bluuebunny/crossref_metadata_2025_split huggingface dataset:
HMOS 2’FL and 3FL prevent house dust mite induced proinflammatory cytokine release in vitro and decrease specific IgE production in a murine allergic asthma model
Authors: Zuurveld Marit , de Kleer Janna W. M. , Berends Alinda J. , Kooy Manou M. , Van Ark Ingrid , Leusink-Muis Thea , Kettelarij Nienke , Folkerts Gert , Garssen Johan , van’t Land Belinda , Willemsen Linette E. M. 
Published: February 2025

IntroductionAllergic asthma is characterized by sensitization to airborne allergens like house dust mite (HDM). Human milk oligosaccharides (HMOS) are linked to improved immune maturation and potentially alleviate allergy development.MethodsA human in vitro model for crosstalk between bronchial epithelial cells (BECs), monocyte-derived DCs (moDCs) and T cells, during HDM exposure, was established. The immunomodulatory effects of the HMOS 2′-fucosyllactose (2’FL) and 3-fucosyllactose (3FL) were investigated in this in vitro model and subsequently in a house dust mite-induced allergic asthma murine model.ResultsHDM exposure during BEC-DC coculture enhanced type 2 instructing TSLP, while reducing regulatory TGFβ secretion. Coculture of HDM-primed DCs with T cells enhanced IL4 secretion. 2’FL or 3FL preincubation prevented HDM-induced TSLP and IL8 release from BEC-DC. HDM-allergic mice receiving a 1% 2’FL or 0,5% 3FL supplemented diet both had lower serum levels of HDM-specific IgE compared to mice fed control diet. In conclusion, a human in vitro coculture model for HDM-induced BEC-DC activation and subsequent type 2 T cell response was established. 2’FL or 3FL preincubation of BEC-DC prevented HDM-induced activation and modified downstream T cell responses in vitro. Both HMOS reduced HDM-specific IgE in a murine model for HDM allergic asthma, but did not protect against airway inflammation.ConclusionHere, we describe an in vitro human airway mucosal HDM sensitization model as relevant tool to reduce use of animals in studies aiming to prevent HDM allergic asthma. Both in vitro as well as in vivo, HMOS were found to drive away from a type 2 immune signature, paving the way to further investigate the potential allergy preventive effects of fucosylated HMOS.
Training modalities for elder sarcopenic obesity: a systematic review and network meta-analysis
Authors: Qiu Hao , Zheng Wanxia , Zhou Xi , Liu Qianrong , Zhao Xuehong 
Published: February 2025

IntroductionSarcopenic obesity (SO) is a condition characterized by the coexistence of age-related obesity and sarcopenia. This systematic review and network meta-analysis (NMA) aimed to compare the effects of different training modalities, such as aerobic training (AT), resistance training (RT), combined resistance with AT (CT), and multicomponent training (MCT) on body composition, muscle strength, and physical performance in elderly patients with SO.MethodsWe electronically searched randomized controlled trials, published from inception to March 2024 in PubMed, Embase, Cochrane Library, Web of Science and Scopus. Effect estimates were presented as mean differences (MD) or Standard Mean Difference (SMD) with 95% confidence interval (CI). The comprehensive effects of all treatments were ranked by the surface under the cumulative ranking (SUCRA) probabilities.Results14 trials enrolling 955 participants were included. The body fat percentage (BFP) in MCT (MD= −6.37, 95% CI: −8.67, −4.07), CT (MD = −2.08, 95% CI: −4.00, −0.16), and RT (MD = −1.85, 95% CI: −3.25, −0.44) was significantly lower than in the normal control group, with MCT showing superior effects compared to CT and RT. Furthermore, only MCT significantly improved fat-free mass (FFM; MD = 5.21, 95% CI:1.51, 8.91), as well as in body mass index (BMI; MD = 0.74, 95% CI:0.08, 1.40). In addition, handgrip strength (HGS) significantly improved under both MCT (SMD = 0.87, 95% CI: 0.19, 1.5) and RT(SMD = 0.84, 95% CI: 0.43, 1.25). The performance on the 30s chair stand test also yielded better outcomes for MCT (MD = 3.10, 95% CI: 1.33, 4 0.86), CT(MD = 2 0.50, 95% CI: 0.18, 5.18), and RT(MD = 3.91, 95% CI: 2.30, 5.52) when compared to the control group. Lastly, gait speed was enhanced by both MCT (MD = 0.35, 95% CI: 0.30, 0.41) and CT(MD = 0.14, 95% CI: 0.06, 0.21). The ranking results indicated that MCT was superior to other training modalities in enhancing body composition and gait speed. In contrast, RT appears to be more advantageous in the 30-second chair standing test and in improving HGS.ConclusionMCT outperformed other training modalities in improving body composition and gait speed. RT was more beneficial for the 30-second chair standing test and enhancing HGS. These findings provide valuable insights for clinicians and researchers to customize exercise prescriptions for older patients with SO.Systematic review registrationhttp://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42024544962.
Clinical effects of Bifidobacterium Longum Subsp. Infantis YLGB-1496 on children with respiratory symptoms
Authors: Li Pin , Mageswary Uma , Ali Adli , Taib Fahisham , Koo Thai Hau , Yusof Azianey , Jiang Hua , Lan Hanglian , Hung Weilian , Liong Min-Tze , Zhang Yumei 
Published: February 2025

