bluuebunny/crossref_metadata_2025 huggingface dataset:
ProcCluster® and procaine hydrochloride inhibit the growth of Aspergillus species and exert antimicrobial properties during coinfection with influenza A viruses and A. fumigatus in vitro
Authors: König Sarah , Schroeder Josefine , Heinekamp Thorsten , Brakhage Axel A. , Löffler Bettina , Engert Beatrice , Ehrhardt Christina
Published: October 2024

Introduction

Influenza-associated pulmonary aspergillosis is associated with high mortality rates and limited treatment options. The current standard practice involves treating each pathogen separately. However, the use of antifungal drugs can lead to serious side effects, and the presence of triazole-resistant Aspergillus strains can complicate antifungal therapy. In addition, drug-resistant influenza viruses are becoming an increasing concern in clinics. A drug that affects fungal and viral propagation could overcome these disadvantages. Thus, we conducted a study to examine the antifungal and antiviral properties of ProcCluster® and procaine hydrochloride (HCl), which are prodrugs derived from the local anesthetic procaine.

Methods

Conidia of different A. fumigatus strains, A. flavus and A. terreus were treated with the test substances in a human cell-free system and antifungal properties were analyzed either by fluorescence microscopy or absorption measurements. Changes in metabolic activity and intracellular Ca2+ distribution during treatment of A. fumigatus with ProcCluster® were observed using fluorescence microscopy. In addition, antifungal and antiviral properties of ProcCluster® and procaine HCl were investigated during in vitro coinfection of lung epithelial cells with A. fumigatus and influenza A viruses (IAV). Analysis was performed by fluorescence microscopy, standard plaque assay and Western blot assay.

Results

Both substances inhibited the growth of the fungus, even when applied after germination or in the presence of purified IAV particles. ProcCluster® remained effective against triazole-resistant A. fumigatus strains. However, the addition of CaCl2 reversed the antifungal effect, indicating that ProcCluster® inhibited fungal growth by disrupting fungal Ca2+ homeostasis. Furthermore, in vitro studies showed that ProcCluster® and procaine HCl reduced the pathogen load of IAV and A. fumigatus during coinfection. Finally, the combination of ProcCluster® with the antiviral drug favipiravir exhibited increased antipathogenic activity, particularly against IAV replication.

Discussion

This research highlights ProcCluster® and procaine HCl as substances with anti-infective properties against various pathogens.
PMCNA_RS00975 activates NF-κB and ERK1/2 through TLR2 and contributes to the virulence of Pasteurella multocida
Authors: Xu Tenglin , Kou Mingxing , Cao Peili , Liu Benjin , Zheng Yating , Jiang Qian , Liu Jiasen , Kang Hongtao , Yang Mingfa , Guo Dongchun , Qu Liandong
Published: October 2024

Introduction

Pasteurella multocida is a pathogenic bacterium known to cause hemorrhagic septicemia and pneumonia in poultry. Reports have indicated that certain proteins, either directly involved in or regulating iron metabolism, are important virulence factors of P. multocida. Therefore, understanding virulent factors and analyzing the role of pro-inflammatory cytokines can help us elucidate the underlying pathogenesis.

Methods

In this study, the PMCNA_RS00975 protein, a putative encapsuling protein encoded by a gene from a specific prophage island of the pathogenic strain C48-1 of P. multocida, was investigated. To further explore the impact of the PMCNA_RS00975 protein on pathogenicity, a PMCNA_RS00975 gene mutant of P. multocida strain C48-1 was constructed using positive selection technology. Subcellular localization was performed to determine the location of the PMCNA_RS00975 protein within P. multocida. The recombinant protein PMCNA_RS00975 of P. multocida was soluble expressed, purified, and its role in pro-inflammatory cytokines was investigated.

Results

The mutant exhibited significantly reduced pathogenicity in the mice model. Furthermore, subcellular localization indicated that the PMCNA_RS00975 protein was located at the outer membrane and expressed during infection of P. multocida. Additionally, our experiments revealed that recombinant PMCNA_RS00975 protein promotes the secretion of the IL-6 pro-inflammatory cytokines triggered by the TLR2 receptor via NF-κB and ERK1/2 signaling pathways in the macrophages.

Discussion

This study identified a novel virulence factor in the C48-1 strain, providing a basis for understanding the pathogenesis and directions for the development of attenuated vaccines against P. multocida.
Investigating the causal relationship between human blood metabolites and pulmonary hypertension: a two-sample Mendelian randomization study
Authors: Zeng Xingdu , Zhong Bin
Published: October 2024

Background

Several recent investigations have posited that distinct metabolites in the bloodstream may be correlated with the pathogenesis of Pulmonary Hypertension (PH). Nonetheless, the interrelationship between the pathogenesis of PH and metabolite fluctuations remains incompletely elucidated, and findings may differ across studies.

