bluuebunny/crossref_metadata_2025_split huggingface dataset:
CohortDiagnostics: phenotype evaluation across a network of observational data sources using population-level characterization
Authors: Rao Gowtham A. , Shoaibi Azza , Makadia Rupa , Hardin Jill , Swerdel Joel , Weaver James , Voss Erica A , Conover Mitchell M. , Fortin Stephen , Sena Anthony G. , Knoll Chris , Hughes Nigel , Gilbert James P. , Blacketer Clair , Andryc Alan , DeFalco Frank , Molinaro Anthony , Reps Jenna , Schuemie Martijn J , Ryan Patrick B 
Published: June 2023

ABSTRACTObjectiveThis paper introduces a novel framework for evaluating phenotype algorithms (PAs) using the open-source tool, Cohort Diagnostics.Materials and MethodsThe method is based on several diagnostic criteria to evaluate a patient cohort returned by a PA. Diagnostics include estimates of incidence rate, index date entry code breakdown, and prevalence of all observed clinical events prior to, on, and after index date. We test our framework by evaluating one PA for systemic lupus erythematosus (SLE) and two PAs for Alzheimer’s disease (AD) across 10 different observational data sources.ResultsBy utilizing CohortDiagnostics, we found that the population-level characteristics of individuals in the cohort of SLE closely matched the disease’s anticipated clinical profile. Specifically, the incidence rate of SLE was consistently higher in occurrence among females. Moreover, expected clinical events like laboratory tests, treatments, and repeated diagnoses were also observed. For AD, although one PA identified considerably fewer patients, absence of notable differences in clinical characteristics between the two cohorts suggested similar specificity.DiscussionWe provide a practical and data-driven approach to evaluate PAs, using two clinical diseases as examples, across a network of OMOP data sources. Cohort Diagnostics can ensure the subjects identified by a specific PA align with those intended for inclusion in a research study.ConclusionDiagnostics based on large-scale population-level characterization can offer insights into the misclassification errors of PAs.
Phylogenomics including new sequence data of phytoplankton-infecting chytrids reveals multiple independent lifestyle transitions across the phylum
Authors: Thomé Pauline C. , Wolinska Justyna , Van Den Wyngaert Silke , Reñé Albert , Ilicic Doris , Agha Ramsy , Grossart Hans-Peter , Garcés Esther , Monaghan Michael T. , Strassert Jürgen F. H. 
Published: June 2023

AbstractParasitism is the most common lifestyle on Earth and has emerged many times independently across the eukaryotic tree of life. It is frequently found among chytrids (Chytridiomycota), which are early-branching unicellular fungi that feed osmotrophically via rhizoids as saprotrophs or parasites. Chytrids are abundant in most aquatic and terrestrial environments and fulfil important ecosystem functions. As parasites, they can have significant impacts on host populations. They cause global amphibian declines and influence the Earth’s carbon cycle by terminating algal blooms. To date, the evolution of parasitism within the chytrid phylum remains unclear due to the low phylogenetic resolution of rRNA genes for the early diversification of fungi, and because few parasitic lineages have been cultured and genomic data for parasites is scarce. Here, we combine transcriptomics, culture-independent single-cell genomics and a phylogenomic approach to overcome these limitations. We newly sequenced 29 parasitic taxa and combined these with existing data to provide a robust backbone topology for the diversification of Chytridiomycota. Our analyses reveal multiple independent lifestyle transitions between parasitism and saprotrophy among chytrids, multiple host shifts by parasites, and suggest that the chytrid last common ancestor was a parasite of phytoplankton.
Bipartite left-right sided endocrine system: processing of contralateral effects of brain injury
Authors: Watanabe Hiroyuki , Kobikov Yaromir , Nosova Olga , Sarkisyan Daniil , Galatenko Vladimir , Carvalho Liliana , Maia Gisela H. , Lukoyanov Nikolay , Lavrov Igor , Hallberg Mathias , Schouenborg Jens , Zhang Mengliang , Bakalkin Georgy 
Published: June 2023

