bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fine particulate matter 2.5 induces susceptibility to Pseudomonas aeruginosa infection via expansion of PD-L1high neutrophils in mice
Authors: Luo Li , Jiang Manling , Xiong Ying , Xiong Anying , Zhang Lei , Wu Dehong , Liu Yao , Ran Qin , Liu Jiliu , Zhang Yi , Li Jiahuan , He Xiang , Wang Junyi , Li Guoping 
Published: February 2024

Abstract
Background
Exposure to PM2.5 has been implicated in a range of detrimental health effects, particularly affecting the respiratory system. However, the precise underlying mechanisms remain elusive.

Methods
To address this objective, we collected ambient PM2.5 and administered intranasal challenges to mice, followed by single-cell RNA sequencing (scRNA-seq) to unravel the heterogeneity of neutrophils and unveil their gene expression profiles. Flow cytometry and immunofluorescence staining were subsequently conducted to validate the obtained results. Furthermore, we assessed the phagocytic potential of neutrophils upon PM2.5 exposure using gene analysis of phagocytosis signatures and bacterial uptake assays. Additionally, we utilized a mouse pneumonia model to evaluate the susceptibility of PM2.5-exposed mice to Pseudomonas aeruginosa infection.

Results
Our study revealed a significant increase in neutrophil recruitment within the lungs of PM2.5-exposed mice, with subclustering of neutrophils uncovering subsets with distinct gene expression profiles. Notably, exposure to PM2.5 was associated with an expansion of PD-L1high neutrophils, which exhibited impaired phagocytic function dependent upon PD-L1 expression. Furthermore, PM2.5 exposure was found to increase the susceptibility of mice to Pseudomonas aeruginosa, due in part to increased PD-L1 expression on neutrophils. Importantly, monoclonal antibody targeting of PD-L1 significantly reduced bacterial burden, dissemination, and lung inflammation in PM2.5-exposed mice upon Pseudomonas aeruginosa infection.

Conclusions
Our study suggests that PM2.5 exposure promotes expansion of PD-L1high neutrophils with impaired phagocytic function in mouse lungs, contributing to increased vulnerability to bacterial infection, and therefore targeting PD-L1 may be a therapeutic strategy for reducing the harmful effects of PM2.5 exposure on the immune system.
PLK1 phosphorylates RhoGDI1 and promotes cancer cell migration and invasion
Authors: Lim Jeewon , Hwang Yo Sep , Yoon Hyang Ran , Yoo Jiyun , Yoon Suk Ran , Jung Haiyoung , Cho Hee Jun , Lee Hee Gu 
Published: February 2024

Abstract
Background
Rho guanine nucleotide dissociation inhibitor 1 (RhoGDI1) plays an important role in diverse cellular processes by regulating Rho guanosine triphosphate (GTP)ases activity. RhoGDI1 phosphorylation regulates the spatiotemporal activation of Rho GTPases during cell migration. In this study, we identified polo-like kinase 1 (PLK1) as a novel kinase of RhoGDI1 and investigated the molecular mechanism by which the interaction between RhoGDI1 and PLK1 regulates cancer cell migration.

Methods
Immunoprecipitation, GST pull-down assay, and proximity ligation assay (PLA) were performed to analyze the interaction between RhoGDI1 and PLK1. In vitro kinase assay and immunoprecipitation were performed with Phospho-(Ser/Thr) antibody. We evaluated RhoA activation using RhoGTPases activity assay. Cell migration and invasion were analyzed by transwell assays.

Results
GST pull-down assays and PLA showed that PLK1 directly interacted with RhoGDI1 in vitro and in vivo. Truncation mutagenesis revealed that aa 90-111 of RhoGDI1 are critical for interacting with PLK1. We also showed that PLK1 phosphorylated RhoGDI1 at Thr7 and Thr91, which induces cell motility. Overexpression of the GFP-tagged RhoGDI1 truncated mutant (aa 90-111) inhibited the interaction of PLK1 with RhoGDI1 and attenuated RhoA activation by PLK1. Furthermore, the overexpression of the RhoGDI1 truncated mutant reduced cancer cell migration and invasion in vitro and suppressed lung metastasis in vivo.

