bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of Hypertension in a STEMI-activated Subset of Patients from 2019 to 2021
Authors: Nguyen Trang , Lee Deborah , Lantz Rebekah , Hefner Dylan , Walk Casey T 
Published: September 2023

ABSTRACTBackgroundAbout 47% of United States adults have hypertension (HTN) per the 2017 Hypertension Clinical Practice Guidelines, where the blood pressure target is <130/90 mmHg. Prevalence is worse in certain distributions of the country with top quartile in the Southeastern pocket. In a subset of patients who present with ST-segment elevated myocardial infarction (STEMI), the prevalence is 30-40%. An interesting further subset of patients are those who presented as STEMI-alert during the COVID-19 pandemic. COVID-19 wreaked havoc on the world with its first confirmed case in 9 January 2020. International followed by national transport became limited, followed by announcement of a pandemic. Quarantines and lockdowns were set in place, especially in March 2020, to prevent epidemiologic spread.HypothesisWe were interested to observe if STEMI-alert patients during this period presented with worse background disease compared to years 2019 and 2021, years before and after COVID-lockdown and peak, including if the prevalence of background HTN increased in the population.MethodsWe evaluated 1001 adults who were STEMI-activated from 1 January 2019 to 31 December 2021 at five sites in Southwest Ohio. We obtained patient demographics and risk factors and performed multinomial logistic regression to compare years 2019 and 2021 to 2020. Statistical analysis was with SAS 9.4.ResultsFor 1001 STEMI-alert patients, 244 patients (72.6%) had HTN in 2019, 250 (78.9%) in 2020 and 261 (75.0%) in 2021. Overall prevalence over the three years was 755 (75.4%). Compared to 2020, 2019 prevalence was not significant (p=0.12) (OR 0.72) (CI 0.47,1.09). Neither was 2021 (p=0.25) (OR 0.78) (CI 0.51,1.19).ConclusionSTEMI-alert patients at our institution appeared to have higher overall prevalence of HTN than reported nationally by the Centers for Disease Control (CDC), 75.4% versus 47%. These may have self-selected for disease severity by STEMI-alert activation status. HTN may also be of higher prevalence in this region, be associated with poor disease detection or there may be patient compliance issues when antihypertensives are prescribed by a healthcare provider. HTN prevalence did not have statistical significance across the three observed years despite our hypothesis that patients would present with more background cardiac comorbidities such as HTN.
Testing the predictions of reinforcement: long-term empirical data from a damselfly mosaic hybrid zone
Authors: Arce-Valdés Luis Rodrigo , Ballén-Guapacha Andrea Viviana , Rivas-Torres Anais , Chávez-Ríos Jesús Ramsés , Wellenreuther Maren , Hansson Bengt , Guillén Rosa Ana Sánchez 
Published: September 2023

AbstractTheoretical work suggests that reinforcement can cause the strengthening of prezygotic isolation in sympatry by mitigating the costs of maladaptive hybridization. However, only a handful of studies have tested all predictions of this theory in natural populations. We investigated reinforcement in a mosaic hybrid zone of the damselfliesIschnura elegansandI. graellsii.Firstly, we tested if the conditions of reinforcement were fulfilled by quantifying whether hybridization was costly, and prezygotic isolation was strengthening in sympatry compared with in allopatry. Secondly, we investigated three specific predictions of reinforcement: rarer female effect, presence of concordant prezygotic and postzygotic isolation asymmetries in sympatry, and greater premating asymmetries associated with weaker postzygotic isolation in sympatry. We found that reinforcement has strengthened mechanical isolation in one cross direction between species in sympatry. Our study details a case of reinforcement and heterospecific gene flow causing opposite effects between reciprocal heterospecific crosses and describes a natural model in which reproductive isolation is built by the simultaneous effects of reinforcement, the lock-and-key model, Bateson-Dobzhansky-Müller incompatibilities and Haldane’s rule.
A genome-scale Opisthokonta tree of life: toward phylogenomic resolution of ancient divergences
Authors: Liu Hongyue , Steenwyk Jacob L. , Zhou Xiaofan , Schultz Darrin T. , Kocot Kevin M. , Shen Xing-Xing , Rokas Antonis , Li Yuanning 
Published: September 2023

