bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biological validation of fecal corticosterone metabolites as a non-invasive stress assessment in translocated California valley quail (Callipepla californica)
Authors: Currier Sarah A. , Whitt Jeffrey G. , Reyna Kelly S. 
Published: October 2023

AbstractU.S. quail species are vulnerable to population declines as a result climate change, habitat loss, and habitat fragmentation; all of which can induce physiological stress. Additionally, population restoration techniques (PRTs), like translocations, also induce stress. Traditional stress assessments include capturing and handling birds to extract blood, methods which are inherently stressful and can compound stress analyses. However, the stress hormone corticosterone is metabolized from the blood and excreted in feces as fecal corticosterone metabolites (FCMs). FCMs have been used as a non-invasive measurement of stress in a variety of species, but must be validated for each species. The objective of this study was to biologically validate the use of FCMs as a non-invasive measurement of stress-hormone levels in California valley quail (Callipepla californica). Reference and treatment quail were acclimated for 3 wks in an outdoor aviary. Subsequently, treatment quail were subjected to a simulated, 48-h translocation, a common and stressful PRT. Fecal samples were collected every 4 h and processed using an enzyme immunoassay. Mean FCM concentrations of treatment quail (41.50 ±16.13 ng/g) were higher than reference FCM concentrations (24.07 ±10.4 ng/g). These results biologically validate the use of FCMs as a non-invasive method to assess stress hormone levels in California valley quail, demonstrate diurnal variation in quail stress levels, and confirms that quail translocations are a stressful PRT. Ultimately, this research validates a new non-invasive tool for stress measurement to advance quail research, management, and conservation.Lay summaryThis study biologically validates the use of fecal corticosterone metabolites as a non-invasive method for detecting stress in quail, demonstrates diurnal variation in quail stress levels, confirms that translocations elevate stress which likely impacts success, and establishes a new non-invasive tool for stress measurement in quail research, management, and conservation.
A Murine Delayed-Healing Model Associates Immune Response with Functional Bone Regeneration after Trauma
Authors: Patrick Matthew , Stromberg Arnold , Ahn Jaimo , Hankenson Kurt , Annamalai Ramkumar T. 
Published: October 2023

AbstractNonunion and delayed-union fractures pose a significant clinical challenge, often leading to prolonged morbidity and impaired quality of life. Fracture-induced hematoma and acute inflammation are crucial for establishing the healing cascade. However, aberrant inflammatory phenotypes can suppress healing and cause bone resorption. Elucidating these mechanisms is necessary to develop potent immunomodulatory therapies and prevent nonunion. Here, we report a delayed fracture healing model enabling the modulation of interfragmentary strain that mimics the etiology of hypertrophic nonunions to elucidate the role of dysregulated immune response in poor healing outcomes. High interfragmentary strain (>15%) was associated with larger callus volumes but delayed bone healing, increased inflammation, and inferior healing outcomes, while lower strain levels (<5%) corresponded to normal bone healing. In addition, we found distinct differences in the ossification, chondrification, and fibrosis patterns between high and low-strain groups, underscoring the significant impact of strain on the healing process. A comprehensive analysis of the systemic immune response revealed dynamic alterations in immune cell populations and factors, particularly within the early hours and days post-fracture. Several immune factors exhibited significant correlations with various functional healing outcomes, indicating their potential as predictive markers for assessing fracture healing progression. Our results also highlighted the significance of timely resolution of proinflammatory signals and the elevation of pro-regenerative immune cell phenotypes in promoting bone regeneration. Multivariate analysis revealed that CD25+ T-regulatory cells were influential in predicting proper bone healing, followed by CD206+ macrophages, underscoring the pivotal role of immune cell populations in the bone healing process. In conclusion, our study provides valuable insights into the intricate interplay between interfragmentary strain, immune response, and the ultimate outcomes of fracture healing. By shedding light on the underlying mechanisms that drive hypertrophic nonunion pathogenesis, our research lays the foundation for enhanced surgical management of nonunions and offers a promising avenue for developing targeted therapeutic interventions and personalized treatment strategies for individuals suffering from fracture nonunion.
Cell segmentation and gene imputation for imaging-based spatial transcriptomics
Authors: Zhong Yunshan , Ren Xianwen 
Published: October 2023