Conclusions
Collectively, we demonstrate that the phosphorylation of RhoGDI1 by PLK1 promotes cancer cell migration and invasion through RhoA activation. This study connects the interaction between PLK1 and RhoGDI1 to the promotion of cancer cell behavior associated with malignant progression, thereby providing opportunities for cancer therapeutic interventions.
Evaluation of the malaria case surveillance system in KwaZulu-Natal Province, South Africa, 2022: a focus on DHIS2
Authors: Mabona Maxwell , Zwane Thembekile , Raman Jaishree , Kuonza Lazarus , Mhlongo Babongile , Phafane Poncho 
Published: February 2024

AbstractBackgroundSouth Africa set a target to eliminate malaria by 2023, with KwaZulu-Natal (KZN) Province the malaria-endemic province closest to achieving this goal. Objective two of the National Malaria Elimination Strategic Plan (NMESP) focused on strengthening surveillance systems to support the country’s elimination efforts. Regular evaluations of the malaria surveillance systems against the targets of the NMESP objective are crucial in improving their performance and impact. This study aimed to assess whether the malaria surveillance system in KwaZulu-Natal Province meets the NMESP surveillance objective and goals.MethodsA mixed-methods cross-sectional study design was used to evaluate the malaria surveillance system, focusing on the District Health Information System 2 (DHIS2). The study assessed the data quality, timeliness, simplicity, and acceptability of the system. Key personnel from KZN’s Provincial malaria control programme were interviewed using self-administered questionnaires to evaluate their perception of the system's simplicity and acceptability. Malaria case data from January 2016 to December 2020 were extracted from the DHIS2 and evaluated for data quality and timeliness.ResultsThe survey respondents generally found the DHIS2-based surveillance system acceptable (79%, 11/14) and easy to use (71%, 10/14), stating that they could readily find, extract, and share data (64%, 9/14). Overall data quality was good (88.9%), although some variables needed for case classification had low completeness and data availability. However, case notifications were not timely, with only 61% (2 622/4 329) of cases notified within 24 h of diagnosis. During the 5-year study period, the DHIS2 captured 4 333 malaria cases. The majority of cases (81%, 3 489/4 330) were categorized as imported, and predominately in males (67%, 2 914/4 333).ConclusionWhile the malaria surveillance system in KZN Province largely met the NMESP surveillance strategic goals, it failed to achieve the overarching surveillance objective of 100% notification of cases within 24 h of diagnosis. The majority of reported cases in KZN Province were classified as imported, emphasizing the importance of complete data for accurate case classification. Engaging with healthcare professionals responsible for case notification and disseminating aggregated data back to them is needed to encourage and improve notification timeliness.
The quest for nanoparticle-powered vaccines in cancer immunotherapy
Authors: Sun Zhe , Zhao Hui , Ma Li , Shi Yanli , Ji Mei , Sun Xiaodong , Ma Dan , Zhou Wei , Huang Tao , Zhang Dongsheng 
Published: February 2024

AbstractDespite recent advancements in cancer treatment, this disease still poses a serious threat to public health. Vaccines play an important role in preventing illness by preparing the body's adaptive and innate immune responses to combat diseases. As our understanding of malignancies and their connection to the immune system improves, there has been a growing interest in priming the immune system to fight malignancies more effectively and comprehensively. One promising approach involves utilizing nanoparticle systems for antigen delivery, which has been shown to potentiate immune responses as vaccines and/or adjuvants. In this review, we comprehensively summarized the immunological mechanisms of cancer vaccines while focusing specifically on the recent applications of various types of nanoparticles in the field of cancer immunotherapy. By exploring these recent breakthroughs, we hope to identify significant challenges and obstacles in making nanoparticle-based vaccines and adjuvants feasible for clinical application. This review serves to assess recent breakthroughs in nanoparticle-based cancer vaccinations and shed light on their prospects and potential barriers. By doing so, we aim to inspire future immunotherapies for cancer that harness the potential of nanotechnology to deliver more effective and targeted treatments.
Graphical abstract
Cost-consequence analysis of tocilizumab versus adalimumab and etanercept among rheumatoid arthritis patients in Saudi Arabia: a single-center study
Authors: Albahdal Areej S. , Alotaibi Amjad M. , Alanazi Miteb A. , Abanmy Norah , Alwhaibi Monira , AlRuthia Yazed 
Published: February 2024

Abstract
Background
The study aimed to examine the direct medical cost and impact of tocilizumab (TOZ) versus adalimumab (ADM) and etanercept (ETC) on reducing the levels of two inflammatory markers (e.g., C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)) among patients with rheumatoid arthritis (RA) using real-world data from Saudi Arabia.