AbstractAncient divergences within Opisthokonta—a major lineage that includes organisms in the kingdoms Animalia, Fungi, and their unicellular relatives— remain contentious, hindering investigations of the evolutionary processes that gave rise to two kingdoms and the repeated emergence of iconic phenotypes like multicellularity. Here, we use genome-scale amounts of data to reconstruct the most taxon-rich Opisthokonta tree of life to date (348 species) and place divergences in geologic time, suggesting a Mesoproterozoic origin (∼ 1.11 billion years ago). By dissecting multiple dimensions of phylogenomic error, such as the influence of taxon sampling and model complexity, we found that deep divergences within Holozoa remain unresolved and suggest Pluriformea is either sister to Ichthyosporea and Filozoa (Pluriformea-sister hypothesis) or is monophyletic to Ichthyosporea, forming the Teretosporea lineage (Teretosporea-sister hypothesis). A combination of information theory and sensitivity analyses revealed that the inferred unicellular Holozoa relationships are largely robust to common sources of analytical error, such as insufficient model complexity, and suggest that previous reports likely suffered from insufficient taxon sampling. Our study presents a robust Opisthokonta phylogenomic framework, highlights the challenges in resolving the relationships of unicellular Holozoa, and paves the way for illuminating ancient evolutionary episodes concerning the origin of two kingdoms.
Context-dependent hyperactivity insyngap1aandsyngap1bzebrafish autism models
Authors: Sumathipala Sureni H. , Khan Suha , Kozol Robert A. , Araki Yoichi , Syed Sheyum , Huganir Richard L. , Dallman Julia E. 
Published: September 2023

AbstractBackground and AimsSYNGAP1 disorder is a prevalent genetic form of Autism Spectrum Disorder and Intellectual Disability (ASD/ID) and is caused byde novoor inherited mutations in one copy of theSYNGAP1gene. In addition to ASD/ID, SYNGAP1 disorder is associated with comorbid symptoms including treatment-resistant-epilepsy, sleep disturbances, and gastrointestinal distress. Mechanistic links between these diverse symptoms andSYNGAP1variants remain obscure, therefore, our goal was to generate a zebrafish model in which this range of symptoms can be studied.MethodsWe used CRISPR/Cas9 to introduce frameshift mutations in thesyngap1aandsyngap1bzebrafish duplicates (syngap1ab) and validated these stable models for Syngap1 loss-of-function. BecauseSYNGAP1is extensively spliced, we mapped splice variants to the two zebrafishsyngap1aandbgenes and identified mammalian-like isoforms. We then quantified locomotory behaviors in zebrafish syngap1ab larvae under three conditions that normally evoke different arousal states in wild type larvae: aversive, high-arousal acoustic, medium-arousal dark, and low-arousal light stimuli.ResultsWe show that CRISPR/Cas9 indels in zebrafishsyngap1aandsyngap1bproduced loss-of-function alleles at RNA and protein levels. Our analyses of zebrafish Syngap1 isoforms showed that, as in mammals, zebrafish Syngap1 N- and C-termini are extensively spliced. We identified a zebrafishsyngap1α1-like variant that maps exclusively to thesyngap1bgene. Quantifying locomotor behaviors showed thatsyngap1ablarvae are hyperactive compared to wild type but to differing degrees depending on the stimulus. Hyperactivity was most pronounced in low arousal settings, with overall movement increasing with the number of mutantsyngap1alleles.ConclusionsOur data support mutations in zebrafishsyngap1abas causal for hyperactivity associated with elevated arousal that is especially pronounced in low-arousal environments.
Estrogen-dependent development and transcriptome regulation of the lateral septal kisspeptin system
Authors: Szentkirályi-Tóth Soma , Göcz Balázs , Takács Szabolcs , Sárvári Miklós , Farkas Imre , Skrapits Katalin , Rumpler Éva , Póliska Szilárd , Wittmann Gábor , Fekete Csaba , Hrabovszky Erik 
Published: September 2023

