bluuebunny/crossref_metadata_2025_split huggingface dataset:
AnchorFCI: harnessing genetic anchors for enhanced causal discovery of cardiometabolic disease pathways
Authors: Ribeiro Adèle H. , Crnkovic Milena , Pereira Jaqueline Lopes , Fisberg Regina Mara , Sarti Flavia Mori , Rogero Marcelo Macedo , Heider Dominik , Cerqueira Andressa 
Published: December 2024

IntroductionCardiometabolic diseases, a major global health concern, stem from complex interactions of lifestyle, genetics, and biochemical markers. While extensive research has revealed strong associations between various risk factors and these diseases, latent confounding and limited causal discovery methods hinder understanding of their causal relationships, essential for mechanistic insights and developing effective prevention and intervention strategies.MethodsWe introduce anchorFCI, a novel adaptation of the conservative Really Fast Causal Inference (RFCI) algorithm, designed to enhance robustness and discovery power in causal learning by strategically selecting and integrating reliable anchor variables from a set of variables known not to be caused by the variables of interest. This approach is well-suited for studies of phenotypic, clinical, and sociodemographic data, using genetic variables that are recognized to be unaffected by these factors. We demonstrate the method’s effectiveness through simulation studies and a comprehensive causal analysis of the 2015 ISA-Nutrition dataset, featuring both anchorFCI for causal discovery and state-of-the-art effect size identification tools from Judea Pearl’s framework, showcasing a robust, fully data-driven causal inference pipeline.ResultsOur simulation studies reveal that anchorFCI effectively enhances robustness and discovery power while handles latent confounding by integrating reliable anchor variables and their non-ancestral relationships. The 2015 ISA-Nutrition dataset analysis not only supports many established causal relationships but also elucidates their interconnections, providing a clearer understanding of the complex dynamics and multifaceted nature of cardiometabolic risk.DiscussionAnchorFCI holds significant potential for reliable causal discovery in complex, multidimensional datasets. By effectively integrating non-ancestral knowledge and addressing latent confounding, it is well-suited for various applications requiring robust causal inference from observational studies, providing valuable insights in epidemiology, genetics, and public health.
Integration of single-cell and bulk analysis reveals TBXAS1 as a key platelet-related gene causing poor prognosis in osteosarcoma
Authors: Liu Han , Da Wacili , Mu Jianhua , He Xuanhong , Li Zhuangzhuang , Gong Taojun , Wang Jingjing , Min Li , Lu Minxun , Tu Chongqi 
Published: December 2024

BackgroundPlatelets are associated with poor prognosis in most tumors, but their specific pathogenic mechanism in osteosarcoma is not yet clear. The objective of this study is to conduct an in-depth analysis of how genes closely related to platelet function impact the prognosis of osteosarcoma patients. We hope that through this research, we can uncover the potential mechanisms of these genes in the development and progression of osteosarcoma, thereby providing new therapeutic strategies and theoretical foundations for improving the prognosis of osteosarcoma patients.MethodWe collected the blood routine test data of patients who were initially diagnosed with osteosarcoma at the Department of Bone Tumors, West China Hospital, from January 2012 to January 2022. By applying the LASSO-COX regression analysis, a statistical method, we found that the platelet count is associated with the prognosis of osteosarcoma patients. To further explore this relationship, we obtained single-cell data and bulk RNA data of osteosarcoma patients from the TARGET database and GEO database, respectively. By analyzing these data, we revealed at the transcriptomic level how platelets contribute to the poor prognosis in osteosarcoma patients.ResultPlatelets are associated with the prognosis of osteosarcoma patients (HR = 3.9, 95% CI = 1.9–8.1, P &lt; 0.001). Through the analysis of transcriptomic data from the TARGET database and GEO database, we found significant heterogeneity in tumor-specific pathways and immune infiltration under different platelet-related gene expression patterns. Among these, TBXAS1 was identified as a key gene that affects the prognosis of osteosarcoma patients. In addition, single-cell data analysis showed that the platelet-related gene TBXAS1 is mainly enriched in macrophages, and markers of macrophages are significantly associated with poor prognosis in osteosarcoma patients.ConclusionTBXAS1 is a key platelet-related gene that leads to poor prognosis in osteosarcoma, and this gene may affect the prognosis of osteosarcoma patients by interacting with macrophages.
Family planning utilization among postpartum women in the Bule Hora District, southern Ethiopia
Authors: Sirage Nurye , Desalegn Zewuditu , Wako Wako Golicha , Yimer Ali , Bizuneh Fassikaw Kebede , Feleke Sefineh Fenta , Yesuf Adem , Beyene Belda Negesa 
Published: December 2024

