wang Qin , Yao Liping , Zhang Zhen , Liu Xiaojun , Zhang Rongqing 
Published: October 2023

AbstractPearls have high medicinal value. In the present study, we discovered the first bioactive peptide in pearls. The bioactive peptide, KKCHFWPFPW, was a novel angiotensin I-converting enzyme (ACE)-inhibitory peptide derived from the pearl matrix ofPinctada fucata. It was screened and identified using quadrupole time-of-flight mass spectrometry. The molecular weight of the peptide was 1417.5 Da, and its theoretical isoelectric point was 9.31. The half-maximal inhibitory concentration of the peptide was 4.17μM, as determined by high-performance liquid chromatography. The Lineweaver–Burk plot showed that this peptide competitively inhibited ACE activity. As the peptide concentration increased, the ACE inhibition rate also increased. The molecular docking was simulated using Maestro 2022-1 Glide software to understand the potential mechanisms underlying the ACE-inhibitory activity of KKCHFWPFPW. These results indicated that the peptide from theP. martensiipearl matrix might be a potential source of antihypertensive peptides.
Complex genomic landscape of inversion polymorphism in Europe’s most destructive forest pest
Authors: Mykhailenko Anastasiia , Zieliński Piotr , Bednarz Aleksandra , Schlyter Fredrik , Andersson Martin N. , Antunes Bernardo , Borowski Zbigniew , Krokene Paal , Melin Markus , Morales-García Julia , Müller Jörg , Nowak Zuzanna , Schebeck Martin , Stauffer Christian , Viiri Heli , Zaborowska Julia , Babik Wiesław , Nadachowska-Brzyska Krystyna 
Published: October 2023

AbstractIn many species, polymorphic inversions underlie complex phenotypic polymorphisms and facilitate local adaptation in the face of gene flow. Multiple polymorphic inversions can co-occur in a genome, but the prevalence, evolutionary significance, and limits to complexity of genomic inversion landscapes remain poorly understood. Here, we examine genome-wide variation in one of Europe’s most destructive forest pests, the spruce bark beetleIps typographus, scan for polymorphic inversions, and test whether inversions are involved in key adaptations in this species. We analyzed 240 individuals from 18 populations across the species’ European range and, using a whole-genome resequencing approach, identified 27 polymorphic inversions covering approximately 28% of the genome. The inversions vary in size and in levels of intra-inversion recombination, are highly polymorphic across the species range, and often overlap, forming a complex genomic architecture. We test several mechanisms, including directional selection, overdominance and associative overdominance that can contribute to the maintenance of inversion polymorphisms in the genome. We show that the heterogeneous inversion landscape is likely maintained by the combined action of several evolutionary forces and that inversions are enriched in odorant receptor genes encoding key elements of recognition pathways for host plants, mates, and symbiotic fungi. Our results indicate that the genome of this major forest pest of growing social, political, and economic importance harbors one of the most complex inversion landscapes described to date posing a question about limits of genomic architecture complexity.