bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between the neutrophil-to-high-density lipoprotein cholesterol ratio with kidney stone risk: a cross-sectional study
Authors: Du Yuan-Zhuo , Yang Jia-Qing , Yao Ji-Ming , Zhang Chi-Teng , Liu Yi-Fu 
Published: February 2025

ObjectiveKidney stones are a major issue for public health worldwide. Discovering potential clues in identifying at-risk individuals is essential for early detection and timely treatment. This study explores the relationship of the neutrophil-to-high-density lipoprotein cholesterol ratio (NHR) with the risk of kidney stones in U.S. adults.MethodsThe analysis involved 24,532 participants with available NHR and kidney stone data from the 2007–2018 NHANES period. Multivariable logistic regression models were used to quantify the relationship between NHR and kidney stone occurrence. Subgroup analyses were conducted to explore variations in effect.ResultsA total of 2,351 participants (9.93%) were diagnosed with kidney stones, and their mean age was 47.20 ± 0.26 years. After full adjustment in the multivariable regression model, higher NHR levels were linked to a greater risk of kidney stones (OR = 1.05, 95% CI: 1.02–1.08, P = 0.002). Participants in the highest tertile of NHR had a 34% increased chance of kidney stone development compared to those in the lowest tertile. A nonlinear connection between NHR and kidney stone risk was identified using restricted cubic spline (RCS) regression models. The relationship between NHR and kidney stone prevalence showed no significant variation across most subgroups (P for interaction &gt; 0.05).ConclusionThe results indicate that increased NHR is linked to a higher risk of kidney stones, with this relationship remaining consistent across various populations. NHR could be a useful biomarker for kidney stone risk, with key implications for early detection and individualized treatment.
Digital rural construction, resource mismatch, and rural land use efficiency
Authors: Fan Zhiguo , Guo Fenghua , Bian Chen 
Published: February 2025

IntroductionWith the acceleration of the allocation of agricultural resource elements in agricultural development, the relationship between digital rural construction and rural land use efficiency has become increasingly close.MethodsIn order to explore the impact and underlying mechanism of digital rural construction on rural land use efficiency, this paper constructs an evaluation system index for China's digital rural construction and uses the SBM-GML model to measure rural land use efficiency. Based on this, data from 30 provinces in China from 2010 to 2022 are used to test it using fixed effects and mediation effects models.Results(1) The construction of digital rural areas can directly promote the improvement of rural land use efficiency. This conclusion still holds true after endogeneity and robustness tests. (2) Mechanism analysis shows that digital rural construction can alleviate the mismatch of land resources, capital resources, and labor resources, thereby indirectly promoting the improvement of rural land use efficiency. (3) Heterogeneity analysis shows that the construction of digital rural areas has a more significant driving effect on the efficiency of rural land use in eastern and southern regions of China, as well as in major grain producing and selling areas.DiscussionThis article suggests continuing to promote the development strategy of digital rural construction, improving the problem of resource mismatch, and paying attention to the regional imbalance of digital rural construction. It is necessary to maintain the leading position of “first mover advantage” areas and also pay attention to filling the gaps in “later mover advantage” areas, in order to comprehensively promote the further improvement of rural land use efficiency.
Hypoxia-driven mobilization of altruistic cancer stem cells in platinum-treated head and neck cancer
Authors: Pathak Lekhika , Pal Bidisha , Talukdar Joyeeta , Saikia Partha Jyoti , Sandhya Sorra , Tasabehji Wale , Li Hong , Phukan Jyotirmoy , Bhuyan Anjan , Patra Sanjukta , Das Bikul 
Published: February 2025

