bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on Pine Wilt Disease Spread Prediction Based on an Improved LGBM Model
Authors: Zhou Hongwei , Zhang Siyan , Chen Yifan , Zhang Shibo , Xu Zihan , Cui Di , Guo Wenhui
Published: January 2025

Pine wilt disease has caused significant damage to China's ecological and financial resources. To prevent its further spread across the country, proactive control measures are necessary. Given the low accuracy of traditional models, we have employed an enhanced LightGBM model to predict the development trend of pine wilt disease in China. By incorporating anthropogenic factors such as the volume of pine wood imports from 2017 to 2022, the density of graded roads, the number of adjacent counties, and the presence of wood processing factories, as well as natural factors like temperature, humidity, and wind speed, we employed Pearson correlation and LightGBM model's feature importance analysis to select the 17 most significant influencing factors. Spatial analysis was conducted on the epidemic sub-compartments (A divisional unit smaller than a township) of pine wilt disease for 2022 and 2023, revealing the distribution patterns of epidemic sub-compartments within 2 km of roads and the spatial relationships between new and old epidemic sub-compartments. We improved the LightGBM model using Bayesian algorithm, SSA, and HPO. By comparison, the enhanced model was validated to outperform in terms of accuracy, precision, recall, sensitivity, and specificity. Based on the results of correlation analysis and spatial analysis, an enhanced model was used to predict the emergence of pine wilt disease in new counties and districts in the future. Currently, pine wilt disease is primarily concentrated in the central-southern and northeastern provinces of China. Predictions indicate that the disease will further spread to the northeastern and southern regions of the country in the future.
Under-five child mortality associated with infection: retrospective study, 2018–2022
Authors: Manikandan Anjana , Lewis Leslie Edward S. , P.V. Mallikarjuna , Varghese Aneena , Shettigar Kavitha S.
Published: December 2024

Purpose:

Mortality in under-five children is a public health concern, and it is an indicator for assessing the progress and overall welfare of a country. Various infectious and noninfectious diseases cause mortality in under-five children. This study was conducted to assess the causes of mortality in under-five children associated with infectious diseases.

Methods:

A retrospective study was conducted by collecting the medical records of under-five children who died because of infectious diseases at Kasturba Hospital, Manipal during the 5-year period from 2018 to 2022. Data analysis was performed to identify the causes, clinical characteristics, and age patterns of the children using Jamovi software.

Results:

Among the total 15 933 live births, 642 patients had mortality. Among 642 mortality, 190 (25.5%) died because of the presence of infectious diseases with overall infant mortality rate per 1000 live births representing 11.9. The highest mortality rate was observed in children aged 0–1 year (81.5%). Respiratory distress was the most common complaint (34.7%). Among the bacterial isolates, Klebsiella pneumoniae was the most predominant bacteria. In addition, Candida spp. and influenza virus were also reported. Sepsis (49%), low birth weight (11%), birth asphyxia (10%), malnutrition (3%) were the other factors found in under-five children who had mortality.

Conclusion:

Pneumonia as the primary cause of death due to infectious diseases in children, followed by other infectious diseases. Clinical sepsis is linked to bacteremia-related deaths. Comprehensive prospective studies and public health measures are needed to improve the prevention, diagnosis, and management of these pediatric conditions.
Plasticity of visual looming response reveals a dissociation of innate and learned components
Authors: Conway Paul B. , Autore Livia , Muñoz Zamora Andrea , Harel Antoine , Tavallaei Arman A. , Winston Stephen M. , Ortega-de San Luis Clara , O’Leary James D. , Brimble Mark A. , Vetere Gisella , Ryan Tomás J.
Published: December 2024

Animals rely on both innate and learned behaviour to respond optimally to their environment. However, little is known about how the brain may reconcile the ability to produce hardwired responses essential to survival while still allowing for adaptive flexibility. Here, we demonstrate that innate looming stimulus responses, an innate predator-evasion behaviour, can be robustly extinguished via repeated unreinforced presentation over several days. We report that this extinction is long-lasting and generalises to other contexts, but can be rapidly recovered via the pairing of the visual stimulus with an aversive electric foot-shock stimulus. Moreover, fiber photometric recordings reveal that this behavioural paradigm results in the attenuation of SC and PAG physiological responses to visual looming stimuli, and that these responses do not recover following recovery of behavioural responses. An analysis of c-Fos expression patterns throughout the midbrain and hippocampus uncovered a ventral CA1 (vCA1) ensemble that is active during both innate and learned visual looming fear responses. We investigate the functional significance of this vCA1 ensemble and report that, while its activity is not necessary for innate defensive behaviour, it is necessary for learned fear responses. Together, these findings reveal a novel role of the hippocampus in enabling adaptive behavioural responses to the innately threatening visual looming stimulus which acts in complement with innate circuitry of the SC and PAG.
Modelling the synergy between single-occupancy and PPE in controlling COVID-19 outbreaks on hospital wards
Authors: Zachreson Cameron , Schofield Robyn , Marshall Caroline , Kainer Marion , Buising Kirsty , Monty Jason , Sullivan Sheena , Subbarao Kanta , Geard Nicholas
Published: December 2024

Background

Outbreaks of respiratory pathogens on hospital wards present a major challenge for control of hospital-acquired infections. When illness presentation is mild or infection is asymptomatic, isolation of recognised cases may be insufficient to prevent outbreaks, as unrecognised cases may be common. In such scenarios, structural controls such as the design of wards with single-occupancy patient rooms, or routine precautions such as the use of N95 respirators by healthcare staff can play an important role in preventing and mitigating outbreaks.