ABSTRACTThe crossed descending neural tracts set a basis for contralateral effects of brain injury. In addition, the left-right side-specific effects of the unilateral brain lesions may be mediated by neurohormones through the humoral pathway as discovered in animals with disabled descending motor tracts. We here examined if counterparts of the endocrine system that convey signals from the left and right brain injuries differ in neural and molecular mechanisms. In rats with completely transected cervical spinal cords a unilateral injury of the hindlimb sensorimotor cortex produced hindlimb postural asymmetry with contralateral hindlimb flexion, a proxy for neurological deficit. The effects of the left and right side brain lesions were differently inhibited by antagonists of the δ-, κ- and µ-opioid receptors suggesting differential neuroendocrine control of the left-right side-specific hormonal signaling. Bilateral deafferentation of the lumbar spinal cord eliminated hormone-mediated effects of the left-side brain injury but not the right-side lesion suggesting their afferent and efferent mechanisms, respectively. Analysis of gene-gene co-expression patterns identified the left and right side-specific gene regulatory networks that were coordinated across the hypothalamus and lumbar spinal cord through the humoral pathway. The coordination was ipsilateral and perturbed by brain injury. These findings suggest that the neuroendocrine system that conveys left-right side-specific hormonal messages from injured brain is bipartite, contributes to contralateral neurological deficits through asymmetric neural mechanisms, and enables ipsilateral coordination of molecular processes across neural areas along the neuraxis.GRAPHICAL ABSTRACT
Semi-automated retrieval of chemical and phylogenetic information from natural products literature
Authors: Coelho Ana Carolina Lunardello , da Silva Ricardo R. 
Published: June 2023

AbstractNatural products (NPs) are metabolites of great importance due to their fundamental biological role in performing specialized activities, ranging from basic cellular functions to complex ecological interactions. These metabolites have contributed to innovating fields such as agriculture and medicine due to their optimized biological activities, a consequence of evolution. A key factor in ensuring that isolated NPs are novel is to search scientific literature and compare pre-existing chemical entities with the new isolate. Unfortunately, articles are typically not machine-readable, a problem that hinders efficient searching and increases the chances of unintended rediscovery. In addition, the time required to add new compound discoveries to compound databases hinders computational studies on cell metabolism and Quantitative Structure-Activity Relationships (QSAR). Here, we present a modularized tool that uses text mining techniques to retrieve chemical entities and taxonomic mentions present in scientific literature, called NPMINE (Natural Products MINIng). We were able to analyze 55,382 scientific articles from some of the most important applied chemistry journals from Brazil and the world, consistently recovering the expected taxonomic and structural information. This processing resulted in 120,970 unique InChI Keys potentially associated with 21,526 unique species mentioned. Using the PubChem BioAssay database we show how QSAR models can be used to mine active leads. The results indicate that NPMINE not only facilitates natural products cataloging, but also assists in biological source assignment and structure-activity relationships, a time-consuming task, typically performed in low throughput.
Development of a CMS Classifier for Clinical CRC Samples
Authors: Torang Arezo , van de Weerd Simone , van Lammers Veerle , van Hooff Sander , Koster Jan , Medema Jan Paul 
Published: June 2023

AbstractColorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide, emphasizing the need for improved predictive biomarkers to guide treatment decisions. A classification system based on gene expression profiles, known as CMS, has shown promise in stratifying CRC into distinct subtypes with varying clinical outcomes. However, the lack of a reliable assay to classify formalin-fixed paraffin-embedded (FFPE) samples poses a challenge for translating this system into routine clinical practice. In this paper, we introduce the NanoClassifier, an NanoString-based CMS classifier to classify both FFPE and Fresh frozen (FF) tumors. We demonstrate the strong accuracy of the NanoClassifier in predicting CMS for CRC samples. By validating its performance on FF and FFPE samples, we highlight the prognostic significance of CMS in CRC.
Adaptive mechanisms of social and asocial learning in immersive collective foraging
Authors: Wu Charley M. , Deffner Dominik , Kahl Benjamin , Meder Björn , Ho Mark H. , Kurvers Ralf H.J.M. 
Published: June 2023