AbstractWhile hypothalamic kisspeptin (KP) neurons play well-established roles in puberty and reproduction, kisspeptin neurons in the lateral septum (KPLSneurons) and other extrahypothalamic sites have received less attention. We found that the onset of LS kisspeptin expression was linked to pubertal development and estrogen receptor signaling. Cell numbers were higher in femalesvs.males, continued to increase in adulthood and exogenous estrogen administered to adult mice was able to switch on theKiss1gene promoter in new sets of septal neurons. Using RNA-Seq studies of laser-microdissected neurons from ovariectomized mice treated with 17β-estradiol (E2)vs. vehicle, we found that KPLSneurons largely differ from hypothalamic KP neurons in their transcriptome profile which included 571 estrogen-dependent transcripts from which 80% were upregulated by a 4-day E2-treatment of ovariectomized mice. Notably,Kiss1expression in the LS was considerably lower than in hypothalamic KP neurons, being undetectable in ovariectomized mice and inducible by E2 supplementation. Finally, immunohistochemical detection of septal kisspeptin neurons and their fibers in the human brain suggested that the functions of this neuronal system are evolutionarily conserved. Ontogeny, sexual dimorphism and robust estrogenic regulation raise the intriguing possibility that the KPLSsystem is a new central player in the estrogen-dependent control of reproductive and/or non-reproductive functions in mice, with a possible human relevance supported by the immunohistochemical observations onpost mortemtissues.
IntegrativePTENEnhancer Discovery Reveals a New Model of Enhancer Organization
Authors: Cerda-Smith Christian G. , Hutchinson Haley M. , Liu Annie , Goel Viraat Y. , Sept Corriene , Kim Holly , Casaní-Galdón Salvador , Burkman Katherine G. , Bassil Christopher F. , Hansen Anders S. , Aryee Martin J. , Johnstone Sarah E. , Eyler Christine E. , Wood Kris C. 
Published: September 2023

AbstractEnhancers possess both structural elements mediating promoter looping and functional elements mediating gene expression. Traditional models of enhancer-mediated gene regulation imply genomic overlap or immediate adjacency of these elements. We test this model by combining densely-tiled CRISPRa screening with nucleosome-resolution Region Capture Micro-C topology analysis. Using this integrated approach, we comprehensively define thecis-regulatory landscape for the tumor suppressorPTEN, identifying and validating 10 distinct enhancers and defining their 3D spatial organization. Unexpectedly, we identify several long-range functional enhancers whose promoter proximity is facilitated by chromatin loop anchors several kilobases away, and demonstrate that accounting for this spatial separation improves the computational prediction of validated enhancers. Thus, we propose a new model of enhancer organization incorporating spatial separation of essential functional and structural components.
A spatially mapped gene expression signature for intestinal stem-like cells identifies high-risk precursors of gastric cancer
Authors: Huang Robert J. , Wichmann Ignacio A. , Su Andrew , Sathe Anuja , Shum Miranda V. , Grimes Susan M. , Meka Rithika , Almeda Alison , Bai Xiangqi , Shen Jeanne , Nguyen Quan , Amieva Manuel R. , Hwang Joo Ha , Ji Hanlee P. 
Published: September 2023

ABSTRACTObjectiveGastric intestinal metaplasia (GIM) is a precancerous lesion that increases gastric cancer (GC) risk. The Operative Link on GIM (OLGIM) is a combined clinical-histopathologic system to risk-stratify patients with GIM. The identification of molecular biomarkers that are indicators for advanced OLGIM lesions may improve cancer prevention efforts.MethodsThis study was based on clinical and genomic data from four cohorts: 1) GAPS, a GIM cohort with detailed OLGIM severity scoring (N=303 samples); 2) the Cancer Genome Atlas (N=198); 3) a collation of in-house and publicly available scRNA-seq data (N=40), and 4) a spatial validation cohort (N=5) consisting of annotated histology slides of patients with either GC or advanced GIM. We used a multi-omics pipeline to identify, validate and sequentially parse a highly-refined signature of 26 genes which characterize high-risk GIM.ResultsUsing standard RNA-seq, we analyzed two separate, non-overlapping discovery (N=88) and validation (N=215) sets of GIM. In the discovery phase, we identified 105 upregulated genes specific for high-risk GIM (defined as OLGIM III-IV), of which 100 genes were independently confirmed in the validation set. Spatial transcriptomic profiling revealed 36 of these 100 genes to be expressed in metaplastic foci in GIM. Comparison with bulk GC sequencing data revealed 26 of these genes to be expressed in intestinal-type GC. Single-cell profiling resolved the 26-gene signature to both mature intestinal lineages (goblet cells, enterocytes) and immature intestinal lineages (stem-like cells). A subset of these genes was further validated using single-molecule multiplex fluorescencein situhybridization. We found certain genes (TFF3andANPEP) to mark differentiated intestinal lineages, whereas others (OLFM4andCPS1) localized to immature cells in the isthmic/crypt region of metaplastic glands, consistent with the findings from scRNAseq analysis.Conclusionsusing an integrated multi-omics approach, we identified a novel 26-gene expression signature for high-OLGIM precursors at increased risk for GC. We found this signature localizes to aberrant intestinal stem-like cells within the metaplastic microenvironment. These findings hold important translational significance for future prevention and early detection efforts.
Inhibitory tagging both speeds and strengthens saccade target selection in the superior colliculus during visual search
Authors: Conroy Christopher , Nanjappa Rakesh , McPeek Robert M. 
Published: September 2023