Methods

In the extant research, data from 486 metabolite-and PH-related genetic variants in human subjects were procured based on Genome-Wide Association Studies (GWAS) and Finnish databases. Univariate Mendelian Randomization analyses were deployed to evaluate the causal relationships between them. The utilization of the randomized Inverse Variance weighted(IVW) method served as the primary analytic framework in this Mendelian Randomization (MR) study. Additionally, four alternative computational strategies, encompassing MR-Egger, were employed as auxiliary methods. A myriad of tests, including Cochran's Q Test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis, and linkage disequilibrium score were incorporated to assess the robustness of the study outcomes. Metabolite pathway analysis was also executed to identify potential metabolic pathways.

Results

After a series of validations and corrected for False discovery rate (FDR), we found a significant association between 1,5-anhydroglucitol (OR = 2.00, 95% CI: 1.39–2.89, P = 0.0002) and PH, and a significant association between pyridoxalate (OR = 0.59, 95% CI: 0.43–0.81, P = 0.0009) and 1-a achidonoylglycerophosphocholine (OR = 1.78, 95% CI: 1.22–2.58, P = 0.0026) had a suggested association with PH. In addition, the vitamin B6 metabolic pathway was also determined to be associated with PH.

Conclusion

Conclusively, we isolated 1,5-anhydroglucitol, 1-arachidonoylglycerophosphocholine, and pyridoxate as causally implicated in PH, thereby proffering substantial theoretical substantiation for the formulation of future PH prevention and screening paradigms.
Sex-specific differences in the association between triglyceride glucose index and carotid plaque in a cardiovascular high-risk population: a cross-sectional study based on a Chinese community-dwelling population
Authors: Lin Weiguo , Xu Mengjie , Zheng Jinbiao , Sun Ruixue , Yan Shaorong , Chen Xiaoshu , Lin Yuzhan
Published: October 2024

Background

To date, numerous studies have investigated the relationship between the triglyceride glucose (TyG) index and carotid plaques, but the impact of gender on this relationship has not been explored. Therefore, this study aims to investigate gender-specific differences in the relationship between the TyG index and carotid plaques in a high cardiovascular risk population in China.

Methods

This cross-sectional study's data were derived from a longitudinal pilot study involving 1,085 high-risk cardiovascular subjects. A multivariable logistic regression model was used to analyze the relationship between the TyG index and carotid plaques. A generalized additive model combined with a stratified regression model was employed to assess the nonlinear relationship between the TyG index and carotid plaques across different genders. In the nonlinear relation, the inflection point was calculated by a two-piecewise linear regression model.

Results

After adjusting for confounders such as age, sex, BMI, SBP, DBP, AST/ALT, TC, LDL-c, HDL-c, creatinine, smoking, and antilipemic medication, the generalized additive model results revealed a nonlinear relationship between the TyG index and carotid plaque formation, with significant differences across genders. In males, the relationship between the TyG index and carotid plaques was S-shaped. The two-piecewise linear regression model identified two inflection points: TyG = 8.39 (P = 0.017) and TyG = 10.2 (P = 0.009).

Conclusion

The relationship between the TyG index and the formation of carotid plaques is nonlinear, and there are significant differences in the correlation between males and females.
Case Report: Laboratory detection of a thrombotic tendency in a family with hypodysfibrinogenemia and a novel FGG mutation
Authors: Monard Amaury , Castoldi Elisabetta , De Simone Ilaria , Wichapong Kanin , van Duijl Tirsa , van den Biggelaar Maartje , Spada Stefano , van Doorn William , Hellenbrand Dave , van der Meijden Paola , Swieringa Frauke , Stork Alexander , ten Cate Hugo , Beckers Erik , Heubel-Moenen Floor , Henskens Yvonne
Published: October 2024

Introduction

Hypodysfibrinogenemia is a rare congenital fibrinogen disorder (CFD) which may induce thrombotic and bleeding events. Therefore, patient management needs careful evaluation. Routine coagulation tests are inadequate to predict the clinical phenotype.

Clinical findings

A 60-year-old woman with both bleeding and thrombotic complications and her two daughters were referred to our center for genotypic and phenotypic analysis of a CFD.

Diagnosis

Conventional laboratory results led to the diagnosis of hypodysfibrinogenemia in all three subjects. They all carried the same heterozygous c.1124A>G mutation in FGG resulting in p.Tyr375Cys amino acid substitution, which was confirmed by protein variant analysis from plasma. In silico structure analysis predicted possible conformational and functional changes of the fibrinogen molecule. Thrombin generation indicated a hypercoagulable state confirmed by microfluidics that showed enhanced fibrin formation in both daughters, regardless of the coagulation trigger.

Conclusion

We report on a family with hypodysfibrinogenemia and a novel FGG heterozygous missense mutation, possibly leading to conformational changes or covalent dimerization. Thrombin generation and particularly microfluidic measurements disclosed a hypercoagulable state, which was not detected with routine coagulation tests, justifying a different patient management.
Elevated non-HDL-C to HDL-C ratio as a marker for NAFLD and liver fibrosis risk: a cross-sectional analysis
Authors: Xuan Yanyan , Zhu Minghui , Xu Linzhi , Huangfu Shujiao , Li Tongyu , Liu Chunbo , Zhou Dongdong
Published: October 2024

Background

Dyslipidemia is a known independent risk factor for Nonalcoholic fatty liver disease (NAFLD). However, the relationship between NAFLD and the serum non-high-density lipoprotein cholesterol (non-HDL-C) to high-density lipoprotein cholesterol (HDL-C) ratio remains unclear. This study examined the association between the non-HDL-C to HDL-C ratio and NAFLD prevalence, including liver steatosis and fibrosis levels in the population.

