bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mapping socio-geographical disparities in the occurrence of teenage maternity in Colombia using multilevel analysis of individual heterogeneity and discriminatory accuracy (MAIHDA)
Authors: Mattsson Hedda , Gustafsson Johanna , Prada Sergio , Jaramillo-Otoya Laura , Leckie George , Merlo Juan , Rodriguez-Lopez Merida 
Published: February 2024

Abstract
Background
The prevalence of teenage pregnancy in Colombia is higher than the worldwide average. The identification of socio-geographical disparities might help to prioritize public health interventions.

Aim
To describe variation in the probability of teenage maternity across geopolitical departments and socio-geographical intersectional strata in Colombia.

Methods
A cross-sectional study based on live birth certificates in Colombia. Teenage maternity was defined as a woman giving birth aged 19 or younger. Multilevel analysis of individual heterogeneity and discriminatory accuracy (MAIHDA) was applied using multilevel Poisson and logistic regression. Two different approaches were used: (1) intersectional: using strata defined by the combination of health insurance, region, area of residency, and ethnicity as the second level (2) geographical: using geopolitical departments as the second level. Null, partial, and full models were obtained. General contextual effect (GCE) based on the variance partition coefficient (VPC) was considered as the measure of disparity. Proportional change in variance (PCV) was used to identify the contribution of each variable to the between-strata variation and to identify whether this variation, if any, was due to additive or interaction effects. Residuals were used to identify strata with potential higher-order interactions.

Results
The prevalence of teenage mothers in Colombia was 18.30% (95% CI 18.20–18.40). The highest prevalence was observed in Vichada, 25.65% (95% CI: 23.71–27.78), and in the stratum containing mothers with Subsidized/Unaffiliated healthcare insurance, Mestizo, Rural area in the Caribbean region, 29.08% (95% CI 28.55–29.61). The VPC from the null model was 1.70% and 9.16% using the geographical and socio-geographical intersectional approaches, respectively. The higher PCV for the intersectional model was attributed to health insurance. Positive and negative interactions of effects were observed.

Conclusion
Disparities were observed between intersectional socio-geographical strata but not between geo-political departments. Our results indicate that if resources for prevention are limited, using an intersectional socio-geographical approach would be more effective than focusing on geopolitical departments especially when focusing resources on those groups which show the highest prevalence. MAIHDA could potentially be applied to many other health outcomes where resource decisions must be made.
Bidirectional two-sample mendelian randomization analysis identifies causal associations of MRI-based cortical thickness and surface area relation to NAFLD
Authors: Mao Zun , Gao Zhi-xiang , Ji Tong , Huan Sheng , Yin Guo-ping , Chen Long 
Published: February 2024

Abstract
Background
Non-alcoholic fatty liver disease (NAFLD) patients have exhibited extra-hepatic neurological changes, but the causes and mechanisms remain unclear. This study investigates the causal effect of NAFLD on cortical structure through bidirectional two-sample Mendelian randomization analysis.

Methods
Genetic data from 778,614 European individuals across four NAFLD studies were used to determine genetically predicted NAFLD. Abdominal MRI scans from 32,860 UK Biobank participants were utilized to evaluate genetically predicted liver fat and volume. Data from the ENIGMA Consortium, comprising 51,665 patients, were used to evaluate the associations between genetic susceptibility, NAFLD risk, liver fat, liver volume, and alterations in cortical thickness (TH) and surface area (SA). Inverse-variance weighted (IVW) estimation, Cochran Q, and MR-Egger were employed to assess heterogeneity and pleiotropy.

Results
Overall, NAFLD did not significantly affect cortical SA or TH. However, potential associations were noted under global weighting, relating heightened NAFLD risk to reduced parahippocampal SA and decreased cortical TH in the caudal middle frontal, cuneus, lingual, and parstriangularis regions. Liver fat and volume also influenced the cortical structure of certain regions, although no Bonferroni-adjusted p-values reached significance. Two-step MR analysis revealed that liver fat, AST, and LDL levels mediated the impact of NAFLD on cortical structure. Multivariable MR analysis suggested that the impact of NAFLD on the cortical TH of lingual and parstriangularis was independent of BMI, obesity, hyperlipidemia, and diabetes.

