bluuebunny/crossref_metadata_2025_split huggingface dataset:
Attenuated vaccine PmCQ2Δ4555–4580 effectively protects mice against Pasteurella multocida infection
Authors: He Fang , Xiong Pan , Zhang Huihui , Yang Liu , Qiu Yangyang , Li Pan , Zhao Guangfu , Li Nengzhang , Peng Yuanyi 
Published: March 2024

AbstractPasteurella multocida type A (PmA) mainly causes respiratory diseases such as pneumonia in bovines, leading to great economic losses to the breeding industry. At present, there is still no effective commercial vaccine against PmA infection. In this study, a mutant strain (PmCQ2Δ4555–4580) with brand-new phenotypes was obtained after serially passaging at 42 °C. Whole genome resequencing and PCR analysis showed that PmCQ2Δ4555–4580 missed six genes, including PmCQ2_004555, PmCQ2_004560, PmCQ2_004565, PmCQ2_004570, PmCQ2_004575, and PmCQ2_004580. Importantly, the virulence of PmCQ2Δ4555–4580 was reduced by approximately 2.8 × 109 times in mice. Notably, live PmCQ2Δ4555–4580 could provide 100%, 100% and 40% protection against PmA, PmB and PmF, respectively; and inactivated PmCQ2Δ4555–4580 could provide 100% and 87.5% protection against PmA and PmB. Interestingly, immune protection-related proteins were significantly upregulated in PmCQ2Δ4555–4580 based on RNA-seq and bioinformatics analysis. Meaningfully, by in vitro expression, purification and in vivo immunization, 12 proteins had different degrees of immune protective effects. Among them, PmCQ2_008205, PmCQ2_010435, PmCQ2_008190, and PmCQ2_004170 had the best protective effect, the protection rates against PmA were 50%, 40%, 30%, and 30%, respectively, and the protective rates against PmB were 62.5%, 42.9%, 37.5%, and 28.6%, respectively. Collectively, PmCQ2Δ4555–4580 is a potential vaccine candidate for the prevention of Pasteurellosis involving in high expression of immune protective related proteins.
Associations between dietary fatty acids intake and abdominal aortic calcification: a national population-based study
Authors: Xiao Yan , Quan Yingping 
Published: March 2024

Abstract
Background
Abdominal aortic calcification (AAC) is a crucial indicator of cardiovascular health. This study aims investigates the associations between dietary fatty acid intake and AAC.

Methods
In this study, a cross-sectional assessment was performed on a group of 2,897 individuals aged 40 and above, utilizing data from the NHANES. The focus was on examining dietary consumption of various fatty acids, including Saturated (SFA), Monounsaturated (MUFA), Polyunsaturated (PUFA), as well as Omega-3 and Omega-6. The evaluation of AAC was done by applying the Kauppila AAC score to results obtained from dual-energy X-ray absorptiometry scans. For statistical analysis, weighted multivariate linear and logistic regression were employed, with adjustments for variables like gender, age, ethnicity, and overall health condition.

Results
Participants with higher intake of SFA and PUFA showed a positive association with AAC score, while higher levels of dietary Omega-3 and Omega-6 fatty acids was connected with a negative correlation. Subgroup analyses indicated consistent associations across different sexes and age groups. The study found that an increase in SFA and PUFA intake correlated with an increase in AAC score, whereas Omega-3 and Omega-6 intake correlated with a decrease.

Conclusion
This study underscores the importance of dietary fatty acid composition in the prevalence of AAC and its potential implications for dietary guidelines and cardiovascular disease prevention strategies.
Dyslipidemia versus obesity as predictors of ischemic stroke prognosis: a multi-center study in China
Authors: Ruan Hang , Ran Xiao , Li Shu-sheng , Zhang Qin 
Published: March 2024

Abstract
Background
This multicenter observational study aimed to determine whether dyslipidemia or obesity contributes more significantly to unfavorable clinical outcomes in patients experiencing a first-ever ischemic stroke (IS).

Methods
The study employed a machine learning predictive model to investigate associations among body mass index (BMI), body fat percentage (BFP), high-density lipoprotein (HDL), triglycerides (TG), and total cholesterol (TC) with adverse outcomes in IS patients. Extensive real-world clinical data was utilized, and risk factors significantly linked to adverse outcomes were identified through multivariate analysis, propensity score matching (PSM), and regression discontinuity design (RDD) techniques. Furthermore, these findings were validated via a nationwide multicenter prospective cohort study.