Method
This was a single-center retrospective cohort study in which data for biologic-naïve RA patients aged ≥ 18 years and treated with TOZ, ADM, ETC were retrieved from the electronic medical records (EMRs) of a university-affiliated tertiary care center in Riyadh, Saudi Arabia. Patients were followed up at least one year after the treatment initiation. Bottom-up microcosting was utilized to estimate the direct medical costs. Additionally, inverse probability treatment weighting and bootstrapping with 10,000 replications were conducted to generate 95% confidence levels for costs and the mean reductions in CRP and ESR levels.

Results
The number of patients who met the inclusion criteria and were included in the analysis was 150 patients (TOZ (n = 56), ADM (n = 41), ETC (n = 53)). Patients on TOZ had 3.96 mg/L (95% CI: -0.229–4.95) and 11.21 mm/hr (95% CI: 10.28–18.11) higher mean reductions in the CRP and ESR levels compared to their counterparts on ADM, ETC, respectively. However, this was associated with mean annual incremental costs of USD 10,087.88 (95% CI: 9494.50–11,441.63) in all cost-effectiveness bootstrap distributions.

Conclusion
Tocilizumab has shown better effectiveness in reducing the levels of CRP and ESR but with higher costs. Future studies should examine whether the reduction of these two inflammatory markers is associated with quality-adjusted life years (QALYs) gains.
Recent advances of m6A methylation in skeletal system disease
Authors: Liang Jianhui , Yi Qian , Liu Yang , Li Jiachen , Yang Zecheng , Sun Wei , Sun Weichao 
Published: February 2024

AbstractSkeletal system disease (SSD) is defined as a class of chronic disorders of skeletal system with poor prognosis and causes heavy economic burden. m6A, methylation at the N6 position of adenosine in RNA, is a reversible and dynamic modification in posttranscriptional mRNA. Evidences suggest that m6A modifications play a crucial role in regulating biological processes of all kinds of diseases, such as malignancy. Recently studies have revealed that as the most abundant epigentic modification, m6A is involved in the progression of SSD. However, the function of m6A modification in SSD is not fully illustrated. Therefore, make clear the relationship between m6A modification and SSD pathogenesis might provide novel sights for prevention and targeted treatment of SSD. This article will summarize the recent advances of m6A regulation in the biological processes of SSD, including osteoporosis, osteosarcoma, rheumatoid arthritis and osteoarthritis, and discuss the potential clinical value, research challenge and future prospect of m6A modification in SSD.
Development and validation of a novel scoring system for acute ischemic stroke
Authors: Xu Rui , Peng Shixin , Qiu Yulong , Zhu Ji , Zhang Xiaodong , Jiang Li 
Published: February 2024

Abstract
Background
This study aimed to assess the clinical application of the Artery Occlusion Image Score (AOIS), a new metric based on computed tomographic angiography (CTA) that reflects the severity of occlusive changes in the main intracranial arteries.

Materials and Methods
Patients diagnosed with acute ischemic stroke (AIS) were divided into three groups: anterior circulation infarcts (ACI group), posterior circulation infarcts (PCI group), and both anterior and posterior circulation infarcts (ACI + PCI group). The sensitivity and specificity of AOIS were evaluated using the Basilar Artery on Computed Tomography Angiography (BATMAN) score, the Clot Burden Score (CBS), and the National Institutes of Health Stroke Scale (NIHSS) as comparators through receiver-operating characteristic (ROC) curve analysis.

Results
The final analysis included 439 consecutive patients. In the ACI group, AOIS demonstrated high sensitivity (86.3%) and specificity (85.0%) and outperformed CBS in predicting patient prognosis. In the PCI group, AOIS also showed high sensitivity (88.9%) and specificity (90.0%) and outperformed BATMAN in predicting patient prognosis. In the ACI + PCI group, AOIS positively correlated with the NIHSS score (Spearman’s ρ = 0.602, P < .001). Additionally, the scoring time of AOIS did not significantly differ from CBS and BATMAN.