Conclusion
This study provides evidence that NAFLD causally influences the cortical structure of the brain, suggesting the existence of a liver-brain axis in the development of NAFLD.
ACACA reduces lipid accumulation through dual regulation of lipid metabolism and mitochondrial function via AMPK- PPARα- CPT1A axis
Authors: Dong Jian , Li Muzi , Peng Runsheng , Zhang Yuchuan , Qiao Zilin , Sun Na 
Published: February 2024

Abstract
Background
Non-alcoholic fatty liver disease (NAFLD) is a multifaceted metabolic disorder, whose global prevalence is rapidly increasing. Acetyl CoA carboxylases 1 (ACACA) is the key enzyme that controls the rate of fatty acid synthesis. Hence, it is crucial to investigate the function of ACACA in regulating lipid metabolism during the progress of NAFLD.

Methods
Firstly, a fatty liver mouse model was established by high-fat diet at 2nd, 12th, and 20th week, respectively. Then, transcriptome analysis was performed on liver samples to investigate the underlying mechanisms and identify the target gene of the occurrence and development of NAFLD. Afterwards, lipid accumulation cell model was induced by palmitic acid and oleic acid (PA ∶ OA molar ratio = 1∶2). Next, we silenced the target gene ACACA using small interfering RNAs (siRNAs) or the CMS-121 inhibitor. Subsequently, experiments were performed comprehensively the effects of inhibiting ACACA on mitochondrial function and lipid metabolism, as well as on AMPK- PPARα- CPT1A pathway.

Results
This data indicated that the pathways significantly affected by high-fat diet include lipid metabolism and mitochondrial function. Then, we focus on the target gene ACACA. In addition, the in vitro results suggested that inhibiting of ACACA in vitro reduces intracellular lipid accumulation, specifically the content of TG and TC. Furthermore, ACACA ameliorated mitochondrial dysfunction and alleviate oxidative stress, including MMP complete, ATP and ROS production, as well as the expression of mitochondria respiratory chain complex (MRC) and AMPK proteins. Meanwhile, ACACA inhibition enhances lipid metabolism through activation of PPARα/CPT1A, leading to a decrease in intracellular lipid accumulation.

Conclusion
Targeting ACACA can reduce lipid accumulation by mediating the AMPK- PPARα- CPT1A pathway, which regulates lipid metabolism and alleviates mitochondrial dysfunction.
Magnetic resonance imaging-based approaches for detecting the efficacy of combining therapy following VEGFR-2 and PD-1 blockade in a colon cancer model
Authors: Xu Xi , Ma Mengjie , Ye Kunlin , Zhang Dong , Chen Xinhui , Wu Jiayang , Mo Xukai , Xiao Zeyu , Shi Changzheng , Luo Liangping 
Published: February 2024

Abstract
Background
Angiogenesis inhibitors have been identified to improve the efficacy of immunotherapy in recent studies. However, the delayed therapeutic effect of immunotherapy poses challenges in treatment planning. Therefore, this study aims to explore the potential of non-invasive imaging techniques, specifically intravoxel-incoherent-motion diffusion-weighted imaging (IVIM-DWI) and blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI), in detecting the anti-tumor response to the combination therapy involving immune checkpoint blockade therapy and anti-angiogenesis therapy in a tumor-bearing animal model.

Methods
The C57BL/6 mice were implanted with murine MC-38 cells to establish colon cancer xenograft model, and randomly divided into the control group, anti-PD-1 therapy group, and combination therapy group (VEGFR-2 inhibitor combined with anti-PD-1 antibody treatment). All mice were imaged before and, on the 3rd, 6th, 9th, and 12th day after administration, and pathological examinations were conducted at the same time points.