Results
In the derived cohort, a total of 45,162 patients diagnosed with IS were assessed, with 522 experiencing adverse outcomes. A multifactorial analysis incorporating PSM and RDD methods identified TG (adjusted odds ratio (OR) = 1.110; 95% confidence interval (CI): 1.041–1.183; P <  0.01) and TC (adjusted OR = 1.139; 95%CI: 1.039–1.248; P <  0.01) as risk factors. However, BMI, BFP, and HDL showed no significant effect. In the validation cohort, 1410 controls and 941 patients were enrolled, confirming that lipid levels are more strongly correlated with the prognosis of IS patients compared to obesity (TC, OR = 1.369; 95%CI: 1.069–1.754; P <  0.05; TG, OR = 1.332; 95%CI: 1.097–1.618; P <  0.01).

Conclusion
This study suggests that dyslipidemia has a more substantial impact on the prognosis of IS patients compared to obesity. This highlights the importance of prioritizing dyslipidemia management in the treatment and prevention of adverse outcomes in IS patients.

Graphical abstract
UiO-66 nanoparticles combat influenza A virus in mice by activating the RIG-I-like receptor signaling pathway
Authors: Su Ruijing , Li Xinsen , Xiao Jin , Xu Jiawei , Tian Jijing , Liu Tianlong , Hu Yanxin 
Published: March 2024

AbstractThe Influenza A virus (IAV) is a zoonotic pathogen that infects humans and various animal species. Infection with IAV can cause fever, anorexia, and dyspnea and is often accompanied by pneumonia characterized by an excessive release of cytokines (i.e., cytokine storm). Nanodrug delivery systems and nanoparticles are a novel approach to address IAV infections. Herein, UiO-66 nanoparticles (NPs) are synthesized using a high-temperature melting reaction. The in vitro and in vivo optimal concentrations of UiO-66 NPs for antiviral activity are 200 μg mL−1 and 60 mg kg−1, respectively. Transcriptome analysis revealed that UiO-66 NPs can activate the RIG-I-like receptor signaling pathway, thereby enhancing the downstream type I interferon antiviral effect. These NPs suppress inflammation-related pathways, including the FOXO, HIF, and AMPK signaling pathways. The inhibitory effect of UiO-66 NPs on the adsorption and entry of IAV into A549 cells is significant. This study presents novel findings that demonstrate the effective inhibition of IAV adsorption and entry into cells via UiO-66 NPs and highlights their ability to activate the cellular RIG-I-like receptor signaling pathway, thereby exerting an anti-IAV effect in vitro or in mice. These results provide valuable insights into the mechanism of action of UiO-66 NPs against IAV and substantial data for advancing innovative antiviral nanomedicine.
Graphical Abstract
Identification and functional activity of Nik related kinase (NRK) in benign hyperplastic prostate
Authors: He Weixiang , Tian Zelin , Dong Bingchen , Cao Yitong , Hu Wei , Wu Peng , Yu Lei , Zhang Xinhua , Guo Shanshan 
Published: March 2024

Abstract
Objective
Benign prostatic hyperplasia (BPH) is common in elder men. The current study aims to identify differentially expressed genes (DEGs) in hyperplastic prostate and to explore the role of Nik related kinase (NRK) in BPH.

Methods
Four datasets including three bulk and one single cell RNA-seq (scRNA-seq) were obtained to perform integrated bioinformatics. Cell clusters and specific metabolism pathways were analyzed. The localization, expression and functional activity of NRK was investigated via RT-PCR, western-blot, immunohistochemical staining, flow cytometry, wound healing assay, transwell assay and CCK-8 assay.

