bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term association of remnant cholesterol with all-cause and cardiovascular disease mortality: a nationally representative cohort study
Authors: Chen Min , Chen Zhi , Ye Huarong , Cheng Yuanling , Jin Zhigang , Cai Shaoqian 
Published: July 2024

Background and objectivesDespite reducing low-density lipoprotein cholesterol (LDL-C) to the normal range, residual cardiovascular risk remain. Remnant cholesterol (RC) exerts a potential residual risk for cardiovascular disease (CVD) prevention, and the long-term longitudinal association between RC and mortality has yet to be well elucidated.MethodsThis study examined a nationally representative sample of 13,383 adults aged 20 years or older (mean age 45.7 and 52% women) who participated in the NHANES III (from1988 to1994). Causes of death were ascertained by linkage to death records through December 31, 2019. The relations of RC with all-cause and CVD mortality were tested using weighted Cox proportional hazard models.ResultsThrough a median follow-up of 26.6 years, 5,044 deaths were reported, comprising 1,741 deaths of CVD [1,409 deaths of ischemic heart disease (IHD) and 332 deaths of stroke] and 1,126 of cancer. Compared to those with RC &lt;14.26 mg/dl (lowest quartile), participants with RC ≥29.80 mg/dl (highest quartile) had multivariable-adjusted HRs of 1.23 (95% CI: 1.07–1.42) for all-cause mortality, 1.22 (95% CI: 0.97–1.53) for CVD mortality, and 1.32 (95% CI: 1.03–1.69) for IHD mortality, and 0.89 (95% CI: 0.55–1.43) for stroke mortality, and 1.17 (95% CI 0.90–1.52) for cancer mortality. We observed that elevated RC levels increased CVD risk and IHD mortality despite LDL-C being in the normal range.ConclusionsElevated blood RC was associated with an increased long-term risk of all-cause, CVD, and IHD mortality. These associations were independent of socioeconomic factors, lifestyles, and history of diseases, and remained robust across the LDL-C stratum. Measuring RC levels might favor clinical assessment of early CVD risk. Further investigation is needed to elucidate the optimal range of RC levels for cardiovascular disease health in the general population.
Clinical and molecular study of patients with thyroid dyshormogenesis and variants in the thyroglobulin gene
Authors: Fernández-Cancio Mónica , Antolín María , Clemente María , Campos-Martorell Ariadna , Mogas Eduard , Baz-Redón Noelia , Leno-Colorado Jordi , Comas-Armangué Gemma , García-Arumí Elena , Soler-Colomer Laura , González-Llorens Núria , Camats-Tarruella Núria , Yeste Diego 
Published: July 2024

IntroductionDefects in any thyroid hormone synthesis steps cause thyroid dyshormonogenesis (THD). THD due to thyroglobulin (TG) gene variants is a cause of congenital hypothyroidism (CH) with a wide clinical spectrum, ranging from mild to severe permanent hypothyroidism. We present high-throughput sequencing results of patients with TG variants.MethodsA CH high-throughput sequencing-panel of the main genes involved in the regulation of thyroid hormonogenesis was performed to identify those TG variants that may be related to patient THD phenotype.ResultsWe identified 21 TG gene variants in 19 patients (11.8%) which could explain their phenotype. Ten of those (47.6%) were not previously described. CH was biochemically severe in these 19 patients. Eight of them were reevaluated after one month of discontinuing LT4 treatment and all had severe permanent hypothyroidism. We also identified another 16 patients who presented heterozygous TG variants, of whom, at reevaluation, five had mild permanent and only one had severe permanent hypothyroidisms.DiscussionsIn this study, 10 novel and 11 previously reported variants in the TG gene have been identified that could explain the phenotype of 19 patients from non-consanguineous families from a large THD cohort. Although not all these TG gene variants can explain all the patients’ THD phenotypes, some of them had severe or mild permanent hypothyroidism at reevaluation.
The predictive role of the platelet-to-lymphocyte ratio for the risk of non-alcoholic fatty liver disease and cirrhosis: a nationwide cross-sectional study
Authors: Yan Cheng , Zhang Weichang , Xiao Yangyan , Sun Yuxin , Peng Xinke , Cai Wenwu 
Published: July 2024

