bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemonucleolysis combined with dynamic loading for inducing degeneration in bovine caudal intervertebral discs
Authors: Vernengo Andrea , Bumann Helen , Kluser Nadine , Soubrier Astrid , Šećerović Amra , Gewiess Jan , Jansen Jan Ulrich , Neidlinger-Wilke Cornelia , Wilke Hans-Joachim , Grad Sibylle 
Published: August 2023

Chemonucleolysis has become an established method of producing whole organ culture models of intervertebral disc (IVD) degeneration. However, the field needs more side-by-side comparisons of the degenerative effects of the major enzymes used in chemonucleolysis towards gaining a greater understanding of how these organ culture models mimic the wide spectrum of characteristics observed in human degeneration. In the current work we induced chemonucleolysis in bovine coccygeal IVDs with 100 µL of papain (65 U/mL), chondroitinase ABC (chABC, 5 U/mL), or collagenase II (col’ase, 0.5 U/mL). Each enzyme was applied in a concentration projected to produce moderate levels of degeneration. After 7 days of culture with daily dynamic physiological loading (0.02–0.2 MPa, 0.2 Hz, 2 h), the cellular, biochemical and histological properties of the IVDs were evaluated in comparison to a PBS-injected control. Papain and collagenase, but not chABC, produced macroscopic voids in the tissues. Compared to day 0 intact IVDs, papain induced the greatest magnitude glycosaminoglycan (GAG) loss compared to chABC and col’ase. Papain also induced the greatest height loss (3%), compared to 0.7%, 1.2% and 0.4% for chABC, col’ase, and PBS, respectively. Cell viability in the region adjacent to papain and PBS-injection remained at nearly 100% over the 7-day culture period, whereas it was reduced to 60%–70% by chABC and col’ase. Generally, enzyme treatment tended to downregulate gene expression for major ECM markers, type I collagen (COL1), type II collagen (COL2), and aggrecan (ACAN) in the tissue adjacent to injection. However, chABC treatment induced an increase in COL2 gene expression, which was significant compared to the papain treated group. In general, papain and col’ase treatment tended to recapitulate aspects of advanced IVD degeneration, whereas chABC treatment captured aspects of early-stage degeneration. Chemonucleolysis of whole bovine IVDs is a useful tool providing researchers with a robust spectrum of degenerative changes and can be utilized for examination of therapeutic interventions.
Impact of growth hormone on IVF/ICSI outcomes and endometrial receptivity of patients undergoing GnRH antagonist protocol with fresh embryo transfer: a pilot study
Authors: Chu Yifan , Wang Luyao , Xie Jiaxin , Yang Shulin , Liu Si , Hu Dan , Yue Jing 
Published: August 2023

IntroductionGonadotropin-releasing hormone antagonist (GnRH-ant) protocol is widely used in the world for controlled ovarian hyperstimulation (COH). However, previous studies have shown that pregnancy outcomes of fresh embryo transfer with GnRH-ant protocol are not ideal. Current studies have demonstrated the value of growth hormone (GH) in improving the pregnancy outcome of elderly women and patients with diminished ovarian reserve, but no prospective studies have confirmed the efficacy of GH in fresh embryo transfer with GnRH-ant protocol, and its potential mechanism is still unclear. This study intends to evaluate the impact of GH on IVF/ICSI outcomes and endometrial receptivity of patients undergoing GnRH-ant protocol with fresh embryo transfer, and preliminarily explore the possible mechanism.MethodsWe designed a randomized controlled trial of 120 infertile patients with normal ovarian response (NOR) who will undergo IVF/ICSI from April 2023 to April 2025, at Department of Reproductive Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. The patients will be divided into the depot gonadotropin-releasing hormone agonist (GnRH-a) protocol group, GnRH-ant protocol control group, and GnRH-ant protocol plus GH intervention group at a ratio of 1:1:1 by block randomization design. Patients will be followed on enrollment day, trigger day, embryo transfer day, 7 days after oocytes pick-up, 15 days after embryo transfer, 28 days after embryo transfer, and 12 weeks of gestation. The primary outcome is the ongoing pregnancy rate. Secondary outcomes include the gonadotropin dosage, duration of COH, endometrial thickness and pattern, luteinizing hormone, estradiol, progesterone level on trigger day, numbers of retrieved oocytes, high-quality embryo rate, biochemical pregnancy rate, clinical pregnancy rate, implantation rate, ectopic pregnancy rate, early miscarriage rate, multiple pregnancy rate and incidence of moderate and severe ovarian hyperstimulation syndrome. The endometrium of certain patients will be collected and tested for endometrial receptivity.Ethics and disseminationThe study was approved by the Ethics Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology [approval number: TJ-IRB20230236; approval date: February 10, 2023]. The research results will be presented at scientific/medical conferences and published in academic journals.Clinical trial registrationChinese Clinical Trial Registry; identifier: ChiCTR2300069397.
18F-labeled PEGylated exendin-4 imaging noninvasively differentiates insulinoma from an accessory spleen: the first case report of [18F]FB(ePEG12)12-exendin-4 positron emission tomography/computed tomography for insulinoma
Authors: Sakaki Kentaro , Murakami Takaaki , Fujimoto Hiroyuki , Shimizu Yoichi , Miyake Kanae Kawai , Otani Daisuke , Kiyobayashi Sakura , Okada Takuya , Fujimoto Masakazu , Hakata Takuro , Yamauchi Ichiro , Shimada Kotaro , Shimizu Hironori , Nagai Kazuyuki , Nakamoto Yuji , Inagaki Nobuya 
Published: August 2023