BackgroundContraception use remains low in Ethiopia, particularly within the first year after childbirth. While some women might have medical conditions that limit their contraceptive options, the primary obstacle to wider family planning adoption is not a specific health problem. Instead, it is the lack of equitable access to high-quality family planning services. This barrier significantly hinders women's ability to make informed decisions about their reproductive health. This study examines postpartum family planning utilization and its associated factors among postpartum mothers in the Bule Hora District.MethodsWe conducted a community-based cross-sectional study. A multistage sampling technique was employed to recruit a total of 630 women who had given birth. To collect the data, structured, standardized, and pretested questionnaires were used, and the collected data were coded and entered into Epi-data version 4.6. The data were analyzed using SPSS version 25. Both bivariable and multivariable logistic regressions were used to identify factors associated with postpartum family planning utilization.ResultsThe study found that 71.3% of women utilized postpartum family planning. Significant associations were found between postpartum family planning utilization and various factors, including counseling on family planning during pregnancy [adjusted odds ratio (AOR) = 1.79, 95% confidence interval (CI) 1.61–2.82], delivery (AOR = 2.62, 95% CI 1.56–4.38), and the postpartum period (AOR = 2.71, 95% CI 1.75–4.21). Women who resumed sexual activity after birth (AOR = 1.92, 95% CI 1.25–2.96), and who had at least four antenatal care visits (AOR = 3.09, 95% CI 1.61–5.92) were also more likely to use postpartum family planning. Women with grand multiparity were 69% less likely to use family planning methods than primiparous women (AOR = 0.31, 95% CI 0.13–0.73).ConclusionPostpartum family planning use in this study was higher than the national average. Factors such as parity; counseling during the pregnancy, delivery, and postpartum periods; and early resumption of sexual activity were linked to increased contraceptive use. These findings suggest that enhanced counseling during antenatal, delivery, and postnatal care could significantly increase contraceptive use.
Generation of a SARS-CoV-2-susceptible mouse model using adenovirus vector expressing human angiotensin-converting enzyme 2 driven by an elongation factor 1α promoter with leftward orientation
Authors: Matsumoto Yusuke , Honda Tomoko , Yasui Fumihiko , Endo Akinori , Sanada Takahiro , Toyama Sakiko , Takagi Asako , Munakata Tsubasa , Kono Risa , Yamaji Kenzaburo , Yamamoto Naoki , Saeki Yasushi , Kohara Michinori 
Published: December 2024

IntroductionTo analyze the molecular pathogenesis of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a small animal model such as mice is needed: human angiotensin converting enzyme 2 (hACE2), the receptor of SARS-CoV-2, needs to be expressed in the respiratory tract of mice.MethodsWe conferred SARS-CoV-2 susceptibility in mice by using an adenoviral vector expressing hACE2 driven by an elongation factor 1α (EF1α) promoter with a leftward orientation.ResultsIn this model, severe pneumonia like human COVID-19 was observed in SARS-CoV-2-infected mice, which was confirmed by dramatic infiltration of inflammatory cells in the lung with efficient viral replication. An early circulating strain of SARS-CoV-2 caused the most severe weight loss when compared to SARS-CoV-2 variants such as Alpha, Beta and Gamma, although histopathological findings, viral replication, and cytokine expression characteristics were comparableDiscussionWe found that a distinct proteome of an early circulating strain infected lung characterized by elevated complement activation and blood coagulation, which were mild in other variants, can contribute to disease severity. Unraveling the specificity of early circulating SARS-CoV-2 strains is important in elucidating the origin of the pandemic.
Chemo-free salvage treatment outperforms traditional chemotherapy in advanced lines of relapsed/refractory subcutaneous panniculitis-like T-cell lymphoma
Authors: Chen Chao , Yin Jingjing , Duan Minghui , Wang Wei , Zhao Danqing , Wei Chong , Jia Congwei , Zhang Wei , Zhou Daobin , Zhang Yan 
Published: December 2024

IntroductionSubcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of non-Hodgkin lymphoma with a good prognosis, but the optimal treatment for relapsed/refractory (R/R) SPTCL has been rarely discussed.MethodsThis study aims to compare the efficacy of conventional chemotherapy and chemo-free immunomodulatory regimen for R/R SPTCL. We retrospectively reviewed the patients with first relapse or primary refractory SPTCL between September 1997 and October 2020.ResultsA total of 19 patients with R/R SPTCL with a median age of 34 were included. All patient received the first-line chemotherapy-based treatment with a median PFS of 1.8 months. In these patients, 16 received salvage second-line treatment with an ORR of 31.3% and a median TTNT of 3.0 months. 13 of these 16 patients received chemotherapy-based treatment, resulting in a median TTNT of 2.4 months. 2 of these 16 patients received allogeneic hematopoietic stem cell transplantation and achieved long term complete remission (CR). In third-line treatment, 7 patients received chemotherapy-based regimen and 6 received chemo-free regimen such as VRMP (bortezomib, lenadomide and methylprednisolone) regimen and CsA plus IFNα regimen. The median TTNT of chemotherapy and chemo-free group were 3.2 months and not reached, respectively.DiscussionChemo-free group had a better TTNT than chemotherapy group (p=0.007). The use of chemotherapy-free regimens for R/R SPTCL appears promising and warrants further validation.
Evaluation of the safety, tolerability, pharmacokinetics and pharmacodynamics of SM17 in healthy volunteers: results from pre-clinical models and a first-in-human, randomized, double blinded clinical trial
Authors: Xu Guolin , Paglialunga Sabina , Qian Xuchen , Ding Ru , Webster Kenneth , van Haarst Aernout , Engel Caroline , Hui Chin Wai , Lam Lik Hang , Li Weimin , Wu Wai Chung , Rasmussen Scott , Hunt Allen , Leung Shui-on 
Published: December 2024

BackgroundAlarmins mediate type 2 T helper cell (Th2) inflammation and serve as upstream signaling elements in allergic inflammation and autoimmune responses. The alarmin interleukin (IL)-25 binds to a multi-domain receptor consisting of IL-17RA and IL-17RB subunits, resulting in the release of Th2 cytokines IL-4, IL-5, IL-9 and IL-13 to drive an inflammatory response. Therefore, the blockage of IL-17RB via SM17, a novel humanized monoclonal antibody, offers an attractive therapeutic target for Th2-mediated diseases, such as asthma.MethodsWild-type mice were stimulated with house dust mite (HDM) extracts for evaluation of SM17’s pre-clinical efficacy in allergic asthma. The safety, pharmacokinectics (PK), pharmacodynamics (PD), and immunogenicity of intravenous (IV) doses of SM17 were assessed in a 2-part clinical study in healthy adult subjects. In Part A, 53 healthy participants were enrolled to receive a single IV dose of SM17 (2, 20, 70, 200, 400, 600, 1200 mg) or placebo. In Part B, 24 healthy subjects were enrolled to receive a single IV dose of SM17 every two weeks (Q2W; 200, 400, 600 mg) or placebo for a total of 3 doses.ResultsAnimal studies demonstrated that SM17 significantly suppressed Th2 inflammation in the bronchoalveolar lavage fluid and infiltration of immune cells into the lungs. In the Phase I clinical study, no drug-related serious adverse events were observed. Total SM17 exposure increased by approximately 60- to 188-fold with a 60-fold increase in dose from 20 to 1200 mg SM17. Upon administration of the third dose, mean accumulation ratios over 200-600 mg was 1.5 to 2.1, which confirms moderate accumulation of SM17. After Q2W dosing of SM17 over 4 weeks, total exposure increased in a dose-proportional manner from 200 mg to 600 mg SM17.ConclusionIn the pre-clinical studies, we demonstrated that SM17 is a potential therapeutic agent to treat allergic asthma. In the Phase 1 clinical trial, a single IV dose of SM17 up to 1200 mg and three Q2W doses up to 600 mg were well tolerated in healthy participants and demonstrated a favorable safety profile. The pre-clinical efficacy and clinical PK and immunogenicity results of SM17 support further clinical development.Clinical trial registrationhttps://clinicaltrials.gov/, identifier NCT05332834.
Reflections on the interpretation and application of the due diligence obligation in international climate litigation: a comparative study of Daniel Billy et al. v. Australia and the COSIS advisory opinion
Authors: Liang Shiqi 
Published: December 2024