BackgroundThe associations between platelet-to-lymphocyte ratio (PLR) and non-alcoholic fatty liver disease (NAFLD) and cirrhosis are unclear, and there are still no effective means for diagnosing or monitoring disease progression.MethodsData from the National Health and Nutrition Examination Surveys were collected for analysis. Logistic regression and restricted cubic splines were used to evaluate the associations between PLR and NAFLD and cirrhosis in different populations. The Area Under Curve Receiver Operating Characteristic (AUCROC) was used to distinguish the models. Threshold analysis was performed by constructing a two-piecewise linear regression. Correlation analysis was performed separately on either side of the inflection point.ResultsA total of 5724 adults were included. Logistic regression analysis revealed that the PLR was associated with NAFLD and cirrhosis (AUCROC of NAFLD: 0.803; AUCROC of cirrhosis: 0.851). The AUCROC of the PLR for predicting NAFLD incidence was 0.762 in the diabetic population and 0.804 in the nondiabetic population. High PLR predicted cirrhosis in the diabetic population, with an AUCROC of 0.824, whereas a high PLR was not associated with cirrhosis in the nondiabetic population. The restricted cubic spline revealed a negative linear correlation between the PLR and NAFLD incidence. The inflection point of the PLR for NAFLD was 180.74. A PLR ≤180.74 was statistically significant (odds ratio=0.997, 95% confidence interval=0.995-0.999). In the NAFLD population, the PLR was negatively correlated with cirrhosis at a PLR ≤130.5 (odds ratio=0.987, 95% confidence interval=0.977-0.996) and positively correlated with cirrhosis at a PLR &gt; 130.5 (odds ratio=1.006, 95% confidence interval=1.001-1.012).ConclusionsThe PLR and NAFLD were negatively correlated in the U.S. population. The PLR had a U-shaped relationship with cirrhosis in the NAFLD population. The PLR has potential value in monitoring NAFLD patient progression to cirrhosis.
Perirenal fat thickness contributes to the estimated 10-year risk of cardiovascular disease and atherosclerotic cardiovascular disease in type 2 diabetes mellitus
Authors: Wang Wei , Lv Feng Yan , Tu Mei , Guo Xiu Li 
Published: July 2024

ObjectivePerirenal adipose tissue (PAT) has emerged as a potential therapeutic target for cardiovascular disease (CVD). However, the relationship between increased perirenal fat thickness (PrFT) and CVD risks in individuals with type 2 diabetes mellitus (T2DM) remains uncertain. This study aimed to evaluate the association between PrFT and the estimated 10-year risk of CVD and atherosclerotic cardiovascular disease (ASCVD) in T2DM.MethodThe final analysis included 704 participants. PrFT was quantified using non-enhanced computed tomography scans, while the estimated 10-year CVD and ASCVD risk assessments were based on the Framingham and China-PAR equation risk scores, respectively. Multiple regression analysis was employed to analyze the correlation between PrFT and these risk scores.ResultsHigher quartiles of PrFT displayed elevated Framingham and China-PAR equation risk scores (P&lt;0.001). After adjusting for cardiometabolic risk factors and visceral fat area, PrFT remained significantly correlated with Framingham equation risk scores in men (β=0.098, P=0.036) and women (β=0.099, P=0.032). Similar correlations were observed between PrFT and China-PAR equation risk scores in men (β=0.106, P=0.009) and women (β=0.108, P=0.007). Moreover, PrFT emerged as an independent variable associated with a high estimated 10-year risk of CVD and ASCVD, with odds ratios (ORs) of 1.14 (95% CI: 1.04-1.25, P=0.016) in men and 1.20 (95% CI: 1.11-1.31, P&lt;0.001) in women for high estimated CVD risk, and ORs of 1.22 (95% CI: 1.08-1.41, P=0.009) in men and 1.34 (95% CI: 1.12-1.60, P&lt;0.001) in women for high estimated 10-year ASCVD risk. Furthermore, restricted cubic spline analyses confirmed a nonlinear relationship between PrFT and high estimated CVD and ASCVD risk in both genders (P for nonlinearity and overall &lt; 0.05).ConclusionsPrFT contributed as an independent variable to the estimated 10-year risk of CVD and ASCVD in T2DM.
Taxonomic and functional diversity along successional stages on post-coalmine spoil heaps
Authors: Bakr Jawdat , Kompała-Bąba Agnieszka , Bierza Wojciech , Chmura Damian , Hutniczak Agnieszka , Błońska Agnieszka , Nowak Teresa , Magurno Franco , Jagodziński Andrzej M. , Woźniak Gabriela 
Published: July 2024