Results
The combination therapy group effectively suppressed tumor growth, exhibiting a significantly higher tumor inhibition rate of 69.96% compared to the anti-PD-1 group (56.71%). The f value and D* value of IVIM-DWI exhibit advantages in reflecting tumor angiogenesis. The D* value showed the highest correlation with CD31 (r = 0.702, P = 0.001), and the f value demonstrated the closest correlation with vessel maturity (r = 0.693, P = 0.001). While the BOLD-MRI parameter, R2* value, shows the highest correlation with Hif-1α(r = 0.778, P < 0.001), indicating the capability of BOLD-MRI to evaluate tumor hypoxia. In addition, the D value of IVIM-DWI is closely related to tumor cell proliferation, apoptosis, and infiltration of lymphocytes. The D value was highly correlated with Ki-67 (r = − 0.792, P < 0.001), TUNEL (r = 0.910, P < 0.001) and CD8a (r = 0.918, P < 0.001).

Conclusions
The combination of VEGFR-2 inhibitors with PD-1 immunotherapy shows a synergistic anti-tumor effect on the mouse colon cancer model. IVIM-DWI and BOLD-MRI are expected to be used as non-invasive approaches to provide imaging-based evidence for tumor response detection and efficacy evaluation.
A pilot investigation of the association between HIV-1 Vpr amino acid sequence diversity and the tryptophan-kynurenine pathway as a potential mechanism for neurocognitive impairment
Authors: Asia Levanco Keegan , Van Vuren Esmé Jansen , Lindeque Zander , Williams Monray Edward 
Published: February 2024

AbstractHIV infection compromises both the peripheral and central immune systems due to its pathogenic and neuropathogenic features. The mechanisms driving HIV-1 pathogenesis and neuropathogenesis involve a series of events, including metabolic dysregulation. Furthermore, HIV-subtype-specific variations, particularly alterations in the amino acid sequences of key viral proteins, are known to influence the severity of clinical outcomes in people living with HIV. However, the impact of amino acid sequence variations in specific viral proteins, such as Viral protein R (Vpr), on metabolites within the Tryptophan (Trp)-kynurenine (Kyn) pathway in people living with HIV remains unclear. Our research aimed to explore the relationship between variations in the Vpr amino acid sequence (specifically at positions 22, 41, 45, and 55, as these have been previously linked to neurocognitive function) and peripheral Trp-Kyn metabolites. Additionally, we sought to clarify the systems biology of Vpr sequence variation by examining the link between Trp-Kyn metabolism and peripheral inflammation, as a neuropathogenic mechanism. In this preliminary study, we analyzed a unique cohort of thirty-two (n = 32) South African cART naïve people living with HIV. We employed Sanger sequencing to ascertain blood-derived Vpr amino acid sequence variations and a targeted LC-MS/MS metabolomics platform to assess Trp-Kyn metabolites, such as Trp, Kyn, kynurenic acid (KA), and quinolinic acid (QUIN). Particle-enhanced turbidimetric assay and Enzyme-linked immunosorbent assays were used to measure immune markers, hsCRP, IL-6, suPAR, NGAL and sCD163. After applying Bonferroni corrections (p =.05/3) and adjusting for covariates (age and sex), only the Vpr G41 and A55 groups was nearing significance for higher levels of QUIN compared to the Vpr S41 and T55 groups, respectively (all p =.023). Multiple regression results revealed that Vpr amino acid variations at position 41 (adj R2 = 0.049, β = 0.505; p =.023), and 55 (adj R2 = 0.126, β = 0.444; p =.023) displayed significant associations with QUIN after adjusting for age and sex. Lastly, the higher QUIN levels observed in the Vpr G41 group were found to be correlated with suPAR (r =.588, p =.005). These results collectively underscore the importance of specific Vpr amino acid substitutions in influencing QUIN and inflammation (specifically suPAR levels), potentially contributing to our understanding of their roles in the pathogenesis and neuropathogenesis of HIV-1.
Incidence and influence factors of venous thromboembolism in traumatic rib fracture patient: a multicenter study
Authors: Zhang Dongsheng , Yang Yi , Yi Yunfeng , Wang Dongbin , Jiang Lei , Huang Hai , Jin Longyu , Meng Hui , Xia Fei , Guo Guangwei 
Published: February 2024

Abstract
Background
This study aimed to determine the incidence and influencing factors of venous thromboembolism (VTE) in patients with traumatic rib fractures.

