bluuebunny/crossref_metadata_2025_split huggingface dataset:
A paradigm for ethanol consumption in head-fixed mice during prefrontal cortical two-photon calcium imaging
Authors: Kalelkar Anagha , Sipe Grayson , Castro E Costa Ana Raquel , Lorenzo Ilka M. , Nguyen My , Linares-Garcia Ivan , Vazey Elena , Huda Rafiq 
Published: July 2023

AbstractThe prefrontal cortex (PFC) is a hub for higher-level cognitive behaviors and is a key target for neuroadaptations in alcohol use disorders. Preclinical models of ethanol consumption are instrumental for understanding how acute and repeated drinking affects PFC structure and function. Recent advances in genetically encoded sensors of neuronal activity and neuromodulator release combined with functional microscopy (multiphoton and one-photon widefield imaging) allow multimodalin-vivoPFC recordings at subcellular and cellular scales. While these methods could enable a deeper understanding of the relationship between alcohol and PFC function/dysfunction, they require animals to be head-fixed. Here, we present a method in mice for binge-like ethanol consumption during head-fixation. Male and female mice were first acclimated to ethanol by providing home cage access to 20% ethanol (v/v) for 4 or 8 days. After home cage drinking, mice consumed ethanol from a lick spout during head-fixation. We used two-photon calcium imaging during the head-fixed drinking paradigm to record from a large population of PFC neurons (>1000) to explore how acute ethanol affects their activity. Drinking modulated activity rates in a subset of neurons on slow (minutes) and fast (seconds) time scales but the majority of neurons were unaffected. Moreover, ethanol intake did not significantly affect network level interactions in the PFC as assessed through inter-neuronal pairwise correlations. By establishing a method for binge-like drinking in head-fixed mice, we lay the groundwork for leveraging advanced microscopy technologies to study alcohol-induced neuroadaptations in PFC and other brain circuits.HighlightsC57BL/6J mice voluntarily consume ethanol to binge-like levels during head-fixation, with females consuming more ethanol than males.Mice show differences in frontloading and licking behavior for head-fixed ethanol and sucrose consumption.Head-fixed paradigm enables two-photon calcium imaging in the anterior cingulate cortex subdivision of the prefrontal cortex.Acute ethanol increases and decreases single neuron activity at fast (seconds) and slow (minutes) time scales but does not alter pairwise correlations between neurons.
Identification of five characteristic ferroptosis-related genes as novel biomarkers for ischemic stroke using bioinformatic and machine learning strategies
Authors: Feng Xin , Huang Chunhua , Ye Lin , Xu Zhongbo 
Published: July 2023

AbstractFerroptosis is crucial in neuronal cell death, associated with various neurological disorders. However, the role of ferroptosis-related genes (FRGs) in ischaemic stroke (IS) has yet to be well elucidated. We downloaded IS-related gene information and FRGs from the Gene Expression Omnibus (GEO) and Ferritin databases (FerrDb). 22 IS-related DE-FRGs were obtained. Functional enrichment analysis showed that these genes involve multiple regulatory pathways related to IS pathogenesis, including redox, amino acid metabolism, and cell cycle. Subsequently, DUOX2, MDM2, EGFR, MAP3K14, and TRIM46 were identified as core marker genes among the 22 DE-FRGs by lasso and SVM-RFE algorithms. The construction of the nomogram using the five marker genes had excellent diagnostic value. In addition, CIBERSORT analysis showed that changes in the immune microenvironment of IS patients might be associated with TRIM46, MDM2, and DUOX2. In addition, a total of 66 drugs targeting two characteristic FRGs were obtained. The ceRNA networks revealed complex regulatory relationships based on characteristic FRGs. These findings provide new insights into the diagnosis and treatment of IS.
Season-dependent processing of innate conspecific vocalizations in the male and female European starling (Sturnus vulgaris)
Authors: Vidas-Guscic N.D. , Jonckers E. , Van Audekerke J. , Orije J. , Hamaide J. , Majumdar G. , Verhoye M. , Van der Linden A. 
Published: July 2023