ObjectivesThis study aimed to examine the effects of Bifidobacterium longum subsp. infantis YLGB-1496 (B. infantis YLGB-1496) on the frequency of respiratory illness symptoms and immunity profiles among toddlers.MethodsIn this double-blind, randomized, placebo-controlled, 12-week intervention study, toddlers with at least 2 respiratory illness symptoms were randomly assigned into the probiotic (YLGB-1496) or placebo group at a 1:1 ratio. Follow-up examinations were conducted at baseline (week 0) and at weeks 6 and 12 of the intervention. The frequency of respiratory illness symptoms was assessed at these time points using validated questionnaires. Oral swabs and fecal samples were collected from participants at weeks 0, 6, and 12 to examine inflammatory cytokines.ResultsAmong the 120 toddlers initially included in the study, 115 completed the 12-week intervention (58 in the YLGB-1496 group and 57 in the placebo group). The risk of antibiotic use or clinical visits was significantly lower in the YLGB-1496 group than in the placebo group (antibiotic use odds ratio (OR) = 0.37 [0.369, 0.372]; clinical visit, OR = 0.743 [0.741, 0.744]), but these differences were nonsignificant after adjusting for other potential confounders (p &gt; 0.05). The YLGB-1496 group presented a lower incidence of several respiratory symptoms than the placebo group, including fever (p &lt; 0.001), cough (p &lt; 0.001), sneezing (p = 0.012), nose block (p = 0.001), and runny nose (p &lt; 0.001). The results also revealed that the salivary cortisol concentration was significantly lower in the YLGB-1496 group than in the placebo group (p = 0.026), but no effects on INF-γ, IL-1β, IL-13, IL-4, or IL-10 were detected.ConclusionBifidobacterium infantis YLGB-1496 may serve as a potential natural, nonpharmacological strategy for the safe management of respiratory tract issues in toddlers.Clinical trial registrationThe trial was registered at ClinicalTrials.gov (identifier number NCT05794815).
A retrospective study of neoadjuvant novel hormonal therapy prior to radical prostatectomy for high-risk prostate cancer
Authors: Shuai Hui , Zhang Wei , Liu Jianping , Zhang Peng , Chang Congwang , Fu Guanghua , Wu Tao 
Published: February 2025

PurposeThis study aims to retrospectively describe the perioperative outcomes and short-term oncological outcomes of high-risk prostate cancer patients treated with neoadjuvant novel hormonal therapy (NNHT) combined with radical prostatectomy (RP) or RP alone.Materials and MethodsFifty-five male patients underwent RP and were categorized based on whether NNHT was administered preoperatively. Clinical baseline characteristics, perioperative outcomes, and biochemical recurrence (BCR) rate were summarized using mean, standard deviation, medians, interquartile ranges, and frequencies. Group 1 (n=20) received NNHT in combination with RP, while Group 2 (n=35) received RP alone. Patients in the NNHT group received androgen deprivation therapy (ADT) combined with either abiraterone (1,000 mg/d), enzalutamide (160 mg/d), or apalutamide (240 mg/d) before RP. SPSS Statistics 27 was used for statistical analysis.ResultsAmong the 55 patients included in the study, the age, clinical T stage, N stage, biopsy Gleason scores, and the number of biopsy-positive needles appeared comparable across the two groups. However, patients in the NNHT+RP group had higher median preoperative serum prostate-specific antigen (PSA) levels (39.3 ng/mL, interquartile range [IQR]: 13.9-92.3) compared to the RP-only group (15.6 ng/mL, IQR: 10.7-19.8). The NNHT+RP group showed a lower proportion of positive surgical margins (PSM) (20%) compared to the RP-only group (49%). Similarly, the proportion of patients experiencing biochemical recurrence (BCR) within the follow-up period appeared lower in the NNHT+RP group (30%) compared to the RP-only group (57%). Additionally, operative time, hemoglobin decrease, transfusion rate, catheterization time, pathological T stage, and overall complication rates showed similar distributions across the two groups.ConclusionThis study suggests that NNHT+RP may be associated with lower rates of PSM and BCR compared to RP alone. However, further studies with larger cohorts and longer follow-up are needed to assess its long-term impact on survival and other outcomes.
Pilot study of an arterial enhancement fraction-based model for progression prediction in HCC undergoing chemoembolization
Authors: Chai Bin , Xiang Dongqiao , Zhou Guofeng , Zheng Chuansheng 
Published: February 2025