This article examines the interpretation and implementation of due diligence obligation in international climate litigation and advisory opinions, specifically by comparing Daniel Billy et al. v. Australia and the COSIS Advisory Opinion. It offers insights into the definition of due diligence obligation, the criteria for breach, and the remedies available under various legal frameworks. The due diligence obligation is not solely a direct duty under a specific treaty; it also imposes a positive obligation of conduct that must be evaluated within a broader legal framework. This method facilitates systemic integration. It facilitates the citation of pertinent regulations and precedents from different domains of international law during treaty interpretation. This approach promotes the harmonization and integration of various legal systems. The essay performs a comparative analysis of two cases. It analyses the implementation of the due diligence obligation in the realms of environmental and human rights protection. The emphasis is on the legal responsibility of States about climate change. The paper ultimately outlines the significance of the two instances for the future of international environmental law and the protection of human rights, highlighting the crucial role of due diligence responsibilities in combating climate change.
Nonspecific cervical spine pain/neck pain/in medical personnel of north-eastern Poland—A cross-sectional study
Authors: Citko Anna , Górski Stanisław , Marcinowicz Ludmiła , Mateusz Cybulski , Matylda Sierakowska 
Published: December 2024

Both mechanical and psychological overload are inherent to the work of nurses and paramedics, resulting spondylogenic pain.Aim of the studyTo identify potential risk factors influencing the prevalence of non-specific cervical spine pain in professionally active nurses and paramedics.Material and methods324 nurses (53.2% of the total) and 285 paramedics (46.8%) were included in the study−609 people in total. The study was carried out using an auditorium survey technique supervised by the researchers. The methods used were: Nordic Musculoskeletal Questionnaire, a spinal pain questionnaire validated according to IEA guidelines, a short version of the IPAQ and the author's survey questionnaire, concerning sociodemographic data, chronic diseases including metabolic syndrome (MetS). A univariate logistic regression model was used in the statistical analysis. The level of statistical significance was taken as p &lt; 0.05.ResultsRecurrent NP was significantly more common in paramedics compared to nurses (29.5 % vs. 9.3 %; p &lt; 0.0001). In a univariate logistic regression model, the risk of NP was significantly increased by: length of service &gt; 15 years (p &lt; 0.024), presence of: low back pain (p &lt; 0.0001), type 2 diabetes (p = 0.013), hypertension (p &lt; 0.001), depression (p &lt; 0.01). Of the modifiable factors, the risk of NP was significantly increased by high physical activity and short sleep &lt;7 h (p &lt; 0.001).
Association of plasma homocysteine with cognitive impairment in patients with Parkinson’s disease
Authors: Xiao Yan , Gan Lin-Hua , Liang Xiao-Niu , Xu Zhi-Heng , Hu Tian-Yu , Li Xiu-Yuan , Tang Yi-Lin , Wang Jian , Liu Yi-Qi 
Published: December 2024

BackgroundElevated plasma homocysteine (Hcy) has been reported as a risk factor for cognitive impairment in the general population. However, there are conflicting results regarding the relationship between Hcy and cognitive impairment across various cognitive domains in Parkinson’s disease (PD).ObjectiveThis study aims to explore the association between plasma Hcy levels, cognitive impairment, and dysfunction in various cognitive domains among PD patients with and without mild cognitive impairment (MCI).MethodsA total of 101 PD patients underwent plasma Hcy measurement, comprising 50 PD-MCI patients and 51 patients with normal cognition (PD-NC). A battery of neuropsychological tests was administered to assess different cognitive domains. Adjusted generalized linear models were used to assess the correlations between Hcy levels and cognitive functions.ResultsAs anticipated, PD-MCI patients demonstrated a significant decline in cognitive function across all five cognitive domains (memory, executive function, attention/working memory, language, and visuospatial function). Elevated plasma Hcy levels (≥ 10 μmol/L) were associated with a higher odds of PD-MCI, even within the normal range of Hcy levels (&lt; 15 μmol/L). After adjusting for confounding factors, a negative correlation was observed between plasma Hcy levels and the performance on specific cognitive tests evaluating executive functions in PD, such as the Stroop Color-Word Test-C (β = −1.123, 95% CI = −1.845 ∼−0.401, p = 0.0023).ConclusionThis study underscores a significant link between plasma Hcy levels and PD-MCI, particularly concerning executive dysfunction, even within the normal range of Hcy levels (&lt; 15 μmol/L).
Effect of micronutrients on the risk of Graves’ disease: a Mendelian randomization study
Authors: Chen Fangsen , Qiu Rongliang , Lin Zhiqing , Chen Junhan , Liu Peitian , Huang Yanling 
Published: December 2024