ABSTRACTHuman cognition is distinguished by our ability to adapt to different environments and circumstances. Yet the mechanisms driving adaptive behavior have predominantly been studied in separate asocial and social contexts, with an integrated framework remaining elusive. Here, we use a collective foraging task in a virtual Minecraft environment to integrate these two fields, by leveraging automated transcriptions of visual field data combined with high-resolution spatial trajectories. Our behavioral analyses capture both the structure and temporal dynamics of social interactions, which are then directly tested using computational models sequentially predicting each foraging decision. These results reveal that adaptation mechanisms of both asocial foraging and selective social learning are driven by individual foraging success (rather than social factors). Furthermore, it is the degree of adaptivity—of both asocial and social learning—that best predicts individual performance. These findings not only integrate theories across asocial and social domains, but also provide key insights into the adaptability of human decision-making in complex and dynamic social landscapes.
Rescuable sleep and synaptogenesis phenotypes in aDrosophilamodel of O-GlcNAc transferase intellectual disability
Authors: Czajewski Ignacy , McDowall Laurin , Ferenbach Andrew , van Aalten Daan M. F. 
Published: June 2023

AbstractO-GlcNAcylation is an essential intracellular protein modification mediated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Recently, missense mutations inOGThave been linked to intellectual disability, indicating that this modification is important for the development and functioning of the nervous system. However, the processes that are most sensitive to perturbations in O-GlcNAcylation remain to be identified. Here, we uncover quantifiable phenotypes in the fruit flyDrosophila melanogastercarrying a patient-derived OGT mutation in the catalytic domain. Hypo-O-GlcNAcylation leads to defects in synaptogenesis and reduced sleep stability. Both these phenotypes can be partially rescued by genetically or chemically targeting OGA, suggesting that a balance of OGT/OGA activity is required for normal neuronal development and function.
Characterization of CAR T Cells Manufactured using Genetically Engineered Artificial Antigen Presenting Cells
Authors: Sayadmanesh Ali , Azadbakht Mohammad , Yari Kheirollah , Abedelahi Ali , Shafaei Hajar , Shanehbandi Dariush , Baradaran Behzad , Basiri Mohsen 
Published: June 2023

AbstractObjectiveChimeric antigen receptor (CAR) T cell therapy has recently emerged as a promising approach for the treatment of different types of cancer. Improving CAR T cell manufacturing in terms of costs and product quality is an important concern for expanding the accessibility of this therapy. One proposed strategy for improving T cell expansion is to use genetically engineered artificial antigen presenting cells (aAPC) expressing a membrane-bound anti-CD3 for T cell activation. In this study, we characterized CAR T cells generated with this approach in terms of expansion efficiency, immunophenotype, and cytotoxicity.Materials and MethodsIn this experimental study, we generated an aAPC line by engineering K562 cells to express a membrane-bound anti-CD3 (mOKT3). T cell activation was performed by culturing PBMCs with either mitomycin C-treated aAPCs or surface-immobilized anti-CD3 and anti-CD28 antibodies. Untransduced and CD19-CAR-transduced T cells were characterized in terms of expansion, activation markers, IFN-γ secretion, CD4/CD8 ratio, memory phenotype, and exhaustion markers. Cytotoxicity of CD19-CAR T cells generated by aAPCs and antibodies was also investigated using a bioluminescence-based co-culture assay.ResultsOur findings showed that the engineered aAPC line has the potential to expand CAR T cells similar to that of the antibody-based method. Although activation with aAPCs leads to a higher ratio of CD8+and effector memory T cells in the final product, we did not observe a significant difference in IFN-γ secretion cytotoxic activity or exhaustion between CAR T cells generated with aAPC or antibodies.ConclusionOur results show that despite the differences in the immunophenotypes of aAPC and antibody-based CAR T cells, both methods can be used to manufacture potent CAR T cells. These findings can be instrumental for the improvement of the T cell manufacturing process and future applications of aAPC-derived CAR T cells.
Cryo-EM structures of lipidic fibrils of amyloid-β (1-40)
Authors: Frieg Benedikt , Han Mookyoung , Giller Karin , Dienemann Christian , Riedel Dietmar , Becker Stefan , Andreas Loren B. , Griesinger Christian , Schröder Gunnar F. 
Published: June 2023