ABSTRACTIt has been suggested that, during difficult visual search tasks involving time pressure and multiple saccades, inhibitory tagging helps to facilitate efficient saccade target selection by reducing responses to objects in the scene once they have been searched and rejected. The superior colliculus (SC) is a midbrain structure involved in target selection, and recent findings suggest an influence of inhibitory tagging on SC activity. Precisely how, and by how much, inhibitory tagging influences target selection by SC neurons, however, is unclear. The purpose of this study, therefore, was to characterize and quantify the influence of inhibitory tagging on target selection in the SC. Rhesus monkeys performed a visual search task involving time pressure and multiple saccades. Early in the fixation period between saccades, a subset of SC neurons reliably discriminated the stimulus selected as the next saccade goal, consistent with a role in target selection. Discrimination occurred earlier and was more robust, however, when unselected stimuli in the search array had been previously fixated on the same trial. This indicates that inhibitory tagging both speeds and strengthens saccade target selection in the SC during multisaccade search. The results provide constraints on models of target selection based on SC activity.NEW AND NOTEWORTHYAn important aspect of efficient behavior during difficult, time-limited visual search tasks is the efficient selection of sequential saccade targets. Inhibitory tagging, i.e., a reduction of neural activity associated with previously fixated objects, may help to facilitate such efficient selection by modulating the selection process in the superior colliculus (SC). In this study, we characterized and quantified this modulation and found that, indeed, inhibitory tagging both speeds and strengthens target selection in the SC.
Circulating Platelets Modulate Oligodendrocyte Progenitor Cell Differentiation During Remyelination
Authors: Philp Amber R. , Reyes Carolina R. , Mansilla Josselyne , Sharma Amar , Zhao Chao , Valenzuela-Krugmann Carlos , Rawji Khalil S. , Gonzalez Martinez Ginez A. , Dimas Penelope , Hinrichsen Bryan , Ulloa-Leal César , Waller Amie K. , Bessa de Sousa Diana M. , Castro Maite A. , Aigner Ludwig , Ehrenfeld Pamela , Silva Maria Elena , Kazanis Ilias , Ghevaert Cedric , Franklin Robin J.M. , Rivera Francisco J. 
Published: September 2023

AbstractRevealing unknown cues that regulate oligodendrocyte progenitor cell (OPC) function in remyelination is important to optimise the development of regenerative therapies for multiple sclerosis (MS). Platelets are present in chronic non-remyelinated lesions of MS and an increase in circulating platelets has been described in experimental autoimmune encephalomyelitis (EAE) mice, an animal model for MS. However, the contribution of platelets to remyelination remains unexplored. Here we show platelet aggregation in proximity to OPCs in areas of experimental demyelination. Partial depletion of circulating platelets impaired OPC differentiation and remyelination, without altering blood-brain barrier stability and neuroinflammation. Transient exposure to platelets enhanced OPC differentiationin vitro, whereas sustained exposure suppressed this effect. In a mouse model of thrombocytosis (CALRHET), there was a sustained increase in platelet aggregation together with a reduction of newly-generated oligodendrocytes following toxin-induced demyelination. These findings reveal a complex bimodal contribution of platelet to remyelination and provide insights into remyelination failure in MS.
Ageing-related defects in macrophage function are driven byMYCandUSF1transcriptional programmes
Authors: Moss Charlotte E. , Johnston Simon , Clements Martha , Codd Veryan , Hamby Stephen , Goodall Alison H. , Deshmukh Sumeet , Sudbery Ian , Coca Daniel , Wilson Heather L. , Kiss-Toth Endre 
Published: September 2023

