bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gestational diabetes mellitus and vascular malperfusion lesions in the placenta: a systematic review and meta-analysis
Authors: Arcot Amrita , Walker Rachel E. , Gallagher Kelly , Goldstein Jeffery A. , Gernand Alison D. 
Published: February 2025

AbstractBackgroundGestational diabetes mellitus (GDM) can result in increased placental lesions related to high maternal blood glucose, but these relationships are not well understood.ObjectiveTo examine the relationship between GDM and placental vascular malperfusion lesions: accelerated villous maturation, increased syncytial knots, delayed villous maturation, and increased fibrin deposition.Search strategyPubMed, BIOSIS, and Web of Science databases were systematically searched for full-text articles in English from inception until August 21, 2024.Selection criteriaOur inclusion criteria were randomized controlled trials, case-control, cohort, and cross-sectional studies that examined the relationship between GDM and selected placental vascular malperfusion lesions. The outcome must have been reported as a total proportion.Data collection and analysisWe included all eligible studies in narrative synthesis. If an outcome of interest was in at least three studies, we calculated the odds ratios (OR) by GDM diagnosis, with 95% confidence intervals, using mixed-effects logistic regression with random study effects. We evaluated the risk of bias with the Newcastle-Ottawa Scale.Main resultsWe screened 151 studies, of which eight were included (n=1,291), and six met the criteria for meta-analysis (n=561). Unadjusted odds (95% confidence interval) of delayed villous maturation were six-fold higher (OR: 6.37 [3.28, 12.37]) in pregnancies with GDM compared to those without GDM. The narrative synthesis of the literature found higher proportions of increased syncytial knots, delayed villous maturation, and increased fibrin deposition, but not accelerated villous maturation, in pregnancies with versus without GDM.ConclusionsGDM was associated with increased risk of three placental malperfusion lesions, although there is a small number of studies in this area. Future investigations should examine if these vascular malperfusions are associated with adverse pregnancy outcomes often linked with GDM.SynopsisGDM is associated with increased syncytial knots, delayed villous maturation, and increased fibrin deposition, but not accelerated villous maturation.FundingHealth Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS) as part of the Maternal Child Health Bureau Nutrition Training Grant, The TRANSCEND Program in Maternal Child Health Nutrition (T7949101).RegistrationRegistered in PROSPERO under protocol number CRD42023449651
Clinical determinants and outcomes associated with the development of acute kidney injury in critically ill patients: a Brazilian retrospective cohort study
Authors: Menezes Rodrigo C. , Meira-Teles Rodrigo S.F. , Moura Lucas G. , Ferreira Isabella B. B. , Filgueiras Filho Nivaldo M. , Andrade Bruno B. 
Published: February 2025

ABSTRACTBackgroundAcute kidney injury (AKI) is a common complication in intensive care unit (ICU) patients and associates with significant morbidity and mortality. Understanding region-specific risk factors is crucial for early identification and management, especially in resource-limited settings. This study aimed to identify characteristics, risk factors, and outcomes related to AKI in critically ill patients from a center in Northeast Brazil.MethodsRetrospective cohort study that used secondary data of adult ICU patients admitted to a medium-sized hospital in Brazil between August 2015 and April 2024. Patients with pre-existing chronic kidney disease or AKI at admission were excluded. Demographic and clinical variables, documented comorbidities, clinical and laboratory data in the first 6 hours of admission, and adverse events during hospitalization were collected. To evaluate risk factors, the variables were included in a multivariable Cox regression model, while to assess complications, a univariable model was employed. Bayesian network modeling was applied to infer causal relations between the presence of AKI and the statistically significant risk factors. Kaplan-Meier curves were used to evaluate survival and length of stay.ResultsOf 5,416 patients analyzed, 369 (6.81%) developed AKI during their ICU stay. Independent risk factors for AKI included advanced age (adjusted Hazard Ratio [aHR] 1.01 per increase in 1 year of age; 95% CI: 1.00–1.02; p=0.008), chronic liver failure (aHR 10.02; 95% CI: 4.91–20.41; p<0.001), arterial hypertension (aHR 1.29; 95% CI: 1.00–1.66; p=0.048), higher heart rate at admission (aHR 1.01 per bpm; 95% CI: 1.00–1.01; p=0.004), and reduced level of consciousness (aHR 1.67 per point decrease in Glasgow Coma Scale; 95% CI: 1.34–2.07; p<0.001). Underweight patients had a lower risk of AKI compared to those with normal weight (aHR 0.59; 95% CI: 0.38–0.91; p=0.017). AKI was associated with higher mortality (37.13% vs. 10.54%; p<0.001) and longer hospital stay (median 16 vs. 10 days; p<0.001).ConclusionsAge, chronic liver failure, arterial hypertension, higher heart rate, and reduced level of consciousness at admission are independent risk factors for AKI development. AKI was associated with poorer outcomes, highlighting the need for early identification and targeted interventions in this population.
Childhood Nutrition and Service Delivery Indicators across and between two Epidemics (Ebola and COVID-19) in Sierra Leone: A Descriptive Study using Serial Cross-Sectional Surveys
Authors: Bangura Kadiatu , Koroma Aminata Shamit , Pyne-Bailey Solade , Koroma Manso M , Lakoh Sulaiman , Sevalie Stephen , Molleh Bailah , Mekonnen Zeleke Abebaw , Chan Adrienne , Mishra Sharmistha , N’jai Alhaji U. 
Published: February 2025