Results
A total of 17 DEGs were identified by merging three bulk RNA-seq datasets. The findings of integrated single-cell analysis showed that NRK remarkably upregulated in fibroblasts and SM cells of hyperplasia prostate. Meanwhile, NRK was upregulated in BPH samples and localized almost in stroma. The expression level of NRK was significantly correlated with IPSS and Qmax of BPH patients. Silencing of NRK inhibited stromal cell proliferation, migration, fibrosis and EMT process, promoted apoptosis and induced cell cycle arrest, while overexpression of NRK in prostate epithelial cells showed opposite results. Meanwhile, induced fibrosis and EMT process were rescued by knockdown of NRK. Furthermore, expression level of NRK was positively correlated with that of α-SMA, collagen-I and N-cadherin, negatively correlated with that of E-cadherin.

Conclusion
Our novel data identified NRK was upregulated in hyperplastic prostate and associated with prostatic stromal cell proliferation, apoptosis, cell cycle, migration, fibrosis and EMT process. NRK may play important roles in the development of BPH and may be a promising therapeutic target for BPH/LUTS.
Incorporating genetic similarity of auxiliary samples into eGene identification under the transfer learning framework
Authors: Zhang Shuo , Jiang Zhou , Zeng Ping 
Published: March 2024

Abstract
Background
The term eGene has been applied to define a gene whose expression level is affected by at least one independent expression quantitative trait locus (eQTL). It is both theoretically and empirically important to identify eQTLs and eGenes in genomic studies. However, standard eGene detection methods generally focus on individual cis-variants and cannot efficiently leverage useful knowledge acquired from auxiliary samples into target studies.

Methods
We propose a multilocus-based eGene identification method called TLegene by integrating shared genetic similarity information available from auxiliary studies under the statistical framework of transfer learning. We apply TLegene to eGene identification in ten TCGA cancers which have an explicit relevant tissue in the GTEx project, and learn genetic effect of variant in TCGA from GTEx. We also adopt TLegene to the Geuvadis project to evaluate its usefulness in non-cancer studies.

Results
We observed substantial genetic effect correlation of cis-variants between TCGA and GTEx for a larger number of genes. Furthermore, consistent with the results of our simulations, we found that TLegene was more powerful than existing methods and thus identified 169 distinct candidate eGenes, which was much larger than the approach that did not consider knowledge transfer across target and auxiliary studies. Previous studies and functional enrichment analyses provided empirical evidence supporting the associations of discovered eGenes, and it also showed evidence of allelic heterogeneity of gene expression. Furthermore, TLegene identified more eGenes in Geuvadis and revealed that these eGenes were mainly enriched in cells EBV transformed lymphocytes tissue.

Conclusion
Overall, TLegene represents a flexible and powerful statistical method for eGene identification through transfer learning of genetic similarity shared across auxiliary and target studies.
Multi-omics analysis of the gut microbiome and metabolites associated with the psychoneurological symptom cluster in children with cancer receiving chemotherapy
Authors: Bai Jinbing , Eldridge Ronald , Houser Madelyn , Martin Melissa , Powell Christie , Sutton Kathryn S. , Noh Hye In , Wu Yuhua , Olson Thomas , Konstantinidis Konstantinos T. , Bruner Deborah W. 
Published: March 2024

Abstract
Background
Children with cancer receiving chemotherapy commonly report a cluster of psychoneurological symptoms (PNS), including pain, fatigue, anxiety, depression, and cognitive dysfunction. The role of the gut microbiome and its functional metabolites in PNS is rarely studied among children with cancer. This study investigated the associations between the gut microbiome–metabolome pathways and PNS in children with cancer across chemotherapy as compared to healthy children.

Methods
A case–control study was conducted. Cancer cases were recruited from Children’s Healthcare of Atlanta and healthy controls were recruited via flyers. Participants reported PNS using the Pediatric Patient-Reported Outcomes Measurement Information System. Data for cases were collected pre-cycle two chemotherapy (T0) and post-chemotherapy (T1), whereas data for healthy controls were collected once. Gut microbiome and its metabolites were measured using fecal specimens. Gut microbiome profiling was performed using 16S rRNA V4 sequencing, and metabolome was performed using an untargeted liquid chromatography–mass spectrometry approach. A multi-omics network integration program analyzed microbiome–metabolome pathways of PNS.