Methods

This study applies an agent-based extension of the Wells-Riley model of airborne pathogen exposure to simulate COVID-19 outbreaks on hospital wards. We simulated the impact of single-vs. double-occupancy patient rooms on secondary attack rates and the sizes of outbreaks resulting from introduction of unrecognised cases. We further simulated the impact of N95 respirator use by nurses during patient care activities, assuming an efficacy of 90% for protection and source control.

Results

In our simulations, the size of outbreaks recorded at day 14 was markedly lower in wards with only single-occupancy rooms, compared to double-occupancy rooms (with means of 15.2 and 25.1 infections, respectively). We found that nurses working on wards were more likely to acquire infection than patients. Higher patient room occupancy was associated with increased outbreak size, with a larger relative impact on patients than staff. N95 respirators were effective at mitigating outbreaks, with higher impacts in wards with single-occupancy patient rooms.

Conclusions

Single-occupancy rooms can greatly decrease the risk of hospital acquired airborne infection for patients. We show that single-occupancy hospital rooms can also reduce the number of healthcare workers infected during an outbreak of an airborne respiratory virus, but not to the same relative extent as patients. Due to the structural constraints limiting transmission between patients in different rooms, outbreaks were driven by transmission events involving nurses, which were effectively mitigated through the use of N95 respirators. Taken together, our results suggest that single-occupancy rooms are effective at reducing outbreak sizes. However, they are insufficient by themselves to prevent large outbreaks without mitigation efforts focused on limiting the potential for transmission involving healthcare workers, such as the use of N95 respirators.
Segpy: a streamlined, user-friendly pipeline for variant segregation analysis
Authors: Fiorini Michael R. , Amiri Saeid , Dilliott Allison A. , Spiegelman Dan , Rouleau Guy , Farhan Sali M.K.
Published: December 2024

Understanding the role of genetic variants in disease is essential for diagnostics and the advancement of genomic medicine. While the advent of high-throughput sequencing has been matched by the development of sophisticated genomic analysis tools, these packages often involve complex analytical procedures that can be challenging for researchers with limited computational experience. Additionally, modern genomic datasets require high-performance computing (HPC) systems, which may be difficult to implement for unfamiliar users. To address these challenges, we introduce Segpy, a streamlined, user-friendly pipeline for variant segregation analysis that integrates seamlessly with HPC environments. Segpy supports single-family, multi-family, and population-based datasets, allowing researchers to evaluate how genetic variants co-segregate with disease in pedigree-based analyses and compare allele frequencies between affected and unaffected individuals in case-control analyses. To date, the application of Segpy has facilitated the identification of genetic variants contributing to many human diseases and is now available as a publicly available framework.
Quantitative Susceptibility Mapping Radiomics with Label Noise Compensation for Predicting Deep Brain Stimulation Outcomes in Parkinson’s Disease
Authors: Roberts Alexandra G. , Zhang Jinwei , Tozlu Ceren , Romano Dominick , Akkus Sema , Kim Heejong , Sabuncu Mert R. , Spincemaille Pascal , Li Jianqi , Wang Yi , Wu Xi , Kopell Brian H.
Published: December 2024

Parkinson’s disease patients with motor complications are often considered for deep brain stimulation (DBS) surgery. DBS candidate selection involves an assessment known as the levodopa challenge test (LCT). The LCT aims to predict DBS outcomes by measuring symptom improvement accompanying changes in levodopa dosage. While used in the patient selection process, inconsistent LCT predictions have been widely documented, verified here with Pearson’s correlationr= 0.12. Estimating symptom improvement to separate DBS responders and non-responders remains an unmet need. Quantitative susceptibility mapping (QSM) is routinely acquired for pre-surgical planning and depicts the iron distribution in substantia nigra and subthalamic nuclei. Iron deposition in these nuclei has correlated with disease progression and motor symptom severity. A novel QSM radiomic approach is presented using a regression model and features extracted from the pre-surgical targeting acquisition. Noise compensation in training labels improves outcome prediction in regression and classification models. The model predicts improvement in the unified Parkinson’s disease rating scale (UPDRS-III) (r= 0.75). Predictive feature maps in deep gray nuclei offer contrast between responders and non-responders. The QSM radiomic approach has potential to improve DBS candidate selection by accurately estimating symptom improvement, eliminating difficult medication manipulation, and avoiding time-consuming evaluations to reduce patient and clinician burden.
Digital health citizenship: Mapping existing tools for digital, health and civic literacy
Authors: Ogundipe Racheal
Published: December 2024

Digital Health Citizenship (DHC) integrates digital, health, and civic literacy to empower individuals, particularly young people, to navigate digital health ecosystems effectively. This framework promotes equitable access to health information, informed decision-making, and active participation in personal and public health outcomes while addressing critical issues of digital literacy disparities, privacy, and inclusivity. Young people often lack access to resources that address their unique challenges, such as navigating misinformation, safeguarding privacy, understanding health and civic responsibilities, and effectively engaging in digital and societal spaces. The research aimed to identify existing DHC tools and evaluate them based on the specific needs of young people, to inform the development of more tools tailored specifically to their needs.