Methods

We conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) 2017–2018, including 4798 participants. Liver ultrasound and Transient Elastography (TE) were used to assess fibrosis and steatosis. Adjusted multivariable regression analyses, subgroup analyses based on BMI and sex, and a generalized additive model were employed to investigate the relationship between the non-HDL-C/HDL-C ratio and NAFLD.

Results

Among the 4798 participants, 39.27% (n = 1,884) had NAFLD. Significant positive correlations between non-HDL-C/HDL-C and NAFLD risk were found across all models, with sex-stratified analyses indicating higher risk in men. Liver fibrosis was also associated with non-HDL-C/HDL-C ratios. The Receiver operating characteristic (ROC) analysis shows non-HDL-C/HDL-C as a better predictor for NAFLD than non-HDL-C or HDL-C alone.

Conclusion

Elevated non-HDL-C/HDL-C levels are independently associated with increased NAFLD and liver fibrosis risk in the American population, suggesting its utility in predicting NAFLD and related liver fibrosis.
Environmental life-cycle analysis of hydrogen technology pathways in the United States
Authors: Elgowainy Amgad , Vyawahare Pradeep , Ng Clarence , Frank Edward D. , Bafana Adarsh , Burnham Andrew , Sun Pingping , Cai Hao , Lee Uisung , Reddi Krishna , Wang Michael
Published: October 2024

Hydrogen is a zero-carbon energy carrier with potential to decarbonize industrial and transportation sectors, but its life-cycle greenhouse gas (GHG) emissions depend on its energy supply chain and carbon management measures (e.g., carbon capture and storage). Global support for clean hydrogen production and use has recently intensified. In the United States, Congress passed several laws that incentivize the production and use of renewable and low-carbon hydrogen, such as the Bipartisan Infrastructure Law (BIL) in 2021 and the Inflation Reduction Act (IRA) in 2022, which provides tax credits of up to $3/kg depending on the carbon intensity of the produced hydrogen. A comprehensive life-cycle accounting of GHG emissions associated with hydrogen production is needed to determine the carbon intensity of hydrogen throughout its value chain. In the United States, Argonne’s R&D GREET® (Greenhouse Gases, Regulated emissions, and Energy use in Technologies) model has been widely used for hydrogen carbon intensity calculations. This paper describes the major hydrogen technology pathways considered in the United States and provides data sources and carbon intensity results for each of the hydrogen production and delivery pathways using consistent system boundaries and most recent technology performance and supply chain data.
The historical evolution and social transformation of settlements in the mountainous regions of western Guangdong: a case study of Xinyi County, China
Authors: Wang Jin , Han Jiarui
Published: October 2024

The formation of China’s territory has a long historical process. Prior research has highlighted the diverse historical development patterns across different regions. To delve deeper into the distinctiveness among regions and their nuanced disparities, the research centers on the settlements within Xinyi County, situated in the mountainous terrain of western Guangdong Province, China. The current study employs the research method of “Backward Observation” by conducting a literature review and utilizing ArcGIS for spatial analysis to investigate the spatial distribution and evolution process of regional settlements in western Guangdong. The results suggest a predominant involvement of the state in propelling the advancement of the indigenous community within Xinyi County, a progression primarily fulfilled by the conclusion of the late Qing and initial Republican eras, guided by the persistent localization and gentrification of migrating populations. Xinyi’s advancement pattern and speed exhibited notable distinctions from neighboring areas within Guangdong Province. This investigation additionally delves into G. William Skinner’s inquiries regarding the exceptional attributes and evolutionary patterns of localities, aligning with the South China School’s viewpoint on the varied nature of regional advancement procedures and cadences. This research on Xinyi’s historical evolution is importance in coordinating the preservation and advancement of historical towns, addressing urban-rural development disparities, and formulating future development strategies.
Single-cell and spatial transcriptome characterize coinhibitory cell-cell communications during histological progression of lung adenocarcinoma
Authors: Luo Judong , Gao Qianman , Wang Meihua , Liu Hui , Zhu Hong
Published: October 2024

Introduction

Lung adenocarcinoma, a prevalent and lethal malignancy globally, is characterized by significant tumor heterogeneity and a complex tumor immune microenvironment during its histologic pattern progression. Understanding the intricate interplay between tumor and immune cells is of paramount importance as it could potentially pave the way for the development of effective therapeutic strategies for lung adenocarcinoma.

Methods

In this study, we run comparative analysis of the single-cell transcriptomic data derived from tumor tissues exhibiting four distinct histologic patterns, lepidic, papillary, acinar and solid, in lung adenocarcinoma. Furthermore, we conducted immunofluorescence assay and spatial transcriptomic sequencing to validated the spatial co-localization of typical co-inhibitory factors.