AbstractIntroductionSierra Leone is one of the worst affected by hunger and food insecurity, but data to understand the impact of public health emergencies on nutrition indicators is limited. In this study, we sought to describe nutrition service delivery and nutritional health among children under age five before and during the Ebola epidemic, the inter-epidemic period, and during the COVID-19 pandemic (2021) in Sierra Leone.MethodsWe conducted a descriptive study using secondary data from five serial cross-sectional surveys conducted using representative sampling as part of programmatic monitoring and evaluation: 2010 (N=14027, before Ebola); 2014 (N=10,975, during Ebola); 2017 and 2019 (N=9059, N=4,870, respectively, inter-pandemic period); 2021 (N=10,165, during COVID-19). We described and compared the prevalence of each of the following indicator at each time-point: shunting, global acute malnutrition, breastfeeding and underweight.ResultsThe prevalence of stunting was 34.1% before the Ebola epidemic, 28.8% during the Ebola epidemic, 31.3% after the Ebola epidemic, 25.9% before the COVID-19 epidemic, and 26.2% during the COVID-19 epidemic. The prevalence of global acute malnutrition was: 6.9% before the Ebola epidemic, 4.7% during the Ebola epidemic, 5.1% after the Ebola epidemic, 5.0% before the COVID-19 epidemic, and 5.2% during the COVID-19 epidemic. Finally, the report showed that the proportion of breastfeeding for up to 23 months was 84.0% (before the Ebola epidemic), 86.0% (during the Ebola epidemic), 85.0% (after the Ebola epidemic), 61.8% (before the COVID-19 epidemic), and 53.1% (during the COVID-19 epidemic).ConclusionWe found a variable effect of the Ebola epidemic and COVID-19 on nutrition health and nutrition indicators. Findings highlight the importance of continuing to strengthen the implementation of nutrition programs during and after public health emergencies.
Direct Retinal Imaging for Shock Resuscitation in Critical Ill Adults II (D-RISC II)
Authors: Cooper George , Burke Jamie , Hamid Charlene , Godden Emily , Dhaun Neeraj , King Stuart , MacGillivray Thomas J. , Baillie J. Kenneth , Griffith David M. , MacCormick Ian J.C. 
Published: February 2025

AbstractBackgroundShock involves microcirculatory dysfunction that is not suitably captured well by measurements of large vessels, such as systemic blood pressure. The outer retinal microcirculation (the choroid) can be measured non-invasively and may reflect dysfunction in other organs. We tested the feasibility of measuring the retinal choroid in an intensive care setting and explored associations between choroidal measurements and severity of disease.MethodsWe performed optical coherence tomography on patients admitted to the intensive treatment unit, and repeated imaging once 12-72 hours later. We measured choroidal anatomy using automated image segmentation, compared this to routine clinical data, and described change over time.ResultsOf fifteen patients recruited, 80% (12) had successful baseline imaging and 40% (6) of these had follow-up imaging within intensive care. At baseline, patients with thicker choroids and larger vascularity had larger cumulative fluid balance, and lower disease severity (Acute Physiology and Chronic Health Evaluation II) score, haematocrit, and albumin. A measurable suprachoroidal space was seen in 75% (9) patients and the size of this space tended to be larger in patients with lower heart rates. There was substantial intraindividual variation in choroidal measurements over time.CommentMeasuring the retinal choroid is feasible in patients with critical illness. Exploratory associations with systemic variables suggest that the choroid may provide information about the microvascular function of other major organs. Size and change of choroidal measurements may reflect perfusion pressure or vascular leak in response to inflammation.
Auditory steady-state response deficits in Fragile X Syndrome implicate deficits in stimulus representation maintenance and GABAergic modulation
Authors: Norris Jordan E. , De Stefano Lisa A. , McKinney Walker S. , Schmitt Lauren M. , Miyakoshi Makoto , Gross Christina , Piloto Sebastian , Heald Braeden , Pedapati Ernest V. , Erickson Craig A. , Sweeney John A. , Ethridge Lauren E. 
Published: February 2025