This research was conducted in two stages: a landscape analysis, followed by an assessment of existing tools and resources for strengths and weaknesses. The research approach integrates a literature review, walkthrough method and comparative analysis to evaluate tools/resources comprehensively and assess their strengths and weaknesses.

The study evaluated 38 existing tools and resources addressing digital, health, and civic literacy, using criteria such as equity, trustworthiness, human-centric design, inclusivity, ethics, and capacity building. The analysis revealed significant gaps in current resources. Most tools lack multilingual support and alternative formats, excluding users with disabilities or limited digital access. The fragmented approach to literacy—where tools typically address only one aspect of DHC—reduces their effectiveness in fostering comprehensive digital health citizenship. Additionally, while existing resources successfully convey information, they often fail to develop practical skills across all three literacy domains. The heavy reliance on internet connectivity further limits accessibility for individuals in low-resource settings.

Digital health citizenship is more than providing information. It is about equipping young people with the skills and confidence to engage with their health in a meaningful way. This can be done by providing DHC toolkits that meet the needs of young people globally, including cultural, social and digital needs. It is also important for stakeholders in the digital, health and civic space to be more proactive in ensuring that adequate resources are available to young people.

Through this targeted approach to developing comprehensive DHC tools/resources, we can better empower young people to become active participants in their health journey while ensuring no one is left behind in the digital health transformation.
IMPACT OF COVID-19 ON EDUCATION: LATEST TRENDS IN K-12 EDUCATION IN THE WORLD
Authors: Bakhsh Khuda , Shoukat Rizwan , Huang Qibing
Published: December 2024

The Covid-19 has closed the whole world including the schools and colleges. This situation never thought before this in the world. Over billions of K-12 students are out of educational institutions due to this novel virus. We cannot put this risk into the future of students. Therefore, this study was conducted to explore the latest trends and practices of educational institutions which are useful during and after the Covid-19. The investigation was a mixed method (quantitative and qualitative) study which focused on questionnaires and interviews of the participants for the data gathering. A sample of 170 respondents in which 10 heads of secondary schools, 10 university professors, 50 K-12 teachers and 100 K-12 students were selected for the collection of quantitative data. However, the sample size in the collection of qualitative data was not fixed. The data collection was stopped when the emerging of new data themes stopped and the final sample of qualitative data collection was 23 participants. The triangulation technique was used to cross check the results and validation of data. The study found that the online education properly planned by the administration in the modern K-12 education in the world is the best solution during the Covid-19.
Genomic-Thermodynamic Phase Synchronization: Maxwell's Demon-Like Regulation of Cell Fate Transition
Authors: Tsuchiya Masa , Yoshikawa Kenichi , Giuliani Alessandro
Published: December 2024

Dynamic criticality - the balance between order and chaos - is fundamental to genome regulation and cellular transitions. In this study, we investigate the distinct behaviors of gene expression dynamics in MCF-7 breast cancer cells under two stimuli: Heregulin (HRG), which promotes cell fate transitions, and Epidermal Growth Factor (EGF), which, despite binding to the same receptor, does not induce cell fate changes. We model the system as an open, non-equilibrium thermodynamic system and introduce a convergence-based approach for robust estimation of information-thermodynamic metrics. Our analysis reveals that the Shannon entropy of the critical point (CP) dynamically synchronizes with the entropy of the rest of the whole expression system (WES), reflecting coordinated transitions between ordered and disordered phases. This phase synchronization is driven by net mutual information scaling with CP entropy dynamics, demonstrating how the CP governs genome-wide coherence. Furthermore, high-order mutual information emerges as a defining feature of the nonlinear gene expression network, capturing collective effects beyond simple pairwise interactions. By achieving thermodynamic phase synchronization, the CP orchestrates the entire expression system. Under HRG stimulation, the CP becomes active, functioning as a Maxwell's demon with dynamic, rewritable chromatin memory to guide a critical transition in cell fate. In contrast, under EGF stimulation, the CP remains inactive in this strategic role, passively facilitating a non-critical transition. These findings establish a biophysical framework for cell fate determination, paving the way for innovative approaches in cancer research and stem cell therapy.
Reshaping epigenomic landscapes in facilitating the speciation of bread wheat
Authors: Zhang Zhaoheng , Lin Xuelei , Yue Jingjing , Xu Yongxin , Miao Lingfeng , Tang Wenqiang , Guo Weilong , Xiao Jun
Published: December 2024

Polyploidization is a driving force of wheat evolution and speciation, yet its impact on epigenetic regulation and gene expression remains unclear.