Results and Discussion

Our analysis unveiled several co-inhibitory receptor-ligand interactions, including PD1-PDL1, PVR-TIGIT and TIGIT-NECTIN2, that potentially exert a pivotal role in recruiting immunosuppressive cells such as M2 macrophages and Tregs into LUAD tumor, thereby establishing immunosuppressive microenvironment and inducing T cells to exhaustion state. Furthermore, The expression level of these co-inhibitory factors, such as NECTIN2 and PVR, were strongly correlated with low immune infiltration, unfavorable patient clinical outcomes and limited efficacy of immunotherapy. We believe this study provides valuable insights into the heterogeneity of molecular, cellular interactions leading to immunosuppressive microenvironment during the histological progression of lung adenocarcinoma. The findings could facilitate the development of novel immunotherapy for lung cancer.
Regulation of BCR-dependent germinal center B-cell formation by HGAL and insight into its emerging myeloid ortholog, C1ORF150
Authors: Toran Paul , Novelli Anthony , Lazor Jennifer , Vachon Alexandra , Wojchowski Don M.
Published: October 2024

The specificity of cytokine and immunoreceptor signaling frequently depends upon receptor recruitment of select adaptor proteins and specifically engaged effectors. This review focuses on the orthologous adaptor proteins, HGAL and C1ORF150, and aims to provide insight into their respective modulation of lymphoid and myeloid cell signaling, formation, and function. HGAL acts predominantly within germinal center B cells as an important BCR signal transducer. Effects on BCR signalosome assembly involve HGAL’s localization to the plasma membrane via its lipidation, initial interactions with SYK, the pY-phosphorylation of HGAL including its recruitment of GRB2, and HGAL engagement of PDZ-RhoGEF and RhoA signaling. At ligated BCRs, this includes HGAL(−GRB2) stimulation of SYK kinase, attenuation of calcium flux-dependent and NF-κB expression, promotion of cSMAC formation, and cytoskeletal remodeling associated with HGAL-attenuated cell migration. HGAL and partnered effectors also impact on DLBCL pathogenesis, and studies are summarized on HGAL’s actions (using DLBCL and Burkitt lymphoma B cells) including cell migration effects, HGAL modulation of cytoskeletal components, and insightful HGAL transgenic mouse and xenograft models. For C1ORF150, its HGAL-homologous subdomains are considered, together with studies that demonstrate C1OR150’s FcϵRI- and KIT-mediated expression and phosphorylation in primary human mast cells. Intriguingly, recent GWAS studies have identified a C1ORF150 in-frame splice variant that is strongly associated with urticaria. Candidate mechanisms via which the encoded “C1ORF150-Δexon2” isoform affects mast cell degranulation are considered, including FcϵR1 and/or KIT receptor connections, and candidate “myristoylation switch” mechanisms.
A framework for reconstructing marine heatwaves from individual foraminifera in sedimentary archives
Authors: Saenger Casey , Jimenez-Diaz Carlos , Gagnon Alexander , Mix Alan , Ross Andrew , Xu Tongtong
Published: October 2024

Marine heatwaves (MHWs) are warm sea surface temperature (SST) anomalies with substantial ecological and economic consequences. Observations of MHWs are based on relatively short instrumental records, which limit the ability to forecast these events on decadal and longer timescales. Paleoclimate reconstructions can extend the observational record and help to evaluate model performance under near future conditions, but paleo-MHW reconstructions have received little attention, primarily because marine sediments lack the temporal resolution to record short-lived events. Individual foraminifera analysis (IFA) of paleotemperature proxies presents an intriguing opportunity to reconstruct past MHW variability if strong relationships exist between SST distributions and MHW metrics. Here, we describe a method to test this idea by systematically evaluating relationships between MHW metrics and SST distributions that mimic IFA data using a 2000-member linear inverse model (LIM) ensemble. Our approach is adaptable and allows users to define MHWs based on multiple duration and intensity thresholds and to model seasonal biases in five different foraminifera species. It also allows uncertainty in MHW reconstructions to be calculated for a given number of IFA measurements. An example application of our method at 12 north Pacific locations suggests that the cumulative intensity of short-duration, low-intensity MHWs is the strongest target for reconstruction, but that the error on reconstructions will rely heavily on sedimentation rate and the number of foraminifera analyzed. This is evident when a robust transfer function is applied to new core-top oxygen isotope data from 37 individual Globigerina bulloides at a site with typical marine sedimentation rates. In this example application, paleo-MHW reconstructions have large uncertainties that hamper comparisons to observational data. However, additional tests demonstrate that our approach has considerable potential to reconstruct past MHW variability at high sedimentation rate sites where hundreds of foraminifera can be analyzed.
Marine protected areas as socio-economic systems: a method for defining socio-economic criteria in marine planning
Authors: Pegorelli Camila , De Andres Maria , García-Onetti Javier , Rayo Silvia , García-Sanabria Javier
Published: October 2024