AbstractAvian innate nestling begging calls are similar to human infant cries in the behavioral response they elicit. However, it remains unknown whether the auditory processing of innate begging calls changes in seasonal songbirds from non-breeding to breeding season when hormonal neuromodulation of the auditory forebrain occurs.An fMRI experiment was set up to expose male and female European starlings (Sturnus vulgaris) to recordings of seasonal conspecific nestling begging calls in the breeding and non-breeding season. This response was compared with their response to conspecific warble motifs and artificial pure tones, both proven seasonally invariable at least in the male starling’s neural response.Our results demonstrate significant seasonal variation in auditory forebrain responses exclusively elicited by begging calls and not by the applied control stimuli. Right Field L and the Caudomedial Nidopallium (NCM) seemed, irrespective of season or sex, more sensitive in response to begging than to control stimuli. A seasonal differential response specifically to begging calls was found in both sexes in a ventral midsagittal region of NCM.Our findings thereby support the functional fine-tuning of vocal communications between sender and receiver in a breeding context for innate vocalizations and are in line with the bi-parenting behavior in this species.
Evolutionary trade-offs in dormancy phenology
Authors: Constant Théo , Dobson F. Stephen , Habold Caroline , Giroud Sylvain 
Published: July 2023

AbstractSeasonal animal dormancy, hibernation or diapause, is widely interpreted as a physiological response for surviving energetic challenges during the harshest times of the year (the physiological constraint hypothesis). However, there are other mutually non-exclusive hypotheses to explain the timing of animal dormancy, that is, entry into and emergence from hibernation (i.e. dormancy phenology). Other survival advantages of dormancy that have been proposed are reduced risks of predation and competition (the “life-history” hypothesis), but comparative tests across animal species are not yet available. Under this hypothesis, dormancy phenology is influenced by a trade-off between reproductive advantages of being active and survival benefits of dormancy. Within a species, males and females differ in the amount of time and energy they invest in reproduction. Thus, the trade-off between reproduction and survival may be reflected by within-species sex differences in the phenology of dormancy. To examine this hypothesis, we used two complementary approaches: (i) a set of phylogenetic comparative analyses on mammals (mainly holarctic rodents), and (ii) a comparison between endotherm and ectotherm dormancy, via analyses of endotherms (including mainly holoarctic rodents) and the existing literature on ectotherms.Using the phylogenetic comparative method applied to more than 20 hibernating mammalian species, we found support for both hypotheses as explanations for the phenology of dormancy. In accordance with the life history hypotheses, sex differences in emergence and immergence were favored by the sex difference in reproductive effort. In addition, physiological constraint may influence the trade-off between survival and reproduction such that, low temperature and precipitation as well as smaller body mass influence sex differences in phenology. We also compiled initial evidence that ectotherm dormancy (invertebrates and reptiles) may be 1) less temperature dependent than previously thought and 2) associated with trade-offs consistent with the life history hypothesis. Dormancy in some endotherms and ectotherms show staggered phenology with respect to the growing season (earlier emergence and immergence than expected) which illustrates the selection pressure exerted by the trade-off between reproduction (earlier emergence than expected) and adult survival (earlier immergence than expected). Thus, dormancy during non-life-threatening periods that are unfavorable for reproduction may be more widespread than previously appreciated.
Diagnostic histone modification analysis of individual preimplantation embryos
Authors: Zeng Yiren , Hoshino Yoichiro , Susami Kazuki , Honda Shinnosuke , Minami Naojiro , Ikeda Shuntaro 
Published: July 2023

AbstractBackgroundWe previously reported a modification of the CUT&Tag method (NTU-CAT) that allows genome-wide histone modification analysis in individual preimplantation embryos. In the present study, NTU-CAT was further simplified by taking advantage of the Well-of-the-Well (WOW) system, which enables the processing of multiple embryos in a shorter time with less reagent and cell loss during the procedure (WOW-CUT&Tag, WOW-CAT).ResultsWOW-CAT allowed histone modification profiling from not only a single blastocyst but also from a portion of it. WOW-CAT generated similar H3K4me3 profiles as NTU-CAT, but they were closer to the profiles produced by chromatin immunoprecipitation-sequencing, such as a valley-like trend, indicating that WOW-CAT may attenuate the bias of Tn5 transposase to cut open chromatin regions. Simultaneous WOW-CAT of two halves of single blastocysts was conducted to analyze two different histone modifications (H3K4me3 and H3K27ac) within the same embryo. Furthermore, trophectoderm cells were biopsied and subjected to WOW-CAT in anticipation of preimplantation diagnosis of histone modifications. WOW-CAT allowed the monitoring of epigenetic modifications in the main body of the embryo. For example, analysis of H3K4me3 modifications ofXISTandDDX3Yin trophectoderm biopsies could be used to sex embryos in combination with quantitative PCR, but without the need for deep sequencing.ConclusionsThese results suggest the applicability of WOW-CAT for flexible epigenetic analysis of individual embryos in preimplantation epigenetic diagnosis.
Functional Regulation of Aquaporin Dynamics by Lipid Bilayer Composition
Authors: Nguyen Anh T. P. , Weigle Austin T. , Shukla Diwakar 
Published: July 2023

