bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global burden of chronic kidney disease in adolescents and young adults, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019
Authors: Sun Ping , Ming Xingyu , Song Tiange , Chen Yan , Yang Xin , Sun Zhaochen , Zheng Xiaoxia , Tong Luyao , Ma Zhiwei , Wan Zhengwei 
Published: September 2024

BackgroundThe global status of chronic kidney disease (CKD) is underestimated, particularly the burden on adolescents and young adults (early-onset, aged 15–39).ObjectiveWe aim to investigate the pattern and trend of early-onset CKD from 1990 to 2019.MethodsWe analyzed age-specific rates of early-onset CKD incidence, death, and disability-adjusted life years (DALY) using Global Burden of Disease Study 2019 data. We examined the global, regional, national, gender-based, age group-based, and temporal changes of early-onset CKD burden from 1990 to 2019, as well as proportional DALY attributions of various risk factors.ResultsFrom 1990 to 2019, the global age-specific incidence rate (per 100,000 population) significantly increased from 25.04 (95% confidence interval 18.51, 31.65) to 32.21 (23.73, 40.81) for early-onset CKD. However, the global age-specific death rate significantly decreased from 2.96 (2.76, 3.15) to 2.86 (2.61, 3.11), and the age-specific DALY rate remained stable. Regarding sociodemographic indexes (SDI), countries with middle SDI had the highest incidence rates and the fastest increasing trends, while those with low and low-middle SDI experienced the highest death and DALY rates. Women had a generally higher age-specific incidence rate than men, whereas men showed higher age-specific death and DALY rates. In addition, the burdens of CKD increased with age among adolescents and young adults. Moreover, the main attributable risk factors for DALY of early-onset CKD were high systolic blood pressure (SBP), fasting plasma glucose (FPG), and body mass index (BMI).ConclusionThe age-specific incidence rate of early-onset CKD increased significantly from 1990 to 2019, and the age-specific DALY rate remained stable. High SBP, high FPG, and high BMI were the primary risk factors. Targeted prevention and healthcare measures should be developed considering age, gender, and region.
The association between the triglyceride-glucose index and bone turnover markers in osteoporotic fractures patients aged 50 and above who are hospitalized for surgical intervention: a retrospective cross-sectional study
Authors: Xu Jian , Guo Shao-han , Xu Min-zhe , Li Chong , Gong Ya-qin , Lu Ke 
Published: September 2024

ObjectiveTo evaluate the correlation between the triglyceride-glucose (TyG) index and bone turnover markers (BTMs) in osteoporotic fractures (OPFs) patients hospitalized for surgical intervention.MethodsA retrospective cross-sectional study was conducted on 3558 OPFs patients hospitalized for surgical intervention between January 2017 and July 2022. The study obtained baseline values for various biomarkers and covariates, including fasting blood glucose, β-C-terminal telopeptide of type I collagen (β-CTX), procollagen type 1 N-terminal propeptide (P1NP), triglycerides, age, sex, body mass index, smoking, drinking, low-density lipoprotein, high-density lipoprotein, aspartate aminotransferase, uric acid, the score of American society of anesthesiologists, homocysteine, parathyroid hormone, apolipoprotein B, apolipoprotein A, magnesium, phosphorus and calcium. Multiple linear regression, curve fitting, threshold effects, and subgroup analyses were also applied.ResultsAfter adjusting for covariates in the regression analysis, the results revealed a negative correlation between β-CTX and P1NP levels and the baseline TyG index. Specifically, a one-unit increase in the TyG index was associated with a reduction in β-CTX levels of -0.06 (95% CI: -0.10, -0.01; P-value = 0.012) and a reduction in P1NP levels of -4.70 (95% CI: -9.30, -0.09; P-value = 0.046). Additionally, the inflection points for the nonlinear correlation between the TyG index and β-CTX and P1NP were found to be K = 6.31 and K = 6.63, respectively.ConclusionThe study demonstrated a negative, non-linear relationship among the TyG index, β-CTX and P1NP in OPFs patients hospitalized for surgical intervention. These findings suggest that elevated TyG index levels may adversely affect bone turnover, potentially contributing to the progression of OP.
Longitudinal associations between microRNAs and weight in the diabetes prevention program
Authors: Flowers Elena , Stroebel Benjamin , Gong Xingyue , Lewis Kimberly A. , Aouizerat Bradley E. , Gadgil Meghana , Kanaya Alka M. , Zhang Li 
Published: September 2024

