bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimating lead-attributable mortality burden by socioeconomic status in the USA
Authors: Tao Chengzhe , Li Zhi , Fan Yun , Huang Yuna , Wan Tingya , Shu Mingxue , Han Shuwen , Qian Hong , Yan Wenkai , Xu Qiaoqiao , Xia Yankai , Lu Chuncheng , Li You 
Published: July 2024

Abstract

Background
This study aimed to estimate population-level and state-level lead-attributable mortality burdens stratified by socioeconomic status (SES) class in the USA.

Methods
Based on the National Health and Nutrition Examination Survey (NHANES), we constructed individual-level SES scores from income, employment, education and insurance data. We assessed the association between the blood lead levels (BLL) and all-cause mortality by Cox regression in the NHANES cohort (n = 31 311, 4467 deaths). With estimated hazard ratios (HR) and prevalences of medium (2–5 μg/dL) and high (≥ 5 μg/dL) BLL, we computed SES-stratified population-attributable fractions (PAFs) of all-cause mortality from lead exposure across 1999–2019. We additionally conducted a systematic review to estimate the lead-attributable mortality burden at state-level.

Results
The HR for every 2-fold increase in the BLL decreased from 1.23 (1.10–1.38) for the lowest SES class to 1.05 (0.90–1.23) for the highest SES class. Across all SES quintiles, medium BLL exhibited a greater mortality burden. Individuals with lower SES had higher lead-attributable burdens, and such disparities haver persisted over the past two decades. In 2017–19, annually 67 000 (32 000–112 000) deaths in the USA were attributable to lead exposure, with 18 000 (2000–41 000) of these deaths occurring in the lowest SES class. Substantial disparities in the state-level mortality burden attributable to lead exposure were also highlighted.

Conclusions
These findings suggested that disparities in lead-attributable mortality burden persisted within US adults, due to heterogeneities in the effect sizes of lead exposure as well as in the BLL among different SES classes.
Mapping complex public health problems with causal loop diagrams
Authors: Uleman Jeroen F , Stronks Karien , Rutter Harry , Arah Onyebuchi A , Rod Naja Hulvej 
Published: July 2024

Abstract
This paper presents causal loop diagrams (CLDs) as tools for studying complex public health problems like health inequality. These problems often involve feedback loops—a characteristic of complex systems not fully integrated into mainstream epidemiology. CLDs are conceptual models that visualize connections between system variables. They are commonly developed through literature reviews or participatory methods with stakeholder groups. These diagrams often uncover feedback loops among variables across scales (e.g. biological, psychological and social), facilitating cross-disciplinary insights. We illustrate their use through a case example involving the feedback loop between sleep problems and depressive symptoms. We outline a typical step-by-step process for developing CLDs in epidemiology. These steps are defining a specific problem, identifying the key system variables involved, mapping these variables and analysing the CLD to find new insights and possible intervention targets. Throughout this process, we suggest triangulating between diverse sources of evidence, including domain knowledge, scientific literature and empirical data. CLDs can also be evaluated to guide policy changes and future research by revealing knowledge gaps. Finally, CLDs may be iteratively refined as new evidence emerges. We advocate for more widespread use of complex systems tools, like CLDs, in epidemiology to better understand and address complex public health problems.
Specific Depletion of Myeloid-Derived Suppressor Cells by the Chemotherapy Agent 5-Fluorouracil Enhances Protective Immune Response in Paracoccidioidomycosis
Authors: Preite Nycolas Willian , Kaminski Valéria de Lima , Borges Bruno Montanari , dos Santos Bianca Vieira , Calich Vera Lúcia Garcia , Loures Flávio Vieira 
Published: July 2024

Abstract

Background
Paracoccidioidomycosis (PCM) is regulated by suppressive mechanisms mediated by plasmacytoid-dendritic cells, regulatory T cells and myeloid-derived suppressor cells (MDSCs). MDSC suppressive activity on Th1/Th17 immunity was shown to be mediated by inhibitory effect of IL-10, IDO-1, and PD-L1. Studies revealed the 5-fluorouracil (5-FU) as a selective MDSC apoptosis-inducing agent, but its in vivo effect on infectious processes remains poorly investigated.