AbstractImaging-based spatial transcriptomics technologies are revolutionary tools for biomedical investigation, but the power is currently limited by small number of measured genes and tricky cell segmentation. Here we introduce RedeFISH to simultaneously conduct cell segmentation and gene imputation for imaging-based spatial transcriptomics with the aid of single-cell RNA sequencing data. Extensive benchmarking across various spatial platforms and tissue types shows the validity and power of the cell-segmented, whole-transcriptome spatial data generated by RedeFISH.
Effects of chronic lithium treatment on neuronal excitability and GABAergic transmission in anAnk3mutant mouse model
Authors: Caballero-Florán René N. , Nelson Andrew D. , Min Lia , Jenkins Paul M. 
Published: October 2023

ABSTRACTBipolar disorder (BD) is a common psychiatric disease that can lead to psychosocial disability, decreased quality of life, and high risk for suicide. Genome-wide association studies have shown that theANK3gene is a significant risk factor for BD, but the mechanisms involved in BD pathophysiology are not yet fully understood. Previous work has shown that ankyrin-G, the protein encoded byANK3, stabilizes inhibitory synapses in vivo through its interaction with the GABAAreceptor-associated protein (GABARAP). We generated a mouse model with a missense p.W1989R mutation inAnk3, that abolishes the interaction between ankyrin-G and GABARAP, which leads to reduced inhibitory signaling in the somatosensory cortex and increased pyramidal cell excitability. Humans with the same mutation exhibit BD symptoms, which can be attenuated with lithium therapy. In this study, we describe that chronic treatment ofAnk3p.W1989R mice with lithium normalizes neuronal excitability in cortical pyramidal neurons and increases inhibitory GABAergic postsynaptic currents. The same outcome in inhibitory transmission was observed when mice were treated with the GSK-3β inhibitor Tideglusib. These results suggest that lithium treatment modulates the excitability of pyramidal neurons in the cerebral cortex by increasing GABAergic neurotransmission, likely via GSK-3 inhibition. In addition to the importance of these findings regardingANK3variants as a risk factor for BD development, this study may have significant implications for treating other psychiatric disorders associated with alterations in inhibitory signaling, such as schizophrenia, autism spectrum disorder, and major depressive disorder.
Identification of potential Auxin Response Candidate genes for soybean rapid canopy coverage through comparative evolution and expression analysis
Authors: Neres Deisiany F. , Taylor Joseph S. , Bryant John A. , Bargmann Bastiaan O. R. , Wright R. Clay 
Published: October 2023

AbstractGlycine max, soybean, is an abundantly cultivated crop worldwide. Efforts have been made over the past decades to improve soybean production in traditional and organic agriculture, driven by growing demand for soybean-based products. Rapid canopy cover development (RCC) increases soybean yields and suppresses early-season weeds.Genome-wide association studies have found natural variants associated with RCC, however causal mechanisms are unclear. Auxin modulates plant growth and development and has been implicated in RCC traits. Therefore, modulation of auxin regulatory genes may enhance RCC. Here, we focus on the use of genomic tools and existing datasets to identify auxin signaling pathway RCC candidate genes, using a comparative phylogenetics and expression analysis approach.We identified genes encoding 14 TIR1/AFB auxin receptors, 61 Aux/IAA auxin co-receptors and transcriptional co-repressors, and 55 ARF auxin response factors in the soybean genome. We used Bayesian phylogenetic inference to identify soybean orthologs ofArabidopsis thalianagenes, and defined an ortholog naming system for these genes. To further define potential auxin signaling candidate genes for RCC, we examined tissue-level expression of these genes in existing datasets and identified highly expressed auxin signaling genes in apical tissues early in development. We identified at least 4TIR1/AFB, 8Aux/IAA, and 8ARFgenes with highly specific expression in one or more RCC-associated tissues. We hypothesize that modulating the function of these genes through gene editing or traditional breeding will have the highest likelihood of affecting RCC while minimizing pleiotropic effects.
Phylogenomics reveals the deep ocean as an accelerator for evolutionary diversification in anglerfishes
Authors: Miller Elizabeth Christina , Faucher Rose , Hart Pamela B. , Rincon-Sandoval Melissa , Santaquiteria Aintzane , White William T. , Baldwin Carole C. , Miya Masaki , Betancur-R Ricardo , Tornabene Luke , Evans Kory , Arcila Dahiana 
Published: October 2023