AbstractWith the diversity of lipid-protein interactions, any observed membrane protein dynamics or functions directly depend on the lipid bilayer selection. However, the implications of lipid bilayer choice are seldom considered unless characteristic lipid-protein interactions have been previously reported. Using molecular dynamics simulation, we characterize the effects of membrane embedding on plant aquaporin SoPIP2;1, which has no reported high-affinity lipid interactions. The regulatory impacts of a realistic lipid bilayer, and nine different homogeneous bilayers, on varying SoPIP2;1 dynamics were examined. We demonstrate that SoPIP2;1s structure, thermodynamics, kinetics, and water transport are altered as a function of each membrane construct’s ensemble properties. Notably, the realistic bilayer provides stabilization of non-functional SoPIP2;1 metastable states. Hydrophobic mismatch and lipid order parameter calculations further explain how lipid ensemble properties manipulate SoPIP2;1 behavior. Our results illustrate the importance of careful bilayer selection when studying membrane proteins. To this end, we advise cautionary measures when performing membrane protein molecular dynamics simulations.
Spatial Modeling of Sociodemographic Risk for COVID-19 Mortality
Authors: Seamon Erich , Ridenhour Benjamin J. , Miller Craig R. , Johnson-Leung Jennifer 
Published: July 2023

AbstractIn early 2020, the Coronavirus Disease 19 (COVID-19) rapidly spread across the United States (US), exhibiting significant geographic variability. While several studies have examined the predictive relationships of differing factors on COVID-19 deaths, few have looked at spatiotemporal variation at refined geographic scales. The objective of this analysis is to examine this spatiotemporal variation in COVID-19 deaths with respect to association with socioeconomic, health, demographic, and political factors. We use multivariate regression applied to Health and Human Services (HHS) regions as well as nationwide county-level geographically weighted random forest (GWRF) models. Analyses were performed on data from three separate time frames which correspond to the spread of distinct viral variants in the US: pandemic onset until May 2021, May 2021 through November 2021, and December 2021 until April 2022. Multivariate regression results for all regions across three time windows suggest that existing measures of social vulnerability for disaster preparedness (SVI) are predictive of a higher degree of mortality from COVID-19. In comparison, GWRF models provide a more robust evaluation of feature importance and prediction, exposing the value of local features for prediction, such as obesity, which is obscured by coarse-grained analysis. Overall, GWRF results indicate that this more nuanced modeling strategy is useful for determining the spatial variation in the importance of sociodemographic risk factors for predicting COVID-19 mortality.
Harnessing ChatGPT and GPT-4 for Evaluating the Rheumatology Questions of the Spanish Access Exam to Specialized Medical Training
Authors: Madrid-García Alfredo , Rosales-Rosado Zulema , Freites-Nuñez Dalifer , Pérez-Sancristobal Inés , Pato-Cour Esperanza , Plasencia-Rodríguez Chamaida , Cabeza-Osorio Luis , León-Mateos Leticia , Abasolo-Alcázar Lydia , Fernández-Gutiérrez Benjamín , Rodríguez-Rodríguez Luis 
Published: July 2023