Results
Cases (n = 21) and controls (n = 14) had mean ages of 13.2 and 13.1 years. For cases at T0, PNS were significantly associated with microbial genera (e.g., Ruminococcus, Megasphaera, and Prevotella), which were linked with carnitine shuttle (p = 0.0003), fatty acid metabolism (p = 0.001) and activation (p = 0.001), and tryptophan metabolism (p = 0.008). Megasphaera, clustered with aspartate and asparagine metabolism (p = 0.034), carnitine shuttle (p = 0.002), and tryptophan (p = 0.019), was associated with PNS for cases at T1. Gut bacteria with potential probiotic functions, along with fatty acid metabolism, tryptophan, and carnitine shuttle, were more clustered in cancer cases than the control network and this linkage with PNS needs further studies.

Conclusions
Using multi-omics approaches, this study indicated specific microbiome–metabolome pathways linked with PNS in children with cancer across chemotherapy. Due to limitations such as antibiotic use in cancer cases, these findings need to be further confirmed in a larger cohort.
High incidence of HPV infection in minors with oral squamous cell carcinoma
Authors: Wu Ningxiang , Li Yonghui , Ma Xiaokun , Huang Zhen , Chen Zhuoxuan , Chen Weihua , Zhang Ran 
Published: March 2024

Abstract
Background
Oral squamous cell carcinoma in minors is considered to be a distinct entity from OSCC in older patients, with an uncertain etiology. Human papillomavirus (HPV) infection may trigger the initiation and promote the progression of OSCC, but these roles have not been firmly established.We aimed to explore the correlation between HPV infection and the development of oral squamous cell carcinoma in minors and know the characteristics of OSCC in young patients more thoroughly.

Method
From January 2013 to December 2022,6 cases of OSCC aged < 15 years were selected from the Department of Oral Pathology, Peking University School of Stomatology, Beijing, China. All cases underwent testing for high-risk HPV mRNA infection using the RNA scope technique, and immunohistochemical staining was performed to investigate the expression of p16, pan-cytokeratin (CK), CK5/6, CK7, CK8/18, epidermal growth factor receptor (EGFR), p53, and Ki-67. Furthermore, we reviewed the literature on OSCC in patients aged < 21 years.

Conclusions
Minors OSCC is associated with HPV infection, and that p16 can serve as an immunohistochemical marker of HPV positivity.
Two-stage palatal repair in non-syndromic CLP patients using anterior to posterior closure is associated with minimal need for secondary palatal surgery
Authors: Kauffmann Philipp , Kolle Johanna , Quast Anja , Wolfer Susanne , Schminke Boris , Meyer-Marcotty Philipp , Schliephake Henning 
Published: March 2024

Abstract
Objective
The aim of the present study was to assess the need for secondary palatal corrective surgery in a concept of palate repair that uses a protocol of anterior to posterior closure of primary palate, hard palate and soft palate.

Methods
A data base of patients primarily operated between 2001 and 2021 at the Craniofacial and Cleft Care Center of the University Goettingen was evaluated. Cleft lips had been repaired using Tennison Randall and Veau-Cronin procedures in conjunction with alveolar cleft repair. Cleft palate repair in CLP patients was accomplished in two steps with repair of primary palate and hard palate first using vomer flaps at the age of 10–12 months and subsequent soft palate closure using Veau/two-flap procedures 3 months later. Isolated cleft palate repair was performed in a one-stage operation using Veau/two-flap procedures. Data on age, sex, type of cleft, date and type of surgery, occurrence and location of oronasal fistulae, date and type of secondary surgery performed for correction of oronasal fistula (ONF)and / or Velophyaryngeal Insufficiency (VPI) were extracted. The rate of skeletal corrective surgery was registered as a proxy for surgery induced facial growth disturbance.

Results
In the 195 patients with non-syndromic complete CLP evaluated, a total number of 446 operations had been performed for repair of alveolar cleft and cleft palate repair (Veau I through IV). In 1 patient (0,5%), an ONF occurred requiring secondary repair. Moreover, secondary surgery for correction of VPI was required in 1 patient (0,5%) resulting in an overall rate of 1% of secondary palatal surgery. Skeletal corrective surgery was indicated in 6 patients (19,3%) with complete CLP in the age group of 15 – 22 years (n = 31).