ABSTRACTColonization of a novel habitat is often followed by radiation in the wake of ecological opportunity. Alternatively, some habitats should be inherently more constraining than others if the challenges of that environment have few evolutionary solutions. We examined the push-and-pull of these factors on evolution following habitat transitions, using anglerfishes (Lophiiformes) as a model. Deep-sea fishes are notoriously difficult to study, and poor sampling has limited progress thus far. Here we present a new phylogeny of anglerfishes with unprecedented taxonomic sampling (1,092 loci and 40% of species), combined with three-dimensional phenotypic data from museum specimens obtained with micro-CT scanning. We use these datasets to examine the tempo and mode of phenotypic and lineage diversification using phylogenetic comparative methods, comparing lineages in shallow and deep benthic versus bathypelagic habitats. Our results show that anglerfishes represent a surprising case where the bathypelagic lineage has greater taxonomic and phenotypic diversity than coastal benthic relatives. This defies expectations based on ecological principles since the bathypelagic zone is the most homogeneous habitat on Earth. Deep-sea anglerfishes experienced rapid lineage diversification concomitant with colonization of the bathypelagic zone from a continental slope ancestor. They display the highest body, skull and jaw shape disparity across lophiiforms. In contrast, reef-associated taxa show strong constraints on shape and low evolutionary rates, contradicting patterns suggested by other shallow marine fishes. We found that Lophiiformes as a whole evolved under an early burst model with subclades occupying distinct body shapes. We further discuss to what extent the bathypelagic clade is a secondary adaptive radiation, or if its diversity can be explained by non-adaptive processes.
Diagnostic Accuracy of GPT Multimodal Analysis on USMLE Questions Including Text and Visuals
Authors: Sorin Vera , Glicksberg Benjamin S. , Barash Yiftach , Konen Eli , Nadkarni Girish , Klang Eyal 
Published: October 2023

AbstractObjectiveLarge Language Models (LLMs) have demonstrated proficiency in free-text analysis in healthcare. With recent advancements, GPT-4 now has the capability to analyze both text and accompanying images. The aim of this study was to evaluate the performance of the multimodal GPT-4 in analyzing medical images using USMLE questions that incorporate visuals.MethodsWe analyzed GPT-4’s performance on 55 USMLE sample questions across the three steps. In separate chat instances we provided the model with each question both with and without the images. We calculated accuracy with and without the images provided.ResultsGPT-4 achieved an accuracy of 80.0% with images and 65.0% without. No cases existed where the model answered correctly without images and incorrectly with them. Performance varied across USMLE steps and was significantly better for questions with figures compared to graphs.ConclusionGPT-4 demonstrated an ability to analyze medical images from USMLE questions, including graphs and figures. A multimodal LLM in healthcare could potentially accelerate both patient care and research, by integrating visual data and text in analysis processes.
Agent-based Model for Microbial Populations Exposed to Radiation (AMMPER) simulates yeast growth for deep-space experiments
Authors: Singh Amrita , Santa Maria Sergio R. , Gentry Diana M. , Liddell Lauren C. , Lera Matthew P. , Lee Jessica A. 
Published: October 2023

AbstractSpace radiation poses a substantial health risk to humans traveling beyond Earth’s orbit to the Moon and Mars. As microbes come with us to space as model organisms for studying radiation effects, a computational model simulating those effects on microorganisms could enable us to better design and interpret those experiments. Here we present Agent-based Model for Microbial Populations Exposed to Radiation (AMMPER), which simulates the effects of protons, a major component of deep-space radiation, on budding yeast (Saccharomyces cerevisiae) growth. The model combines radiation track structure data from the RITRACKS package with novel algorithms for cell replication, motion, damage, and repair. We demonstrate that AMMPER qualitatively reproduces the effects of 150 MeV proton radiation on growth rate, but not lag time, of wild type and DNA repair mutant yeast strains. The variance in AMMPER’s results is consistent with the variance in experimental results, suggesting that AMMPER can recapitulate the stochasticity of empirical experiments. Finally, we used AMMPER to predict responses to deep space radiation that may be tested in future experiments. A user-friendly, open-source, extendable Python package for studying the relationship between single-particle radiation events and population-level responses, AMMPER can facilitate the basic research necessary to ensure safe and sustainable exploration of deep space.
Local cortical network stimulation as a concept for focal epilepsy treatment
Authors: van Blooijs D. , van der Stoel M.D. , Huiskamp G.J.M. , Demuru M. , Ramsey N.F. , Leijten F.S.S. 
Published: October 2023