ObjectiveCirculating microRNAs show cross-sectional associations with overweight and obesity. Few studies provided data to differentiate between a snapshot perspective on these associations versus how microRNAs characterize prodromal risk from disease pathology and complications. This study assessed longitudinal relationships between circulating microRNAs and weight at multiple time-points in the Diabetes Prevention Program trial.Research design and methodsA subset of participants (n=150) from the Diabetes Prevention Program were included. MicroRNAs were measured from banked plasma using a Fireplex Assay. We used generalized linear mixed models to evaluate relationships between microRNAs and changes in weight at baseline, year-1, and year-2. Logistic regression was used to evaluate whether microRNAs at baseline were associated with weight change after 2 years.ResultsIn fully adjusted models that included relevant covariates, seven miRs (i.e., miR-126, miR-15a, miR-192, miR-23a, and miR-27a) were statistically associated with weight over 2 years. MiR-197 and miR-320a remained significant after adjustment for multiple comparisons. Baseline levels of let-7f, miR-17, and miR-320c were significantly associated with 3% weight loss after 2 years in fully adjusted models.DiscussionThis study provided evidence for longitudinal relationships between circulating microRNAs and weight. Because microRNAs characterize the combined effects of genetic determinants and responses to behavioral determinants, they may provide insights about the etiology of overweight and obesity in the context or risk for common, complex diseases. Additional studies are needed to validate the potential genes and biological pathways that might be targeted by these microRNA biomarkers and have mechanistic implications for weight loss and disease prevention.
Identification of novel targets associated with cholesterol metabolism in nonalcoholic fatty liver disease: a comprehensive study using Mendelian randomization combined with transcriptome analysis
Authors: Chen Juan , Rao Huajing , Zheng Xiaoling 
Published: September 2024

BackgroundThere is limited research on cholesterol metabolism-related genes (CM-RGs) in non-alcoholic fatty liver disease (NAFLD), despite hypercholesterolemia being a recognized risk factor. The role of CM-RGs in NAFLD remains unclear.MethodsThe differentially expressed genes (DEGs) between NAFLD and control were acquired by differential expression analysis. The differentially expressed genes associated with cholesterol metabolism (DE-CM-RGs) were identified and functional enrichment analyses were performed. Protein-protein interaction network analysis and a two-sample Mendelian randomization study were utilized for identifying hub genes. Nomogram model, competing endogenous RNA and messenger RNA-drug networks were established. In addition, immunoinfiltration analysis was performed.ResultsWe identified four hub genes (MVK, HMGCS1, TM7SF2, and FDPS) linked to NAFLD risk. MVK and TM7SF2 were protective factors, HMGCS1 and FDPS were risk factors for NAFLD. The area under the curve values of nomograms in GSE135251 and GSE126848 were 0.79 and 0.848, respectively. The gene set enrichment analysis indicated that hub genes participated in calcium signaling pathways and biosynthesis of unsaturated fatty acids. NAFLD patients showed increased CD56dim NK cells and Th17. Tretinoin, alendronate, zoledronic acid, and quercetin are potential target agents in NAFLD.ConclusionOur study has linked cholesterol metabolism genes (MVK, HMGCS1, TM7SF2, and FDPS) to NAFLD, providing a promising diagnostic framework, identifying treatment targets, and offering novel perspectives into its mechanisms.
Addressing GPU memory limitations for Graph Neural Networks in High-Energy Physics applications
Authors: Lee Claire Songhyun , Hewes V. , Cerati Giuseppe , Wang Kewei , Aurisano Adam , Agrawal Ankit , Choudhary Alok , Liao Wei-Keng 
Published: September 2024