ObjectiveTo develop a prognostic model including arterial enhancement fraction of residual tumor (AEF-RT) for predicting progression-free survival (PFS) in hepatocellular carcinoma (HCC) patients after drug-eluting beads transarterial chemoembolization (DEB-TACE).Materials and methodsBetween March 2019 and March 2024, 111 HCC patients undergoing DEB-TACE were randomly allocated to a training cohort and a validation cohort in a 7:3 ratio. LASSO regression was applied in the training cohort to identify risk factors for recurrence, which were subsequently used to construct the Cox model. Model performance was assessed using the concordance index (C-index, where 0.5 indicates non-informative discrimination and 1 represents perfect discrimination) and Brier score (ranging from 0 to 1, 0 indicating higher calibration) and was compared with five existing prognostic models.ResultsThe final model, termed ADMAN model, incorporated AEF-RT, Diameter, Margin appearance, Aspartate transaminase, and Neutrophil-to-lymphocyte ratio. High-risk patients defined by ADMAN had 4.69 times greater progression risk than low-risk ones in the training cohort (p &lt; 0.001) and 3.52 times greater in the validation cohort (p = 0.005). The C-index of ADMAN (0.75) was significantly higher than that of other models in the training cohort (p &lt; 0.05 for all) and remained significantly higher than three of them in the validation cohort [0.71 vs. 0.55 (p = 0.041), 0.54 (p = 0.033), 0.53 (p = 0.004)]. The ADMAN model showed a significantly lower Brier score than that of other models at 6 months and 12 months in the training cohort (p &lt; 0.05 for all). In the validation cohort, the ADMAN model remained to have significantly lower Brier score than the four models (p &lt; 0.05) at 6 months, while it had significantly lower score than one model at 12 months.ConclusionsThe AEF-based model may be a promising tool for progression risk stratification in HCC patients undergoing DEB-TACE. Further external validation in independent cohorts with larger sample sizes is necessary to confirm the robustness of the ADMAN model.
Predicting microvascular invasion in solitary hepatocellular carcinoma: a multi-center study integrating clinical, MRI assessments, and radiomics indicators
Authors: Jian Wang , Zhan Lin , Zhaowang Lin , Ling Yang , Min Yu , Rong Xie , Wanxing Lin , Yongfei Yang , Haibin Tu 
Published: February 2025

BackgroundMicrovascular invasion (MVI) is a key prognostic factor in solitary hepatocellular carcinoma (HCC), significantly affecting treatment decisions and outcomes. Early prediction of MVI is crucial for enhancing clinical decision-making.ObjectivesThis study aimed to develop and evaluate four predictive models for MVI: one based on clinical indicators, one on MRI assessments, one using radiomics, and a combined model integrating all data across multiple medical centers.MethodsThe study included patients with solitary HCC from three centers (Mengchao Hepatobiliary Hospital, The Second Hospital of Nanping, and Datian County General Hospital). The dataset was divided into an internal training set, validation set, and two external validation sets. Predictive models were built using clinical indicators, MRI, radiomics, and a combination of these. Model performance was assessed through ROC curves, calibration curves, and decision curve analysis (DCA). Lasso regression identified significant features, and SHAP analysis interpreted the model predictions.ResultsA total of 319 patients were analyzed: 199 from the internal center, 67 from Nanping, and 53 from Datian. The combined model, which integrated clinical, MRI, and radiomics features, showed superior performance, with an AUC of 0.95(95%CI:0.92-0.98) in the internal training set, 0.92(95%CI:0.83-1.00) in the internal validation set, 0.96(95%CI:0.92-1.00) in Nanping, and 0.94(95%CI:0.88-0.99) in Datian. Calibration curves confirmed the model’s accuracy, and NRI/IDI analyses highlighted its advantage over individual models. Key predictive indicators included pseudocapsule, peritumoral enhancement, and wavelet-based MRI features.ConclusionThis multi-center study demonstrates the effectiveness of combining clinical, MRI, and radiomics data in predicting MVI in solitary HCC, with robust results across different medical centers. These models have potential to improve patient management and treatment planning.
Combinatorial genetic manipulation of Cx50, PI3K and PTEN alters postnatal mouse lens growth and homeostasis
Authors: Sellitto Caterina , White Thomas W. 
Published: February 2025