BackgroundHead and neck cancers harbor dormant cancer stem cells (CSCs). This study explores how platinum therapy impacts these cells in a non-genetic manner and the role of hypoxia in this process. Previously, we identified a novel population of CSCs exhibiting an “altruistic” phenotype, sacrificing self-renewal to promote niche defense (tumor stemness defense, TSD), potentially protecting a dormant subpopulation of CSCs, the reawakening CSC (R-CSC) retaining stress memory. This TSD phenotype involves the activation of the MYC-HIF2α pathway and, importantly, is linked to a hypoxic tumor microenvironment. We termed these TSD+ CSCs “altruistic cancer stem cells” (A-CSCs). Here we investigated the potential role of tumor hypoxia in the mobilization of TSD+ CSCs to the circulation as a part of niche defense against platinum therapy.MethodsWe isolated CTCs and primary tumor cells from head and neck squamous cell carcinoma (HNSCC) patients undergoing platinum therapy (n = 14). We analyzed the TSD phenotype and markers of hypoxia in these cells. Additionally, we further characterized a previously reported pre-clinical model of platinum-induced tumor stemness to study the link between hypoxia, TSD+ CSC emergence, and mobilization to the circulation and bone marrow.ResultsWe isolated TSD+ CTCs with a hypoxic signature from eight out of 14 HNSCC patients. These cells displayed increased proliferation and invasion upon cisplatin treatment, suggesting a role in niche defense. Our pre-clinical model confirmed that hypoxia directly correlates with the expansion of TSD+ CSCs and their mobilization into the circulation and bone marrow following cisplatin treatment. We demonstrated the protection of R-CSCs by TSD+ CSCs. Notably, inhibiting hypoxia alone with tirapazamine did not reduce TSD+ CSCs, CTCs, or R-CSCs. However, combining tirapazamine with FM19G11, a MYC-HIF2α pathway inhibitor, significantly reduced the platinum-induced expansion of both TSD+ CSCs, CTCs, and the presence of R-CSCs in the bone marrow.ConclusionsThis study reveals that HNSCC patients undergoing platinum therapy can harbor TSD+ CTCs exhibiting an altruistic phenotype and a hypoxic signature. Additionally, the pre-clinical study provides a novel non-genetic mechanism of therapy resistance-the altruistic tumor self-defense. The tumor microenvironment, through the emergence of TSD+ CSCs, appears to act collectively to defend the tumor self-identity by hijacking an altruistic stem cell niche defense mechanism.
Resveratrol contributes to NK cell-mediated breast cancer cytotoxicity by upregulating ULBP2 through miR-17-5p downmodulation and activation of MINK1/JNK/c-Jun signaling
Authors: Ding Bisha , Li Jie , Yan Jia-Lin , Jiang Chun-Yan , Qian Ling-Bo , Pan Jie 
Published: February 2025

BackgroundsNatural killer (NK) cell mediated cytotoxicity is a crucial form of anti-cancer immune response. Natural killer group 2 member D (NKG2D) is a prominent activating receptor of NK cell. UL16-binding protein 2 (ULBP2), always expressed or elevated on cancer cells, functions as a key NKG2D ligand. ULBP2-NKG2D ligation initiates NK cell activation and subsequent targeted elimination of cancer cells. Enhanced expression of ULBP2 on cancer cells leads to more efficient elimination of these cells by NK cells. Resveratrol (RES) is known for its multiple health benefits, while current understanding of its role in regulating cancer immunogenicity remains limited. This study aims to investigate how RES affects the expression of ULBP2 and the sensitivity of breast cancer (BC) cells to NK cell cytotoxicity, along with the underlying mechanisms.MethodsThe effects of RES on ULBP2 expression were detected with qRT-PCR, western blot, flow cytometry analysis and immunohistochemistry. The effects of RES on sensitivity of BC cells to NK cell cytotoxicity were evaluated in vitro and in vivo. The target gene of miR-17-5p were predicted with different algorithms from five databases and further confirmed with dual-luciferase reporter assay. Overexpression and knockdown experiments of miR-17-5p and MINK1 were conducted to investigate their roles in regulating ULBP2 expression and subsequent JNK/c-Jun activation. The JNK inhibitor sp600125 was utilized to elucidate the specific role of JNK in modulating ULBP2 expression.ResultsRES increased ULBP2 expression on BC cells, thereby augmenting their vulnerability to NK cell-mediated cytotoxicity both in vitro and in vivo. RES administration led to a reduction in cellular miR-17-5p level. MiR-17-5p negatively regulated ULBP2 expression. Specifically, miR-17-5p directly targeted MINK1, leading to its suppression. MINK1 played a role in facilitating the activation of JNK and its downstream effector, c-Jun. Furthermore, treatment with sp600125, a JNK inhibitor, resulted in the suppression of ULBP2 expression.Conclusions：RES potentiates ULBP2-mediated immune eradication of BC cells by NK cells through the downregulation of miR-17-5p and concurrent activation of the MINK1/JNK/c-Jun cascade. This finding identifies RES as a potentially effective therapeutic agent for inhibiting BC progression and optimizing NK cell-based cancer immunotherapy.
Terroir and farming practices drive arbuscular mycorrhizal fungal communities in French vineyards
Authors: Battie-Laclau Patricia , Taudière Adrien , Bernard Mathilde , Bodénan Lucas , Duchemin Myriam , de Roman Yvan , Yol Azimê , Barry-Etienne Dominique 
Published: February 2025