AbstractBackgroundElectrical stimulation therapy for epilepsy patients is applied either to the epileptogenic region or to a larger network (e.g. with deep brain stimulation).Objective/hypothesisResponses to single pulse electrical stimuli (SPES) reveal potential stimulation sites that target the epileptogenic region for cortical network stimulation therapy.MethodsWe applied SPES to ten epilepsy patients who underwent intracranial electrocorticography recordings for pre-surgical evaluation. We detected cortico-cortical evoked potentials (CCEPs) in response electrodes after stimulating other pairs of electrodes, revealing effective connections. We calculated event-related spectral perturbation (ERSP) plots in all response electrodes after stimulating other electrode pairs. We detected interictal epileptic discharges (IEDs) before and after each single pulse and calculated the logarithmic IED ratio.We analyzed whether power suppression in the ERSP occurred in a response electrode when connected with the stimulus pair. We analyzed whether a larger change in IED ratio was accompanied by power suppression in the response electrode or when this electrode was connected with the stimulus pair.ResultsWe found that SPES has a neuromodulatory effect measured as: 1) the relationship of a CCEP and power suppression, 2) a larger change in IED rate when a CCEP was present, 3) a decrease in IED rate when power suppression was observed.Conclusion(s)Results suggest that stimulation in an area connected to the epileptogenic region can modulate IEDs in this region. SPES might provide a template for localizing a stimulation site outside the epileptogenic region for electrical stimulation treatment of epilepsy.HighlightsStimulation of an electrode pair can suppress power in an electrode on connected tissue.Stimulation of an electrode pair changes IED rate in an electrode on connected tissue.A decrease in IED rate was accompanied by power suppression.SPES indicates potential stimulation sites for neurostimulation therapy in epilepsy.
Nationwide population-based infection- and vaccine-induced SARS-CoV-2 seroprevalence in Germany at the end of 2021
Authors: Mercuri Elisabetta , Schmid Lorenz , Poethko-Müller Christina , Schlaud Martin , Kußmaul Cânâ , Ordonez-Cruickshank Ana , Haller Sebastian , Rexroth Ute , Hamouda Osamah , Schaade Lars , Wieler Lothar H. , Gößwald Antje , Schaffrath Rosario Angelika ,   the RKI-SOEP-2 Study Group
Published: October 2023

SummaryBackgroundThe first wave of the Corona Monitoring Nationwide (RKI-SOEP) Study drawn from the German Socio-Economic Panel proved a low pre-vaccine SARS-CoV-2 seroprevalence in the German adult population of 2.1%.MethodsIn this second wave of the study (RKI-SOEP-2, November 2021-March 2022), we used combined serological and self-reported data on infection and vaccination to estimate the prevalence of SARS-CoV-2-specific anti-spike and/or anti-nucleocapsid IgG antibodies (combined seroprevalence), past infection, and basic immunization in individuals aged 14+.FindingsCombined seroprevalence was 90.7% (95% CI 89.7% - 91.6%) without correction for antibody waning and 94.6% (95% CI 93.6% - 95.7%) with correction. While 1 in 10 individuals had been infected (9.9%, 95% CI 9.0% - 10.9%), 9 in 10 had at least a basic immunization (90%, 95% CI 88.9%-90.9%). Population-weighted estimates differed by age, region, and socioeconomic deprivation. Infection-induced seroprevalence with correction for antibody waning was 1.55 (95% CI 1.3 - 1.8) times higher than the cumulative proportion based on national surveillance data.InterpretationAt the beginning of the SARS-CoV-2-Omicron wave, the vast majority of the population had been vaccinated, infected, or both. Our results show how large-scale vaccination, but not a high infection rate, was able to fill the immunity gap, especially in older individuals (aged 65+) who are known to be at higher risk of severe COVID-19. Our data point towards a targeted demographically and regionally stratified mitigation strategy, to optimize future pandemic mitigation efforts.
Lipid-lowering therapy for patients with arterial hypertension and concomitant chronic obstructive pulmonary disease in a south American cohort
Authors: Lobo Diego , Bermudez Santiago , Dulcey Sarmiento Luis Andrés , Gomez Jaime , Hernandez Carlos , Theran Leon Juan Sebastián , Caltagirone Raimondo , Amaya Maria Camila , Estévez Gómez Maria Juliana , Acevedo Peña Diego Andrey , Castillo Goyeneche Silvia Fernanda , Arias Anderson Felipe , Blanco Edgar , Ciliberti Maria , Calderon Silvia , Gutierrez Emily , Lizcano Angie , Bacca Lizeth , Martinez Juan Camilo 
Published: October 2023