Here, we constructed a high-resolution epigenetic landscape across leaves, spikes, and roots of hexaploidy wheat and its tetraploid and diploid relatives. Inter-species stable-expression genes exhibited conserved amino acid sequences under strong purifying selection, while dynamic-expression genes were linked to species-specific adaptation. During hexaploidization, dominant D-subgenome homoeolog expression was suppressed via reduced activating epigenetic signals, converging expression with the A and B subgenomes. Proximal chromatin regions near genes were more stable, whereas distal regions, particularly enhancer-like elements mediated by H3K27ac and H3K4me3, exhibit higher dynamism. Sequence variations in these enhancers lead to differential gene regulation, influencing traits such as spike development. For instance, the two haplotypes of dCRE region ofTaDEP-B1resulted in significant differences in its expression and spikelet numbers. We also observed a coevolution of transcription factors and their binding sites, particularly within the expanded ERF family, which regulates spike morphology.

This study highlights the interplay between sequence variation and epigenetic modifications in shaping transcriptional regulation during wheat speciation, offering valuable insights for genetic improvement.
ATP synthesis ofEnterococcus hiraeV-ATPase driven by sodium motive force
Authors: Otomo Akihiro , Hui Zhu Lucy Gao , Okuni Yasuko , Yamamoto Mayuko , Iino Ryota
Published: December 2024

V-ATPases generally function as ion pumps driven by ATP hydrolysis in the cell, but their capability of ATP synthesis remains largely unexplored. Here we show ATP synthesis of Na+-transportingEnterococcus hiraeV-ATPase (EhVoV1) driven by electrochemical potential gradient of Na+across the membrane (sodium motive force,smf). We reconstituted EhVoV1into liposome and performed a luciferin/luciferase-based assay to analyze ATP synthesis quantitatively. Our result demonstrates that EhVoV1synthesizes ATP with a rate of 4.7 s-1under highsmf(269.3 mV). The Michaelis constants for ADP (21 µM) and inorganic phosphate (2.1 mM) in ATP synthesis reaction were comparable to those for ATP synthases, suggesting similar substrate affinities among rotary ATPases regardless of their physiological functions. Both components ofsmf, Na+concentration gradient across the membrane (ΔpNa) and membrane potential (Δψ), contributed to ATP synthesis, with ΔpNa showing a slightly larger impact. At the equilibrium points wheresmfand Gibbs free energy of ATP synthesis are balanced, EhVoV1showed reversible reactions between ATP synthesis and hydrolysis. The obtained Na+/ATP ratio (3.2 ± 0.4) closely matched the value expected from the structural symmetry ratio between EhVoand EhV1(10/3 = 3.3), indicating tight coupling between ATP synthesis/hydrolysis and Na+transport. These results reveal inherent functional reversibility of EhVoV1. We propose that physiological function of EhVoV1in vivois determined by relatively smallsmfagainst large Gibbs free energy of ATP synthesis, in addition to the absence of inhibitory mechanisms of ATP hydrolysis which are known for ATP synthases.
Whole genome sequence-based association analysis of African American individuals with bipolar disorder and schizophrenia
Authors: Li Runjia , Gagliano Taliun Sarah A. , Liao Kevin , Flickinger Matthew , Sobell Janet L. , Genovese Giulio , Locke Adam E. , Chiu Rebeca Rothwell , LeFaive Jonathon , Wang Jiongming , Martins Taylor , Chapman Sinéad , Neumann Anna , Handsaker Robert E. , Arnett Donna K. , Barnes Kathleen C. , Boerwinkle Eric , Braff David , Cade Brian E. , Fornage Myriam , Gibbs Richard A. , Hoth Karin F. , Hou Lifang , Kooperberg Charles , Loos Ruth J.F. , Metcalf Ginger A. , Montgomery Courtney G. , Morrison Alanna C. , Qin Zhaohui S. , Redline Susan , Reiner Alexander P. , Rich Stephen S. , Rotter Jerome I. , Taylor Kent D. , Viaud-Martinez Karine A. ,   NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium,   Genomic Psychiatry Cohort investigators, Bigdeli Tim B. , Gabriel Stacey , Zollner Sebastian , Smith Albert V. , Abecasis Goncalo , McCarroll Steve , Pato Michele T. , Pato Carlos N. , Boehnke Michael , Knowles James , Kang Hyun Min , Ophoff Roel A. , Ernst Jason , Scott Laura J.
Published: December 2024

In studies of individuals of primarily European genetic ancestry, common and low-frequency variants and rare coding variants have been found to be associated with the risk of bipolar disorder (BD) and schizophrenia (SZ). However, less is known for individuals of other genetic ancestries or the role of rare non-coding variants in BD and SZ risk. We performed whole genome sequencing of African American individuals: 1,598 with BD, 3,295 with SZ, and 2,651 unaffected controls (InPSYght study). We increased power by incorporating 14,812 jointly called psychiatrically unscreened ancestry-matched controls from the Trans-Omics for Precision Medicine (TOPMed) Program for a total of 17,463 controls. To identify variants and sets of variants associated with BD and/or SZ, we performed single-variant tests, gene-based tests for singleton protein truncating variants, and rare and low-frequency variant annotation-based tests with conservation and universal chromatin states and sliding windows. We found suggestive evidence of BD association with single-variants on chromosome 18 and of lower BD risk associated with rare and low-frequency variants on chromosome 11 in a region with multiple BD GWAS loci, using a sliding window approach. We also found that chromatin and conservation state tests can be used to detect differential calling of variants in controls sequenced at different centers and to assess the effectiveness of sequencing metric covariate adjustments. Our findings reinforce the need for continued whole genome sequencing in additional samples of African American individuals and more comprehensive functional annotation of non-coding variants.
An approach for early diagnosis of atherosclerosis: correlation between blood levels of endothelin and D-dimers with atherogenic index in African black subjects
Authors: Tchame Claudric Roosvelt , Yiagnigni Mfopou Euloge
Published: December 2024

Global mortality due to cardiovascular disease (CVDs) is continuously increasing. In this regard, several authors have investigated the origins of CVD, with atherosclerosis being the most involved pathological process in CVD. In our study, we aimed to measure some parameters (endothelin, D-dimers) that could be involved in the early diagnosis of atherosclerosis and compare them to a classical marker Atherogenic index (AI) to see if there would be a correlation between these parameters and a possible use of them in diagnosis.