AbstractAlzheimer’s disease (AD) is a progressive and incurable neurodegenerative disease characterized by the extracellular deposition of amyloid plaques. Investigation into the composition of these plaques revealed a high amount of amyloid-β (Aβ) fibrils and a high concentration of lipids, suggesting that fibril-lipid interactions may also be relevant for the pathogenesis of AD. Therefore, we grew Aβ40 fibrils in the presence of lipid vesicles and determined their structure by cryo-electron microscopy (cryo-EM) to high resolution. The fold of the major polymorph is similar to the structure of brain-seeded fibrils reported previously. The majority of the lipids are bound to the fibrils as we show by cryo-EM and NMR spectroscopy. This apparent lipid extraction from vesicles observed here in vitro provides structural insights into potentially disease-relevant fibril-lipid interactions.
Perturbations in eIF3 subunit stoichiometry alter expression of ribosomal proteins and key components of the MAPK signaling pathways
Authors: Herrmannová Anna , Jelínek Jan , Pospíšilová Klára , Kerényi Farkas , Vomastek Tomáš , Watt Kathleen , Brábek Jan , Mohammad Mahabub Pasha , Wagner Susan , Topisirovic Ivan , Valášek Leoš Shivaya 
Published: June 2023

ABSTRACTProtein synthesis plays a major role in homeostasis and when dysregulated leads to various pathologies including cancer. To this end, imbalanced expression of eukaryotic translation initiation factors (eIFs) is not only a consequence but also a driver of neoplastic growth. eIF3 is the largest, multi-subunit translation initiation complex with a modular assembly, where aberrant expression of one subunit generates only partially functional subcomplexes. To comprehensively study the effects of eIF3 remodeling, we contrasted the impact of eIF3d, eIF3e or eIF3h depletion on the translatome of HeLa cells using Ribo-seq. Depletion of eIF3d or eIF3e, but not eIF3h reduced the levels of multiple components of the MAPK signaling pathways. Surprisingly, however, depletion of all three eIF3 subunits increased MAPK/ERK pathway activity. Depletion of eIF3e and partially eIF3d also increased translation of TOP mRNAs that encode mainly ribosomal proteins and other components of the translational machinery. Moreover, alterations in eIF3 subunit stoichiometry were often associated with changes in translation of mRNAs containing short uORFs, as in the case of the proto-oncogene MDM2 and the transcription factor ATF4. Collectively, perturbations in eIF3 subunit stoichiometry exert specific effect on the translatome comprising signaling and stress-related transcripts with complex 5’ UTRs that are implicated in homeostatic adaptation to stress and cancer.
Relationship between the colors of the rivers in the Amazon and the incidence of malaria
Authors: Fonseca Fernanda , Martinez Jean-Michel , Balieiro Antônio , Orellana Jesem , Filizola Naziano 
Published: June 2023