This research aims to define socio-economic criteria for prioritizing proposals related to new marine protected areas, boundary adjustments, area relocations, and network corridors within marine management approaches. The study also focuses on identifying ecosystem services (ES) that address the social dimensions of various spatial management approaches in the marine realm. The presented method quantifies nature’s significance to human communities through stakeholder perceptions, bridging the gap between human activities and ecosystem services. The research defines essential socio-economic criteria, identifies the corresponding ecosystem services, and assesses their societal values within the socio-ecological system of a specific area, thereby enhancing the effectiveness of marine management processes such as marine spatial planning and marine protected areas.
Pandemic-induced healthcare shifts: an observational analysis of maternal and neonatal outcomes in adolescent pregnancies
Authors: Grobeisen-Duque Orly , Villavicencio-Carrisoza Oscar , Mora-Vargas Carlos Daniel , Arteaga-Lopez Carolina Penelope , Martinez-Salazar Maria Guadalupe , Rosas-Balan Alejandro , Leon-Juarez Moises , Flores-Herrera Hector , Zaga-Clavellina Veronica , Aguilera-Arreola Ma Guadalupe , Helguera-Repetto Addy Cecilia
Published: October 2024

Introduction

The COVID-19 pandemic caused widespread changes in healthcare delivery, particularly affecting vulnerable populations such as pregnant adolescents. These patients faced additional challenges, including developmental and gestational changes, stress from isolation, and altered healthcare access, which may have impacted the incidence and prevalence of maternal and neonatal complications. This study aims to compare maternal and neonatal outcomes in adolescent pregnancies before and during the pandemic, focusing on how shifts in healthcare delivery influenced these outcomes.

Methodology

A retrospective cohort study was conducted, including 340 adolescent pregnant patients who received prenatal care at a tertiary care institution. Patients were divided into two groups: pre-pandemic (n = 209) and pandemic (n = 131). Maternal data, including pre-BMI and gestational weight gain (GWG), were collected to evaluate maternal and neonatal outcomes. Statistical analysis was performed using chi-square tests, Fisher’s exact tests, and odds ratio (OR) calculations.

Results

The pandemic group showed a statistically significant increase in cesarean deliveries (p = 0.002; OR = 1.99) and cervicovaginitis, particularly caused by Ureaplasma spp. Conversely, the pre-pandemic group had higher rates of psychoactive substance use, maternal urinary tract infections, and neonatal transient tachypnea. In the pandemic group, overweight pre-gestational BMI and cervicovaginitis were more prevalent in patients with adequate GWG, while inadequate GWG was associated with an increased risk of urinary tract infection (UTI). A significant association between pre-gestational overweight/obesity and excessive GWG was also observed (p < 0.05).

Conclusion

The COVID-19 pandemic altered both healthcare delivery and maternal and neonatal outcomes in adolescent pregnancies. Changes in healthcare access, isolation, and shifts in medical management during the pandemic resulted in higher cesarean rates and infection rates among pregnant adolescents. These findings underscore the need for adaptable, resilient healthcare systems capable of maintaining comprehensive care even in the face of global crises. Further studies are needed to explore long-term effects on adolescent maternal and neonatal health.
Quantifying measurement uncertainty in renal transplant biopsy assessment
Authors: Loizeau Xavier , Romanchikova Marina , Thomas Spencer A. , Alsuleman Moulham , Ayorinde John O. O. , Pettigrew Gavin J.
Published: October 2024

Introduction

Renal transplant biopsies provide insights into graft health and support decision making. The current evidence on links between biopsy scores and transplant outcomes suggests there may be numerous factors affecting biopsy scores. Here we adopt measurement science approach to investigate the sources of uncertainty in biopsy assessment and suggest techniques to improve its robustness.

Methods

Histological assessments, Remuzzi scores, biopsy processing and clinical variables are obtained from 144 repeat biopsies originating from 16 deceased-donor kidneys. We conducted sensitivity analysis to find the morphometric features with highest discriminating power and studied the dependencies of these features on biopsy and stain type. The analysis results formed a basis for recommendations on reducing the assessment variability.

Results

Most morphometric variables are influenced by the biopsy and stain types. The variables with the highest discriminatory power are sclerotic glomeruli counts, healthy glomeruli counts per unit area, percentages of interstitial fibrosis and tubular atrophy as well as diameter and lumen of the worst artery. A revised glomeruli adequacy score is proposed to improve the robustness of the glomeruli statistics, whereby a minimum of 104 µm2 of cortex tissue is recommended to keep type 1 and type 2 error probabilities below 0.15 and 0.2.

Discussion

The findings are transferable to several biopsy scoring systems. We hope that this work will help practitioners to understand the sources of statistical uncertainty and improve the utility of renal biopsy.
Insights into the UO2+x/U4O9 phase characterization in oxidized UO2 pellets as a function of hyper-stoichiometry
Authors: Gaillard C. , Lotz H. , Sarrasin L. , Pipon Y. , Ducher R. , Moncoffre N.
Published: October 2024

We present new insights into the study of the UO2+x/U4O9 equilibrium in UO2 as a function of the hyper-stoichiometry (x) by coupling HERFD-XANES at the uranium M4-edge with micro-Raman spectroscopy mapping. XANES allowed the measurement of uranium speciation in the samples, while Raman spectroscopy was used to individually characterize the composition and localization of the different oxide phases. UO2 pellets were oxidized under dry conditions at temperatures above the UO2+x/U4O9 phase transition to reach hyper-stoichiometries in the range of 0.01 ≤ x ≤ 0.1. Combining both techniques, we could determine the proportions of U4O9 and UO2+x. We show that at a low O/U ratio, U4O9 is present as small clusters inside UO2 grains. As the O/U increases, we found evidence of the formation of a network of U4O9 crystallized inside the UO2+x grains. The variation of the UO2+x phase hyper-stoichiometry (x) was evaluated as a function of the sample oxidation.
Global burden of anemia and cause among children under five years 1990–2019: findings from the global burden of disease study 2019
Authors: Liu Yujuan , Ren Weifang , Wang Shuying , Xiang Minmin , Zhang Shunxian , Zhang Feng
Published: October 2024