Coal is the most abundant fossil fuel in Europe, but the excavation of hard coal has covered large areas with disposed rock waste, and turned the natural habitats into disturbed novel ecosystems with harsh conditions differ in time and space. To examine the spontaneous complex successional gradient, we studied a large number of post coalmine heaps in Upper Silesia, which differ in vegetation type and age. Cluster analysis based on plant community composition (367 species in total) separated all surveyed plots on coal mining spoil heaps with herbaceous vegetation from Late Stage (LS) forests aged 14–56 years. Furthermore, the herbaceous vegetation was sub-grouped to three stages: Initial Stage (IS) aged 2–5 years, Early Stage (ES) aged 3–8 years and Mid-Stage (MS) aged 5–12 years. MS vegetation was characterised by the highest species richness and diversity (47 and 2.79) compared to ES (30 and 2.18) and IS (9 and 1.6), but higher species number and a similar diversity index occurred in LS (37 and 2.81). Functional diversity (FD) and community weighted mean (CWM) of nine functional traits showed higher (23.1) functional richness, higher (0.72) functional divergence, higher (4.5) functional dispersion, and higher value (24.4) of Rao’s quadratic entropy in LS compared to those calculated from the first three stages. Species at the initial successional stage (IS) were characterised by lower canopy height, seed mass, higher lateral spread, and specific leaf area (SLA). Additionally, the lowest (0.22 mg CO2 per hour per square metre) soil respiration (Sr) rate was recorded from IS compared to (0.53, 0.82 and 1.00) from ES, LS and MS, respectively. The soil water content (SWC) was the most important factor affecting the soil respiration, while the soil temperature (St) did not follow the well-studied relationship between soil respiration and soil temperature. Our spatial and temporal analyses illustrated changes in plant community assembly processes in the course of spontaneous vegetation succession on post coalmine spoil heaps. The importance of trait mediated abiotic filtration in community assembly in initial-, early-, and mid-stages of succession with an increase in competitive exclusion at the late successional stage was emphasized.
Fingerprint profiling for quality evaluation and the related biological activity analysis of polysaccharides from Liuweizhiji Gegen-Sangshen beverage
Authors: Wei Shulin , Li Mingxing , Zhao Long , Wang Tiangang , Wu Ke , Yang Jiayue , Tang Mingyun , Zhao Yueshui , Shen Jing , Du Fukuan , Chen Yu , Deng Shuai , Xiao Zhangang , Wei Mei , Li Zhi , Wu Xu 
Published: July 2024