BackgroundInsulinomas are the most common functioning pancreatic neuroendocrine neoplasms, and these tumors induce hypoglycemia due to hyperinsulinemia. Hypoglycemia caused by insulinomas can cause seizures, coma or death due to the delayed diagnosis. The only curative treatment is surgical resection. To perform curative surgical resection of insulinomas, preoperative localization is crucial. However, localization of insulinomas is often challenging using conventional imaging methods such as computed tomography (CT) and magnetic resonance imaging. Although endoscopic ultrasound (EUS) fine-needle aspiration and selective arterial calcium stimulation test, which can reflect the endocrine character of the tumor, are performed in such cases, these modalities are invasive and require operator-dependent techniques. Additionally, somatostatin receptor (SSTR)-targeted imaging has a relatively low sensitivity for detecting insulinomas due to its low SSTR type 2 expression. Thus, there is an urgent need for developing a noninvasive diagnostic technique which is specific for detecting insulinomas. Consequently, glucagon-like peptide-1 receptor-targeted imaging has recently emerged and gained a wide interest. Recently, we have developed a novel 18F-labeled exendin-4-based probe conjugated with polyethylene glycol, [18F]FB(ePEG12)12-exendin-4 (18F-exendin-4), for positron emission tomography (PET) imaging. Here we report a case of insulinoma in which 18F-exendin-4 PET/CT noninvasively provided critical information for localization.Case descriptionThis is a case of a 58-year-old male with symptomatic hypoglycemia for 10 years; however, a preoperative diagnosis of insulinoma was not established due to the difficulty in differentiating it from an accessory spleen using conventional imaging. Moreover, the patient requested to avoid invasive diagnostic procedures including EUS. 18F-exendin-4 PET/CT revealed significant uptakes in the pancreatic tail whereas no apparent uptakes were observed in the spleen; thus, curative laparoscopic enucleation of the pancreatic tail was performed. The diagnosis of insulinoma was confirmed via histopathological examination. This is the first case report of insulinoma diagnosed using 18F-exendin-4 PET/CT.ConclusionIn this case, PET information led to curative resection through enucleation of the pancreas. 18F-exendin-4 PET/CT may serve as a useful noninvasive clinical tool for insulinoma localization.
Mercury transport and methylmercury production in the lower Cedar River (Iowa) floodplain
Authors: Graham Andrew M. , Van Helten Seth , Wadle Austin , Mamrak Emily , Morsch Jacob , Lopez Samuel , Smith Katherine 
Published: August 2023