Conclusion
AOIS is a convenient and reliable method for guiding treatment and predicting outcomes in patients with ACI or/and PCI. Furthermore, AOIS is the first CTA-based scoring system that covers both the anterior and posterior circulation, providing a convenient and reliable evaluation for patients with concurrent acute ischemic stroke in both circulations.
Intracerebellar injection of monocytic immature myeloid cells prevents the adverse effects caused by stereotactic surgery in a model of cerebellar neurodegeneration
Authors: del Pilar Carlos , Garrido-Matilla Lucía , del Pozo-Filíu Lucía , Lebrón-Galán Rafael , Arias Raúl F. , Clemente Diego , Alonso José Ramón , Weruaga Eduardo , Díaz David 
Published: February 2024

Abstract
Background
Myeloid-derived suppressor cells (MDSCs) constitute a recently discovered bone-marrow-derived cell type useful for dealing with neuroinflammatory disorders. However, these cells are only formed during inflammatory conditions from immature myeloid cells (IMCs) that acquire immunosuppressive activity, thus being commonly gathered from diseased animals. Then, to obtain a more clinically feasible source, we characterized IMCs directly derived from healthy bone marrow and proved their potential immunosuppressive activity under pathological conditions in vitro. We then explored their neuroprotective potential in a model of human cerebellar ataxia, the Purkinje Cell Degeneration (PCD) mouse, as it displays a well-defined neurodegenerative and neuroinflammatory process that can be also aggravated by invasive surgeries.

Methods
IMCs were obtained from healthy bone marrow and co-cultured with activated T cells. The proliferation and apoptotic rate of the later were analyzed with Tag-it Violet. For in vivo studies, IMCs were transplanted by stereotactic surgery into the cerebellum of PCD mice. We also used sham-operated animals as controls of the surgical effects, as well as their untreated counterparts. Motor behavior of mice was assessed by rotarod test. The Purkinje cell density was measured by immunohistochemistry and cell death assessed with the TUNEL technique. We also analyzed the microglial phenotype by immunofluorescence and the expression pattern of inflammation-related genes by qPCR. Parametric tests were applied depending on the specific experiment: one or two way ANOVA and Student’s T test.

Results
IMCs were proven to effectively acquire immunosuppressive activity under pathological conditions in vitro, thus acting as MDSCs. Concerning in vivo studios, sham-operated PCD mice suffered detrimental effects in motor coordination, Purkinje cell survival and microglial activation. After intracranial administration of IMCs into the cerebellum of PCD mice, no special benefits were detected in the transplanted animals when compared to untreated mice. Nonetheless, this transplant almost completely prevented the impairments caused by the surgery in PCD mice, probably by the modulation of the inflammatory patterns.

Conclusions
Our work comprise two main translational findings: (1) IMCs can be directly used as they behave as MDSCs under pathological conditions, thus avoiding their gathering from diseased subjects; (2) IMCs are promising adjuvants when performing neurosurgery.
Documentation of prenatal contraceptive counseling and fulfillment of permanent contraception: a retrospective cohort study
Authors: Viswanathan Ambika V. , Berg Kristen A. , Bullington Brooke W. , Miller Emily S. , Boozer Margaret , Serna Tania , Bailit Jennifer L. , Arora Kavita Shah 
Published: February 2024

Abstract
Background
Barriers exist for the provision of surgery for permanent contraception in the postpartum period. Prenatal counseling has been associated with increased rates of fulfillment of desired postpartum contraception in general, although it is unclear if there is impact on permanent contraception specifically. Thus, we aimed to investigate the association between initial timing for prenatal documentation of a contraceptive plan for permanent contraception and fulfillment of postpartum contraception for those receiving counseling.

Methods
This is a planned secondary analysis of a multi-site cohort study of patients with documented desire for permanent contraception at the time of delivery at four hospitals located in Alabama, California, Illinois, and Ohio over a two-year study period. Our primary exposure was initial timing of documented plan for contraception (first, second, or third trimester, or during delivery hospitalization). We used univariate and multivariable logistic regression to analyze fulfillment of permanent contraception before hospital discharge, within 42 days of delivery, and within 365 days of delivery between patients with a documented plan for permanent contraception in the first or second trimester compared to the third trimester. Covariates included insurance status, age, parity, gestational age, mode of delivery, adequacy of prenatal care, race, ethnicity, marital status, and body mass index.

Results
Of the 3103 patients with a documented expressed desire for permanent contraception at the time of delivery, 2083 (69.1%) had a documented plan for postpartum permanent contraception prenatally. After adjusting for covariates, patients with initial documented plan for permanent contraception in the first or second trimester had a higher odds of fulfillment by discharge (aOR 1.57, 95% C.I 1.24–2.00), 42 days (aOR 1.51, 95% C.I 1.20–1.91), and 365 days (aOR 1.40, 95% C.I 1.11–1.75), compared to patients who had their first documented plan in the third trimester.