IntroductionPhosphoinositide 3-kinase (PI3K), Phosphatase and tensin homolog (PTEN) and connexin50 (Cx50) have individually been shown to play critical roles in the growth, development and maintenance of the lens and to functionally interact in vitro. To elucidate how gap junctional coupling mediated by Cx50 and intracellular signaling mediated by PI3K and PTEN synergistically interact to regulate lens homeostasis in vivo, we generated and characterized double knockout animal models lacking the p110α subunit of PI3K and Cx50, or PTEN and Cx50.MethodsWe interbred lens specific p110α and PTEN conditional knockout animals with Cx50 deficient mice to generate double knockouts. Animals and eyes were weighed, lenses were dissected, photographed, measured, fixed and sectioned for histological analysis. Lens epithelial cell proliferation was determined using 5-ethynyl-2’-deoxyuridine (EdU) labeling.ResultsDouble knockout of p110α and Cx50 led to a significant reduction in lens and eye size, and a high rate of lens rupture. The individual cell proliferation defects of the Cx50 and p110α single knockout lenses both persisted in the double KO. Double deletion of Cx50 and PTEN produced severe lens defects, including cataract, aberrant cell migration, altered cell proliferation, vacuole formation and lens rupture.ConclusionThe severe phenotypes in p110α/Cx50 and PTEN/Cx50 double deficient lenses suggest that PI3K, PTEN and Cx50 participate in both distinct and common regulatory pathways that are necessary to maintain normal lens growth and homeostasis.
Case report: Pharmacokinetic interaction involving sirolimus and regorafenib in patients with post-transplant recurrent hepatocellular carcinoma
Authors: Zhu Kongcai , Xiong Fang , Bai Haihong , Liu Wei 
Published: February 2025

BackgroundSirolimus is primarily metabolized by CYP3A4 and transported by P-gp. Drug interactions that affect this pathway can alter its plasma exposures, resulting in untargeted sirolimus concentrations.Case summaryIn this case report, we investigate a pharmacokinetic drug-drug interaction between regorafenib and sirolimus, mediated by CYP3A4 and P-gp, in a 56-year-old Chinese male with recurrent hepatocellular carcinoma post-liver transplantation. In this case, the patient’s baseline sirolimus trough blood concentration was 5.0 ng/mL prior to initiating a new cycle of regorafenib (80 mg once daily). Following a 7-day administration period of regorafenib, a notable elevation in sirolimus trough blood concentration to 12.3 ng/mL was observed. Upon cessation of regorafenib therapy for one week, the sirolimus trough blood concentration reverted back to 5.2 ng/mL. Nevertheless, upon resumption of regorafenib (160 mg once daily) treatment for an additional 10 days, the sirolimus trough blood concentration experienced a recurrence of increase, reaching 11.0 ng/mL. Following the confirmation of tumor progression, the discontinuation of regorafenib was deemed necessary. Consequently, a subsequent medical evaluation of the patient’s sirolimus trough blood concentration, undertaken precisely one month after cessation of regorafenib therapy, revealed a concentration level of 2.8 ng/mL. Based on the Drug Interaction Probability Scale, this interaction was deemed probable.ConclusionRegorafenib exerts a regulatory influence on the blood concentrations of sirolimus by inhibiting the activity of CYP3A4 and P-gp, potentially altering its pharmacokinetic profile. Given the potential for both excessive and inadequate immunosuppression to adversely affect patients with recurrent hepatocellular carcinoma post-liver transplantation, clinicians must maintain a heightened awareness of this drug-drug interaction.
The neutrophil-to-C3 ratio: unveiling diagnostic efficacy for lupus nephritis and association with reduced retinal vascular density in systemic lupus erythematosus
Authors: Maitiyaer Maierhaba , Li Peiyi , Li Huangdong , Jiang Dingwen , Zhang Jingyu , Yang Chuwei , Yang Xiaobin , Chen Chengmei , Huang Wenhui , Liu Zhiping , Yu Shuilian 
Published: February 2025