Conclusions
The presented data have shown that two-step sequential cleft palate closure of primary palate and hard palate first followed by soft palate closure has been associated with minimal rate of secondary corrective surgery for ONF and VPI at a relatively low need for surgical skeletal correction.
Suicide prevention for substance using youth experiencing homelessness: study protocol for a randomized controlled trial
Authors: Slesnick Natasha , Brakenhoff Brittany , Chavez Laura J. , Cuthbertson Caleb L. , Famelia Ruri , Feng Xin , Ford Jodi , Holowacz Eugene , Jaderlund Soren , Kelleher Kelly , Luthy Ellison , Mallory Allen M. , Pizzulo Alexis , Slesnick Tatiana D. , Yilmazer Tansel 
Published: March 2024

Abstract
Background
While research on substance using youth experiencing homelessness (YEH) is increasing, there is a dearth of information regarding effective prevention interventions for these youth. Suicide is the leading cause of death among YEH and most youth do not access services that may be available to them. Therefore, this study seeks to address this gap in the research literature with the goal to identify an effective suicide prevention intervention that can be readily adopted by communities that serve these youth.

Methods
Three hundred (N = 300) YEH with recent substance use and suicidal ideation or a recent suicide attempt will be recruited from the streets as well as a drop-in center serving YEH. After the baseline assessment, all youth will be randomly assigned to Cognitive Therapy for Suicide Prevention (CTSP) + Services as Usual (SAU) (N = 150) or to SAU alone (N = 150). SAU includes outreach, advocacy, and service linkage whereas YEH who receive CTSP will also receive ten CTSP sessions and an optional nine booster sessions. Follow-up assessments will be conducted at 3, 6, 9, and 12 months post-baseline. Theoretically derived mediators (e.g., cognitive distortions) will be tested to shed light on mechanisms associated with change, and the moderating effects of sex, race, sexual orientation, and baseline service connection will be examined. In order to ease future dissemination of the intervention to agencies serving YEH, we will rigorously assess acceptability, feasibility, fidelity, and cost associated with the delivery of our intervention approach using a mixed-methods approach.

Discussion
This study adds to a very small number of clinical trials seeking to prevent lethal suicide among a very high-risk group by addressing suicidal ideation directly rather than underlying conditions. It is hypothesized that youth receiving CTSP + SAU will show greater reductions in suicidal ideation (primary outcome), substance use, and depressive symptoms (secondary outcomes) over time compared to SAU alone, as well as improved risk and protective factors.

Trial registration
NCT05994612. Date of Registration: August 16, 2023.
Behavioral economic and wellness-based approaches for reducing alcohol use and consequences among diverse non-student emerging adults: study protocol for Project BLUE, a randomized controlled trial
Authors: Murphy James G. , Dennhardt Ashley A. , Tempchin Jacob , Colgonis Hannah E. , McDevitt-Murphy Meghan E. , Borsari Brian , Berlin Kristoffer S. 
Published: March 2024

Abstract
Background
Emerging adults (EAs) who are not 4-year college students nor graduates are at elevated risk for lifetime alcohol use disorder, comorbid drug use, and mental health symptoms, compared to college graduates. There is a need for tailored brief alcohol intervention (BAI) approaches to reduce alcohol risk and to facilitate healthy development in this high-risk population. Most BAIs include a single session focused on discussing risks associated with drinking and correcting normative beliefs about drinking rates. EAs may benefit from additional elements that enhance general wellness. The substance-free activity session (SFAS) aims to clarify life goals and values and increase goal-directed activities that provide alternatives to alcohol use, and the relaxation training (RT) session teaches relaxation and stress reduction skills.

Methods
The present study is a randomized 3-group (BAI + SFAS vs. RT + SFAS vs. education control) trial with 525 EAs (175 per group; estimated 50% women and 50% African American) who report recent risky drinking and who are not students or graduates of 4-year colleges. Participants will have the option of completing the intervention sessions in person or via a secure video teleconference. Levels of drinking and alcohol-related problems will be evaluated at baseline and 1, 3, 6, and 12 months post-intervention. The primary hypothesis is that both BAI + SFAS and RT + SFAS participants will report significantly greater reductions in alcohol use and problems relative to education control participants, with no differences in outcomes between the two active treatment conditions.

Discussion
The results of this study will inform alcohol prevention efforts for high-risk community dwelling emerging adults.

Trial registration
ClinicalTrials.gov Identifier: NCT04776278.