IntroductionReconstructing low-level particle tracks in neutrino physics can address some of the most fundamental questions about the universe. However, processing petabytes of raw data using deep learning techniques poses a challenging problem in the field of High Energy Physics (HEP). In the Exa.TrkX Project, an illustrative HEP application, preprocessed simulation data is fed into a state-of-art Graph Neural Network (GNN) model, accelerated by GPUs. However, limited GPU memory often leads to Out-of-Memory (OOM) exceptions during training, due to the large size of models and datasets. This problem is exacerbated when deploying models on High-Performance Computing (HPC) systems designed for large-scale applications.MethodsWe observe a high workload imbalance issue during GNN model training caused by the irregular sizes of input graph samples in HEP datasets, contributing to OOM exceptions. We aim to scale GNNs on HPC systems, by prioritizing workload balance in graph inputs while maintaining model accuracy. Our paper introduces diverse balancing strategies aimed at decreasing the maximum GPU memory footprint and avoiding the OOM exception, across various datasets.ResultsOur experiments showcase memory reduction of up to 32.14% compared to the baseline. We also demonstrate the proposed strategies can avoid OOM in application. Additionally, we create a distributed multi-GPU implementation using these samplers to demonstrate the scalability of these techniques on the HEP dataset.DiscussionBy assessing the performance of these strategies as data loading samplers across multiple datasets, we can gauge their effectiveness in both single-GPU and distributed environments. Our experiments, conducted on datasets of varying sizes and across multiple GPUs, broaden the applicability of our work to various GNN applications that handle input datasets with irregular graph sizes.
Chemotherapy combined with regorafenib and immune checkpoint inhibitors as a first-line treatment for patients with advanced biliary tract cancer: a single arm phase II trial
Authors: Liu Jianwei , Bai Shilei , Sun Yanfu , Hu Lei , Ge Ruiliang , Xue Feng 
Published: September 2024

ObjectiveThis study aimed to investigate the efficacy, long-term prognosis and safety of combining chemotherapy with regorafenib and immune checkpoint inhibitors as first-line treatment for patients with advanced biliary tract carcinoma (BTC).MethodsIn this single arm phase II trial, twenty-nine patients with advanced BTC were included, all of whom received gemcitabine-based chemotherapy combined with regorafenib and immune checkpoint inhibitors as the first-line treatment. And the study analyzed anti-tumor efficacy, long-term prognosis, and adverse reactions.ResultsAmong the patients, 0 patient achieved complete response, 18 patients (62.1%) achieved partial response, 8 patients (27.6%) had stable disease, and 3 patients (10.3%) experienced progressive disease. The corresponding objective response rate (ORR) was 18/29 (62.1%), and the disease control rate (DCR) was 26/29 (89.7%). The median overall survival (OS) was 16.9 months (95% confidence interval [CI]: 12.0 -21.8) and the median progress free survival (PFS) was 10.2 months (95% CI: 7.8- 12.6). The 1-year OS and PFS were 65% (95% CI: 0.479-0.864) and 41% (95% CI: 0.234-0.656), respectively. The incidence of adverse reactions was 27/29 (93.1%), and the incidence of grade III/IV adverse reactions was 5/29 (17.2%).ConclusionThe combination of chemotherapy, regorafenib, and immune checkpoint inhibitors as a first-line treatment for patients with advanced BTC may has good anti-tumor efficacy without causing serious adverse reactions, and can significantly improve the long-term prognosis.
Development and characterization of segment-specific enteroids from the pig small intestine in Matrigel and transwell inserts: insights into susceptibility to porcine epidemic diarrhea Virus
Authors: Yen Lu , Nelli Rahul K. , Twu Ning-Chieh , Mora-Díaz Juan Carlos , Castillo Gino , Sitthicharoenchai Panchan , Giménez-Lirola Luis G. 
Published: September 2024

IntroductionThe critical early stages of infection and innate immune responses to porcine epidemic diarrhea virus (PEDV) at the intestinal epithelium remain underexplored due to the limitations of traditional cell culture and animal models. This study aims to establish a porcine enteroid culture model to investigate potential differences in susceptibility to infection across segments of the porcine small intestine (duodenum, jejunum, and ileum).MethodsIntestinal crypt cells from nursery pigs were cultured in Matrigel to differentiate into porcine enteroid monolayer cultures (PEMCs). Following characterization, PEMCs were enzymatically dissociated and subcultured on transwell inserts (PETCs) for apical surface exposure and infection studies. Characterization of region-specific PEMCs and PETCs included assessment of morphology, proliferation, viability, and cellular phenotyping via immunohistochemistry/immunocytochemistry and gene expression analysis. Subsequently, PETCs were inoculated with 105 TCID50 (50% tissue culture infectious dose)/mL of a high pathogenic PEDV non-S INDEL strain and incubated for 24 h. Infection outcomes were assessed by cytopathic effect, PEDV N protein expression (immunofluorescence assay, IFA), and PEDV N-gene detection (quantitative reverse transcription polymerase chain reaction, RT-qPCR).ResultsNo significant morphological and phenotypical differences were observed among PEMCs and PETCs across intestinal regions, resembling the porcine intestinal epithelium. Although PETCs established from different segments of the small intestine were susceptible to PEDV infection, jejunum-derived PETCs exhibited higher PEDV replication, confirmed by IFA and RT-qPCR.DiscussionThis segment-specific enteroid culture model provides a reliable platform for virological studies, offering a controlled environment that overcomes the limitations of in vivo and traditional cell culture methods. Standardizing culture conditions and characterizing the model are essential for advancing enteroid-based infection models.
The iNKT cell ligand α-GalCer prevents murine septic shock by inducing IL10-producing iNKT and B cells
Authors: Park Yun Hoo , Lee Sung Won , Kim Tae-Cheol , Park Hyun Jung , Van Kaer Luc , Hong Seokmann 
Published: September 2024