SummaryMacrophages are central innate immune cells whose function declines with age. The molecular mechanisms underlying age-related immunity changes remain poorly understood, particularly in human macrophages. We report a substantial reduction in phagocytosis, migration and chemotaxis in human monocyte-derived macrophages (MDMs) from older (>50 years) compared with younger (18-30 years) donors, alongside downregulation of transcription factorsMYCandUSF1with age. In MDMs from young donors, knockdown ofMYCorUSF1decreased phagocytosis and chemotaxis and altered expression of genes associated with these functions, as well as adhesion and extracellular matrix remodelling. A concordant dysregulation ofMYCandUSF1target genes was also seen in MDMs from older donors. Furthermore, older age and loss of eitherMYCorUSF1in MDMs led to an increased cell size, altered morphology and reduced actin content. Together, these results defineMYCandUSF1as key drivers of MDM age-related functional decline and identify downstream targets to improve macrophage function in ageing.
Theta mediated dynamics of human hippocampal-neocortical learning systems in memory formation and retrieval
Authors: Gattas Sandra , Larson Myra Sarai , Mnatsakanyan Lilit , Sen-Gupta Indranil , Vadera Sumeet , Swindlehurst Lee , Rapp Paul E. , Lin Jack J. , Yassa Michael A. 
Published: September 2023

AbstractEpisodic memory arises as a function of dynamic interactions between the hippocampus and the neocortex, yet the mechanisms have remained elusive. Here, using human intracranial recordings during a mnemonic discrimination task, we report that 4-5 Hz (theta) power is differentially recruited during discrimination vs. overgeneralization, and its phase supports hippocampal-neocortical when memories are being formed and correctly retrieved. Interactions were largely bidirectional, with small but significant net directional biases; a hippocampus-to-neocortex bias during acquisition of new information that was subsequently correctly discriminated, and a neocortex-to-hippocampus bias during accurate discrimination of new stimuli from similar previously learned stimuli. The 4-5 Hz rhythm may facilitate the initial stages of information acquisition by neocortex during learning and the recall of stored information from cortex during retrieval. Future work should further probe these dynamics across different types of tasks and stimuli and computational models may need to be expanded accordingly to accommodate these findings.
Molecular and phylogenetic characterization of the monkeypox outbreak in the South of Spain
Authors: Casimiro-Soriguer Carlos S. , Perez-Florido Javier , Lara Maria , Camacho-Martinez Pedro , Merino-Diaz Laura , Pupo-Ledo Inmaculada , de Salazar Adolfo , Fuentes Ana , Viñuela Laura , Chueca Natalia , Martinez-Martinez Luis , Lorusso Nicola ,   The Andalusian genomic surveillance network, Lepe Jose A , Dopazo Joaquín , Garcia Federico 
Published: September 2023

AbstractUntil the May 2022 Monkeypox outbreak, which spread rapidly to many non-endemic countries, the virus was considered a viral zoonosis limited to some African countries. The Andalusian circuit of genomic surveillance was rapidly applied to characterize the Monkeypox outbreak in the South of Spain. Whole genome sequencing was used to obtain the genomic profiles of samples collected across the south of Spain, representative of all the provinces of Andalusia. Phylogenetic analysis was used to study the relationship of the isolates and the available sequences of the 2022 outbreak. Whole genome sequencing of a total of 160 monkeypox viruses from the different provinces that reported cases were obtained. Interestingly, we report the sequences of monkeypox viruses obtained from two patients who died. While one of the isolates bore no noteworthy mutations that explain a potential heightened virulence, in another patient the second consecutive genome sequence, performed after the administration of tecovirimat, uncovered a mutation within the A0A7H0DN30 gene, known to be a prime target for tecovirimat in its Vaccinia counterpart. In general, a low number of mutations were observed in the sequences reported, which were very similar to the reference of the 2022 outbreak (OX044336), as expected from a DNA virus. The samples likely correspond to several introductions of the circulating monkeypox viruses from the last outbreak. The virus sequenced from one of the two patients that died presented a mutation in a gene that bears potential connections to drug resistance. This mutation was absent in the initial sequencing prior to treatment.