Scant attention has been paid to cycling of total mercury (THg) and methylmercury (MeHg) in agriculturally intensive watersheds. Monitoring of Hg and MeHg in river basins provides valuable information on the efficacy of environmental policy and the impacts of land use and climate change on Hg fluxes and biogeochemistry. We report on Hg and MeHg yields in the Cedar River (Iowa), a major tributary of the Upper Mississippi River, and on Hg biogeochemistry in a floodplain of the lower Cedar River, with emphasis on Hg cycling in groundwater and wetland ponds. For the period 2016 to 2018, total Hg yields for the 21,000 km2 Cedar River watershed ranged from 2.6 to 6.9 μg m−2 yr−1, or 25% to 70% of estimated wet deposition, and MeHg yields ranged from 0.09 to 0.18 μg m−2 yr−1. High watershed transfer efficiencies for THg are driven by soil erosion and suspended sediment delivery. Policies and land management practices targeting soil conservation are thus likely to have significant impacts on downstream transport of Hg. Within alluvial groundwaters, Hg and MeHg concentrations were highly spatiotemporally variable, ranging from 0.5 to 2.0 ng/L for THg and 0.03–1.50 ng/L for MeHg. Microtopography exerted strong control on groundwater geochemistry and Hg biogeochemical cycling, with groundwater sampled from lower lying swales exhibiting less dissolved oxygen (DO), higher conductivity, higher dissolved organic carbon (DOC), and higher THg and MeHg. The alluvial aquifer exhibits high hydrologic connectivity with the river and groundwater THg and MeHg concentrations responded rapidly to hydrologic events, with MeHg concentrations increasing with a rising water table. Concentrations of THg and MeHg in wetland ponds were elevated compared to groundwater and most strongly correlated with DOC and UV-absorbance. Methylation potentials in pond sediments were among the highest reported for freshwater sediments, up to 0.15 d−1, which we hypothesize to be linked to high primary productivity associated with nutrient enrichment. Floodplain groundwaters and wetlands constitute important ecosystem control points for downstream MeHg delivery, the magnitude of which is sensitive to changing hydroclimate, especially flood frequency.
Development of a novel, clinically relevant anoikis-related gene signature to forecast prognosis in patients with prostate cancer
Authors: Liu Xiaolin , Wang Kunming 
Published: August 2023

Introduction: Anoikis is a specific form of programmed cell death and is related to prostate cancer (PC) metastasis. This study aimed to develop a reliable anoikis-related gene signature to accurately forecast PC prognosis.Methods: Based on anoikis-related genes and The Cancer Genome Atlas (TCGA) data, anoikis-related molecular subtypes were identified, and their differences in disease-free survival (DFS), stemness, clinical features, and immune infiltration patterns were compared. Differential expression analysis of the two subtypes and weighted gene co-expression network analysis (WGCNA) were employed to identify clinically relevant anoikis-related differentially expressed genes (DEGs) between subtypes, which were then selected to construct a prognostic signature. The clinical utility of the signature was verified using the validation datasets GSE116918 and GSE46602. A nomogram was established to predict patient survival. Finally, differentially enriched hallmark gene sets were revealed between the different risk groups.Results: Two anoikis-related molecular subtypes were identified, and cluster 1 had poor prognosis, higher stemness, advanced clinical features, and differential immune cell infiltration. Next, 13 clinically relevant anoikis-related DEGs were identified, and five of them (CKS2, CDC20, FMOD, CD38, and MSMB) were selected to build a prognostic signature. This gene signature had a high prognostic value. A nomogram that combined Gleason score, T stage, and risk score could accurately predict patient survival. Furthermore, gene sets closely related with DNA repair were differentially expressed in the different risk groups.Conclusion: A novel, clinically relevant five-anoikis-related gene signature was a powerful prognostic biomarker for PC.
Cost-effectiveness of serplulimab as first-line therapy for extensive-stage small cell lung cancer in China
Authors: Xiang Guiyuan , Jiang Tingting , Gan Lanlan , Wu Yuanlin , Zhang Ni , Xing Haiyan , Su Hui , Li Yanping , Peng Dan , Ni Rui , Liu Yao 
Published: August 2023