BackgroundMicronutrient research on Graves’ disease (GD) is limited and controversial. Therefore, in order to explore possible correlations between genetically predicted amounts of six micronutrients [Copper (Cu), Iron (Ir), Zinc (Zn), Calcium (Ca), Vitamin C (VC), and Vitamin D (VD)] and GD risk, we carried out Mendelian randomization research (MR).MethodsWe conducted an MR analysis using genome-wide association studies (GWAS) from people of European ancestry and aggregated information from UK Biobank to provide insight into the relationships between micronutrients and GD. The causal link between exposure and outcome was tested using three different techniques: Inverse Variance Weighted (IVW), MR-Egger, and Weighted Median Estimator (WME). The heterogeneity of outcomes was also assessed using Cochran’s Q statistic, and pleiotropy was assessed by MR-Egger intercept, MR-PRESSO.ResultsIVW analyses showed evidence of no significant effect of genetically predicted micronutrient concentrations on GD, except for Cu. (Cu: OR = 1.183, p = 0.025; Ir: OR = 1.031, p = 0.794; Zn: OR = 1.072, p = 0.426; Ca: OR = 1.040, p = 0.679; VC: OR = 1.011, p = 0.491; VD: OR = 0.902, p = 0.436). Significant heterogeneity was observed in Ca and VD (Ca: Q = 264.2, p = 0.002; VD: Q = 141.42, p = 0.047). The MR-Egger intercept method identified horizontal pleiotropy between serum Ca levels and GD (MR-Egger intercept = −0.010, p = 0.030), with no similar findings for other micronutrients.ConclusionMR analysis showed a possible causal relationship between the genetically predicted concentration of Cu and the risk of GD, whereas the genetically predicted concentrations of Ir, Zn, Ca, VC, and VD may not be causally related to the risk of GD.
Activation of cannabinoid receptor 2 by turmeric oleoresin reduces inflammation and oxidative stress in an osteoarthritis in vitro model
Authors: Ghiselli Federico , Majer Roberta , Piva Andrea , Grilli Ester 
Published: December 2024

IntroductionOsteoarthritis (OA) is a chronic degenerative joint disease characterized by the progressive degradation of articular cartilage, resulting in pain and reduced mobility. Turmeric (Curcuma longa L.) has been widely recognized for its anti-inflammatory and antioxidant properties, but the molecular mechanisms underlying its therapeutic effects remain inadequately explored. This study investigates the potential of turmeric oleoresin (TUR) to activate Cannabinoid Receptor 2 (CBR2) and its role in mediating anti-inflammatory and antioxidant effects in an in vitro OA model.Material and methodsMolecular docking and cAMP quantification assays were used to evaluate TUR’s agonistic activity on CBR2. Human chondrosarcoma cells (SW-1353) were treated with TUR under oxidative stress induced by menadione or inflammatory conditions simulated with IL-1β and TNF-α. The effects of TUR were assessed in the presence and absence of the CBR2 antagonist SR144528. Outcomes included changes in reactive oxygen species (ROS) production, inflammatory marker expression, oxidative defense markers and endocannabinoid system components and receptors.ResultsTUR was confirmed as a CBR2 agonist and significantly reduced ROS production, downregulated pro-inflammatory cytokines (IL-6, COX-2, metalloproteases), and suppressed signaling pathways such as NFKB1, ERK 1/2, and c-Myc. These effects were reversed upon CBR2 inhibition. TUR also enhanced HMOX-1 expression and modulated endocannabinoid-related enzymes, highlighting its impact on oxidative stress and the endocannabinoid system.DiscussionThese findings suggest that CBR2 activation is central to TUR’s anti-inflammatory and antioxidant effects. By modulating key pathways and endocannabinoid system components, TUR demonstrates potential as a novel therapeutic agent for OA management. Future studies could explore its clinical applications and further validate its molecular mechanisms in vivo.