Background

Anemia represents a significant global health issue affecting numerous children and women, characterized by diminished hemoglobin levels that may impede cognitive and developmental progress. Although commonly attributed to iron deficiency, the etiology of anemia in this demographic is multifaceted, encompassing nutritional, genetic, and infectious contributors. Nonetheless, there is a lack of high-quality data on anemia prevalence and causes analysis among children under 5 years. The aim of this study was to provide a comprehensive global assessment of the burden of anemia and its causes among children under 5 years, using data from the Global Burden of Disease Study 2019.

Methods

This investigation utilized data from the Global Burden of Disease Study (GBD) 2019 to assess the prevalence and years lived with disability (YLD) attributable to anemia in children under five from 1990 to 2019. Analyses were conducted to delineate age-specific YLD, prevalence rates, and etiological factors, with stratification by gender and Socio-Demographic Index (SDI).

Results

In 2019, anemia imposed a substantial global burden on children under five, with a reported YLD of 1,252.88 (95% UI: 831.62–1,831.34) per 100,000 population. The prevalence of moderate anemia was highest at 985.46 (95% UI: 646.24–1,450.49) per 100,000, surpassing both severe anemia at 197.82 (95% UI: 132.53–277.80) per 100,000 and mild anemia at 69.59 (95% UI: 24.62–152.53) per 100,000. Globally, the total prevalence was 39,517.75 (95% UI: 38,784.81 - 40,239.62) cases per 100,000 population. Notably, disparities were evident between genders, with males demonstrating higher YLD and prevalence rates than females. Iron deficiency emerged as the leading cause globally, with significant contributions from hemoglobinopathies and other nutritional deficiencies. Regions with a low Socio-Demographic Index, particularly sub-Saharan Africa and South Asia, exhibited the most pronounced burdens. Despite a declining trend over three decades, persistent regional and gender-based disparities highlight the necessity for continuous and focused public health interventions.

Conclusion

The burden of anemia among children under five continues to be considerable, marked by stark regional and socioeconomic disparities. These findings underscore the urgent need for advanced nutritional and healthcare strategies tailored to alleviate anemia in this vulnerable population, with a particular emphasis on regions exhibiting low SDIs. The sustained prevalence of high anemia rates in these areas underscores the imperative for persistent, localized intervention efforts.
Current situation of neuropathology in Central America
Authors: Delgado Mónica Núñez
Published: October 2024

The present situation of neuropathology practice in the Central American region has not been addressed in the past. These are low middle-income countries, and therefore, many do not have a basic immunohistochemistry panel. Cytogenetics and molecular studies are not available in most of Central America. Pediatric brain tumors are diagnosed either by anatomical pathologists or by pediatric pathologists. Access to a weakly Latin American Tumor Board is available to consult cases, but most countries do not participate in these expert meetings. The most recent World Health Organization brain tumor book has a very broad molecular classification of pediatric brain tumors. All these factors make it very difficult to properly diagnose pediatric brain tumors in the region, and this impacts the treatment and overall survival of children with brain tumors.
Case Report: A case study and literature review on teeth discoloration caused by linezolid with the shortest incubation period in a pediatric patient
Authors: Le-le Sun , Qun Zhao , Lei Qi , Xiangwei Meng , Jigang Si
Published: October 2024

Background

When it comes to the adverse reactions of linezolid, people always call to mind primarily nausea, vomiting, bone marrow suppression, and so on. Few people are aware of the rare adverse reaction of teeth discoloration.

Case presentation

We describe the case of a child affected by bacterial meningitis. After admission, a combination of ceftriaxone and linezolid was administered for anti-infection, and dexamethasone was used to inhibit inflammatory reactions. On the 5th day of treatment with linezolid, the child's teeth appeared brownish color and could not be removed with normal oral hygiene. Upon reviewing the drug instructions and literature, it was found that the discoloration of teeth is a rare adverse reaction of linezolid, which is pseudo discoloration. After stopping the medication for 28 days or up to 5 months, the normal color can be restored. There is no significant impact on the life of the patient, therefore, continue to use linezolid to complete the anti-infection course.

Results

After 14 days of anti-infection treatment, the inflammatory indicators of the child decreased to normal, and the condition was close to recovery before discharge. After stopping the medication for 28 days, the color of the teeth returned to normal.