ABSTRACTThe emergence of Large Language Models (LLM) with remarkable performance such as ChatGPT and GPT-4, has led to an unprecedented uptake in the population. One of their most promising and studied applications concerns education due to their ability to understand and generate human-like text, creating a multitude of opportunities for enhancing educational practices and outcomes. The objective of this study is two-fold: to assess the accuracy of ChatGPT/GPT-4 in answering rheumatology questions from the access exam to specialized medical training in Spain (MIR), and to evaluate the medical reasoning followed by these LLM to answer those questions. A dataset, RheumaMIR, of 145 rheumatology-related questions, extracted from the exams held between 2010 and 2023, was created for that purpose, used as a prompt for the LLM, and was publicly distributed. Six rheumatologists with clinical and teaching experience evaluated the clinical reasoning of the chatbots using a 5-point Likert scale and their degree of agreement was analyzed. The association between variables that could influence the models’ accuracy (i.e., year of the exam question, disease addressed, type of question and genre) was studied. ChatGPT demonstrated a high level of performance in both accuracy, 66.43%, and clinical reasoning, median (Q1-Q3), 4.5 (2.33-4.67). However, GPT-4 showed better performance with an accuracy score of 93.71% and a median clinical reasoning value of 4.67 (4.5-4.83). These findings suggest that LLM may serve as valuable tools in rheumatology education, aiding in exam preparation and supplementing traditional teaching methods.What is already known on this topicLarge Language Models have demonstrated remarkable performance when presented with medical exam questions. However, no study has evaluated their clinical reasoning in the rheumatology field.What this study addsThis is the first study to evaluate the accuracy and clinical reasoning of ChatGPT and GPT-4 when rheumatology questions from an official access exam to specialized medical training are used as prompts.How this study might affect research, practice or policy?This study highlights the usefulness of two Large Language Models, ChatGPT and GPT-4, in the training of medical students in the field of rheumatology.HighlightsChatGPT showed an accuracy of 66.43% in answering MIR questions, while GPT-4 exhibits a significantly higher proficiency with an accuracy of 93.71%.The median (Q1-Q3) value of the average score for the clinical reasoning of GPT-4 was 4.67 (4.5-4.83), while for ChatGPT was 4.5 (2.33-4.67).
Cortical thickness alterations and systemic inflammation define long-COVID patients with cognitive impairment
Authors: Besteher Bianca , Rocktäschel Tonia , Garza Alejandra P. , Machnik Marlene , Ballez Johanna , Helbing Dario-Lucas , Finke Kathrin , Reuken Philipp , Güllmar Daniel , Gaser Christian , Walter Martin , Opel Nils , Dunay Ildiko Rita 
Published: July 2023

AbstractAs the heterogeneity of symptoms is increasingly recognized among long-COVID patients, it appears highly relevant to study potential pathophysiological differences along the different subtypes. Preliminary evidence suggests distinct alterations in brain structure and systemic inflammatory patterns in specific groups of long-COVID patients.To this end, we analyzed differences in cortical thickness and peripheral immune signature between clinical subgroups based on 3T-MRI scans and signature inflammatory markers in n=120 participants comprising healthy never-infected controls, healthy COVID-19 survivors, and subgroups of long-COVID patients with and without cognitive impairment according to screening with Montreal Cognitive Assessment. Whole-brain comparison of cortical thickness between the 4 groups was conducted by surface-based morphometry.We identified distinct cortical areas showing a progressive increase in cortical thickness across different groups, starting from healthy individuals who had never been infected with COVID-19, followed by healthy COVID-19 survivors, long-COVID patients without cognitive deficits (MoCA ≥ 26), and finally, long-COVID patients exhibiting significant cognitive deficits (MoCA < 26). These findings highlight the continuum of cortical thickness alterations associated with COVID-19, with more pronounced changes observed in individuals experiencing cognitive impairment (p<0.05, FWE-corrected). Affected cortical regions covered prefrontal and temporal gyri, insula, posterior cingulate, parahippocampal gyrus, and parietal areas. Additionally, we discovered a distinct immunophenotype, with elevated levels of IL-10, IFNγ, and sTREM2 in long-COVID patients, especially in the group suffering from cognitive impairment.We demonstrate lingering cortical and immunological alterations in healthy and impaired subgroups of COVID-19 survivors. This implies a complex underlying pathomechanism in long-COVID and emphasizes the necessity to investigate the whole spectrum of post-COVID biology to determine targeted treatment strategies targeting specific sub-groups.
Relationship between topological efficiency of white matter structural connectome and plasma biomarkers across Alzheimer’s disease continuum
Authors: Zhang Mingkai , Chen Haojie , Huang Weijie , Guo Tengfei , Ma Guolin , Han Ying , Shu Ni 
Published: July 2023