IntroductionLiuweizhiji Gegen-Sangshen beverage (LGS) is popular in China, which has been used for alleviating alcohol-mediated discomfort and preventing alcoholic liver disease (ALD). This beverage is consisted of six herbal components that are known as functional foods and fruits. LGS is rich in polysaccharides, however, the activity and quality evaluation of LGS-derived polysaccharides remain unexplored. The purpose of this study is thus to establish a comprehensive quality control methodology for the assessment of LGS polysaccharides (LGSP) and to further explore the anti-oxidant, anti-inflammatory as well as prebiotic effect of LGSP.MethodsLGSP was extracted, followed by analysis of molecular weight distribution, monosaccharide content and structural characterization via integrating the application of high-performance size exclusion chromatography (HPSEC), 1-phenyl-3-methyl-5-pyrazolone-HPLC (PMP-HPLC), fourier transform infrared spectroscopy (FT-IR) as well as nuclear magnetic resonance spectroscopy (NMR) techniques. The anti-oxidation activity of LGSP was determined by DPPH, ABTS, hydroxyl radical scavenging capacity and total antioxidant capacity. The anti-inflammation of LGSP were assessed on the RAW 264.7 cells. The effect of LGSP on growth of Lactobacillus, Bifidobacterium bifidum and Bifidobacterium adolescentis was evaluated.ResultsThe results demonstrated that LGSP had two molecular weight distribution peaks, with the average molecular weights of (6.569 ± 0.12) × 104 Da and (4.641 ± 0.30) × 104 Da. LGSP was composed of 8 monosaccharides, with galacturonic acid, glucose rhamnose and galactose representing the highest molar ratios. Homogalacturonic acid (HG) type and rhamnosegalacturonic acid glycans I (RG-I) type and α-1,4-glucan were present in LGSP. LGSP concentration in LGS was 17.94 ± 0.28 mg/mL. Furthermore, fingerprint analysis combined with composition quantification of 10 batches of LGSP demonstrated that there was a high similarity among batches. Notably, LGSP exhibited anti-oxidant effect and inhibited expressions of pro-inflammatory factors (TNF-α and IL-6) in LPS-stimulated RAW 264.7 cells. In addition, LGSP remarkably promoted the proliferation of probiotics Lactobacillus, Bifidobacterium bifidum and Bifidobacterium adolescentis, showing good prebiotic activity.DiscussionThe results of present study would be of help to gain the understanding of structure–activity relationship of LGSP, provide a reference for quality evaluation of bioactive LGSP, and facilitate development of unique health and functional products in the future.
Camrelizumab combined with anlotinib as second-line therapy for metastatic or recurrent small cell lung cancer: a retrospective cohort study
Authors: Shen Shujing , Li Xingya , Guo Sanxing , Xu Liang , Yan Ningning 
Published: July 2024

IntroductionThis retrospective study evaluates the efficacy of camrelizumab combined with anlotinib versus chemotherapy in patients with extensive-stage small-cell lung cancer (ES-SCLC) undergoing second-line treatment.MethodsData were sourced from medical records at a Chinese medical facility, involving 34 patients diagnosed with ES-SCLC after failing first-line treatment. Patients were divided into two groups: one received camrelizumab (200 mg every 3 weeks) with anlotinib (12 mg daily for 14 days followed by a 7-day rest), while the other group received physician-chosen chemotherapy administered every 3 weeks. The primary endpoint was progression-free survival (PFS), with secondary endpoints including overall survival (OS), objective response rate (ORR), and disease control rate (DCR).ResultsThe combination therapy group showed a significant improvement in PFS compared to the chemotherapy group (median PFS: 7 months vs. 3 months; hazard ratio (HR): 0.34; 95% confidence interval (CI): 0.15-0.77; p&lt;0.001). However, there was no statistically significant difference in OS between the groups (16.3 months vs. 17.3 months; p=0.82). The ORR was 52.9% in the combination therapy group versus 23.5% in the chemotherapy group (p=0.08), and the DCR was 82.4% compared to 58.8% (p=0.26). Grade 3 or higher adverse events were observed in 17.6% of the combination therapy group and 29.4% of the chemotherapy group.ConclusionsThe findings suggest that the combination of camrelizumab and anlotinib offers a superior anti-tumor response with a manageable safety profile in a second-line setting for ES-SCLC patients. This combination regimen may be a viable option for second-line ES-SCLC treatment.
Neutrophilia in the bronchoalveolar lavage fluid increases coughing during flexible fiberoptic bronchoscopy in a pediatric cohort
Authors: Danino Laura , Stehling Florian , Eckerland Maximilian , Orhan Eser , Tschiedel Eva 
Published: July 2024