Conclusions

This rare adverse reaction sheds light on a previously unreported side effect of this widely used antibiotic. In our case, the discoloration of the teeth occurred earlier, updating the latent period of the adverse reaction.
Naringenin modulates oxidative stress and lipid metabolism: Insights from network pharmacology, mendelian randomization, and molecular docking
Authors: Gao Jian , Yuan Linjie , Jiang Huanyu , Li Ganggang , Zhang Yuwei , Zhou Ruijun , Xian Wenjia , Zou Yutong , Du Quanyu , Zhou Xianhua
Published: October 2024

Background

Previous studies have demonstrated that naringenin possesses lipid-lowering effects; however, the underlying mechanisms, particularly its specific molecular targets, remain uncertain.

Methods

Using bioinformatics, three traditional Chinese medicine databases and one human disease database were integrated to establish two naringenin-target-hyperlipidemia modules: naringenin-oxidative stress (OS) and naringenin-lipid metabolism (LM). Data on 1,850 proteins from 1,871 genetic instruments were sourced from seven previous studies. Using Mendelian randomization based on data from the Integrative Epidemiology Unit genome-wide association study (case, n = 5,153; control, n = 344,069), we identified potential drug targets that were subsequently validated in the UK Biobank (396,565 individuals) and FinnGen (412,181 individuals) cohorts. Using molecular docking and molecular dynamics simulation to verify the binding ability of naringenin and causal protein.

Results

In plasma, every standard deviation increase in apolipoprotein B (APOB) was associated with an increased risk of hyperlipidemia (odds ratio [OR] = 9.37, 95% confidence interval [CI], 5.12–17.12; P = 3.58e-13; posterior probability of hypothesis 4 [PPH4] = 0.997), and the same was observed for proprotein convertase subtilisin/kexin type 9 (OR = 1.81, 95% CI, 1.51–2.16; P = 6.87e-11; PPH4 = 1) and neurocan (OR = 2.34, 95% CI, 1.82–3.01; P = 4.09e-11; PPH4 = 0.932). The intersection of two modules and Mendelian randomization result identified APOB as a key regulatory target of naringenin in the treatment of hyperlipidemia. The binding energy between naringenin and APOB was determined to be −7.7 kcal/mol. Additionally, protein-protein interactions and protein-disease networks were analyzed to uncover potential connections between proteins and hyperlipidemia.

Conclusion

This Mendelian randomization-based combined analysis offers a robust framework for elucidating the pharmacological effects of naringenin and identifying candidate proteins for further investigation in the context of hyperlipidemia treatment.
Predictive modeling of biomedical temporal data in healthcare applications: review and future directions
Authors: Patharkar Abhidnya , Cai Fulin , Al-Hindawi Firas , Wu Teresa
Published: October 2024

Predictive modeling of clinical time series data is challenging due to various factors. One such difficulty is the existence of missing values, which leads to irregular data. Another challenge is capturing correlations across multiple dimensions in order to achieve accurate predictions. Additionally, it is essential to take into account the temporal structure, which includes both short-term and long-term recurrent patterns, to gain a comprehensive understanding of disease progression and to make accurate predictions for personalized healthcare. In critical situations, models that can make multi-step ahead predictions are essential for early detection. This review emphasizes the need for forecasting models that can effectively address the aforementioned challenges. The selection of models must also take into account the data-related constraints during the modeling process. Time series models can be divided into statistical, machine learning, and deep learning models. This review concentrates on the main models within these categories, discussing their capability to tackle the mentioned challenges. Furthermore, this paper provides a brief overview of a technique aimed at mitigating the limitations of a specific model to enhance its suitability for clinical prediction. It also explores ensemble forecasting methods designed to merge the strengths of various models while reducing their respective weaknesses, and finally discusses hierarchical models. Apart from the technical details provided in this document, there are certain aspects in predictive modeling research that have arisen as possible obstacles in implementing models using biomedical data. These obstacles are discussed leading to the future prospects of model building with artificial intelligence in healthcare domain.
OsPDIL1-5: dual role in promoting growth and development while modulating drought stress tolerance in rice (Oryza sativa L.)
Authors: Chen Jilin , Zhang Jin , Fang Chao , Ren Lijun , Lan Tong , Wu Weiren , Lan Tao
Published: October 2024

Drought tolerance and plant growth are critical factors affecting rice yield, and identifying genes that can enhance these traits is essential for improving crop resilience and productivity. Using a growth-depressed and drought-tolerant (gddt) mutant of the indica rice variety Huanghuazhan (HHZ) generated by radiation mutagenesis, we discovered a novel gene, GDDT, which plays a dual role in plant biology: it acts as a positive regulator of growth and development, but as a negative regulator of drought resistance. The gddt mutant displayed a marked reduction in plant growth and seed setting rate, yet exhibited an unexpected advantage in terms of drought tolerance. Our research revealed that the enhanced drought tolerance of the gddt mutant is primarily due to a decrease in stomatal size, density, and aperture, which reduces water loss, and an activation of the reactive oxygen species (ROS) scavenging system, which helps protect the plant from oxidative stress. These physiological changes are observed both under drought conditions and in normal growth conditions. This discovery highlights the importance of GDDT as a pleiotropic gene with significant implications for both plant growth and drought resistance. Through map-based cloning, we determined that the protein disulfide isomerase-like (PDIL) gene OsPDIL1-5 is the GDDT gene. The protein encoded by this gene was localized to the endoplasmic reticulum, consistent with its predicted function. Our findings provide new insights into the role of PDIL genes in rice and suggest that further study of GDDT could lead to a better understanding of how these genes contribute to the complex interplay between plant growth, development, and stress responses. This knowledge could pave the way for the development of rice varieties that are more resilient to drought, thereby increasing crop yields and ensuring food security in water-limited environments.
From the lab to the field and back: the effects of need satisfaction on reconciliation among Germans and Israelis
Authors: Pesin-Michael Gali , Ditlmann Ruth K. , Shnabel Nurit
Published: October 2024