AbstractBackgroundFragile X Syndrome (FXS) is a rare, neurodevelopmental disorder caused by a mutation to the Fragile X messenger ribonucleoprotein 1 (Fmr1) gene and characterized by sensory processing abnormalities and sensitivities, including neural auditory oscillatory disruptions and reduced neural entrainment to chirp stimuli. The present study aims to evaluate the 40 Hz auditory steady state response (ASSR) in FXS to evaluate stimulus representation maintenance in FXS.MethodsAdolescents and adults (N = 67; 34 FXS and 33 age, sex-matched typically developed controls (TDC)) completed a 40 Hz auditory steady state task during electroencephalography (EEG). Time-frequency analyses using Morlet wavelets were completed to evaluate intertrial phase coherence (ITC) and event-related spectral perturbation (ERSP), including characterization of the transient and sustained components of the 40 Hz ASSR.ResultsBoth ITC (p= .003) and ERSP (p= .004) at 40 Hz were reduced for FXS compared to TDC. Interestingly, TDC exhibited a significantly elevated early, transient component (100 – 400 ms) which reduced in both ITC and ERSP during transition to the sustained component (650 – 3000 ms) whereas FXS were consistently reduced across the ASSR suggesting a reduced ability for FXS to mount a transient response.ConclusionsIndividuals with FXS exhibit robust reductions in magnitude and temporal precision of neural entrainment to the steady state stimulus. The reduced ability to mount a transient response may represent reduced GABAergic modulation where the overall reduction in ITC and ERSP may reflect reduced excitatory/inhibitory balance between NMDA and GABAergic input.
Modern approaches to predicting vaccine hesitancy: A scoping review
Authors: Gandhi Keshav , Alahmadi Sami , Hanneke Rosie , Gutfraind Alexander 
Published: February 2025

AbstractIntroductionMotivated by the disproportionate burden of infectious diseases on vulnerable populations and the risk of future pandemics, we conducted a scoping review to analyze the state of the literature about “vaccine uptake indices,” defined as models that predict vaccination rates by geospatial area. We analyzed novel vaccine uptake indices created in response to the recent COVID-19 pandemic. The aim of this scoping review is to survey the state of the literature regarding vaccine uptake indices relating to COVID-19 and other infectious diseases.MethodsWe conducted a scoping review with a systematic search strategy to identify relevant articles from the databases Embase, PubMed, and Web of Science with title and abstract screening, full-text review, and data extraction.ResultsDatabase searches resulted in 3,615 potential articles, of which 229 reports were included. Fifteen studies (7%) were determined to be methodologically advanced vaccine uptake indices that had at least three of the following characteristics: the use of individual- and population-level predictor variables (100 [44%]), geo-spatiotemporal analysis (58 [25%]), data usage agnostic to vaccine specificity (50 [22%]), or sociobehavioral frameworks of health (such as the Health Belief Model and Theory of Planned Behavior) (30 [13%]).ConclusionThis scoping review offers suggestions for future research of next-generation vaccine uptake indices before use in vaccination campaigns of recurring or novel infectious diseases. Areas to pursue include utilizing individual-level data about vaccination behaviors in conjunction with administrative data, solving the challenge of implementing small-area spatiotemporal analysis, using vaccine-agnostic methods that consider data from more than one infectious disease, and assisting causal inference with theoretical frameworks.
Incorporating exon-exon junction reads enhances differential splicing detection
Authors: Pham Mai T. , Milevskiy Michael J.G. , Visvader Jane E. , Chen Yunshun 
Published: February 2025