AbstractBackgroundMalaria is an infection caused by parasites of the genus Plasmodium, which are transmitted to humans via the bite of the female Anopheles mosquito. In Brazil, approximately 99% of malaria cases are concentrated in the Amazon region. Os rios desempenham um papel importante no ciclo de vida da malária, uma vez que o vetor se reproduz em ambiente aquático. The waters of the rivers in the Amazon have distinct chemical characteristics and this prompted us to analyze the influence of the color of the waters of the rivers in the Amazon on the distribution of malaria.MethodologyThis study was conducted for a period of seventeen years (2003-2019) in 50 municipalities in the state of Amazonas, Brazil. A generalized linear mixed model was developed to analyze the association of malaria incidence and three types of river color: white, black and mixed.Principal FindingsThe results suggest that there is a trend towards a decrease in malaria cases until 2015, with a possible resumption of the incidence of the disease from 2017 onwards, in all types of river color. In addition, the research indicates that places located near black-or mixed-water rivers have a higher incidence of malaria when compared to places on the banks of white-water rivers.ConclusionsHistorically, the hydrological regime has played an important role in the dynamics of malaria in the Amazon, but little is known about the relationship between river colors and the incidence of the disease. In this sense, our results, by showing a significant association between the colors of the rivers and the incidence of malaria over time, seem to expand the understanding between physical-chemical characteristics of the rivers and the occurrence of malaria.Author summaryMalaria is a disease that has a major impact on morbidity in tropical and subtropical countries. In Brazil, most of the cases registered in the country are concentrated in the northern region. A variety of factors can contribute to the occurrence of malaria outbreaks or epidemics, and rivers play an important role in the transmission of the disease. The waters of the rivers in the Amazon have distinct chemical characteristics and this study sought to analyze the influence of the color of the waters of the rivers in the Amazon on the distribution of malaria. Data on the incidence of malaria, from 2003 to 2019, in 50 municipalities in the state of Amazonas, Brazil, were associated with three types of river coloration: white, black and mixed. The results demonstrated the existence of a trend towards a decrease in malaria over the years, in all types of river coloration, and that this trend does not seem to be associated with the different types of water. However, the research indicates that places located near black-or mixed-water rivers have a higher incidence of malaria, when compared to places on the banks of white-water rivers.
Predicting Executive Functioning from Brain Networks: Modality Specificity and Age Effects
Authors: Heckner Marisa K. , Cieslik Edna C. , Paas Oliveros Lya K. , Eickhoff Simon B. , Patil Kaustubh R. , Langner Robert 
Published: June 2023

AbstractHealthy aging is associated with structural and functional network changes in the brain, which have been linked to deterioration in executive functioning (EF), while their neural implementation at the individual level remains unclear. As the biomarker potential of individual resting-state functional connectivity (RSFC) patterns has been questioned, we investigated to what degree individual EF abilities can be predicted from gray-matter volume (GMV), regional homogeneity, fractional amplitude of low-frequency fluctuations (fALFF), and RSFC within EF-related, perceptuo-motor, and whole-brain networks in young and old adults. We examined whether differences in out-of-sample prediction accuracy were modality-specific and depended on age or task-demand levels. Both uni- and multivariate analysis frameworks revealed overall low prediction accuracies and moderate to weak brain–behavior associations (R2< .07,r< .28), further challenging the idea of finding meaningful markers for individual EF performance with the metrics used. Regional GMV, well linked to overall atrophy, carried the strongest information about individual EF differences in older adults, whereas fALFF, measuring functional variability, did so for younger adults. Our study calls for future research analyzing more global properties of the brain, different task-states and applying adaptive behavioral testing to result in sensitive predictors for young and older adults, respectively.
Gle1 is required for tRNA to stimulate Dbp5 ATPase activityin vitroand to promote Dbp5 mediated tRNA exportin vivo
Authors: Rajan Arvind Arul Nambi , Asada Ryuta , Montpetit Ben 
Published: June 2023

ABSTRACTCells must maintain a pool of processed and charged transfer RNAs (tRNA) to sustain translation capacity and efficiency. Numerous parallel pathways support the processing and directional movement of tRNA in and out of the nucleus to meet this cellular demand. Recently, several proteins known to control messenger RNA (mRNA) transport were implicated in tRNA export. The DEAD-box Protein 5, Dbp5, is one such example. In this study, genetic and molecular evidence demonstrates that Dbp5 functions parallel to the canonical tRNA export factor Los1.In vivoco-immunoprecipitation data further shows Dbp5 is recruited to tRNA independent of Los1, Msn5 (another tRNA export factor), or Mex67 (mRNA export adaptor), which contrasts with Dbp5 recruitment to mRNA that is abolished upon loss of Mex67 function. However, as with mRNA export, overexpression of Dbp5 dominant-negative mutants indicates a functional ATPase cycle and that binding of Dbp5 to Gle1 is required by Dbp5 to direct tRNA export. Biochemical characterization of the Dbp5 catalytic cycle demonstrates the direct interaction of Dbp5 with tRNA (or double stranded RNA) does not activate Dbp5 ATPase activity, rather tRNA acts synergistically with Gle1 to fully activate Dbp5. These data suggest a model where Dbp5 directly binds tRNA to mediate export, which is spatially regulated via Dbp5 ATPase activation at nuclear pore complexes by Gle1.