Methods
MDSCs and other leukocytes were evaluated in the lungs of 5-FU–treated mice after 4, 6, and 8 weeks of Paracoccidioides brasiliensis infection. Disease severity and immunological response were evaluated in MDSCs-depleted mice.

Results
5-FU treatment caused a reduction of pulmonary MDSCs and fungal loads. The specific depletion of MDSCs reduced all pulmonary CD4+ T-cell populations resulting in improved tissue pathology and increased survival. This reduction was concomitant with increased frequencies of Th1/Th17 cells and the increased levels of Th1/Th2/Th17 cytokines in the lungs and liver of treated mice, suggesting an early and efficient protective effect of these cells. Furthermore, the immune protection conferred by the 5-FU treatment could be reversed by the MDSC-adoptive transfer.

Conclusions
5-FU depletes MDSCs of P. brasiliensis-infected mice, resulting in enhanced immunity. This protective effect can be viewed as a potential immunotherapeutic tool for PCM.
Nasal commensals reduce Staphylococcus aureus proliferation by restricting siderophore availability
Authors: Zhao Yanfeng , Bitzer Alina , Power Jeffrey John , Belikova Darya , Torres Salazar Benjamin Orlando , Adolf Lea Antje , Gerlach David , Krismer Bernhard , Heilbronner Simon 
Published: July 2024

Abstract
The human microbiome is critically associated with human health and disease. One aspect of this is that antibiotic-resistant opportunistic bacterial pathogens, such as methicillin-resistant Staphylococcus aureus, can reside within the nasal microbiota, which increases the risk of infection. Epidemiological studies of the nasal microbiome have revealed positive and negative correlations between non-pathogenic species and S. aureus, but the underlying molecular mechanisms remain poorly understood. The nasal cavity is iron-limited, and bacteria are known to produce iron-scavenging siderophores to proliferate in such environments. Siderophores are public goods that can be consumed by all members of a bacterial community. Accordingly, siderophores are known to mediate bacterial competition and collaboration, but their role in the nasal microbiome is unknown. Here, we show that siderophore acquisition is crucial for S. aureus nasal colonization in vivo. We screened 94 nasal bacterial strains from seven genera for their capacity to produce siderophores as well as to consume the siderophores produced by S. aureus. We found that 80% of the strains engaged in siderophore-mediated interactions with S. aureus. Non-pathogenic corynebacterial species were found to be prominent consumers of S. aureus siderophores. In co-culture experiments, consumption of siderophores by competitors reduced S. aureus growth in an iron-dependent fashion. Our data show a wide network of siderophore-mediated interactions between the species of the human nasal microbiome and provide mechanistic evidence for inter-species competition and collaboration impacting pathogen proliferation. This opens avenues for designing nasal probiotics to displace S. aureus from the nasal cavity of humans.
Network Context and the Effectiveness of International Agreements
Authors: Kinne Brandon J 
Published: July 2024

Abstract
Why do some international agreements yield more cooperation than others? I argue that the network context of agreements conditions their effectiveness. I focus on bilateral defense cooperation agreements (DCAs), which promote defense activities like joint military exercises, peacekeeping, arms trade, and the sharing of classified information. Because DCAs emphasize ongoing cooperative actions, they offer an ideal setting to assess treaty effectiveness. The analysis shows that when agreements are embedded in transitive “friend of friend” relations, characterized by extensive ties to common third parties, they generate higher levels of cooperation. I argue that this network effect is the result of policy convergence. When states share ties with common third parties, their own policies become more closely aligned, and this alignment in turn reduces the costs and increases the benefits of cooperative actions. The theory and findings developed here apply to a wide array of cooperative interactions across multiple issue areas. The effectiveness of international agreements depends on network context.
Identification of antimicrobial-susceptible Pseudomonas aeruginosa RpoA variant strains through positional conservation pattern
Authors: Chen Huali , Zhou Xiaoqing , Dai Weijun 
Published: July 2024

Abstract

Background
Bacterial RNA polymerase (RNAP) is a promising target for antimicrobial chemotherapy due to its indispensable role in bacterial growth and survival. Among its components, only the rpoB gene encoding the β-subunit is known for its association with rifampicin resistance. We recently identified a variant of the RNAP α-subunit (RpoA) in Pseudomonas aeruginosa, conferring heightened bacterial susceptibility to antimicrobials. This susceptibility was attributed to the specific down-regulation of the MexEF-OprN efflux pump.