AbstractMotivationRNA sequencing (RNA-seq) is a gold standard technology for studying gene and transcript expression. Different transcripts from the same gene are usually determined by varying combinations of exons within the gene, formed by splicing events. One method of studying differential alternative splicing between groups in short-read RNA-seq experiments is through differential exon usage (DEU) analyses, which use exon-level read counts along with downstream statistical testing strategies. Popular pipelines for these analyses includeRsubreadfor read alignment and exon-level count quantification, andedgeRandlimmafor statistical testing of differential splicing. However, the standardRsubread::featureCountscount summarization method does not consider exon-junction information, which may reduce the statistical power in differential splicing analyses.ResultsA new feature quantification approach is proposed to incorporate both exon and exon-junction reads into the popularRsubread-edgeRandRsubread-limmaframeworks for detecting differential splicing events. This new Differential Exon-Junction Usage (DEJU) analysis pipeline demonstrates increased statistical power compared to existing popular methods while effectively controlling the false discovery rate.Availability and implementationData and code to reproduce the results shown in this article are available fromhttps://github.com/TamPham271299/DEJU.
Anxiety-like behavior during protracted morphine withdrawal is driven by gut microbial dysbiosis and attenuated with probiotic treatment
Authors: Oppenheimer Mark , Tao Junyi , Moidunny Shamsudheen , Roy Sabita 
Published: February 2025

AbstractThe development of anxiety during protracted opioid withdrawal heightens the risk of relapse into the cycle of addiction. Understanding the mechanisms driving anxiety during opioid withdrawal could facilitate the development of therapeutics to prevent negative affect and promote continued abstinence. Our lab has previously established the gut microbiome as a driver of various side effects of opioid use, including analgesic tolerance and somatic withdrawal symptoms. We therefore hypothesized that the gut microbiome contributes to the development of anxiety-like behavior during protracted opioid withdrawal.In this study, we first established a mouse model of protracted morphine withdrawal, characterized by anxiety-like behavior and gut microbial dysbiosis. Next, we used fecal microbiota transplantation (FMT) to show that gut dysbiosis alone is sufficient to induce anxiety-like behavior. We further demonstrate that probiotic therapy during morphine withdrawal attenuates the onset of anxiety-like behavior, highlighting its therapeutic potential. Lastly, we examined transcriptional changes in the amygdala of morphine-withdrawn mice treated with probiotics to explore mechanisms by which the gut-brain axis mediates anxiety-like behavior.Our results support the use of probiotics as a promising therapeutic strategy to prevent gut dysbiosis and associated anxiety during opioid withdrawal, with potential implications for improving treatment outcomes in opioid recovery programs.
Salicylic acid represses primary root growth through the Glucose-Target of Rapamycin-E2Fa pathway in Arabidopsis
Authors: Rawat Sanjay Singh , Laxmi Ashverya 
Published: February 2025

AbstractIn addition to their role as energy sources, sugars function as signaling molecules, modulating gene expression. Plants perceive nutrient availability and translate this information into cellular signals, to trigger various developmental responses, including primary root growth. In particular, glucose stimulates root development by activating the root meristem. Recent studies have documented the role of the defense hormone, salicylic acid (SA) as a negative regulator of root growth and developmental processes. Here, we characterized the modulation of primary root growth by the cross-talk of glucose and SA. Our results indicate that auxin is a critical mediator of SA-induced root growth inhibition. Attenuation of auxin signaling or transport pathways alters the inhibitory effect of SA on root growth. Moreover, we provide evidence for the involvement of the role of Target of Rapamycin (TOR) signaling in SA-induced root growth repression. Furthermore, SA negatively regulates the expression of E2Fa, a key transcription factor required for cell cycle progression and root growth and development. Our findings elucidate mechanism(s) whereby SA, through the interconnected glucose, auxin and TOR signaling pathways, inhibits primary root growth.
c-Rel drives pancreatic cancer metastasis through Fibronectin-Integrin signaling-induced isolation stress resistance and EMT activation
Authors: Bakırdöğen D. , Görgülü K. , Xin J. , Alcalá S. , Ruiz-Cañas L. , Frank K. , Wu N. , Diakopoulos K. N. , Dai C. , Öztürk H. , Demircioğlu D. , Peschke K. , Ranjan R. , Fusco F. , Martinez-Useros J. , Fernandez-Aceñero M. J. , Chhabra N. F. , López-Gil J.C. , Ai J. , Ruess D. A. , Kaya-Aksoy E. , Steiger K. , Schmidt F. , Kohlmann L. , Berninger A. , Schmid R. M. , Reichert M. , Adli M. , Lesina M. , Sainz B. , Algül H. 
Published: February 2025