To do this, patients at risk of atherosclerosis, hypertensive and diabetic, were recruited over a period of 5 months at the Bonne Santé clinic in Yaounde. Out of a population of 84 patients, 10 hypertensive diabetics were selected, 77 hypertensive and 17 diabetics. The data analysis was conducted using the Spearman’s Rho test, after which we did not observe any significant correlation between endothelin and AI, with a correlation coefficient of 0.065 and a P value of 0.556. However, a significant correlation between D-dimers and AI was observed, with a correlation coefficient of 0.231 and a P value of 0.034; and a significant negative correlation between endothelin and D-dimers was observed, with a correlation coefficient of -0.232 and a P value of 0.033.

By comparing these data with those from other articles, we concluded that endothelin alone is not a good diagnostic marker for atherosclerosis. However, D-dimers can be used as associated markers for atherosclerosis diagnosis. These results directed us towards the process and different initiatic factors of atherosclerosis.
Consistent Differential Effects of Bupropion and Mirtazapine in Major Depression
Authors: Strobl Eric V
Published: December 2024

Background: Patients with major depression exhibit a wide range of responses to antidepressants. Unfortunately, most clinical trials fail to differentiate the effects of treatments on the primary symptoms of major depression, partially because they rely on fixed outcome measures such as total symptom severity scores or remission rates. Methods: We performed a comprehensive analysis of the STAR*D trial with the Supervised Varimax (SV) algorithm incorporating post-model selection inference in order to learn outcome measures that differentiate between antidepressants. We also ran the algorithm on an independent clinical trial called CO-MED. Outcomes: We differentiated bupropion and mirtazapine from multiple other antidepressants in STAR*D with replication in every relevant trial level. We further differentiated bupropion augmentation from mirtazapine augmentation in CO-MED. In particular, bupropion monotherapy had a greater therapeutic effect on hypersomnia than venlafaxine monotherapy in Levels 2 and 2A of STAR*D (n=686, difference = 0.384, p_{FWER} = 0.007). Bupropion augmentation outperformed buspirone augmentation in Level 2, especially in patients with increased weight, increased appetite and fatigue (n=520, difference = -0.322, p_{FWER} = 0.005). In contrast, mirtazapine monotherapy had greater therapeutic effects on insomnia, decreased weight and decreased appetite than nortriptyline monotherapy in Level 3 (n=214, difference = 0.401, p_{FWER} = 0.022). Similarly, venlafaxine with mirtazapine augmentation outperformed tranylcypromine in Level 4, especially in patients with insomnia, decreased weight and decreased appetite (n=102, difference = -0.722, p_{FWER} = 0.004). Finally, escitalopram with bupropion had larger therapeutic effects on increased weight, increased appetite and fatigue in CO-MED, while venlafaxine with mirtazapine had larger therapeutic effects on decreased weight, decreased appetite and insomnia (n=640, difference = -0.302, p_{FWER} = 0.022). Interpretation: Bupropion monotherapy and augmentation are effective specifically when a patient suffers from hypersomnia, increased weight, increased appetite or fatigue. Mirtazapine monotherapy and augmentation are effective in the opposite scenario, when a patient suffers from insomnia, decreased weight or decreased appetite.
Early pregnancy health behaviors, hypertensive disorders of pregnancy, and maternal blood pressure after pregnancy
Authors: Kozai Andrea C , Levine Lisa D , Lane Abbi D , Grobman William , Greenland Philip , Hoffman Matthew K , Zee Phyllis C , Mims Lisa , Cameron Natalie A , Saade George , Silver Robert M , Miller Eliza C , Reddy Uma M , Whitaker Kara M
Published: December 2024

Background

Individual health behaviors are associated with pregnancy outcomes, but their joint effects are rarely considered. We aimed to examine associations between combinations of first trimester health behaviors and hypertensive disorders of pregnancy (HDP), normotensive adverse pregnancy outcomes (APOs), and blood pressure (BP) 2-7 years after delivery.

Methods

Participants in the nuMoM2b and follow-up Heart Health Study were included. Physical activity, diet, smoking, and sleep duration were scored using the Life’s Essential 8 metric. APOs were categorized as HDP (gestational hypertension, preeclampsia, super-imposed preeclampsia, or eclampsia) or normotensive APOs: preterm birth, gestational diabetes, small-for-gestational-age birth, and/or stillbirth. Latent profiles of health behaviors were constructed with structural equation modelling. Differences in risk of HDP, normotensive APOs, and BP 2-7 years after delivery based on behavioral profiles were assessed with multinomial logistic or linear regression. Mediation analysis examined the proportion of associations between behavioral profiles and BP mediated by APOs.