Introductionα-galactosylceramide (α-GalCer), a prototypical agonist of invariant natural killer T (iNKT) cells, stimulates iNKT cells to produce various cytokines such as IFNγ and IL4. Moreover, repeated α-GalCer treatment can cause protective or pathogenic outcomes in various immune-mediated diseases. However, the precise role of α-GalCer-activated iNKT cells in sepsis development remains unclear. To address this issue, we employed a lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced murine sepsis model and two alternative models.MethodsSepsis was induced in wild-type (WT) C57BL/6 (B6) mice by three methods (LPS/D-GalN, α-GalCer/D-GalN, and cecal slurry), and these mice were monitored for survival rates. WT B6 mice were intraperitoneally injected with α-GalCer or OCH (an IL4-biased α-GalCer analog) one week prior to the induction of sepsis. To investigate the effects of α-GalCer-mediated iNKT cell activation on sepsis development, immune responses were analyzed by flow cytometry using splenocytes and liver-infiltrating leukocytes. In addition, a STAT6 inhibitor (AS1517499) and an IL10 inhibitor (AS101) were employed to evaluate the involvement of IL4 or IL10 signaling. Furthermore, we performed B cell adoptive transfers to examine the contribution of α-GalCer-induced regulatory B (Breg) cell populations in sepsis protection.ResultsIn vivo α-GalCer pretreatment polarized iNKT cells towards IL4- and IL10-producing phenotypes, significantly attenuating LPS/D-GalN-induced septic lethality in WT B6 mice. Furthermore, α-GalCer pretreatment reduced the infiltration of immune cells to the liver and attenuated pro-inflammatory cytokine production. Treatment with a STAT6 inhibitor was unable to modulate disease progression, indicating that IL4 signaling did not significantly affect iNKT cell-mediated protection against sepsis. This finding was confirmed by pretreatment with OCH, which did not alter sepsis outcomes. However, interestingly, prophylactic effects of α-GalCer on sepsis were significantly suppressed by treatment with an IL10 antagonist, suggesting induction of IL10-dependent anti-inflammatory responses. In addition to IL10-producing iNKT cells, IL10-producing B cell populations were significantly increased after α-GalCer pretreatment.ConclusionOverall, our results identify α-GalCer-mediated induction of IL10 by iNKT and B cells as a promising option for controlling the pathogenesis of postoperative sepsis.
Evaluation of the effectiveness and safety of combining PD-1/PD-L1 inhibitors with anti-angiogenic agents in unresectable hepatocellular carcinoma: a systematic review and meta-analysis
Authors: Zhu Hengzhou , Zhao Wenyue , Chen Haoyan , Zhu Xiaodan , You Jianliang , Jin Chunhui 
Published: September 2024

BackgroundHepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality globally, particularly when diagnosed at an unresectable stage. Traditional treatments for advanced HCC have limited efficacy, prompting the exploration of combination therapies. This systematic review and meta-analysis evaluate the effectiveness and safety of combining PD-1/PD-L1 inhibitors with anti-angiogenic agents in patients with unresectable HCC.MethodsA comprehensive literature search was conducted in PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science, including studies up to June 2024. Randomized controlled trials (RCTs) comparing combination therapy (PD-1/PD-L1 inhibitors with anti-angiogenic agents) to monotherapy or standard treatments in unresectable HCC patients were included. Data were synthesized using random-effects models, with pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and risk ratios (RRs) for objective response rate (ORR) and adverse events (AEs).ResultsFive Phase III RCTs involving 1515 patients were included. Combination therapy significantly improved OS (HR: 0.71, 95% CI: 0.60-0.85) and PFS (HR: 0.64, 95% CI: 0.53-0.77) compared to monotherapy or standard treatments. The pooled OR for ORR was 1.27 (95% CI: 1.57-2.11), indicating a higher response rate with combination therapy. However, the risk of AEs was also higher in the combination therapy group (RR: 1.04, 95% CI: 1.02-1.06). Subgroup analyses revealed consistent benefits across different types of PD-1/PD-L1 inhibitors and anti-angiogenic agents, with no significant publication bias detected.ConclusionsThe combination of PD-1/PD-L1 inhibitors with anti-angiogenic agents offers significant benefits in improving OS and PFS in patients with unresectable HCC, although it is associated with an increased risk of adverse events.
Nutrient upcycling and flows of carbon, nitrogen, and phosphorus in Hediste diversicolor (OF Müller, 1776) (Annelida: Nereididae) fed aquaculture sludge
Authors: Anglade Inka , Sæther Håkon O. E. , Hagemann Andreas , Reitan Kjell Inge , Malzahn Arne M. 
Published: September 2024