ABSTRACTPancreatic ductal adenocarcinoma remains one of the deadliest malignancies, with limited treatment options and a high recurrence rate. Recurrence happens often with metastasis, for which cancer cells must adapt to isolation stress to successfully colonize distant organs. While the fibronectin-integrin axis has been implicated in this adaptation, its regulatory mechanisms require further elaboration. Here, we identify c-Rel as an oncogenic driver in PDAC, promoting epithelial-to-mesenchymal transition (EMT) plasticity, extracellular matrix (ECM) remodeling, and resistance to isolation stress. Mechanistically, c-Rel directly regulates fibronectin (Fn1) and CD61 (itgb3) transcription, enhancing cellular plasticity and survival under anchorage-independent conditions. Fibronectin is not essential for EMT, but its absence significantly impairs metastatic colonization, highlighting a tumor-autonomous role for FN1 in isolation stress adaptation. These findings establish c-Rel as a key regulator of PDAC metastasis by controlling circulating tumor cell (CTC) niche and survival, suggesting that targeting the c-Rel–fibronectin–integrin axis could provide new therapeutic strategies to mitigate disease progression and recurrence.
Arctic plant species display contrasting levels of chloroplast DNA copy numbers
Authors: Kamenova Stefaniya , Moinard Sylvain , Dwinnell Samantha Paige Huset , Laporte Frédéric , Coissac Éric 
Published: February 2025

AbstractDNA metabarcoding has revolutionised our ability to characterise biodiversity at unprecedented spatial and temporal scales, outperforming most traditional methods for biodiversity monitoring. However, DNA metabarcoding is not without limitations, in particular regarding the quantitative relationship between sequence read abundances and species numerical abundances or biomass (i.e., quantitative performance). Variation in DNA copy numbers has been often pinpointed as a potentially important factor biasing DNA metabarcoding quantitative performance but empirical comparisons of DNA copy number variation across species remain rare. Here, we identify chloroplast DNA copy number variation (cpDNA CNV) in plants as a potentially important factor that could impact quantitative performance in DNA metabarcoding studies. Using digital droplet PCR, we quantified chloroplast copy number variation in four common high Arctic plant species and between two plant tissue types (green tissues and roots). The amount of cpDNA per unit of dry mass varied by a factor of 3 (for roots) to 7.6 (for green tissues) among species, and up to 67 when comparing cpDNA copy numbers between green and root tissues from the same species. Despite significant differences in cpDNA copy numbers among species for both green tissues and roots, the most pronounced differences in cpDNA copy numbers were clearly between the two tissue types tested. These findings suggest that variation in cpDNA copy numbers among plant species and particularly plant tissue types can be an important but underestimated factor impacting plant sequence reads abundance in DNA metabarcoding datasets. We call for more extensive cpDNA CNV referencing efforts from wild-ranging plants to improve the use of DNA metabarcoding for research and biodiversity monitoring.
Preventing large deletions and chromosome loss in engineered human primary T cells by CasPlus with optimized guide RNAs
Authors: Yang Qiaoyan , Abebe Jonathan S. , Mai Michelle , Konishi Colin , Devinsky Orrin , Long Chengzu 
Published: February 2025

AbstractGenetically engineered T-cell therapies rely heavily on genome editing tools, such as the CRISPR/Cas9 system. However, unintended on-target chromosomal alterations, including large deletions and chromosome loss can occur and pose significant risks including tumorigenesis. Here we combined CasPlus and optimized guide RNAs to reduce these issues in CRISPR/Cas9 engineering human primary T cells. CasPlus, which integrates an engineered T4 DNA polymerase with Cas9 nuclease and guide RNA, promotes favorable small insertions (1-2 bp) while reducing large deletions and chromosome loss in T cells. Our optimized guide RNAs favoring small insertions reduced large deletions and chromosome loss by two- to five-fold versus those favoring small deletions. Moreover, combining optimized guide RNA with T4 DNA polymerase further synergistically reduced large deletions and chromosome loss by additional two-fold. Notably, replacing currently used guide RNA pairs in clinically applications with optimized pairs biased towards small insertions, along with CasPlus instead of Cas9, for editing greatly reduced large deletions and chromosome loss in gene-edited human primary T cells. These findings demonstrated that pre-selecting target sites favoring small insertions via guide RNA optimization coupled with CasPlus editing is a safer and more effective strategy to improve genome stability in T-cell engineering and other gene-editing applications.