Results

Among 8,508 nulliparas, four behavioral profiles were identified: Healthiest Behaviors (37%), Healthy Activity/Sleep with Poor Diet/Smoking (20%), Healthy Sleep Only (32%), and Least Healthy Behaviors (11%). Adjusted risk of HDP and normotensive APOs was 21-41% higher in those with poorer behavioral patterns compared to the Healthiest Behaviors profile. Diastolic BP was 1.04 mmHg higher2-7 years after delivery in the Healthy Sleep Only profile compared to the Healthiest Behaviors profile. Associations between behavioral profiles and BP were not significantly mediated by APOs.

Conclusions

Combined health behavior profiles in early pregnancy were associated with APOs and higher diastolic BP 2-7 years after delivery.
Inter-laboratory comparison of HbA1c can effectively improve test consistency of primary medical institutions
Authors: Liping Pan , Jun Yang , Kun Luo , Hao Yun , Shen Wei , Jin Tan , Ming Lin
Published: December 2024

Background

Glycated hemoglobin (HbA1c) represents a diagnostic index and an important long-term measure for monitoring Diabetes mellitus (DM). In this study, we investigated the quality of HBA1c test in primary medical institutions, and conducted a comparison project of HBA1c test for two years, analyzed and evaluated the test consistency of HBA1c.

Methods

A cohort study was conducted by Wuhan Center for Clinical Laboratory, involving 51 primary medical institutions and 29 tier-three hospitals. Fresh frozen blood samples were prepared by a clinical laboratory certificated by the National Glycohemoglobin Standardization Program (NGSP), and distributed to 80 participating institutions every three months. Microsoft Excel 2021 software was employed to analyze the mean, standard deviation and coefficient of variation of the test results.

Results

Results showed that 60.8% HBA1c test results cannot reach the quality requirements of HbA1c measurement (CV<3.5%) in primary medical institutions. After executing the project, the laboratory pass rate of HBA1c test increased from 39.2% to 64.6%, and the maximum coefficient of variation (CV) within the immunological assays of HBA1c test dropped from 18.0% to 11.4%.

Conclusions

Inter-laboratory comparison of HbA1c can effectively improve test consistency of primary medical institutions. The finding has implications for diabetes management strategies, emphasizing the importance of continuous comparison of HBA1c test in primary medical institutions, providing a practical example to accelerate the mutual recognition of medical test results in a wider range.
Sex Disparities in Cognitive Impairment Research: A Scoping Review in Informatics Literature
Authors: Garg Muskan , Liu Xingyi , Lin Jie , Vassilaki Maria , Petersen Ronald C , St Sauver Jennifer , Kapoor Ekta , Sohn Sunghwan
Published: December 2024

Rationale

A scoping review was conducted to investigate knowledge gaps in the informatics research literature regarding sex differences in cognitive decline, identifying existing studies and areas where further studies are needed.

Materials and Methods

We searched Ovid and other databases for studies on sex differences and cognitive decline, focusing on publications in peer-reviewed informatics journals and conference proceedings from 2000 to 2023. The selected manuscripts were analyzed and summarized through discussion among three reviewers.

Results

A total of 13 articles were selected and examined for metadata and attributes analysis. Most studies are conducted in United States (n=5) and European Union (n=4), about a half are published after 2020 (n=6), and most studies are published in Springer and Elsevier. Our attributes-based analysis highlights the different aspects of reported studies such as task, method, dataset and its size, and sex-specific inferences.

Discussion

Sex-specific disparities in cognitive decline remain a critical issue in healthcare, yet most informatics research has primarily concentrated on identifying basic sex differences, such as tracking the progression of cognitive decline in men and women. While these studies are valuable, they fall short of addressing the more complex underlying causes of these sex-specific disparities in progression of cognitive decline.

Conclusion

There is a significant gap using informatics in understanding how biological, social, and behavioral factors contribute to sex-specific disparities. This limited focus restricts the development of effective intervention strategies for mitigating sex-specific differences in cognitive health outcomes, underscoring the need for more comprehensive research that goes beyond mere identification to find the root cause of these disparities in healthcare.
Integration of Transplanted Interneurons Over a New Period of Ocular Dominance Plasticity in Adult Visual Cortex
Authors: Rakela Benjamin , Sun Jennifer , Marchetta Philine , Alvarez-Buylla Arturo , Hasenstaub Andrea , Stryker Michael
Published: December 2024

Cortical interneurons play an important role in mediating the juvenile critical period for ocular dominance plasticity in the mouse primary visual cortex. Previously, we showed that transplantation of cortical interneurons derived from the medial ganglionic eminence (MGE) opens a robust period of ocular dominance plasticity 33-35 days after transplantation into neonatal host visual cortex. The plasticity can be induced by transplanting either PV or SST MGE-derived cortical interneurons; it requires transplanted interneurons to express the vesicular GABAergic transporter; and it is manifested by changes to the host visual circuit. Here, we show that transplantation of MGE-derived cortical interneurons into the adult host visual cortex also opens a period of ocular dominance plasticity. The transplanted interneurons must be active to induce plasticity, and the neuronal activity and tuning of visually evoked responses in transplanted and host PV and SST interneurons are modulated by the locomotor state of the host. We also show that changes in activity over the period of plasticity induction are different between PV and SST interneurons but similar between host and transplanted interneurons of each type. The present findings demonstrate that the transplant-induced plasticity generated in adult visual cortex has many features in common with the role of these interneurons during the normal, juvenile critical period.
ThermoPlex: An Automated Design Tool for Target-specific Multiplex PCR Primers based on DNA Thermodynamics
Authors: Agmata Altair , Labrador Kevin , Palermo Joseph Dominic , Pante Maria Josefa
Published: December 2024