Objectives
We asked how to distinguish antimicrobial-susceptible variant strains from clinical isolates.

Methods
In this study, we identified various P. aeruginosa RpoA variants from clinical sources. Using the sequence alignment of different bacterial RpoA species, we computed the positional conservation of substitutions in RpoA variants using Shannon Entropy.

Results
Our findings revealed that selective RpoA variant strains exhibited distinct profiles of antimicrobial susceptibility. Notably, RpoA variant strains, containing single-substitutions in the C-terminal domain (α-CTD) but not the N-terminal domain (α-NTD), showed attenuated MexEF-OprN expression and increased susceptibility to MexEF-OprN-specific antibiotics. Furthermore, we observed a close correlation between the susceptibility of these α-CTD RpoA variant strains to antibiotics and the conservation degrees of positional substitutions.

Conclusions
Our findings demonstrate the prevalence of antimicrobial-susceptible RpoA variant strains among P. aeruginosa clinical isolates. The identified positional conservation pattern in our study facilitates the rapid classification of RpoA variant strains with distinct drug resistances. Given the high conservation of RNAP across bacterial species, our findings open a new therapeutic perspective for precisely and efficiently combating pathogenic RpoA variant strains with specific antimicrobials.
Measuring the Scientific Impact of Growth Hormone Treatment in Burns: A Bibliometric Analysis Based on CiteSpace
Authors: Shao Yang , Han Mei , Song Guodong 
Published: July 2024

Abstract
This study utilized CiteSpace software to conduct a bibliometric analysis of the literature related to the use of growth hormones in treating burns. The results showed that the research on this topic has attracted increasing attention from scholars worldwide, with the number of publications increasing annually. The research teams and institutions involved in this field are mainly concentrated in China, followed by the United States, Russia, and other countries. The analysis also revealed the prominent co-cited literature and the most influential authors in the field, such as D. N. Herndon and Y. Li. The main research themes identified in the literature included the effects of growth hormones on wound healing, tissue repair and regeneration, inflammatory responses, and cell proliferation. In addition, the research on the clinical applications of growth hormone in burn treatment has been expanded to include areas such as metabolic regulation, immune function, and the prevention of infections. The findings of this study provide useful insights into the current status and future directions of research in the field of growth hormone treatment of burns.
Breeding phenology drives variation in reproductive output, reproductive costs, and offspring fitness in a viviparous ectotherm
Authors: Bodineau Théo , de Villemereuil Pierre , Agostini Simon , Decencière Beatriz , Le Galliard Jean-François , Meylan Sandrine 
Published: July 2024

Abstract
Phenological advances are a widespread response to global warming and can contribute to determine the climate vulnerability of organisms, particularly in ectothermic species, which are highly dependent on ambient temperatures to complete their life cycle. Yet, the relative contribution of breeding dates and temperature conditions during gestation on fitness of females and their offspring is poorly documented in reptiles. Here, we exposed females of the common lizard Zootoca vivipara to contrasting thermal scenarios (cold vs. hot treatment) during gestation and quantified effects of parturition dates and thermal treatment on life-history traits of females and their offspring for 1 year. Overall, our results suggest that parturition date has a greater impact than thermal conditions during gestation on life history strategies. In particular, we found positive effects of an earlier parturition date on juvenile survival, growth, and recruitment suggesting that environmental-dependent selection and/or differences in parental quality between early and late breeders underlie seasonal changes in offspring fitness. Yet, an earlier parturition date compromised the energetic condition of gravid females, which suggests the existence of a mother–offspring conflict regarding the optimization of parturition dates. While numerous studies focused on the direct effects of alterations in incubation temperatures on reptile life-history traits, our results highlight the importance of considering the role of breeding phenology in assessing the short- and long-term effects of thermal developmental plasticity.
Exploring the anxiolytic mechanism of Fructus gardeniae based on metabolomics, network pharmacology, and molecular docking
Authors: Tian Yue , Yuan Fuli , Kong Jiao , Yuan Zhenshuang , Jia Chunxue , Kui Hongqian , Yin Ziqiang , Liu Chuanxin , Huang Jianmei 
Published: July 2024