AbstractIntroductionThe associations between plasma AD biomarkers, brain network topology, and cognition across AD continuum remained unknown.MethodsFrom the cohort of Sino Longitudinal Study of Cognitive Decline, we analyzed plasma biomarkers of 287 participants, including the levels of β-amyloid (Aβ), phosphorylated-tau181 (p-tau181), glial-fibrillary-acidic-protein (GFAP), and neurofilament-light-chain (NfL), and we assessed white matter network efficiency of 395 participants. Trend analyses evaluated the sensitivity of plasma markers and network efficiency with AD progression. Correlation and mediation analyses further explored the relationships among plasma markers, network efficiency, and cognition across AD continuum.ResultsAmong the plasma markers, GFAP exhibited the highest sensitivity with AD progression, followed by NfL, p-tau18, and Aβ42/Aβ40. Local efficiency decreased in multiple brain regions and correlated with GFAP, NfL, and p-tau181. Network efficiency mediated the relationship between plasma markers and cognition.DiscussionOur findings highlight the potential of network-plasma approaches for early detection and intervention of AD.
Comparing the accuracy of an ultrasound height measurement device with a wooden measurement board among children aged 2-5 years in rural Lao People’s Democratic Republic: a methods-comparison study
Authors: Huang Shan , Homer Caroline S.E. , Conkle Joel , Kounnavong Sengchanh , Phongluxa Khampheng , Vogel Joshua P. 
Published: July 2023

AbstractBackgroundHeight is a key component of nutrition assessments in children from limited-resource settings. Traditional measurement boards are bulky and difficult to transport. We aimed to assess whether a handheld digital ultrasound device provides comparable accuracy to the measurement board for measuring children’s height.MethodsWe trained 12 health workers to measure the standing height of 222 children aged 2-5 years in rural Lao People’s Democratic Republic using the ultrasound device and measurement board. The Bland-Altman method was used to depict limits of agreement and potential bias. We reported the technical error of measurement (TEM) for precision, accuracy and assessed results against the Standardized Monitoring and Assessment for Relief and Transition (SMART) Manual 2.0 and the WHO Multicentre Growth Reference Study (MGRS).ResultsThe average difference between the ultrasound and board measurements was 0.096 cm (95% limits-of-agreement: 0.041cm, 0.61cm) with a systematic bias of 0.1cm (95% confidence interval: 0.067,0.134), suggesting the ultrasound measurements measured slightly higher than those from the board. The ultrasound and board TEMs for precision were 0.157cm and 0.113 respectively. The accuracy TEM was 0.208cm. All TEMs were within SMART and WHO MGRS limits.ConclusionThe ultrasound device is comparable to the measurement board among standing Lao children aged 2-5 years for precision and accuracy TEMs but showed a bias of 0.1cm. Further studies are required to assess whether calibration of device can minimise this bias and determine the ultrasound’s accuracy on recumbent length for infants and younger children.
National trends in suicides and male twin live births in the US, 2003 to 2019: an updated test of collective optimism and selectionin utero
Authors: Singh Parvati , Gailey Samantha , Das Abhery , Bruckner Tim A. 
Published: July 2023

AbstractPrior research based on Swedish data suggests that collective optimism, as measured by monthly incidence of suicides, correlates inversely with selectionin uteroagainst male twins in a population. We test this finding in the US, which reports the highest suicide rate of all high-income countries, and examine whether monthly changes in overall suicides precede changes in the ratio of male twin to male singleton live births. Consistent with prior work, we also examine as a key independent variable, suicides among women aged 15-49 years. We retrieved monthly data on suicides and the ratio of male twin to singleton live births from CDC WONDER, 2003 to 2019, and applied Box-Jenkins iterative time-series routines to detect and remove autocorrelation from both series. Results indicate that a one percent increase in monthly change in overall suicides precedes a 0.005 unit decline in male twin live births ratio 6 months later (coefficient = -0.005,Pvalue = 0.004). Results remain robust to use of suicides among reproductive-aged women as the independent variable (coefficient = -0.0012,Pvalue = 0.014). Our study lends external validity to prior research and supports the notion that a decline in collective optimism corresponds with greater selectionin utero.