Multiplex PCR-based assays are indispensable platforms for rapid and cost-effective DNA-based multi-target detection. The success of such an assay highly depends on the accurate design of oligonucleotide primers, arguably its most vital component. In this study, the ThermoPlex design tool is introduced, offering an automated design pipeline for target-specific multiplex PCR primers motivated by DNA thermodynamics. From a sequence alignment of all relevant target and non-target sequences, ThermoPlex automatically designs multiplex PCR primer candidates in just a matter of minutes. The software also offers tools for thermodynamic calculations that can either be used apart from the automated primer screening routine or in conjunction with other existing primer design tools, depending on the on the needs of the user. Evidences presented here in this study provide insights on the performance of the software through theoretical and experimental analyses, serving to establish the reliability of its framework.
A new class of penicillin-binding protein inhibitors to address drug-resistantNeisseria gonorrhoeae
Authors: Uehara Tsuyoshi , Zulli Allison L. , Miller Brittany , Avery Lindsay M. , Boyd Steven A. , Chatwin Cassandra L. , Chu Guo-Hua , Drager Anthony S. , Edwards Mitchell , Emeigh Hart Susan G. , Myers Cullen L. , Rongala Gopinath , Stevenson Annie , Uehara Kyoko , Yi Fan , Wang Bibo , Liu Zhenwu , Wang Mingyue , Zhao Zhichao , Zhou Xinming , Zhao Haiyan , Stratton Caleb M. , Bala Sandeepchowdary , Davies Christopher , Tkavc Rok , Jerse Ann E. , Pevear Daniel C. , Burns Christopher J. , Daigle Denis M. , Condon Stephen M.
Published: December 2024

β-Lactams are the most widely used antibiotics for the treatment of bacterial infections because of their proven track record of safety and efficacy. However, susceptibility to β-lactam antibiotics is continually eroded by resistance mechanisms. Emerging multidrug-resistant (MDR)Neisseria gonorrhoeaestrains possessing alteredpenAalleles (encoding PBP2) pose a global health emergency as they threaten the utility of ceftriaxone, the last remaining outpatient antibiotic. Here we disclose a novel benzoxaborinine-based penicillin-binding protein inhibitor series (boro-PBPi) that is envisioned to addresspenA-mediated resistance while offering protection against evolution and expansion of β-lactamases. Optimization of boro-PBPi led to the identification of compound21(VNRX-14079) that exhibits potent antibacterial activity against MDRN. gonorrhoeaeachieved by high affinity binding to the PBP2 target. Boro-PBPi/PBP2 complex structures confirmed covalent interaction of the boron atom with Ser310 and the importance of the β3-β4loop for improved affinity.21elicits bactericidal activity, a low frequency of resistance, a good safety profile, suitable pharmacokinetic properties, and in vivo efficacy in a murine infection model against ceftriaxone-resistantN. gonorrhoeae.21is a promising anti-gonorrhea agent poised for further advancement.
Human precentral gyrus neurons link speech sequences from listening to speaking
Authors: Xu Duo , Chung Jason E. , Silva Alexander B. , Metzger Sean L. , Greicius Quinn R. , Zhang Yizhen , Leonard Matthew K. , Aghi Manish K. , Hervey-Jumper Shawn L. , Chang Edward F.
Published: December 2024

Speech perception and production are interconnected processes, but the underlying neural mechanisms remain unclear. We investigated this relationship by recording large-scale single-neuron activity in the human brain during a delayed sentence repetition task. Contrary to the traditional view that the precentral gyrus is solely responsible for motor execution, we found that neurons there encoded activity across all task phases of listening, delay, initiation, and speaking. Notably, we discovered “mirror” neurons that activated transiently after hearing and before producing specific speech sounds, and “bridge” neurons that maintained activity between the same speech elements during listening and speaking. Population analysis revealed distinct latent components for each task phase and persistent dynamics for specific sentences. Overall, this study provides novel insights into the neuronal basis of speech processing, emphasizing the intricate interplay between perception, production, and verbal working memory.
Inhibition of the extracellular matrix protein fibulin-3 reduces immunosuppressive signaling in tumor stem cells and increases macrophage activation against glioblastoma
Authors: Kundu Somanath , Mitra Soham , Roshini Arivazhagan , Longo John A. , Longo Sharon L. , Venskus Abigail , Babu Harish , Viapiano Mariano S.
Published: December 2024