BackgroundLupus nephritis (LN) frequently manifests as a significant complication in systemic lupus erythematosus (SLE) patients, with emerging research indicating a plausible correlation between subclinical retinal involvement and renal manifestations. This study aims to investigate the relationship between the neutrophil-to-C3 ratio (NC3R) and both LN as well as retinal microvasculature damage among SLE patients.MethodsIn this cross-sectional study, a cohort of 220 participants (78 LN and 142 non-LN) was recruited. We assessed clinical indicators and organ involvement and conducted correlation analyses between NC3R and markers of lupus activity. Additionally, we analyzed the diagnostic performance of NC3R in diagnosing LN and constructed ROC curves. Variables such as clinical and laboratory data were screened by univariate and least absolute shrinkage and selection operator (LASSO) logistic regression modeling. After 10-fold cross-validation, the predictive model was built by multivariate logistic regression. We further examined the influence of NC3R on retinal vasculature density based on its cutoff value and conducted correlation analyses accordingly.ResultsThe LN group exhibited a significant increase in NC3R compared to the group without LN (5.9 vs. 4.5, p = 0.007). NC3R demonstrated positive correlations with 24-h proteinuria (R = 0.329, p &lt; 0.001) and systemic lupus erythematosus disease activity index (SLEDAI) score (R = 0.268, p &lt; 0.001). Multiple regression analysis revealed NC3R as an independent risk factor for LN (OR: 2.03, p = 0.025). NC3R was proven valuable in distinguishing LN patients (AUC: 0.613), with an optimal cutoff value of 6.40 (sensitivity: 48.1%, specificity: 72.0%). Our results indicated that the lower NC3R group (NC3R &lt; 6.40) exhibited reduced vascular density, particularly within the macular region. Furthermore, we observed a positive correlation between NC3R levels and vascular density.ConclusionNC3R demonstrated promising potential as a reliable indicator for predicting both LN and retinal microvasculature involvement. Consequently, the pre-treatment evaluation of NC3R had the potential to assist clinicians in identifying potential organ involvement among SLE patients.
Pharmacokinetics and bioequivalence of two formulations of the S-1 (tegafur/gimeracil/oxonate) capsule in Chinese cancer patients under fasting and fed conditions: a multicenter, randomized, open-label, single-dose, double-cycle crossover study
Authors: Lu Junli , Lei Yuyan , Mo Yuanyuan , Wang Xiangping , Liu Wanying , Yan Yu , Yang Hongying , Li Canxia , Huang Lifeng , Shen Qiuxia , Wang Caihong , Chen Jingjie , Chen Lulu , Li Xiaohui 
Published: February 2025

ObjectiveS-1, an oral multicomponent capsule containing tegafur, gimeracil, and potassium oxonate, has demonstrated efficacy in various tumor types. This study aimed to assess the pharmacokinetics, bioequivalence (BE), and safety of a newly developed generic S-1 capsule compared to the original brand-name formulation in Chinese cancer patients under fasting and fed conditions.MethodsA multicenter, randomized, open-label, single-dose, double-cycle crossover study was conducted in Chinese cancer patients. The study involved 120 subjects, with 60 assigned to the fasting group and another 60 to the fed group. In each study cycle, subjects were randomly assigned toreceive either the reference or test S-1 capsule at a 7-day interval. Blood samples were collected for analysis within 48 h after ingestion. The plasma concentrations of tegafur, 5-fluorouracil, gimeracil, and potassium oxonate were determined by liquid chromatography–tandem mass spectrometry (LC-MS/MS). The main pharmacokinetic (PK) parameters were calculated using the non-compartmental approach. BE was assessed through geometric mean ratios (GMRs) between the two formulations and their respective 90% confidence intervals (CIs). The safety of the two formulations was also evaluated.ResultsThe pharmacokinetics of the two formulations were similar under both fasting and fed conditions. The 90% CIs of the GMRs for the maximum observed serum concentration (Cmax), AUC0-t, and AUC0-∞ ratios were observed to lie within the BE acceptance range of 80%–125%. Both formulations of the S-1 capsule exhibited similar adverse events (AEs), primarily including decreased white blood cell count and hypertension. These AEs were generally mild and transient. The safety profiles of the two formulations were found to be good and comparable, with no serious adverse events (SAEs) reported.ConclusionThe newly developed generic S-1 and reference formulations exhibit comparable PK in Chinese cancer patients in the fasting and fed state. The formulations of S-1 showed good tolerability and a similar safety profile.Clinical Trial Registrationhttp://www.chinadrugtrials.org.cn/index.html, identifier CTR20171562.