ABSTRACTIntroductionto assess the lipid-lowering effect, the effect on endothelial function, oxidative stress of Rosuvastatin at a dose of 40 mg in patients with dyslipidemia, arterial hypertension (AH) and chronic obstructive pulmonary disease (COPD) initially, over time after 4 weeks and 12 months of treatment.Material and methodsThe prospective study included 33 patients (mean age 60 [54;61] years) with hypertension, COPD and dyslipidemia. The laboratory examination consisted of determining the lipid spectrum and the level of lipid peroxidation products (LPO). To assess the tolerability of the prescribed therapy, creatinine, bilirubin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were studied. To assess endothelial function, an endothelium-dependent vasodilation test (EDVD) was performed. Rosuvastatin at a dose of 40 mg was prescribed as lipid-lowering therapy. Initially, after 12 months, an ultrasound duplex scanning of the carotid arteries was performed to assess the presence of atherosclerotic plaques (AP) in the lumen of the vessel. The study was approved by the Local Ethics Committee of the Andes University in Merida, Venezuela (protocol No. 10 of December 25, 2017).Resultsafter 4 weeks of treatment with Rosuvastatin at a dose of 40 mg, there was a significant decrease in total cholesterol levels by 26%, low-density lipoproteins (LDL) by 33%, triglycerides (TG) by 19%, while high-density lipoproteins (HDL) increased by 18%. Improvements in endothelial dysfunction (ED) and lipid peroxidation were observed during treatment with Rosuvastatin. Treatment with Rosuvastatin at a dose of 40 mg did not cause adverse reactions in patients.Conclusioncorrection of lipid metabolism disorders in patients with hypertension and COPD by prescribing Rosuvastatin at a dose of 40 mg can quickly reduce total cholesterol, LDL and TG, positively affecting endothelial function and lipid peroxidation processes. Therapy with Rosuvastatin at a starting dose of 40 mg in patients with dyslipidemia, hypertension and COPD is safe. After 12 months of regular use of Rosuvastatin at a dose of 40 mg, regression of AB was observed.
Histomorphometric features of placentae from women having malaria and HIV coinfection with preterm births
Authors: Adam Khalil Y. , Moses Obimbo M. , Jesse Gitaka , Edwin Walong , Omondi Ogutu , Ojwang Stephen.B.O. 
Published: October 2023

AbstractBackgroundMalaria and HIV are associated with preterm births possibly due to partial maternal vascular malperfusion resulting from altered placental angiogenesis. There is a paucity of data describing structural changes associated with malaria and HIV coinfection in the placentae of preterm births thus limiting the understanding of biological mechanisms by which preterm birth occurs.ObjectivesThis study aimed to determine the differences in clinical characteristics, placental parenchymal histological, and morphometric features of the terminal villous tree among women with malaria and HIV coinfection having preterm births.MethodsTwenty-five placentae of preterm births with malaria and HIV coinfection (cases) were randomly selected and compared to twenty-five of those without both infections (controls). Light microscopy was used to determine histological features on H&E and MT-stained sections while histomorphometric features of the terminal villous were analyzed using image analysis software. Clinical data regarding maternal age, parity, marital status, level of education, gestational age and placental weight were compared.ResultsPlacental weight, villous perimeter and area were significantly lower in cases as compared to controls 454g vs. 488g, 119.32µm vs. 130.47µm, and 937.93µm2vs. 1132.88µm2respectively. Increased syncytial knots and accelerated villous maturity were significantly increased in the cases. The relative risk of development of partial maternal vascular malperfusion was 2.1 (CI: 1.26-3.49).ConclusionThese findings suggest that malaria and HIV coinfection leads to partial maternal vascular malperfusion that may lead to chronic hypoxia in the placenta and altered weight, villous perimeter and surface area. This may represent a mechanism by which malaria and HIV infection results in pre-term births.