Glioblastoma tumors remain a formidable challenge for immune-based treatments because of their molecular heterogeneity, poor immunogenicity, and growth in the largely isolated and immunosuppressive neural environment. As the tumor grows, GBM cells change the composition and architecture of the neural extracellular matrix (ECM), affecting the mobility, survival, and function of immune cells such as tumor-associated microglia and infiltrated macrophages (TAMs). We have previously described the unique expression of the ECM protein EFEMP1/fibulin-3 in GBM compared to normal brain and demonstrated that this secreted protein promotes the growth of the GBM stem cell (GSC) population. Here, we describe a novel immunomodulatory role of fibulin-3 and the immuno-boosting effects of targeting this ECM protein. Mice carrying fibulin-3-deficient intracranial tumors showed increased myeloid infiltration and reduced expression of TAM pro-tumoral markers (Arginase, CD206) compared to controls. The opposite was observed in orthotopic tumors overexpressing fibulin-3.In silicodataset analysis of clinical datasets revealed positive correlation of fibulin-3 with an immunosuppressive signature, which was validated in GSCs andin vivo. We further demonstrated that fibulin-3 regulates the expression of immunosuppressive signals (CSF-1, TGFβ) and the innate immune checkpoint CD47 in GSCs via autocrine activation of NF-κB signaling. Accordingly, immunosuppressive signals were downregulated in GSCs by knockdown of fibulin-3 or inhibition of this protein with an anti-fibulin-3 antibody. Co-culture of GBM cells with syngeneic macrophage lines or primary macrophages in presence of anti-fibulin-3 antibody increased macrophage phagocytosis and antibody-dependent killing of the tumor cells, Furthermore, locoregional delivery of anti-fibulin-3 antibody in mice carrying intracranial GBM increased the infiltration of TAMs expressing pro-inflammatory markers, reducing tumor viability. Our findings show that anti-fibulin-3 approaches, which impact the pericellular ECM surrounding tumor cells and TAMs, can diminish immunosuppression in GBM and boost innate immune responses against the tumor.
Expandable, Functional Hepatocytes Derived from Primary Cells Enable Liver Therapeutics
Authors: Mallanna Sunil K. , Karanth Soujanya S. , Marturano Joseph E. , Kudva Abhijith K. , Lehmann Marcus , Morse Julie K. , Jamiel Morgan , Norman Timothy , Wilson Christopher , Munarin Fabiola , Broderick David , Buskirk Maxwell Van , Uddin Esha , Ret Michael , Steele Christopher , Cheema Mehar , Black Justin , Vanderploeg Eric , Chen Christopher , Bhatia Sangeeta , Rezania Alireza , Lowery Thomas J. , Cazanave Sophie , Chhabra Arnav
Published: December 2024

Liver disease affects millions annually in the United States, with orthotopic transplantation as the only curative option for many patients. However, the scarcity of donor organs highlights a need for alternative cell-based therapies. Hepatocyte-based approaches are promising due to the cells’ inherent synthetic, metabolic, and detoxifying functions, but they face critical barriers, including the lack of a scalable source of functional hepatocytes and poor engraftment. In this study, we developed a scalable process for expanding primary human hepatocytes (PHHs) while preserving their identity and function. By leveraging heterocellular aggregation with stromal cells, we generated cryopreserved “seed” constructs that maintained viability and function post-thaw. Seeds demonstrated enhanced metabolic and detoxification functions and robust engraftment across multiple anatomic sites outside of the liver. Our approach addresses key limitations of hepatocyte-based therapies, offering a stable, scalable, and clinically viable platform for liver cell therapy applications.
Biofilm formation on glycated collagen modulatesStreptococcus mutansbacterial extracellular vesicle production and cargo
Authors: Leiva-Sabadini Camila , Berríos Pablo , Saavedra Paula , Carrasco-Rojas Javiera , González-Aramundiz José Vicente , Vera Mario , Tarifeño-Saldivia Estefanía , Schuh Christina MAP , Aguayo Sebastian
Published: December 2024

Streptococcus mutansis the major microbial etiological agent of dental caries and can adhere to surfaces such as type-I collagen, present in dentin and periodontal tissues. Recent studies have characterized planktonicS. mutansbacterial extracellular vesicles (bEVs) and demonstrated environmental-induced changes due to sugar presence or pH alterations. However, to date there are no studies exploring if surface-derived changes - such as tissue glycation - can modulate bEV production in the context of oral biofilm formation in the elderly. Therefore, the aim of this work was to determine the role of biofilm formation and collagen glycation on the morphology and composition ofS. mutansbEVs. For this, bEVs fromS. mutansbiofilms on native and glycated collagen surfaces were isolated, characterized, and compared to bEVs from planktonic cells. Nanoparticle tracking analysis and microscopy confirmed bEV production and showed that bEVs from biofilms are smaller in size and less abundant than those from planktonic cells. Furthermore, proteome analysis revealed thatS. mutansbiofilm formation on native and glycated collagen led to the enrichment of several key virulence proteins such as Eno, LuxS, Tpx, and ScrB. Also, a shift towards proteins involved in metabolic processes was found in bEVs following biofilm formation on collagen surfaces, whereas glucan metabolism proteins were overexpressed in vesicles from the planktonic state. These results demonstrate that biofilm formation, as well as the glycation of collagen associated with aging and hyperglycemia, can modulate bEV characteristics and cargo and could play a central role inS. mutansvirulence and the development of diseases such as dental caries and periodontal disease.