IntroductionWith the continuous growth of Atlantic salmon (Salmo salar L.) aquaculture, appropriate management of nutrient-rich waste streams from both land- and sea-based production has become increasingly important. Following a circular approach, nutrients contained in aquaculture sludge can be utilized for biomass production of the polychaete Hediste diversicolor. While the potential for upcycling nutrients has been established previously, this study aimed to assess nutrient flows in H. diversicolor fed aquaculture sludge as understanding these will be crucial for optimizing future large-scale production of this species.Materials and methodsWe investigated the effect of low and high feed supply of smolt sludge on the nutrient flows of carbon (C), nitrogen (N), and phosphorus (P) in H. diversicolor on an individual level. Hereby we assessed ingestion, defecation, excretion, respiration, and uptake for growth.Results and discussionNutrient flows differed between the nutrients C, N, and P in the high feed supply group where C uptake for growth was significantly higher than N and P uptake, and N uptake was significantly higher than P uptake. In contrast, no significant differences were observed in the low feed supply group. In the high feed supply group, most of the ingested C, N, and P by H. diversicolor was allocated to uptake for growth (76% C, 83% N, 85% P) with smaller proportions allocated to defecation (7% C, 7% N, 11% P) and respiration/excretion (18% C, 9% N, 5% P). The results from the low feed supply group suggest insufficient nutrient supply as most ingested C was allocated to respiration (84%), while most N was expended on uptake for growth (45%), and ingested P was either taken up for growth (58%) or spent on defecation (34%). Overall, nutrient uptake reflected the smolt sludge composition rather than nutrient requirements for H. diversicolor, which may be a short-term effect and needs to be investigated further. The flow of nutrients was strongly affected by feed supply, as ingestion, defecation, excretion, and uptake for growth were significantly higher in the high feed supply group than in the low feed supply group.
Continuous serratus anterior plane block for postoperative analgesia following lung transplantation via anterolateral incision: a pilot study
Authors: Luo Ge , Ni Tingting , Tao Xinchen , Xiao Jie , Yao Yuanyuan , Huang Man , Chen Jingyu , Yan Min 
Published: September 2024

BackgroundUnilateral or bilateral anterolateral thoracotomy May lead to severe acute pain in lung transplantation (LTx). Although serratus anterior plane block (SAPB) is apparently effective for pain control after open thoracic surgery, there remains a lack of evidence for the application of SAPB for postoperative analgesia after LTx.ObjectiveIn this case series pilot study, we describe the feasibility of continuous SAPB after lung transplantation and provide a preliminary investigation of its safety and efficacy.MethodsAfter chest incisions closure was complete, all patients underwent ultrasound-guided SAPB with catheter insertion. Numerical rating scale (NRS), additional opioid consumption, time to endotracheal tube removal, ICU length of stay, and catheter-related adverse events were followed up and recorded for each patient within 1 week after the procedure.ResultsA total of 14 patients who received LTx at this center from August 2023 to November 2023 were included. All patients received anterolateral approaches, and 10 (71.4%) of them underwent bilateral LTx. The duration of catheter placement was 2 (2–3) days, and the Resting NRS during catheter placement was equal to or less than 4. A total of 11 patients (78.6%) were supported by extracorporeal membrane oxygenation (ECMO) in LTx, whereas 8 patients (57.1%) removed the tracheal tube on the first day after LTx. Intensive care unit (ICU) stay was 5 (3–6) days, with tracheal intubation retained for 1 (1–2) days, and only one patient was reintubated. The morphine equivalent dose (MED) in the first week after LTx was 11.95 mg, and no catheter-related adverse events were detected.LimitationsWe did not assess the sensory loss plane due to the retrospective design. In addition, differences in catheter placement time May lead to bias in pain assessment.ConclusionAlthough continuous SAPB May be a safe and effective fascial block technique for relieving acute pain after LTx, it should be confirmed by high-quality clinical studies.