Introduction

Previous lab experiments supported the needs-based model of reconciliation, which posits that discussing historical transgressions enhances the need for acceptance in groups perceived as perpetrators and empowerment in groups perceived as victims. Addressing these needs (e.g., through accepting or empowering messages from outgroup members) increases willingness to reconcile. This study tests this model in a real-world settings.

Methods

Study 1 examined 143 German and Israeli Jewish participants from youth exchange programs, measuring their feelings of acceptance/empowerment, program satisfaction, outgroup attitudes, and keeping in touch with outgroup members. Study 2 examined 293 Israeli Jews, manipulating the salience of the conflict between Israelis and Palestinians in a pre-registered laboratory experiment and measuring responses to accepting versus empowering messages from Germans.

Results

As expected, Study 1 (N =143) found Germans’ feelings of acceptance were linked to program satisfaction, positive outgroup attitudes, and keeping in touch. For Israeli Jews, feelings of empowerment were linked to satisfaction and positive attitudes, but keeping in touch was unexpectedly linked to acceptance. This unexpected effect maybe because keeping in touch is done mainly through social networks that focus on the conflict between Israelis and Palestinians, often with a focus on Israel’s transgressions against Palestinians. Consistent with this explanation, Study 2 (N=293, pre-registered) showed that Israeli Jews viewed accepting messages from Germans as more conciliatory when presented with transgressions against Palestinians, and empowering messages as more effective when presented with reminders of historical victimization by Nazis.

Discussion

The findings from Study 1 partially support the needs-based model of reconciliation and additionally suggest that reconciliation needs vary with context. Implications for people-to-people peace-building interventions are discussed.
The impact of the COVID-19 pandemic on nostalgic social media use
Authors: Xiang Peng , Chen Lijuan , Xu Fuming , Du Shasha , Liu Mingxuan , Zhang Yimeng , Tu Jiayu , Yin Xiaoyuan
Published: October 2024

Introduction

Despite popular speculation that nostalgic social media use skyrocketed during the COVID-19 pandemic, this has yet to be formally investigated in the scientific literature.

Methods

Interrupted time series analysis (ITSA) using a segmented regression model was performed to examine the changes in the weekly volume of searches for nostalgic songs on Douyin (the Chinese version of TikTok), as a proxy for nostalgic social media use, before and after the lockdown of Wuhan (signaled the start of the pandemic on a national scale in China).

Results

Across the study period (January 1, 2019–February 28, 2021), an immediate and significant increase in nostalgic social media use was observed when the pandemic initially started (95% CI = [47314.30, 154969.60], p < 0.001) compared with the pre-pandemic baseline.

Discussion

This study provides empirical evidence for the impact of the pandemic on nostalgic social media use. It also advances our understanding of the increased usage of social media during the pandemic. Additionally, as nostalgia has drawn increasing attention from media researchers, this study offers methodological insights into the quantification of nostalgia.
Applying a new theoretical and methodological approach for behavior-change campaign planning: identifying the critical determinants for reducing littering and evaluating the resulting large-scale campaign
Authors: Tobias Robert , Moraz Nicole , Degenhardt Barbara
Published: October 2024

Introduction

This paper presents a theoretical concept and methodological approach for identifying critical determinants for behavior change interventions. The approach is based on established theories and constructs but represents them in an intervention- instead of questionnaire-oriented form. Six discriminant and targetable dimensions of behavior determinants are proposed: Consideration, feasibility, instrumental evaluation, norms and goals, affective evaluation, and needs and tension states.

Methods

For estimating the importance of these dimensions for a specific behavior to be changed in a specific situation and population, a quasi-experimental approach is proposed, in which interventions are designed to have effects on one of these dimensions but none on the other dimensions. By measuring changes of the target behavior or its consequences, the impact of each dimension on changing the behavior can be estimated in-situ without questionnaires. The approach was applied to develop a campaign for reducing picnic littering in an urban park in Zurich (Switzerland). In 2019, posters targeting four dimensions were set up during three waves in up to four zones with two control zones without posters. Before, between, and after the intervention waves, for at least 2 weeks, no interventions were in place. The volume of litter was measured on 119 days at 55 points.

Results

In some cases, the amount of litter was too small for effects to be detected, but where enough littering occurred, posters providing information, inducing positive emotions, or activating reciprocity norms—as well as providing the option of separating fractions of waste for recycling as a structural measure—reduced litter significantly. Interventions targeting the tension state of disgust had no effect. Posters targeting descriptive and injunctive norms increased the amount of litter.

Discussion

Based on the results of the preparative study, a large-scale campaign was designed, implemented, and evaluated in 2022, which led to promising effects.