BackgroundNature-based management of vineyards is at the heart of a sustainable development for the next decades. Although much is known about grapevine benefits from Arbuscular Mycorrhizal Fungi (AMF), little is known about the influence of vineyard terroir and farming practices on AMF communities.MethodsWe examined the relative effect of wine terroir and agricultural practices (organic, conversion, and conventional) on AMF abundance and diversity across 75 vineyards distributed over 14 wine terroirs in 6 winegrowing regions in France. We estimate AMF abundance by measuring spore density and root mycorrhization rates, and characterize AMF communities composition using metabarcoding by sampling both root and spore compartments for each vineyard.ResultsOrganic farming slightly increases AMF abundance (spore density and mycorrhization rate). Vineyards under conversion and using organic practices display a higher AMF diversity than conventional ones. Terroirs vary widely in terms of AMF abundance and diversity, with the median of OTUs count per sample ranging from 9 (Côte des Blancs) to 35 (Gigondas). The composition of AMF communities is structured mainly by terroir and in a lesser extent by practice. The effect of terroir on AMF communities is partially explained by distance decay and soil properties, but the majority of variation is still explained only by the terroir identity. Organic practices improve both abundance and diversity of AMF in vineyards, possibly leading to more productivity and resilience of grapevines.ConclusionThis large-scale study highlights the importance of terroir in our understanding of vineyard microbiome and paves the way to incorporation of AMF in microbial terroir studies and applications.
The role of statins in dementia or Alzheimer’s disease incidence: a systematic review and meta-analysis of cohort studies
Authors: Du Ye , Yu Zhangjie , Li Chengyi , Zhang Yanxing , Xu Buyun 
Published: February 2025

BackgroundThe effect of statins on the risk of dementia and Alzheimer’s disease (AD) is unclear.MethodsWe systematically searched EMBASE, Web of Science, PubMed, CENTRAL and ClinicalTrail.gov for cohort studies comparing incidence of new-onset dementia and AD between statin users and non-users. We applied the DerSimonian–Laird random effects method to pool hazard ratio (HR) with 95% confidence intervals (CI).ResultsWe included forty-two studies comprising 6,325,740 patients. Thirty-five cohort studies involving 6,306,043 participants were pooled and indicated that statin use was associated with a reduced risk of dementia (HR: 0.79, 95% CI: 0.71–0.88). Similarly, an analysis of 19 studies comprising 1,237,341 participants demonstrated a 29% decrease in the risk of AD among statin users (HR: 0.71, 95% CI: 0.60–0.85). In sensitivity analyses, diagnostic criteria for dementia/AD significantly affected the combined risk estimates. In subgroup analyses, compared to studies enrolling participants with a mean/median age over 70 years, those younger than 70 years exhibited greater efficacy of statins in preventing dementia (HR: 0.67, 95% CI: 0.56–0.81 vs HR: 0.86, 95% CI: 0.78–0.95; P = 0.02) and AD (HR: 0.47, 95% CI: 0.44–0.50 vs. HR: 0.81, 95% CI: 0.71–0.92; P &lt; 0.01). Due to significant heterogeneity in the definitions of statin dosage and exposure duration, pooling the results was abandoned and most studies suggested that higher dosages and longer exposure duration of statins further reduce the risk of dementia and AD.ConclusionStatin use is associated with a reduced incidence of dementia and AD, which might be modified by ages.
Discovery of novel and highly potent small molecule inhibitors targeting FLT3-ITD for the treatment of acute myeloid leukemia using structure-based virtual screening and biological evaluation
Authors: Shi Kun , Hong Ye , Liu Huajing , Yang Xiaotian , Wang Fengzhen , Zhang Yanming 
Published: February 2025