ObjectiveThe ASTRUM-005 trial demonstrated that adding serplulimab to chemotherapy significantly prolonged the survival of patients with extensive-stage small cell lung cancer (SCLC), but also increased the risk of adverse events. Given the high cost of serplulimab compared to chemotherapy, this study aimed to evaluate the cost-effectiveness of serplulimab plus chemotherapy as a first-line treatment for extensive-stage SCLC from the perspective of China’s healthcare system.MethodsA Markov model was developed to simulate the disease process of extensive-stage SCLC and estimate the health outcomes and direct medical costs of patients. Scenario analyses, univariate sensitivity analyses, and probabilistic sensitivity analyses were conducted to explore the impact of different parameters on model uncertainty. The primary model outcomes included costs, life-years (LYs), quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER).ResultsCompared to placebo plus chemotherapy, serplulimab plus chemotherapy resulted in an additional 0.25 life-years and 0.15 QALYs, but also increased costs by $26,402, resulting in an ICER of 179,161 USD/QALY. Sensitivity analysis showed that the ICER was most sensitive to the cost of serplulimab, and the probability that serplulimab was cost-effective when added to chemotherapy was only 0 at the willingness-to-pay threshold of 37,423 USD/QALY. Scenario analysis revealed that price discounts on serplulimab could increase its probability of being cost-effective.ConclusionSerplulimab plus chemotherapy is not a cost-effective strategy for first-line treatment of extensive-stage SCLC in China. Price discounts on serplulimab can enhance its cost-effectiveness.
Activity of granulomatosis with polyangiitis and its correlation with mTOR phosphoproteomics in neutrophils
Authors: Surmiak Marcin , Wawrzycka-Adamczyk Katarzyna , Kosałka-Węgiel Joanna , Włudarczyk Anna , Sanak Marek , Musiał Jacek 
Published: August 2023

IntroductionGranulomatosis with polyangiitis (GPA) is a small vessel vasculitis with a complex pathomechanism. Organ damage in GPA is also mediated by extracellular trap formation (NETosis). We analyzed the functional status of phosphoproteins modulating NETosis in neutrophils by the mammalian target of rapamycin (mTOR) pathway in GPA along with NETosis biomarkers.MethodsPhosphoproteins levels measured in isolated neutrophils from 42 patients with GPA (exacerbation n=21; remission n=21) and 21 healthy controls were compared to serum biomarkers of the disease.ResultsNeutrophils in active disease manifested lowered levels of phosphorylated mTOR(Ser2448), PTEN(Ser380) and ULK1(Ser555), whereas phosphorylated GSK-3α/β(Ser21/Ser9) was elevated. Exacerbation of GPA was characterized by elevated neutrophil dsDNA in serum, circulating mitochondrial DNA, and DNA-MPO complexes. A significant negative correlation between mTOR or PTEN phosphoproteins and biomarkers of GPA activity was also present, reflecting the clinical activity score of GPA. Positive correlations between phosphorylated GSK-3 α/β and circulating mtDNA, DNA-MPO complexes, neutrophil-released dsDNA, or circulating proteins were also significant. Increased serum levels of IGFBP-2, TFF-3, CD147, and CHI3L1 accompanied GPA exacerbation, whereas DPP-IV levels were the lowest in active GPA. Using a principal component analysis basigin, PTEN and mTOR had the highest loadings on the discrimination function, allowing classification between active, remission, and control subjects with 98% performance.ConclusionsWe present evidence that inhibited mTOR signaling accompanies NETosis in patients with GPA. The functional status of phosphoproteins suggests simultaneous activation of NETosis and autophagy. These results give rise to the study of autophagy as a mechanism underlying granuloma formation in GPA.
Causal effects of systemic inflammatory regulators on chronic kidney diseases and renal function: a bidirectional Mendelian randomization study
Authors: Li Hongdian , Li Mingxuan , Liu Cong , He Pengfei , Dong Ao , Dong Shaoning , Zhang Mianzhi 
Published: August 2023

BackgroundWhile targeted systemic inflammatory modulators show promise in preventing chronic kidney disease (CKD) progression, the causal link between specific inflammatory factors and CKD remains uncertain.MethodsUsing a genome-wide association study of 41 serum cytokines from 8,293 Finnish individuals, we conducted a bidirectional two-sample Mendelian randomization (MR) analysis. In addition, we genetically predicted causal associations between inflammatory factors and 5 phenotypes, including CKD, estimated glomerular filtration rate (eGFR), dialysis, rapid progression of CKD, and rapid decline in eGFR. Inverse variance weighting (IVW) served as the primary MR method, while MR-Egger, weighted median, and MR-pleiotropy residual sum and outlier (MR-PRESSO) were utilized for sensitivity analysis. Cochrane’s Q test for heterogeneity. Leave-one-out method ensured stability of MR results, and Bonferroni correction assessed causal relationship strength.ResultsSeventeen cytokines were associated with diverse renal outcomes. Among them, after Bonferroni correction test, higher tumor necrosis factor alpha levels were associated with a rapid decrease in eGFR (OR = 1.064, 95% CI 1.028 – 1.103, P = 0.001), higher interleukin-4 levels were associated with an increase in eGFR (β = 0.003, 95% CI 0.001 – 0.005, P = 0.002), and higher growth regulated oncogene alpha (GROα) levels were associated with an increased risk of CKD (OR=1.035, 95% CI 1.012 - 1.058, P = 0.003). In contrast, genetic susceptibility to CKD was associated with an increase in GROa, and a decrease in eGFR may lead to an increase in stem cell factor. We did not find the presence of horizontal pleiotropy during the analysis.ConclusionWe discovered causally related inflammatory factors that contribute to the initiation and progression of CKD at the genetic prediction level.
Exploring the potential relationship between frozen shoulder and Dupuytren’s disease through bioinformatics analysis and machine learning
Authors: Ouyang Yulong , Chen Shuilin , Tu Yuanqing , Wan Ting , Fan Hao , Sun Guicai 
Published: August 2023