Methods
The retrospective study analyzed medical records of patients with traumatic rib fractures from 33 hospitals.

Results
The overall incidence of VTE in hospitalized patients with traumatic rib fractures was 8.1%. Patients with isolated traumatic rib fractures had a significantly lower incidence of VTE (4.4%) compared to patients with rib fractures combined with other injuries (12.0%). Multivariate analysis identified the number of rib fractures as an independent risk factor for thrombosis. Surgical stabilization of isolated rib fractures involving three or more ribs was associated with a lower VTE incidence compared to conservative treatment.

Conclusions
Patients with rib fractures have a higher incidence of VTE, positively correlated with the number of rib fractures. However, the occurrence of thrombosis is relatively low in isolated rib fractures. Targeted thromboprophylaxis strategies should be implemented for these patients, and surgical stabilization of rib fractures may be beneficial in reducing the risk of VTE.
Biomechanical comparison of all-polyethylene total knee replacement and its metal-backed equivalent on periprosthetic tibia using the finite element method
Authors: Apostolopoulos Vasileios , Boháč Petr , Marcián Petr , Nachtnebl Luboš , Mahdal Michal , Pazourek Lukáš , Tomáš Tomáš 
Published: February 2024

Abstract
Background
Total knee arthroplasty (TKA) with all-polyethylene tibial (APT) components has shown comparable survivorship and clinical outcomes to that with metal-backed tibial (MBT). Although MBT is more frequently implanted, APT equivalents are considered a low-cost variant for elderly patients. A biomechanical analysis was assumed to be suitable to compare the response of the periprosthetic tibia after implantation of TKA NexGen APT and MBT equivalent.

Methods
A standardised load model was used representing the highest load achieved during level walking. The geometry and material models were created using computed tomography data. In the analysis, a material model was created that represents a patient with osteopenia.

Results
The equivalent strain distribution in the models of cancellous bone with an APT component showed values above 1000 με in the area below the medial tibial section, with MBT component were primarily localised in the stem tip area. For APT variants, the microstrain values in more than 80% of the volume were in the range from 300 to 1500 με, MBT only in less than 64% of the volume.

Conclusion
The effect of APT implantation on the periprosthetic tibia was shown as equal or even superior to that of MBT despite maximum strain values occurring in different locations. On the basis of the strain distribution, the state of the bone tissue was analysed to determine whether bone tissue remodelling or remodelling would occur. Following clinical validation, outcomes could eventually modify the implant selection criteria and lead to more frequent implantation of APT components.
Novel prognostic marker TGFBI affects the migration and invasion function of ovarian cancer cells and activates the integrin αvβ3-PI3K-Akt signaling pathway
Authors: Wang Hao , Xu Yin-hai , Guo Yi 
Published: February 2024

Abstract
Background
Individual patients with ovarian cancer show remarkably different prognosis. Present prognostic models for ovarian cancer mainly focus on clinico-pathological parameters, so quantifiable prognostic markers at molecular level are urgently needed. Platelets contribute to ovarian cancer progression, but have not been considered as biomarkers likely due to their instability. Here, we aimed to search for a stable prognostic marker from platelet-treated ovarian cancer cells, and explore its functions and mechanisms.

Methods
Microarrays analysis was done with platelet-treated SKOV-3 ovarian cancer cells. Relevant studies were searched in the Gene Expression Omnibus (GEO) database. The candidate genes were determined by differentially expressed genes (DEGs), Venn diagram drawing, protein-protein interaction (PPI) network, Cox proportional hazards model and Kaplan-Meier analysis. The expression of TGFBI in clinical samples was assessed by immunehistochemical staining (IHC), and the association of TGFBI levels with the clinic-pathological characteristics and prognosis in ovarian cancer patients was evaluated by univariate and multivariate analysis. The functions of TGFBI were predicted using data from TCGA, and validated by in vitro and in vivo experiments. The mechanism exploration was performed based on proteomic analysis, molecular docking and intervention study.