ObjectiveThis study is an addition to the already published prospective randomized double-blinded trial by Tschiedel et al. that compared two different sedation regimes in fiberoptic flexible bronchoscopy in pediatric subjects. The objective of the presented study is to analyze the correlation between the neutrophil percentage of the bronchoalveolar lavage fluid (BALF) and coughing episodes during bronchoscopy.MethodsFifty subjects, aged 1–17 years, received flexible fiberoptic bronchoscopy under deep sedation. The BALF of 39 subjects was analyzed with reference to cytology and microbiology.ResultsThe percentage of neutrophils from the total cell count ranged from 0% to 95.3% (median 2.7). Nineteen patients (49%) had a percentage of ≥3.0%. Pearson's correlation showed a high correlation (r = 0.529, p = 0.001) between the coughing episodes per minute and the neutrophil percentage in the BALF. Analysis of variance showed a significant difference in neutrophil percentage between the indication groups (p = 0.013). The t-test (p = 0.019) showed a significant difference between the neutrophil percentage for patients with a probable airway infection under immunosuppression (median 2.9) and patients with cystic fibrosis (median 49.6). The linear regression analysis showed a significantly stronger impact of the neutrophil percentage on coughing frequency than the sedation regime (βneutrophils = 0.526 with p = 0.001 vs. βsedation = 0.165 with p = 0.251).ConclusionWhen bronchoscopy is to be performed on a pediatric patient with suspected bacterial or viral infection, and therefore neutrophilic airway inflammation, coughing is to be expected.
FGF21-dependent alleviation of cholestasis-induced liver fibrosis by sodium butyrate
Authors: Yang Jing , Chen Lei , Zhao Shan-Shan , Du Chuang , Fan Yi-Zhe , Liu Hui-Xin , Li Yongchun , Li Yong-Zhi 
Published: July 2024

BackgroundThe beneficial effects of fibroblast growth factor 21 (FGF21) and sodium butyrate (NaB) on protection against cholestasis-induced liver fibrosis are not well known. This study aimed to explore the effects of FGF21 and NaB on bile duct ligation (BDL)-induced liver fibrosis.MethodsWild-type (WT) and FGF21 knockout (KO) mice received BDL surgery for 14 days. Liver fibrosis was assessed by Masson’s staining for fibrosis marker expressions at the mRNA or protein levels. Adenovirus-mediated FGF21 overexpression in the WT mice was assessed against BDL damage. BDL surgeries were performed in WT and FGF21 KO mice that were administered either phosphate-buffered saline or NaB. The effects of NaB on the energy metabolism and gut microbiota were assessed using stable metabolism detection and 16S rRNA gene sequencing.ResultsBDL-induced liver fibrosis in the WT mice was accompanied by high induction of FGF21. Compared to the WT mice, the FGF21 KO mice showed more severe liver fibrosis induced by BDL. FGF21 overexpression protected against BDL-induced liver fibrosis, as proved by the decreasing α-SMA at both the mRNA and protein levels. NaB administration enhanced the glucose and energy metabolisms as well as remodeled the gut microbiota. NaB alleviated BDL-induced liver fibrosis in the WT mice but aggravated the same in FGF21 KO mice.ConclusionFGF21 plays a key role in alleviating cholestasis-induced liver damage and fibrosis. NaB has beneficial effects on cholestasis in an FGF21-dependent manner. NaB administration can thus be a novel nutritional therapy for treating cholestasis via boosting FGF21 signaling and regulating the gut microbiota.
Dentin matrix protein 1 and HUVEC-ECM scaffold promote the differentiation of human dental pulp stem cells into endothelial lineage: implications in regenerative medicine
Authors: Ganapathy Amudha , Narayanan Karthikeyan , Chen Yinghua , Villani Cassandra , George Anne 
Published: July 2024