Abstract

Objective
To explore the effect and anxiolytic mechanism of a natural remedy called Fructus gardeniae (FG).

Methods
The elevated-plus maze (EPM) test was used to confirm the anxiolytic effect of FG. The potential and anxiolytic components, targets, and route processes of FG were investigated using the network pharmacology method in conjunction with metabolomics and molecular docking technologies.

Results
FG could greatly enhance the proportion of time and times of opening arms, according to the EPM data. As to the metabolomics findings, a total of 61 distinct metabolites were found, mainly involved in glycine, serine, and threonine metabolism as well as alanine, aspartate, and glutamate metabolism. The primary active ingredients of FG, nicotiflorin, jasminodiol, and crocetin, demonstrated substantial binding affinities with monoamine oxidase A (MAOA), monoamine oxidase A (ACHE), malate dehydrogenase 2 (MDH2), glutamate decarboxylase 2 (GAD2), glutamate decarboxylase 1 (GAD1), and nitric oxide synthase (NOS1), according to the findings of network pharmacology and molecular docking.

Conclusion
FG exerts an anxiolytic action via targeting MAOA, ACHE, MDH2, GAD2, GAD1, and NOS1, and regulating the metabolism of glycine, serine, and threonine as well as alanine, aspartic acid, and glutamic acid.
Safety of topical sildenafil cream, 3.6% in a randomized, placebo-controlled trial for the treatment of female sexual arousal disorder
Authors: Thurman Andrea R , Johnson Isabella , Cornell Katherine A , Hatheway Jessica , Kim Noel N , Parish Sharon J , Dart Clint , Friend David R , Goldstein Andrew 
Published: July 2024

Abstract

Background
There are currently no Food and Drug Administration–approved treatments for female sexual arousal disorder (FSAD), which is physiologically analogous to male erectile dysfunction.

Aims
The study sought to test the systemic and local genital safety of topical sildenafil cream, 3.6% (sildenafil cream) among healthy premenopausal women with FSAD and their sexual partners over a 12-week treatment period.

Methods
This was a phase 2b, exploratory, randomized, placebo-controlled, double-blind study of sildenafil cream among healthy premenopausal women with FSAD. Safety was assessed by the frequency and incidence of treatment-emergent adverse events (TEAEs) among participants and their sexual partners. Participants recorded the incidence of TEAEs in a daily eDiary (electronic diary). Sexual partners were contacted within 72 hours of each sexual event in which investigational product was used. All participants used placebo cream for 1 month, during a single-blind run-in period, and then if eligible, were randomized 1:1 to sildenafil cream or placebo cream. Participants used their assigned investigational product over a 12-week double-blind dosing period. They attended monthly follow-up visits, in which their eDiary TEAE data were reviewed by the study staff and graded for severity and relationship to study product.

Outcomes
The frequency and incidence of TEAEs among participants and their sexual partners.

Results
During the 12-week double-blind dosing period, there were 78 TEAEs reported by 29 of 99 sildenafil-assigned participants and 65 TEAEs reported by 28 of 94 placebo-assigned participants (P = .76). All TEAEs were mild or moderate in severity. The most common treatment-related TEAE among active and placebo-assigned participants was application site discomfort. There were no differences in the number of treatment-related TEAEs among sildenafil cream vs placebo cream users (P &gt; .99). Four sildenafil cream participants and 3 placebo cream participants discontinued the study due to TEAEs involving application site discomfort (P &gt; .99). There were 9 TEAEs reported by 7 of 91 sexual partners exposed to sildenafil cream vs 4 TEAEs reported by 4 of 84 sexual partners exposed to placebo cream (P = .54).