BackgroundFrozen shoulder (FS) and Dupuytren’s disease (DD) are two closely related diseases, but the mechanism of their interaction is unknown. Our study sought to elucidate the molecular mechanism of these two diseases through shared gene and protein interactions.MethodsGSE75152 and GSE140731 data were downloaded from the Gene Expression Omnibus (GEO) database, and shared genes between FS and DD were selected by using R packages. Then, we used Cytoscape software and the STRING database to produce a protein−protein interaction (PPI) network. Important interaction networks and hub genes were selected through MCODE and cytoHubba algorithms. To explore the potential mechanisms of the development of the two diseases, the hub genes were further enriched by GO and KEGG analyses. We predicted the transcription factors (TFs) of hub genes with Transcriptional Regulatory Relationships Unraveled by Sentence-based Text mining (TRRUST). Moreover, we identified candidate genes for FS with DD with cytoHubba and machine learning algorithms. Finally, we analyzed the role of immunocyte infiltration in FS and constructed the relationship between candidate genes and immunocytes in FS.ResultsWe identified a total of 321 shared genes. The results of GO and KEGG enrichment of shared genes showed that extracellular matrix and collagen fibril tissue play a certain role in the occurrence and development of disease. According to the importance of genes, we constructed the key PPI network of shared genes and the top 15 hub genes for FS with DD. Then, we predicted that five TFs are related to the hub genes and are highly expressed in the FS group. Machine learning results show that the candidate genes POSTN and COL11A1 may be key for FS with DD. Finally, immune cell infiltration revealed the disorder of immunocytes in FS patients, and expression of candidate genes can affect immunocyte infiltration.ConclusionWe identified a PPI network, 15 hub genes, and two immune-related candidate genes (POSTN and COL11A1) using bioinformatics analysis and machine learning algorithms. These genes have the potential to serve as diagnostic genes for FS in DD patients. Furthermore, our study reveals disorder of immunocytes in FS.
Enhancement of heat transfer in heat sink under the effect of a magnetic field and an impingement jet
Authors: Azadi Shervin , Abjadi Ali , Vahdat Azad Abazar , Ahmadi Danesh Ashtiani Hossein , Afshar Hossein 
Published: August 2023

Improving the performance of heat sinks is very important in the development of cooling systems. In this study, the use of a novel combination method [magnetic field impingement jet (MF-IJ)] to improve the convective heat transfer coefficient in a designed heat sink is numerically investigated. To model heat transfer, a steady three-dimensional computational fluid dynamics (CFD) approach is employed. Numerical results including velocity and temperature contours, as well as the distribution of wall temperature of the heat sink and also the convective heat transfer coefficient are analyzed. The results show that the use of ferrofluid (Fe3O4/water) flow with an external magnetic field alone increases the heat transfer coefficient by 10%, while the use of an air impingement jet with pure water and without a magnetic field increases it by 22.4%. By using the MF-IJ method, a 32% enhancement of heat transfer coefficient is achieved compared to the case of pure water flow and without MF-IJ. Based on results, at a Reynolds number of 600, by applying the magnetic field intensities of 400, 800, and 1600 G, the average heat transfer coefficient increases by 5.35, 11.77, and 16.11%, respectively. It is also found that the cooling of the heat sink and temperature distribution is improved by increasing the Reynolds number and the inlet mass flow rate of the impingement jet. For instance, at z = 0.02 m, the application of an impingement jet with mass flow rates of 0.001, 0.004, and 0.005 kg/s results in a respective decrease of 0.36, 1.62, and 1.82% in wall temperature. The results of the current study suggest that the combination method of MF-IJ can be utilized for heat sinks with high heat flux generation as a flow control device.