Results
TGFBI was significantly higher expressed in the platelet-treated ovarian cancer cells. An analysis of bioinformatics data revealed that increased expression of TGFBI led to significant decrease of overall survival (OS), progression-free survival (PFS) and post-progression survival (PPS) in ovarian cancer patients. Tissue microarray results showed that TGFBI was an independent factor for ovarian cancer, and TGFBI expression predict poor prognosis. Functionally, TGFBI affected the migration and invasion of ovarian cancer cells by regulation of epithelial mesenchymal transition (EMT) markers (CDH1 and CDH2) and extracellular matrix (ECM) degradation proteins (MMP-2). Mechanistically, TGFBI phosphorylated PI3K and Akt by combining integrin αvβ3.

Conclusions
We found out TGFBI as a novel prognostic indicator for ovarian cancer patients. TGFBI could promote metastasis in ovarian cancer by EMT induction and ECM remodeling, which might be associated with the activation of integrin αvβ3-PI3K-Akt signaling pathway.
SHARE-Topic: Bayesian interpretable modeling of single-cell multi-omic data
Authors: Kazwini Nour El , Sanguinetti Guido 
Published: February 2024

AbstractMulti-omic single-cell technologies, which simultaneously measure the transcriptional and epigenomic state of the same cell, enable understanding epigenetic mechanisms of gene regulation. However, noisy and sparse data pose fundamental statistical challenges to extract biological knowledge from complex datasets. SHARE-Topic, a Bayesian generative model of multi-omic single cell data using topic models, aims to address these challenges. SHARE-Topic identifies common patterns of co-variation between different omic layers, providing interpretable explanations for the data complexity. Tested on data from different technological platforms, SHARE-Topic provides low dimensional representations recapitulating known biology and defines associations between genes and distal regulators in individual cells.
Trial protocol for the Building Resilience through Socio-Emotional Training (ReSET) programme: a cluster randomised controlled trial of a new transdiagnostic preventative intervention for adolescents
Authors: Viding Essi , Lloyd Alex , Law Roslyn , Martin Peter , Lucas Laura , Wu Tom Chin-Han , Steinbeis Nikolaus , Midgley Nick , Veenstra René , Smith Jaime , Ly Lili , Bird Geoffrey , Murphy Jennifer , Plans David , Munafo Marcus , Penton-Voak Ian , Deighton Jessica , Richards Kathleen , Richards Mya , Fearon Pasco 
Published: February 2024

Abstract
Background
Adolescence is a period of heightened vulnerability to developing mental health problems, and rates of mental health disorder in this age group have increased in the last decade. Preventing mental health problems developing before they become entrenched, particularly in adolescents who are at high risk, is an important research and clinical target. Here, we report the protocol for the trial of the ‘Building Resilience through Socioemotional Training’ (ReSET) intervention. ReSET is a new, preventative intervention that incorporates individual-based emotional training techniques and group-based social and communication skills training. We take a transdiagnostic approach, focusing on emotion processing and social mechanisms implicated in the onset and maintenance of various forms of psychopathology.

Methods
A cluster randomised allocation design is adopted with randomisation at the school year level. Five-hundred and forty adolescents (aged 12–14) will be randomised to either receive the intervention or not (passive control). The intervention is comprised of weekly sessions over an 8-week period, supplemented by two individual sessions. The primary outcomes, psychopathology symptoms and mental wellbeing, will be assessed pre- and post-intervention, and at a 1-year follow-up. Secondary outcomes are task-based assessments of emotion processing, social network data based on peer nominations, and subjective ratings of social relationships. These measures will be taken at baseline, post-intervention and 1-year follow-up. A subgroup of participants and stakeholders will be invited to take part in focus groups to assess the acceptability of the intervention.

Discussion
This project adopts a theory-based approach to the development of a new intervention designed to target the close connections between young people’s emotions and their interpersonal relationships. By embedding the intervention within a school setting and using a cluster-randomised design, we aim to develop and test a feasible, scalable intervention to prevent the onset of psychopathology in adolescence.

Trial registration
ISRCTN88585916. Trial registration date: 20/04/2023.