Clinical Implications
These data support further clinical development of topical sildenafil cream for the treatment of FSAD.

Strengths and Limitations
Safety was assessed among participants and their sexual partners after 1357 and 1160 sexual experiences in which sildenafil cream or placebo cream were used, respectively. The phase 2b study was powered for the primary objectives of efficacy, rather than safety.

Conclusion
These data demonstrate that topically applied sildenafil cream was safe and well tolerated by exposed users and their sexual partners.
Partial wrapping of single-stranded DNA by replication protein A and modulation through phosphorylation
Authors: Chadda Rahul , Kaushik Vikas , Ahmad Iram Munir , Deveryshetty Jaigeeth , Holehouse Alex S , Sigurdsson Snorri Th , Biswas Gargi , Levy Yaakov , Bothner Brian , Cooley Richard B , Mehl Ryan A , Dastvan Reza , Origanti Sofia , Antony Edwin 
Published: July 2024

Abstract
Single-stranded DNA (ssDNA) intermediates which emerge during DNA metabolic processes are shielded by replication protein A (RPA). RPA binds to ssDNA and acts as a gatekeeper to direct the ssDNA towards downstream DNA metabolic pathways with exceptional specificity. Understanding the mechanistic basis for such RPA-dependent functional specificity requires knowledge of the structural conformation of ssDNA when RPA-bound. Previous studies suggested a stretching of ssDNA by RPA. However, structural investigations uncovered a partial wrapping of ssDNA around RPA. Therefore, to reconcile the models, in this study, we measured the end-to-end distances of free ssDNA and RPA–ssDNA complexes using single-molecule FRET and double electron–electron resonance (DEER) spectroscopy and found only a small systematic increase in the end-to-end distance of ssDNA upon RPA binding. This change does not align with a linear stretching model but rather supports partial wrapping of ssDNA around the contour of DNA binding domains of RPA. Furthermore, we reveal how phosphorylation at the key Ser-384 site in the RPA70 subunit provides access to the wrapped ssDNA by remodeling the DNA-binding domains. These findings establish a precise structural model for RPA-bound ssDNA, providing valuable insights into how RPA facilitates the remodeling of ssDNA for subsequent downstream processes.
Structural basis of water-mediated cis Watson–Crick/Hoogsteen base-pair formation in non-CpG methylation
Authors: Lin Shan-Meng , Huang Hsiang-Ti , Fang Pei-Ju , Chang Chi-Fon , Satange Roshan , Chang Chung-ke , Chou Shan-Ho , Neidle Stephen , Hou Ming-Hon 
Published: July 2024

Abstract
Non-CpG methylation is associated with several cellular processes, especially neuronal development and cancer, while its effect on DNA structure remains unclear. We have determined the crystal structures of DNA duplexes containing -CGCCG- regions as CCG repeat motifs that comprise a non-CpG site with or without cytosine methylation. Crystal structure analyses have revealed that the mC:G base-pair can simultaneously form two alternative conformations arising from non-CpG methylation, including a unique water-mediated cis Watson–Crick/Hoogsteen, (w)cWH, and Watson–Crick (WC) geometries, with partial occupancies of 0.1 and 0.9, respectively. NMR studies showed that an alternative conformation of methylated mC:G base-pair at non-CpG step exhibits characteristics of cWH with a syn-guanosine conformation in solution. DNA duplexes complexed with the DNA binding drug echinomycin result in increased occupancy of the (w)cWH geometry in the methylated base-pair (from 0.1 to 0.3). Our structural results demonstrated that cytosine methylation at a non-CpG step leads to an anti→syntransition of its complementary guanosine residue toward the (w)cWH geometry as a partial population of WC, in both drug-bound and naked mC:G base pairs. This particular geometry is specific to non-CpG methylated dinucleotide sites in B-form DNA. Overall, the current study provides new insights into DNA conformation during epigenetic regulation.