Considering the essential role of FLT3-ITD mutations in the development of acute myeloid leukemia (AML), the research and development of FLT3 inhibitors hold significant therapeutic potential. In this study, we identified a novel, highly potent small molecule inhibitor, FLIN-4, targeting FLT3 through structure-based virtual screening. Notably, FLIN-4 showed exceptional inhibitory effects in kinase activity inhibition assays, exhibiting a potent inhibitory effect against FLT3 (IC50 = 1.07 ± 0.04 nM). This potency was significantly superior to that of the known positive inhibitor Midostaurin, showing approximately 27 times higher inhibitory potency. Molecular dynamics simulations have confirmed the stable interaction between FLIN-4 and FLT3. Furthermore, cytotoxicity assays revealed that FLIN-4 has significant anti-proliferative activity against the AML cell line MV4-11 (IC50 = 1.31 ± 0.06 nM). Overall, these data suggest that FLIN-4, as a potential therapeutic candidate for AML, is valuable for further research and development.
Angel or devil: the dual roles of 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucopyranoside in the development of liver injury based on integrating pharmacological techniques: a systematic review
Authors: Jiang Jiajie , Wang Qixiu , Wu Qiang , Deng Bobin , Guo Cui , Chen Jie , Zeng Jinhao , Guo Yaoguang , Ma Xiao 
Published: February 2025

Background and purpose2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside (TSG) exhibits a dualistic pharmacological profile, acting as both a hepatoprotective and hepatotoxic agent, which is intricately linked to its interaction with multiple signaling pathways and its stereoisomeric forms, namely, cis-SG and trans-SG. The purpose of this study is to evaluate both the hepatoprotective and hepatotoxic effects of TSG and give therapeutic guidance.MethodsThis study performed a systematic search of eight databases to identify preclinical literature up until March 2024. The CAMARADES system evaluated evidence quality and bias. STATA and Python were used for statistical analysis, including dose-effect maps, 3D maps and radar charts to show the dose-time-effect relationship of TSG on hepatoprotection and hepatotoxicity.ResultsAfter a rigorous screening process, a total of 24 studies encompassing 564 rodents were selected for inclusion in this study. The findings revealed that TSG exhibited bidirectional effects on the levels of ALT and AST, while also regulating the levels of ALT, AST, TNF-α, IL-6, serum TG, serum TC, SOD, MDA, IFN-γ, and apoptosis rate. The histological analysis of liver tissue confirmed the regulatory effects of TSG, and a comprehensive analysis revealed the optimal protective dosage range was 27.27–38.81 mg/kg/d and the optimal toxic dosage range was 51.93–76.07 mg/kg/d. TSG exerts the dual effects on liver injury (LI) through the network of Keap1/Nrf2/HO-1/NQO1, NF-κB, PPAR, PI3K/Akt, JAK/STAT and TGF-β pathways.ConclusionTSG could mediate the pathways of oxidation, inflammation, and metabolism to result in hepatoprotection (27.27–38.81 mg/kg/d) and hepatotoxicity (51.93–76.07 mg/kg/d).
Narrative approach to understanding compassion: a mixed methods study in a Polish sample
Authors: Zieba Mariusz , Zatorski Mateusz P. , Wójcik Natalia E. 
Published: February 2025