Conclusions
Patients who had a documented prenatal plan for permanent contraception in trimester one and two experienced higher likelihood of permanent contraception fulfillment compared to those with documentation in trimester three. Given the barriers to accessing permanent contraception, it is imperative that comprehensive, patient-centered counseling and documentation regarding future reproductive goals begin early prenatally.
Optimizing speed breeding and seed/pod chip based genotyping techniques in pigeonpea: A way forward for high throughput line development
Authors: Gangashetty Prakash I. , Belliappa Shruthi H. , Bomma Naresh , Kanuganahalli Vinutha , Sajja Sobhan Babu , Choudhary Sunita , Gaviyappanavar Ramanagouda , Bomireddy Deekshitha , Anil Kumar V. , Pranati Jwala , Sharma Mamta , Pandey Manish K. 
Published: February 2024

Abstract
Background
The challenge of pigeonpea breeding lies in its photosensitivity and seasonal specificity. This poses a problem to the breeder, as it restricts to single generation advancement in a year. Currently, the cross to cultivar gap is twelve to thirteen years resulting in a limited number of varietal releases over the past six decades. Shortening the breeding cycle was need of the hour, unlikely achieved by conventional breeding. To overcome these hindrances speed breeding was a necessary leap. An experiment was planned to optimize the speed breeding coupled with single seed descent and seed or pod chip-based genotyping to shorten the breeding cycle in pigeonpea at ICRISAT, Hyderabad. Monitored photoperiod, light wavelength, temperature and crop management regime were the indicators attributing to the success of speed breeding.

Result
A photoperiod of 13 h: 8 h: 13 h at vegetative: flowering and pod filling stages is ideal for shortening the breeding cycle. Broad spectrum light (5700 K LED) hastened early vegetative growth and pod formation. Whereas far-red (735 nm) light favoured early flowering. A significant difference between the photoperiods, genotypes as well as photoperiod x genotype interaction for both days to flowering and plant height was noted.

Conclusion
The optimized protocol serves as a road map for rapid generation advancement in pigeonpea. Deploying this protocol, it is possible to advance 2–4 generations per year. The breeding cycle can be reduced to 2–4 years which otherwise takes 7 years under conventional breeding. Single Seed Descent and seed or pod chip-based genotyping for early generation marker assisted selection, strengthened the precision of this technique aiding in high throughput line development.
Application of a combined cancellous lag screw enhances the stability of locking plate fixation of osteoporotic lateral tibial plateau fracture by providing interfragmentary compression force
Authors: Jiang Jiang , Xu Daqiang , Ji Zhenhua , Wang Fei , Jia Rui , Wang Jun , Hong Hong , Zhang Hongtao , Li Jianyi 
Published: February 2024

Abstract
Background
Insufficient interfragmentary compression force (IFCF) frequently leads to unstable fixation of osteoporotic lateral tibial plateau fractures (OLTPFs). A combined cancellous lag screw (CCLS) enhances IFCF; however, its effect on OLTPF fixation stability remains unclear. Therefore, we investigated the effect of CCLS on OLTPF stability using locking plate fixation (LPF).

Materials and methods
Twelve synthetic osteoporotic tibial bones were used to simulate OLTPFs, which were fixed using LPF, LPF-AO cancellous lag screws (LPF-AOCLS), and LPF-CCLS. Subsequently, 10,000 cyclic loadings from 30 to 400 N were performed. The initial axial stiffness (IAS), maximal axial micromotion of the lateral fragment (MAM-LF) measured every 1000 cycles, and failure load after 10,000 cycles were tested. The same three fixations for OLTPF were simulated using finite element analysis (FEA). IFCFs of 0, 225, and 300 N were applied to the LPF, LPF-AOCLS, and LPF-CCLS, respectively, with a 1000-N axial compressive force. The MAM-LF, peak von Mises stress (VMS), peak equivalent elastic strain of the lateral fragment (EES-LF), and nodes of EES-LF > 2% (considered bone destruction) were calculated.

Results
Biomechanical tests revealed the LPF-AOCLS and LPF-CCLS groups to be superior to the LPF group in terms of the IAS, MAM-LF, and failure load (all p < 0.05). FEA revealed that the MAM-LF, peak VMS, peak EES-LF, and nodes with EES-LF > 2% in the LPF were higher than those in the LPF-AOCLS and LPF-CCLS.

Conclusion
IFCF was shown to enhance the stability of OLTPFs using LPF. Considering overscrewing, CCLS is preferably recommended, although there were no significant differences between CCLS and AOCLS.