Reprograming of the dental pulp somatic cells to endothelial cells is an attractive strategy for generation of new blood vessels. For tissue regeneration, vascularization of engineered constructs is crucial to improve repair mechanisms. In this study, we show that dentin matrix protein 1 (DMP1) and HUVEC-ECM scaffold enhances the differentiation potential of dental pulp stem cells (DPSCs) to an endothelial phenotype. Our results show that the differentiated DPSCs expressed endothelial markers CD31 and VE-Cadherin (CD144) at 7 and 14 days. Expression of CD31 and VE-Cadherin (CD144) were also confirmed by immunofluorescence. Furthermore, flow cytometry analysis revealed a steady increase in CD31 and VE-Cadherin (CD144) positive cells with DMP1 treatment when compared with control. In addition, integrins specific for endothelial cells were highly expressed during the differentiation process. The endothelial cell signature of differentiated DPSCs were additionally characterized for key endothelial cell markers using gene expression by RT-PCR, Western blotting, immunostaining, and RNA-seq analysis. Furthermore, the angiogenic phenotype was confirmed by tubule and capillary sprout formation. Overall, stimulation of DPSCs by DMP1 and use of HUVEC-ECM scaffold promoted their differentiation into phenotypically, transcriptionally, and functionally differentiated bonafide endothelial cells. This study is novel, physiologically relevant and different from conventional strategies.
Cariprazine in the management of emotionally unstable personality disorder in female patients: a case series
Authors: Pappa Sofia , Caldwell-Dunn Ellice , Kalniunas Arturas , Kamal Manzar 
Published: July 2024

BackgroundEmotionally unstable personality disorder (EUPD) is debilitating psychiatric disorder, particularly common in female and forensic populations. However, appropriate pharmacological treatment to effectively manage symptoms of EUPD remains an unmet clinical need. Dopamine receptor partial agonists (DRPAs), such as aripiprazole, have a favourable tolerability profile and have demonstrated some benefits in targeting symptoms of emotional dysregulation, although, evidence regarding the effects of novel D2/D3 DRPA cariprazine in EUPD patients has been limited.ObjectivesTo evaluate the efficacy and tolerability of cariprazine for EUPD in a case series of female forensic inpatients where the diagnosis is more prevalent.MethodsDemographic and clinical information of the patients were collected from patient electronic records during their admission in a specialized NHS forensic service. Treatment response was measured using the Positive and Negative Syndrome Scale (PANSS) at baseline, 3 and 6 months and Global Clinical Impression Scale (CGI-scores) at baseline and 6 months. Tolerability and BMI, ECG QTc interval and prolactin levels were recorded prior to initiation and at 6 months.ResultsEight female patients with EUPD (mean age 29.8 years, SD 5.3) were treated with cariprazine (range 3–6mg). Total CGI-scores modestly improved from 5.6 baseline to 5.0 at 6 months. There was a reduction in mean total PANSS scores from baseline to 6 months (92.5, SD 8.1 to 72.4, SD 15.8), general psychopathology (56.1 SD 6.7 to 42.5, SD9.7), positive (21.9 SD 4.6 to 17.1, SD4.8) and negative PANSS scores (14.5 SD 6.3 to 12.8, SD4.6), corresponding to a 21%, 23%, 20% and 3% mean score reduction, respectively. Cariprazine demonstrated a favourable metabolic and hormonal side effect profile with no treatment discontinuation at 6 months follow up.ConclusionThis is the first case series to evaluate the effectiveness of cariprazine in EUPD. Its efficacy in improving PANSS and CGI-S scores was overall modest and highly variable, reflective of an inherently heterogenous and comorbid patient sample but the benefits on treatment perseverance and tolerability were considerable. Cariprazine may be of particular benefit in EUPD where psychotic symptoms are co-morbid, as an augmentation strategy to clozapine, or where previous antipsychotics have caused metabolic or hormonal side effects.