ObjectivesThis study investigates the relationship between compassion, defined by Gilbert as “a sensitivity to suffering in self and others, with a commitment to try to alleviate and prevent it” and narrative identity. We explored whether individuals with high and low levels of compassion differ in narrative characteristics such as affective tone, agency, and communion themes, as well as the use of redemption or contamination sequences in stressful life event narratives.MethodsA mixed-method study was conducted with Polish adult participants (N = 63), half of whom had low and the other half high levels of compassion. Participants completed several questionnaires, including the Compassion Action and Engagement Scale. A few weeks later, they participated in individual interviews where they narrated several key life events. The interviews were recorded, transcribed, and coded by an individual blind to the participants' compassion levels and other identifying information. The self-narratives were analyzed for affective tone, agency and communion themes, and redemption and contamination sequences. Differences in these elements between individuals with low and high compassion were analyzed using t-tests.ResultsOur findings indicate that individuals with higher compassion more frequently incorporate themes of agency and communion in their narratives, particularly in stories of failure and the past year's most difficult event. The narrative identity of a highly compassionate person includes more content related to seeing oneself as sensitive to suffering and actively working to reduce or prevent it.ConclusionsThis study highlights how individuals with varying levels of compassion construct narratives about significant life events. Narrative approaches can foster compassionate engagements and actions, potentially improving therapeutic practices and personal development strategies. The results underscore the importance of narrative analysis in understanding compassion and suggest that compassion levels may influence how individuals interpret and narrate their life experiences, offering valuable insights for future research.
Real-world cost-effectiveness of nirmatrelvir-ritonavir as treatment for SARS-CoV-2 infection in the Belgian setting with omicron variant
Authors: Marbaix Sophie , Simoens Steven , Clevenbergh Philippe , Van Bleyenbergh Pascal , Liberman Keliane , Dehenau Dimitri 
Published: February 2025

BackgroundNirmatrelvir-ritonavir is an oral treatment for SARS-CoV-2 infection in patients who are at high risk of developing severe COVID-19 disease. This antiviral has proven to significantly reduce the risk of hospitalization and death compared to no anti-SARS-CoV-2 treatment in this target population. This paper aims to assess the cost-effectiveness of nirmatrelvir-ritonavir in Belgium using real-world evidence.MethodsA static decision tree model was developed to capture the health progression of patients infected with the SARS-CoV-2 virus. Outcomes were expressed in Quality Adjusted-Life Years (QALYs), hospitalizations, Intensive Care Unit (ICU) admissions, deaths and Long Covid cases, derived from epidemiological data over the first full year of the Omicron variant’s circulation (2022). Costs were calculated for the year 2023 from the healthcare payer’s perspective. Extensive sensitivity analyses were conducted to test the robustness of the cost-effectiveness results.ResultsIn a cohort of 1,000 patients, treatment with nirmatrelvir-ritonavir is projected to save 95 QALYs and €82,658 compared to no anti-SARS-CoV-2 treatment over a lifetime horizon. These savings primarily stem from the reduction in hospitalizations among vulnerable patients who typically require a longer recovery time. The analysis also indicates 5 fewer ICU admissions and 8 fewer premature deaths per 1,000 infected patients.ConclusionIn the context of Omicron SARS-CoV-2 infection, administering nirmatrelvir-ritonavir to patients at high risk of severe disease improves health outcomes and reduces costs. Nirmatrelvir-ritonavir is 100% likely to be cost-effective at a willingness to pay of €2,000 per QALY.
Micro- and Mesoplastic Consumption Tendency of Exaiptasia diaphana Sea Anemones
Authors: Kaliszewicz Anita , Czyżewska Agata , Karaban Kamil , Olejniczak Izabella , Boniecki Paweł 
Published: February 2025

Microplastics are an increasingly common threat to the aquatic environment, and, due to their small size, it is easy for them to spread and enter the seas and oceans. Micro- and mesoplastic particles are often ingested by marine organisms, especially those that have the potential for successful settlement on artificial substrata, including plastic. In laboratory experiments, we tested the tendency of the sea anemone Exaiptasia diaphana to consume plastic fragments and fibers of various sizes and shapes; these organisms are widely distributed in coastal waters, tide pools, and coral reefs. The plastic fragments and fibers were placed either in natural food or covered with a special food in gel form, which allowed them to retain their original shape. Our studies have shown that plastic in the shape of fibers is less readily consumed than in the form of fragments. The E. diaphana anemones with oral discs of diameter 10–12 mm had difficulty consuming long fibers. A total of 67% of the studied animals were unable to consume fibers of 13 mm length, while those of 3 and 7 mm length were consumed by 100% of the sea anemones. We have also established that microplastics taken with food are harmful to these cnidarians: mechanical injury to the body column was caused by the ingested polypropylene microfragments, and we also observed significantly increased mortality. Injuries, combined with the possible toxicological effects of the polymers, may have been the cause of increased mortality of the Exaiptasia diaphana.